Enantioselective C-H Lactonization of Unactivated Methylenes Directed by Carboxylic Acids

The formidable challenges of controlling site-selectivity, enantioselectivity, and product chemoselectivity make asymmetric C-H oxidation a generally unsolved problem for nonenzymatic systems. Discrimination between the two enantiotopic C-H bonds of an unactivated methylenic group is particularly de...

Full description

Bibliographic Details
Authors: Cianfanelli, Marco, Olivo, Giorgio, Milan, Michela, Gebbink, Robertus J. M. Klein, Ribas Salamaña, Xavi, Bietti, Massimo, Costas Salgueiro, Miquel
Format: article
Status:Versión aceptada para publicación
Publication Date:2019
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/17615
Online Access:http://hdl.handle.net/10256/17615
Access Level:Open access
Keyword:Reacció d'oxidació-reducció
Oxidation-reduction reaction
id ES_412f9a9ff665a0749cff97b3fa65ccc0
oai_identifier_str oai:recercat.cat:10256/17615
network_acronym_str ES
network_name_str España
repository_id_str
spelling Enantioselective C-H Lactonization of Unactivated Methylenes Directed by Carboxylic AcidsCianfanelli, MarcoOlivo, GiorgioMilan, MichelaGebbink, Robertus J. M. KleinRibas Salamaña, XaviBietti, MassimoCostas Salgueiro, MiquelReacció d'oxidació-reduccióOxidation-reduction reactionThe formidable challenges of controlling site-selectivity, enantioselectivity, and product chemoselectivity make asymmetric C-H oxidation a generally unsolved problem for nonenzymatic systems. Discrimination between the two enantiotopic C-H bonds of an unactivated methylenic group is particularly demanding and so far unprecedented, given the similarity between their environments and the facile overoxidation of the initially formed hydroxylation product. Here we show that a Mn-catalyzed C-H oxidation directed by carboxylic acids can overcome these challenges to yield γ-lactones in high enantiomeric excess (up to 99%) using hydrogen peroxide as oxidant and a Brønsted acid additive under mild conditions and short reaction times. Coordination of the carboxylic acid group to the bulky Mn complex ensures the rigidity needed for high enantioselectivity and dictates the outstanding γ site-selectivity. When the substrate contains nonequivalent γ-methylenes, the site-selectivity for lactonization can be rationally predicted on the basis of simple C-H activation/deactivation effects exerted by proximal substituents. In addition, discrimination of diastereotopic C-H bonds can be modulated by catalyst design, with no erosion of enantiomeric excess. The potential of this reaction is illustrated in the concise synthesis of a tetrahydroxylated bicyclo[3.3.1]nonane enabled by two key, sequential γ-C-H lactonizations, with the latter that fixes the chirality of five stereogenic centers in one step with 96% eeSupport by the Spanish Ministry of Science (PGC2018-101737-B-I00 to M.C. and J.d.C. grant to G.O., FJCI-2016-30243), and Gen-eralitat de Catalunya (ICREA Academia Award to M.C. and 2014SGR 862), and from EU (MSCA-ITN-2015 Action NoNoMeCat, 675020) is acknowledgedAmerican Chemical Society (ACS)Agencia Estatal de Investigacióninfo2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/17615http://hdl.handle.net/10256/17615© Journal of the American Chemical Society, 2019, vol.142, núm. 3, p.1584-1593Articles publicats (D-Q)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1021/jacs.9b12239info:eu-repo/semantics/altIdentifier/issn/0002-7863info:eu-repo/semantics/altIdentifier/eissn/1520-5126info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-101737-B-I00info:eu-repo/grantAgreement/EC/H2020/675020Tots els drets reservatsinfo:eu-repo/semantics/openAccessoai:recercat.cat:10256/176152026-05-29T05:05:01Z
dc.title.none.fl_str_mv Enantioselective C-H Lactonization of Unactivated Methylenes Directed by Carboxylic Acids
title Enantioselective C-H Lactonization of Unactivated Methylenes Directed by Carboxylic Acids
spellingShingle Enantioselective C-H Lactonization of Unactivated Methylenes Directed by Carboxylic Acids
Cianfanelli, Marco
Reacció d'oxidació-reducció
Oxidation-reduction reaction
title_short Enantioselective C-H Lactonization of Unactivated Methylenes Directed by Carboxylic Acids
title_full Enantioselective C-H Lactonization of Unactivated Methylenes Directed by Carboxylic Acids
title_fullStr Enantioselective C-H Lactonization of Unactivated Methylenes Directed by Carboxylic Acids
title_full_unstemmed Enantioselective C-H Lactonization of Unactivated Methylenes Directed by Carboxylic Acids
title_sort Enantioselective C-H Lactonization of Unactivated Methylenes Directed by Carboxylic Acids
dc.creator.none.fl_str_mv Cianfanelli, Marco
Olivo, Giorgio
Milan, Michela
Gebbink, Robertus J. M. Klein
Ribas Salamaña, Xavi
Bietti, Massimo
Costas Salgueiro, Miquel
author Cianfanelli, Marco
author_facet Cianfanelli, Marco
Olivo, Giorgio
Milan, Michela
Gebbink, Robertus J. M. Klein
Ribas Salamaña, Xavi
Bietti, Massimo
Costas Salgueiro, Miquel
author_role author
author2 Olivo, Giorgio
Milan, Michela
Gebbink, Robertus J. M. Klein
Ribas Salamaña, Xavi
Bietti, Massimo
Costas Salgueiro, Miquel
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación
dc.subject.none.fl_str_mv Reacció d'oxidació-reducció
Oxidation-reduction reaction
topic Reacció d'oxidació-reducció
Oxidation-reduction reaction
description The formidable challenges of controlling site-selectivity, enantioselectivity, and product chemoselectivity make asymmetric C-H oxidation a generally unsolved problem for nonenzymatic systems. Discrimination between the two enantiotopic C-H bonds of an unactivated methylenic group is particularly demanding and so far unprecedented, given the similarity between their environments and the facile overoxidation of the initially formed hydroxylation product. Here we show that a Mn-catalyzed C-H oxidation directed by carboxylic acids can overcome these challenges to yield γ-lactones in high enantiomeric excess (up to 99%) using hydrogen peroxide as oxidant and a Brønsted acid additive under mild conditions and short reaction times. Coordination of the carboxylic acid group to the bulky Mn complex ensures the rigidity needed for high enantioselectivity and dictates the outstanding γ site-selectivity. When the substrate contains nonequivalent γ-methylenes, the site-selectivity for lactonization can be rationally predicted on the basis of simple C-H activation/deactivation effects exerted by proximal substituents. In addition, discrimination of diastereotopic C-H bonds can be modulated by catalyst design, with no erosion of enantiomeric excess. The potential of this reaction is illustrated in the concise synthesis of a tetrahydroxylated bicyclo[3.3.1]nonane enabled by two key, sequential γ-C-H lactonizations, with the latter that fixes the chirality of five stereogenic centers in one step with 96% ee
publishDate 2019
dc.date.none.fl_str_mv 2019
info
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
peer-reviewed
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/17615
http://hdl.handle.net/10256/17615
url http://hdl.handle.net/10256/17615
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/jacs.9b12239
info:eu-repo/semantics/altIdentifier/issn/0002-7863
info:eu-repo/semantics/altIdentifier/eissn/1520-5126
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-101737-B-I00
info:eu-repo/grantAgreement/EC/H2020/675020
dc.rights.none.fl_str_mv Tots els drets reservats
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Tots els drets reservats
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society (ACS)
publisher.none.fl_str_mv American Chemical Society (ACS)
dc.source.none.fl_str_mv © Journal of the American Chemical Society, 2019, vol.142, núm. 3, p.1584-1593
Articles publicats (D-Q)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406828879675392
score 15,811543

Similar Items