Isothiourea-catalyzed asymmetric synthesis of β-lactams and β-amino esters from arylacetic acid derivatives and N-sulfonylaldimines

Siobhan R. Smith; James Douglas; Hugues Prevet; Peter Shapland; Alexandra M. Z. Slawin; Andrew D. Smith

doi:10.1021/jo402590m

Isothiourea-catalyzed asymmetric synthesis of β-lactams and β-amino esters from arylacetic acid derivatives and N-sulfonylaldimines

Siobhan R. Smith, James Douglas, Hugues Prevet, Peter Shapland, Alexandra M. Z. Slawin, Andrew D. Smith^*

^*Corresponding author for this work

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

Abstract

The isothiourea HBTM-2.1 (5 mol %) catalyzes the asymmetric formal [2 + 2] cycloaddition of both arylacetic acids (following activation with tosyl chloride) and preformed 2-arylacetic anhydrides with N-sulfonylaldimines, generating stereodefined 2,3-diaryl-β-amino esters (after ring-opening) and 3,4-diaryl-anti-β-lactams, respectively, with high diastereocontrol (up to >95:5 dr) and good to excellent enantiocontrol. Deprotection of the N-tosyl substituent within the β-lactam framework was possible without racemization by treatment with SmI₂.

Original language	English
Pages (from-to)	1626-1639
Number of pages	14
Journal	The Journal of Organic Chemistry
Volume	79
Issue number	4
Early online date	5 Feb 2014
DOIs	https://doi.org/10.1021/jo402590m
Publication status	Published - 21 Feb 2014

Keywords

Human Cytomegalovirus Protease
Promoted Bis-Cyclizations
Acyl Transfer Catalyst
Pure Lithium Amides
Enantioselective Synthesis
Kinugasa Reaction
Aldol-Lactonization
Staudinger Reaction
Kinetic Resolution
Dyotropic Rearrangements

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10.1021/jo402590m

Slawin_2014_JOC_Isothiourea_AM
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Organic Chemistry, copyright © 2014 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jo402590m
Accepted author manuscript, 1.66 MB

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@article{8146cf5a4f5940edb7b977b6790246c5,

title = "Isothiourea-catalyzed asymmetric synthesis of β-lactams and β-amino esters from arylacetic acid derivatives and N-sulfonylaldimines",

abstract = "The isothiourea HBTM-2.1 (5 mol %) catalyzes the asymmetric formal [2 + 2] cycloaddition of both arylacetic acids (following activation with tosyl chloride) and preformed 2-arylacetic anhydrides with N-sulfonylaldimines, generating stereodefined 2,3-diaryl-β-amino esters (after ring-opening) and 3,4-diaryl-anti-β-lactams, respectively, with high diastereocontrol (up to >95:5 dr) and good to excellent enantiocontrol. Deprotection of the N-tosyl substituent within the β-lactam framework was possible without racemization by treatment with SmI2.",

keywords = "Human Cytomegalovirus Protease, Promoted Bis-Cyclizations, Acyl Transfer Catalyst, Pure Lithium Amides, Enantioselective Synthesis, Kinugasa Reaction, Aldol-Lactonization, Staudinger Reaction, Kinetic Resolution, Dyotropic Rearrangements",

author = "Smith, {Siobhan R.} and James Douglas and Hugues Prevet and Peter Shapland and Slawin, {Alexandra M. Z.} and Smith, {Andrew D.}",

note = "This work is supported by a Royal Society for a University Research Fellowship and the EPSRC and GSK (Case Award) as well as by the European Research Council under the European Unionʼs Seventh Framework Programme (FP7/2007-2013) (ERC Grant Agreement No.279850) ",

year = "2014",

month = feb,

day = "21",

doi = "10.1021/jo402590m",

language = "English",

volume = "79",

pages = "1626--1639",

journal = "The Journal of Organic Chemistry",

issn = "0022-3263",

publisher = "American Chemical Society (ACS)",

number = "4",

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TY - JOUR

T1 - Isothiourea-catalyzed asymmetric synthesis of β-lactams and β-amino esters from arylacetic acid derivatives and N-sulfonylaldimines

AU - Smith, Siobhan R.

AU - Douglas, James

AU - Prevet, Hugues

AU - Shapland, Peter

AU - Slawin, Alexandra M. Z.

AU - Smith, Andrew D.

N1 - This work is supported by a Royal Society for a University Research Fellowship and the EPSRC and GSK (Case Award) as well as by the European Research Council under the European Unionʼs Seventh Framework Programme (FP7/2007-2013) (ERC Grant Agreement No.279850)

PY - 2014/2/21

Y1 - 2014/2/21

N2 - The isothiourea HBTM-2.1 (5 mol %) catalyzes the asymmetric formal [2 + 2] cycloaddition of both arylacetic acids (following activation with tosyl chloride) and preformed 2-arylacetic anhydrides with N-sulfonylaldimines, generating stereodefined 2,3-diaryl-β-amino esters (after ring-opening) and 3,4-diaryl-anti-β-lactams, respectively, with high diastereocontrol (up to >95:5 dr) and good to excellent enantiocontrol. Deprotection of the N-tosyl substituent within the β-lactam framework was possible without racemization by treatment with SmI2.

AB - The isothiourea HBTM-2.1 (5 mol %) catalyzes the asymmetric formal [2 + 2] cycloaddition of both arylacetic acids (following activation with tosyl chloride) and preformed 2-arylacetic anhydrides with N-sulfonylaldimines, generating stereodefined 2,3-diaryl-β-amino esters (after ring-opening) and 3,4-diaryl-anti-β-lactams, respectively, with high diastereocontrol (up to >95:5 dr) and good to excellent enantiocontrol. Deprotection of the N-tosyl substituent within the β-lactam framework was possible without racemization by treatment with SmI2.

KW - Human Cytomegalovirus Protease

KW - Promoted Bis-Cyclizations

KW - Acyl Transfer Catalyst

KW - Pure Lithium Amides

KW - Enantioselective Synthesis

KW - Kinugasa Reaction

KW - Aldol-Lactonization

KW - Staudinger Reaction

KW - Kinetic Resolution

KW - Dyotropic Rearrangements

U2 - 10.1021/jo402590m

DO - 10.1021/jo402590m

M3 - Article

SN - 0022-3263

VL - 79

SP - 1626

EP - 1639

JO - The Journal of Organic Chemistry

JF - The Journal of Organic Chemistry

IS - 4

ER -

Isothiourea-catalyzed asymmetric synthesis of β-lactams and β-amino esters from arylacetic acid derivatives and N-sulfonylaldimines

Abstract

Keywords

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