A Ring Expansion Procedure Based on the Tandem Dealkoxycarbonylation-Michael Addition Reaction

Article abstract of DOI:10.1021/jo00114a024

A three-step ring expansion procedure has been developed to convert methyl α,α-dialkyl-1-cyclopenteneacetates to highly functionalized cyclohexaneacetic esters.The procedure involves (1) ozonolytic double bond cleavage, (2) chemoselective Wittig olefination of the aldehyde carbonyl of the resulting keto aldehyde, and (3) tandem dealkoxycarbonylation-Michael addition to close the ring.The transformation proceeds best when the α-carbon of the starting acetate is quaternary, and thus, the method is unique in yielding hindered 2,2-dialkyl-3-oxocyclohexaneacetic esters.The reaction sequence is easily performed, and overall yields of 40-50percent are readily achieved.The synthetic and mechanistic details of this process as well as optimization studies are presented.An analogous five-membered cyclization process was also investigated.Tandem dealkoxycarbonylation-Michael addition of 1-ethyl methyl (E)-7,7-dimethyl-6-oxo-2-octenedioate was found to afford a 24percent isolated yield of ethyl 2,2-dimethyl-3-oxocyclopentaneacetate by a disfavored 5--exo-trig process.