Isoprene → (1R)-4-methylcyclohex-3-ene-1-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

To a 0° C. solution of 5 (32 mg, 0.12 mmol) in CH3NO2/H2O (95/5 v/v, 1.0 M) was added acrolein (1.0 mL, 15 mmol), and isoprene (0.50 mL, 5 mmol). The solution was stirred at 0° C. for 7 hr, then directly placed onto a silica gel column and eluted with 3% Et2O/pentane, affording the title compound as a colorless oil in 84% yield (745 mg, 89% ee). Product ratios were determined by GLC (Bodman Γ-TA column, 35° C., 0.25° C./min gradient, 23 psi) t4=84.1 min, 85.3 min. 1H NMR, 13C NMR, and IR data were consistent with previously reported values (see Ishihara et al. (1998), supra). The absolute configuration was determined by oxidation to 4-methyl-3-cyclohexene-1-carboxylic acid and correlation of the optical rotation to the reported value; see Poll et al. (1985) Tetrahedron Lett. 26:3095-3098. To the aldehyde (255 mg, 2 mmol) was added a solution of isobutylene in THF (2.0 M, 30 mL) followed by tBuOH-H2O (5/1, 20 mL), KH2PO4 (840 mg, 6 mmol), and NaClO2 (540 mg, 6 mmol). The heterogenous mixture was stirred for 4 hr, then partitioned between EtOAc and H2O. The organic extract was washed with brine, dried (MgSO4), and concentrated. The white solid was purified by silica gel chromatography (20% EtOAc/hex): [α]D20=+89®=4.0, 95% EtOH). Literature [α]D20=−107 ®=4, 95% EtOH) for (S)-4-methyl-3-cyclohexene-1-carboxylic acid.

Provenance & Evidence