Enantioselective (8+3) Cycloadditions by Activation of Donor–Acceptor Cyclopropanes Employing Chiral Brønsted Base Catalysis

David A. McLeod; Mathias Kirk Thøgersen; Casper Larsen Barløse; Mette Louise Skipper; Erlaitz Basabe Obregón; Karl Anker Jørgensen

doi:10.1002/anie.202206096

Enantioselective (8+3) Cycloadditions by Activation of Donor–Acceptor Cyclopropanes Employing Chiral Brønsted Base Catalysis

David A. McLeod, Mathias Kirk Thøgersen, Casper Larsen Barløse, Mette Louise Skipper, Erlaitz Basabe Obregón, Karl Anker Jørgensen^*

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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Abstract

A novel enantioselective (8+3) cycloaddition between donor–acceptor cyclopropanes and heptafulvenoids catalysed by a chiral bifunctional Brønsted base is described. Importantly, the reaction, which leverages an anionic activation strategy, is divergent from prototypical Lewis-acid activation protocols. A series of cyclopropylketones react with tropones affording the desired (8+3) cycloadducts in high yield and enantiomeric excess. For barbiturate substituted heptafulvenes, the (8+3) cycloaddition with cyclopropylketones proceeds in good yield, excellent diastereoselectivity and high enantiomeric excess. The experimental work is supported by DFT calculations, which indicate that the bifunctional organocatalyst activates both the donor–acceptor cyclopropane and tropone; the reaction proceeds in a step-wise manner with the ring-closure being the stereodetermining step.

Original language	English
Article number	e202206096
Journal	Angewandte Chemie - International Edition
Volume	61
Issue	29
ISSN	1433-7851
DOIs	https://doi.org/10.1002/anie.202206096
Publication status	Published - Jul 2022

Keywords

Brønsted Base
Cyclopropanes
Heptafulvenoids
Organocatalysis
Tropones

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10.1002/anie.202206096Licence: CC BY-NC-ND

Angew Chem Int Ed - 2022 - McLeodFinal published version, 4.51 MBLicence: CC BY-NC-ND

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@article{59831176451d47e092039f69ac4a6090,

title = "Enantioselective (8+3) Cycloadditions by Activation of Donor–Acceptor Cyclopropanes Employing Chiral Br{\o}nsted Base Catalysis",

abstract = "A novel enantioselective (8+3) cycloaddition between donor–acceptor cyclopropanes and heptafulvenoids catalysed by a chiral bifunctional Br{\o}nsted base is described. Importantly, the reaction, which leverages an anionic activation strategy, is divergent from prototypical Lewis-acid activation protocols. A series of cyclopropylketones react with tropones affording the desired (8+3) cycloadducts in high yield and enantiomeric excess. For barbiturate substituted heptafulvenes, the (8+3) cycloaddition with cyclopropylketones proceeds in good yield, excellent diastereoselectivity and high enantiomeric excess. The experimental work is supported by DFT calculations, which indicate that the bifunctional organocatalyst activates both the donor–acceptor cyclopropane and tropone; the reaction proceeds in a step-wise manner with the ring-closure being the stereodetermining step.",

keywords = "Br{\o}nsted Base, Cyclopropanes, Heptafulvenoids, Organocatalysis, Tropones",

author = "McLeod, {David A.} and Th{\o}gersen, {Mathias Kirk} and Barl{\o}se, {Casper Larsen} and Skipper, {Mette Louise} and Obreg{\'o}n, {Erlaitz Basabe} and J{\o}rgensen, {Karl Anker}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.",

year = "2022",

month = jul,

doi = "10.1002/anie.202206096",

language = "English",

volume = "61",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "Wiley - VCH Verlag GmbH & CO. KGaA",

number = "29",

}

Enantioselective (8+3) Cycloadditions by Activation of Donor–Acceptor Cyclopropanes Employing Chiral Brønsted Base Catalysis. / McLeod, David A.; Thøgersen, Mathias Kirk; Barløse, Casper Larsen et al.
In: Angewandte Chemie - International Edition, Vol. 61, No. 29, e202206096, 07.2022.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Enantioselective (8+3) Cycloadditions by Activation of Donor–Acceptor Cyclopropanes Employing Chiral Brønsted Base Catalysis

AU - McLeod, David A.

AU - Thøgersen, Mathias Kirk

AU - Barløse, Casper Larsen

AU - Skipper, Mette Louise

AU - Obregón, Erlaitz Basabe

AU - Jørgensen, Karl Anker

PY - 2022/7

Y1 - 2022/7

N2 - A novel enantioselective (8+3) cycloaddition between donor–acceptor cyclopropanes and heptafulvenoids catalysed by a chiral bifunctional Brønsted base is described. Importantly, the reaction, which leverages an anionic activation strategy, is divergent from prototypical Lewis-acid activation protocols. A series of cyclopropylketones react with tropones affording the desired (8+3) cycloadducts in high yield and enantiomeric excess. For barbiturate substituted heptafulvenes, the (8+3) cycloaddition with cyclopropylketones proceeds in good yield, excellent diastereoselectivity and high enantiomeric excess. The experimental work is supported by DFT calculations, which indicate that the bifunctional organocatalyst activates both the donor–acceptor cyclopropane and tropone; the reaction proceeds in a step-wise manner with the ring-closure being the stereodetermining step.

AB - A novel enantioselective (8+3) cycloaddition between donor–acceptor cyclopropanes and heptafulvenoids catalysed by a chiral bifunctional Brønsted base is described. Importantly, the reaction, which leverages an anionic activation strategy, is divergent from prototypical Lewis-acid activation protocols. A series of cyclopropylketones react with tropones affording the desired (8+3) cycloadducts in high yield and enantiomeric excess. For barbiturate substituted heptafulvenes, the (8+3) cycloaddition with cyclopropylketones proceeds in good yield, excellent diastereoselectivity and high enantiomeric excess. The experimental work is supported by DFT calculations, which indicate that the bifunctional organocatalyst activates both the donor–acceptor cyclopropane and tropone; the reaction proceeds in a step-wise manner with the ring-closure being the stereodetermining step.

KW - Brønsted Base

KW - Cyclopropanes

KW - Heptafulvenoids

KW - Organocatalysis

KW - Tropones

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AN - SCOPUS:85131005003

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JO - Angewandte Chemie - International Edition

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Enantioselective (8+3) Cycloadditions by Activation of Donor–Acceptor Cyclopropanes Employing Chiral Brønsted Base Catalysis

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