The Stereochemistry of SN2' Addition to Macrocyclic α-Methylenecycloalkylidene Epoxides by Organocopper Reagents

Article abstract of DOI:10.1021/jo00382a024

The addition of n-butylmagnesium bromide-copper(I) iodide in THF-dimethyl sulfide has been carried out with the 12-, 14-, and 16-membered optically active (R)-2-methylenecycloalkylidene epoxides 9a, 9b, and 9d.In each case, the S_N2' substitution products 10 and 11 were formed with the trans predominating by 9:1 or better.The 12- and 14-membered cycloalkylidene epoxides 9a and 9b gave the (R)-cycloalkenylcarbinols 10a and 10b of over 90percent optical purity.Accordingly, attack on the double bond must occur syn to the epoxide oxygen via the O-exo s-trans conformer of 9a and 9b.The 16-membered cycloalkylidene epoxide 9d gave racemic cycloalkenylcarbinol 10d upon treatment with the foregoing organocopper reagent.This result is attributable to racemization of 10d rather than nonselective S_N2' addition.