Catalytic Enantioselective Synthesis of N-C Axially Chiral Mebroqualone and Its Derivatives through Reductive Asymmetric Desymmetrization

Motohiro Hirai; Shumpei Terada; Hiroaki Yoshida; Kenki Ebine; Tomoaki Hirata; Osamu Kitagawa

doi:10.1021/acs.orglett.6b02865

Catalytic Enantioselective Synthesis of N-C Axially Chiral Mebroqualone and Its Derivatives through Reductive Asymmetric Desymmetrization

Motohiro Hirai, Shumpei Terada, Hiroaki Yoshida, Kenki Ebine, Tomoaki Hirata, Osamu Kitagawa

Research output: Contribution to journal › Article › peer-review

48 Citations (Scopus)

Abstract

In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)₂ catalyst, treatment of various 3-(2,6-dibromophenyl)quinazolin-4-ones with NaBH₄ gave optically active N-C axially chiral quinazolinone (mebroqualone) derivatives through reductive asymmetric desymmetrization (enantioselective monohydrodebromination) followed by kinetic resolution of the resulting monobromophenyl products (up to 99% ee). The enantioselectivity strongly depended on the substituent (R²) at the C4′position, amount of NaBH₄, and reaction temperature.

Original language	English
Pages (from-to)	5700-5703
Number of pages	4
Journal	Organic Letters
Volume	18
Issue number	21
DOIs	https://doi.org/10.1021/acs.orglett.6b02865
Publication status	Published - 2016 Nov 4

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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title = "Catalytic Enantioselective Synthesis of N-C Axially Chiral Mebroqualone and Its Derivatives through Reductive Asymmetric Desymmetrization",

abstract = "In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)2 catalyst, treatment of various 3-(2,6-dibromophenyl)quinazolin-4-ones with NaBH4 gave optically active N-C axially chiral quinazolinone (mebroqualone) derivatives through reductive asymmetric desymmetrization (enantioselective monohydrodebromination) followed by kinetic resolution of the resulting monobromophenyl products (up to 99% ee). The enantioselectivity strongly depended on the substituent (R2) at the C4′position, amount of NaBH4, and reaction temperature.",

author = "Motohiro Hirai and Shumpei Terada and Hiroaki Yoshida and Kenki Ebine and Tomoaki Hirata and Osamu Kitagawa",

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T1 - Catalytic Enantioselective Synthesis of N-C Axially Chiral Mebroqualone and Its Derivatives through Reductive Asymmetric Desymmetrization

AU - Hirai, Motohiro

AU - Terada, Shumpei

AU - Yoshida, Hiroaki

AU - Ebine, Kenki

AU - Hirata, Tomoaki

AU - Kitagawa, Osamu

PY - 2016/11/4

Y1 - 2016/11/4

N2 - In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)2 catalyst, treatment of various 3-(2,6-dibromophenyl)quinazolin-4-ones with NaBH4 gave optically active N-C axially chiral quinazolinone (mebroqualone) derivatives through reductive asymmetric desymmetrization (enantioselective monohydrodebromination) followed by kinetic resolution of the resulting monobromophenyl products (up to 99% ee). The enantioselectivity strongly depended on the substituent (R2) at the C4′position, amount of NaBH4, and reaction temperature.

AB - In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)2 catalyst, treatment of various 3-(2,6-dibromophenyl)quinazolin-4-ones with NaBH4 gave optically active N-C axially chiral quinazolinone (mebroqualone) derivatives through reductive asymmetric desymmetrization (enantioselective monohydrodebromination) followed by kinetic resolution of the resulting monobromophenyl products (up to 99% ee). The enantioselectivity strongly depended on the substituent (R2) at the C4′position, amount of NaBH4, and reaction temperature.

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Catalytic Enantioselective Synthesis of N-C Axially Chiral Mebroqualone and Its Derivatives through Reductive Asymmetric Desymmetrization

Abstract

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