Acrolein → (1R)-4-phenyl-3-cyclohexene-1-carboxaldehyde

HRID 841095Notes

Reaction equation

[C:1]1([C:7]([CH:9]=[CH2:10])=[CH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH2:12]([C@@H:19]1NC(C)(C)N(C)[C:20]1=[O:27])C1C=CC=CC=1.C(C=C)=O>C[N+]([O-])=O.O>[C:1]1([C:7]2[CH2:8][CH2:12][C@@H:19]([CH:20]=[O:27])[CH2:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a 0° C. solution of 2-phenyl-1,3-butadiene (89 mg, 0.68 mmol) in CH3NO2/H2O (95/5 v/v, 1.0 M) was added 7(29.8 mg, 0.14 mmol) and acrolein (135 μL, 2.1 mmol). The solution was stirred at 0° C. for 7 hr, then directly placed onto a silica gel column and eluted with 5% EtOAc/hex affording the title compound as a colorless oil in 90% yield (114 mg, 0.61 mmol, 83% ee). Product ratios were determined, after reduction to the corresponding alcohol (4 eq NaBH4, MeOH (0.1 M)), by HPLC (Chiralcel OD-H column, 6% isopropanol in hexanes, 1 mL/min) tr=16.2 and 20.4, min. (1R)-4-phenyl-3-cyclohexene-1-carboxaldehyde: IR (CH2Cl2) 2926, 2837, 2714, 1722, 1494, 1444 cm−1; 1H NMR (400 MHz, CDCl3) δ 9.78(s, 1H, CHO), 7.40-7.23(m, 5H, ArH), 6.16-6.12(m, 1H, PhC═CH), 2.64-2.50(m, 5H), 2.23-2.15(m, 1H), 1.90-1.79(m, 1H). 13C NMR (100 MHz, CDCl3) δ 204.2, 141.6, 136.8, 128.2, 126.9, 125.0, 122.0, 45.7, 26.0, 25.0, 22.6; HRMS (CI) exact mass calcd for (C13H19N2OCl) requires m/z 186.1045, found m/z 186.1041. (1R)-4-phenyl-3-cyclohexene-1-ol: IR (CH2Cl2) 3374, 3289, 2918, 2860, 1444, 1034 cm−1; 1H NMR (500 Mhz, CDCl3) δ 7.41-7.39(d, J=7.6 Hz, 2H, o-PhH), 7.34-7.31(t,J=7.7 Hz, 2H, m-PhH), 7.26-7.22(m, 1H, p-PhH), 6.13(br, 1H, PhC═CH), 3.66-3.58(m, 2H, CH2OH), 2.58-2.41(m, 2H), 2.40-2.31(m, 1H), 2.05-1.83(m, 3H), 1.72-1.68 (s, 1H), 1.50-1.41(m, 1H); 13C NMR (125 MHz, CDCl3) δ 142.1, 136.5, 128,2, 126.6, 124.9, 123.3, 67.6, 35.9, 28.8, 26.8, 25.7; HRMS (CI) exact mass calcd for (C13H19N2OCl) requires m/z 188.1201, found m/z 188.1203.

Workup

washeluted with 5% EtOAc/hex

Sources & evidence

ORD record: ord-3eafaa5fe46249f697efc2db85b390f4
Source dataset: uspto-grants-2002_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06369243B1

Reaction notes

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