Highly efficient substitution of allylic picolinates with copper reagents derived from aryl-, alkenyl-, furyl-, and thienyl-lithiums

Abstract

Substitution of optically active allylic picolinate, cis R1-CH(OC(O)(2-Py))CHCHR2 (R1=(CH2)2Ph, R2=CH2OTBS), with phenylcopper reagents derived from salt free PhLi (2equiv) and CuBr·Me2S (2 and 1equiv, respectively) was highly promoted by MgBr2 (3equiv), producing anti SN2′ product regio- and stereoselectively. This reagent system was proven to be general with several picolinates (R1, R2: Ph(CH2)2, PMBO(CH2)3, Me, TBSOCH2, PMBOCH2, c-Hex). Furthermore, aryl copper reagents prepared from ArLi, which was in turn prepared by Li–halogen exchange, was proven to be compatible with the substitution in the presence of larger quantity of MgBr2 than that of LiX coproduced by the exchange. Substitution was not interfered with the steric hindrance on aryl coppers (Ar: 2-MeOC6H4, 2,6-(MOMO)2-4-MeC6H2, 2,6-Me2C6H3, etc.). Similarly, stereodefined cis and trans alkenyl, furyl, and thienyl reagents gave the corresponding anti SN2′ products efficiently.