Carbonyl umpolung as an organometallic reagent surrogate

Construction of new carbon-carbon bonds is the cornerstone of organic chemistry. Organometallic reagents are amongst the most robust and versatile nucleophiles for this purpose. Polarization of the metal-carbon bonds in these reagents facilitates their reactions with a vast array of electrophiles to...

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Published inChemical Society reviews Vol. 5; no. 19; pp. 1733 - 1742
Main Authors Dai, Xi-Jie, Li, Chen-Chen, Li, Chao-Jun
Format Journal Article
LanguageEnglish
Published London Royal Society of Chemistry 04.10.2021
Subjects
Alcohols
Aldehydes
Alkylation
Allyl compounds
allylation
Carbon
Carbonyl groups
Carbonyls
Carboxylation
Chemical bonds
Chemical reactions
Covalent bonds
Cross coupling
cross-coupling reactions
Deoxygenation
evolution
feedstocks
Hydrazones
Ketones
Lewis acids
Lewis bases
Metal halides
Nucleophiles
Organic chemistry
Reagents
stoichiometry
Transition metals
wastes
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ISSN0306-0012
1460-4744
1460-4744
DOI10.1039/d1cs00418b

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Summary:Construction of new carbon-carbon bonds is the cornerstone of organic chemistry. Organometallic reagents are amongst the most robust and versatile nucleophiles for this purpose. Polarization of the metal-carbon bonds in these reagents facilitates their reactions with a vast array of electrophiles to achieve chemical diversification. The dependence on stoichiometric quantities of metals and often organic halides as feedstock precursors, which in turn produces copious amounts of metal halide waste, is the key limitation of the classical organometallic reactions. Inspired by the classical Wolff-Kishner reduction converting carbonyl groups in aldehydes or ketones into methylene derivatives, our group has recently developed strategies to couple various alcohols, aldehydes, and ketones with a broad range of both hard and soft carbon electrophiles in the presence of catalytic amounts of transition metals, via the hydrazone derivatives: i.e. , as organometallic reagent surrogates. This Tutorial Review describes the chronological development of this concept in our research group, detailing its creation in the context of a deoxygenation reaction and evolution to a more general carbon-carbon bond-forming strategy. The latter is demonstrated by the employment of carbonyl-derived alkyl carbanions in various transition-metal catalyzed chemical transformations, including 1,2-carbonyl/imine addition, conjugate addition, carboxylation, olefination, cross-coupling, allylation, alkylation and hydroalkylation. Carbonyls can serve as surrogates for organometallic reagents via hydrazones.
Bibliography:Chao-Jun Li is the E. B. Eddy Chair Professor and Canada Research Chair (Tier I) in Green Chemistry at McGill University. He received his PhD at McGill University (1992) and was an NSERC Postdoctoral Fellow at Stanford University (1992-1994). He was an Assistant (1994), Associate (1998) and Full Professor (2000) at Tulane University until 2003. He was elected as a Fellow of the Royal Society of Chemistry (2007), the Royal Society of Canada (2012), the AAAS (2012), the CIC (2013), the ACS (2015), the CCS (2020), the World Academy of Sciences (TWAS) (2016), and the European Academy of Sciences (2020).
Xi-Jie Dai earned his MSc under the supervision of Prof. Pei-Qiang Huang at Xiamen Univ., China. In 2012, he joined Prof. Chao-Jun Li's group at McGill in Canada to pursue his PhD, where his research focus was exploring oxygenated organic compounds for efficient metal-catalyzed reactions. Following passion on practical applications of emerging synthetic technologies, he spent his NSERC postdoctoral tenure with Prof. Stephen L. Buchwald at MIT in USA, where he and his colleagues developed copper-catalyzed enantioselective synthesis of pharmaceutically relevant nitrogen heterocycles. He is currently a Scientist at Amgen and has been a critical member advancing the first-in-class KRAS G12C inhibitor-LUMAKRAS to benefit KRAS-mutant lung cancer patients worldwide.
Chen-Chen Li was born on April 1, 1993 in Nanjing, Jiangsu, China. He earned a BS degree from Lanzhou University in 2016 during which time he was an undergraduate researcher supervised by Dr Shang-Dong Yang and mainly focused on rhodium-catalyzed alkene functionalization. From 2016 to the present, he has been studying for his PhD degree in McGill University and working in Dr Chao-Jun Li's research group. In Li's group, he has contributed mostly to the research of transition-metal-catalyzed hydrogen-transfer C-C bond-formation reactions.
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ISSN:0306-0012
1460-4744
1460-4744
DOI:10.1039/d1cs00418b