Asymmetric synthesis of 3,4-anti- and 3,4-syn-substituted aminopyrrolidines via lithium amide conjugate addition

Stephen G. Davies; A. Christopher Garner; Euan C. Goddard; Dennis Kruchinin; Paul M. Roberts; Andrew D. Smith; Humberto Rodriguez-Solla; James E. Thomson; Steven M. Toms

doi:10.1039/b704932c

Asymmetric synthesis of 3,4-anti- and 3,4-syn-substituted aminopyrrolidines via lithium amide conjugate addition

Stephen G. Davies, A. Christopher Garner, Euan C. Goddard, Dennis Kruchinin, Paul M. Roberts, Andrew D. Smith, Humberto Rodriguez-Solla, James E. Thomson, Steven M. Toms

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

25 Citations (Scopus)

Abstract

The diastereoselective conjugate addition of homochiral lithium amides to methyl 4-(N-allyl-N-benzylamino)but-2-enoate has been used as the key step in a simple and efficient protocol for the preparation of 3,4- substituted aminopyrrolidines. This protocol provides a complementary and stereoselective route to both anti- and syn-3-amino-4-alkylpyrrolidines as well as anti- and syn-3-hydroxy-4-aminopyrrolidines, in high de and ee via beta-amino enolate functionalisation. This methodology has been applied to the synthesis of anti-(3S,4S)- and syn-(3R,4S)-3-methoxy-4-(N-methylamino)pyrrolidine.

Original language	English
Pages (from-to)	1961-1969
Number of pages	9
Journal	Organic & Biomolecular Chemistry
Volume	5
Issue number	12
DOIs	https://doi.org/10.1039/b704932c
Publication status	Published - 2007

Keywords

PARALLEL KINETIC RESOLUTION
BETA-AMINO ACIDS
STEREOSELECTIVE-SYNTHESIS
AMMONIA EQUIVALENTS
PROTECTING GROUP
DERIVATIVES
PIPERIDINES
3-AMINOPYRROLIDINES
3-ALKYL-CISPENTACIN
STEREOCHEMISTRY

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@article{9370d6618530497ca437fe3a26f91a4b,

title = "Asymmetric synthesis of 3,4-anti- and 3,4-syn-substituted aminopyrrolidines via lithium amide conjugate addition",

abstract = "The diastereoselective conjugate addition of homochiral lithium amides to methyl 4-(N-allyl-N-benzylamino)but-2-enoate has been used as the key step in a simple and efficient protocol for the preparation of 3,4- substituted aminopyrrolidines. This protocol provides a complementary and stereoselective route to both anti- and syn-3-amino-4-alkylpyrrolidines as well as anti- and syn-3-hydroxy-4-aminopyrrolidines, in high de and ee via beta-amino enolate functionalisation. This methodology has been applied to the synthesis of anti-(3S,4S)- and syn-(3R,4S)-3-methoxy-4-(N-methylamino)pyrrolidine.",

keywords = "PARALLEL KINETIC RESOLUTION, BETA-AMINO ACIDS, STEREOSELECTIVE-SYNTHESIS, AMMONIA EQUIVALENTS, PROTECTING GROUP, DERIVATIVES, PIPERIDINES, 3-AMINOPYRROLIDINES, 3-ALKYL-CISPENTACIN, STEREOCHEMISTRY",

author = "Davies, {Stephen G.} and Garner, {A. Christopher} and Goddard, {Euan C.} and Dennis Kruchinin and Roberts, {Paul M.} and Smith, {Andrew D.} and Humberto Rodriguez-Solla and Thomson, {James E.} and Toms, {Steven M.}",

year = "2007",

doi = "10.1039/b704932c",

language = "English",

volume = "5",

pages = "1961--1969",

journal = "Organic & Biomolecular Chemistry",

issn = "1477-0539",

publisher = "Royal Society of Chemistry",

number = "12",

}

TY - JOUR

T1 - Asymmetric synthesis of 3,4-anti- and 3,4-syn-substituted aminopyrrolidines via lithium amide conjugate addition

AU - Davies, Stephen G.

AU - Garner, A. Christopher

AU - Goddard, Euan C.

AU - Kruchinin, Dennis

AU - Roberts, Paul M.

AU - Smith, Andrew D.

AU - Rodriguez-Solla, Humberto

AU - Thomson, James E.

AU - Toms, Steven M.

PY - 2007

Y1 - 2007

N2 - The diastereoselective conjugate addition of homochiral lithium amides to methyl 4-(N-allyl-N-benzylamino)but-2-enoate has been used as the key step in a simple and efficient protocol for the preparation of 3,4- substituted aminopyrrolidines. This protocol provides a complementary and stereoselective route to both anti- and syn-3-amino-4-alkylpyrrolidines as well as anti- and syn-3-hydroxy-4-aminopyrrolidines, in high de and ee via beta-amino enolate functionalisation. This methodology has been applied to the synthesis of anti-(3S,4S)- and syn-(3R,4S)-3-methoxy-4-(N-methylamino)pyrrolidine.

AB - The diastereoselective conjugate addition of homochiral lithium amides to methyl 4-(N-allyl-N-benzylamino)but-2-enoate has been used as the key step in a simple and efficient protocol for the preparation of 3,4- substituted aminopyrrolidines. This protocol provides a complementary and stereoselective route to both anti- and syn-3-amino-4-alkylpyrrolidines as well as anti- and syn-3-hydroxy-4-aminopyrrolidines, in high de and ee via beta-amino enolate functionalisation. This methodology has been applied to the synthesis of anti-(3S,4S)- and syn-(3R,4S)-3-methoxy-4-(N-methylamino)pyrrolidine.

KW - PARALLEL KINETIC RESOLUTION

KW - BETA-AMINO ACIDS

KW - STEREOSELECTIVE-SYNTHESIS

KW - AMMONIA EQUIVALENTS

KW - PROTECTING GROUP

KW - DERIVATIVES

KW - PIPERIDINES

KW - 3-AMINOPYRROLIDINES

KW - 3-ALKYL-CISPENTACIN

KW - STEREOCHEMISTRY

U2 - 10.1039/b704932c

DO - 10.1039/b704932c

M3 - Article

SN - 1477-0539

VL - 5

SP - 1961

EP - 1969

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

IS - 12

ER -

Asymmetric synthesis of 3,4-anti- and 3,4-syn-substituted aminopyrrolidines via lithium amide conjugate addition

Abstract

Keywords

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