Electrocatalyzed Direct Arene Alkenylations without Directing Groups: Selective Late-Stage Drug Diversification [post]

Lutz Ackermann, Zhipeng Lin, Uttam Dhawa, Binbin Yuan, Yan-Cheng Liou, Magnus Johansson
2022 unpublished
Electrocatalysis has emerged as an increasingly viable platform for molecular syntheses, that can replace chemical redox agents and enable unprecedented reaction pathways. Despite major progress in electrooxidative C−H activations, these arene transformations generally require directing groups for chelation-induced efficiency and control of position-selectivity in the C−H activation. The installation and removal of these directing groups calls for additional synthesis operations, which
more » ... es the inherent efficacy of the C−H activation approach in terms of undesired waste formation and low resource economy. In sharp contrast, we herein present molecular electrocatalyzed C−H olefinations of simple arenes devoid of exogenous directing groups. The robust palladaelectro-catalysis proved amenable to a wide range of both electronically-diverse arenes under exceedingly mild reaction conditions. The strategy avoids sacrificial chemical oxidants, but operates by the reductive hydrogen evolution reaction (HER). This study points to a remarkable strategy comprising two electrochemical transformations to guarantee unprecedented levels of position-selectivities in direct arene olefinations. Cyclic voltammetry studies and computational analysis identified a direct correlation between the redox potential and catalysis efficacy. The palladaelectro-catalysis strategy avoids protecting and directing group interconversions, the practical importance of which is reflected by direct late-stage functionalizations of structurally complex compounds of relevance to drug discovery and pharmaceutical industries.
doi:10.21203/rs.3.rs-1607467/v1 fatcat:7r5iasfhyfeuhl3mvle6hciumq