Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling

Seunghwan Byun; Meemie U. Hwang; Henry R. Wise; Anna V. Bay; Paul H.Y. Cheong; Karl A. Scheidt

doi:10.1002/anie.202312829

Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling

Seunghwan Byun, Meemie U. Hwang, Henry R. Wise, Anna V. Bay, Paul H.Y. Cheong^*, Karl A. Scheidt^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

An enantioselective carbene-catalyzed radical-radical coupling of acyl imidazoles and racemic Hantzsch esters is disclosed. This method involves the coupling of an N-heterocyclic carbene-derived ketyl radical and a secondary sp³-carbon radical and allows access to chiral α-aryl aliphatic ketones in moderate-to-good yields and enantioselectivities without any competitive epimerization. The utility of this protocol is highlighted by the late-stage functionalization of various pharmaceutical compounds and is further demonstrated by the transformation of the enantioenriched products to biologically relevant molecules. Computational investigations reveal the N-heterocyclic carbene controls the double-facial selectivity of the ketyl radical and the alkyl radicals, respectively.

Original language	English (US)
Article number	e202312829
Journal	Angewandte Chemie - International Edition
Volume	62
Issue number	49
DOIs	https://doi.org/10.1002/anie.202312829
State	Published - Dec 4 2023

Funding

K.A.S. thanks NIGMS for support of this work (R35GM136440). P.H.‐Y.C. is the Bert and Emelyn Christensen professor of OSU and gratefully acknowledges financial support from the Vicki & Patrick F. Stone family and the National Science Foundation (NSF, CHE1352663). We thank Charlotte Stern and Cullen Schull for X‐ray crystallographic assistance as well as Dalton Kim for assistance with HRMS.

Keywords

Asymmetric Catalysis
N-Heterocyclic Carbenes
Organocatalysis
Photoredox Catalysis
Radicals

ASJC Scopus subject areas

General Chemistry
Catalysis

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10.1002/anie.202312829

Cite this

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title = "Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling",

abstract = "An enantioselective carbene-catalyzed radical-radical coupling of acyl imidazoles and racemic Hantzsch esters is disclosed. This method involves the coupling of an N-heterocyclic carbene-derived ketyl radical and a secondary sp3-carbon radical and allows access to chiral α-aryl aliphatic ketones in moderate-to-good yields and enantioselectivities without any competitive epimerization. The utility of this protocol is highlighted by the late-stage functionalization of various pharmaceutical compounds and is further demonstrated by the transformation of the enantioenriched products to biologically relevant molecules. Computational investigations reveal the N-heterocyclic carbene controls the double-facial selectivity of the ketyl radical and the alkyl radicals, respectively.",

keywords = "Asymmetric Catalysis, N-Heterocyclic Carbenes, Organocatalysis, Photoredox Catalysis, Radicals",

author = "Seunghwan Byun and Hwang, {Meemie U.} and Wise, {Henry R.} and Bay, {Anna V.} and Cheong, {Paul H.Y.} and Scheidt, {Karl A.}",

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T1 - Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling

AU - Byun, Seunghwan

AU - Hwang, Meemie U.

AU - Wise, Henry R.

AU - Bay, Anna V.

AU - Cheong, Paul H.Y.

AU - Scheidt, Karl A.

PY - 2023/12/4

Y1 - 2023/12/4

N2 - An enantioselective carbene-catalyzed radical-radical coupling of acyl imidazoles and racemic Hantzsch esters is disclosed. This method involves the coupling of an N-heterocyclic carbene-derived ketyl radical and a secondary sp3-carbon radical and allows access to chiral α-aryl aliphatic ketones in moderate-to-good yields and enantioselectivities without any competitive epimerization. The utility of this protocol is highlighted by the late-stage functionalization of various pharmaceutical compounds and is further demonstrated by the transformation of the enantioenriched products to biologically relevant molecules. Computational investigations reveal the N-heterocyclic carbene controls the double-facial selectivity of the ketyl radical and the alkyl radicals, respectively.

AB - An enantioselective carbene-catalyzed radical-radical coupling of acyl imidazoles and racemic Hantzsch esters is disclosed. This method involves the coupling of an N-heterocyclic carbene-derived ketyl radical and a secondary sp3-carbon radical and allows access to chiral α-aryl aliphatic ketones in moderate-to-good yields and enantioselectivities without any competitive epimerization. The utility of this protocol is highlighted by the late-stage functionalization of various pharmaceutical compounds and is further demonstrated by the transformation of the enantioenriched products to biologically relevant molecules. Computational investigations reveal the N-heterocyclic carbene controls the double-facial selectivity of the ketyl radical and the alkyl radicals, respectively.

KW - Asymmetric Catalysis

KW - N-Heterocyclic Carbenes

KW - Organocatalysis

KW - Photoredox Catalysis

KW - Radicals

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ER -

Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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CCDC 2254033: Experimental Crystal Structure Determination

Cite this

Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Datasets

CCDC 2254033: Experimental Crystal Structure Determination

Cite this