Synthesis of the Verapamil Intermediate through the Quaternary Carbon-Constructing Allylic SubstitutionThis work was supported by JSPS KAKENHI Grant Number 26410111 and the Kobayashi International Scholarship
Received: 08 May 2017
Accepted after revision: 04 July 2017
08 August 2017 (eFirst)
In the present study, the key secondary allylic picolinate was synthesized via Pd(PPh3)4-catalyzed coupling of the TBS ether of (R,Z)-4-iodo-5-methylhex-3-en-2-ol with allyl-MgBr. Allylic substitution of the picolinate with the copper reagent derived from 3,4-(MeO)2C6H3MgBr and Cu(acac)2 in a 2:1 ratio afforded the anti SN2′ product with complete chirality transfer and 91% regioselectivity. Synthetic manipulation of the olefin moiety led to the nitrile group, generating the intermediate for the synthesis of (S)-verapamil.