Synlett
DOI: 10.1055/s-0036-1588518
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of the Verapamil Intermediate through the Quaternary Carbon-Constructing Allylic Substitution

Yuichi Kobayashi*, Ryohei Saeki, Yutaro Nanba, Yuta Suganuma, Masao Morita, Keita Nishimura
  • Department of Bioengineering, Tokyo Institute of Technology, Box B-52, Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501, Japan   Email: ykobayas@bio.titech.ac.jp
This work was supported by JSPS KAKENHI Grant Number 26410111 and the Kobayashi International Scholarship
Further Information

Publication History

Received: 08 May 2017

Accepted after revision: 04 July 2017

Publication Date:
08 August 2017 (eFirst)

Abstract

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.

Supporting Information