Development of direct enantioselective alkynylation of αketoester and α-ketiminoesters catalyzed by phenylbis(oxazoline)Rh(III) complexes

Kazuhiro Morisaki, Hiroyuki Morimoto, Kazushi Mashima, Takashi Ohshima

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Abstract

Direct catalytic enantioselective alkynylation of carbonyl compounds and imines is one of the most efficient approaches for the synthesis of propargylic alcohols and propargylamines, which are potent building blocks for synthesizing functionalized molecules. While a variety of methods for the reactions with aldehydes and aldimines have been established, the reactions with ketones and ketimines remain underdeveloped due to their reduced reactivity and difficulty in stereocontrol. In this account, we summarized our studies on direct enantioselective alkynylation reaction of α-ketoester and α-ketiminoesters catalyzed by phenylbis(oxazolinephebox)-rhodium(III) complexes, affording enantioenriched propargyl alcohols and propargylamines with a tetrasubsti-tuted carbon stereocenter under proton-transfer conditions. The catalytic system was compatible to a wide range of functional groups, including electrophilic formyl groups, and allowed for the development of an efficient method to access enantioenriched α-CF3-substituted thalidomide analogs. Mechanistic studies revealed that generation of the (alkynyl(phebox)Rh(III) complex from the (diacetatophebox)Rh(III) complex determined the overall reaction rate in the initial stages of the reaction. These results, along with the observed facile exchange of the alkynyl ligand on the (alkynylphebox)Rh(III) complexes, led us to use (trimethylsilylethynylphebox)Rh(III) complexes as a new pre-catalyst. The new catalytic system with (trimethylsilylethynylphebox)Rh (III) precatalysts exhibited enhanced catalytic performance, reduced catalyst loading to as low as 0.5 mol%, and expanded the substrate scope of the reaction with less reactive α-ketiminophos-phonate and cyclic N-sulfonyl α-ketiminoesters.

Original languageEnglish
Pages (from-to)226-240
Number of pages15
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume76
Issue number3
DOIs
Publication statusPublished - Jan 1 2018

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Carbonyl compounds
Rhodium
Catalysts
Proton transfer
Thalidomide
Imines
Ketones
Aldehydes
Functional groups
Reaction rates
Carbon
Alcohols
Ligands
Molecules
Substrates
propargylamine
propargyl alcohol
ketimine

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

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title = "Development of direct enantioselective alkynylation of αketoester and α-ketiminoesters catalyzed by phenylbis(oxazoline)Rh(III) complexes",
abstract = "Direct catalytic enantioselective alkynylation of carbonyl compounds and imines is one of the most efficient approaches for the synthesis of propargylic alcohols and propargylamines, which are potent building blocks for synthesizing functionalized molecules. While a variety of methods for the reactions with aldehydes and aldimines have been established, the reactions with ketones and ketimines remain underdeveloped due to their reduced reactivity and difficulty in stereocontrol. In this account, we summarized our studies on direct enantioselective alkynylation reaction of α-ketoester and α-ketiminoesters catalyzed by phenylbis(oxazolinephebox)-rhodium(III) complexes, affording enantioenriched propargyl alcohols and propargylamines with a tetrasubsti-tuted carbon stereocenter under proton-transfer conditions. The catalytic system was compatible to a wide range of functional groups, including electrophilic formyl groups, and allowed for the development of an efficient method to access enantioenriched α-CF3-substituted thalidomide analogs. Mechanistic studies revealed that generation of the (alkynyl(phebox)Rh(III) complex from the (diacetatophebox)Rh(III) complex determined the overall reaction rate in the initial stages of the reaction. These results, along with the observed facile exchange of the alkynyl ligand on the (alkynylphebox)Rh(III) complexes, led us to use (trimethylsilylethynylphebox)Rh(III) complexes as a new pre-catalyst. The new catalytic system with (trimethylsilylethynylphebox)Rh (III) precatalysts exhibited enhanced catalytic performance, reduced catalyst loading to as low as 0.5 mol{\%}, and expanded the substrate scope of the reaction with less reactive α-ketiminophos-phonate and cyclic N-sulfonyl α-ketiminoesters.",
author = "Kazuhiro Morisaki and Hiroyuki Morimoto and Kazushi Mashima and Takashi Ohshima",
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T1 - Development of direct enantioselective alkynylation of αketoester and α-ketiminoesters catalyzed by phenylbis(oxazoline)Rh(III) complexes

AU - Morisaki, Kazuhiro

AU - Morimoto, Hiroyuki

AU - Mashima, Kazushi

AU - Ohshima, Takashi

PY - 2018/1/1

Y1 - 2018/1/1

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