Allylic Substitution of Allylic Picolinates with Various Copper Reagents and Synthetic Applications

Abstract

Previously, organocopper reagents that were compatible with allylic substitution of secondary allylic esters were limited in most cases to alkyl reagents, whereas arylcopper species have often resulted in poor results due to less nucleophilic property than that of alkylcopper species. To find a reactive class of allylic esters and arylcopper reagents, we selected allylic picolinates of a (Z)-R¹CH=CHCH(OCOPy)R² structure, which reacted with arylcopper reagents derived from ArMgBr and CuBr·Me₂S, furnishing anti S_N2’ products in good yields with high regio- and stereoselectivity. Next, allylic substitution was extended successfully to organolithium-based arylcopper reagents. Furthermore, we established allylic substitution with heteroaryl and alkynyl reagents, which are in general less nucleophilic than aryl reagents. Furthermore, allylic substitutions of R¹R²C=CHCH(OCOPy)R³ and cyclohexylidene picolinates furnished corresponding quaternary carbons. The stereochemical outcome in the latter case was explained by a stable chair conformer and the equatorial attack of the reagent to the conformer. Synthetic applications using allylic substitution are described as well.