Isobutyraldehyde → HCID 60004597, compound

HRID 1983436Notes

Reaction equation

HRID 1983436 reaction equation
[CH:1](=[O:10])[CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH:11](=[O:15])[CH:12]([CH3:14])[CH3:13].N1CCC[C@H]1C(O)=O>CN(C)C=O.C(OCC)(=O)C>[CH2:3]([C@@H:2]([C@@H:11]([OH:15])[CH:12]([CH3:14])[CH3:13])[CH:1]=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 6561IsobutyraldehydeHCID 7707BenzenepropanalHCID 145742L-Proline

Product 1

HCID 60004597HCID 60004597, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of freshly distilled hydrocinnamaldehyde (132 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 26 h, the resulting solution was diluted with ethyl acetate 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 Na2SO4, and concentrated in vacuo. Flash chromatography (3:1 hexanes:ethyl acetate) afforded the title compound as a clear, colorless oil in 75% yield (155 mg, 0.75 mmol), 91% ee and 95:5 anti: syn. IR (film) 3466, 3086, 3063, 3028, 2962, 2932, 2834, 2733, 1950, 1875, 1806, 1722, 1604, 1496, 1454, 1390, 1368, 1244, 1180, 1136, 1049, 1031, 993.0, 964.3, 849.7, 800.6, 739.8, 700.2 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.83 (d, 1H, J=2.1 Hz, CHO); 7.27 (m, 5H, Ar—H); 3.43 (ddd, 1H, J=6.6, 6.6, 4.5 Hz, CHOH); 3.06 (dd, 1H, J=13.2, 7.8 Hz, PhCH2); 2.92 (dd, 1H, J=13.2, 6.9 Hz, PhCH2); 2.81 (m, 1H, CHCH2); 2.15 (d, 1H, J=6.0 Hz, OH); 1.90 (m, 1H, CH(CH3)2); 0.96 (d, 3H, J=6.6 Hz, CH(CH3)2); 0.92 (d, 3H, J=7.2 Hz, CH(CH3)2); 13C NMR (75 MHz, CDCl3) δ 205.6, 129.2, 128.9, 128.6, 126.8, 76.9, 55.8, 33.4, 32.0, 19.7, 18.2; HRMS (CI) exact mass calcd for [M+H]+(C13H19O2) requires m/z 207.1385, found m/z 207.1386; [α]D=−7.9 (c=1.0, CHCl3). The product ratios were determined by HPLC analysis of the corresponding alcohol (obtained by NaBH4 reduction) using a Chiracel OJ and OJ guard column (1.0% ethanol/hexanes, 1 mL/min); (2S,3S) anti isomer tr=7.5 min, (2R,3R) anti isomer tr=9.4 min, (2R,3S) and (2S,3R) syn isomers tr=6.3, 6.9 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 Na2SO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f860c303903e4e08ba00c998700abb20
Source dataset
uspto-grants-2009_06
Patent number
US07541456B2

Reaction notes

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