Tetrahydrofuran → Diisopropylamine

Participants

Reaction Steps

A solution of keto acid 21 (752 mg, 4.42 mmol, 1.0 equiv) in THF (22 mL) was added dropwise at −78° C. to a freshly prepared solution of LDA [formed by addition of n-BuLi (6.49 mL, 1.6 M solution in hexanes, 10.4 mmol, 2.35 equiv) to a solution of diisopropylamine (1.43 mL, 10.2 mmol, 2.3 equiv) in THF (44 mL) at −10° C. and stirring for 30 min]. After stirring for 15 min the reaction mixture was allowed to warm to −30° C. and stirred at that temperature for 1.5 h. The reaction mixture was cooled back to −78° C. and a solution of aldehyde 7 (0.891 g, 7.07 mmol, 1.6 equiv) in THF (22 mL) was added via cannula. The resulting mixture was stirred for 15 min at −78° C., then warmed to −40° C. and stirred for 1 h, cooled to −78° C. and quenched by slow addition of saturated aqueous NH4Cl (10 mL) solution. The reaction mixture was warmed to 0° C., and acetic acid (1.26 mL, 22.1 mmol, 5.0 equiv) was added, followed by warming to 25° C. Extractions with EtOAc (6×15 mL), filtration througth a short plug of silica gel and concentration afforded, in high yield, a mixture of aldol products 33 and 34 along with unreacted starting acid 21 in a 35:50:15 ratio (1H NMR). This crude material was used without further purification. 1H NMR (500 MHz, CDCl3; only signals for 33 and 34 are reported) d 7.16 (d, J=16.0 Hz, 1H, CH═CHCOOH), 5.95 (d, J=16.0 Hz, 1H, CH═CHCOOH), 5.86-5.73 (m, 1H, CH2CH═CH2), 5.02-4.91 (m, 2H, CH2CH═CH2), 3.46-3.32 (m, 1H, CHOH(CHCH3)), 3.17-3.11 (m, 1H, CH3CH(C═O)), 2.09-1.98 (m, 2H, CH2CH═CH2), 1.72-1.24 (m, 9H), 1.14-1.02 (m, 5H), 0.95-0.81 (m, 3H); HRMS (FAB), calcd for C17H29O4 (M+H+) 297.2066, found 297.2074.

Provenance & Evidence