An Asymmetric Aromatic Finkelstein Reaction: A Platform for Remote Diarylmethane Desymmetrization

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2023 Oct 3

PMID 37788150

Authors

Tobias Morack

Tyler E Myers

Lucas J Karas

Melissa A Hardy

Brandon Q Mercado

Matthew S Sigman

Scott J Miller

Affiliations

Soon will be listed here.

Abstract

A first-of-its-kind enantioselective aromatic Finkelstein reaction is disclosed for the remote desymmetrization of diarylmethanes. The reaction operates through a copper-catalyzed C-I bond-forming event, and high levels of enantioselectivity are achieved through the deployment of a tailored guanidinylated peptide ligand. Strategic use of transition-metal-mediated reactions enables the chemoselective modification of the aryl iodide products; thus, the synthesis of a diverse set of otherwise difficult-to-access diarylmethanes with excellent levels of selectivity is realized from a common intermediate. A mixed experimental/computational analysis of steric parameters and substrate conformations identifies the importance of remote conformational effects as a key to achieving high enantioselectivity in this desymmetrization reaction.

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