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Enantioselective α-functionalizations of ketones via allylic substitution of silyl enol ethers

Journal Article · · Nature Chemistry
 [1];  [1]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Chemistry
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The enantioselective construction of carbon-heteroatom and carbon-carbon bonds that are alpha to ketones leads to the formation of substructures that are ubiquitous in natural products, pharmaceuticals and agrochemicals. Traditional methods to form such bonds have relied on combining ketone enolates with electrophiles. Reactions with heteroatom-based electrophiles require special reagents in which the heteroatom, which is typically nucleophilic, has been rendered electrophilic by changes to the oxidation state. The resulting products usually require post-synthetic transformations to unveil the functional group in the final desired products. Moreover, different catalytic systems are typically required for the reaction of different electrophiles. In this work, we report a strategy for the formal enantioselective α-functionalization of ketones to form products containing a diverse array of substituents at the alpha position with a single catalyst. This strategy involves an unusual reversal of the role of the nucleophile and electrophile to form C-N, C-O, C-S and C-C bonds from a series of masked ketone electrophiles and a wide range of conventional heteroatom and carbon nucleophiles catalysed by a metallacyclic iridium catalyst.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1571965
Journal Information:
Nature Chemistry, Journal Name: Nature Chemistry Journal Issue: 2 Vol. 11; ISSN 1755-4330
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

References (42)

Copper-Catalyzed Asymmetric Allylic Alkylation of Halocrotonates: Efficient Synthesis of Versatile Chiral Multifunctional Building Blocks journal April 2010
Recent Advances in Catalytic, Enantioselective α Aminations and α Oxygenations of Carbonyl Compounds journal July 2005
Direct Asymmetric Alkylation of Ketones: Still Unconquered journal June 2017
Direct Catalytic Enantioselective α-Aminoxylation of Ketones: A Stereoselective Synthesis of α-Hydroxy and α,α′-Dihydroxy Ketones. journal June 2004
Oxidative Coupling of Enolates, Enol Silanes, and Enamines: Methods and Natural Product Synthesis journal July 2012
Concise total syntheses of heliannuols B and D journal January 2014
A Series of Cinchona-Derived N -Oxide Phase-Transfer Catalysts: Application to the Photo-Organocatalytic Enantioselective α-Hydroxylation of β-Dicarbonyl Compounds journal June 2016
Iridium-Catalyzed Diastereo-, Enantio-, and Regioselective Allylic Alkylation with Prochiral Enolates journal August 2016
Mechanistically Driven Development of Iridium Catalysts for Asymmetric Allylic Substitution journal December 2010
Transition Metal Catalyzed Enantioselective α-Heterofunctionalization of Carbonyl Compounds journal March 2011
Transition Metal-Catalyzed Direct Arylation of Substrates with Activated sp 3 -Hybridized C−H Bonds and Some of Their Synthetic Equivalents with Aryl Halides and Pseudohalides journal February 2010
Enantioselective Synthesis of α-Alkyl-β,γ-unsaturated Esters through Efficient Cu-Catalyzed Allylic Alkylations journal April 2003
Lewis Base Activation of Grignard Reagents with N -Heterocyclic Carbenes. Cu-Free Catalytic Enantioselective Additions to γ-Chloro-α,β-Unsaturated Esters journal December 2006
Direct Asymmetric Amination of α-Branched Cyclic Ketones Catalyzed by a Chiral Phosphoric Acid journal February 2015
Asymmetric Catalysis with Organic Azides and Diazo Compounds Initiated by Photoinduced Electron Transfer journal September 2016
Direct, Stereoselective Substitution in [Rh(CO) 2 Cl] 2 -Catalyzed Allylic Alkylations of Unsymmetrical Substrates journal April 2004
Effects of Catalyst Activation and Ligand Steric Properties on the Enantioselective Allylation of Amines and Phenoxides journal March 2005
Development of Tartaric Acid Derived Chiral Guanidines and Their Application to Catalytic Enantioselective α-Hydroxylation of β-Dicarbonyl Compounds journal June 2013
Iridium-Catalyzed Asymmetric Allylic Amination with Polar Amines: Access to Building Blocks with Lead-Like Molecular Properties journal December 2010
Direct Catalytic Enantioselectiveα-Aminoxylation of Ketones: A Stereoselective Synthesis ofα-Hydroxy andα,α′-Dihydroxy Ketones journal February 2004
Enantioselective Allylation of Aromatic Amines after In Situ Generation of an Activated Cyclometalated Iridium Catalyst journal September 2004
Quaternary Carbon Stereogenic Centers through Copper-Catalyzed Enantioselective Allylic Substitutions with Readily Accessible Aryl- or Heteroaryllithium Reagents and Aluminum Chlorides journal September 2010
Direct Catalytic Enantioselectiveα-Aminoxylation of Ketones: A Stereoselective Synthesis ofα-Hydroxy andα,α′-Dihydroxy Ketones journal February 2004
Enantioselective Allylation of Aromatic Amines after In Situ Generation of an Activated Cyclometalated Iridium Catalyst journal September 2004
Quaternary Carbon Stereogenic Centers through Copper-Catalyzed Enantioselective Allylic Substitutions with Readily Accessible Aryl- or Heteroaryllithium Reagents and Aluminum Chlorides journal September 2010
Direct, Stereoselective Substitution in [Rh(CO)2Cl]2-Catalyzed Allylic Alkylations of Unsymmetrical Substrates. journal August 2004
Effects of Catalyst Activation and Ligand Steric Properties on the Enantioselective Allylation of Amines and Phenoxides. journal August 2005
Recent Advances in Catalytic, Enantioselective α Aminations and α Oxygenations of Carbonyl Compounds journal October 2005
Lewis Base Activation of Grignard Reagents with N-Heterocyclic Carbenes. Cu-Free Catalytic Enantioselective Additions to γ-Chloro-α,β-Unsaturated Esters. journal April 2007
Enantioselective Organocatalytic Singly Occupied Molecular Orbital Activation: The Enantioselective α-Enolation of Aldehydes. journal October 2007
A Modular Strategy for the Direct Catalytic Asymmetric α-Amination of Carbonyl Compounds journal November 2016
Applications of Iridium-Catalyzed Asymmetric Allylic Substitution Reactions in Target-Oriented Synthesis journal September 2017
Catalytic Enantioselective Construction of Sulfur-Containing Tetrasubstituted Carbon Stereocenters journal July 2016
.alpha.-Sulfenylated carbonyl compounds in organic synthesis journal August 1978
Direct l -Proline-Catalyzed Asymmetric α-Amination of Ketones journal June 2002
Enantioselective Organocatalytic Singly Occupied Molecular Orbital Activation:  The Enantioselective α-Enolation of Aldehydes journal June 2007
Exploiting the Modularity of Ion-Paired Chiral Ligands for Palladium-Catalyzed Enantioselective Allylation of Benzofuran-2(3 H )-ones journal December 2012
Asymmetric α-Photoalkylation of β-Ketocarbonyls by Primary Amine Catalysis: Facile Access to Acyclic All-Carbon Quaternary Stereocenters journal September 2014
Frustrated Lewis Acid/Brønsted Base Catalysts for Direct Enantioselective α-Amination of Carbonyl Compounds journal December 2016
Asymmetric Direct α-Hydroxylation of β-Oxo Esters Catalyzed by Chiral Quaternary Ammonium Salts Derived from Cinchona Alkaloids journal October 2012
Catalytic Asymmetric Electrophilic Amination Reactions To Form Nitrogen-Bearing Tetrasubstituted Carbon Stereocenters journal October 2014
Use of In Situ Generated Nitrosocarbonyl Compounds in Catalytic Asymmetric α-Hydroxylation and α-Amination Reactions journal June 2015

Cited By (2)

Catalytic Asymmetric Synthesis of Diketopiperazines by Intramolecular Tsuji–Trost Allylation journal August 2019
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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY