enantioselective desymmetrization of prochiral 1,3 ... · enantioselective desymmetrization of...

Enantioselective desymmetrization of prochiral 1,3-dinitropropanes via organocatalytic allylic alkylation

Soumya Jyoti Singha Roy and Santanu Mukherjee*

Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, INDIA

[email protected]

SUPPORTING INFORMATION: PART A

General: Unless stated otherwise, all reactions were carried out with distilled and dried solvents under an atmosphere of N2 or argon, oven (120 °C) dried glassware with standard vacuum line techniques were used. Organic solvents used for carrying out reactions were dried using standard methods. All work up and purification were carried out with reagent grade solvents in air. Thin-layer chromatography was performed using Merck silica gel 60 F254 pre-coated plates (0.25 mm). Column chromatography was performed using silica gel (230-400 or 100- 200 mesh). Infrared (FT-IR) spectra were recorded on a Perkin Elmer Spectrum BX spectrophotometer in cm-1 and the bands are characterized as broad (br), strong (s), medium (m), and weak (w). NMR spectra were recorded on Bruker Ultrashield spectrometer at 400MHz (1H) and 100 MHz (13C). Chemical shifts are reported in ppm from tetramethylsilane (δ 0.00) with the solvent resonance as internal standard (CDCl3: δ 7.26, CD3OD: δ 3.31 for 1H-NMR and CDCl3: δ 77.0, CD3OD: δ 49.00 for 13C NMR). For 1H-NMR, data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, dd = double doublet, t = triplet, q = quartet, br = broad, m = multiplet), coupling constants (Hz) and integration. High-resolution mass spectrometry was performed on Micromass Q-TOF Micro instrument. Optical rotations were measured on JASCO P-1020 polarimeter. Melting points were measured using ANALAB µ-Thermocal 10 melting point apparatus. All melting points were measured in open glass capillary and values are uncorrected. Enantiomeric ratios were determined by HPLC analysis using chiral columns in comparison with authentic racemic materials. Aldehydes were not purified before use. Nitromethane and basic alumina was used as obtained by commercial suppliers. Ethyl acrylate was freshly distilled before use.

Electronic Supplementary Material (ESI) for Chemical CommunicationsThis journal is © The Royal Society of Chemistry 2013

Singha Roy & Mukherjee, SI-Part-A, Page S-2

Preparation of 2-substituted 1,3-dinitropropanes:

Procedure A: For the preparation of 1a, 1c-f, 1h-n modified literature1 procedure was followed.

In an oven-dried round bottom flask fitted with a magnetic stir-bar, aldehyde (1.0 equiv.) was dissolved in nitromethane (25.0 equiv.). To this solution basic alumina (0.6 g/mmol of the aldehyde) was added; the resulting slurry was heated (at the temperature specified for the corresponding compounds) for required amount of time in an argon atmosphere. After completion of the reaction, the reaction mixture was allowed to attain room temperature; the alumina was then filtered off and the filtrate was concentrated to obtain, in all the cases, a thick oil. This was purified by silica gel (230-400 mesh) column chromatography. In most of the cases, the oil obtained after column purification, were crystallized/solidified using appropriate solvent system to obtain solid/crystalline dinitropropanes that were used for the catalytic reactions.

1-(1,3-Dinitropropan-2-yl)-4-methylbenzene (1a): Reaction was performed at 105 °C for 12 h.

Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 7-10% EtOAc/pet ether) afforded a red oil. This was subjected to solidification using EtOAc-toluene-pet ether (1:3:5) mixture at –20 °C for overnight to get 1a as a brownish solid (1.975 g, 8.802 mmol; 48% yield). Rf

= 0.30 (25% EtOAc in pet ether); Melting point = 49-50 °C; FT-IR (KBr): ν 2921 (m), 1564 (s), 1557 (s), 1378 (s), 818 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.17 (d, J = 8 Hz; 2H), 7.10 (d, J = 8 Hz; 2H), 4.69-4.79 (m; 4H), 4.23-4.30 (m; 1H), 2.33 (s; 3H); 13C-NMR (100 MHz, CDCl3): δ 139.1, 131.0, 130.2, 127.2, 76.8, 41.4, 21.1; HRMS (ESI+): Calculated for C10H12N2O4Na ([M+Na]+): 247.0695, found: 247.0695. 1-Chloro-4-(1,3-dinitropropan-2-yl)benzene (1c): Reaction was performed at 110 °C for 12 h.

Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 5-15% EtOAc/ pet ether) afforded a red oil. This was subjected to crystallization (DCM-pentane 1:3) to get pure 1c as an off-white crystalline solid (2.450 g, 10.0 mmol; 47% yield). Rf = 0.10 (10% EtOAc in pet ether);

Melting point = 79 °C; FT-IR (KBr): ν 2920 (m), 1564 (s), 1558 (s), 1382 (s), 825 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.37 (d, J = 8.4 Hz; 2H), 7.17 (d, J = 8.4 Hz; 2H), 4.70-4.81 (m;

(1) R. Ballini, G. Bosica, D. Fiorini and A. Palmieri, Synthesis, 2004, 1938.

1c

NO2

NO2Cl



4H), 4.27-4.34 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 135.2, 132.5, 129.8, 128.7, 76.4, 41.1; HRMS (ESI+): Calculated for C9H9N2O4ClNa ([M + Na]+): 267.0149, found: 267.0151. 1-Bromo-2-(1,3-dinitropropan-2-yl)benzene (1d): Reaction was performed at 110 °C for 6 h.

Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 10-12% EtOAc in pet ether) afforded a red oil. This was subjected to solidification using DCM-pet ether mixture (1:3) to get pure 1d as an off-white solid (650 mg, 2.248 mmol; 28% yield). Rf = 0.30 (20% EtOAc in pet ether);

Melting point = 45 °C; FT-IR (neat): ν 2926 (m), 1560 (s), 1551 (s), 1385(s), 1374 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.64 (dd, J = 1.3, 8.0 Hz; 1H), 7.33 (dt, J = 1.3, 7.6 Hz; 1H), 7.20-7.25 (m; 1H), 7.17-7.19 (m; 1H), 4.87-4.89 (m; 4H), 4.78-4.84 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 134.1, 133.2, 130.4, 128.4, 127.8, 124.3, 75.2, 40.5; HRMS (ESI+): Calculated for C9H9N2O4BrNa ([M + Na]+): 310.9643, found: 310.9646. 1-(1,3-Dinitropropan-2-yl)-2-fluorobenzene (1e): Reaction was performed at 110 °C for 8 h.

Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 10-12% EtOAc/pet ether) afforded 1e as a orange-yellow oil (1.186 g, 5.2 mmol; 42% yield). Rf = 0.40 (20% EtOAc in pet ether); FT-IR (neat): ν 2922 (m), 1557 (s), 1494 (m), 1433 (m), 1378 (s) cm−1; 1H-NMR (400 MHz, CDCl3):

δ 7.31-7.37 (m; 1H), 7.20-7.25 (m; 1H), 7.08-7.16 (m; 2H), 4.77-4.87 (m; 4H), 4.46-4.53 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 160.6 (d, J = 247 Hz), 130.8 (d, J = 8 Hz), 129.8 (d, J = 4 Hz), 125.0 (d, J = 3 Hz), 121.1 (d, J = 13 Hz), 116.3 (d, J = 22 Hz), 75.1 (d, J = 3 Hz), 37.4. 2,4-Dichloro-1-(1,3-dinitropropan-2-yl)benzene (1f): Reaction was performed at 110 °C for 6

h. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 10-12% EtOAc/pet ether) afforded a orange-yellow oil. This was subjected to solidification using a chloroform-pet ether mixture (1:3) to obtain 1f as an off-white solid (470 mg, 1.68 mmol; 20% yield). Rf = 0.30 (20%

EtOAc in pet ether); Melting point = 95 °C; FT-IR (KBr): ν 2925 (m), 1571 (s), 1382 (s), 1102 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.49 (d, J = 2.1 Hz; 1H), 7.29 (dd, J = 2.1, 8.4 Hz; 1H), 7.15 (d, J = 8.4 Hz; 1H), 4.87-4.90 (m; 4H), 4.69-4.78 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 135.8, 134.5, 130.7, 130.1, 129.1, 128.2, 74.9, 38.1. 1-(1,3-Dinitropropan-2-yl)naphthalene (1h): Reaction was performed at 110 °C for 6 h.

Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 10-12% EtOAc/pet ether) afforded a red oil. This was subjected to solidification with EtOAc-toluene-pentane (3:3:4) mixture to obtain pure 1h as

1d

NO2

NO2

Br



an off-white amorphous solid (526 mg, 2.0 mmol; 20% yield). Rf = 0.55 (25% EtOAc in pet ether); Melting point = 86 °C; FT-IR (neat): ν 2924 (w), 1569 (s), 1550 (s), 1387 (m), 1372 (m), 805(m), 784 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 8.10-8.13 (m; 1H), 7.89-7.91 (m; 1H), 7.84-7.86 (m; 1H), 7.63-7.67 (m; 1H), 7.55-7.59 (m; 1H), 7.42-7.46 (m; 1H), 7.31-7.33 (m; 1H), 5.22-5.29 (m; 1H), 4.87-4.96 (m; 4H); 13C-NMR (100 MHz, CDCl3): δ 134.2, 130.6, 129.9, 129.7, 129.5, 127.6, 126.5, 125.2, 123.8, 121.5, 76.2, 36.2; HRMS (ESI+): Calculated for C13H12N2O4Na ([M + Na]+): 283.0695, found: 283.0697. 5-(1,3-Dinitropropan-2-yl)benzo[d][1,3]dioxole (1i): Reaction was performed at 110 °C for 5

h. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 10-25% EtOAc/pet ether) afforded a orange colored solid. It was re-crystallized from a DCM-pet ether mixture to obtain pure 1i as a white flaky solid (603 mg, 2.370 mmol; 35% yield). Rf = 0.20 (20% EtOAc in pet ether);

Melting point = 89 °C; FT-IR (KBr): ν 2921 (m), 1560 (s), 1547 (s), 1443 (m), 1382 (s), 1257 (s), 1045 (m), 641 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 6.73-6.83 (m; 1H), 6.59-6.72 (m; 2H), 5.89-6.02 (m; 2H), 4.60-4.79 (m; 4H), 4.15-4.30 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 148.4, 148.1, 127.4, 120.9, 109.0, 107.4, 101.5, 76.8, 41.5; HRMS (ESI+): Calculated for C10H10N2O6Na ([M + Na]+): 277.0437, found: 277.0438. 2-(1,3-Dinitropropan-2-yl)furan (1j): Reaction was performed at 100 °C for 12 h. Furfural

used was purified by distillation prior to its use. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 2-7% EtOAc/pet ether) afforded 1j as a grey oil (2.082 g, 10.404 mmol; 51% yield). Rf = 0.35 (10% EtOAc in pet ether); FT-IR (neat): ν 2922 (w), 1560 (s), 1506 (s), 1431 (s), 1376 (s), 1348 (s)

cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.38-7.40 (m; 1H), 6.34-6.35 (m; 1H), 6.28-6.29 (m; 1H), 4.76-4.85 (m; 4H), 4.41-4.48 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 147.1, 143.4, 110.8, 108.8, 74.5, 35.8; HRMS (ESI+): Calculated for C7H8N2O5Na ([M + Na]+): 223.0331, found: 223.0324. 2-(1,3-Dinitropropan-2-yl)thiophene (1k): Reaction was performed at 110 °C for 7 h.

Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 5-8% EtOAc/pet ether) afforded 1k as a grey semi-solid. (351 mg, 1.620 mmol; 31% yield). Rf = 0.20 (10% EtOAc in pet ether); FT-IR (neat): ν 2921 (w), 1557 (s), 1428 (m), 1377 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.30-7.32 (m;

1H), 6.97-7.01 (m; 2H), 4.76-4.86 (m; 4H), 4.59-4.67 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 135.9, 127.6, 126.7, 126.1, 76.9, 37.1.

1i

NO2

NO2

O

O



3-(1,3-Dinitropropan-2-yl)-1H-indole (1l): Reaction was performed at 100 °C for 12 h. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 10-25% EtOAc/pet ether) afforded pure 1l as a light brown solid (375 mg, 1.505 mmol; 36% yield). Rf = 0.20 (30% EtOAc in pet ether); Melting point = 104 °C; FT-IR (KBr): ν 3431 (br), 2916 (w), 1560 (s), 1547 (s), 1379

(m), 763 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 8.22 (bs; 1H), 7.58 (d, J = 7.9 Hz; 1H), 7.40 (d, J = 8.1 Hz; 1H), 7.25-7.29 (m; 1H), 7.18-7.22 (m; 1H), 7.11-7.12 (m; 1H), 4.85-4.94 (m; 4H), 4.61-4.68 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 136.2, 125.2, 123.2, 122.3, 120.6, 117.8, 111.8, 108.7, 76.3, 34.2; HRMS (ESI+): Calculated for C11H11N3O4Na ([M + Na]+): 272.0647, found: 272.0650. (1,3-Dinitropropan-2-yl)cyclohexane (1m): Reaction was performed at 110 °C for 6 h.

Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 2-5% EtOAc/pet ether) afforded pure 1m as a orange-yellow semi-solid (1.064 g, 4.920 mmol; 37% yield). Rf = 0.25 (5% EtOAc in pet ether); FT-IR (neat): ν 2929 (s), 2856 (s), 1557 (s), 1434 (m), 1379 (s) cm−1; 1H-NMR (400

MHz, CDCl3): δ 4.52-4.61 (m; 4H), 2.83-2.91 (m; 1H), 1.68-1.82 (m; 5H), 1.48-1.57 (m; 1H), 0.99-1.31 (m; 5H); 13C-NMR (100 MHz, CDCl3): δ 74.5, 41.0, 37.6, 29.4, 25.9, 25.7; HRMS (ESI+): Calculated for C9H16N2O4Na ([M + Na]+): 239.1008, found: 239.1002. 1-Nitro-2-(nitromethyl)heptane (1n): Reaction was performed at 95 °C for 10 h. Purification

by silica gel (230-400 mesh) column chromatography (gradient elution: 2-5% EtOAc/pet ether) afforded pure 1n as a yellow oil (1.031 g, 5.053 mmol; 31% yield). Rf = 0.60 (20% EtOAc in pet ether); FT-IR (neat): ν 2958 (s), 2933 (s), 2863 (m), 1558 (s), 1432 (m), 1381 (s) cm−1; 1H-NMR (400 MHz,

CDCl3): δ 4.50-4.63 (m; 4H), 2.87-2.97 (m; 1H), 1.37-1.51 (m; 4H), 1.25-1.34 (m; 4H), 0.87-0.91 (m; 3H); 13C-NMR (100 MHz, CDCl3): δ 75.9, 35.8, 31.2, 28.8, 25.7, 22.1, 13.7; HRMS (ESI+): Calculated for C8H16N2O4Na ([M + Na]+): 227.1008, found: 227.1011.

1n

NO2

NO2



Procedure B: For preparation of 1b and 1o following procedure was adapted:

Nitroolefin2 (1.0 equiv.) was dissolved in nitromethane (15.0 equiv.) and to it basic alumina (0.5 g/mmol of the nitroolefin substrate) was added. The resulting slurry was heated for required amount of time. After complete consumption of the starting material the reaction mixture was cooled to the room temperature. Basic alumina was filtered off and the filtrate was concentrated to obtain, in both the cases, a red oil. This was purified by silica gel (230-400 mesh) column chromatography to obtain the dinitro compounds. (1,3-Dinitropropan-2-yl)benzene (1b): Reaction was performed at 110 °C for 12 h. Purification

by silica gel (230-400 mesh) column chromatography (gradient elution: 10-15% EtOAc/pet ether) afforded pure 1b as a grey semisolid (413 mg, 1.964 mmol; 61% yield). Rf = 0.10 (10% EtOAc in pet ether); FT-IR (neat): ν 1557 (s), 1549 (s), 1374(s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.31-7.36 (m; 3H), 7.18-7.21 (m;

2H), 4.67-4.76 (m; 4H), 4.24-4.31 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 134.2, 129.3, 128.8, 127.3, 76.5, 41.5; HRMS (ESI+): Calculated for C9H10N2O4Na ([M + Na]+): 233.0538, found: 233.0537. (E)-(4-Nitro-3-(nitromethyl)but-1-enyl)benzene (1o): Reaction was performed at 65 °C for 3

h. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 10-15% EtOAc/pet ether) afforded a thick grey oil which was subjected to crystallization using DCM-pet ether-pentane (1:2:2) mixture to obtained pure 1o as a light brown needle shaped crystalline solid (181 mg,

0.766 mmol; 30% yield). Rf = 0.15 (15% EtOAc in pet ether); Melting point = 50 °C; FT-IR (neat): ν 2919(w), 1698 (m), 1526 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.23-7.35 (m; 5H), 6.62 (d, J = 15.8 Hz; 1H), 5.96 (dd, J = 8.7, 15.8 Hz; 1H), 4.54-4.64 (m; 4H), 3.74-3.83 (m; 1H); 13C-NMR (100 MHz, CDCl3): δ 136.1, 135.2, 128.6, 128.5, 126.5, 121.0, 76.0, 39.6; HRMS (ESI+): Calculated for C11H12N2O4Na ([M + Na]+): 259.0695, found: 259.0695.

(2) For preparation of the corresponding nitro-olefins, see: C. B. Tripathi, S. Kayal, S. Mukherjee, Org. Lett., 2012, 14, 3296.



Synthesis of (2-(1,3-dinitropropan-2-yl)phenyl)methanol 1g:

(S2): In an oven-dried round bottom flask fitted with a magnetic stir bar aldehyde S13 (2.4 g, 9.58 mmol, 1.0 equiv.) was dissolved in 6 mL nitromethane. To this solution basic alumina (4.0 g) and activated 4Å MS (2.0 g) was added. The resulting slurry was heated at reflux at 110 °C for 12 h. in an argon atmosphere. After completion of the reaction, the resulting red slurry was allowed to attain room

temperature. The alumina was then filtered off and the filtrate was concentrated to obtain a thick oil. This was purified by silica gel (230-400 mesh) column chromatography (gradient elution: 2-5% EtOAC/pet ether) as eluent to obtain S2 as a yellow solid (2.256 g, 6.365 mmol; 67% yield). Rf = 0.90 (25% EtOAc in pet ether); 1H-NMR (400 MHz, CDCl3): δ 7.25-7.35 (m; 3H), 7.16-7.18 (m; 1H), 4.77-4.87 (m; 7H), 0.91 (s; 9H), 0.13 (s; 6H); 13C-NMR (100 MHz, CDCl3): δ 139.2, 133.5, 129.9, 128.7, 128.6, 125.9, 76.5, 64.6, 36.6, 25.8, 18.3, –5.4. (1g): S4 (500 mg, 1.41 mmol, 1.0 equiv.) was taken in a round bottom flask and to it a mixture

of glacial AcOH (2.0 mL) and H2O (1.0 mL) was added at r.t. overnight. The resulting clear yellow color solution was diluted with DCM (35 mL) and washed with sat. aq. NaHCO3 solution (10 mL) and brine (10 mL). The organic layer was dried over anh. Na2SO4 and concentrated to obtain a thick semisolid.

This was then purified by silica gel (230-400 mesh) column chromatography (25% EtOAC/pet ether) afforded pure 1g as a off-white solid (315 mg, 1.310 mmol; 93% yield). Rf = 0.15 (25% EtOAc in pet ether); Melting point = 83-84 °C; FT-IR (KBr): ν 3368 (bs), 2920 (w), 1563 (s), 1428 (w), 1380 (m), 1203 (w), 1004 (m), 981 (w), 772 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.29-7.37 (m; 3H), 7.18-7.20 (m; 1H), 4.77-4.89 (m; 7H), 2.09 (bs; 1H); 13C-NMR (100 MHz, CDCl3): δ 138.8, 133.8, 130.5, 129.2, 128.9, 126.0, 76.7, 64.0, 36.8; HRMS (ESI+): Calculated for C10H12N2O5Na ([M + Na]+): 263.0644, found: 263.0641. (3) C. Aïssa and A. Fürstner, J. Am. Chem. Soc., 2007, 129, 14836.

1g

NO2

NO2

HO



Representative procedure for the preparation of allylic alcohols:

(S3): Aldehyde (1.0 equiv.) and ethyl acrylate (3-4 equiv.) was taken in a round bottom flask fitted with a magnetic stir bar. To this neat mixture, was added required amount of DABCO (1.0 equiv.) and the resulting slurry was stirred under ambient condition. After stirring vigorously for the specified time, the reaction mixture was diluted with DCM. This solution was then washed with 4 N aqueous HCl followed by saturated aqueous NaHCO3 solution and brine. The organic layer, after drying over anh. Na2SO4, was concentrated in rotary evaporator to get a thick oil that was purified by silica gel (230-400) column chromatography. Ethyl 2-(hydroxy(phenyl)methyl)acrylate (S3a): Reaction time = 3 d. Purification by silica gel

(230-400 mesh) column chromatography (50% EtOAc/pet ether) afforded pure S3a as a colorless oil (3.65 g, 17.697 mmol; 31% yield). Rf = 0.40 (20% EtOAc in pet ether); FT-IR (neat): ν 3447 (brs), 2982 (m), 1717 (s), 1708 (s), 1628 (m), 1271 (m), 1147 (s), 1038 (s), 1025 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.29-7.36 (m; 4H), 7.23-7.27 (m; 1H), 6.31-6.32 (m; 1H), 5.81-5.82 (m; 1H), 5.51-5.53 (m; 1H),

4.12 (t, J = 7.1 Hz; 2H), 3.33 (bs; 1H), 1.21 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.2, 142.2, 141.3, 128.2, 127.6, 126.5, 125.6, 73.0, 60.8, 13.9.

Ethyl 2-(hydroxy(o-tolyl)methyl)acrylate (S3b): Reaction time = 9 days. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 10-15% EtOAc /pet ether) afforded pure S3b as a colorless oil (1.476 g, 6.701 mmol; 52% yield). Rf = 0.25 (15% EtOAc in pet ether); FT-IR (neat): ν 3430 (brs), 2982 (m), 1714 (s), 1634 (s), 1267 (s), 1147 (s), 1031 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.37-7.40 (m; 1H), 7.17-7.22 (m; 2H), 7.13-7.16 (m; 1H), 6.31 (s; 1H), 5.78 (d, J = 3.4

Hz; 1H), 5.59-5.61 (m; 1H), 4.14-4.22 (m; 2H), 3.00-3.02 (m; 1H), 2.32 (s; 3H), 1.24 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.6, 141.9, 138.8, 135.6, 130.3, 127.7, 126.2, 126.1, 125.8, 69.2, 60.9, 19.0, 14.0.

Ethyl 2-((2-fluorophenyl)(hydroxy)methyl)acrylate (S3c): Reaction time = 48 h. Purification by silica gel (230-400 mesh) column chromatography (10% EtOAc/pet ether) afforded pure S3c as a colorless oil (2.87 g, 12.799 mmol; 89% yield). Rf = 0.15 (10% EtOAc in pet ether); FT-IR (neat): ν 3448 (brs), 2984 (m), 1717 (s), 1631 (s), 1490 (s), 1456 (s), 1270 (s), 1151 (s), 1033 (s) cm−1; 1H-NMR (400 MHz,

S3cCO2Et

OH

F



CDCl3): δ 7.42 (t, J = 7.4 Hz; 1H), 7.21-7.27 (m; 1H), 7.11 (t, J = 7.4 Hz; 1H), 6.97-7.02 (m; 1H), 6.32 (s; 1H), 5.86 (s; 1H), 5.77 (s; 1H), 4.15 (t, J = 7.1 Hz; 2H), 3.63 (bs; 1H), ), 1.22 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.1, 159.8 (d, J = 248 Hz), 141.1, 129.2 (d, J = 8 Hz), 128.2 (d, J = 13 Hz), 128.0 (d, J = 4 Hz), 125.8, 124.0 (d, J = 3 Hz), 115.1 (d, J = 22 Hz), 66.5, 60.9, 13.8; HRMS (ESI+): Calculated for C12H13O3FNa ([M + Na]+): 247.0746, found: 247.0750.

Ethyl 2-(hydroxy(4-(trifluoromethyl)phenyl)methyl)acrylate (S3d): Reaction time = 24 h. Purification by silica gel (230-400 mesh) column chromatography (30% EtOAc/pet ether) afforded pure S3d as a colorless oil (1.897 g, 6.917 mmol; quantitative yield). Rf = 0.25 (20% EtOAc in pet ether); FT-IR (neat): ν 3451 (brs), 2986 (m), 2938 (w), 1713 (s), 1700 (s), 1326 (s), 1164 (s), 1126 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.56 (d, J = 8.2 Hz; 2H), 7.46 (d, J = 8.2 Hz; 2H), 6.34 (s; 1H), 5.85 (s; 1H), 5.55 (d, J = 5 Hz; 1H), 4.11 (q, J = 7.2 Hz; 2H), 3.84-3.88 (m; 1H), 1.20 (t, J = 7.2 Hz; 3H);

13C-NMR (100 MHz, CDCl3): δ 166.0, 145.5, 141.7, 129.7 (q, J = 32 Hz), 126.9, 126.1, 125.1 (q, J = 4 Hz), 124.0 (q, J = 272 Hz), 72.3, 61.0, 13.7; HRMS (ESI+): Calculated for C13H13O3F3Na ([M + Na]+): 297.0714, found: 297.0717.

Ethyl 2-(hydroxy(naphthalen-2-yl)methyl)acrylate (S3e): Reaction time = 5 days. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 8-10% EtOAc in pet ether) afforded pure S3e as a colorless oil (863 mg, 3.367 mmol; 44% yield). Rf = 0.10 (10% EtOAc in pet ether); FT-IR (neat): ν 3442 (brs), 2982 (m), 1714 (s), 1633 (s), 1269 (s), 1149 (s), 1037 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.75-7.81 (m; 4H), 7.41-7.45 (m; 3H), 6.33 (s; 1H), 5.84 (s; 1H), 5.67 (d, J= 4.9 Hz; 1H), 4.09 (q, J= 7.1 Hz; 2H), 3.41-3.45 (m; 1H), 1.17 (t, J= 7.1 Hz; 3H);

13C-NMR (100 MHz, CDCl3): δ 166.2, 142.1, 138.7, 133.1, 132.9, 128.0, 127.98, 127.5, 126.0, 125.9, 125.8, 125.5, 124.6, 73.1, 60.8, 13.9. Ethyl 3-hydroxy-2-methylenepentanoate (S3f): Reaction time = 20 days. Purification by silica

gel (230-400 mesh) column chromatography (gradient elution: 5-10% EtOAc/pet ether) afforded pure S3f as a colorless oil (2.3 g, 17.673 mmol; 34% yield). Rf = 0.10 (8% EtOAc in pet ether); FT-IR (neat): ν 3443 (brs), 2977 (s), 2938 (s), 2879 (m), 1712 (s), 1632 (s), 1274 (s), 1176 (s), 1160 (s), 1101 (s) cm−1; 1H-NMR (400 MHz,

CDCl3): δ 6.23 (s; 1H), 5.79 (s; 1H), 4.31-4.37 (m; 1H), 4.23 (q, J = 7.1 Hz; 2H), 2.99-3.00 (m; 1H), 1.58-1.77 (m; 2H), 1.31 (t, J = 7.1 Hz; 3H), 0.94 (t, J = 7.4 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.5, 142.5, 124.6, 72.6, 60.6, 29.0, 13.96, 9.9; HRMS (ESI+): Calculated for C8H14O3Na ([M + Na]+): 181.0841, found: 181.0840.

S3dCO2Et

OH

CF3

S3e

CO2EtOH



Preparation of ethyl 2-(hydroxymethyl)acrylate S3g:

In a round bottom flask, phosphonate ester4 (2.0 g, 8.92 mmol, 1.0 equiv.) was taken along with formalin solution (2.67 mL, 97.4 mmol, 11.0 equiv.). To this mixture saturated K2CO3 solution (4.0 mL) was added dropwise while stirring. After the addition was complete the reaction mixture was stirred at the ambient condition for 4 h. It was then extracted with diethyl ether (50 mL). The organic layer was dried over anh. Na2SO4, concentrated in a rotary evaporator to obtained an oil. The resulting oil was purified by silica gel column chromatography (gradient elution: 10-15% EtOAc/pet ether) to afford pure S3g as a colorless oil (520 mg, 3.995 mmol; 43% yield). Rf = 0.25 (20% EtOAc in pet ether); FT-IR (neat): ν 3432 (brs), 2984 (m), 1712 (s), 1638 (m), 1307 (s), 1217 (s), 1177 (s), 1157 (s), 1057 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 6.26 (s; 1H), 5.84 (d, J = 1.4 Hz; 1H), 4.33 (s; 2H), 4.24 (q, J = 7.1 Hz; 2H), 1.32 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.3, 139.5, 125.3, 62.1, 60.8, 14.0; HRMS (ESI+): Calculated for C6H10O3Na ([M + Na]+): 153.0528, found: 153.0523. Preparation of Boc carbonate of allylic alcohols:

Allylic alcohol S3 (1.0 equiv.) was dissolved in DCM (0.6 mL/mmol of S3) in a round bottom flask containing a magnetic stir bar. To this solution, was added Boc2O (1.1 equiv.) as a DCM (0.6 mL/mmol of S3) solution. The resulting solution was cooled to 0 °C. To this well stirred solution was added DMAP (10 mol%) in one portion. The reaction mixture was allowed to attain room temperature and further stirred for the specified time. The reaction mixture was diluted with CH2Cl2. The combined organic layer was washed with 4 N aq. HCl solution followed by saturated aq. NaHCO3 and brine. The organic layer, after drying over anhydrous Na2SO4, was concentrated in rotary evaporator to obtain an oil that was purified by silica gel (230-400) column chromatography.

(4) A. R. Choudhury and S. Mukherjee, Adv. Synth. Catal., 2013, 355, 1989.



Ethyl 2-((tert-butoxycarbonyloxy)(phenyl)methyl)acrylate (2a): Reaction time = 6 h. Purification by silica gel (230-400 mesh) column chromatography (1% EtOAc in pet) afforded pure 2a as a colorless liquid which solidifies on standing in freezer to produce a white semisolid (5.013 g, 16.360 mmol; 96% yield). Rf = 0.40 (10% EtOAc in pet ether); FT-IR (neat): ν 2985 (m), 1745 (s), 1713 (s), 1297 (s), 1277 (s), 1250 (s), 1153 (s), 1081 (m), 880 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ

7.37-7.41 (m; 3H), 7.29-7.35 (m; 3H), 6.48 (s; 1H), 6.40 (s; 1H), 5.88-5.89 (s; 1H), 4.09-4.21 (m; 2H), 1.46 (s; 9H), 1.22 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 164.9, 152.4, 139.8, 137.5, 128.4, 127.6, 125.5, 82.5, 75.8, 60.9, 27.7, 13.9; HRMS (ESI+): Calculated for C17H22O5Na ([M + Na]+): 329.1365, found: 329.1360. Ethyl 2-((tert-butoxycarbonyloxy)(o-tolyl)methyl)acrylate (2b): Reaction time = 9 h.

Purification by silica gel (230-400 mesh) column chromatography (2% EtOAc in pet) afforded pure 2b as a colorless oil (595 mg, 1.857 mmol; 59% yield). Rf = 0.30 (6% EtOAc in pet ether); FT-IR (neat): ν 2981 (m), 2936 (w), 1745 (s), 1727 (s), 1635 (w), 1278 (s), 1254 (s), 1158 (m), 1083 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.29-7.32 (m; 1H), 7.15-7.22 (m; 3H), 6.73 (s; 1H), 6.42 (s; 1H), 5.70

(s; 1H), 4.17 (q, J = 7.1 Hz; 2H); 2.40 (s; 3H), 1.46 (s; 9H), 1.22 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 165.1, 152.5, 139.3, 136.3, 135.5, 130.5, 128.3, 126.96, 126.6, 82.4, 72.7, 60.9, 27.7, 19.1, 14.0; HRMS (ESI+): Calculated for C18H24O5Na ([M + Na]+): 343.1521, found: 343.1526.

Ethyl 2-((tert-butoxycarbonyloxy)(2-fluorophenyl)methyl)acrylate (2c): Reaction time = 8 h. Purification by silica gel (230-400 mesh) column chromatography (2-4% EtOAc in pet) afforded pure 2c as a yellow oil (995 mg, 3.067 mmol; 77% yield). Rf = 0.10 (3% EtOAc in pet ether); FT-IR (neat): ν 2983 (m), 2937 (w), 1749 (s), 1730 (s), 1618 (w), 1275 (s), 1256 (s), 1233 (m), 1157 (s) , 1083 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.33-7.38 (m; 1H), 7.27-7.31 (m; 1H), 7.10-7.15 (m; 1H), 7.02-

7.08 (m; 1H), 6.79 (s; 1H), 6.45-6.48 (m; 1H), 5.85-5.87 (m; 1H), 4.13-4.20 (m; 2H), 1.46-1.48 (m; 9H), 1.20-1.25 (m; 3H); 13C-NMR (100 MHz, CDCl3): δ 164.5, 160.2 (d, J = 249 Hz), 152.1, 138.5, 130.1 (d, J = 8 Hz), 128.7 (d, J = 3 Hz), 126.3, 124.8 (d, J = 13 Hz), 124.0 (d, J = 4 Hz), 115.5 (d, J = 22 Hz), 82.6, 69.6 (d, J = 3 Hz), 60.9, 27.6, 13.8; HRMS (ESI+): Calculated for C17H21O5FNa ([M + Na]+): 347.1271, found: 347.1273.

2aCO2Et

OBoc

2bCO2Et

OBoc

Me

2cCO2Et

OBoc

F



Ethyl 2-((tert-butoxycarbonyloxy)(4-(trifluoromethyl)phenyl)methyl)acrylate (2d): Reaction time = 8 h. Purification by silica gel (230-400 mesh) column chromatography (2% EtOAc in pet ether) afforded pure 2d as a yellow oil that solidified in freezer (987 mg, 2.638 mmol; 66% yield). Rf = 0.20 (3% EtOAc in pet ether); FT-IR (neat): ν 2984 (m), 2936 (w), 1746 (s), 1733 (s), 1622 (w), 1326 (s), 1277 (s), 1255 (s), 1164 (s) , 1128 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.60 (d, J = 8.2 Hz; 2H), 7.53 (d, J = 8.2 Hz; 2H), 6.51 (s; 1H), 6.44 (s; 1H), 5.94 (s;

1H), 4.16 (dq, J = 2.1, 7.1 Hz; 2H), 1.46 (s; 9H), 1.24 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 164.6, 152.2, 141.8, 139.2, 130.4 (q, J = 32 Hz), 127.9, 126.1, 125.3 (q, J = 4 Hz), 123.9 (q, J = 272 Hz), 82.9, 75.0, 61.1, 27.6, 13.9; HRMS (ESI+): Calculated for C18H21F3O5Na ([M + Na]+): 397.1239, found: 397.1238. Ethyl 2-((tert-butoxycarbonyloxy)(naphthalen-2-yl)methyl)acrylate (2e): Reaction time =

12h. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 50-70% DCM/pet ether) afforded pure 2e as a yellow semisolid (451 mg, 1.260 mmol; 56% yield). Rf = 0.30 (6% EtOAc in pet ether); FT-IR (neat): ν 2987 (m), 2928 (m), 1743 (s), 1726 (s), 1629 (w), 1368 (m), 1333 (m), 1276 (s), 1249 (s), 1160 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.88 (bs; 1H), 7.79-7.85 (m; 3H), 7.45-7.51 (m; 3H), 6.65 (s; 1H), 6.45 (s; 1H), 5.96 (s; 1H), 4.12-4.17 (m; 2H),

1.46 (s; 9H), 1.22 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 164.9, 152.4, 139.8, 134.9, 133.2, 133.1, 128.22, 128.19, 127.6, 127.1, 126.3, 126.2, 125.7, 125.2, 82.7, 75.96, 60.98, 27.7, 14.0; HRMS (ESI+): Calculated for C21H24O5Na ([M + Na]+): 379.1521, found: 379.1525.

Ethyl 3-(tert-butoxycarbonyloxy)-2-methylenepentanoate (2f): Reaction time = 6 h. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: 2-5% EtOAc in pet ether) afforded pure 2f as a colorless oil (815 mg, 3.155 mmol; 38% yield). Rf = 0.50 (4% EtOAc in pet ether); FT-IR (neat): ν 2980 (s), 2939 (m), 1746 (s), 1731 (s), 1716 (s), 1626 (w), 1370 (m), 1278 (s), 1255 (s),

1167 (s), 1094 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 6.31 (s; 1H), 5.82 (s; 1H), 5.38-5.41 (m; 1H), 4.20-4.26 (m; 2H), 1.47-1.49 (m; 11H), 1.31 (t, J = 7.1 Hz; 3H), 0.94 (t, J = 7.4 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 165.2, 152.7, 140.2, 124.7, 82.0, 75.5, 60.8, 27.8, 27.7, 27.4, 14.0, 9.5; HRMS (ESI+): Calculated for C13H22O5Na + ([M + Na]+): 281.1365, found: 281.1379.

2dCO2Et

OBoc

CF3



Ethyl 2-((tert-butoxycarbonyloxy)methyl)acrylate (2g): Rection time = 5h. Purification by silica gel (230-400 mesh) column chromatography (2% EtOAc in pet ether) afforded pure 2g as a colorless oil (1.214 g, 5.270 mmol; 69% yield). Rf = 0.50 (10% EtOAc in pet ether). FT-IR (neat): ν 2919 (m), 2852 (w), 1743 (s), 1612 (s),

1448 (m), 1278 (s), 1258 (s), 1159 (s), 1103 (s), 1018 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 6.37 (s; 1H), 5.87 (s; 1H), 4.80 (s; 2H), 4.24 (q, J = 7.1 Hz; 2H), 1.49 (s; 9H), 1.31 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 165.0, 153.0, 135.3, 127.2, 82.4, 64.7, 60.9, 27.7, 14.1; HRMS (ESI+): Calculated for C11H18O5Na ([M + Na]+): 253.1052, found: 253.1054. Preparation of Catalysts:

The 9-amino(9-deoxy)epicinchonidine S5,2 9-amino(9-deoxy)dihydroepicinchonidine S6,5 and 9-amino(9-deoxy)epicinchonine6 S7 were prepared according to the literature procedures. Catalysts I,2 III,6 IV,7 V,5 VIII,8 IX9 were prepared by following literature procedures.2,5,6, The procedure of preparing catalysts II, VI and VII are mentioned below: Catalyst II:

A solution of 4-(trifluoromethyl)phenyl isothiocyanate (316.0 mg, 1.554 mmol, 1.2 equiv.) in THF (2.0 mL) was added slowly to the solution of S5 (380.0 mg, 1.295 mmol, 1.0 equiv.) in THF (2.0 mL) in a 25 mL round bottom flask at room temperature and stirred at room temperature for 18 h. The reaction mixture was then concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (230-400 mesh silica gel; gradient elution: 99:1 DCM-MeOH to 100:0.5:0.5 DCM-MeOH-Et3N to 100:1.0:0.5 DCM-MeOH-Et3N) to afford a white amorphous solid (419 mg, 0.843 mmol; 65% yield). Melting point = 122-123 °C; FT-IR (thin film): 2929 (m), 1611 (m), 1323 (s); 1H-NMR (400 MHz, CD3OD): δ 8.83 (d, J = 4.6 Hz, 1H), 8.71 (d, J = 8.5 Hz, 1H), 8.07 (d, J = 8.5 Hz, 1H), 7.79 (t, J = 7.2 Hz, 1H), 7.74-

(5) C. B. Tripathi, S. Mukherjee, Angew. Chem., Int. Ed., 2013, 52, 8450. (6) M. S. Manna, V. Kumar, S. Mukherjee, Chem. Commun., 2012, 48, 5193. (7) R. Miyaji, K. Asano and S. Matsubara, Org. Lett., 2013, 15, 3658. (8) W. Yang and D.-M. Du., Org. Lett., 2010, 12, 5450. (9) A. Berkessel, S. Mukherjee, T. N. Müller, F. Cleemann, K. Roland, M. Brandenburg, J.-M. Neudörfl and J. Lex, Org. Biomol. Chem., 2006, 4, 4319.

2gCO2Et

OBoc



7.65 (m, 3H), 7.63 (d, J = 4.7 Hz, 1 H), 7.55 (d, J = 8.6 Hz, 2 H), 6.24-6.19 (m, 1 H), 5.85-5.71 (m, 1H), 5.03-4.95 (m, 2H), 3.46-3.19 (m, 4H), 2.89-2.73 (m, 2H), 2.39-2.26 (m, 1H), 1.79-1.54 (m, 3H), 1.36-1.22 (m, 2H), 1.00-0.84 (m, 1H); 13C-NMR (100 MHz, CD3OD): δ 182.1, 150.9, 150.0, 148.9, 144.2, 142.5, 130.9, 129.8, 128.0, 126.7 (q, J = 4.0 Hz), 125.9, 125.7 (q, J = 270.0 Hz), 123.4, 115.0, 61.9, 56.5, 42.4, 40.7, 28.8, 28.5, 26.5; HRMS (ESI+): Calculated for C27H28F3N4S ([M+H]+): 497.1987, Found: 497.1986; Optical rotation: [α]D

26 –132.4 (c = 1.0, CHCl3). Catalyst VI:

NH

NHN

NH

S

CF3THFr.t., 24 h

NH

NH2

NS6

F3C

NCS

VI

Dihydrocinchonidine amine S6 (210 mg, 0.71 mol, 1.0 equiv.) was taken in a 10 mL oven dried round bottom flask having an argon inlet and dissolved in dry THF (2 mL). A solution of the 4-(trifluoromethyl)phenyl isothiocyanate in THF (0.8 mL) was added dropwise to this solution. The resulting mixture was stirred at the room temperature for 24 h. Solvent was then evaporated and the resulting residue was purified by silica gel (230-400 mesh) column chromatography (gradient elution: 99:1 DCM-MeOH to 100:0.5:0.5 DCM-MeOH-Et3N to 100:1.0:0.5 DCM-MeOH-Et3N) to obtain VI as a off-white solid (244 mg, 0.227 mmol; 32% yield). Melting point = 80-81 °C; FT-IR (thin film): 2932 (m), 1509 (m), 1384 (s), 1277 (s); 1H-NMR (400 MHz, CD3OD): δ 8.93 (d, J = 4.6 Hz; 1H), 8.78 (d, J = 8.5 Hz; 1H), 8.09 (d, J = 8.5 Hz; 1H), 7.81-7.85 (m; 2H), 7.70-7.76 (m; 3H), 7.52 (d, J = 8.5 Hz; 1H), 6.92 (d, J = 10.8 Hz; 1 H), 4.21-4.29 (m; 2H), 3.58-3.64 (m; 1H), 3.16-3.27 (m; 1H), 3.03-3.07 (m; 1H), 1.87-1.89 (m; 1H), 1.65-1.72 (m; 1H), 1.37-1.49 (m; 2H), 1.25-1.29 (m; 3H), 0.87 (t, J = 7.2 Hz, 3H); 13C-NMR (100 MHz, CD3OD): δ 182.6, 151.3, 149.3, 146.2, 143.9, 131.5, 130.2 128.9, 128.2, 127.4, 127.0, 126.6 (q, J = 3.7 Hz), 125.9, 125.6 (q, J = 271.0 Hz), 123.9, 117.6, 61.7, 58.1, 42.6, 38.2, 29.0, 28.2, 26.3, 26.2, 12.2; HRMS (ESI+): Calculated for C27H30F3N4S ([M+H]+): 499.2143, Found: 499.2149. Optical rotation: [α]D

25 –74.4 (c = 1.0, CHCl3).



Catalyst VII :

THFr.t., 24 h

F3C

NCS

S7 VII

N

HN

N

N

S

H

HN

HN

NH2

F3C

9-Amino(9-deoxy)epicinchonine S7 (257 mg, 0.875 mol, 1.0 equiv.) was taken in 10 mL oven dried round bottom flask fitted with an argon inlet. This was dissolved in 2 mL dry THF and a solution of the isothiocyanate in 1.5 mL THF was added dropwise. The resulting solution was stirred at the room temperature for 24 h. Solvent was then evaporated and the resulting residue was purified by silica gel (230-400 mesh) column chromatography (gradient elution: 99:1 DCM-MeOH to 100:0.5:0.5 DCM-MeOH-Et3N to 100:1.0:0.5 DCM-MeOH-Et3N) to obtain VII as a white amorphous solid (170 mg, 0.341 mmol; 39% yield). Melting point = 156-157 °C; FT-IR (neat): ν 3422 (brs), 2933 (m), 2867 (w), 1645 (s), 1523 (m), 1322 (s), 1119 (s) cm−1; 1H-NMR (400 MHz, CD3OD): δ 8.83 (d, J = 4.6 Hz; 1H), 8.65 (d, J = 8.4 Hz; 1H), 8.05 (d, J = 8.4 Hz; 1H), 7.79 (t, J = 7.4 Hz; 1H), 7.66-7.71 (m; 3H), 7.62 (d, J = 4.7 Hz; 1 H), 7.55 (s; 1H), 7.53 (s; 1H), 6.33-6.36 (m; 1H), 5.90-5.99 (m; 1H), 5.18-5.24 (m; 2H), 3.27-3.39 (m; 1H), 3.01-3.10 (m; 3H), 2.36-2.43 (m; 1H), 1.58-1.64 (m; 3H), 1.23-1.29 (m, 3H), 0.87-0.95 (m, 2H); 13C-NMR (100 MHz, CD3OD): δ 182.4, 150.9, 149.6, 148.9, 144.2, 141.2, 130.99, 129.9, 128.9, 128.0, 126.7 (q, J = 3.9 Hz), 125.9, 125.7 (q, J = 270.0 Hz), 123.5, 115.6, 61.9, 50.1, 49.3, 48.4, 40.1, 28.7, 26.9, 25.9; HRMS (ESI+): Calculated for for C27H28F3N4S ([M+H]+): 497.1987, Found: 497.1983; Optical rotation: [α]D

25 +166.9 (c = 2.0, CHCl3). General procedure for the preparation of racemic desymmetrized products (rac-3):

Racemic products were prepared using the achiral bifunctional catalyst S8.10

In a glass vial fitted with a magnetic stir bar, 10 mg activated 4Å MS was taken along with 1,3-dinitropropane 1 (0.02 mmol, 1.0 equiv.) and the catalyst S8 (0.70 mg, 0.002 mmol, 0.1 equiv.).These three components were mixed properly through stirring. A solution of allylic carbonate 2 (0.022 mmol, 1.1 equiv.) in 0.1 mL CH2Cl2 was added to it; the glass vial was

(10) S. M. Opalka, J. L. Steinbacher, B. A. Lambiris and D. T. McQuade, J. Org. Chem., 2011, 76, 6503.



purged with argon and was sealed. The resulting mixture was then stirred at 25 °C until complete conversion (followed by TLC). The reaction mixture was then filtered using CH2Cl2 (2 mL) and the filtrate was concentrated. The crude mixture was purified by preparative TLC (Merck silica gel 60 F254 pre-coated plates of 0.25 mm thickness) to obtain the racemic desymmetrized products (ent-3).

Optimization of catalyst and reaction conditions: Catalyst Screening:a-c

a All reactions are carried out using 1.0 equiv. of 1a and 1.1 equiv. of 2a. b Conversion and diastereomeric ratio (dr) determined by 1H-NMR analysis of the crude reaction mixture. c Enantiomeric ratio (er) was determined by HPLC analysis using a stationary phase chiral column. n.d. = not determined.



Best catalysts emerged from the above studies:

Solvent Screening:

Entry Solvent Time (h) Conv. (%) dr er 1 Toluene 40 >95 3.7:1 96.5:3.5 2 o-Xylene 34 >95 3:1 96:4 3 Mesitylene 26 >95 3:1 97:3 4 Chlorobenzene 48 >95 4.8:1 97:3 5 PhCF3 40 >95 7:1 97.5:2.5 6 THF 48 64 3.2:1 96.5:3.5 7 2-MeTHF 48 72 3:1 96.5:3.5 8 TBME 48 >95 3.8:1 97.5:2.5 9 CH2Cl2 14 >95 6.8:1 97:3 10 CHCl3 30 >95 7.8:1 96.5:3.5 11 (CH2Cl)2 40 >95 7.8:1 >97:3 12 Cyclohexane 48 >95 7:1 97:3



Comparison between catalysts II and V: Result with catalyst II:

Solvent Time (h) Conv. (%) dr er PhCF3 40 >95 7:1 97.5:2.5 (CH2Cl)2 40 >95 7.8:1 >97:3

Result with catalyst V:

Solvent Time (h) Conv. (%) dr er PhCF3 24 >95 12:1 95.5:4.5 (CH2Cl)2 24 >95 10:1 95.5:4.5

Optimization of reaction temperature and concentration:

Entry T (°C) x Time (h) Conv. (%) dr er 1 25 0.4 40 >95 7.8:1 >97:3 2 25 0.2 48 66 7:1 97:3 3 25 1.0 8 >95 7.7:1 97:3 4 0 1.0 48 >95 9.5:1 >97.5:2.5 5 –10 2.0 48 >95 10:1 98.5:1.5 6 –20 2.0 60 86 10:1 >98:2



Representative procedure for the catalytic allylic alkylative desymmetrization of prochiral 1,3-dinitropropanes (1) with allylic carbonates (2):

(CH2Cl)2 (2.0 M)4Å MS, -10 °C

R1

NO2

NO2 CO2Et

R2

R1

NO2

NO2 CO2Et

R2

OBoc+II (10 mol%)

1(1.0 equiv.)

2(1.1 equiv.)

3

In a reaction tube fitted with a magnetic stir bar, 100 mg activated 4Å MS was taken along with 1,3-dinitropropane 1 (0.2 mmol, 1.0 equiv.) and the catalyst II (10 mg, 0.02 mmol, 0.1 equiv.) under a postive argon pressure. These three components were mixed properly through stirring and then it was cooled to –78 °C. A solution of allylic carbonate 2 (0.22 mmol, 1.1 equiv.) in 0.1 mL (CH2Cl)2 was added to it. The resulting mixture was then stirred at specified temperature until complete conversion (followed by TLC). The reaction mixture was then diluted with CH2Cl2 (7 mL) at the reaction temperature and molecular sieves were filtered off. The filtrate was washed with 2 N HCl (5 mL) and the organic layer was washed with sat. aq. NaHCO3 (3 mL) and brine (3 mL). The organic layer, after drying over anh. Na2SO4, concentrated to a semisolid which was purified by silica gel (230-400 mesh) column chromatography to obtain the desymmetrized allylic alkylated products 3. (4S,5R,E)-Ethyl 2-benzylidene-4,6-dinitro-5-p-tolylhexanoate (3aa): Purification by silica gel

(230-400 mesh) column chromatography (gradient elution: pet ether to 5% EtOAc in pet ether) afforded 3aa as a colorless thick oil (61 mg, 0.148 mmol; 74% yield). Rf = 0.40 (10% EtOAc in pet ether); FT-IR (neat): ν 2926 (w), 1702 (m), 1557 (s), 1431 (w), 1377 (m), 1263 (m),

1203 (w), 1103 (m), 1021 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.85 (s; 1H), 7.36-7.39 (m; 3H), 7.14-7.16 (m; 4H), 7.05-7.07 (m; 2H), 5.16-5.22 (m; 1H), 4.68 (dd, J = 10.4, 12.9 Hz; 1H), 4.47 (dd, J = 4, 12.9 Hz; 1H), 4.26 (q, J = 7.1 Hz; 2H), 5.89-5.95 (m; 1H), 3.15-3.22 (m; 1H), 2.64-2.68 (m; 1H), 2.32 (s; 3H), 1.34 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.7, 144.0, 138.9, 134.3, 130.5, 130.1, 128.9, 128.7, 128.5, 127.9, 126.5, 87.9, 77.0, 61.4, 46.6, 30.3, 21.1, 14.2; HRMS (ESI+): Calculated for C22H24N2O6Na ([M + Na]+): 435.1532, found: 435.1536; Optical rotation: [α]D

22 –123.8 (c 1.0, CHCl3) for an enantiomerically enriched sample with 98.5:1.5 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/EtOH = 90:10, 1.0 mL min−1, τminor = 11.02 min, τmajor = 11.77 min).

NO2

NO2 CO2Et

Ph

Me3aa



(4R,5S,E)-Ethyl 2-benzylidene-4,6-dinitro-5-p-tolylhexanoate (ent-3aa): Reaction was performed on a 0.2 mmol scale under the identical condition as 3aa using the pseudoenantiomeric catalyst VII. Purification by silica gel (230-400 mesh) column chromatography afforded ent-3aa as a colorless thick oil (50 mg, 0.122 mmol; 61% yield). Optical rotation: [α]D

23 +132.1 (c 1.0, CHCl3) for an enantiomerically enriched sample with >99:1 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/EtOH = 90:10, 1.0 mL min−1, τmajor = 11.03 min, τminor = 11.84 min). (4S,5R,E)-Ethyl 2-benzylidene-4,6-dinitro-5-phenylhexanoate (3ba): Purification by silica gel

(230-400 mesh) column chromatography (gradient elution: pet ether/4% EtOAc in pet ether) afforded pure 3ba as white crystalline solid (59.8 mg, 0.150 mmol; 75% yield). Rf = 0.4 (10% EtOAc in pet ether); Melting point = 125 °C; FT-IR (neat): ν 2926 (w), 1704 (s), 1557 (s), 1435 (w),

1378 (m), 1264 (s), 1203 (m), 1105 (m), 1020 (m), cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.86 (s; 1H), 7.35-7.39 (m; 6H), 7.15-7.26 (m; 4H), 5.19-5.25 (m; 1H), 4.72 (dd, J = 10.5, 12.9 Hz; 1H), 4.49 (dd, J = 3.9, 13.1 Hz; 1H), 4.27 (q, J = 7.1 Hz; 2H), 3.93-3.99 (m; 1H), 3.17-3.23 (m; 1H), 2.63-2.67 (m; 1H), 1.34 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.7, 144.2, 134.3, 133.7, 129.5, 129.1, 128.9, 128.7, 128.5, 128.1, 126.4, 87.8, 76.9, 61.4, 46.9, 30.3, 14.2; HRMS (ESI+): Calculated for C21H22N2O6Na ([M + Na]+): 421.1376, found: 421.1374; Optical rotation: [α]D

22 –117.2 (c 2.0, CHCl3) for an enantiomerically enriched sample with 97:3 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/EtOH = 90:10, 1.0 mL min−1, τminor = 11.64 min, τmajor = 13.35 min). (4S,5R,E)-Ethyl 2-benzylidene-5-(4-chlorophenyl)-4,6-dinitrohexanoate (3ca): Purification

by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/5% EtOAc in pet ether) afforded 3ca as a yellow thick oil (63 mg, 0.145 mmol; 73% yield). Rf = 0.30 (10% EtOAc in pet ether); FT-IR (neat): ν 2983 (w), 2928 (w), 1702 (s), 1636 (w), 1557 (s), 1494 (m),

1445 (w), 1377 (m), 1263 (m), 1099 (m), 1015 (w) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.87 (s; 1H), 7.37-7.40 (m; 3H), 7.33-7.34 (m; 1H), 7.31-7.32 (m; 1H), 7.12-7.16 (m; 3H), 7.10-7.11 (m; 1H), 5.14-5.20 (m; 1H), 4.64-4.70 (m; 1H), 4.49 (dd, J = 4.0, 13.1 Hz; 1H), 4.27 (q, J = 7.1 Hz; 2H), 3.92-3.98 (m; 1H), 3.18 (dd, J = 10.4, 14.6 Hz; 1H), 2.63-2.68 (m; 1H), 1.35 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.6, 144.3, 135.1, 134.2, 132.2, 129.7, 129.4, 129.0, 128.7, 128.4, 126.3, 87.6, 76.6, 61.5, 46.2, 30.2, 14.2; HRMS (ESI+): Calculated for C21H21ClN2O6Na ([M + Na]+): 455.0986, found: 455.0980; Optical rotation: [α]D

23 –103.0 (c 2.0, CHCl3) for an enantiomerically enriched sample with 97.5:2.5 er. Enantiomeric purity was

NO2

NO2 CO2Et

Ph

Cl3ca

NO2

NO2 CO2Et

Ph

3ba



determined by HPLC analysis (Phenomenex Cellulose-1 column, 254 nm, n-Hexane/EtOH = 90:10, 1.0 mL min−1, τmajor = 11.57 min, τminor =15.46 min). (4S,5R,E)-Ethyl 2-benzylidene-5-(2-bromophenyl)-4,6-dinitrohexanoate (3da): Purification by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/5% EtOAc in

pet ether) afforded 3da as a thick yellow thick oil (81 mg, 0.169 mmol; 84% yield). Rf = 0.22 (10% EtOAc in pet ether); FT-IR (neat): ν 2922 (w), 1705 (m), 1556 (s), 1474 (w), 1433 (w), 1376 (m), 1261 (w), 1101 (w), 1025 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.93 (s; 1H), 7.59-7.61 (m;

1H), 7.13-7.38 (m; 8H), 5.22-5.30 (m; 1H), 4.83-4.91 (m; 1H), 4.55-4.62 (m; 2H), 4.27-4.29 (m; 2H), 3.32-3.38 (m; 1H), 2.84-2.87 (m; 1H), 1.33-1.36 (m; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.6, 144.3,134.2, 134.0, 133.4, 130.3, 129.0, 128.8, 128.5, 128.4, 126.2, 87.6, 74.7, 61.5, 44.1, 29.6, 14.2; HRMS (ESI+): Calculated for C21H21N2O6BrNa ([M + Na]+): 499.0481, found: 499.0482; Optical rotation: [α]D

21 –52.7 (c 2.0, CHCl3) for an enantiomerically enriched sample with 98.5:1.5 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/EtOH = 90:10, 1.0 mL min−1, τminor = 9.86 min, τmajor = 13.93 min). (4S,5R,E)-Ethyl 2-benzylidene-5-(2-fluorophenyl)-4,6-dinitrohexanoate (3ea): Purification

by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/4% EtOAc in pet ether) afforded 3ea as a white solid (69 mg, 0.166 mmol; 83% yield). Rf = 0.4 (10% EtOAc in pet ether); Melting point = 97 °C; FT-IR (neat): ν 2925 (m), 1695 (m), 1560 (s), 1550 (s), 1435 (w),

1380 (m), 1368 (m), 1262 (s), 1109 (s), 1020 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.88 (s; 1H), 7.32-7.42 (m; 4H), 7.08-7.21 (m; 5H), 5.29-5.35 (m; 1H), 4.83-4.89 (m; 1H), 4.49 (dd, J = 3.9, 13.3 Hz; 1H), 4.20-4.30 (m; 3H), 3.23 (dd, J = 10.6, 14.5 Hz; 1H), 2.67 (dd, J = 3.7, 14.5 Hz; 1H), 1.34 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.5, 160.7 (d, J = 247 Hz), 144.3, 134.2, 130.0 (d, J = 9 Hz), 130.3 (d, J = 4 Hz), 129.0, 128.7, 128.4, 126.3, 125.1 (d, J = 4 Hz), 120.8 (d, J = 13 Hz), 116.5 (d, J = 22 Hz), 86.6, 75.1, 61.5, 42.1, 30.4, 14.1; HRMS (ESI+): Calculated for C21H21N2O6FNa ([M + Na]+): 439.1281, found: 439.1281; Optical rotation: [α]D

23 –108.9 (c 2.0, CHCl3) for an enantiomerically enriched sample with 98:2 er. Enantiomeric purity was determined by HPLC analysis (Phenomenex Cellulose-1 column, 254 nm, n-Hexane/EtOH = 95:5, 1.0 mL min−1, τmajor = 12.75 min, τminor =14.73 min).

3da

NO2

NO2 CO2Et

PhBr



(4S,5R,E)-Ethyl 2-benzylidene-5-(2,4-dichlorophenyl)-4,6-dinitrohexanoate (3fa): Purification by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/4% EtOAc in pet ether) afforded 3fa as a thick white oil (70.6 mg, 0.151 mmol; 76% yield). Rf = 0.25 (10% EtOAc in pet ether); FT-IR (neat): ν 2924 (m), 1704 (s), 1623 (w), 1558

(s), 1474 (w), 1374 (m), 1262 (m), 1202 (m), 1104 (m), 1020 (w) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.94 (s; 1H), 7.36-7.44 (m; 5H), 7.21-7.26 (m; 2H), 7.10-7.12 (m; 1H), 5.22-5.28 (m; 1H), 4.83-4.89 (m; 1H), 4.51-4.58 (m; 2H), 4.30 (q, J = 7.1 Hz; 2H), 3.31 (dd, J = 9.6, 14.1 Hz; 1H), 2.85 (dd, J = 4.3, 14.1 Hz; 1H), 1.37 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.6, 144.4, 135.5, 135.2, 134.1, 130.5, 130.3, 129.1, 128.8, 128.7, 128.4, 128.2, 126.1, 87.2, 74.4, 61.5, 41.8, 29.7, 14.2; HRMS (ESI+): Calculated for C21H20N2O6Cl2Na ([M + Na]+): 489.0596, found: 489.0596; Optical rotation: [α]D

20 –68.2 (c 2.0, CHCl3) for an enantiomerically enriched sample with 98:2 er. Enantiomeric purity was determined by HPLC analysis (Phenomenex Cellulose-1 column, 254 nm, n-Hexane /EtOH = 90:10, 1.0 mL min−1, τmajor = 10.12 min, τminor = 12.16 min). (4S,5R,E)-Ethyl 2-benzylidene-5-(2-(hydroxymethyl)phenyl)-4,6-dinitrohexanoate (3ga):

Reaction was performed at 5 °C. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/5% EtOAc in pet ether/10% EtOAc in pet ether) afforded pure 3ga as colorless thick oil (62 mg, 0.145 mmol; 73% yield). Rf = 0.25 (20% EtOAc in pet ether); FT-IR

(neat): ν 3460 (br), 2922 (w), 1703 (m), 1633 (w), 1557 (s), 1446 (w), 1378 (m), 1264 (m), 1203 (m), 1099 (m), 1017 (w) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.87 (s; 1H), 7.29-7.38 (m; 6H), 7.19-7.21 (m; 2H), 7.13-7.15 (m; 1H), 5.25-5.31 (m; 1H), 4.48-4.85 (m; 2H), 4.65 (d, J = 12.3 Hz; 1H), 4.53-4.58 (m; 1H), 4.44-4.50 (m; 1H), 4.25 (q, J = 7.1 Hz; 2H), 3.35 (dd, J = 9.8, 14.5 Hz; 1H), 2.73 (dd, J = 4.4, 14.5 Hz; 1H), 2.00 (bs; 1H), 1.34 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.8, 144.0, 139.2, 134.3, 133.4, 130.4, 129.2, 129.0, 128.8, 128.7, 128.6, 126.6, 88.5, 76.6, 63.6, 61.4, 40.8. 30.0, 14.1; HRMS (ESI+): Calculated for C22H24N2O7Na ([M + Na]+): 451.1481, found: 451.1486; Optical rotation: [α]D

22 –73.2 (c 2.0, CHCl3) for an enantiomerically enriched sample with 99:1 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/IPA = 90:10, 1.0 mL min−1, τminor = 20.26 min, τmajor = 21.89 min).



(4S,5R,E)-Ethyl 2-benzylidene-5-(naphthalen-1-yl)-4,6-dinitrohexanoate (3ha): Purification by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/4% EtOAc in pet ether) afforded pure 3ha as thick oil (74 mg, 0.165 mmol; 83% yield). Rf = 0.20 (10% EtOAc in pet ether); FT-IR (neat): ν 2925 (w), 1702 (m), 1628 (w), 1554 (s), 1431 (w), 1376 (m),

1262 (m), 1201 (w), 1107 (m), 1020 (w) cm−1; 1H-NMR (400 MHz, CDCl3): δ 8.07 (d, J = 6.4 Hz; 1H), 7.83-7.89 (m; 3H), 7.58-7.62 (m; 1H), 7.52-7.56 (m; 1H), 7.44-7.47 (m; 1H), 7.33-7.36 (m; 4H), 7.11-7.12 (m; 2H), 5.29-5.37 (m; 1H), 4.93-4.97 (m; 2H), 4.69-4.71 (m; 1H), 4.23-4.29 (m; 2H), 3.28 (dd, J = 10.3, 14.4 Hz; 1H), 2.69-2.73 (m; 1H), 1.31-1.34 (m; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.7, 144.1, 134.2, 129.6, 129.4, 129.0, 128.7, 128.4, 127.3, 126.4, 126.3, 125.3, 121.9, 88.6, 76.2, 61.4, 39.8, 30.0, 14.2; HRMS (ESI+): Calculated for C25H24N2O6Na ([M + Na]+): 471.1532, found: 471.1534; Optical rotation: [α]D

21 –111.7 (c 2.0, CHCl3) for an enantiomerically enriched sample with 98.5:1.5 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/EtOH = 95:5, 1.0 mL min−1, τminor = 15.19 min, τmajor = 18.26 min). (4S,5R,E)-Ethyl 5-(benzo[d][1,3]dioxol-5-yl)-2-benzylidene-4,6-dinitrohexanoate (3ia):

Purification by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/5% EtOAc in pet ether) afforded pure 3ia as colorless thick oil (66 mg, 0.142 mmol; 78% yield). Rf = 0.40 (25% EtOAc in pet ether); FT-IR (neat): ν 2921 (w), 1702 (s), 1630 (w),

1556 (s), 1446 (m), 1377 (m), 1252 (s), 1202 (m), 1101 (m), 1038 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.86 (s; 1H), 7.36-7.42 (m; 3H), 7.15-7.18 (m; 2H), 6.75-6.77 (m; 1H), 6.62-6.65 (m; 2H), 5.98 (d, J = 1.4 Hz; 1H), 5.97 (d, J = 1.4 Hz; 1H), 5.09-5.15 (m; 1H), 4.64 (dd, J = 10.5, 12.9 Hz; 1H), 4.45 (dd, J = 4.1, 12.9 Hz; 1H), 4.27 (q, J = 7.1 Hz; 2H), 3.84-3.90 (m; 1H), 3.19 (dd, J = 10.5, 14.7 Hz; 1H), 2.69-2.73 (m; 1H), 1.35 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.7, 148.5, 148.2, 144.1, 134.2, 128.9, 128.7, 128.5, 126.9, 126.4, 121.8, 109.0, 108.0, 101.5, 87.9, 77.0, 61.4, 46.7, 30.2, 14.1; HRMS (ESI+): Calculated for C22H22N2O8Na ([M + Na]+): 465.1274, found: 465.1278; Optical rotation: [α]D

23 –109.8 (c 2.0, CHCl3) for an enantiomerically enriched sample with 98:2 er. Enantiomeric purity was determined by HPLC analysis (Phenomenex Cellulose-1 column, 254 nm, n-Hexane/EtOH = 90:10, 1.0 mL min−1, τmajor = 14.71 min, τminor = 19.14 min).



(4S,5R,E)-Ethyl 2-benzylidene-5-(furan-2-yl)-4,6-dinitrohexanoate (3ja): Purification by silica gel (230-400mesh) column chromatography (gradient elution: pet ether/ 2% EtOAc in pet ether/ 4% EtOAc in pet ether) afforded pure 3ja as thick yellowish oil, which was crystallized from CHCl3/Hexane mixture (57.6 mg, 0.147 mmol; 74% yield). Rf = 0.20 (10% EtOAc in pet ether);

Melting point = 99°C (CHCl3/Hexane 1:3); FT-IR (neat): ν 2926 (w), 1706 (m), 1617 (w), 1559 (s), 1438 (w), 1375 (m), 1263 (m), 1201 (w), 1105 (m), 1017 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.89 (s; 1H), 7.37-7.42 (m; 4H), 7.19-7.21 (m; 2H), 6.31-6.32 (m; 1H), 6.27-6.28 (m; 1H), 5.22-5.28 (m; 1H), 4.72-4.78 (m; 1H), 4.49 (dd, J = 3.8, 13.4 Hz; 1H), 4.29 (q, J = 7.1 Hz; 2H), 4.13-4.19 (m; 1H), 3.26 (dd, J = 9.9, 14.5 Hz; 1H), 2.81 (dd, J = 4.3, 14.6 Hz; 1H), 1.36 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.6, 146.8, 144.1, 143.5, 134.2, 129.0, 128.8, 128.5, 126.2, 110.8, 110.2, 86.0, 74.4, 61.5, 40.5, 29.9, 14.1; HRMS (ESI+): Calculated for C19H20N2O7Na ([M + Na]+): 411.1168, found: 411.1170; Optical rotation: [α]D

23 –54.9 (c 1.0, CHCl3) for an enantiomerically enriched sample with 97:3 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/EtOH = 90:10, 1.5 mL min−1, τminor = 16.10 min, τmajor = 17.23 min). (4S,5R,E)-Ethyl 2-benzylidene-4,6-dinitro-5-(thiophen-2-yl)hexanoate (3ka): Purification by

silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/ 5% EtOAc in pet ether) afforded pure 3ka as light brown solid (59 mg, 0.146 mmol; 73% yield). Rf = 0.20 (10% EtOAc in pet ether); Melting point = 96 °C (EtOAc-Heptane 1:3); FT-IR (neat): ν 2924 (m), 1703 (s),

1636 (m), 1556 (s), 1435 (w), 1370 (m), 1257 (m), 1201 (w), 1156 (m), 1099 (m), 1018 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.90 (s; 1H), 7.37-7.42 (m; 3H), 7.29-7.30 (m; 1H), 7.18-7.20 (m; 2H), 6.93-6.98 (m; 2H), 5.20-5.26 (m; 1H), 4.69 (dd, J = 9.9, 13.2 Hz; 1H), 4.54 (dd, J = 3.9, 13.2 Hz; 1H), 4.27-4.33 (m; 1H), 3.24 (dd, J = 10.4, 14.5 Hz; 1H), 1.36 (t, J = 7.2 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.6, 144.3, 135.5, 134.2, 128.9, 128.8, 128.5, 127.5, 126.5, 126.3, 88.0, 77.2, 61.5, 42.2, 30.2, 14.2; HRMS (ESI+): Calculated for C19H20N2O6SNa ([M + Na]+): 427.0940, found: 427.0940; Optical rotation: [α]D

22 –96.1 (c 1.0, CHCl3) for an enantiomerically enriched sample with >98:2 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/EtOH = 95:5, 1.0 mL min−1, τminor = 21.07 min, τmajor = 26.12 min).

NO2

NO2 CO2Et

Ph

3ja

O

NO2

NO2 CO2Et

Ph

3ka

S



(4S,5R,E)-Ethyl 2-benzylidene-5-(1H-indol-3-yl)-4,6-dinitrohexanoate (3la): Reaction was performed at 5 °C. Product was purified by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/ 10% EtOAc in pet ether) afforded pure 3al as a reddish thick oil (68.8 mg, 0.157 mmol; 79% yield). Rf = 0.25 (30% EtOAc in pet ether); FT-IR (neat): ν 3421 (br),

2919 (w), 1698 (s), 1541 (s), 1260 (m), 1186 (w), 1101 (m), 1016 (w) cm−1; 1H-NMR (400 MHz, CDCl3): δ 8.35 (bs; 1H), 7.85 (s; 1H), 7.52 (d, J =7.8 Hz; 1H), 7.31-7.33 (m; 3H), 7.12-7.23 (m; 5H), 7.01-6.99 (m; 1H), 5.40-5.46 (m; 1H), 4.78-4.84 (m; 1H), 4.56-4.61 (m; 1H), 4.19-4.33 (m; 1H), 3.24-3.31 (m; 1H), 2.86-2.91 (m; 1H), 1.30 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.9, 143.9, 136.1, 134.2, 128.8, 128.6, 128.5, 126.7, 87.7, 76.2, 61.4, 38.9, 30.4, 14.1; HRMS (ESI+): Calculated for C23H23N3O6Na ([M + Na]+): 460.1485, found: 460.1488; Optical rotation: [α]D

22 –99.7 (c 2.0, CHCl3) for an enantiomerically enriched sample with >99:1 er. Enantiomeric purity was determined by HPLC analysis (Phenomenex Cellulose-1column, 254 nm, n-Hexane/EtOH = 85:15, 1.0 mL min−1, τmajor = 17.09 min, τmajor = 24.78 min). (4S,5R,E)-Ethyl 2-benzylidene-5-cyclohexyl-4,6-dinitrohexanoate (3ma): Reaction was

performed at 5 °C. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/ 1% EtOAc in pet ether) afforded pure 3ma as yellowish viscous oil (54 mg, 0.133 mmol; 67% yield). Rf = 0.20 (2 % EtOAc in pet ether); FT-IR (neat): ν 2928 (s), 2855

(m), 1745 (s), 1557 (s), 1457 (w), 1370 (m), 1276 (s), 1254 (s), 1157 (s), 1086 (m), 1027 (w) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.94 (s; 1H), 7.36-7.44 (m; 3H), 7.24-7.26 (m; 2H), 5.21-5.25 (m; 1H), 4.31 (q, J = 7.1 Hz; 2H), 3.33 (dd, J = 9.1, 14.4 Hz; 1H), 3.03 (dd, J = 5.2, 14.4 Hz; 1H), 2.53-2.58 (m; 1H), 1.70-1.73 (m; 3H), 1.63-1.65 (m; 1H), 1.55-1.57 (m; 1H), 1.36-1.39 (m; 4H), 1.11-1.25 (m; 3H), 0.83-0.88 (m; 2H); 13C-NMR (100 MHz, CDCl3): δ 166.8, 144.1, 134.3, 129.1, 128.9, 128.5, 126.6, 85.4, 73.9, 61.6, 44.6, 39.2, 30.1, 29.7, 29.3, 26.0, 25.8, 14.2; HRMS (ESI+): Calculated for C21H28N2O6Na ([M + Na]+): 427.1845, found: 427.1842; Optical rotation: [α]D

23 –6.8 (c 1.0, CHCl3) for an enantiomerically enriched sample with >99:1 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/EtOH = 95:5, 0.5 mL min−1, τmajor = 12.78 min, τminor = 13.51 min).



(4S,5R,E)-Ethyl 2-benzylidene-4-nitro-5-(nitromethyl)decanoate (3na): Reaction was performed at 5 °C. Purification by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/ 1% EtOAc in pet ether) afforded pure 3na as colorless viscous oil (57 mg, 0.145 mmol; 73% yield). Rf = 0.30 (2% EtOAc in pet ether); FT-IR (neat): ν 2956 (s),

2925 (s), 2855 (s), 1702 (s), 1637 (w), 1553 (s), 1452 (m), 1370 (m), 1262 (m), 1223 (m), 1100 (m), 1018 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.95 (s; 1H), 7.36-7.44 (m; 3H), 7.24-7.27 (m; 2H), 5.06-5.12 (m; 1H), 4.46 (dd, J = 3.4, 13.7 Hz; 1H), 4.31 (q, J = 7.1 Hz; 2H), 4.22-4.27 (m; 1H), 3.31 (dd, J = 8.9, 14.3 Hz; 1H), 3.04 (dd, J =5.4, 14.3 Hz; 1H), 2.59-2.66 (m; 1H), 1.36-1.39 (m; 5H), 1.23-1.29 (m; 6H), 0.85-0.88 (m; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.8, 144.1, 134.3, 129.1, 128.9, 128.4, 126.6, 86.3, 75.4, 61.6, 39.5, 31.2, 29.1, 28.98, 25.6, 22.2, 14.2, 13.8; HRMS (ESI+): Calculated for C20H28N2O6FNa ([M + Na]+): 415.1845, found: 415.1840; Optical rotation: [α]D

25 +9.94 (c 1.0, CHCl3) for an enantiomerically enriched sample with 97.5:2.5 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/IPA = 98:2, 1.0 mL min−1, τminor = 10.18 min, τmajor = 11.59 min). (2E,4S,5R,6E)-Ethyl 2-benzylidene-4-nitro-5-(nitromethyl)-7-phenylhept-6-enoate (3oa):

Purification by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/ 5% EtOAc in pet ether) afforded pure 3oa as yellowish oil (65.3 mg, 0.153 mmol; 77% yield). Rf = 0.20 (15% EtOAc in pet ether); FT-IR (neat): ν 2935 (w), 1704 (s), 1654 (w), 1557 (s),

1447 (w), 1375 (m), 1263 (m), 1202 (m), 1103 (m), 1024 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.92 (s; 1H), 7.36-7.41 (m, 3H), 7.29-7.32 (m; 5H), 7.22-7.26 (m; 2H), 6.59 (d, J = 15.7 Hz; 1H), 5.86 (dd, J = 9.5, 15.7 Hz; 1H), 4.99-5.06 (m; 1H), 4.38-4.49 (m; 2H), 4.29 (q, J = 7.1 Hz; 2H), 3.49-3.58 (m; 1H), 3.28 (dd, J = 10.0, 14.7 Hz; 1H), 3.07 (dd, J = 3.9, 14.7 Hz; 1H), 1.36 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.8, 144.1, 137.5, 135.2, 134.3, 129.0, 128.77, 128.69, 128.65, 128.47, 126.73, 126.69, 120.7, 87.0, 76.1, 61.5, 44.9, 30.1, 14.2; HRMS (ESI+): Calculated for C23H24N2O6Na ([M + Na]+): 447.1532, found: 447.1534; Optical rotation: [α]D

23 –175.8 (c 2.0, CHCl3) for an enantiomerically enriched sample with 97:3 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak ID column, 254 nm: n-Hexane/EtOH = 98.5:1.5, 1.3 mL min−1, τmajor = 15.22 min, τminor = 16.20 min).

NO2

NO2 CO2Et

Ph

3na

NO2

NO2 CO2Et

Ph

3oa



(4S,5R,E)-Ethyl 5-(4-chlorophenyl)-2-(2-fluorobenzylidene)-4,6-dinitrohexanoate (3cc): Purification by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/ 4% EtOAc in pet ether) afforded pure 3cc as yellowish viscous oil (69 mg, 0.153 mmol; 77% yield). Rf = 0.20 (10% EtOAc in pet ether); FT-IR (neat): ν 2920 (w), 1710 (m), 1555 (s), 1467 (w), 1372 (m), 1264 (s), 1096 (w), 1016 (w) cm−1; 1H-NMR

(400 MHz, CDCl3): δ 7.77 (s; 1H), 7.31-7.41 (m; 3H), 7.07-7.19 (m; 5H), 5.12-5.19 (m; 1H), 4.67 (dd, J = 10.4, 13.1 Hz; 1H), 4.49 (dd, J = 4.0, 13.1 Hz; 1H), 4.27 (q, J = 7.1 Hz; 2H), 3.89-3.95 (m; 1H), 3.03 (dd, J = 10.6, 14.6 Hz; 1H), 2.61 (dd, J = 2.5, 14.6 Hz; 1H), 1.34 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.1, 159.4 (d, J = 249Hz), 137.3, 135.1, 132.1, 130.9 (d, J = 8Hz), 129.7, 129.4, 128.8, 124.3 (d, J = 3Hz), 122.1, 121.9, 115.9 (d, J = 22 Hz), 87.6, 76.7, 61.6, 46.3, 30.8, 14.1; HRMS (ESI+): Calculated for C21H20N2O6ClFNa ([M + Na]+): 473.0892, found: 473.0890; Optical rotation: [α]D

22 –132.5 (c 2.0, CHCl3) for an enantiomerically enriched sample with 97:3 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/IPA = 95:5, 1.0 mL min−1, τmajor = 20.15 min, τminor = 24.06 min). (4S,5R,E)-ethyl 5-(4-chlorophenyl)-4,6-dinitro-2-(4-(trifluoromethyl)benzylidene)hexanoate

(3cd): Purification by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/ 3% EtOAc in pet ether) afforded pure 3cd as thick yellow oil (69 mg, 0.137 mmol; 69% yield). Rf = 0.20 (8% EtOAc in pet ether); FT-IR (neat): ν 2922 (m), 1630 (br), 1440 (br), 1324 (m), 1264 (m), 1166 (w), 1125 (m), 1018 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.85 (s; 1H), 7.65 (d, J = 8.1 Hz;

2H), 7.35 (d, J = 8.4 Hz; 2H), 7.24 (d, J = 8.1 Hz; 2H), 7.15 (d, J = 8.4 Hz; 2H), 5.18-5.25 (m; 1H), 4.66 (dd, J = 10.2, 13.1 Hz; 1H), 4.49 (dd, J = 4.0, 13.1 Hz; 1H), 4.28 (q, J = 7.1 Hz; 2H), 3.94 (dt, J = 4.0, 10.2 Hz; 1H), 3.04 (dd, J = 10.9, 14.5 Hz; 1H), 2.58 (dd, J = 1.9, 14.5 Hz; 1H), 1.36 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.1, 142.6, 137.8, 135.3, 131.9, 130.7 (q, J = 33 Hz), 129.8, 129.4, 128.6, 128.2, 123.7 (q, J = 272 Hz), 125.6 (q, J = 4 Hz), 87.4, 76.8, 61.7, 46.4, 30.5, 14.1; HRMS (ESI+): Calculated for C22H20N2O6ClF3Na ([M + Na]+): 523.0860, found: 523.0861; Optical rotation: [α]D

22 –112.1 (c 2.0, CHCl3) for an enantiomerically enriched sample with 96:4 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/EtOH = 90:10, 1.0 mL min−1, τmajor = 10.55 min, τminor = 13.13 min).

NO2

NO2 CO2Et

F

3ccCl



(4S,5R,E)-Ethyl 5-(2,4-dichlorophenyl)-2-(naphthalen-2-ylmethylene)-4,6-dinitrohexanoate (3fe): Purification by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/ 5% EtOAc in pet ether) afforded pure 3fe as white thick oil (68.3 mg, 0.132 mmol; 66% yield). Rf = 0.40 (20% EtOAc in pet ether); FT-IR (neat): ν 2924 (w), 1703 (m), 1629 (w), 1557 (s), 1472 (w), 1436 (w), 1371 (m), 1265 (m), 12010 (w), 1104 (m), 1019 (w) cm−1; 1H-NMR (400 MHz,

CDCl3): δ 8.06 (s; 1H), 7.82-7.87 (m; 3H), 7.67-7.68 (m; 1H), 7.53-7.55 (m; 2H), 7.33-7.35 (m; 1H), 7.28-7.30 (m; 1H), 7.01-7.12 (m; 1H), 7.00-7.03 (m; 1H), 5.22-5.28 (m; 1H), 4.80 (dd, J = 10.4, 13.5 Hz; 1H), 4.49-4.58 (m; 1H), 4.30 (q, J = 7.0 Hz; 2H), 3.38 (dd, J = 9.7, 14.4 Hz; 1H), 2.88 (dd, J = 4.3, 14.4 Hz; 1H), 1.37 (t, J = 7.0 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ166.6, 144.4, 135.4, 135.1, 133.1, 132.98, 131.6, 130.5, 130.2, 128.6, 128.3, 128.1, 127.7, 127.1, 126.8, 126.3, 125.5, 87.2, 74.5, 61.6, 41.9, 29.8, 14.2; HRMS (ESI+): Calculated for C25H22N2O6Cl2Na ([M + Na]+): 539.0753, found: 539.0758; Optical rotation: [α]D

20 –77.2 (c 2.0, CHCl3) for an enantiomerically enriched sample with 98.5:1.5 er. Enantiomeric purity was determined by HPLC analysis (Phenomex Cellulose-1 column, 254 nm, n-Hexane/EtOH = 90:10, 1.0 mL min−1, τmajor = 14.99 min, τminor = 16.34 min). (4S,5R,E)-Ethyl 5-(2-bromophenyl)-2-(2-methylbenzylidene)-4,6-dinitrohexanoate (3db):

Purification by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/ 4% EtOAc in pet ether) afforded pure 3db as yellow thick oil (76 mg, 0.156 mmol; 78% yield). Rf = 0.20 (10% EtOAc in pet ether); FT-IR (neat): ν 2922 (w), 1702 (s), 1633 (w), 1556 (s), 1433 (w), 1374 (m), 1263 (m), 1208 (w), 1102 (m), 1022 (m),

cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.93 (s; 1H), 7.59-7.61 (m; 1H), 7.13-7.38 (m; 8H), 5.22-5.30 (m; 1H), 4.83-4.91 (m; 1H), 4.55-4.62 (m; 2H), 4.27-4.29 (m; 2H), 3.32-3.38 (m; 1H), 2.84-2.87 (m; 1H), 1.33-1.36 (m; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.6, 144.3, 134.2, 134.0, 133.4, 130.3, 129.0, 128.8, 128.5, 128.4, 126.2, 87.6, 74.7, 61.5, 44.1, 29.6, 14.2; HRMS (ESI+): Calculated for C22H23N2O6BrNa ([M + Na]+): 513.0637, found: 513.0638; Optical rotation: [α]D

21 –92.5 (c 2.0, CHCl3) for an enantiomerically enriched sample with >98.5:1.5 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/EtOH = 90:10, 1.0 mL min−1, τminor = 6.85 min, τmajor = 8.42 min). (4S,5R,E)-Ethyl 5-(benzo[d][1,3]dioxol-5-yl)-4,6-dinitro-2-propylidenehexanoate (3if):

Purification by silica gel (230-400 mesh) column chromatography (gradient elution: pet ether/ 4% EtOAc in pet ether) afforded pure 3if as colorless viscous oil (50 mg, 0.126 mmol; 63% yield). Rf = 0.25 (10%

NO2

NO2 CO2Et

Br Me

3db



EtOAc in pet ether); FT-IR (neat): ν 2972 (m), 2925 (m), 1703 (s), 1647 (w), 1556 (s), 1446 (w), 1374 (m), 1277 (m), 1250 (m), 1107 (w), 1038 (m), cm−1; 1H-NMR (400 MHz, CDCl3): δ 6.89-6.93 (m; 1H), 6.79-6.82 (m; 1H), 6.74-6.76 (m; 1H), 5.97-6.00 (m; 1H), 5.04-5.11 (m; 1H), 4.69-4.74 (m; 1H), 4.54-4.58 (m; 1H), 4.15-4.20 (m; 2H), 3.95-4.01 (m; 1H), 2.85-2.91 (m; 1H), 2.45-2.50 (m; 1H), 2.07-2.14 (m; 2H), 1.27-1.30 (m; 3H), 0.97-1.01 (m; 3H); 13C-NMR (100 MHz, CDCl3): δ 166.4, 149.7, 148.5, 148.2, 127.0, 124.5, 121..9, 109.0, 108.0, 101.5, 88.6, 77.2, 60.9, 47.2, 30.2, 21.95, 14.1, 13.2; HRMS (ESI+): Calculated for C18H22N2O8Na ([M + Na]+): 417.1274, found: 417.1275; Optical rotation: [α]D

21 –28.5 (c 2.0, CHCl3) for an enantiomerically enriched sample with 96:4 er. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralpak AD-H column, 254 nm, n-Hexane/EtOH = 90:10, 1.0 mL min−1, τmajor = 11.47 min, τminor = 12.65 min). (4S,5R)-Ethyl 5-(1H-indol-3-yl)-2-methylene-4,6-dinitrohexanoate (3lg): Purification by

silica gel (230-400 mesh) column chromatography (gradient elution: toluene/ 40% DCM in toluene) afforded pure 3lg as thick yellow oil (30.5 mg, 0.084 mmol; 42% yield). Rf = 0.20 (50% DCM in toluene); FT-IR (neat): ν 3421 (br), 2926 (w), 1717 (m), 1634 (w), 1558 (s), 1375

(w), 1199 (w), 1104 (m), 1018 (m); 1H-NMR (400 MHz, CDCl3): δ 8.35 (bs; 1H), 7.62(d, J = 7.8 Hz; 1H), 7.37(d, J = 7.9 Hz; 1H), 7.15-7.27 (m; 3H), 6.21 (s; 1H), 5.58 (s; 1H), 5.36-5.42 (m; 1H), 4.87 (dd, J = 9.3, 12.9 Hz; 1H), 4.70 (dd, J = 4.2, 12.9 Hz; 1H), 4.39 (dt, J = 4.3, 9.5 Hz; 1H), 4.20 (q, J = 7.1 Hz; 2H), 2.80-2.84 (m; 1H), 2.68-2.74 (m; 1H), 1.23 (t, J = 7.1 Hz; 3H); 13C-NMR (100 MHz, CDCl3): δ 165.6, 136.2, 134.1, 129.8, 125.7, 123.2, 123.1, 120.6, 118.1, 111.8, 108.1, 88.7, 76.5, 61.2, 39.3, 35.8, 14.0; HRMS (ESI+): Calculated for C17H19N3O6Na ([M + Na]+): 384.1172, found: 384.1172; Optical rotation: [α]D

25 –20.4 (c 1.0, CHCl3) for an enantiomerically enriched sample with 90:10 er. Enantiomeric purity was determined by HPLC analysis (Phenomenex Cellulose-1 column, 254 nm, n-Hexane/EtOH = 90:10, 1.0 mL min−1, τmajor = 28.54 min, τminor = 37.62 min).



Conversion of 3ca to 4:

In a 10 mL round bottom flask, 3ca (100 mg, 0.230 mmol, 1.0 equiv.) was dissolved in 5 mL glacial AcOH. To this solution, Zn dust was added portion wise over 15 minutes while stirring. After addition was over the resulting slurry was heated at 100 °C for 24 h. The reaction mixture was then allowed to attain room temperature. The white heterogenous mass was then cooled to 0 °C and basified by dropwise addition of an aqueous ammonia solution (10%) until pH 10; during basification the white solid was dissolved resulting in a clear colorless solution. This solution was extracted with CH2Cl2. The organic layer was dried over anh. Na2SO4 and concentrated in vacue to obtain a thick yellow oil (Rf = 0.30; 10% MeOH in DCM). This oil was used directly for the next step without further purification. The oil was dissolved in 1:1 THF/water mixture (0.8 mL). To the resulting solution, Boc2O (75 mg, 0.345 mmol, 1.5 equiv.) was added as a solution in THF (0.4 mL) while vigorously stirring at room temperature. After stirring for 1.5 h the reaction mixture was diluted with CH2Cl2 (15 mL) and washed with brine (5 mL). The organic layer was separated and after drying over anh. Na2SO4, concentrated to obtain a grey semisolid. The product was purified by silica gel (230-400 mess) column chromatography (gradient elution: 40-100% EtOAc/pet ether) to obtain 4 as a white solid (79 mg, 0.185 mmol; 81% yield). Rf = 0.20 (50% EtOAc in pet ether); Melting point = 163-165 °C; FT-IR (KBr): ν 3396 (br), 3204 (m), 2926 (m), 1619 (s), 1654 (s), 1522 (m), 1276 (m), 1249 (m), 1092 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.51 (bs; 1H), 7.37 (s; 1H), 7.28-7.35 (m; 7H), 7.12-7.14 (m; 2H), 4.54-4.58 (m; 1H), 4.02-4.06 (m; 1H), 3.77-3.84 (m; 1H), 3.16-3.19 (m; 1H), 3.03-3.10 (m; 1H), 2.66-2.71 (m; 1H), 2.54-2.58 (m; 1H), 1.44 (s; 9H); 13C-NMR (100 MHz, CDCl3): δ 171.7, 156.5, 137.9, 135.4, 133.2, 130.9, 129.7, 129.6, 129.5, 129.2, 128.6, 128.5, 80.0, 77.2, 52.3, 43.0, 31.8, 28.3; HRMS (ESI+): Calculated for C24H29N2O3ClNa ([M + Na]+): 451.1764, found: 451.1764; Optical rotation: [α]D

24 –47.7 (c 2.0, CHCl3).



Conversion of 3ca to 5:

In a 25 mL round bottom flask equipped with an argon inlet, 3ca (210 mg, 0.485 mmol; 1.0 equiv.) was dissolved in 6 mL CH2Cl2 and cooled to –78 °C. To this solution, 1M DIBAL-H solution in cyclohexane (2.4 mL, 2.4 mmol; 5 equiv.) was added dropwise at –78 °C and the resulting mixture was allowed to warm to –45 °C over 30 min while stirring. The reaction mixture was again cooled down to –78 °C and to it 2N HCl in MeOH was added dropwise and resulting yellow solution was allowed to attain room temperature. Removal of solvents afforded a thick reddish yellow oil. Purification by silica gel (230-400 mess) column chromatography (gradient elution: toluene to 4% EtOAc in toluene) yield 5 as colorless oil (127 mg, 0.324 mmol; 64% yield). Rf = 0.20 (4% EtOAc in toluene); FT-IR (neat): ν 3418 (bs), 2924 (w), 1744 (m), 1644 (m), 1557 (s), 1494 (m), 1433 (w), 1377 (m), 1228 (m), 1095 (w), 1015 (w), 832 (m) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.25-7.33 (m; 5H), 7.02-7.04 (m; 2H), 6.96-6.98 (m; 2H), 6.70 (s; 1H), 4.94-5.00 (m; 1H), 4.59-4.65 (m; 1H), 4.41 (dd, J = 4.0, 13.2 Hz; 1H), 4.21 (d, J = 13.2 Hz; 1H), 4.12 (d, J = 13.2 Hz; 1H), 3.85-3.91 (m; 1H), 2.88 (dd, J = 10.7, 14.9 Hz; 1H), 2.56 (dd, J = 2.9, 14.9 Hz; 1H), 1.85 (bs; 1H); 13C-NMR (100 MHz, CDCl3): δ 135.9, 135.0, 134.5, 132.3, 131.5, 129.7, 129.2, 128.6, 128.1, 127.5, 87.5, 76.2, 67.0, 46.2, 31.3; HRMS (ESI+): Calculated for C19H19N2O5ClNa ([M + Na]+): 413.0880, found: 413.0881; Optical rotation: [α]D

23 –22.9 (c 1.0, CHCl3). Conversion of 5 to 6:

In a 10 mL round bottom flask 5 (50 mg, 0.127 mmol; 1.0 equiv.) was taken in 3:1 THF/H2O mixture (4 mL). Aluminium foil (100 mg) was cut into small pieces and was soaked in 2% HgCl2 solution (aqueous) for 10-15 seconds, washed by dipping in THF and added to the vigorously stirred reaction mixture. The resulting heterogeneous mixture was stirred for 2 h and filtered through filter paper washing with THF. The filtrate was dried over anh. Na2SO4 and evaporated under reduced pressure to obtain a white foam. This was purified by silica gel (230-400 mess) column chromatography (gradient elution: DCM to 10% EtOAc in DCM to 20% EtOAc in CH2Cl2) to obtain 6 as a white thick oil (25 mg, 0.076 mmol; 60% yield). Rf = 0.20 (20% EtOAc



in CH2Cl2). Crystallization from 1:1 hexane/iso-propanol afforded diffraction quality crystals. FT-IR (neat): ν 3408 (brs), 2922 (s), 2853 (m), 1606 (m), 1484 (m), 1092 (s), 1014 (s) cm−1; 1H-NMR (400 MHz, CDCl3): δ 7.24-7.25 (m; 1H), 7.22-7.23 (m; 1H), 7.17-7.19 (m; 3H), 7.04-7.07 (m; 2H), 6.84-6.86 (m; 2H), 6.71 (s; 1H), 4.91-4.98 (m; 1H), 4.48-4.53 (m; 1H), 4.31 (s; 2H), 4.24-4.29 (m; 1H), 2.86 (dd, J = 5.5, 14.2 Hz; 1H), 2.63-2.70 (m; 2H); 13C-NMR (100 MHz, CDCl3): δ 139.4, 138.4, 136.7, 132.7, 129.3, 129.1, 128.6, 128.3, 128.2, 126.9, 94.7, 83.3, 67.9, 43.7, 31.9; HRMS (ESI+): Calculated for C19H19N2OClNa ([M + Na]+): 349.1084, found: 349.1084; Optical rotation: [α]D

22 –191.7 (c 2.0, CHCl3).



Single crystal X-ray diffraction analysis of 3ka:

A single crystal of 3ka was mounted and the diffraction data were collected at 100 K on a Bruker SMART APEX CCD diffractometer using SMART/SAINT software. Intensity data were collected using graphite-monochromatized Mo-Ka radiation (0.71073 Å) at 100 K. The structures were solved by direct methods using Olex2 and refined using Least Squares minimization. Empirical absorption corrections were applied with SADABS. All Non-hydrogen atoms were refined anisotropically, and hydrogen atoms were included in geometric positions. Structure was drawn using ORTEP-3 and Olex2. The crystallographic refinement parameters are given below:

Table 1. Crystal data and structure refinement for 3ka:

Identification code 3ka Empirical formula C19H20N2O6S Formula weight 404.44 Temperature 100 K Crystal system Monoclinic Space group P21 Unit cell demensions a = 9.9605(13) Å α = 90.00°

b = 7.5342(10) Å β = 98.095(7)° c = 12.8020(16) Å γ = 90.00°

Volume 951.1(2) Å3 Z 2 Density (calculated) (ρcalc) 1.465 mg/mm3 Absorption coefficient 0.315 mm-1 F(000) 438.0 Crystal size 0.25 × 0.23 × 0.20 mm3 Theta range for data collection 3.22 to 55.24° Index ranges -11 ≤ h ≤ 12, -9 ≤ k ≤ 9, -16 ≤ l ≤ 16 Reflections collected 11810 Independent reflections 4045 [Rint = 0.0390] Data/restraints/parameters 3224/1/248 Goodness-of-fit on F2 0.781 Final R indexes [I>2σ (I)] R1 = 0.0466, ωR2 = 0.1299 Final R indexes [all data] R1 = 0.0428, ωR2 = 0.1257 Largest diff. peak and hole 0.88 and –0.50 e.Å–3 Flack parameter –0.02(11)



Table 2. Fractional atomic coordinates (×104) and equivalent isotropic displacement parameters (Å2×103) for 3ka. U(eq) is defined as 1/3 of the trace of the orthogonalised Uij

tensor:

Atom x y z U(eq) S1 2885.4(8) 7296.2(14) 3911.7(7) 36.5(2) C9 3530(3) 4743(4) 7569(2) 15.9(5) C7 1596(3) 5399(4) 8484(2) 15.3(5) C8 2264(3) 5765(4) 7667(2) 15.3(5) C16 462(2) 8309(3) 4130.3(17) 7.4(4) O3 4628(2) 8774(3) 7935.4(16) 24.9(5) O4 2839(2) 10459(3) 7756.5(16) 23.6(5) C18 1558(4) 6619(5) 3029(3) 40.0(9) O6 1933.1(19) 12658(3) 4513.0(16) 24.0(5) C1 -2251(3) 6896(4) 9348(2) 23.1(6) C2 -1217(3) 6221(4) 10087(2) 24.3(6) C3 24(3) 5770(4) 9785(2) 21.1(6) C4 258(3) 5975(4) 8732(2) 17.0(5) C12 1818(3) 7037(4) 6773(2) 17.1(5) C13 2962(3) 8229(4) 6479.5(19) 14.4(5) C14 2448(3) 9539(4) 5583(2) 14.0(5) C19 3599(3) 10791(4) 5398(2) 14.9(5) N2 3120(2) 12222(3) 4624.2(17) 15.8(4) O5 3986.8(19) 12907(3) 4153.6(16) 23.4(5) C17 369(3) 7255(5) 3255(3) 34.7(8) C15 1888(3) 8524(4) 4606(2) 16.3(5) O2 4201.6(18) 4205(3) 8490.1(15) 17.5(4) C10 5460(3) 3249(4) 8422(2) 18.6(6) C11 6004(3) 2617(5) 9519(2) 26.5(7) O1 3897(2) 4438(3) 6716.9(15) 19.6(4) C6 -2037(3) 7071(4) 8307(2) 22.4(6) C5 -796(3) 6615(4) 7995(2) 19.5(6) N1 3521(2) 9249(3) 7465.0(18) 15.3(5)



Table 3. Anisotropic displacement parameters (Å2×103) for 3ka. The anisotropic displacement factor exponent takes the form: -2π2[h2a*2U11 + ... + 2hka*b*U12]:

Atom U11 U22 U33 U23 U13 U12 S1 23.7(4) 51.7(6) 33.6(4) -16.0(4) 2.0(3) 2.0(4) C9 19.1(14) 11.5(12) 15.9(12) 1.9(10) -2(1) -2.7(11) C7 14.8(13) 15.8(13) 14.6(11) -0.1(10) -1.1(9) -1.2(11) C8 14.0(12) 14.4(13) 16.5(12) 0.6(11) -1.1(9) -3.7(11) O3 16.5(10) 31.6(12) 23.9(11) 1.1(9) -6.5(8) -0.4(9) O4 22.6(10) 25.0(11) 24.3(10) -4.0(9) 7.0(8) 2.7(9) C18 67(3) 30.4(19) 19.5(15) -7.1(14) -3.5(15) -2.4(18) O6 14.1(9) 25.4(11) 32.6(11) 9.3(9) 3.5(8) 3.6(9) C1 17.0(13) 19.8(15) 33.7(15) -5.1(13) 8.1(11) -4.0(12) C2 26.7(15) 26.0(16) 22.2(14) -3.2(12) 10.6(12) -3.2(13) C3 22.6(14) 20.3(15) 20.3(14) 0.8(12) 2.6(11) -1.1(12) C4 15.1(13) 15.8(13) 20.2(13) -1.8(11) 3.5(10) -1.9(11) C12 10.5(11) 18.5(13) 21.9(12) 5.1(11) 0.6(9) 0.3(11) C13 10.7(12) 14.7(12) 17.0(12) -0.2(11) -0.5(9) 1.3(10) C14 10.8(12) 14.4(13) 16.8(12) 1.8(10) 1.6(9) -0.6(10) C19 11.5(12) 13.9(13) 18.4(12) 2.2(10) -1.1(9) 0.4(11) N2 13.3(10) 16.2(11) 17.8(10) 0.6(9) 1.5(8) -2.7(10) O5 18.4(10) 25.9(12) 26.7(10) 7.1(9) 6.6(8) -4.1(9) C17 26.6(16) 32.7(18) 38.9(18) 14.5(16) -15.6(13) -13.5(16) C15 13.7(12) 15.9(13) 18.5(13) 4.7(11) -0.7(10) -1.8(11) O2 13.2(9) 21.1(10) 17.7(9) 0.7(8) 0.1(7) 3.3(8) C10 12.9(12) 21.1(14) 22.2(13) 0.6(12) 3.6(10) 2.3(11) C11 18.8(14) 33.7(18) 26.6(15) 6.6(13) 1.3(11) 8.0(13) O1 22.8(10) 17.9(10) 18.6(9) 0.2(8) 4.8(7) 3.1(9) C6 12.8(12) 23.7(15) 30.5(14) -4.7(13) 1.7(10) -2.8(12) C5 16.5(13) 24.1(15) 18.2(12) 0.3(11) 2.8(10) -4.0(11) N1 13.8(11) 16.4(11) 15.9(10) 3.2(9) 3.0(8) -2.1(10)



Table 4. Bond lengths (Å) for 3ka :

Atom Atom Length Atom Atom Length S1 C18 1.692(4) C1 C6 1.385(4) S1 C15 1.697(3) C2 C3 1.388(4) C9 C8 1.498(4) C3 C4 1.408(4) C9 O2 1.334(3) C4 C5 1.395(4) C9 O1 1.219(3) C12 C13 1.538(4) C7 C8 1.345(4) C13 C14 1.545(3) C7 C4 1.478(4) C13 N1 1.515(3) C8 C12 1.511(4) C14 C19 1.529(4) C16 C17 1.366(4) C14 C15 1.505(4) C16 C15 1.474(3) C19 N2 1.497(3) O3 N1 1.233(3) N2 O5 1.234(3) O4 N1 1.226(3) O2 C10 1.459(3) C18 C17 1.347(6) C10 C11 1.509(4) O6 N2 1.216(3) C6 C5 1.394(4) C1 C2 1.394(4)

Table 5. Bond angles (°) for 3ka:

Atom Atom Atom Angle Atom Atom Atom Angle C18 S1 C15 93.10(17) N1 C13 C14 109.8(2) O2 C9 C8 113.9(2) C19 C14 C13 109.3(2) O1 C9 C8 122.3(2) C15 C14 C13 109.8(2) O1 C9 O2 123.9(3) C15 C14 C19 112.5(2) C8 C7 C4 131.9(3) N2 C19 C14 111.7(2) C9 C8 C12 115.1(2) O6 N2 C19 119.1(2) C7 C8 C9 118.4(2) O6 N2 O5 124.4(2) C7 C8 C12 126.4(2) O5 N2 C19 116.4(2) C17 C16 C15 110.6(2) C18 C17 C16 115.0(3) C17 C18 S1 112.2(3) C16 C15 S1 109.00(19) C6 C1 C2 119.3(3) C16 C15 C14 128.4(2) C3 C2 C1 120.1(3) C14 C15 S1 122.47(19) C2 C3 C4 120.9(3) C9 O2 C10 115.1(2) C3 C4 C7 116.7(2) O2 C10 C11 107.4(2) C5 C4 C7 124.8(2) C1 C6 C5 121.0(3) C5 C4 C3 118.4(2) C6 C5 C4 120.3(3)



C8 C12 C13 114.0(2) O3 N1 C13 117.3(2) C12 C13 C14 112.0(2) O4 N1 O3 124.3(2) N1 C13 C12 106.9(2) O4 N1 C13 118.5(2)

Table 6. Torsion angles (°) for 3ka:

A B C D Angle A B C D Angle S1 C18 C17 C16 0.4(4) C12 C13 N1 O4 -73.4(3) C9 C8 C12 C13 -48.0(3) C13 C14 C19 N2 -173.5(2) C9 O2 C10 C11 -175.2(2) C13 C14 C15 S1 -67.9(3) C7 C8 C12 C13 136.5(3) C13 C14 C15 C16 107.9(3) C7 C4 C5 C6 178.0(3) C14 C13 N1 O3 -133.3(2) C8 C9 O2 C10 -178.4(2) C14 C13 N1 O4 48.3(3) C8 C7 C4 C3 -162.2(3) C14 C19 N2 O6 25.3(3) C8 C7 C4 C5 21.1(5) C14 C19 N2 O5 -156.2(2) C8 C12 C13 C14 -178.5(2) C19 C14 C15 S1 54.0(3) C8 C12 C13 N1 -58.1(3) C19 C14 C15 C16 -130.1(3) C18 S1 C15 C16 2.3(2) C17 C16 C15 S1 -2.4(3) C18 S1 C15 C14 178.8(2) C17 C16 C15 C14 -178.7(3) C1 C2 C3 C4 -0.4(5) C15 S1 C18 C17 -1.6(3) C1 C6 C5 C4 -0.2(5) C15 C16 C17 C18 1.4(4) C2 C1 C6 C5 -1.3(5) C15 C14 C19 N2 64.3(3) C2 C3 C4 C7 -178.0(3) O2 C9 C8 C7 -29.5(4) C2 C3 C4 C5 -1.0(4) O2 C9 C8 C12 154.6(2) C3 C4 C5 C6 1.3(4) O1 C9 C8 C7 150.3(3) C4 C7 C8 C9 -170.9(3) O1 C9 C8 C12 -25.6(4) C4 C7 C8 C12 4.5(5) O1 C9 O2 C10 1.8(4) C12 C13 C14 C19 174.9(2) C6 C1 C2 C3 1.5(5) C12 C13 C14 C15 -61.2(3) N1 C13 C14 C19 56.3(3) C12 C13 N1 O3 105.0(3) N1 C13 C14 C15 -179.8(2)



ORTEP representation of the X-ray structure of 3ka (thermal ellipsoids at 50% probability).

Table 7. Hydrogen atom coordinates (Å×104) and isotropic displacement parameters (Å2×103) for 3ka:

Atom x y z U(eq) H7 2062 4646 8985 18 H16 -274 8821 4390 9 H18 1641 5892 2454 48 H1 -3076 7226 9551 28 H2 -1358 6071 10784 29 H3 710 5327 10285 25 H12A 1101 7786 6969 21 H12B 1443 6360 6156 21 H13 3680 7485 6260 17 H14 1713 10248 5806 17 H19A 3980 11327 6064 18 H19B 4311 10115 5137 18 H17 -455 6995 2846 42 H10A 6112 4025 8156 22 H10B 5289 2245 7947 22 H11A 6837 1984 9502 40 H11B 5354 1846 9772 40 H11C 6168 3621 9982 40 H6 -2731 7499 7808 27 H5 -670 6737 7293 23



Single crystal X-ray diffraction analysis of 6:

A single crystal of 6 was mounted and the diffraction data were collected at 296 K on a Bruker SMART APEX CCD diffractometer using SMART/SAINT software. Intensity data were collected using graphite-monochromatized Mo-Ka radiation (0.71073 Å) at 296 K. The structures were solved by direct methods using Olex2, the structure was solved with the XS structure solution program using Direct Methods and refined with the XL refinement package using Least Squares minimisation. Empirical absorption corrections were applied with SADABS. All Non-hydrogen atoms were refined anisotropically, and hydrogen atoms were included in geometric positions. Structure was drawn using ORTEP-3 and Olex2. The crystallographic refinement parameters are given below:

Table 8. Crystal data and structure refinement for 6:

Identification code 6 Empirical formula C19H19ClN2O Formula weight 326.81 Temperature/K 296 Crystal system monoclinic Space group C2 Unit cell dimensions a = 75.874(8) α = 90.00°

b = 5.7768(7) β = 92.437(12)° c = 7.7098(8) γ = 90.00°

Volume 3376.2(7) Å3 Z 4 Density (calculated) (ρcalc) 1.286 mg/mm3 Absorption coefficient 0.232 mm-1 F(000) 1376.0 Crystal size 0.24 × 0.21 × 0.2 mm3 Theta range for data collection 2.14 to 50° Index ranges -89 ≤ h ≤ 89, -6 ≤ k ≤ 6, -9 ≤ l ≤ 9 Reflections collected 19770 Independent reflections 5705 [Rint = 0.0675] Data / restraints / parameters 5705 / 1 / 417 Goodness-of-fit on F2 0.980 Final R indexes [I>2σ (I)] R1 = 0.0556, ωR2 = 0.1219 Final R indexes [all data] R1 = 0.1244, ωR2 = 0.1492 Largest diff. peak and hole 0.23 and -0.22 e.Å-3 Flack parameter 0.00(10)



Table 9. Fractional atomic coordinates (×104) and equivalent isotropic displacement parameters (Å2×103) for 6. U(eq) is defined as 1/3 of of the trace of the orthogonalised Uij

tensor:

Atom x y z U(eq) Cl1 2326.80(17) -97(3) 6069.3(18) 83.8(5) Cl2 87.72(17) 5373(4) -2343(2) 109.1(7) C1 1836.6(6) 2092(8) 5215(6) 50.6(12) C2 1772.9(6) 8722(8) -415(5) 43.3(11) O3 1458.1(4) 10376(6) -1746(4) 67.5(9) O4 1120.8(5) -1017(7) 5581(5) 85.7(13) C3 1980.5(6) 770(9) 5722(5) 54.8(13) C4 1855.6(5) 4209(8) 4352(5) 42.6(11) N3 1399.3(5) 5502(8) 2699(7) 69.7(12) C5 924.3(6) 3671(8) 2719(5) 45.6(11) C6 2148.5(6) 1566(9) 5409(6) 51.4(12) C7 1698.9(5) 5684(8) 3760(5) 51.3(12) C8 1577.8(5) 4578(8) 2348(5) 49.3(12) C9 1630.9(5) 4982(8) 470(5) 49.2(11) C10 1627.6(6) 7453(8) -210(5) 43.9(12) C11 1960.2(5) 8066(7) -124(5) 39.4(11) C12 2033.5(6) 6066(8) -793(5) 46.6(12) C13 2208.6(6) 5536(9) -486(6) 56.4(13) C14 2316.1(6) 6997(10) 480(6) 57.7(13) N10 1396.7(6) 6348(8) 4205(7) 78.1(14) C15 1566.8(6) 6173(10) 5141(6) 68.8(15) C16 2249.3(6) 9020(9) 1129(6) 55.1(13) C17 2072.7(6) 9558(8) 809(5) 48.2(12) C18 1448.4(6) 8387(9) -682(6) 59.4(14) C19 2025.0(5) 4937(9) 4052(5) 49.6(11) C1A 2168.4(6) 3643(9) 4594(6) 52.7(12) C1B 311.3(6) 5377(10) -1833(6) 57.5(13) C1C 414.7(6) 3592(9) -2428(6) 55.6(13) C1D 593.1(6) 3585(8) -1984(5) 48.7(12) C20 671.5(5) 5314(8) -972(5) 44.7(11) C21 864.1(5) 5178(9) -409(5) 53.4(12) C22 905.5(5) 3124(8) 781(5) 45.4(12) C23 930.8(6) 1540(8) 3851(5) 46.4(11) C24 792.1(6) 259(9) 4271(5) 49.9(12)



C25 603.1(5) 403(8) 3850(5) 44.7(11) C26 515.0(6) 2139(9) 2924(6) 54.4(13) C27 335.1(7) 2129(10) 2604(6) 62.8(14) C28 234.7(6) 335(11) 3197(6) 70.1(15) C29 384.6(7) 7104(11) -853(6) 68.7(15) C30 562.1(7) 7081(9) -421(6) 58.6(13) C31 1114.4(6) 930(10) 4481(6) 62.2(15) C32 315.7(7) -1405(10) 4117(6) 67.7(15) C33 496.0(7) -1374(9) 4444(6) 59.4(13) N34 1074.1(5) 2106(9) 191(5) 69.9(13) N35 1119.8(5) 3000(9) -1191(6) 76.2(14) C36 993.8(6) 4734(12) -1859(6) 79.5(17)

Table 10. Anisotropic displacement parameters (Å2×103) for 6. The anisotropic displacement factor exponent takes the form: -2π2[h2a*2U11

+ ... + 2hka*b*U12]

Atom U11 U22 U33 U23 U13 U12 Cl1 72.0(9) 93.5(11) 84.5(10) 13.1(9) -13.9(7) 20.9(8) Cl2 51.1(8) 162.0(18) 114.4(13) 39.0(13) 5.8(8) 9.8(10) C1 56(3) 49(3) 47(3) 3(3) 12(2) -10(3) C2 50(3) 37(3) 43(3) -1(2) -1(2) 5(2) O3 53.7(19) 67(2) 81(2) 11(2) -8.8(17) 12.4(18) O4 68(2) 115(3) 76(3) 45(3) 23.9(19) 40(2) C3 65(3) 55(3) 44(3) 9(3) 1(2) 3(3) C4 50(3) 51(3) 27(2) -2(2) -2(2) 1(2) N3 48(3) 77(3) 85(3) 20(3) 13(2) 1(2) C5 47(3) 51(3) 39(3) 1(2) 6(2) 3(2) C6 52(3) 62(3) 40(3) 0(3) -7(2) 4(2) C7 53(3) 56(3) 45(3) -9(3) 9(2) -6(2) C8 44(3) 43(3) 61(3) 0(2) 5(2) -3(2) C9 52(3) 45(3) 50(3) -4(3) -4(2) 1(2) C10 50(3) 49(3) 32(3) -7(2) -2(2) 10(2) C11 43(3) 39(3) 36(3) 8(2) 2(2) 3(2) C12 49(3) 51(3) 40(3) 0(2) -1(2) 4(2) C13 51(3) 57(3) 63(3) 9(3) 15(2) 13(3) C14 38(3) 80(4) 56(3) 15(3) 2(2) 0(3) N10 66(3) 90(4) 80(4) 19(3) 26(3) 14(3) C15 70(4) 74(4) 63(3) -5(3) 9(3) 9(3)



C16 50(3) 67(4) 48(3) 5(3) 0(2) -13(3) C17 59(3) 45(3) 40(3) 7(2) 7(2) 0(2) C18 48(3) 66(3) 64(3) 4(3) 3(2) 11(3) C19 51(3) 47(3) 51(3) 2(3) 8(2) -7(3) C1A 42(3) 66(3) 50(3) 4(3) 2(2) -10(3) C1B 46(3) 72(4) 54(3) 9(3) 7(2) 6(3) C1C 60(3) 62(3) 44(3) 0(3) 0(2) -6(3) C1D 48(3) 51(3) 47(3) -1(3) 6(2) 10(2) C20 53(3) 44(3) 36(2) 6(2) -5(2) -4(3) C21 54(3) 51(3) 54(3) 13(3) -9(2) -6(2) C22 44(3) 51(3) 42(3) 3(2) 1(2) 1(2) C23 43(3) 57(3) 41(3) 8(2) 10(2) 6(2) C24 62(3) 55(3) 34(3) 1(3) 8(2) 11(3) C25 56(3) 45(3) 34(2) 2(2) 7(2) 1(3) C26 50(3) 56(3) 58(3) 5(3) 12(2) 2(2) C27 60(4) 69(4) 60(3) 5(3) 5(3) 3(3) C28 56(3) 89(4) 65(3) -2(4) 0(3) -17(4) C29 66(4) 79(4) 62(4) 13(3) 18(3) 33(3) C30 83(4) 49(3) 45(3) -5(3) 3(3) 8(3) C31 54(3) 88(4) 46(3) 26(3) 13(2) 12(3) C32 67(4) 70(4) 66(4) 13(3) -2(3) -26(3) C33 72(4) 55(3) 51(3) 3(3) 4(3) -7(3) N34 75(3) 93(3) 43(3) 4(3) 13(2) 15(3) N35 60(3) 119(4) 50(3) 5(3) 5(2) 7(3) C36 60(3) 118(5) 61(3) 28(4) 6(3) -20(4)

Table 11. Bond lengths (Å) for 6:

Atom Atom Length Atom Atom Length Cl1 C6 1.718(5) C14 C16 1.376(7) Cl2 C1B 1.725(4) N10 C15 1.455(6) C1 C3 1.376(6) C16 C17 1.387(6) C1 C4 1.402(6) C19 C1A 1.370(6) C2 C10 1.339(6) C1B C1C 1.386(7) C2 C11 1.478(5) C1B C29 1.356(7) O3 C18 1.416(6) C1C C1D 1.382(5) O4 C31 1.408(6) C1D C20 1.386(6) C3 C6 1.386(6) C20 C21 1.509(5)



C4 C7 1.517(6) C20 C30 1.393(6) C4 C19 1.381(5) C21 C22 1.524(6) N3 C8 1.491(6) C21 C36 1.542(6) N3 N10 1.260(5) C22 N34 1.496(6) C5 C22 1.528(5) C23 C24 1.337(6) C5 C23 1.509(6) C23 C31 1.498(6) C6 C1A 1.366(7) C24 C25 1.459(6) C7 C8 1.534(6) C25 C26 1.386(6) C7 C15 1.520(6) C25 C33 1.399(6) C8 C9 1.537(6) C26 C27 1.377(6) C9 C10 1.520(6) C27 C28 1.376(7) C10 C18 1.493(6) C28 C32 1.362(7) C11 C12 1.390(6) C29 C30 1.374(6) C11 C17 1.392(6) C32 C33 1.380(6) C12 C13 1.375(6) N34 N35 1.246(5) C13 C14 1.371(6) N35 C36 1.463(7)

Table 12. Bond angles (°) for 6:

Atom Atom Atom Angle Atom Atom Atom Angle C3 C1 C4 121.5(4) C6 C1A C19 121.1(4) C10 C2 C11 129.2(4) C1C C1B Cl2 119.2(4) C1 C3 C6 119.4(5) C29 C1B Cl2 120.3(4) C1 C4 C7 122.5(4) C29 C1B C1C 120.5(4) C19 C4 C1 117.4(4) C1D C1C C1B 118.8(4) C19 C4 C7 120.1(4) C1C C1D C20 122.0(4) N10 N3 C8 110.9(4) C1D C20 C21 120.8(4) C23 C5 C22 113.3(4) C1D C20 C30 116.9(4) C3 C6 Cl1 118.8(4) C30 C20 C21 122.2(4) C1A C6 Cl1 121.8(4) C20 C21 C22 112.7(3) C1A C6 C3 119.5(4) C20 C21 C36 116.1(4) C4 C7 C8 114.7(4) C22 C21 C36 100.7(4) C4 C7 C15 115.2(4) C21 C22 C5 115.8(4) C15 C7 C8 100.5(3) N34 C22 C5 109.5(3) N3 C8 C7 104.1(4) N34 C22 C21 106.3(3) N3 C8 C9 113.2(4) C24 C23 C5 125.8(4) C7 C8 C9 115.6(4) C24 C23 C31 121.5(4) C10 C9 C8 117.8(4) C31 C23 C5 112.7(4)



C2 C10 C9 123.6(4) C23 C24 C25 133.6(4) C2 C10 C18 121.3(4) C26 C25 C24 127.2(4) C18 C10 C9 115.1(4) C26 C25 C33 115.2(4) C12 C11 C2 123.6(4) C33 C25 C24 117.7(4) C12 C11 C17 117.4(4) C27 C26 C25 122.8(5) C17 C11 C2 118.9(4) C28 C27 C26 120.2(5) C13 C12 C11 121.4(4) C32 C28 C27 119.0(5) C14 C13 C12 120.3(5) C1B C29 C30 120.2(5) C13 C14 C16 120.0(4) C29 C30 C20 121.6(5) N3 N10 C15 112.4(4) O4 C31 C23 113.0(4) N10 C15 C7 105.2(4) C28 C32 C33 120.5(5) C14 C16 C17 119.6(4) C32 C33 C25 122.4(5) C16 C17 C11 121.3(4) N35 N34 C22 111.7(4) O3 C18 C10 111.4(4) N34 N35 C36 112.6(4) C1A C19 C4 121.0(5) N35 C36 C21 106.6(4)

Table 13. Torsion angles (°) for 6:

A B C D Angle A B C D Angle Cl1 C6 C1A C19 179.1(3) C15 C7 C8 N3 24.3(5) Cl2 C1B C1C C1D -178.7(3) C15 C7 C8 C9 149.0(4) Cl2 C1B C29 C30 178.8(4) C17 C11 C12 C13 2.5(6) C1 C3 C6 Cl1 179.4(3) C19 C4 C7 C8 115.0(4) C1 C3 C6 C1A -0.4(6) C19 C4 C7 C15 -129.1(4) C1 C4 C7 C8 -65.2(5) C1B C1C C1D C20 -0.4(6) C1 C4 C7 C15 50.7(6) C1B C29 C30 C20 0.2(7) C1 C4 C19 C1A -0.5(6) C1C C1B C29 C30 -0.9(7) C2 C10 C18 O3 15.7(6) C1C C1D C20 C21 175.9(4) C2 C11 C12 C13 179.9(4) C1C C1D C20 C30 -0.2(6) C2 C11 C17 C16 179.6(4) C1D C20 C21 C22 -64.0(5) C3 C1 C4 C7 179.2(4) C1D C20 C21 C36 51.4(6) C3 C1 C4 C19 -1.0(6) C1D C20 C30 C29 0.3(6) C3 C6 C1A C19 -1.1(7) C20 C21 C22 C5 -100.5(4) C4 C1 C3 C6 1.5(7) C20 C21 C22 N34 137.7(4) C4 C7 C8 N3 148.4(4) C20 C21 C36 N35 -136.2(4) C4 C7 C8 C9 -86.8(5) C21 C20 C30 C29 -175.8(4) C4 C7 C15 N10 -148.4(4) C21 C22 N34 N35 -8.3(5) C4 C19 C1A C6 1.6(7) C22 C5 C23 C24 -78.3(5)



N3 C8 C9 C10 55.7(5) C22 C5 C23 C31 101.0(4) N3 N10 C15 C7 16.7(6) C22 C21 C36 N35 -14.2(5) C5 C22 N34 N35 -134.1(4) C22 N34 N35 C36 -1.5(6) C5 C23 C24 C25 0.0(8) C23 C5 C22 C21 169.1(4) C5 C23 C31 O4 178.2(4) C23 C5 C22 N34 -70.9(5) C7 C4 C19 C1A 179.3(4) C23 C24 C25 C26 -4.8(8) C7 C8 C9 C10 -64.2(5) C23 C24 C25 C33 175.8(5) C8 N3 N10 C15 0.0(6) C24 C23 C31 O4 -2.5(6) C8 C7 C15 N10 -24.6(5) C24 C25 C26 C27 -179.4(4) C8 C9 C10 C2 104.7(5) C24 C25 C33 C32 -180.0(4) C8 C9 C10 C18 -76.6(5) C25 C26 C27 C28 -0.7(7) C9 C10 C18 O3 -163.1(4) C26 C25 C33 C32 0.5(7) C10 C2 C11 C12 49.7(6) C26 C27 C28 C32 0.8(8) C10 C2 C11 C17 -133.0(5) C27 C28 C32 C33 -0.3(8) C11 C2 C10 C9 2.7(7) C28 C32 C33 C25 -0.4(7) C11 C2 C10 C18 -176.0(4) C29 C1B C1C C1D 1.0(7) C11 C12 C13 C14 -0.7(6) C30 C20 C21 C22 111.9(5) C12 C11 C17 C16 -2.9(6) C30 C20 C21 C36 -132.7(5) C12 C13 C14 C16 -0.9(7) C31 C23 C24 C25 -179.3(4) C13 C14 C16 C17 0.5(7) C33 C25 C26 C27 0.0(7) C14 C16 C17 C11 1.4(6) N34 N35 C36 C21 10.6(6) N10 N3 C8 C7 -16.4(5) C36 C21 C22 C5 135.1(4) N10 N3 C8 C9 -142.7(4) C36 C21 C22 N34 13.4(4)

Table 14. Hydrogen atom coordinates (Å×104) and isotropic displacement parameters (Å2×103) for 6:

Atom x y z U(eq) H1 1724 1571 5450 61 H2 1753 10232 -794 52 H3 1365 11100 -1719 101 H4 1205 -1835 5345 128 H3A 1965 -646 6270 66 H5A 1031 4560 2940 55 H5B 826 4626 3037 55 H7 1743 7161 3325 62 H8 1576 2904 2553 59 H9A 1749 4385 364 59



H9B 1553 4061 -287 59 H12 1963 5067 -1461 56 H13 2254 4180 -936 68 H14 2434 6621 698 69 H15A 1566 4925 5983 83 H15B 1595 7607 5743 83 H16 2322 10020 1777 66 H17 2029 10942 1227 58 H18A 1379 7204 -1291 71 H18B 1389 8779 368 71 H19 2042 6326 3474 60 H1A 2281 4189 4402 63 H1C 365 2420 -3115 67 H1D 663 2384 -2376 58 H21 898 6609 201 64 H22 812 1970 602 54 H24 823 -990 4984 60 H26 580 3362 2500 65 H27 281 3338 1987 75 H28 113 310 2972 84 H29 314 8307 -472 82 H30 610 8274 255 70 H31A 1185 627 3487 75 H31B 1166 2244 5100 75 H32 249 -2623 4529 81 H33 548 -2578 5081 71 H36A 931 4166 -2896 95 H36B 1055 6152 -2145 95



ORTEP representation of the X-ray structure of 6 (thermal ellipsoids at 40% probability).


enantioselective desymmetrization of prochiral 1,3 ... · enantioselective desymmetrization of...

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