Dihydrooxazine N-Oxide Intermediates as Resting States in Organocatalytic Kinetic Resolution of Functionalized Nitroallylic Amines with Aldehydes

Ramani Gurubrahamam; Yan Ming Chen; Wan Yun Huang; Yu Te Chan; Hsiang Kai Chang; Ming Kang Tsai; Kwunmin Chen

doi:10.1021/acs.orglett.6b00493

Dihydrooxazine N-Oxide Intermediates as Resting States in Organocatalytic Kinetic Resolution of Functionalized Nitroallylic Amines with Aldehydes

Ramani Gurubrahamam, Yan Ming Chen, Wan Yun Huang, Yu Te Chan, Hsiang Kai Chang, Ming Kang Tsai^*, Kwunmin Chen

^*Corresponding author for this work

Department of Chemistry

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

18 Citations (Scopus)

Abstract

Kinetic resolution of nitroallylic amines was established using chiral α,α-l-diphenylprolinol silyl ether auxiliary through isolation of the dihydrooxazine N-oxide intermediates. Further hydrolyzing the resting states provided tetrahydropyridines in high chemical yields and high to excellent stereoselectivities (up to >20:1 dr and 98% ee). A detailed mechanistic explanation for stereoselective protonation in the dihydrooxazine was probed computationally. In addition, the probable intermediates in α-halogenation of aldehydes (masked with enamines) were isolated to provide crystallographic evidence.

Original language	English
Pages (from-to)	3046-3049
Number of pages	4
Journal	Organic Letters
Volume	18
Issue number	13
DOIs	https://doi.org/10.1021/acs.orglett.6b00493
Publication status	Published - 2016 Jul 1

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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10.1021/acs.orglett.6b00493

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title = "Dihydrooxazine N-Oxide Intermediates as Resting States in Organocatalytic Kinetic Resolution of Functionalized Nitroallylic Amines with Aldehydes",

abstract = "Kinetic resolution of nitroallylic amines was established using chiral α,α-l-diphenylprolinol silyl ether auxiliary through isolation of the dihydrooxazine N-oxide intermediates. Further hydrolyzing the resting states provided tetrahydropyridines in high chemical yields and high to excellent stereoselectivities (up to >20:1 dr and 98% ee). A detailed mechanistic explanation for stereoselective protonation in the dihydrooxazine was probed computationally. In addition, the probable intermediates in α-halogenation of aldehydes (masked with enamines) were isolated to provide crystallographic evidence.",

author = "Ramani Gurubrahamam and Chen, {Yan Ming} and Huang, {Wan Yun} and Chan, {Yu Te} and Chang, {Hsiang Kai} and Tsai, {Ming Kang} and Kwunmin Chen",

note = "Publisher Copyright: {\textcopyright} 2016 American Chemical Society.",

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doi = "10.1021/acs.orglett.6b00493",

language = "English",

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T1 - Dihydrooxazine N-Oxide Intermediates as Resting States in Organocatalytic Kinetic Resolution of Functionalized Nitroallylic Amines with Aldehydes

AU - Gurubrahamam, Ramani

AU - Chen, Yan Ming

AU - Huang, Wan Yun

AU - Chan, Yu Te

AU - Chang, Hsiang Kai

AU - Tsai, Ming Kang

AU - Chen, Kwunmin

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Kinetic resolution of nitroallylic amines was established using chiral α,α-l-diphenylprolinol silyl ether auxiliary through isolation of the dihydrooxazine N-oxide intermediates. Further hydrolyzing the resting states provided tetrahydropyridines in high chemical yields and high to excellent stereoselectivities (up to >20:1 dr and 98% ee). A detailed mechanistic explanation for stereoselective protonation in the dihydrooxazine was probed computationally. In addition, the probable intermediates in α-halogenation of aldehydes (masked with enamines) were isolated to provide crystallographic evidence.

AB - Kinetic resolution of nitroallylic amines was established using chiral α,α-l-diphenylprolinol silyl ether auxiliary through isolation of the dihydrooxazine N-oxide intermediates. Further hydrolyzing the resting states provided tetrahydropyridines in high chemical yields and high to excellent stereoselectivities (up to >20:1 dr and 98% ee). A detailed mechanistic explanation for stereoselective protonation in the dihydrooxazine was probed computationally. In addition, the probable intermediates in α-halogenation of aldehydes (masked with enamines) were isolated to provide crystallographic evidence.

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Dihydrooxazine N-Oxide Intermediates as Resting States in Organocatalytic Kinetic Resolution of Functionalized Nitroallylic Amines with Aldehydes

Abstract

ASJC Scopus subject areas

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CCDC 1453873: Experimental Crystal Structure Determination

CCDC 1453874: Experimental Crystal Structure Determination

CCDC 1453775: Experimental Crystal Structure Determination

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Dihydrooxazine N-Oxide Intermediates as Resting States in Organocatalytic Kinetic Resolution of Functionalized Nitroallylic Amines with Aldehydes

Abstract

ASJC Scopus subject areas

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Datasets

CCDC 1453873: Experimental Crystal Structure Determination

CCDC 1453874: Experimental Crystal Structure Determination

CCDC 1453775: Experimental Crystal Structure Determination

Cite this