Asymmetric Synthesis of Efavirenz via Organocatalyzed Enantioselective Trifluoromethylation

Okusu, Satoshi; Kawai, Hiroyuki; Yasuda, Yoshimasa; Sugita, Yutaka; Kitayama, Takashi; Tokunaga, Etsuko; Shibata, Norio

doi:10.1002/ajoc.201402016

Cited by 23 publications

(15 citation statements)

References 23 publications

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“…In order to acquire a high degree of enantiocontrol in the asymmetric trifluoromethylation step, modifying the cinchona alkaloid derived catalyst structure with two alkyoxyl groups and a bulkier benzyl group (3 i) resulted in a substantial increasing in the ee value (the results are indicated in parentheses in Scheme 18). [61] …”

Section: Efavirenzmentioning

confidence: 97%

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF₃ Stereogenic Center

Huang

Yang

Chen

et al. 2015

Chemistry A European J

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133

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Given the important agricultural and medicinal application of optically pure heterocycles bearing a trifluoromethyl group at the stereogenic carbon center in the heterocyclic framework, the exploration of efficient and practical synthetic strategies to such types of molecules remains highly desirable. Catalytic enantioselective synthesis has one clear advantage that it is more cost-effective than other synthetic methods, but remains limited by challenges in achieving excellent yield and stereoselectivities with a low catalyst loading. Thus far, numerous models of organo- and organometal-catalyzed asymmetric reactions have been exploited to achieve this elusive goal over the past decade. This review article describes recent progress on this research topic, and focuses on an understanding of the catalytic asymmetric protocols exemplified in the catalytic enantioselective synthesis of a wide range of complex enantioenriched trifluoromethylated heterocycles.

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Section: Efavirenzmentioning

confidence: 97%

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF₃ Stereogenic Center

Huang

Yang

Chen

et al. 2015

Chemistry A European J

Self Cite

133

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“… 109 Subsequent catalyst modifications have allowed for improvement in selectivity in the key step. 110 …”

Section: Catalytic Enantioselective Trifluoromethylation and Perfluormentioning

confidence: 99%

Advances in Catalytic Enantioselective Fluorination, Mono-, Di-, and Trifluoromethylation, and Trifluoromethylthiolation Reactions

et al. 2014

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“…Alcohol 14 was then reacted with chlorosulfonyl isocyanate to afford carbamate 15, which underwent a copper-catalyzed Ullman-type cyclization to establish the dihydrobenzoxazinone core structure of Efavirenz. 31 With chiral tertiary alcohol 19 in hand, the asymmetric synthesis of Efavirenz was completed in a two-step process: the chemoselective reduction of the nitro group in 19 furnished corresponding aniline 6, which underwent ringclosure using Merck's procedure 13 to afford Efavirenz. 29 From the viewpoint of synthetic organofluorine chemistry, the chiral tertiary alcohol motif in Efavirenz could also be constructed by an enantioselective trifluoromethylation of alkynylketone.…”

Section: Catalytic Asymmetric Addition Reactionsmentioning

confidence: 99%

Core-structure-inspired asymmetric addition reactions: enantioselective synthesis of dihydrobenzoxazinone- and dihydroquinazolinone-based anti-HIV agents

Shen

2015

Chem. Soc. Rev.

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Dihydrobenzoxazinones and dihydroquinazolinones are the core units present in many anti-HIV agents, such as Efavirenz, DPC 961, DPC 963, and DPC 083. All these molecules contain a trifluoromethyl moiety at the quaternary stereogenic carbon center with S configuration. The enantioselective addition of carbon nucleophiles to ketones or cyclic ketimines could serve as a key step to access these molecules. This tutorial review provides an overview of significant advances in the synthesis of dihydrobenzoxazinone- and dihydroquinazolinone-based anti-HIV agents and relative analogues, with an emphasis on asymmetric addition reactions for the establishment of the CF3-containing quaternary carbon centers.

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Asymmetric Synthesis of Efavirenz via Organocatalyzed Enantioselective Trifluoromethylation

Abstract: Scheme 1. Catalytic asymmetric synthesis of efavirenz (1) by direct trifluoromethylation.

Cited by 23 publications

References 23 publications

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF₃ Stereogenic Center

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF₃ Stereogenic Center

Advances in Catalytic Enantioselective Fluorination, Mono-, Di-, and Trifluoromethylation, and Trifluoromethylthiolation Reactions

Core-structure-inspired asymmetric addition reactions: enantioselective synthesis of dihydrobenzoxazinone- and dihydroquinazolinone-based anti-HIV agents

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Asymmetric Synthesis of Efavirenz via Organocatalyzed Enantioselective Trifluoromethylation

Abstract: Scheme 1. Catalytic asymmetric synthesis of efavirenz (1) by direct trifluoromethylation.

Cited by 23 publications

References 23 publications

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF3 Stereogenic Center

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF3 Stereogenic Center

Advances in Catalytic Enantioselective Fluorination, Mono-, Di-, and Trifluoromethylation, and Trifluoromethylthiolation Reactions

Core-structure-inspired asymmetric addition reactions: enantioselective synthesis of dihydrobenzoxazinone- and dihydroquinazolinone-based anti-HIV agents

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Product

Resources

About

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF₃ Stereogenic Center

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF₃ Stereogenic Center