title: Enantioselective decarboxylative alkylation reactions: catalyst development, substrate scope, and mechanistic studies.
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.
authors.affiliation: The 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.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Behenna
authors.forename: Justin T
authors.initials: JT
authors.lastname: Mohr
authors.forename: Nathaniel H
authors.initials: NH
authors.lastname: Sherden
authors.forename: Smaranda C
authors.initials: SC
authors.lastname: Marinescu
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Harned
authors.forename: Kousuke
authors.initials: K
authors.lastname: Tani
authors.forename: Masaki
authors.initials: M
authors.lastname: Seto
authors.forename: Sandy
authors.initials: S
authors.lastname: Ma
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Novák
authors.forename: Michael R
authors.initials: MR
authors.lastname: Krout
authors.forename: Ryan M
authors.initials: RM
authors.lastname: McFadden
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Roizen
authors.forename: John A
authors.initials: JA
authors.lastname: Enquist
authors.forename: David E
authors.initials: DE
authors.lastname: White
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Levine
authors.forename: Krastina V
authors.initials: KV
authors.lastname: Petrova
authors.forename: Akihiko
authors.initials: A
authors.lastname: Iwashita
authors.forename: Scott C
authors.initials: SC
authors.lastname: Virgil
authors.forename: Brian M
authors.initials: BM
authors.lastname: Stoltz
mesh_terms: D000478:Alkylation; D000498:Allyl Compounds / Q000737:chemistry*; D002254:Carbonates / Q000737:chemistry*; D002384:Catalysis; D003653:Decarboxylation; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000498:Allyl Compounds; D002254:Carbonates; D007659:Ketones; D008024:Ligands; D010165:Palladium
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