1General Procedure for the Α-Aminoxylation of Aldehydes

Data of α-aminoxylation reactions

1General procedure for the α-aminoxylation of aldehydes

PBS (phosphate buffered solutions, 0.20 mL) was added to a stirred mixture of corresponding aldehydes and catalyst at 0 °C, followed by nitrosobenzene. The reaction was stirred at room temperature until the green solution turned yellow which indicated complete consumption of the nitrosobenzene. The reaction mixture was then treated with NaBH4 in EtOH at 0 °C. The excess NaBH4 was quenched by the addition of water, and the mixture was extracted with CH2Cl2. The combined organic extracts were dried with over anhydrous Na2SO4 and evaporated under vacuum. The crude oil was purified by thin layer chromatography on silica gel (petroleum ether/ethyl acetate).

1.1 (R)-2-(N-Phenylaminoxy)butan-1-ol 4a

1H NMR (400 MHz, CDCl3): δ 7.27-7.23 (2H, m), 6.98-6.93 (3H, m), 3.86-3.81 (2H, m), 3.75-3.72(1H, m), 1.71-1.67 (1H, m), 1.61-1.55 (1H, m), 1.02-0.98 (3H, t, J=7.5 Hz);13C NMR (100 MHz, CDCl3):δ 148.5, 128.5, 122.2, 114.7, 85.2, 64.5, 22.8, 10.1; HPLC: Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL/min, λ= 242 nm),tR (minor) = 10.0 min, tR (major) = 11.3 min; 97% ee; [α]25D = + 20.0 (c = 0.7, CHCl3).

1.2 (R)-2-(N-Phenylaminoxy)propan-1-ol 4b

1H NMR (400 MHz, CDCl3):δ 7.26-7.22 (2H, m), 6.96-6.93 (3H, m), 4.09-4.05 (1H, m), 3.72-3.65 (2H,m), 3.02 (1H, brs), 1.23-1.21 (3H, d, J=6.4 Hz);13C NMR (100 MHz, CDCl3):δ 148.6, 129.0, 122.2, 114.6, 80.1, 66.1, 15.4; HPLC: Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL/min, λ= 242 nm), tR (minor) = 10.6 min, tR (major) =12.1 min; 95% ee; [α]25D = + 2.7 (c = 0.5, CHCl3).

1.3 (R)-2-(N-Phenylaminoxy)pentan-1-ol 4c

1H NMR (400 MHz, CDCl3): δ 7.25-7.21 (2H, m), 6.93-6.93 (3H, m), 3.91-3.90 (1H, m), 3.84-3.81 (1H, dd, J=12.0, 2.6 Hz), 3.73-3.68 (1H, dd, J=12.0, 6.2 Hz), 1.67-1.62 (1H, m), 1.49-1.31 (3H, m), 0.96-0.92 (3H, t, J=7.0 Hz); 13C NMR (100 MHz, CDCl3):δ 148.6, 128.9, 122.1, 114.6, 83.7, 64.8, 32.1, 19.0, 14.2; HPLC: Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL/min, λ= 242 nm),tR (minor) = 9.3 min, tR (major) = 10.6 min; 98% ee; [α]25D = + 24.7 (c = 0.6, CHCl3).

1.4 (R)-2-(N-Phenylaminoxy)hexan-1-ol 4d

1H NMR (400 MHz, CDCl3): δ 7.22-7.20 (2H, m), 6.95-6.92 (3H, m), 3.99-3.84 (1H, m), 3.83-3.80 (1H, m), 3.71-3.66 (1H, m), 1.66-1.63 (3H, m), 1.51-1.35 (5H, m), 0.92-0.88 (t, 3H, J=7.3 Hz);13C NMR (100 MHz, CDCl3):δ 148.7, 128.9, 122.0, 114.6, 83.9, 64.6, 29.6, 27.9, 22.8, 13.9; HPLC: Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL/min, λ= 242 nm),tR (minor) = 9.1 min, tR (major) = 10.9 min;99% ee; [α]25D = + 25.6 (c = 0.5, CHCl3).

1.5 (R)-2-(N-Phenylaminoxy)decan-1-ol 4e

1H NMR (400 MHz, CDCl3): δ 7.20 (2H, m), 6.95-6.89 (3H, m), 3.85-3.81 (1H, m), 3.85-3.56 (2H, m), 1.53 (2H, m), 1.27 (12H, m), 0.89-0.88 (3H, m); 13C NMR (100 MHz, CDCl3):δ 148.8, 128.6, 121.5, 114.3, 83.8, 62.2, 31.8, 29.9, 29.5, 29.4, 29.2, 25.7, 22.5, 13.8; HPLC: Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL/min, λ= 242 nm),tR (minor) = 7.0 min, tR (major) = 8.2 min; > 99% ee; [α]25D = + 30.4 (c = 0.5, CHCl3).

1.6 (R)-2-Phenyl-2-(N-phenylaminoxy)ethanol 4f

1H NMR (400 MHz, CDCl3): δ 7.42-7.35 (5H, m), 7.30-7.26 (2H, m), 7.00-6.98 (3H, m), 5.05-5.02 (1H, dd, J = 3.4, 8.1 Hz), 4.02-3.97 (1H, dd, J = 8.1, 12.2 Hz), 3.87-3.85 (1H, m); 13C NMR (100 MHz, CDCl3):δ 147.9, 137.8, 129.0, 128.7, 128.5, 127.1, 122.5, 115.0, 86.5, 66.4; HPLC: Chiralpak AD-H (hexane/i-PrOH, 96/4, flow rate 1 mL/min, λ= 242 nm),tR (minor) = 32.8 min, tR (major) = 34.6 min; > 99% ee; [α]25D = -127.4 (c = 0.7, CHCl3).

1.7(R)-3-Phenyl-2-(N-phenylaminoxy)propan-1-ol 4g

1H NMR (400 MHz, CDCl3):δ 7.26-7.13 (7H, m), 6.91-6.87 (1H, t, J = 7.3 Hz), 6.76-6.74 (2H, d, J = 7.6 Hz), 4.09-4.07 (1H, m), 3.82-3.79 (1H, dd, J = 2.8, 12.0 Hz), 3.68-3.63 (1H, dd, J = 5.6, 12.0 Hz), 3.02-2.97 (1H, dd, J = 6.9, 13.7 Hz), 2.83-2.78 (1H, dd, J = 6.8, 13.7 Hz); 13C NMR (100 MHz, CDCl3):δ 48.5, 138.0, 129.5, 128.9, 128.5, 128.4, 122.1, 114.5, 85.1, 63.7, 36.5; HPLC: Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL/min, λ= 242 nm),tR (minor) = 15.1 min, tR (major) = 19.1 min; 98% ee; [α]25D = +51.7 (c = 0.5, CHCl3).

1.8 (R)-2-(o- Tolylaminoxy)butan-1-ol 4h

1H NMR (400 MHz, CDCl3):δ 7.24-7.22 (1H, m), 7.22-7.15 (1H, m), 7.06-7.04 (1H, m), 6.90-6.86 (1H, m), 3.87-3.84 (2H, m), 3.77-3.73 (1H, t, J = 6.5, 12.2 Hz), 1.75-1.68 (1H, m), 1.58-1.54 (1H, m), 0.94-0.88 (3H, t, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3):δ146.3, 130.1, 126.8, 123.1, 121.8, 114.2, 85.1, 64.8, 22.9, 16.8, 10.1; HPLC: Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL/min, λ= 242 nm),tR (minor) = 6.9 min, tR (major) = 8.1 min; 94% ee; [α]25D = +25.9 (c = 0.5, CHCl3).

2 General procedure for the α-aminoxylation of cyclohexanone

PBS (0.20 mL) was added to a stirred mixture of cyclohexanone and catalyst at 0 °C, and then the substitute nitrosobenzene was added. The reaction was stirred at room temperature until the green solution turned yellow which indicated complete consumption of the nitrosobenzene. The reaction mixture was then extracted with CH2Cl2. The combined organic extracts were dried with anhydrous Na2SO4 and evaporated under vacuum. The crude oil was purified by thin layer chromatography on silica gel (petroleum ether/ethyl acetate).

2.1 (R)- 2- (N-Phenylaminoxy) cyclohexanone 6a

1H NMR (400 MHz, CDCl3):δ 7.82 (1H, s), 7.28-7.21 (2H, m), 6.97-6.91 (3H, m), 4.42-4.37 (1H, q, J = 6.0 Hz), 2.53-2.31 (3H, m), 2.07-1.96 (2H, m), 1.88-1.66 (3H, m); 13C NMR (100 MHz, CDCl3):δ 209.9, 148.0, 128.9, 122.0, 114.3, 86.2, 40.8, 32.4, 27.2, 23.7; HPLC: Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL/min, λ= 242 nm),tR (minor) = 18.9 min, tR (major) = 22.7 min;99% ee; [α]25D = +110.8 (c = 0.5, CHCl3).

2.2 (2R)- 2- (N-2-Tolylaminoxy) cyclohexanone 6b

1H NMR (400 MHz, CDCl3):δ 7.81 (1H, s), 7.16-7.12 (2H, m), 7.05-7.03 (1H, d, J = 7.5 Hz), 6.88-6.86 (1H, m), 4.41-4.37 (1H, dd, J = 6.6, 11.2 Hz), 2.51-2.48 (1H, m), 2.40-2.30 (2H, m), 2.11 (3H, s), 2.05-2.02 (1H, m), 1.90-1.87 (1H, m), 1.82-1.68 (3H, m); 13C NMR (100 MHz, CDCl3): 209.9, 145.7, 130.0, 126.5, 123.4, 121.7, 114.4, 85.9, 41.8, 32.4, 26.9, 24.5, 16.8; HPLC: Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL/min, λ= 242 nm),tR (minor) = 7.3 min, tR (major) = 9.4 min;99% ee; [α]25D = +124.9 (c = 1.0, CHCl3).

2.3 (2R)- 2- (N-3-Tolylaminoxy) cyclohexanone 6c

1H NMR (400 MHz, CDCl3):δ 7.77 (1H, s), 7.14-7.10 (1H, t, J = 8.0 Hz), 6.76-6.71 (3H, m), 4.40-4.35 (1H, m), 2.33 (3H, s), 2.51-2.35 (2H, m), 2.08-1.96 (1H, m), 1.88-1.79 (3H, m), 1.74-1.68 (2H, m); 13C NMR (100 MHz, CDCl3):δ 209.8, 148.0, 138.7, 128.7, 122.8, 115.0, 111.5, 86.2, 41.9, 32.5, 27.2, 24.9, 21.5; HPLC: Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL/min, λ= 242 nm),tR (minor) = 13.1min, tR (major) = 20.1 min; > 99% ee; [α]25D = +101.3 (c = 1.0, CHCl3).

2.4 (2R)- 2- (N-4-Tolylaminoxy) cyclohexanone 6d

1H NMR (400 MHz, CDCl3):δ 7.74 (1H, s), 7.06-7.04 (2H, d, J = 8.1 Hz), 6.85-6.83 (2H, d, J = 8.3 Hz), 4.40-4.36 (1H, ddd, J = 10.6, 5.3, 0.7 Hz), 2.51-2.48 (1H, m), 2.38- 2.32 (2H, m), 2.27 (3H, s), 1.89-1.83 (2H, m), 1.74-1.69 (3H, m); 13C NMR (100 MHz, CDCl3):δ209.9, 145.5, 131.6, 129.3 (2C), 115.0 (2C), 86.1, 40.7, 32.5, 27.2, 23.2, 20.6; HPLC: Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL/min, λ= 242 nm),tR (minor) = 14.5 min, tR (major) = 17.7 min; > 99% ee; [α]25D = +110.8 (c = 1.0, CHCl3).

2.5 (2R)- 2- (N-4-Chlorophenyl aminoxy) cyclohexanone 6e

1H NMR (400 MHz, CDCl3):δ 7.82 (1H, s), 7.21-7.18 (2H, d, J = 8.7 Hz), 7.21-7.18 (2H, d, J = 8.7 Hz), 4.39-4.35 (1H, q, J = 6.2 Hz), 3.65 (1H, s), 2.55-2.31 (3H, m), 2.14-1.97 (2H, m), 1.78-1.62 (3H, m); 13C NMR (100 MHz, CDCl3):δ209.7, 146.7, 128.8 (2C), 126.7, 115.6 (2C), 86.3, 40.8, 32.4, 27.2, 23.7; HPLC: Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL/min, λ= 242 nm),tR (minor) = 15.6 min, tR (major) = 18.3 min; > 99% ee; [α]25D = +117.6 (c = 1.0, CHCl3).

2.6 (2R)- 2- (N-4-Fluorophenyl aminoxy) cyclohexanone 6f

1H NMR (400 MHz, CDCl3):δ 6.98-6.89 (4H, m), 4.41-4.37 (1H, q, J = 6.2 Hz), 2.42-2.33 (3H, m), 2.09-2.01 (2H, m), 1.99-1.74 (3H, m); 13C NMR (100 MHz, CDCl3):δ 209.9, 159.7, 144.1, 116.4, 116.3, 115.6, 115.3, 86.2, 40.8, 32.5, 27.2, 23.7; HPLC: Chiralpak AD-H (hexane/i-PrOH, 90/10, flow rate 1 mL/min, λ= 242 nm),tR (minor) = 12.9 min, tR (major) = 15.1 min;99% ee.

[α]25D = +102.3 (c = 1.0, CHCl3).