Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

Handle URI:
http://hdl.handle.net/10754/598161
Title:
Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies
Authors:
Behenna, Douglas C.; Mohr, Justin T.; Sherden, Nathaniel H.; Marinescu, Smaranda C.; Harned, Andrew M.; Tani, Kousuke; Seto, Masaki; Ma, Sandy; Novák, Zoltán; Krout, Michael R.; McFadden, Ryan M.; Roizen, Jennifer L.; Enquist, John A.; White, David E.; Levine, Samantha R.; Petrova, Krastina V.; Iwashita, Akihiko; Virgil, Scott C.; Stoltz, Brian M.
Abstract:
α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursor: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center.
Citation:
Behenna DC, Mohr JT, Sherden NH, Marinescu SC, Harned AM, et al. (2011) Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies. Chem Eur J 17: 14199–14223. Available: http://dx.doi.org/10.1002/chem.201003383.
Publisher:
Wiley-Blackwell
Journal:
Chemistry - A European Journal
KAUST Grant Number:
KUS-11-006-02
Issue Date:
14-Nov-2011
DOI:
10.1002/chem.201003383
PubMed ID:
22083969
PubMed Central ID:
PMC3365686
Type:
Article
ISSN:
0947-6539
Sponsors:
This publication is based on work supported by award number KUS-11-006-02, made by the King Abdullah University of Science and Technology (KAUST). We thank the NIH-NIGMS (R01 GM080269-01 and postdoctoral fellowships to AMH and DEW), The Fannie and John Hertz Foundation (predoctoral fellowship to DCB), Eli Lilly (predoctoral fellowships to JTM, RMM, and MRK), Ono Pharmaceutical Co., Ltd. (postdoctoral fellowship to KT), The Hungarian-American Enterprise Scholarship Fund (postdoctoral fellowship to ZN), Takeda Pharmaceutical Co., Ltd. (postdoctoral fellowship to MS), The California Tobacco-Related Disease Research Program of the University of California (predoctoral fellowship to JLR, grant number 14DT-0004), Marcella R. Bonsall and the Dalton Fund (undergraduate fellowships to SRL), the Caltech Amgen Scholars Program (undergraduate fellowship to KVP), The 21st Century COE Program for Frontiers in Fundamental Chemistry from the Ministry of Education, Culture, Sports, Science and Technology, Japan (financial support to AI), the A. P. Sloan Foundation, Research Corporation, the Dreyfus Foundation, Bristol-Myers Squibb, GlaxoSmithKline, Johnson and Johnson, Amgen, Merck Research Laboratories, Pfizer, Novartis, Roche, Abbott Laboratories, Boehringer-Ingelheim, AstraZeneca, and Caltech for financial support. We acknowledge Dr. Mike Day and Larry Henling for assistance with X-ray crystallography. Ruthenium olefin metathesis catalysts were generously donated by Materia.
Appears in Collections:
Publications Acknowledging KAUST Support

Full metadata record

DC FieldValue Language
dc.contributor.authorBehenna, Douglas C.en
dc.contributor.authorMohr, Justin T.en
dc.contributor.authorSherden, Nathaniel H.en
dc.contributor.authorMarinescu, Smaranda C.en
dc.contributor.authorHarned, Andrew M.en
dc.contributor.authorTani, Kousukeen
dc.contributor.authorSeto, Masakien
dc.contributor.authorMa, Sandyen
dc.contributor.authorNovák, Zoltánen
dc.contributor.authorKrout, Michael R.en
dc.contributor.authorMcFadden, Ryan M.en
dc.contributor.authorRoizen, Jennifer L.en
dc.contributor.authorEnquist, John A.en
dc.contributor.authorWhite, David E.en
dc.contributor.authorLevine, Samantha R.en
dc.contributor.authorPetrova, Krastina V.en
dc.contributor.authorIwashita, Akihikoen
dc.contributor.authorVirgil, Scott C.en
dc.contributor.authorStoltz, Brian M.en
dc.date.accessioned2016-02-25T13:13:51Zen
dc.date.available2016-02-25T13:13:51Zen
dc.date.issued2011-11-14en
dc.identifier.citationBehenna DC, Mohr JT, Sherden NH, Marinescu SC, Harned AM, et al. (2011) Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies. Chem Eur J 17: 14199–14223. Available: http://dx.doi.org/10.1002/chem.201003383.en
dc.identifier.issn0947-6539en
dc.identifier.pmid22083969en
dc.identifier.doi10.1002/chem.201003383en
dc.identifier.urihttp://hdl.handle.net/10754/598161en
dc.description.abstractα-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursor: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center.en
dc.description.sponsorshipThis publication is based on work supported by award number KUS-11-006-02, made by the King Abdullah University of Science and Technology (KAUST). We thank the NIH-NIGMS (R01 GM080269-01 and postdoctoral fellowships to AMH and DEW), The Fannie and John Hertz Foundation (predoctoral fellowship to DCB), Eli Lilly (predoctoral fellowships to JTM, RMM, and MRK), Ono Pharmaceutical Co., Ltd. (postdoctoral fellowship to KT), The Hungarian-American Enterprise Scholarship Fund (postdoctoral fellowship to ZN), Takeda Pharmaceutical Co., Ltd. (postdoctoral fellowship to MS), The California Tobacco-Related Disease Research Program of the University of California (predoctoral fellowship to JLR, grant number 14DT-0004), Marcella R. Bonsall and the Dalton Fund (undergraduate fellowships to SRL), the Caltech Amgen Scholars Program (undergraduate fellowship to KVP), The 21st Century COE Program for Frontiers in Fundamental Chemistry from the Ministry of Education, Culture, Sports, Science and Technology, Japan (financial support to AI), the A. P. Sloan Foundation, Research Corporation, the Dreyfus Foundation, Bristol-Myers Squibb, GlaxoSmithKline, Johnson and Johnson, Amgen, Merck Research Laboratories, Pfizer, Novartis, Roche, Abbott Laboratories, Boehringer-Ingelheim, AstraZeneca, and Caltech for financial support. We acknowledge Dr. Mike Day and Larry Henling for assistance with X-ray crystallography. Ruthenium olefin metathesis catalysts were generously donated by Materia.en
dc.publisherWiley-Blackwellen
dc.subjectalkylationen
dc.subjectallylic compoundsen
dc.subjectasymmetric catalysisen
dc.subjectenolatesen
dc.subjectreaction mechanismsen
dc.subjectsynthetic methodsen
dc.titleEnantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studiesen
dc.typeArticleen
dc.identifier.journalChemistry - A European Journalen
dc.identifier.pmcidPMC3365686en
dc.contributor.institutionThe Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd., MC 101-20, Pasadena, CA 91125, USA.en
kaust.grant.numberKUS-11-006-02en
All Items in KAUST are protected by copyright, with all rights reserved, unless otherwise indicated.