Hexanal → HCID 60004593, compound

HRID 1983435Notes

Reaction equation

HRID 1983435 reaction equation
[CH:1](=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH:8](=[O:12])[CH:9]([CH3:11])[CH3:10].N1CCC[C@H]1C(O)=O>CN(C)C=O.C(OCC)C>[OH:12][C@H:8]([C@H:2]([CH2:3][CH2:4][CH2:5][CH3:6])[CH:1]=[O:7])[CH:9]([CH3:11])[CH3:10]

Participants

6

Reactant 3

HCID 6184HexanalHCID 6561IsobutyraldehydeHCID 145742L-Proline

Product 1

HCID 60004593HCID 60004593, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of freshly distilled hexanal (120 μL, 1.0 mmol) in 500 μL dimethylformamide was added slowly over the course of 24 h to a stirring suspension of isobutyraldehyde (272 μL, 3.0 mmol), L-proline (11.5 mg, 0.10 mmol) and 500 μL dimethylformamide at room temperature. After 24 h, the resulting solution was diluted with diethyl ether and washed successively with water and brine. The combined aqueous layers were back-extracted with 3 portions dichloromethane. The organic layers were combined, dried over anhydrous MgSO4, and concentrated in vacuo. Flash chromatography (7:3 pentane:diethyl ether) afforded the title compound as a clear, colorless oil in 80% yield (127 mg, 0.80 mmol), 98% ee and 96:4 anti: syn. IR (film) 3458, 2960, 2934, 2874, 2725, 1720, 1467, 1328, 1220, 1146, 1024, 991.2, 959.9, 901.1, 775.6 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.75 (d, 1H, J=3.3 Hz, CHO); 3.56 (dd (apparent q), 1H, J=6.0, 5.7 Hz, CHOH); 2.46 (dddd, 1H, J=8.4, 5.7, 5.7, 3.3 Hz, CHCH2); 1.99 (d, 1H, J=6.0 Hz, OH); 1.82 (m, 1H, CH(CH3)2); 1.70 (m, 1H, CHCH2); 1.58 (m, 1H, CHCH2); 1.30 (m, 4H, CH2CH2CH3); 0.97 (d, 3H, J=6.6 Hz, CH(CH3)2); 0.93 (d, 3H, J=6.6 Hz, CH(CH3)2); 0.90 (dd (apparent t), 3H, J=6.6, 6.6 Hz); 3C NMR (75 MHz, CDCl3) δ 206.1, 76.7, 54.9, 31.3, 29.5, 26.7, 23.2, 20.0, 17.1, 14.2; HRMS (CI) exact mass calcd for [M+H]+(C10H21O2) requires m/z 173.1541, found m/z 173.1540; [α]D=−15.4 (c=1.0, CHCl3). The product ratios were determined by GLC analysis of the acetal derived from 2,2-dimethylpropane-1,3-diol (obtained by the method of Yamamoto, supra) using a Bodman Chiraldex β-DM (30 m×0.25 mm) column (110° C. isotherm, 23 psi); (2S,3S) anti isomer tr=97.8 min, (2R,3R) anti isomer tr=102.7 min, (2R,3S) and (2S,3R) syn isomers tr, =94.4, 96.5 min.

Workup

  1. washwashed successively with water and brine
  2. extractionThe combined aqueous layers were back-extracted with 3 portions dichloromethane
  3. dry with materialdried over anhydrous MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a8787206953f4043b55617bd31578520
Source dataset
uspto-grants-2009_06
Patent number
US07541456B2

Reaction notes

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