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

Department of Chemistry

Research output: Contribution to journal › Article

7 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

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ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

Cite this

Gurubrahamam, R., Chen, Y. M., Huang, W. Y., Chan, Y. T., Chang, H. K., Tsai, M. K., & Chen, K. (2016). Dihydrooxazine N-Oxide Intermediates as Resting States in Organocatalytic Kinetic Resolution of Functionalized Nitroallylic Amines with Aldehydes. Organic Letters, 18(13), 3046-3049. https://doi.org/10.1021/acs.orglett.6b00493

Dihydrooxazine N-Oxide Intermediates as Resting States in Organocatalytic Kinetic Resolution of Functionalized Nitroallylic Amines with Aldehydes. / Gurubrahamam, Ramani; Chen, Yan Ming; Huang, Wan Yun; Chan, Yu Te; Chang, Hsiang Kai; Tsai, Ming Kang ; Chen, Kwunmin.

In: Organic Letters, Vol. 18, No. 13, 01.07.2016, p. 3046-3049.

Research output: Contribution to journal › Article

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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.",

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10.1021/acs.orglett.6b00493