A diastereoselective radical cyclization approach to substituted quinuclidines

T.A. Hunt; A.F. Parsons; R. Pratt

doi:10.1021/jo060349q

A diastereoselective radical cyclization approach to substituted quinuclidines

T.A. Hunt, A.F. Parsons, R. Pratt

Chemistry

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

Abstract

A new, concise, and flexible approach to novel quinuclidines has been developed, which employs a phosphorus hydride mediated radical addition/cyclization reaction in the key step. 1,7-Diene 5 reacts with diethyl thiophosphite in an efficient and diastereoselective radical addition/cyclization reaction to give trisubstituted piperidines 4ab. Piperidines 4ab are subsequently converted into 2,5-disubstituted quinuclidines using SN2-type cyclizations. Finally, the resulting quinuclidines are shown to undergo novel Horner-Wadsworth-Emmons-type (HWE-type) reactions to give unsaturated quinuclidines 21a and 21b, which have structures similar to that of (-)-quinine 1.

Original language	English
Pages (from-to)	3656-3659
Number of pages	3
Journal	Journal of Organic Chemistry
Volume	71
Issue number	9
DOIs	https://doi.org/10.1021/jo060349q
Publication status	Published - 28 Apr 2006

Keywords

STEREOSELECTIVE TOTAL-SYNTHESIS
COBALT-MEDIATED CYCLIZATION
CINCHONA ALKALOIDS
ENANTIOSPECIFIC SYNTHESIS
RECEPTOR
QUININE
LIGANDS
ORGANOMETALLICS
DERIVATIVES
ANTAGONISTS

Access to Document

10.1021/jo060349q

http://dx.doi.org/10.1021/jo060349q

Cite this

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title = "A diastereoselective radical cyclization approach to substituted quinuclidines",

abstract = "A new, concise, and flexible approach to novel quinuclidines has been developed, which employs a phosphorus hydride mediated radical addition/cyclization reaction in the key step. 1,7-Diene 5 reacts with diethyl thiophosphite in an efficient and diastereoselective radical addition/cyclization reaction to give trisubstituted piperidines 4ab. Piperidines 4ab are subsequently converted into 2,5-disubstituted quinuclidines using SN2-type cyclizations. Finally, the resulting quinuclidines are shown to undergo novel Horner-Wadsworth-Emmons-type (HWE-type) reactions to give unsaturated quinuclidines 21a and 21b, which have structures similar to that of (-)-quinine 1.",

keywords = "STEREOSELECTIVE TOTAL-SYNTHESIS, COBALT-MEDIATED CYCLIZATION, CINCHONA ALKALOIDS, ENANTIOSPECIFIC SYNTHESIS, RECEPTOR, QUININE, LIGANDS, ORGANOMETALLICS, DERIVATIVES, ANTAGONISTS",

author = "T.A. Hunt and A.F. Parsons and R. Pratt",

year = "2006",

month = apr,

day = "28",

doi = "10.1021/jo060349q",

language = "English",

volume = "71",

pages = "3656--3659",

journal = "Journal of Organic Chemistry",

issn = "0022-3263",

publisher = "American Chemical Society",

number = "9",

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TY - JOUR

T1 - A diastereoselective radical cyclization approach to substituted quinuclidines

AU - Hunt, T.A.

AU - Parsons, A.F.

AU - Pratt, R.

PY - 2006/4/28

Y1 - 2006/4/28

N2 - A new, concise, and flexible approach to novel quinuclidines has been developed, which employs a phosphorus hydride mediated radical addition/cyclization reaction in the key step. 1,7-Diene 5 reacts with diethyl thiophosphite in an efficient and diastereoselective radical addition/cyclization reaction to give trisubstituted piperidines 4ab. Piperidines 4ab are subsequently converted into 2,5-disubstituted quinuclidines using SN2-type cyclizations. Finally, the resulting quinuclidines are shown to undergo novel Horner-Wadsworth-Emmons-type (HWE-type) reactions to give unsaturated quinuclidines 21a and 21b, which have structures similar to that of (-)-quinine 1.

AB - A new, concise, and flexible approach to novel quinuclidines has been developed, which employs a phosphorus hydride mediated radical addition/cyclization reaction in the key step. 1,7-Diene 5 reacts with diethyl thiophosphite in an efficient and diastereoselective radical addition/cyclization reaction to give trisubstituted piperidines 4ab. Piperidines 4ab are subsequently converted into 2,5-disubstituted quinuclidines using SN2-type cyclizations. Finally, the resulting quinuclidines are shown to undergo novel Horner-Wadsworth-Emmons-type (HWE-type) reactions to give unsaturated quinuclidines 21a and 21b, which have structures similar to that of (-)-quinine 1.

KW - STEREOSELECTIVE TOTAL-SYNTHESIS

KW - COBALT-MEDIATED CYCLIZATION

KW - CINCHONA ALKALOIDS

KW - ENANTIOSPECIFIC SYNTHESIS

KW - RECEPTOR

KW - QUININE

KW - LIGANDS

KW - ORGANOMETALLICS

KW - DERIVATIVES

KW - ANTAGONISTS

U2 - 10.1021/jo060349q

DO - 10.1021/jo060349q

M3 - Article

SN - 0022-3263

VL - 71

SP - 3656

EP - 3659

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 9

ER -