Synthesis of Azaspiro Ketones via Ring Contraction of Heterocyclic Enamino Esters

Article abstract of DOI:10.1021/jo00348a015

Upon treatment by bromine followed by water-triethylamine, six- and seven-membered heterocyclic enamino esters 4a,b underwent easily ring contraction, giving five- and six-membered azacyclic aldehydes 5a,b, respectively.The resulted aldehydes 5 were converted to azaspiro ketones 8a,b in three steps.Starting 3-substituted seven-membered heterocyclic enamino ester 4a was synthesized by desulfurization of ketene acetal 12 with Raney nickel. 3-(Methoxycarbonyl)-N-methylcaprolactam, prepared from N-methylcaprolactam , was converted to the corresponding thio lactam by treatment with P2S5 in CS2, which upon reaction with CH3I followed by deprotonation with NEt3 afforded the ketene acetal 12.