Synthesis of 2,6-Dimethyltropone - A New, Convenient Methodology from 2,6-Dimethylcyclohexanone

Abstract

Until now, 2,6-dialkyltropones have not been described. 2,6-Dimethyltropone (5) represents an appropriate material for synthesis of naturally occurring antiviral compounds. A new, convenient method for synthesis of 2,6-dimethyltropone (5) from 2,6dimethylcyclohexanone in five optimized steps and 52% overall yield has been developed. Trimethylsilyl enol ether 1, prepared from 2,6-dimethylcyclohexan-1-one, was treated with dichlorocarbene, to give 7,7-dichloro-2,6-dimethyl-1-trimethylsilyloxybicyclo[4.1.0]heptanes (2). Acid promoted ring opening of 2 at room temperature gave 2-chloro-3,7-dimethylcyclohept-2-ene-1-one (3a). At higher temperatures (150-300°C) a mixture of 3a and 2chloro-3,7-dimethyl-1-trimethylsilyloxycyclohepta-1,3-diene (3b) was obtained in the ratio 2.1:1.0, respectively. Gamma bromination of 3a by NBS/AIBN gave diastereoisomers 4a and 4b in the ratio 5:1, which were converted to 2,6-dimethyltropone (5) by Li 2 CO 3 in DMF at 120°C. All new compounds were characterized by their NMR and HRMS spectra. The relative configuration and the structure of the preferred conformer of 3a and 4a were determined by HMQC, COSY and NOE NMR measurements.