Stereoconvergent approach for synthesizing enantiopure 5,6-dialkylpipecolic acids

Martin E. Swarbrick,

Martin E. Swarbrick

Département de Chimie, Université de Montréal, Montréal, Québec, Canada

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William D. Lubell,

Corresponding Author

William D. Lubell

[email protected]

Département de Chimie, Université de Montréal, Montréal, Québec, Canada

Département de Chimie, Université de Montréal, C.P. 6128, Succursale Centre Ville, Montréal, Québec, H3C 3J7 CanadaSearch for more papers by this author

Martin E. Swarbrick,

Martin E. Swarbrick

Département de Chimie, Université de Montréal, Montréal, Québec, Canada

Search for more papers by this author

William D. Lubell,

Corresponding Author

William D. Lubell

[email protected]

Département de Chimie, Université de Montréal, Montréal, Québec, Canada

Département de Chimie, Université de Montréal, C.P. 6128, Succursale Centre Ville, Montréal, Québec, H3C 3J7 CanadaSearch for more papers by this author

First published: 19 May 2000

https://doi.org/10.1002/(SICI)1520-636X(2000)12:5/6<366::AID-CHIR12>3.0.CO;2-E

Citations: 11

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Abstract

Investigating a general route for synthesizing pipecolic acid )piperidine-2-carboxylic acid( derivatives with substituents at the 3-, 4-, 5- and 6-position, we discovered a stereoconvergent process that provides an effective means for making 5,6-dialkyl-ϵpipecolate (Scheme 1, PhF = 9-phenylfluoren-9-yl). Hydrogenation of diastereomeric mixtures of γ-oxo γ-hydroxy and γ-acetoxy α-N-(PhF)amino tert-butyl esters causes the eventual loss of the γ-substituent to furnish an azadiene intermediate that can reduce diastereoselectively to 5,6-dialkylpipecolate having the all cis relative stereoconfiguration. Five enantiopure (>94° ee) 5,6-dialkylpipecolic acids were synthesized, employing aspartic acid as an inexpensive chiral educt in this process. Chirality 12:366–373, 2000. © 2000 Wiley-Liss, Inc.

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Volume12, Issue5-6

SPECIAL COMMEMORATIVE ISSUE HONORING PROFESSOR RYOJI NOYORI

2000

Pages 366-373

Stereoconvergent approach for synthesizing enantiopure 5,6-dialkylpipecolic acids

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Stereoconvergent approach for synthesizing enantiopure 5,6-dialkylpipecolic acids

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