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Title: Copper‐Catalyzed C(sp 3 )−H α‐Acetylation: Generation of Quaternary Centers

Journal Article · · Angewandte Chemie (International Edition)
 [1];  [2];  [1];  [3];  [4]; ORCiD logo [2]
  1. Department of Chemistry Georgetown University Box 571227 20057-1227 Washington DC USA
  2. Department of Chemistry Georgetown University Box 571227 20057-1227 Washington DC USA, Department of Chemistry Michigan State University 578 S. Shaw Lane 48824 East Lansing MI USA
  3. Department of Chemistry University of Bath BA2 7AY Bath UK
  4. Department of Chemistry Center for Advanced Scientific Computing and Modeling (CASCaM) University of North Texas 76203 Denton TX USA
+ Show Author Affiliations

Abstract α‐substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in natural products and pharmaceuticals. We report the α‐acetylation of C(sp 3 )−H substrates R−H with arylmethyl ketones ArC(O)Me to provide α‐alkylated ketones ArC(O)CH 2 R at RT with t BuOO t Bu as oxidant via copper(I) ‐diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α‐substitution with bulky substituents without competing elimination that occurs in more traditional alkylation reactions between enolates and alkyl electrophiles. DFT studies suggest the intermediacy of copper(II) enolates [Cu II ](CH 2 C(O)Ar) that capture alkyl radicals R• to give R−CH 2 C(O)Ar outcompeting dimerization of the copper(II) enolate to give the 1,4‐diketone ArC(O)CH 2 CH 2 C(O)Ar.

Sponsoring Organization:
USDOE
Grant/Contract Number:
NONE; FG02-03ER15387
OSTI ID:
2507264
Journal Information:
Angewandte Chemie (International Edition), Journal Name: Angewandte Chemie (International Edition) Journal Issue: 5 Vol. 64; ISSN 1433-7851
Publisher:
Wiley Blackwell (John Wiley & Sons)Copyright Statement
Country of Publication:
Germany
Language:
English

References (37)

Direct Catalytic Intermolecular α‐Allylic Alkylation of Aldehydes by Combination of Transition‐Metal and Organocatalysis journal March 2006
FeCl2‐Catalyzed Selective CC Bond Formation by Oxidative Activation of a Benzylic CH Bond journal August 2007
C-Alkylation of Ketones and Related Compounds by Alcohols: Transition-Metal-Catalyzed Dehydrogenation journal December 2015
Copper catalyzed allylic oxidation with peresters journal January 2002
Palladium-catalyzed addition of ketones to alkylidenecyclopropanes journal April 2002
Ruthenium-catalyzed regioselective α-alkylation of ketones with primary alcohols journal October 2002
Recent Advances in Radical C–H Activation/Radical Cross-Coupling journal March 2017
Revisiting the Synthesis and Nucleophilic Reactivity of an Anionic Copper Superoxide Complex journal March 2019
Copper-Catalyzed C(sp3)–H Methylation via Radical Relay journal September 2022
Recent Advances in α - Alkylation Reactions using Alcohols with Hydrogen Borrowing Methodologies journal October 2014
Reaction of ketone enolates with copper dichloride. Synthesis of 1,4-diketones journal May 1975
Reactions of t-Butyl Peresters. I. The Reaction of Peresters with Olefins1 journal November 1959
THE REACTIONS OF t-BUTYL PERBENZOATE AND OLEFINS—A STEREOSPECIFIC REACTION 1 journal February 1958
Chemistry of the t -Butoxyl Radical:  Evidence that Most Hydrogen Abstractions from Carbon are Entropy-Controlled journal June 2004
Reaction of Cu I with Dialkyl Peroxides: Cu II -Alkoxides, Alkoxy Radicals, and Catalytic C–H Etherification journal October 2012
Copper(II) Anilides in sp 3 C-H Amination journal July 2014
Simple, Highly Active Palladium Catalysts for Ketone and Malonate Arylation:  Dissecting the Importance of Chelation and Steric Hindrance journal February 1999
Direct Catalytic Asymmetric Aldol Reaction journal April 1999
Highly Active and Selective Catalysts for the Formation of α-Aryl Ketones journal February 2000
Three-Coordinate Copper(II) Alkynyl Complex in C–C Bond Formation: The Sesquicentennial of the Glaser Coupling journal September 2020
Rapid and Modular Access to Quaternary Carbons from Tertiary Alcohols via Bimolecular Homolytic Substitution journal July 2023
Copper Catalyzed sp3 C–H Etherification with Acyl Protected Phenols journal December 2016
Enantioselective Construction of Quaternary All-Carbon Centers via Copper-Catalyzed Arylation of Tertiary Carbon-Centered Radicals journal January 2019
Alkylation of enolates with triflates journal July 1993
Copper-Catalyzed Oxidative Coupling of Benzylic C−H Bonds with 1,3-Dicarbonyl Compounds journal September 2008
Asymmetric catalytic formation of quaternary carbons by iminium ion trapping of radicals journal April 2016
Radical C(sp3)–H functionalization and cross-coupling reactions journal May 2022
Catalytic enantioconvergent coupling of secondary and tertiary electrophiles with olefins journal October 2018
Peroxide promoted tunable decarboxylative alkylation of cinnamic acids to form alkenes or ketones under metal-free conditions journal January 2015
Transition metal-catalyzed ketone-directed or mediated C–H functionalization journal January 2015
Enantioselective formation of quaternary carbon stereocenters in natural product synthesis: a recent update journal January 2020
Copper-catalyzed radical relay in C(sp3)–H functionalization journal January 2022
Ketones as strategic building blocks for the synthesis of natural product-inspired compounds journal January 2022
Copper catalyzed benzylic sp3 C–H alkenylation journal January 2024
One-Step Substitutive Acyloxylation at Carbon. Part I. Reactions Involving Peroxides journal January 1972
Asymmetric Catalysis Special Feature Part I: Catalytic asymmetric synthesis of all-carbon quaternary stereocenters journal January 2004
Regioselective ketone α-alkylation with simple olefins via dual activation journal July 2014

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