Enantioselective C-H Lactonization of Unactivated Methylenes Directed by Carboxylic Acids
dc.contributor.author
dc.date.accessioned
2020-01-22T13:11:07Z
dc.date.available
2020-01-22T13:11:07Z
dc.date.issued
2019-12-27
dc.identifier.issn
0002-7863
dc.identifier.uri
dc.description.abstract
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
dc.description.sponsorship
Support 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 acknowledged
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
American Chemical Society (ACS)
dc.relation
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-101737-B-I00/ES/CATALISIS DE OXIDACION BIOINSPIRADA MEDIANTE DISEÑO RACIONAL DE CATALIZADORES/
dc.relation.isformatof
Versió postprint del document publicat a: https://doi.org/10.1021/jacs.9b12239
dc.relation.ispartof
© Journal of the American Chemical Society, 2019, vol.142, núm. 3, p.1584-1593
dc.relation.ispartofseries
Articles publicats (D-Q)
dc.rights
Tots els drets reservats
dc.title
Enantioselective C-H Lactonization of Unactivated Methylenes Directed by Carboxylic Acids
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.date.embargoEndDate
info:eu-repo/date/embargoEnd/2020-12-27
dc.relation.projectID
info:eu-repo/grantAgreement/EC/H2020/675020/EU/Non-Noble Metal Catalysis/NoNoMeCat
dc.type.version
info:eu-repo/semantics/acceptedVersion
dc.identifier.doi
dc.contributor.funder
dc.type.peerreviewed
peer-reviewed
dc.relation.FundingProgramme
dc.relation.ProjectAcronym
dc.identifier.eissn
1520-5126