title: Lithium Enolates in the Enantioselective Construction of Tetrasubstituted Carbon Centers with Chiral Lithium Amides as Noncovalent Stereodirecting Auxiliaries.
abstract: Lithium enolates derived from carboxylic acids are ubiquitous intermediates in organic synthesis. Asymmetric transformations with these intermediates, a central goal of organic synthesis, are typically carried out with covalently attached chiral auxiliaries. An alternative approach is to utilize chiral reagents that form discrete, well-defined aggregates with lithium enolates, providing a chiral environment conducive of asymmetric bond formation. These reagents effectively act as noncovalent, or traceless, chiral auxiliaries. Lithium amides are an obvious choice for such reagents as they are known to form mixed aggregates with lithium enolates. We demonstrate here that mixed aggregates can effect highly enantioselective transformations of lithium enolates in several classes of reactions, most notably in transformations forming tetrasubstituted and quaternary carbon centers. Easy recovery of the chiral reagent by aqueous extraction is another practical advantage of this one-step protocol. Crystallographic, spectroscopic, and computational studies of the central reactive aggregate, which provide insight into the origins of selectivity, are also reported.
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Santa Barbara, California 93106, United States.
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Santa Barbara, California 93106, United States.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Santa Barbara, California 93106, United States.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Jackson
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Santa Barbara, California 93106, United States.
authors.forename: Thuy-Ai D
authors.initials: TD
authors.lastname: Nguyen
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Santa Barbara, California 93106, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Alvarado
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Santa Barbara, California 93106, United States.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Stivala
authors.affiliation: Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University , Ithaca, New York 14853, United States.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University , Ithaca, New York 14853, United States.
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Mack
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Santa Barbara, California 93106, United States.
authors.forename: Trevor W
authors.identifier: 0000-0003-4370-1424
authors.initials: TW
authors.lastname: Hayton
authors.affiliation: Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University , Ithaca, New York 14853, United States.
authors.forename: David B
authors.initials: DB
authors.lastname: Collum
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Santa Barbara, California 93106, United States.
authors.forename: Armen
authors.identifier: 0000-0002-9120-1232
authors.initials: A
authors.lastname: Zakarian
mesh_terms: D000577:Amides / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D008094:Lithium / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000577:Amides; D002264:Carboxylic Acids; D002244:Carbon; D008094:Lithium