Substitution of Allylic Picolinates with Various Copper Reagents and Synthetic Applications

Abstract

Allylic substitution of secondary allylic picolinates of a (Z)-R1CH=CHCH(OCOPy)R2 structure is summarized. This substitution proceeds with copper reagents derived from Grignard reagents and organolithiums, furnishing anti SN2′ products in good yields, with high regio- and stereoselectivity. Alkyl as well as less reactive alkenyl and aryl copper reagents are suitable reagents. Under optimized reaction conditions, the substitution proceeds with heteroaryl and alkynyl reagents, which are much less nucleophilic than aryl reagents. Picolinates possessing an additional substituent on the olefinic carbon, i.e., R1R2C=CHCH(OCOPy)R3, and cyclohexylidene picolinates, produce quaternary carbons on acyclic and cyclohexane carbons. In the latter case, the stereochemical course is determined by the equatorial attack of the reagent to the stable chair conformer. Synthetic application using allylic substitution is presented as well.