One-pot reductive amination of carbonyl compounds with ammonia via ‘hydrogen

borrowing’ using hydrido- and bis-ammine P,O(Me)-ruthenacycles

Frederick P. Malan, Ji-Hyang Noh, Gadada Naganagowda, Eric Singleton, Reinout Meijboom*

Research Centre for Synthesis and Catalysis, Department of Chemistry, University of Johannesburg, PO Box 524, Auckland Park, 2006, Johannesburg, South Africa. *E-mail: rmeijboom@uj.ac.za

Supplementary information

1. Characterization of 3 I

2. Characterization of 4 IV

3. Synthesis and Characterization of benzylaminium cyclohexanoate VI

4. Scheme A: Proposed routes in the mechanism of formation of 4 VII

5. Table A: Selected bond distances (Å) and angles (°) in 4 VII

6. UV/Vis and IR spectra of 3 and (4) VIII

7. Alcohol amination (from aldehydes) with 4 IX

8. 1H- and 31P-NMR spectra of 600 min RA sample X

9. Procedure for H2(g)-assisted reductive amination X

I

1. Characterization of 3:

Yield = 33%. m.p.: 177 – 179°C. IR (ν, δ in cm-1): 3416 (ν(OH), w); 3126 (ν(=CH), w); 3057

(ν(=CH), w); 3015 (ν(=CH), w); 2999 (ν(=CH), w); 2931 (ν(=CH), w); 2038 (ν(RuH), m);

1647 (m); 1587 (ν(C=C), m); 1570 (m); 1470 (s); 1450 (s); 1415 (s); 1385 (δ(OH), br); 1272

(s); 1246 (δ(=CH), s); 1182 (m); 1160 (m); 1130 (ν(C-O), m); 1088 (m); 1067 (m); 1024 (s);

1000 (m); 847 (m); 835 (δ(para =CH), m); 799 (s); 752 (ν(BC), s); 737 (δ(=CH ortho), s);

677 (δ(=CH meta), s); 671 (m). 1H-NMR (400 MHz, CDCl3, δH) -8.57 (t, 3JHP = 36 Hz, RuH,

1H); 1.52 (s, H2O, 2H); 3.30 (s, OCH3, 6H); 4.83 (d, 3JHH = 24 Hz, P(C6H4), 4H); 5.70 (s,

P(C6H4), 2H); 6.60 (t, 3JHH = 8 Hz, P(C6H4), 2H); 6.69 (d, 3JHH = 8 Hz, P(C6H5), 6H); 6.81 (t, 3JHH = 8 Hz, B(C6H5), 4H); 7.00 (m, B(C6H5), 14H); 7.10 (t, 3JHH = 7 Hz, P(C6H5), 8H); 7.29

(t, 3JHH = 8 Hz, B(C6H5), 2H); 7.52 (d, 3JHH = 6 Hz, P(C6H5), 6H). 13C{1H}-NMR (101 MHz,

CDCl3, δC) 54.5 (s, OCH3), 92.2 (s, P(C6H4O)); 93.5 (s, P(C6H4O)); 100.4 (s, P(C6H4O));

111.0 (s, P(C6H4O)); 120.4 (t, 3JCC = 6 Hz, P(C6H5)); 122.9 (s, B(C6H5)); 126.1 (s, P(C6H5));

127.0 (q, 3JCC = 5 Hz, P(C6H5)); 128.5 (s, P(C6H5)); 128.8 (s, P(C6H5)); 132.2 (t, 3JCC = 8 Hz,

P(C6H5)); 133.1 (t, 3JCC = 4 Hz, P(C6H5)); 136.6 (s, B(C6H5)); 137.8 (s, B(C6H5)); 159.6 (s,

B(C6H5)). 31P{1H}-NMR (162 MHz, CDCl3, δP) 49.9 (s, PPh2{2-MeOC6H4}). CHN (%):

[RuH(PPh2{2-MeOC6H4})2]BPh4.1.5H2O: C, 71.87 (72.09); H, 5.53 (5.66); N, 0.04 (0.00).

1H-NMR

II

13C-NMR

III

31P-NMR

2. Characterization of 4:

IV

Yield = 58%. m.p.: > 158°C (decomposition without melt). IR (ν, δ in cm -1): 3264 (ν(NH),

w); 3155 (ν(NH), w); 3046 (ν(=CH), w); 2969 (ν(=CH), w); 2104 (w); 1633 (m); 1596

(ν(C=C), m); 1580 (δ(NH), asym, m); 1544 (δ(NH), asym, m); 1479 (m); 1453 (s); 1433 (s);

1309 (m); 1263 (m); 1240 (δ(=CH), m); 1205 (m); 1056 (δ(NH), sym, m); 1026 (δ(NH), sym,

m); 999 (m); 848 (δ(para =CH), s); 752 (s); 744 (δ(=CH ortho), s); 727 (m); 697 (s); 677

(δ(=CH meta), s). 1H-NMR (400 MHz, CDCl3, δH) 0.91 (s, NH3, 3H); 1.24 (m, H2O, 2H);

1.89 (s, NH3, 3H); 6.52 (s, P(OC6H4), 2H); 7.04 (m, P(OC6H4), 6H); 7.09 (s, P(C6H5), 2H);

7.14 (m, P(C6H5), 12H); 7.29 (t, 3JHH = 7 Hz, P(C6H5), 6H). 13C{1H}-NMR (101 MHz, CDCl3,

δC) 113.4 (s, P(C6H4O)); 128.2 (t, 3JCC = 11 Hz, P(OC6H4)); 129.5 (s, P(OC6H4)); 130.4 (s,

P(C6H5)); 131.8 (t, 3JCC = 11 Hz, P(C6H5)); 133.7 (d, 3JCC = 33 Hz, P(C6H5)); 137.1 (s,

P(C6H5)). 31P{1H}-NMR (162 MHz, CDCl3, δP) 66.3 (s, PPh2{2-OC6H4}). 15N-1H-NMR

(MHz, CDCl3, δP) 191 (s, NH3). CHN (%): [Ru(NH3)2(PPh2{2-OC6H4})2]: C, 60.33 (60.16);

H, 5.19 (5.47); N, 3.74 (3.90).

1H-NMR

13C-NMR

V

31P-NMR

15N-1H-NMR

VI

3. Synthesis and Characterization of benzylaminium cyclohexanoate:

A methanolic solution of the formed amine was treated with a saturated methanolic solution

of cyclohexanoic acid, from which colorless needles formed upon slow evaporation (in air). 1H-NMR (400 MHz, (CD3)2SO, δH) 1.17 – 1.32 (m, CH2, 4H); 1.56 (s, CH2, 2H); 1.63 (s,

CH2, 2H); 1.78 (d, 3JHH = 11 Hz, CH2, 2H); 2.09 (s, -CH, 1H); 4.40 (m, CH2N, 2H); 5.47 (s,

NH3, 3H); 7.22 – 7.31 (m, C6H4, 5H). 13C{1H}-NMR (101 MHz, (CD3)2SO, δC) 25.0, 25.5,

28.9, 30.0, 38.7, and 39.6 (s, C7H11O2); 43.0 (s, CH2N); 127.7 (s, C6H5); 128.0 (s, C6H5);

128.2 (s, C6H5); 128.9 (s, C6H5); 144.4 (s, ipso C6H5); 177.5 (s, C7H11O2).

X-ray crystallography of 3 and benzylaminium cyclohexanoate (SI)

Single crystals of compounds 3 and benzylaminium cyclohexanoate (SI) were mounted on a

fine glass rod and diffracted with graphite-monochromated Mo Kα radiation (k = 0.71069 Å)

using a Bruker APEX-II CCD area-detector diffractometer. X-ray diffraction measurements

were made at 293(2) K. Absorption corrections were carried out using SADABS [1]. All

structures were solved by direct methods with SHELXS-97 [2] using the OLEX2 [3]

VII

interface. All H atoms were placed in geometrically idealized positions and constrained to

ride on their parent atoms.

References

[1] G.M. Sheldrick, SHELXL96, Program for the Refinement of Crystal Structures,University of Göttingen, Germany, 1996.

[2] G.M. Sheldrick, Acta Cryst. A64 (2008) 112.[3] O.V. Dolomanov, L.J. Bourhis, R.J. Gildea, J.A.K. Howard, H. Puschmann, J. Appl.

Cryst. 42 (2009) 339.

VIII

4. Scheme A: Proposed routes in the mechanism of formation of 4:

5. Table A: Selected bond distances (Å) and angles (°) in 4:

Ru1-P1 2.2487(6) O1-C112 1.322(3) P2-Ru1-O1 168.69(6)

Ru1-P2 2.2389(6) P1-Ru1-P2 108.66(2) P2-Ru1-O2 83.10(5)

Ru1-O1 2.1175(2) N1-Ru1-N2 170.01(9) O1-Ru1-N1 87.50(9)

Ru1-O2 2.1350(2) O1-Ru1-O2 85.60(7) O1-Ru1-N2 84.58(1)

Ru1-N1 2.104(2) P1-Ru1-O1 82.64(6) O2-Ru1-N1 87.68(8)

Ru1-N2 2.120(2) P1-Ru1-O2 168.19(5) O2-Ru1-N2 85.65(9)

IX

6.

400 450 500 550 600 650 700 750 8000

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

Wavelength (nm)

Abso

rban

ce (a

.u.)

Figure 2: UV/Vis (upper graph) and IR (lower graph) spectra of [RuH{PPh2(2-

MeOC6H4)}2]BPh4 (3), and trans-[Ru(NH3)2{PPh2(2-OC6H4)}2] (4).

X

43

7. Alcohol amination (from aldehydes) with 4

In the inset is a perspective view of the crystal structure of benzylamine (from benzaldehyde)

crystallized as its aminium cyclohexanoate salt.

8. 1H- and 31P-NMR spectra of 600 min RA sample:

A sample containing 20 mol% of 4 was used in a reductive amination experiment under the usual conditions, i.e. to a heated (90 ºC) EtOD solution (4 mL) of the carbonyl substrate (0.1 mmol), catalyst (20 mol%), (NH4)(OOCCH3) (1 mmol, 77 mg), and NH4OH (50 μmol, 7 μL of a 28% w/w aqueous solution) was added a EtOD solution (1 mL) of NaBH4 (0.1 mmol, 4 mg) and heated in a Schleck flask fitted with a dropping funnel and a bubbler under Ar(g) at 90ºC for 10 hours.

XI

1H-NMR spectrum at time = 600 min.

31P-NMR spectrum at time = 600 min.

9. Procedure for H2(g)-assisted reductive amination.

Benzaldehyde (0.6 mmol), 4 (1 mol%, 5 mg), NH3 (excess, 2 mL of a 2M MeOH solution),

NH4OH (0.3 mmol, 42 μL of a 28% w/w aqueous solution), n-decane (0.6 mmol, 117 μL,

internal standard), and EtOH (5 mL) were added together in an autoclave reactor. The

reaction mixture was purged with Ar(g) after which the autoclave was pressurized with H2(g)

(30 bar). The reaction mixture was heated at the 90 °C for 24 h. After cooling, the mixture

was quenched with water, extracted with EtOAc, and purified using flash column

chromatography (silica, EtOAc). The collected fraction were concentrated to near-dryness

and made up as a solution with either CH2Cl2, and analysed using GC(FID) and GC/MS.

XII