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

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)3046-3049
Number of pages4
JournalOrganic Letters
Volume18
Issue number13
DOIs
Publication statusPublished - 2016 Jul 1

Fingerprint

Halogenation
halogenation
Stereoselectivity
Protonation
aldehydes
Aldehydes
Oxides
Amines
ethers
isolation
amines
Kinetics
oxides
kinetics
diphenylprolinol silyl ether

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

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 journalArticle

Gurubrahamam, Ramani ; Chen, Yan Ming ; Huang, Wan Yun ; Chan, Yu Te ; Chang, Hsiang Kai ; Tsai, Ming Kang ; Chen, Kwunmin. / Dihydrooxazine N-Oxide Intermediates as Resting States in Organocatalytic Kinetic Resolution of Functionalized Nitroallylic Amines with Aldehydes. In: Organic Letters. 2016 ; Vol. 18, No. 13. pp. 3046-3049.
@article{e746d3f1c5894d699549b56be382ecb9,
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",
year = "2016",
month = "7",
day = "1",
doi = "10.1021/acs.orglett.6b00493",
language = "English",
volume = "18",
pages = "3046--3049",
journal = "Organic Letters",
issn = "1523-7060",
publisher = "American Chemical Society",
number = "13",

}

TY - JOUR

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.

UR - http://www.scopus.com/inward/record.url?scp=84977279591&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84977279591&partnerID=8YFLogxK

U2 - 10.1021/acs.orglett.6b00493

DO - 10.1021/acs.orglett.6b00493

M3 - Article

AN - SCOPUS:84977279591

VL - 18

SP - 3046

EP - 3049

JO - Organic Letters

JF - Organic Letters

SN - 1523-7060

IS - 13

ER -