Stereoselective synthesis of piperidine derivatives [3,2-c]-fused with oxygen heterocycles

Abstract

The reaction of tert-butyl 4-oxopiperidine-1-carboxylate dimethylhydrazone with BuLi and further with iodides of protected alcohols ICH2(CH2) n OSiMe2(t-Bu) (n = 1–4) led to the formation of the corresponding tert-butyl 3-{[tert-butyl(dimethyl)silyl]alkyl}-4-oxopiperidine-1-carboxylates that under the treatment with triethylsilane in the presence of anhydrous BiBr3 underwent cyclization with a high stereoselectivity into cis-isomers of N-Boc piperidine derivatives [3,2-c]-fused with oxygen heterocycles. The latter at the treatment with anhydrous HCl eliminate the Boc group affording hydrochlorides of stereochemically homogeneous N-unsubstituted fused bicyclic systems.