Synthesis of the natural enantiomers of irones from (+)-citronellal

Abstract

Some irone isomers with the natural chirality have been synthesised from (+)-citronellal (7). (+)-Methyl citronellate (21) obtained from compound (7) was methylated stepwise to give methyl 2,2,3,7-tetramethyloct-6-enoate (23). After hydrolysis of the ester (23), the resulting acid was converted into the corresponding acyl chloride, which was then cyclised by means of tin(IV) chloride to give 2,2,3-trimethyl-6-(1-chloro-1-methylethyl)cyclohexanone (24). The cyclohexanone (24) was dehydrochlorinated, reduced, acetylated, and then ozonised to give 2-acetoxy-3,3,4-trimethylcyclohexanone (27). The Wittig reaction of the ketone (27) with methoxymethylenetriphenylphosphorane followed by hydrolysis and elimination of acetic acid provided 3,3,4-trimethylcyclohexene-1-carbaldehyde (28). The vinyl ether of an allylic alcohol obtained by reduction of the aldehyde (28) was thermolysed to give the key intermediate, 1-(2,2,3-trimethyl-6-methylenecyclohexyl)acetaldehyde (13), stereoselectively. Elongation of the side-chain in (13) afforded (+)-trans-γ-irone (32a) as the major product. Treatment of the irone (32a) with phosphoric acid yielded (–)-trans-α-irone (2).