supporting information for synthesis of n,n,o

S-1

Supporting Information for

Synthesis of N,N,O-Trisubstituted Hydroxylamines By Stepwise Reduction

and Substitution of O-Acyl N,N-Disubstituted Hydroxylamines

Sandeep Dhanju and David Crich*

Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, MI 48202, USA.

Table of Content

Compound Expt Spectra General Experimental S-4 -- General procedure (A) for synthesis of O-benzoyl hydroxylamines from secondary amines

S-4 --

O-Benzoyl-N,N-dibenzylhydroxylamine (2a) S-4 S-28, S-29 O-Benzoyl-N-benzyl-N-methylhydroxylamine (2b) S-5 S-30, S-31 1-Piperidinyloxy benzoate (2c) S-5 S-32, S-33 4-Methylpiperidin-1-yl benzoate (2d) S-5 S-34, S-35 General procedure (B) for synthesis of N,N-disubstituted hydroxylamines

from O-benzoyl hydroxylamines

S-6 --

N,N-Dibenzylhydroxylamine (3a) S-6 S-36, S-37

N-Benzyl-N-methylhydroxylamine (3b) S-6 S-38, S-39

Piperidin-1-ol (3c) S-7 S-40, S-41

4-Methylpiperidin-1-ol (3d) S-7 S-42, S-43

3-(1-Pyrrolidinyl)propanenitrile (4) S-8 S-44, S-45

1-Pyrrolidinyloxy 4-phenylbutanoate (2e) S-8 S-46, S-47

General procedure (C) for synthesis of O-acyl hydroxylamines from N,N-

disubstitued hydroxylamines

S-8 --

N,N-Dibenzyl-O-(4-phenylbutanoyl)hydroxylamine (2f) S-9 S-48, S-49

O-(1-Adamantanecarbonyl)-N,N-dibenzylhydroxylamine (2g) S-9 S-50, S-51

N,N-Dibenzyl-O-(3,3-dimethylbutanoyl)hydroxylamine (2h) S-10 S-52, S-53

N-Benzyl-N-methyl-O-(5-phenylpentanoyl)hydroxylamine (2i) S-10 S-54, S-55

1-Piperidinyloxy 4-phenylbutanoate (2j) S-10 S-56, S-57

S-2

4-Methyl-1-piperidinyloxy 4-phenylbutanoate (2k) S-11 S-58, S-59

N,N-Dibenzyl-O-(2-(2-naphthalenyloxy)acetyl)hydroxylamine (2l) S-11 S-60, S-61

N,N-Dibenzyl-O-nicotinoylhydroxylamine (2m) S-12 S-62, S-63

General procedure (D) for synthesis of O-(α-acetoxy) hydroxylamines S-12 --

4-Phenyl-1-(1-pyrrolidinyloxy)butyl acetate (5e) S-12 S-64, S-65

O-(1-Acetoxy-4-phenylbutyl-N,N-dibenzylhydroxylamine (5f) S-13 S-66, S-67

O-(1-Acetoxy-1-adamantanylmethyl)-N,N-dibenzylhydroxylamine (5g) S-14 S-68, S-69

O-(1-Acetoxy-3,3-dimethylbutyl)-N,N-dibenzylhydroxylamine (5h) S-14 S-70, S-71

O-(1-Acetoxy-5-phenylpentyl)-N-benzyl-N-methylhydroxylamine (5i) S-14 S-72, S-73

4-Phenyl-1-(1-piperidinyloxy)butyl acetate (5j) S-15 S-74 S-75

1-(4-Methyl-1-piperidinyloxy)-4-phenylbutyl acetate (5k) S-15 S-76, S-77

O-(1-Acetoxy-2-(naphthalen-2-yloxy)ethyl)-N,N-dibenzylhydroxylamine

(5l)

S-16 S-78, S-79

General procedure (E) for direct synthesis of N,N,O-trisubstituted

hydroxylamines from O-acyl hydroxylamines

S-16 --

N,N,O-Tribenzylhydroxylamine (6a) S-17 S-80, S-81

N,O-Dibenzyl-N-methylhydroxylamine (6b) S-17 S-82, S-83

General procedure (F) for synthesis of N,N,O-trisubstituted

hydroxylamines from O-(α-acetoxy)hydroxylamines

S-18 --

1-(4-Phenylbutoxy)pyrrolidine (6e) S-18 S-84, S-85

N,N-Dibenzyl-O-(4-phenylbutyl)hydroxylamine (6f) S-18 S-86, S-87

O-(1-Adamantanylmethyl)-N,N-dibenzylhydroxylamine (6g) S-18 S-88, S-89

N,N-Dibenzyl-O-(3,3-dimethylbutyl)hydroxylamine (6h) S-19 S-90, S-91

N-Benzyl-N-methyl-O-(5-phenylpentyl)hydroxylamine (6i) S-19 S-92, S-93

1-(4-Phenylbutoxy)piperidine (6j) S-19 S-94, S-95

4-Methyl-1-(4-phenylbutoxy)piperidine (6k) S-20 S-96, S-97

N,N-Dibenzyl-O-(2-(2-naphthalenyloxy)ethyl)hydroxylamine (6l) S-21 S-98, S-99

N,N-Dibenzyl-O-(pyridin-3-ylmethyl)hydroxylamine (6m) S-21 S-100, S-101

N,N-Dibenzyl-O-(1-phenyl-3-buten-1-yl)hydroxylamine (7a) S-22 S-102, S-103

N-Benzyl-N-methyl-O-(1-phenylbut-3-en-1-yl)hydroxylamine (7b) S-22 S-104, S-105

S-3

O-(1-(Adamantan-1-yl)but-3-en-1-yl)-N,N-dibenzylhydroxylamine (7c) S-24 S-106, S-107

1-(Dibenzylaminoxy)-4,4-dimethyl-1-phenylpentan-3-one (7d) S-24 S-108, S-109

N,N-Dibenzyl-O-((5-methylfuran-2-yl)benzyl)hydroxylamine (7e) S-25 S-110, S-111

N,N-Dibenzyl-O-(1-(5-methylfuran-2-yl)-4-phenylbutyl)hydroxylamine

(7f)

S-26 S-112, S-113

References S-27 --

S-4

General Experimental

All reactions were carried out in oven dried glassware under an argon atmosphere. All reagents

and solvents were purchased from commercial suppliers and were used without further

purification unless otherwise specified. All separations were carried out by flash chromatography

using silica gel (230-400 mesh) or neutral alumina (32-63 μm) as stationary phase unless

otherwise specified. Thin layer chromatography was performed with pre-coated glass backed

plates (w/UV 254) and visualized by UV irradiation (254 nm) or by charring in cerium-

ammonium-molybdate (CAM) or ninhydrin solution. 1H and 13C NMR spectra of all compounds

were recorded using 400 MHz or 500 MHz instruments. High resolution mass spectra were

recorded under electrospray conditions with a time of flight mass analyzer. Melting points were

determined using an electrothermal melting point apparatus.

General procedure (A) for synthesis of O-benzoyl hydroxylamines from secondary amines.

O-Benzoyl hydroxylamines were prepared by a modification of the Ganem protocol.1 To a

stirred suspension of benzoyl peroxide (50 % w/w blended with dicyclohexyl phthalate, 1.1

mmol, 1.1 equiv) and K2HPO4 (1.5 mmol, 1.5 equiv) in dry DMF (2.5 mL) was added secondary

amine (1 mmol, 1 equiv) at room temperature. The reaction mixture was stirred at room

temperature until the completion as indicated by TLC analysis. The reaction was quenched by

addition of water (10 mL) and then was stirred vigorously for 1 h. The resultant mixture was

extracted with ethyl acetate (10 mL x 2), the combined ethyl acetate layer was washed with

saturated aq. NaHCO3, water, and brine, dried over anhydrous Na2SO4, and concentrated under

reduced pressure. The resulting crude product was purified by flash column chromatography on

silica gel to afford the desired O- benzoyl hydroxylamine.

O-Benzoyl-N,N-dibenzylhydroxylamine (2a).

The title compound2 was prepared according to general procedure A using N,N-dibenzylamine

(0.5 mL, 2.60 mmol) as substrate with stirring for 10 h. It was isolated (eluent: 0 – 5 % of

acetone in hexane) as a white solid (0.67 g, 81 %). M.p. 97 – 98 oC; lit2 m.p. 96 – 98 oC; IR

S-5

(neat, cm-1) √ 1734; 1H NMR (400 MHz, CDCl3) δ 7.86 – 7.80 (m, 2H), 7.50 (t, J = 7.3 Hz, 1H),

7.46 – 7.44 (m, 4H), 7.39 – 7.22 (m, 8H), 4.21 (s, 4H); 13C NMR (100 MHz, CDCl3) δ 164.9,

135.9, 132.8, 129.4, 129.3, 128.3, 128.3, 127.6, 62.1.

O-Benzoyl-N-benzyl-N-methylhydroxylamine (2b).

The title compound was prepared according to general procedure A using N-benzyl-N-

methylamine (0.5 mL, 3.88 mmol) as substrate with stirring for 10 h. It was isolated (eluent: 0 –

5 % of ethyl acetate in toluene) as a colorless oil (0.77 g, 82 %). IR (neat, cm-1) √ 1737; 1H

NMR (400 MHz, CDCl3) δ 7.93 – 7.88 (m, 2H), 7.52 (t, J = 7.3 Hz, 1H), 7.45 – 7.36 (m, 4H),

7.34 – 7.22 (m, 3H), 4.16 (s, 2H), 2.93 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.9, 135.6,

132.9, 129.4, 129.3, 128.4, 128.3, 127.7, 65.1, 46.1; ESIHRMS calculated for C15H15NO2Na

[M+Na]+, 264.1000; found, 264.1006.

1-Piperidinyloxy benzoate (2c).

The title compound2 was prepared according to general procedure A using piperidine (1.0 mL,

10.12 mmol) as substrate with stirring for 1.5 h. It was isolated (eluent: 0 – 5 % of ethyl acetate

in toluene) as a white solid (1.80 g, 86 %). M.p. 58 – 60 oC; lit2 m.p. 55 – 59 oC; IR (neat, cm-1)

√ 1734; 1H NMR (400 MHz, CDCl3) δ 8.02 – 7.96 (m, 2H), 7.53 (t, J = 7.3 Hz, 1H), 7.41 (t, J =

7.8 Hz, 2H), 3.48 (br s, 2H), 2.76 (d, J = 5.9 Hz, 2H), 1.86 – 1.76 (m, 4H), 1.64 (br s, 1H), 1.36 –

1.18 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 164.7, 132.9, 129.6, 129.4, 128.3, 57.5, 25.0, 23.3.

4-Methylpiperidin-1-yl benzoate (2d).

The title compound3 was prepared according to general procedure A using 4-methylpiperidine

(2.5 mL, 20.57 mmol) as substrate with stirring for 1 h. It was isolated (eluent: 0 – 10 % of ethyl

S-6

acetate in toluene) as a white solid (3.71 g, 82 %). M.p. 91 – 92 oC; IR (neat, cm-1) √ 1732; 1H

NMR (400 MHz, CDCl3) δ 7.99 (d, J = 7.3 Hz, 2H), 7.53 (t, J = 7.3 Hz, 1H), 7.41 (t, J = 7.6 Hz,

2H), 3.51 (d, J = 8.8 Hz, 2H), 2.72 (t, J = 10.5 Hz, 2H), 1.75 (d, J = 13.2 Hz, 2H), 1.65 – 1.52

(m, 2H), 1.52 – 1.40 (m, 1H), 0.93 (d, J = 5.9 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 164.8,

132.9, 129.6, 129.4, 128.3, 57.2, 33.5, 30.1, 21.2.

General procedure (B) for synthesis of N,N-disubstituted hydroxylamines from O-benzoyl

hydroxylamines.

To a stirred solution of the O-benzoyl hydroxylamine (1 mmol, 1 equiv) in dry CH2Cl2 (6 mL)

was added DIBAL (1 M solution in hexane, 2.5 mmol, 2.5 equiv) slowly via syringe at 0 oC (ice-

bath). The reaction mixture was stirred for 15 minutes and quenched by addition of saturated aq.

NH4Cl (10 mL) and saturated aq. sodium potassium tartrate (8 mL) at 0 oC. The resultant mixture

was warmed to room temperature and stirred vigorously for 1 h and extracted with CH2Cl2 (10

mL x 4). The combined organic layer was washed with brine (20 mL), dried over anhydrous

Na2SO4, and concentrated under reduced pressure. The resulting crude product was purified by

flash column chromatography on silica gel to afford the desired hydroxylamine.

N,N-Dibenzylhydroxylamine (3a).

According to the general procedure B, compound 2a (100 mg, 0.32 mmol) was converted to 3a4

(60 mg, 90 %) which was isolated as a white solid (eluent: 5 – 15 % of ethyl acetate in hexane).

M.p. 119 – 121 oC; lit4 m.p. 118 – 119 oC; 1H NMR (400 MHz, CDCl3) δ 7.37 – 7.24 (m, 10H),

6.90 (br s, 1H), 3.69 (s, 4H); 13C NMR (100 MHz, CDCl3) δ 137.1, 129.8, 128.3, 127.5, 63.7.

N-Benzyl-N-methylhydroxylamine (3b).

According to the general procedure B, compound 2b (500 mg, 2.07 mmol) was converted to 3b5

(265 mg, 93 %) which was isolated as a colorless oil (eluent :10 – 30 % of ethyl acetate in

S-7

hexane). 1H NMR (400 MHz, CDCl3) δ 7.36 – 7.24 (m, 5H), 3.70 (s, 2H), 2.51 (s, 3H); 13C NMR

(100 MHz, CDCl3) δ 136.9, 129.9, 128.3, 127.5, 66.4, 47.5.

Piperidin-1-ol (3c).

According to the general procedure B, compound 2c (1 g, 4.87 mmol) was converted to 3c6 (313

mg, 63 %) which was isolated as a colorless oil (eluent: ether). 1H NMR (400 MHz, CDCl3) δ

8.09 (br s, 1H), 3.22 (d, J = 9.8 Hz, 2H), 2.41 (t, J = 11.0 Hz, 2H), 1.70 (d, J = 13.2 Hz, 2H),

1.60 – 1.42 (m, 3H), 1.18 – 1.02 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 59.0, 25.4, 23.0.

4-Methylpiperidin-1-ol (3d).

According to the general procedure B, compound 2d (1 g, 4.56 mmol) was converted to 3d7 (443

mg, 84 %) which was isolated as a colorless oil (eluent: ether). The NMR data suggest a mixture

of two stereo-isomers in 8.4:1 ratio. Major isomer; 1H NMR (400 MHz, CDCl3) δ 8.60 (br s, 1H)

3.22 (d, J = 10.8 Hz, 2H), 2.44 (t, J = 11.7 Hz, 2H), 1.71 – 1.62 (m, 2H), 1.42 – 1.30 (m, 1H),

1.30 – 1.17 (m, 2H), 0.86 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 58.7, 34.0, 29.8,

21.3. The minor isomer was identified by 1H NMR (400 MHz, CDCl3) δ 3.00 – 2.83 (m, 4H),

1.61 – 1.46 (m, 4H), 0.94 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 54.6, 29.4, 20.0

(a 4th C is not resolved from that of the major isomer).

S-8

3-(1-Pyrrolidinyl)propanenitrile (4).

To an ice cooled stirred solution of acrylonitrile (4.0 mL, 60.88 mmol, 1.25 equiv) and

Amberlyst-15 (1 g, 30 % w/w) was added pyrrolidine (4.0 mL, 48.70 mmol, 1 equiv) slowly via

syringe. The reaction mixture was warmed to room temperature and stirred for 0.5 h then was

diluted with CH2Cl2 (100 mL), filtered, and concentrated under reduced pressure to yield 48

(5.57 g, 92 %) as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ 2.71 (t, J = 7.2 Hz, 2H), 2.53

– 2.44 (m, 6H), 1.79 – 1.68 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 118.9, 53.8, 51.2, 23.5,

17.6.

1-Pyrrolidinyloxy 4-phenylbutanoate (2e).

To a stirred solution of 4 (0.50 g, 4.03 mmol, 1 equiv) in dry CH2Cl2 (40 mL) was added m-

CPBA (0.95 g 77 % m-CPBA, 6.05 mmol, 1.5 equiv) and K2CO3 (1.11 g, 8.06 mmol, 2 equiv) at

–78 oC. The reaction mixture was stirred at –78 oC for 3 h, warmed slowly to room temperature,

and stirred for an additional 12 h at room temperature. The resultant suspension was filtered and

4-phenylbutyric acid (0.99 g, 6.05 mmol, 1.5 equiv), DMAP (0.10 g, 0.81 mmol, 0.2 equiv), and

N,N'-dicyclohexylcarbodiimide (1.25 g, 6.05 mmol, 1.5 equiv) were added to the filtrate. The

reaction mixture was stirred for 2 h at room temperature, filtered through a pad of Celite, and

was washed with saturated aq. NaHCO3 (40 mL), brine (40 mL), dried over anhydrous Na2SO4,

concentrated under reduced pressure, and purified by flash column chromatography on silica gel

(10 – 30 % of ethyl acetate in hexane) to afford 2e (0.49 g, 52 %) as a light red oil. 1H NMR (400

MHz, CDCl3) δ 7.31 – 7.23 (m, 2H), 7.22 – 7.13 (m, 3H), 3.14 (s, 4H), 2.64 (t, J = 7.5 Hz, 2H),

2.25 (t, J = 7.5 Hz, 2H), 2.00 – 1.90 (m, 2H), 1.85 (s, 4H); 13C NMR (100 MHz, CDCl3) δ 172.0,

141.2, 128.5, 128.4, 126.0, 57.4, 35.1, 32.4, 26.6, 22.0; ESIHRMS calculated for C14H19NO2Na

[M+Na]+, 256.1313; found, 256.1319.

General procedure (C) for synthesis of O-acyl hydroxylamines from N,N-disubstitued

hydroxylamines.

To a stirred solution of N,N-disubstituted hydroxylamine (1 mmol), carboxylic acid (1.25 – 2.5

mmol) and DMAP (0.2 mmol, 0.2 equiv) in dry CH2Cl2 (10 mL) at room temperature, a solution

of N,N'-dicyclohexylcarbodiimide (1.25 – 2.5 mmol, 1.25 – 2.5 equiv) in dry CH2Cl2 (1 mL) was

added. The reaction mixture was stirred at room temperature until completion (indicated by TLC

S-9

analysis) then was filtered through a pad of Celite. The filtrate was washed with saturated aq.

NaHCO3 (10 mL), brine solution (10 mL), dried over anhydrous Na2SO4, concentrated under

reduced pressure, and purified by flash column chromatography on silica gel to afford the O-acyl

hydroxylamine.

N,N-Dibenzyl-O-(4-phenylbutanoyl)hydroxylamine (2f).

The title compound was prepared according to general procedure C using 3a (1 g, 4.69 mmol, 1

equiv), 4-phenylbutyric acid (0.96 g, 5.86 mmol, 1.25 equiv) and N,N'-dicyclohexylcarbodiimide

(1.22 g, 5.86 mmol, 1.25 equiv) with stirring for 40 mins. It was isolated (1.67 g, 98 %) as a

colorless oil (eluent: 0 – 5 % of ethyl acetate in hexane). IR (neat, cm-1) √ 1756; 1H NMR (400

MHz, CDCl3) δ 7.42 – 7.41 (m, 4H), 7.34 – 7.23 (m, 8H), 7.19 – 7.16 (m, 1H), 7.02 (d, J = 6.9

Hz, 2H), 4.07 (s, 4H), 2.37 (t, J = 7.6 Hz, 2H), 2.06 (t, J = 7.3 Hz, 2H), 1.75 – 1.62 (m, 2H); 13C

NMR (100 MHz, CDCl3) δ 171.8, 141.3, 136.1, 129.4, 128.4, 128.3, 128.3, 127.7, 125.8, 62.5,

34.7, 31.9, 26.2; ESIHRMS calculated for C24H25NO2Na [M+Na]+, 382.1783; found, 382.1779.

O-(1-Adamantanecarbonyl)-N,N-dibenzylhydroxylamine (2g).


equiv), 1-adamantanecarboxylic acid (1.69 g, 9.38 mmol, 2 equiv) and N,N'-

dicyclohexylcarbodiimide (1.94 g, 9.38 mmol, 2 equiv) with stirring for 28 h. It was isolated

(1.27 g, 72 %) as a white solid (eluent: 0 – 5 % of ethyl acetate in hexane). M.p. 110 – 111 o C;

IR (neat, cm-1) √ 1747; 1H NMR (400 MHz, CDCl3) δ 7.40 (d, J = 7.3 Hz, 4H), 7.34 – 7.23 (m,

6H), 4.05 (s, 4H), 1.89 (s, 3H), 1.69 – 1.53 (m, 12H); 13C NMR (100 MHz, CDCl3) δ 175.2,

136.1, 129.4, 128.1, 127.5, 62.1, 40.4, 38.5, 36.4, 27.8; ESIHRMS calculated for C25H29NO2Na

[M+Na]+, 398.2096; found, 398.2103.

S-10

N,N-Dibenzyl-O-(3,3-dimethylbutanoyl)hydroxylamine (2h).


equiv), 3,3-dimethylbutanoic acid (0.75 mL, 5.86 mmol, 1.25 equiv) and N,N'-

dicyclohexylcarbodiimide (1.22 g, 5.86 mmol, 1.25 equiv) with stirring for 1.5 h. It was isolated

(0.91 g, 63 %) as a white solid (eluent: 0 – 5 % of ethyl acetate in hexane). M.p. 53 – 54 oC; IR

(neat, cm-1) √ 1752; 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 6.9 Hz, 4H), 7.34 – 7.22 (m, 6H),

4.05 (s, 4H), 1.95 (s, 2H), 0.77 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 170.2, 136.3, 129.3,

128.3, 127.5, 62.2, 46.2, 30.5, 29.3; ESIHRMS calculated for C20H25NO2Na [M+Na]+, 334.1783;

found, 334.1782.

N-Benzyl-N-methyl-O-(5-phenylpentanoyl)hydroxylamine (2i).

The title compound was prepared according to general procedure C using 3b (210 mg, 1.53

mmol, 1 equiv), 5-phenylvaleric acid (341 mg, 1.91 mmol, 1.25 equiv) and N,N'-

dicyclohexylcarbodiimide (394 mg, 1.91 mmol, 1.25 equiv) with stirring for 0.5 h. It was

isolated (396 mg, 87 %) as a colorless oil (eluent: 5 – 20 % of ethyl acetate in hexane). 1H NMR

(400 MHz, CDCl3) δ 7.38 – 7.33 (m, 2H), 7.33 – 7.22 (m, 5H), 7.21 – 7.16 (m, 1H), 7.13 (d, J =

7.3 Hz, 2H), 3.99 (s, 2H), 2.81 (s, 3H), 2.54 (t, J = 7.0 Hz, 2H), 2.17 (t, J = 7.0 Hz, 2H), 1.58 –

1.45 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 171.8, 142.0, 135.9, 129.3, 128.4, 128.3, 128.3,

127.7, 125.8, 65.0, 46.2, 35.4, 32.7, 30.6, 24.5; ESIHRMS calculated for C19H23NO2Na

[M+Na]+, 320.1626; found, 320.1625.

1-Piperidinyloxy 4-phenylbutanoate (2j).

S-11

The title compound was prepared according to general procedure C using 3c (170 mg, 1.68

mmol, 1 equiv), 4-phenylbutyric acid (355 mg, 2.10 mmol, 1.25 equiv) and N,N'-


isolated (387 mg, 93 %) as a colorless oil (eluent: 5 – 20 % of ethyl acetate in hexane). IR (neat,

cm-1) √ 1753; 1H NMR (400 MHz, CDCl3) δ 7.31 – 7.24 (m, 2H), 7.21 – 7.14 (m, 3H), 3.35 (br

s, 2H), 2.70 – 2.51 (m, 4H), 2.28 (t, J = 7.3 Hz, 2H), 2.01 – 1.90 (m, 2H), 1.82 – 1.69 (m, 4H),

1.61 (br s, 1H), 1.34 – 1.10 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 171.5, 141.3, 128.5, 128.4,

126.0, 57.4, 35.1, 32.4, 26.7, 25.0, 23.2; ESIHRMS calculated for C15H21NO2Na [M+Na]+,

270.1470; found, 270.1465.

4-Methyl-1-piperidinyloxy 4-phenylbutanoate (2k).

The title compound was prepared according to general procedure C using 3d (360 mg, 3.13

mmol, 1 equiv), 4-phenylbutyric acid (642 mg, 3.91 mmol, 1.25 equiv) and N,N'-


isolated (740 mg, 91 %) as a colorless oil (eluent: 10 – 20 % of ethyl acetate in hexane). IR

(neat, cm-1) √ 1752; 1H NMR (400 MHz, CDCl3) δ 7.31 – 7.24 (m, 2H), 7.21 – 7.14 (m, 3H),

3.36 (d, J = 8.8 Hz, 2H), 2.65 (t, J = 7.6 Hz, 2H), 2.57 (t, J = 10.5 Hz, 2H), 2.27 (t, J = 7.6 Hz,

2H), 2.02 – 1.90 (m, 2H), 1.70 (d, J = 12.7 Hz, 2H), 1.57 – 1.34 (m, 3H), 0.91 (d, J = 5.9 Hz,

3H); 13C NMR (100 MHz, CDCl3) δ 171.6, 141.3, 128.5, 128.4, 126.0, 57.1, 35.1, 33.4, 32.4,


N,N-Dibenzyl-O-(2-(2-naphthalenyloxy)acetyl)hydroxylamine (2l).


equiv), 2-(naphthalen-2-yloxy)acetic acid (1.19 g, 5.86 mmol, 1.25 equiv) and N,N'-

dicyclohexylcarbodiimide (1.22 g, 5.86 mmol, 1.25 equiv) with stirring for 0.5 h. It was isolated

S-12

(1.67 g, 89 %) as a white solid (eluent: 10 – 45 % of ethyl acetate in hexane). M.p. 87 – 89 oC;

IR (neat, cm-1) √ 1768; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.8 Hz, 1H), 7.69 (d, J = 9.3

Hz, 1H), 7.60 (d, J = 8.3 Hz, 1H), 7.47 – 7.28 (m, 12H), 6.99 (dd, J = 8.8, 2.5 Hz, 1H), 6.66 (d, J

= 2.5 Hz, 1H), 4.44 (s, 2H), 4.13 (s, 4H); 13C NMR (100 MHz, CDCl3) δ 168.4, 155.6, 135.5,

134.2, 129.6, 129.5, 129.3, 128.6, 128.1, 127.6, 127.0, 126.3, 124.0, 118.2, 107.1, 64.6, 63.1;

ESIHRMS calculated for C26H23NO3Na [M+Na]+, 420.1576; found, 420.1575.

N,N-Dibenzyl-O-nicotinoylhydroxylamine (2m).


equiv), nicotinic acid (0.72 g, 5.86 mmol, 1.25 equiv) and N,N'-dicyclohexylcarbodiimide (1.22

g, 5.86 mmol, 1.25 equiv) with stirring for 1 h. It was isolated (1.45 g, 97 %) as a white solid

(eluent: 10 – 45 % of ethyl acetate in hexane). M.p. 117 – 118 oC; IR (neat, cm-1) √ 1742; 1H

NMR (400 MHz, CDCl3) δ 8.99 (d, J = 1.5 Hz, 1H), 8.70 (dd, J = 4.9, 2.0 Hz, 1H), 8.05 (td, J =

7.9, 2.0 Hz, 1H), 7.44 (d, J = 6.7 Hz, 4H), 7.34 – 7.22 (m, 7H), 4.22 (s, 4H); 13C NMR (100

MHz, CDCl3) δ 163.6, 153.3, 150.3, 136.8, 135.7, 129.4, 128.4, 127.8, 125.3, 123.3, 62.4;

ESIHRMS calculated for C20H18N2O2Na [M+Na]+, 341.1266; found, 341.1261.

General procedure (D) for synthesis of O-(α-acetoxy) hydroxylamines.

To a stirred solution of O-acyl hydroxylamines (0.5 mmol) at –78 oC in dry CH2Cl2 (3 mL) were

added sequentially, dropwise DIBAL (1 M in hexane, 0.63 – 1 mmol, 1.25 – 2 equiv), pyridine

(1.5 mmol, 3 equiv), a solution of DMAP (1 mmol, 2 equiv) in dry CH2Cl2 (1.5 mL), and Ac2O

(3 mmol, 6 equiv). The reaction mixture was stirred for 12 h (overnight) at –78 oC, warmed

slowly to 0 oC, and quenched by addition of saturated aq. NH4Cl (5 mL) and saturated aq.

sodium potassium tartrate (4 mL) at 0 oC. The resultant mixture was warmed to room

temperature and stirred vigorously for 1 h and extracted with CH2Cl2 (5 mL x 4). The combined

organic layer was washed with brine (10 mL), dried over anhydrous Na2SO4, concentrated under

reduced pressure, and purified by flash column chromatography on silica gel unless otherwise

noted.

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4-Phenyl-1-(1-pyrrolidinyloxy)butyl acetate (5e).

The title compound was prepared according to general procedure D using 2e (100 mg, 0.43

mmol, 1 equiv) and DIBAL (0.64 mL, 1 M in hexane, 0.64 mmol, 1.5 equiv). Flash column

chromatography (10 – 20 % of ethyl acetate in hexane) gave 5e (75 mg, 63 %) as a colorless oil.

Analytical data: 1H NMR (400 MHz, CDCl3) δ 7.31 – 7.24 (m, 2H), 7.21 – 7.14 (m, 3H), 6.13 –

6.08 (m, 1H), 3.00 (s, 4H), 2.67 – 2.59 (m, 2H), 2.09 (s, 3H), 1.76 (s, 4H), 1.71 – 1.64 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 170.4, 142.0, 128.4, 128.3, 125.8, 100.2, 57.4, 35.5, 32.5, 26.1,

21.9, 21.5; ESIHRMS calculated for C16H23NO3Na [M+Na]+, 300.1576; found, 300.1582.

O-(1-Acetoxy-4-phenylbutyl-N,N-dibenzylhydroxylamine (5f).

The title compound was prepared by following general procedure D using 2f (100 mg, 0.28

mmol, 1 equiv) and DIBAL (0.56 mL, 1 M in hexane, 0.56 mmol, 2 equiv). Flash column

chromatography (0 – 5 % of ethyl acetate in hexane) gave 5f (102 mg, 88 %) as a colorless oil.

IR (neat, cm-1) √ 1737; 1H NMR (400 MHz, CDCl3) δ 7.40 – 7.21 (m, 12H), 7.19 – 7.16 (m, 1H),

7.07 (d, J = 7.3 Hz, 2H), 5.88 (t, J = 5.4 Hz, 1H), 4.01 (br s, 2H), 3.78 (d, J = 12.7 Hz, 2H), 2.41

(t, J = 7.3 Hz, 2H), 1.85 (s, 3H), 1.51 – 1.22 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 170.2,

141.9, 137.1, 129.5, 128.4, 128.3, 128.2, 127.4, 125.7, 100.4, 62.9, 35.3, 32.4, 25.4, 21.2;


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O-(1-Acetoxy-1-adamantanylmethyl)-N,N-dibenzylhydroxylamine (5g).

The title compound was prepared according to general procedure D using 2g (300 mg, 0.80

mmol, 1 equiv) and DIBAL (1 mL, 1 M in hexane, 1 mmol, 1.25 equiv). Flash column

chromatography (0 – 8 % of ethyl acetate in hexane) gave 5g (217 mg, 65 %) as a colorless oil.

IR (neat, cm-1) √ 1747; 1H NMR (400 MHz, CDCl3) δ 7.36 – 7.28 (m, 8H), 7.28 – 7.22 (m, 2H),

5.58 (s, 1H), 3.91 (d, J = 13.2 Hz, 2H), 3.82 (d, J = 13.2 Hz, 2H), 1.89 (s, 3H), 1.82 (s, 3H), 1.65

(d, J = 11.7 Hz, 3H), 1.58 (d, J = 11.7 Hz, 3H), 1.49 (d, J = 12.2 Hz, 3H), 1.33 (d, J = 12.2 Hz,

3H); 13C NMR (100 MHz, CDCl3) δ 170.6, 137.2, 129.6, 128.1, 127.2, 103.1, 62.2, 37.0, 36.7,


O-(1-Acetoxy-3,3-dimethylbutyl)-N,N-dibenzylhydroxylamine (5h).

The title compound was prepared according to general procedure D using 2h (100 mg, 0.32


chromatography (0 – 5 % of ethyl acetate in hexane) gave 5h (85 mg, 75 %) as a colorless oil. 1H

NMR (400 MHz, CDCl3) δ 7.39 – 7.29 (m, 8H), 7.28 – 7.22 (m, 2H), 6.00 (t, J = 5.4 Hz, 1H),

4.00 (br s, 2H), 3.77 (d, J = 13.2 Hz, 2H), 1.88 (s, 3H), 1.40 (dd, J = 14.2, 5.9 Hz, 1H), 1.34 (dd,

J = 14.2, 4.9 Hz, 1H), 0.68 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 170.1, 137.3, 129.4, 128.3,

127.3, 98.5, 62.8, 46.1, 29.6, 29.1, 21.5; ESIHRMS calculated for C22H29NO3Na [M+Na]+,

378.2045; found, 378.2046.

O-(1-Acetoxy-5-phenylpentyl)-N-benzyl-N-methylhydroxylamine (5i).

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O

O

NMe

Bn

Ph

O

The title compound was prepared according to general procedure D using 2i (50 mg, 0.17 mmol,

1 equiv) and DIBAL (0.30 mL, 1 M in hexane, 0.30 mmol, 1.75 equiv). Flash column

chromatography (5 – 10 % of ethyl acetate in hexane) gave 5i (51 mg, 89 %) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.35 – 7.23 (m, 7H), 7.20 – 7.11 (m, 3H), 5.91 (br s, 1H), 3.88 (br

s, 1H), 3.76 (d, J = 12.7 Hz, 1H), 2.64 (s, 3H), 2.53 (t, J = 7.6 Hz, 2H), 1.99 (s, 3H), 1.52 (s, 4H),

1.22 (br s, 2H); 13C NMR (100 MHz, CDCl3) δ 170.3, 142.4, 136.9, 129.6, 128.4, 128.2, 128.2,

127.4, 125.6, 100.3, 65.4, 46.5, 35.7, 32.7, 31.0, 23.6, 21.3; ESIHRMS calculated for

C21H27NO3Na [M+Na]+, 364.1889; found, 364.1885.

4-Phenyl-1-(1-piperidinyloxy)butyl acetate (5j).

OPh

O

N

O

The title compound was prepared according to general procedure D using 2j (100 mg, 0.40


chromatography on neutral alumina (0 – 8 % of ethyl acetate in hexane) gave 5j (64 mg, 55 %)

as a colorless oil. Analytical data: 1H NMR (400 MHz, CDCl3) δ 7.31 – 7.25 (m, 2H), 7.21 –

7.15 (m, 3H), 6.07 (t, J = 4.6 Hz, 1H), 3.24 (br s, 2H), 2.63 (t, J = 6.9 Hz, 2H), 2.54 – 2.36 (m,

2H), 2.06 (s, 3H), 1.79 – 1.62 (m, 6H), 1.55 (br s, 3H), 1.14 (br s, 1H); 13C NMR (100 MHz,

CDCl3) δ 170.3, 142.0, 128.4, 128.3, 125.8, 99.8, 58.2, 57.0, 35.5, 32.6, 26.1, 25.3, 23.4, 21.4;


1-(4-Methyl-1-piperidinyloxy)-4-phenylbutyl acetate (5k).

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The title compound was prepared according to general procedure D using 2k (100 mg, 0.38


chromatography (5 – 10 % of ethyl acetate in hexane) gave 5k (98 mg, 84 %) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.31 – 7.25 (m, 2H), 7.21 – 7.14 (m, 3H), 6.06 (t, J = 4.8 Hz, 1H),

3.32 – 3.17 (m, 2H), 2.63 (t, J = 6.9 Hz, 2H), 2.53 – 2.36 (m, 2H), 2.06 (s, 3H), 1.77 – 1.58 (m,

6H), 1.40 – 1.19 (m, 3H), 0.88 (d, J = 5.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 170.4, 142.0,

128.4, 128.3, 125.8, 99.9, 57.8, 56.7, 35.5, 34.0, 33.9, 32.6, 30.1, 26.1, 21.4, 21.3; ESIHRMS

calculated for C18H27NO3Na [M+Na]+, 328.1889; found, 328.1888.

O-(1-Acetoxy-2-(naphthalen-2-yloxy)ethyl)-N,N-dibenzylhydroxylamine (5l).

The title compound was prepared according to general procedure D using 2l (100 mg, 0.25


chromatography (0 – 10 % of ethyl acetate in hexane) gave 5l (100 mg, 90 %) as a colorless oil.

IR (neat, cm-1) √ 1746; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.3 Hz, 1H), 7.73 – 7.67 (m,

2H), 7.44 (t, J = 7.1 Hz, 1H), 7.41 – 7.30 (m, 9H), 7.30 – 7.23 (m, 2H), 7.04 (dd, J = 8.8, 2.5 Hz,

1H), 6.95 (d, J = 2.0 Hz, 1H), 6.26 (t, J = 5.4 Hz, 1H), 4.04 (d, J = 13.2 Hz, 2H), 3.97 – 3.87 (m,

3H), 3.84 (dd, J = 10.3, 5.4 Hz, 1H) 1.86 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 169.9, 156.1,

136.9, 134.4, 129.7, 129.3, 129.1, 128.3, 127.6, 127.5, 126.8, 126.3, 123.8, 118.7, 106.9, 96.7,


General procedure (E) for direct synthesis of N,N,O-trisubstituted hydroxylamines from O-

acyl hydroxylamines.

To a stirred solution of O-acyl hydroxylamine (0.5 mmol) in dry CH2Cl2 (3 mL) were added

sequentially, dropwise DIBAL (1 M in hexane, 1 mmol, 2 equiv), pyridine (1.5 mmol, 3 equiv),

a solution of DMAP (1 mmol, 2 equiv) in dry CH2Cl2 (1.5 mL), and Ac2O (3 mmol, 6 equiv) at –

78 oC. The reaction mixture was stirred for 12 h (overnight) at –78 oC, warmed slowly to 0 oC,

and quenched by adding saturated aq. NH4Cl (5 mL) and saturated aq. sodium potassium tartrate

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(4 mL) at 0 oC. The resultant mixture was warmed to room temperature and stirred vigorously

for 1 h. Then the mixture was extracted with CH2Cl2 (5 mL x 4), and the combined organic layer

was washed with brine (10 mL), dried over anhydrous Na2SO4, and concentrated under reduced

pressure. The so obtained crude intermediate was dissolved in dry CH2Cl2 (10 mL) to which then

were added dropwise and sequentially Et3SiH (1.25, 2.5 equiv) and BF3.OEt2 (1.25, 2.5 equiv) at

–78 oC. The reaction mixture was warmed slowly to 0 oC and partitioned between pentane (30

mL) and saturated aq. NaHCO3 (30 mL). The aqueous layer was extracted with pentane (10 mL

x 2) and the combined organic layer was dried over anhydrous Na2SO4, concentrated under

reduced pressure, and purified by flash column chromatography on silica gel (0 – 5 % of ethyl

acetate in hexane) to afford desired hydroxylamines.

N,N,O-Tribenzylhydroxylamine (6a).

According to general procedure E, compound 2a (300 mg, 0.95 mmol) was converted to 6a9

(143 mg, 50 %) which was a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.43 – 7.42 (m, 4H),

7.39 – 7.27 (m, 6H), 7.25 – 7.20 (m, 3H), 6.98 – 6.96 (m, 2H), 4.19 (s, 2H), 3.90 (s, 4H); 13C

NMR (100 MHz, CDCl3) δ 137.8, 137.0, 129.8, 129.1, 128.13, 128.11, 127.7, 127.3, 76.1, 62.9.

N,O-Dibenzyl-N-methylhydroxylamine (6b).

According to general procedure E, compound 2b (68 mg, 0.28 mmol) was converted to 6b (34

mg, 53 %) which was a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.40 – 7.24 (m, 8H), 7.24 –

7.19 (m, 2H), 4.51 (s, 2H), 3.83 (s, 2H), 2.65 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 137.5 (2C),

129.7, 128.8, 128.2, 128.2, 127.7, 127.3, 74.9, 65.2, 45.6; ESIHRMS calculated for C15H18NO

[M+H]+, 228.1388; found, 228.1385.

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General procedure (F) for synthesis of N,N,O-trisubstituted hydroxylamines from O-(α-

acetoxy)hydroxylamines.

To a stirred solution of O-(α-acetoxy)hydroxylamine (0.25 mmol) in dry CH2Cl2 (5 mL) were

added dropwise and sequentially Et3SiH (0.63 mmol, 2.5 equiv) and BF3.OEt2 (0.63 mmol, 2.5

equiv) at –78 oC. The reaction mixture was warmed slowly to 0 oC or room temperature and

stirred until completion as indicated by TLC analysis. The reaction mixture was partitioned

between pentane (15 mL) and saturated aq. NaHCO3 (15 mL) and the aqueous layer was

extracted with pentane (5 mL x 2). The combined organic layer was dried over anhydrous

Na2SO4, concentrated under reduced pressure, and purified by flash column chromatography on

silica gel to give the trisubstituted hydroxylamines.

1-(4-Phenylbutoxy)pyrrolidine (6e).

The title compound was prepared according to general procedure F using 5e (50 mg, 0.18 mmol,

1 equiv) with warming slowly to room temperature and stirring for an additional 3 h at room

temperature. It was isolated (30 mg, 77 %) as a colorless oil (0 – 10 % ethyl acetate in hexane). 1H NMR (400 MHz, CDCl3) δ 7.31 – 7.24 (m, 2H), 7.21 – 7.15 (m, 3H), 3.71 (t, J = 6.4 Hz, 2H),

3.01 – 2.92 (m, 4H), 2.63 (t, J = 7.6 Hz, 2H), 1.77 (br s, 4H), 1.71 – 1.55 (m, 4H); 13C NMR

(100 MHz, CDCl3) δ 142.5, 128.4, 128.2, 125.7, 72.1, 56.6, 35.8, 28.6, 28.1, 21.9; ESIHRMS

calculated for C14H22NO [M+H]+, 220.1701; found, 220.1702.

N,N-Dibenzyl-O-(4-phenylbutyl)hydroxylamine (6f).

The title compound was prepared according to general procedure F using 5f (47 mg, 0.12 mmol)

with warming slowly to 0 oC. It was isolated (33 mg, 83 %) as a colorless oil (0 – 5 % ethyl

acetate in hexane). 1H NMR (400 MHz, CDCl3) δ 7.40 (d, J = 6.9 Hz, 4H), 7.34 – 7.24 (m, 8H),

7.22 – 7.14 (m, 1H), 7.09 (d, J = 6.9 Hz, 2H), 3.86 (s, 4H), 3.34 (t, J = 6.4 Hz, 2H), 2.42 (t, J =

7.6 Hz, 2H), 1.44 – 1.37 (m, 2H), 1.34 – 1.27 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 142.5,

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137.9, 129.6, 128.4, 128.1, 128.1, 127.2, 125.5, 72.9, 62.6, 35.5, 28.1, 27.8; ESIHRMS

calculated for C24H28NO [M+H]+, 346.2171; found, 346.2177.

O-(1-Adamantanylmethyl)-N,N-dibenzylhydroxylamine (6g).

The title compound was prepared according to general procedure F using 5g (50 mg, 0.12 mmol,

1 equiv) with warming slowly to 0 oC. It was isolated (39 mg, 89 %) as a white solid (0 – 5 %

ethyl acetate in hexane). M.p. 48 – 49 oC; 1H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 6.9 Hz,

4H), 7.34 – 7.22 (m, 6H), 3.83 (s, 4H), 2.91 (s, 2H), 1.85 (s, 3H), 1.64 (d, J = 12.2 Hz, 3H), 1.56

(d, J = 11.3 Hz, 3H), 1.30 (d, J = 2.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 137.9, 129.8,

128.0, 127.0, 83.5, 62.5, 39.6, 37.2, 33.4, 28.2; ESIHRMS calculated for C25H32NO [M+H]+,

362.2484; found, 362.2498.

N,N-Dibenzyl-O-(3,3-dimethylbutyl)hydroxylamine (6h).

The title compound was prepared according to general procedure F using 5h (75 mg, 0.21 mmol,

1 equiv) with warming slowly to 0 oC and stirring for an additional 0.5 h at 0 oC. It was isolated

(50 mg, 81 %) as a colorless oil (0 – 5 % ethyl acetate in hexane). 1H NMR (400 MHz, CDCl3) δ

7.40 (d, J = 7.3 Hz, 4H), 7.36 – 7.23 (m, 6H), 3.85 (s, 4H), 3.32 (t, J = 7.6 Hz, 2H), 1.17 (t, J =

7.6 Hz, 2H), 0.69 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 137.9, 129.7, 128.1, 127.1, 70.5, 62.7,

41.5, 29.5, 29.3; ESIHRMS calculated for C20H28NO [M+H]+, 298.2171; found, 298.2175.

N-Benzyl-N-methyl-O-(5-phenylpentyl)hydroxylamine (6i).

The title compound was prepared according to general procedure F using 5i (50 mg, 0.15 mmol,

1 equiv) with warming slowly to 0 oC and stirring for an additional 45 min at 0 oC. It was

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isolated (35 mg, 85 %) as a colorless oil (0 – 5 % ethyl acetate in hexane). 1H NMR (400 MHz,

CDCl3) δ 7.39 – 7.25 (m, 7H), 7.21 – 7.14 (m, 3H), 3.79 (s, 2H), 3.52 (t, J = 6.4 Hz, 2H), 2.62 (s,

3H), 2.57 (t, J = 7.8 Hz, 2H), 1.60 – 1.51 (m, 2H), 1.51 – 1.42 (m, 2H), 1.32 – 1.21 (m, 2H); 13C

NMR (100 MHz, CDCl3) δ 142.7, 137.6, 129.7, 128.4, 128.2, 128.1, 127.2, 125.6, 72.1, 65.1,

45.5, 35.9, 31.3, 28.6, 25.8; ESIHRMS calculated for C19H26NO [M+H]+, 284.2014; found,

284.2016.

1-(4-Phenylbutoxy)piperidine (6j).

The title compound was prepared according to general procedure F using 5j (61 mg, 0.21 mmol,

1 equiv) with warming slowly to 0 oC and stirring for an additional 2 h at 0 oC. It was isolated

(37 mg, 75 %) as isolated as a colorless oil (0 – 10 % ethyl acetate in hexane). 1H NMR (400

MHz, CDCl3) δ 7.31 – 7.24 (m, 2H), 7.21 – 7.13 (m, 3H), 3.71 (t, J = 6.4 Hz, 2H), 3.26 (br s,

2H), 2.63 (t, J = 7.6 Hz, 2H), 2.34 (br s, 2H), 1.80 – 1.45 (m, 9H), 1.14 (br s, 1H); 13C NMR

(100 MHz, CDCl3) δ 142.5, 128.4, 128.2, 125.6, 71.2, 56.9, 35.8, 28.6, 28.2, 25.5, 23.5;

ESIHRMS calculated for C15H24NO [M+H]+, 234.1858; found, 234.1863.

4-Methyl-1-(4-phenylbutoxy)piperidine (6k).

The title compound was prepared according to general procedure F using 5k (98 mg, 0.32 mmol,

1 equiv) with warming slowly to 0 oC and stirring for an additional 2 h at 0 oC. It was isolated

(60 mg, 76 %) as a colorless oil (0 – 5 % ethyl acetate in hexane). 1H NMR (500 MHz, toluene-

d8, T = 363 K) δ 7.14 – 6.95 (m, 5H), 3.66 (t, J = 6.2 Hz, 2H), 3.17 (d, J = 10.4 Hz, 2H), 2.50 (t,

J = 7.5 Hz, 2H), 2.39 (t, J = 9.6 Hz, 2H), 1.67 – 1.59 (m, 2H), 1.59 – 1.52 (m, 2H), 1.43 (d, J =

13.1 Hz, 2H), 1.30 – 1.13 (m, 3H), 0.76 (d, J = 6.1 Hz, 3H); 13C NMR (125 MHz, toluene-d8) δ

143.2, 129.1, 128.9, 126.3, 71.7, 57.3, 36.6, 34.9, 31.1, 29.5, 29.1, 22.0; ESIHRMS calculated

for C16H26NO [M+H]+, 248.2014; found, 248.2009.

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N,N-Dibenzyl-O-(2-(2-naphthalenyloxy)ethyl)hydroxylamine (6l).

To a stirred solution of 5l (160 mg, 0.36 mmol, 1 equiv) in dry CH2Cl2 (7.2 mL) were added

dropwise and sequentially Et3SiH (290 μL, 1.80 mmol, 5 equiv) and BF3.OEt2 (230 μL, 1.80

mmol, 2.5 equiv) at 0 oC. The reaction mixture was warmed to room temperature and stirred for

7 days. The reaction mixture was partitioned between pentane (30 mL) and saturated aq.

NaHCO3 (30 mL), and aqueous layer was extracted with pentane (10 mL x 2). The combined

organic layer was dried over anhydrous Na2SO4, concentrated under reduced pressure, and

purified by flash column chromatography on silica gel (0 – 5 % ethyl acetate in hexane) to afford

6l (52 mg, 38 %) as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.3 Hz, 1H),

7.71 – 7.65 (m, 2H), 7.46 – 7.38 (m, 5H), 7.36 – 7.28 (m, 5H), 7.28 – 7.22 (m, 2H), 7.06 (dd, J =

8.8, 2.5 Hz, 1H), 6.87 (d, J = 2.5 Hz, 1H), 3.93 (s, 4H), 3.78 (t, J = 4.9 Hz, 2H), 3.71 (t, J = 4.9

Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 156.6, 137.4, 134.5, 129.8, 129.1, 128.9, 128.2, 127.6,

127.4, 126.6, 126.2, 123.5, 119.0, 106.5, 71.3, 65.8, 62.7; ESIHRMS calculated for

C26H25NO2Na [M+Na]+, 406.1783; found, 406.1778.

N,N-Dibenzyl-O-(pyridin-3-ylmethyl)hydroxylamine (6m).

To a stirred solution of 2m (100 mg, 0.31 mmol, 1 equiv) in dry CH2Cl2 (1.9 mL) were added

sequentially, drpwise DIBAL (0.63 mL, 1 M in hexane, 0.63 mmol, 2 equiv), pyridine (76 μL,

0.94 mmol, 3 equiv), a solution of DMAP (77 mg, 0.63 mmol, 2 equiv) in dry CH2Cl2 (0.9 mL),

and Ac2O (178 μL, 1.88 mmol, 6 equiv) at –78 oC. The reaction mixture was stirred for 12 h

(overnight) at –78 oC, warmed slowly to 0 oC, and quenched by adding saturated aq. NH4Cl (3.2

mL) and saturated aq. sodium potassium tartrate (2.4 mL) at 0 oC. The resultant mixture was

warmed to room temperature and stirred vigorously for 1 h. Then the mixture was extracted with

CH2Cl2 (3 mL x 4), the combined organic layer was washed with brine (5 mL), dried over

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anhydrous Na2SO4, and concentrated under reduced pressure. The crude intermediate 5m was

dissolved in dry CH2Cl2 (6.3 mL) to which were added sequentially, dropwise Et3SiH (252 μL,

1.58 mmol, 5 equiv) and BF3.OEt2 (200 μL, 1.58 mmol, 5 equiv) at –78 oC. The reaction mixture

was warmed slowly to room temperature and stirred additional 36 h at room temperature. The

reaction mixture was partitioned between pentane (20 mL) and saturated aqueous NaHCO3 (20

mL), the aqueous layer was extracted with pentane (8 mL x 2), the combined organic layer was

dried over anhydrous Na2SO4, concentrated under reduced pressure, and purified by flash

column chromatography on neutral alumina (5 – 20 % of ethyl acetate in hexane) to afford

product 6m (40 mg, 42 %) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.45 (s, 1H), 8.16 (s,

1H), 7.41 – 7.24 (m, 10H), 7.20 – 7.15 (m, 1H), 7.13 – 7.07 (m, 1H), 4.12 (s, 2H), 3.88 (s, 4H); 13C NMR (100 MHz, CDCl3) δ 150.3, 149.0, 137.5, 136.7, 132.4, 129.8, 128.2, 127.4, 123.2,

73.3, 63.1; ESIHRMS calculated for C20H21N2O [M+H]+, 305.1654; found, 305.1657.

N,N-Dibenzyl-O-(1-phenyl-3-buten-1-yl)hydroxylamine (7a).

To a stirred solution of 2a (51 mg, 0.16 mmol, 1 equiv) in dry CH2Cl2 (1 mL) were added

sequentially, dropwise DIBAL (0.32 mL, 1 M in hexane, 0.32 mmol, 2 equiv), pyridine (39 μL,



(overnight) at –78 oC, warmed slowly to 0 oC, and quenched by addition of saturated aq. NH4Cl

(1.6 mL) and saturated aq. sodium potassium tartrate (1.2 mL) at 0 oC. The resultant mixture was



anhydrous Na2SO4, and concentrated under reduced pressure. The crude intermediate 5a was

dissolved in dry CH2Cl2 (3.2 mL) to which were added sequentially, dropwise

allyltributylstannane (124 μL, 0.40 mmol, 2.5 equiv) and BF3.OEt2 (51 μL, 0.40 mmol, 2.5 equiv)

at –78 oC and warmed slowly to 0oC. The reaction mixture was partitioned between pentane (10

mL) and saturated aq. NaHCO3 (10 mL), the aqueous layer was extracted with pentane (3 mL x

2), the combined organic layer was dried over anhydrous Na2SO4, concentrated under reduced

S-23

pressure, and purified by flash column chromatography on silica gel (0 – 5 % of ethyl acetate in

hexane) to afford product 7a (45 mg, 82 %) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ

7.35 – 7.18 (m, 15H), 5.45 – 5.32 (m, 1H), 4.90 – 4.81 (m, 2H), 4.18 (t, J = 7.1 Hz, 1H), 3.83 (d,

J = 13.2 Hz, 2H), 3.71 (d, J = 12.7 Hz, 2H), 2.56 – 2.46 (m, 1H), 2.25 – 2.15 (m, 1H); 13C NMR

(100 MHz, CDCl3) δ 141.7, 137.8, 134.7, 129.7, 128.1, 128.0, 127.7, 127.5, 127.2, 116.5, 84.7,

62.5, 39.5; ESIHRMS calculated for C24H26NO [M+H]+, 344.2014; found, 344.2012.

N-Benzyl-N-methyl-O-(1-phenylbut-3-en-1-yl)hydroxylamine (7b).

To a stirred solution of 2b (100 mg, 0.41 mmol, 1 equiv) in dry CH2Cl2 (2.5 mL) were added




(overnight) at –78 oC, warmed slowly to 0 oC, and quenched by addition of saturated aq. NH4Cl

(4 mL) and saturated aq. sodium potassium tartrate (3 mL) at 0 oC. The resultant mixture was



anhydrous Na2SO4, and concentrated under reduced pressure. The crude intermediate 5b was

dissolved in dry CH2Cl2 (8.3 mL) to which were added sequentially, dropwise

allyltributylstannane (322 μL, 1.04 mmol, 2.5 equiv) and BF3.OEt2 (131 μL, 1.04 mmol, 2.5

equiv) at –78 oC and warmed slowly to 0 oC. The reaction mixture was partitioned between

pentane (25 mL) and saturated aq. NaHCO3 (25 mL) and the aqueous layer was extracted with

pentane (8 mL x 2). The combined organic layer was dried over anhydrous Na2SO4, concentrated

under reduced pressure, and purified by flash column chromatography on silica gel (0 – 5 % of

ethyl acetate in hexane) to afford product 7b (59 mg, 54 %) as a colorless oil. 1H NMR (500

MHz, toluene-d8, T = 323 K) δ 7.25 – 6.99 (m, 10H), 5.70 – 5.58 (m, 1H), 4.95 – 4.86 (m, 2H),

4.46 (t, J = 6.9 Hz, 1H), 3.66 (s, 2H), 2.62 – 2.53 (m, 1H), 2.40 – 2.25 (m, 4H); 13C NMR (125

MHz, toluene-d8, T = 323 K) δ 143.5, 138.5, 135.7, 130.4, 128.7, 128.6, 127.9, 127.8, 117.0,

84.6, 66.1, 45.9, 41.0; ESIHRMS calculated for C18H22NO [M+H]+, 268.1701; found, 268.1699.

S-24

O-(1-(Adamantan-1-yl)but-3-en-1-yl)-N,N-dibenzylhydroxylamine (7c).

To a stirred solution of 2g (100 mg, 0.24 mmol, 1 equiv) in dry CH2Cl2 (4.8 mL) were added

sequentially, dropwise allyltributylstannane (186 μL, 0.60 mmol, 2.5 equiv) and BF3.OEt2 (76

μL, 0.60 mmol, 2.5 equiv) at –78 oC. The reaction mixture was warmed slowly to 0 oC and

partitioned between pentane (15 mL) and saturated aq. NaHCO3 (15 mL). The aqueous layer was

extracted with pentane (5 mL x 2), the combined organic layer was dried over anhydrous

Na2SO4, concentrated under reduced pressure, and passed through small silica pad buffered with

2 % triethyl amine in 2:98 ethyl acetate and hexane (200 mL), then concentrated under reduced

pressure, and purified by column chromatography on silica gel (eluent: same buffered solution of

ethyl acetate in hexane) to afford product 7c (76 mg, 79 %) as a colorless oil. 1H NMR (400

MHz, CDCl3) δ 7.36 – 7.21 (m, 10H), 5.88 – 5.77 (m, 1H), 4.93 – 4.82 (m, 2H), 3.90 (d, J = 10.3

Hz, 2H), 3.73 (d, J = 13.2 Hz, 2H), 3.04 (dd, J = 4.4, 5.3 Hz, 1H), 2.23 – 2.14 (m, 1H), 2.03 –

1.95 (m, 1H), 1.90 (s, 3H), 1.70 – 1.54 (m, 9H), 1.47 – 1.39 (m, 3H); 13C NMR (100 MHz,

CDCl3) δ 139.2, 137.9, 129.8, 128.0, 127.1, 113.9, 87.6, 61.4, 38.6, 37.3, 37.0, 33.4, 28.4;

ESIHRMS calculated for C28H36NO [M+H]+, 402.2797; found, 402.2809.

1-(Dibenzylaminoxy)-4,4-dimethyl-1-phenylpentan-3-one (7d).

To a stirred solution of 2a (100 mg, 0.32 mmol, 1 equiv) in dry CH2Cl2 (1.9 mL) were added






S-25




dissolved in dry CH2Cl2 (6.4 mL) to which were added sequentially, dropwise 3,3-dimethyl-2-

(trimethylsilyloxy)butene (173 μL, 0.80 mmol, 2.5 equiv) and BF3.OEt2 (101 μL, 0.80 mmol, 2.5

equiv) at –78 oC and warmed slowly to 0 oC. The reaction mixture was partitioned between

pentane (20 mL) and saturated aqueous NaHCO3 (20 mL), the aqueous layer was extracted with

pentane (8 mL x 2), the combined organic layer was dried over anhydrous Na2SO4, concentrated

under reduced pressure, and purified by flash column chromatography on neutral alumina (10 –

25 % of CH2Cl2 in hexane) to afford product 7d (85 mg, 66 %) as a colorless oil. 1H NMR (400

MHz, CDCl3) δ 7.32 – 7.19 (m, 13H), 7.17 – 7.13 (m, 2H), 4.82 (dd, J = 8.3, 5.4 Hz, 1H), 3.85

(d, J = 12.7 Hz, 2H), 3.74 (d, J = 12.7 Hz, 2H), 2.80 (dd, J = 16.6, 5.4 Hz, 1H), 2.38 (dd, J =

16.6, 8.3 Hz, 1H), 0.87 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 213.2, 141.3, 137.5, 129.9, 128.1,

128.0, 127.6, 127.4, 127.2, 79.6, 61.9, 44.1, 42.2, 25.8; ESIHRMS calculated for C27H32NO2

[M+H]+, 402.2433; found, 402.2431.

N,N-Dibenzyl-O-((5-methylfuran-2-yl)benzyl)hydroxylamine (7e).

To a stirred solution of 2a (100 mg, 0.32 mmol, 1 equiv) in dry CH2Cl2 (1.9 mL) were added









dissolved in dry CH2Cl2 (6.4 mL) to which were added sequentially, dropwise 2-methylfuran (72

S-26

μL, 0.80 mmol, 2.5 equiv) and BF3.OEt2 (101 μL, 0.80 mmol, 2.5 equiv) at –78 oC. The reaction

mixture was stirred for additional 45 min at –78 oC and quenched by adding saturated aq.

NaHCO3 (20 mL). The resultant mixture was extracted with pentane (20 mL x 2), the combined

organic layer was dried over anhydrous Na2SO4, concentrated under reduced pressure, and

purified by flash column chromatography on neutral alumina (0 – 5 % of ethyl acetate in hexane)

to afford product 7e (63 mg, 51 %) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.32 – 7.23

(m, 15H), 5.96 (d, J = 2.9 Hz, 1H), 5.87 (dd, J = 2.9, 1.0 Hz, 1H), 5.16 (s, 1H), 3.86 (d, J = 12.7

Hz, 2H), 3.80 (d, J = 12.7 Hz, 2H), 2.26 (d, J = 0.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ

152.2, 151.9, 139.0, 137.8, 129.7, 128.1, 128.0, 127.9, 127.7, 127.1, 110.5, 106.0, 80.3, 62.4,

13.7; ESIHRMS calculated for C26H26NO2 [M+H]+, 384.1964; found, 384.1965.

N,N-Dibenzyl-O-(1-(5-methylfuran-2-yl)-4-phenylbutyl)hydroxylamine (7f).

To a stirred solution of 5f (50 mg, 0.12 mmol, 1 equiv) in dry CH2Cl2 (2.5 mL) were added

sequentially, dropwise 2-methylfuran (28 μL, 0.31 mmol, 2.5 equiv) and BF3.OEt2 (40 μL, 0.31

mmol, 2.5 equiv) at –78 oC. The reaction was warmed slowly to 0 oC and quenched by adding

saturated aq. NaHCO3 (8 mL). The resultant mixture was extracted with pentane (8 mL x 2),

combined organic layer was dried over anhydrous Na2SO4, and concentrated under reduced

pressure. Purification of the crude mixture by flash column chromatography on neutral alumina

(0 – 5 % of ethyl acetate in hexane) afforded product 7f (11 mg, 20 %) as a colorless oil along

with recovered starting material 5f (35 mg, 70 %). 1H NMR (400 MHz, CDCl3) δ 7.32 – 7.19 (m,

12H), 7.16 (t, J = 7.3 Hz, 1H), 7.04 (d, J = 6.9 Hz, 2H), 6.06 (d, J = 2.9 Hz, 1H), 5.87 – 5.85 (m,

1H), 4.12 (t, J = 7.1 Hz, 1H), 3.78 (d, J = 12.7 Hz, 2H), 3.62 (d, J = 13.2 Hz, 2H), 2.45 – 2.30

(m, 2H), 2.24 (s, 3H), 1.76 – 1.64 (m, 1H), 1.61 – 1.49 (m, 1H), 1.44 – 1.31 (m, 1H), 1.30 – 1.13

(m, 1H); 13C NMR (100 MHz, CDCl3) δ 153.1, 151.4, 142.3, 137.9, 129.6, 128.4, 128.1, 128.0,

127.1, 125.5, 109.1, 105.9, 77.7, 62.4, 35.4, 31.6, 27.2, 13.6; ESIHRMS calculated for

C29H32NO2 [M+H]+, 426.2433; found, 426.2426.

S-27

Reference:

(1) Biloski, A. J.; Ganem, B. Synthesis 1983, 1983, 537-538.

(2) Berman, A. M.; Johnson, J. S. J. Org. Chem. 2006, 71, 219-224.

(3) Shang, M.; Zeng, S.-H.; Sun, S.-Z.; Dai, H.-X.; Yu, J.-Q. Org. Lett. 2013, 15,

5286-5289.

(4) Fernandes, L.; Fischer, F. L.; Ribeiro, C. W.; Silveira, G. P.; Sá, M. M.; Nome,

F.; Terenzi, H. Bioorg. Med. Chem. Lett. 2008, 18, 4499-4502.

(5) Wazeer, M. M.; Perzanowski, H.; áAsrof Ali, S. J. Chem. Soc., Perkin Trans. 2

1997, 411-418.

(6) Sammelson, R. E.; Kurth, M. J. Tetrahedron Lett. 2001, 42, 3419-3422.

(7) Windle, J.; Kuhnle, J.; Beck, B. H. The Journal of Chemical Physics 1969, 50,

2630-2641.

(8) López‐Iglesias, M.; Busto, E.; Gotor, V.; Gotor‐Fernández, V. Adv. Synth. Catal.

2011, 353, 2345-2353.

(9) R. Ravichandran, Compositions Stabilized with Ethers of Di- and Tri-substituted

Hydroxylamines. U.S. Patents 4,696,964, September 29, 1987..

S-28

1H NMR (400 MHz, CDCl3) spectrum of O-benzoyl-N,N-dibenzylhydroxylamine (2a)

S-29

13C NMR (100 MHz, CDCl3) spectrum of O-benzoyl-N,N-dibenzylhydroxylamine (2a)

405060708090100110120130140150160170180190f1 (ppm)

S-30

1H NMR (400 MHz, CDCl3) spectrum of O-benzoyl-N-benzyl-N-methylhydroxylamine (2b)

2.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0

f1 (ppm)

S-31

13C NMR (100 MHz, CDCl3) spectrum of O-benzoyl-N-benzyl-N-methylhydroxylamine (2b)

30405060708090100110120130140150160170180

f1 (ppm)

S-32

1H NMR (400 MHz, CDCl3) spectrum of piperidin-1-yl benzoate (2c)

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

S-33

13C NMR (100 MHz, CDCl3) spectrum of piperidin-1-yl benzoate (2c)

102030405060708090100110120130140150160170180

f1 (ppm)

S-34

1H NMR (400 MHz, CDCl3) spectrum of 4-methylpiperidin-1-yl benzoate (2d)

3.18

0.98

2.37

1.96

1.70

0.32

0.31

1.80

2.00

1.00

1.96

S-35

13C NMR (100 MHz, CDCl3) spectrum of 4-methylpiperidin-1-yl benzoate (2d)

S-36

1H NMR (400 MHz, CDCl3) spectrum of N,N-dibenzyl hydroxylamine (3a)

2.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

S-37

13C NMR (100 MHz, CDCl3) spectrum of N,N-dibenzyl hydroxylamine (3a)

63.7

2

76.7

377

.05

77.3

7

127.

4512

8.29

129.

82

137.

13

S-38

1H NMR (400 MHz, CDCl3) spectrum of N-benzyl-N-methylhydroxylamine (3b)

OHN

Me

Bn

S-39

13C NMR (100 MHz, CDCl3) spectrum of N-benzyl-N-methylhydroxylamine (3b)

OHN

Me

Bn

S-40

1H NMR (400 MHz, CDCl3) spectrum of piperidin-1-ol (3c)

S-41

13C NMR (100 MHz, CDCl3) spectrum of piperidin-1-ol (3c)

S-42

1H NMR (400 MHz, CDCl3) spectrum of 4-methylpiperidin-1-ol (3d)

S-43

13C NMR (100 MHz, CDCl3) spectrum of 4-methylpiperidin-1-ol (3d)

19.9

521

.25

29.3

829

.84

33.9

8

54.6

3

58.6

5

76.7

077

.02

77.3

4

S-44

1H NMR (400 MHz, CDCl3) spectrum of 3-(pyrrolidin-1-yl)propanenitrile (4)

S-45

13C NMR (100 MHz, CDCl3) spectrum of 3-(pyrrolidin-1-yl)propanenitrile (4)

5101520253035404550556065707580859095100105110115120125130135f1 (ppm)

S-46

1H NMR (400 MHz, CDCl3) spectrum of pyrrolidin-1-yl 4-phenylbutanoate (2e)

S-47

13C NMR (100 MHz, CDCl3) spectrum of pyrrolidin-1-yl 4-phenylbutanoate (2e)

102030405060708090100110120130140150160170180f1 (ppm)

21.9

9

26.5

9

32.3

835

.06

57.4

4

76.7

577

.07

77.3

9

125.

9912

8.38

128.

47

141.

24

171.

98

S-48

1H NMR (400 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(4-phenylbutanoyl)hydroxylamine (2f)

2.08

2.00

2.06

4.06

1.82

0.87

7.62

3.82

S-49

13C NMR (100 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(4-phenylbutanoyl)hydroxylamine (2f)

S-50

1H NMR (400 MHz, CDCl3) spectrum of O-(adamantane-1-carbonyl)-N,N-dibenzylhydroxylamine (2g)

12.4

7

2.94

4.00

5.90

3.79

S-51

13C NMR (100 MHz, CDCl3) spectrum of O-(adamantane-1-carbonyl)-N,N-dibenzylhydroxylamine (2g)

S-52

1H NMR (400 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(3,3-dimethylbutanoyl)hydroxylamine (2h)

S-53

13C NMR (100 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(3,3-dimethylbutanoyl)hydroxylamine (2h)

102030405060708090100110120130140150160170180190

f1 (ppm)

S-54

1H NMR (400 MHz, CDCl3) spectrum of N-benzyl-N-methyl-O-(5-phenylpentanoyl)hydroxylamine (2i)

S-55

13C NMR (100 MHz, CDCl3) spectrum of N-benzyl-N-methyl-O-(5-phenylpentanoyl)hydroxylamine (2i)

0102030405060708090100110120130140150160170180

f1 (ppm)

S-56

1H NMR (400 MHz, CDCl3) spectrum of piperidin-1-yl 4-phenylbutanoate (2j)

1.25

1.11

4.31

2.18

2.00

4.17

1.96

2.79

1.93

S-57

13C NMR (100 MHz, CDCl3) spectrum of piperidin-1-yl 4-phenylbutanoate (2j)

S-58

1H NMR (400 MHz, CDCl3) spectrum of 4-methylpiperidin-1-yl 4-phenylbutanoate (2k)

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

S-59

13C NMR (100 MHz, CDCl3) spectrum of 4-methylpiperidin-1-yl 4-phenylbutanoate (2k)

102030405060708090100110120130140150160170180190f1 (ppm)

S-60

1H NMR (400 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(2-(naphthalen-2-yloxy)acetyl)hydroxylamine (2l)

3.98

2.00

0.92

0.88

12.1

9

0.95

0.99

1.06

S-61

13C NMR (100 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(2-(naphthalen-2-yloxy)acetyl)hydroxylamine (2l)

S-62

1H NMR (400 MHz, CDCl3) spectrum of N,N-dibenzyl-O-nicotinoylhydroxylamine (2m)

4.24

7.36

4.00

0.97

0.93

0.84

S-63

13C NMR (100 MHz, CDCl3) spectrum of N,N-dibenzyl-O-nicotinoylhydroxylamine (2m)

2030405060708090100110120130140150160170180190f1 (ppm)

S-64

1H NMR (400 MHz, CDCl3) spectrum of 4-phenyl-1-(pyrrolidin-1-yloxy)butyl acetate (5e)

S-65

1H NMR (400 MHz, CDCl3) spectrum of 4-phenyl-1-(pyrrolidin-1-yloxy)butyl acetate (5e)

S-66

1H NMR (400 MHz, CDCl3) spectrum of 1-((dibenzylamino)oxy)-4-phenylbutyl acetate (5f)

4.35

3.00

2.11

2.09

1.96

0.98

1.88

0.90

11.8

0

S-67

13C NMR (100 MHz, CDCl3) spectrum of 1-((dibenzylamino)oxy)-4-phenylbutyl acetate (5f)

S-68

1H NMR (400 MHz, CDCl3) spectrum of (Adamantan-1-yl)((dibenzylamino)oxy)methyl acetate (5g)

S-69

1C NMR (100 MHz, CDCl3) spectrum of (Adamantan-1-yl)((dibenzylamino)oxy)methyl acetate (5g)

S-70

1H NMR (400 MHz, CDCl3) spectrum of 1-((dibenzylamino)oxy)-3,3-dimethylbutyl acetate (5h)

S-71

13C NMR (100 MHz, CDCl3) spectrum of 1-((dibenzylamino)oxy)-3,3-dimethylbutyl acetate (5h)

102030405060708090100110120130140150160170180

f1 (ppm)

S-72

1H NMR (400 MHz, CDCl3) spectrum of 1-((benzyl(methyl)amino)oxy)-5-phenylpentyl acetate (5i)

S-73

13C NMR (400 MHz, CDCl3) spectrum of 1-((benzyl(methyl)amino)oxy)-5-phenylpentyl acetate (5i)

S-74

1H NMR (400 MHz, CDCl3) spectrum of 4-phenyl-1-(piperidin-1-yloxy)butyl acetate (5j)

S-75

13C NMR (100 MHz, CDCl3) spectrum of 4-phenyl-1-(piperidin-1-yloxy)butyl acetate (5j)

102030405060708090100110120130140150160170180

f1 (ppm)

S-76

1H NMR (400 MHz, CDCl3) spectrum of 1-((4-methylpiperidin-1-yl)oxy)-4-phenylbutyl acetate (5k)

3.20

2.87

6.36

3.09

1.81

2.17

1.89

1.00

3.04

2.13

S-77

13C NMR (100 MHz, CDCl3) spectrum of 1-((4-methylpiperidin-1-yl)oxy)-4-phenylbutyl acetate (5k)

102030405060708090100110120130140150160170180f1 (ppm)

S-78

1H NMR (400 MHz, CDCl3) spectrum of 1-((dibenzylamino)oxy)-2-(naphthalen-2-yloxy)ethyl acetate (5l)

S-79

1C NMR (100 MHz, CDCl3) spectrum of 1-((dibenzylamino)oxy)-2-(naphthalen-2-yloxy)ethyl acetate (5l)

S-80

1H NMR (400 MHz, CDCl3) spectrum of N,N,O-tribenzyl hydroxylamine (6a)

S-81

13C NMR (100 MHz, CDCl3) spectrum of N,N,O-tribenzyl hydroxylamine (6a)

S-82

1H NMR (400 MHz, CDCl3) spectrum of N,O-dibenzyl-N-methylhydroxylamine (6b)

3.29

2.05

2.00

2.04

8.39

S-83

13C NMR (100 MHz, CDCl3) spectrum of N,O-dibenzyl-N-methylhydroxylamine (6b)

S-84

1H NMR (400 MHz, CDCl3) spectrum of 1-(4-phenylbutoxy)pyrrolidine (6e)

S-85

13C NMR (100 MHz, CDCl3) spectrum of 1-(4-phenylbutoxy)pyrrolidine (6e)

S-86

1H NMR (400 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(4-phenylbutyl)hydroxylamine (6f)

2.30

2.15

2.00

2.06

4.28

1.90

1.05

7.87

3.89

S-87

1C NMR (100 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(4-phenylbutyl)hydroxylamine (6f)

S-88

1H NMR (400 MHz, CDCl3) spectrum of O-((adamantan-1-yl)methyl)-N,N-dibenzylhydroxylamine (6g)

S-89

13C NMR (100 MHz, CDCl3) spectrum of O-((adamantan-1-yl)methyl)-N,N-dibenzylhydroxylamine (6g)

S-90

1H NMR (400 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(3,3-dimethylbutyl)hydroxylamine (6h)

S-91

13C NMR (100 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(3,3-dimethylbutyl)hydroxylamine (6h)

S-92

1H NMR (400 MHz, CDCl3) spectrum of N-benzyl-N-methyl-O-(5-phenylpentyl)hydroxylamine (6i)

S-93

13C NMR (100 MHz, CDCl3) spectrum of N-benzyl-N-methyl-O-(5-phenylpentyl)hydroxylamine (6i)

101520253035404550556065707580859095100105110115120125130135140145150155160f1 (ppm)

S-94

1H NMR (400 MHz, CDCl3) spectrum of 1-(4-phenylbutoxy)piperidine (6j)

S-95

13C NMR (100 MHz, CDCl3) spectrum of 1-(4-phenylbutoxy)piperidine (6j)

101520253035404550556065707580859095105115125135145155

f1 (ppm)

S-96

1H NMR (500 MHz, tolune-d8, T = 363 K) spectrum of 4-methyl-1-(4-phenylbutoxy)piperidine (6k)

S-97

13C NMR (125 MHz, tolune-d8) spectrum of 4-methyl-1-(4-phenylbutoxy)piperidine (6k)

S-98

1H NMR (400 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(2-(naphthalen-2-yloxy)ethyl)hydroxylamine (6l)

S-99

13C NMR (100 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(2-(naphthalen-2-yloxy)ethyl)hydroxylamine (6l)

S-100

1H NMR (400 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(pyridin-3-ylmethyl)hydroxylamine (6m)

S-101

13C NMR (100 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(pyridin-3-ylmethyl)hydroxylamine (6m)

S-102

1H NMR (400 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(1-phenylbut-3-en-1-yl)hydroxylamine (7a)

S-103

13C NMR (100 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(1-phenylbut-3-en-1-yl)hydroxylamine (7a)

1520253035404550556065707580859095100105110115120125130135140145150155160

f1 (ppm)

S-104

1H NMR (500 MHz, tolune-d8, T = 323 K) spectrum N-benzyl-N-methyl-O-(1-phenylbut-3-en-1-yl)hydroxylamine (7b)

1.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.8

f1 (ppm)

S-105

13C NMR (125 MHz, tolune-d8, T = 323 K) spectrum N-benzyl-N-methyl-O-(1-phenylbut-3-en-1-yl)hydroxylamine (7b)

102030405060708090100110120130140150160

f1 (ppm)

S-106

1H NMR (400 MHz, CDCl3) spectrum of O-(1-(adamantan-1-yl)but-3-en-1-yl)-N,N-dibenzylhydroxylamine (7c)

2.97

8.92

2.90

1.03

0.98

0.96

2.00

1.79

1.90

0.93

9.87

S-107

13C NMR (100 MHz, CDCl3) spectrum of O-(1-(adamantan-1-yl)but-3-en-1-yl)-N,N-dibenzylhydroxylamine (7c)

28.4

1

33.4

236

.96

37.2

738

.64

61.3

9

76.6

977

.00

77.3

2

87.5

5

113.

89

127.

0512

7.97

129.

80

137.

8913

9.22

S-108

1H NMR (400 MHz, CDCl3) spectrum of 1-((dibenzylamino)oxy)-4,4-dimethyl-1-phenylpentan-3-one (7d)

S-109

13C NMR (100 MHz, CDCl3) spectrum of 1-((dibenzylamino)oxy)-4,4-dimethyl-1-phenylpentan-3-one (7d)

102030405060708090100110120130140150160170180190200210220

f1 (ppm)

S-110

1H NMR (400 MHz, CDCl3) spectrum of N,N-dibenzyl-O-((5-methylfuran-2-yl)(phenyl)methyl)hydroxylamine (7e)

O PhN

Bn

BnO

S-111

13C NMR (100 MHz, CDCl3) spectrum of N,N-dibenzyl-O-((5-methylfuran-2-yl)(phenyl)methyl)hydroxylamine (7e)

102030405060708090100110120130140150160

f1 (ppm)

S-112

1H NMR (400 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(1-(5-methylfuran-2-yl)-4-phenylbutyl)hydroxylamine (7f)

S-113

1C NMR (100 MHz, CDCl3) spectrum of N,N-dibenzyl-O-(1-(5-methylfuran-2-yl)-4-phenylbutyl)hydroxylamine (7f)

supporting information for synthesis of n,n,o

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