A new route to chiral hydroxypyrrolidines from D-erythrose via intramolecular 1,3-cycloaddition

J. Grant Buchanan, Alan R. Edgar, Brian D. Hewitt

Research output: Contribution to journalArticle

Abstract

2,3-O-Isopropylidene-D-erythrose (1) reacted with ethoxycarbonylmethylene(triphenyl)phosphorane in refluxing benzene to give the E and Z alkene esters (2a) and (2b). The ester (2a) was converted, via the 6-triflate (7a) and 6-azide (3a), into the dihydrotriazole (8) by 1,3-cycloaddition. Ring opening of compound (8) with sodium ethoxide gave the pyrrolidine diazo ester (9) which on hydrogenolysis gave (2R,3S,4R)-ethyl (3,4-isopropylidenedioxypyrrolidin-2-yl)acetate (5). A similar series of reactions from the Z-ester (2b) gave the pyrrolidine ester (6), the 2S-isomer of (5). Thermolysis of the diazo ester (10), the 2S-isomer of (9), gave (Z)-(3S,4R)-ethyl (3,4-isopropylidenedioxypyrrolidin-2-ylidene)acetate (12) which was reduced with sodium cyanoborohydride to give the ester (5). The esters (2a) and (2b) undergo rapid and quantitative cyclisation in the presence of ethoxide ion. Kinetically the ß-isomer (18) is preferred [100% from (2b), 86% from (2a)]; at equilibrium the a-isomer (19) is favoured (82%).

Original languageEnglish
Pages (from-to)2371-2376
Number of pages6
JournalJournal of the Chemical Society, Perkin Transactions 1
Publication statusPublished - 1987

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Cycloaddition
Esters
Isomers
Acetates
Phosphoranes
Hydrogenolysis
Thermolysis
Azides
erythrose
Cyclization
Alkenes
Benzene
Ions

Cite this

@article{4500db179370457187652a12bec62d70,
title = "A new route to chiral hydroxypyrrolidines from D-erythrose via intramolecular 1,3-cycloaddition",
abstract = "2,3-O-Isopropylidene-D-erythrose (1) reacted with ethoxycarbonylmethylene(triphenyl)phosphorane in refluxing benzene to give the E and Z alkene esters (2a) and (2b). The ester (2a) was converted, via the 6-triflate (7a) and 6-azide (3a), into the dihydrotriazole (8) by 1,3-cycloaddition. Ring opening of compound (8) with sodium ethoxide gave the pyrrolidine diazo ester (9) which on hydrogenolysis gave (2R,3S,4R)-ethyl (3,4-isopropylidenedioxypyrrolidin-2-yl)acetate (5). A similar series of reactions from the Z-ester (2b) gave the pyrrolidine ester (6), the 2S-isomer of (5). Thermolysis of the diazo ester (10), the 2S-isomer of (9), gave (Z)-(3S,4R)-ethyl (3,4-isopropylidenedioxypyrrolidin-2-ylidene)acetate (12) which was reduced with sodium cyanoborohydride to give the ester (5). The esters (2a) and (2b) undergo rapid and quantitative cyclisation in the presence of ethoxide ion. Kinetically the {\ss}-isomer (18) is preferred [100{\%} from (2b), 86{\%} from (2a)]; at equilibrium the a-isomer (19) is favoured (82{\%}).",
author = "Buchanan, {J. Grant} and Edgar, {Alan R.} and Hewitt, {Brian D.}",
year = "1987",
language = "English",
pages = "2371--2376",
journal = "Journal of the Chemical Society, Perkin Transactions 1",
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A new route to chiral hydroxypyrrolidines from D-erythrose via intramolecular 1,3-cycloaddition. / Buchanan, J. Grant; Edgar, Alan R.; Hewitt, Brian D.

In: Journal of the Chemical Society, Perkin Transactions 1, 1987, p. 2371-2376.

Research output: Contribution to journalArticle

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T1 - A new route to chiral hydroxypyrrolidines from D-erythrose via intramolecular 1,3-cycloaddition

AU - Buchanan, J. Grant

AU - Edgar, Alan R.

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PY - 1987

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N2 - 2,3-O-Isopropylidene-D-erythrose (1) reacted with ethoxycarbonylmethylene(triphenyl)phosphorane in refluxing benzene to give the E and Z alkene esters (2a) and (2b). The ester (2a) was converted, via the 6-triflate (7a) and 6-azide (3a), into the dihydrotriazole (8) by 1,3-cycloaddition. Ring opening of compound (8) with sodium ethoxide gave the pyrrolidine diazo ester (9) which on hydrogenolysis gave (2R,3S,4R)-ethyl (3,4-isopropylidenedioxypyrrolidin-2-yl)acetate (5). A similar series of reactions from the Z-ester (2b) gave the pyrrolidine ester (6), the 2S-isomer of (5). Thermolysis of the diazo ester (10), the 2S-isomer of (9), gave (Z)-(3S,4R)-ethyl (3,4-isopropylidenedioxypyrrolidin-2-ylidene)acetate (12) which was reduced with sodium cyanoborohydride to give the ester (5). The esters (2a) and (2b) undergo rapid and quantitative cyclisation in the presence of ethoxide ion. Kinetically the ß-isomer (18) is preferred [100% from (2b), 86% from (2a)]; at equilibrium the a-isomer (19) is favoured (82%).

AB - 2,3-O-Isopropylidene-D-erythrose (1) reacted with ethoxycarbonylmethylene(triphenyl)phosphorane in refluxing benzene to give the E and Z alkene esters (2a) and (2b). The ester (2a) was converted, via the 6-triflate (7a) and 6-azide (3a), into the dihydrotriazole (8) by 1,3-cycloaddition. Ring opening of compound (8) with sodium ethoxide gave the pyrrolidine diazo ester (9) which on hydrogenolysis gave (2R,3S,4R)-ethyl (3,4-isopropylidenedioxypyrrolidin-2-yl)acetate (5). A similar series of reactions from the Z-ester (2b) gave the pyrrolidine ester (6), the 2S-isomer of (5). Thermolysis of the diazo ester (10), the 2S-isomer of (9), gave (Z)-(3S,4R)-ethyl (3,4-isopropylidenedioxypyrrolidin-2-ylidene)acetate (12) which was reduced with sodium cyanoborohydride to give the ester (5). The esters (2a) and (2b) undergo rapid and quantitative cyclisation in the presence of ethoxide ion. Kinetically the ß-isomer (18) is preferred [100% from (2b), 86% from (2a)]; at equilibrium the a-isomer (19) is favoured (82%).

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