Carbonyl transposition and regio- and stereo-specific syntheses of new alcohols, amino-alcohols, and ketones in the monoterpenoid 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane

Abstract

An efficient transposition of carbonyl group R¹–CO–CH₂–R²→ R¹–CH₂–CO–R² in the 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane system was carried out via hydroboration–oxidation of 6-dialkylamino-1,3,3-trimethyl-2-oxabicyclo[2.2.2]oct-5-enes (3a–c), which gave regio- and stereo-specifically 6-cis-dialkylamino-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-5-trans-ols (4a–c) in high yield. Cope reaction of the N-oxide (5b) obtained from the amino-alcohol (4b) with hydrogen peroxide led to 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-5-one (6), the other possible isomer of the long-known 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-one (1b). The ketone (6) was also obtained from 1,3,3-trimethyl-2-oxabicyclo[2.2.2]oct-5-ene (2)via its trans-epoxide (11), lithium aluminium hydride reduction at 160–165 °C of which gave stereo- and regio-specifically 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-5-trans–ol (9b). Chromic acid oxidation of (9b) and (4a–c) under various conditions gave the ketone (6) and the amino-ketones (7a–c), respectively. Lithium aluminium hydride reduction of (6) and (7a–c) afforded stereospecifically the cis-alcohol (9a) and 6-cis-dialkylamino-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-5-cis-ols (8a–c), respectively. Hydroboration–oxidation of the alkene (2) was not regiospecific, giving a 3 : 1 mixture of the trans-alcohols (9b) and (10b), respectively.