Concise stereoselective synthesis of cis-3-alkoxy-2-carbomethoxy medium-ring oxacycles from (R)-3-(3-butenyl)-4-propynoyloxazolidin-2-one

A concise process for the stereoselective synthesis of chiral cis-3-alkoxy-2-carbomethoxy medium-ring oxacycles from (R)-3-(3-butenyl)-4-propynoyloxazolidin-2-one (1) was developed. The process includes five major steps: (i) hetero-Michael reaction between an alcohol and 1, (ii) stereoselective reduction of the resulting ketone, featuring stereochemical assistance of the neighboring oxazolidin-2-one group, (iii) esterification with an alkoxy acetic acid, (iv) chirality-transferring Ireland-Claisen rearrangement of the resulting 3-alkoxyallyl glycolate ester to provide a syn-2,3-dialkoxy carboxylate ester, and (v) relay ring-closing olefin metathesis to form a medium-ring ether along with the simultaneous removal of the oxazolidin-2-one moiety.