Enantioselective fluoride ring opening of aziridines enabled by cooperative Lewis acid catalysis

Julia A. Kalow; Abigail G. Doyle

doi:10.1016/j.tet.2013.01.062

Enantioselective fluoride ring opening of aziridines enabled by cooperative Lewis acid catalysis

Julia A. Kalow, Abigail G. Doyle^*

^*Corresponding author for this work

Chemistry

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

90 Scopus citations

Abstract

The enantioselective ring opening of aziridines using a latent source of HF is described. A combination of two Lewis acids, (salen)Co and an achiral Ti(IV) cocatalyst, provided optimal reactivity and enantioselectivity for the trans β-fluoroamine product. The use of a chelating aziridine protecting group was crucial. Acyclic and cyclic meso N-picolinamide aziridines underwent fluoride ring opening in up to 84% ee, and the kinetic resolution of a piperidine-derived aziridine was performed with k_rel=6.6. The picolinamide group may be readily removed without epimerization of the fluoroamine. Preliminary studies revealed a bimetallic mechanism wherein the chiral (salen)Co catalyst delivers the nucleophile and the Ti(IV) cocatalyst activates the aziridine.

Original language	English (US)
Pages (from-to)	5702-5709
Number of pages	8
Journal	Tetrahedron
Volume	69
Issue number	27-28
DOIs	https://doi.org/10.1016/j.tet.2013.01.062
State	Published - Jul 8 2013

Keywords

Asymmetric catalysis
Aziridine opening
Cooperative catalysis
Fluorination
β-Fluoroamine

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/j.tet.2013.01.062

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title = "Enantioselective fluoride ring opening of aziridines enabled by cooperative Lewis acid catalysis",

abstract = "The enantioselective ring opening of aziridines using a latent source of HF is described. A combination of two Lewis acids, (salen)Co and an achiral Ti(IV) cocatalyst, provided optimal reactivity and enantioselectivity for the trans β-fluoroamine product. The use of a chelating aziridine protecting group was crucial. Acyclic and cyclic meso N-picolinamide aziridines underwent fluoride ring opening in up to 84% ee, and the kinetic resolution of a piperidine-derived aziridine was performed with krel=6.6. The picolinamide group may be readily removed without epimerization of the fluoroamine. Preliminary studies revealed a bimetallic mechanism wherein the chiral (salen)Co catalyst delivers the nucleophile and the Ti(IV) cocatalyst activates the aziridine.",

keywords = "Asymmetric catalysis, Aziridine opening, Cooperative catalysis, Fluorination, β-Fluoroamine",

author = "Kalow, {Julia A.} and Doyle, {Abigail G.}",

note = "Funding Information: We thank Dana Schmitt for studies of the deprotection of 2a and Phil Jeffrey for X-ray crystallographic structure determination of 2b . Financial support was provided by Princeton University (fellowship to J.A.K.), the NSF (CAREER-1148750) and the ACS Division of Organic Chemistry (fellowship to J.A.K. sponsored by Pfizer). ",

year = "2013",

month = jul,

day = "8",

doi = "10.1016/j.tet.2013.01.062",

language = "English (US)",

volume = "69",

pages = "5702--5709",

journal = "Tetrahedron",

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T1 - Enantioselective fluoride ring opening of aziridines enabled by cooperative Lewis acid catalysis

AU - Kalow, Julia A.

AU - Doyle, Abigail G.

N1 - Funding Information: We thank Dana Schmitt for studies of the deprotection of 2a and Phil Jeffrey for X-ray crystallographic structure determination of 2b . Financial support was provided by Princeton University (fellowship to J.A.K.), the NSF (CAREER-1148750) and the ACS Division of Organic Chemistry (fellowship to J.A.K. sponsored by Pfizer).

PY - 2013/7/8

Y1 - 2013/7/8

N2 - The enantioselective ring opening of aziridines using a latent source of HF is described. A combination of two Lewis acids, (salen)Co and an achiral Ti(IV) cocatalyst, provided optimal reactivity and enantioselectivity for the trans β-fluoroamine product. The use of a chelating aziridine protecting group was crucial. Acyclic and cyclic meso N-picolinamide aziridines underwent fluoride ring opening in up to 84% ee, and the kinetic resolution of a piperidine-derived aziridine was performed with krel=6.6. The picolinamide group may be readily removed without epimerization of the fluoroamine. Preliminary studies revealed a bimetallic mechanism wherein the chiral (salen)Co catalyst delivers the nucleophile and the Ti(IV) cocatalyst activates the aziridine.

AB - The enantioselective ring opening of aziridines using a latent source of HF is described. A combination of two Lewis acids, (salen)Co and an achiral Ti(IV) cocatalyst, provided optimal reactivity and enantioselectivity for the trans β-fluoroamine product. The use of a chelating aziridine protecting group was crucial. Acyclic and cyclic meso N-picolinamide aziridines underwent fluoride ring opening in up to 84% ee, and the kinetic resolution of a piperidine-derived aziridine was performed with krel=6.6. The picolinamide group may be readily removed without epimerization of the fluoroamine. Preliminary studies revealed a bimetallic mechanism wherein the chiral (salen)Co catalyst delivers the nucleophile and the Ti(IV) cocatalyst activates the aziridine.

KW - Asymmetric catalysis

KW - Aziridine opening

KW - Cooperative catalysis

KW - Fluorination

KW - β-Fluoroamine

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U2 - 10.1016/j.tet.2013.01.062

DO - 10.1016/j.tet.2013.01.062

M3 - Article

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SN - 0040-4020

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JO - Tetrahedron

JF - Tetrahedron

IS - 27-28

ER -

Enantioselective fluoride ring opening of aziridines enabled by cooperative Lewis acid catalysis

Abstract

Keywords

ASJC Scopus subject areas

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