Exploiting Interfacial Design for the Electrocatalytic Construction of C-C bonds

NIH RePORTER · NIH · R35 · $385,136 · view on reporter.nih.gov ↗

Abstract

PROJECT ABSTRACT The objective of our research is to access new chemical spaces in drug discovery and development by reimagining the catalytic conditions for electricity-driven organic transformations. We propose a synthetic platform to couple every major class of C(sp3) organic halide electrophile with aldehyde and ketones. By fine- tuning the key electrophile interactions with the electrode material by interfacial design, we propose to forge C(sp3)–C(sp3) bonds with high selectivity and stereoselectivity. Our approach will provide direct and catalytic access to new chiral alcohol and α,α-difluorobenzylic derivatives, prevalent motifs in several high-profile pharmaceuticals, from accessible feedstocks. Our synthetic methods will provide complementary and direct approaches to access (enantio)selective C(sp3)–C(sp3) bonds that are restricted to non-catalytic or multi-step reactions. Non-catalytic reactions require either the generation of highly reactive reaction intermediates that degrade bioactive functional groups or the use of expensive and rare elements that limit wide-spread adoption. In addition to increasing the accessibility to prepare and diversify pharmaceuticals via electrocatalytic C(sp3)– C(sp3) bond formation, our mechanistic and structural analyses of electrified interfaces will dissect the fundamental properties that control interfacial reactivity in complex electrosynthetic manifolds. Thus, our program will reveal how new mechanisms to construct C(sp3)–C(sp3) can be accessed by engaging a recoverable and infinitely reusable solid electrocatalyst interface; an inherently sustainable synthetic approach that can be readily adoptable by medicinal chemists.

Key facts

NIH application ID
10890063
Project number
5R35GM150845-02
Recipient
UNIVERSITY OF CHICAGO
Principal Investigator
Anna Wuttig
Activity code
R35
Funding institute
NIH
Fiscal year
2024
Award amount
$385,136
Award type
5
Project period
2023-08-01 → 2028-05-31