title: Structure-Reactivity Relationships in Lithiated Evans Enolates: Influence of Aggregation and Solvation on the Stereochemistry and Mechanism of Aldol Additions.
abstract: Aldol additions to isobutyraldehyde and cyclohexanone with lithium enolates derived from acylated oxazolidinones (Evans enolates) are described. Previously characterized trisolvated dimeric enolates undergo rapid addition to isobutyraldehyde to give a 12:1 syn:syn selectivity in high yield along with small amounts of one anti isomer. The efficacy of the addition depends critically on aging effects and the reaction quench. Unsolvated tetrameric enolates that form on warming the solutions are unreactive toward isobutyraldehyde and undergo retroaldol reaction under forcing conditions. Additions to cyclohexanone are relatively slow but form a single isomeric adduct in >80% yield. The ketone-derived aldolates are robust. All attempts to control stereoselectivity by controlling aggregation failed. Rate studies of addition to cyclohexanone trace the lack of aggregation-dependent selectivities to a monomer-based mechanism. The synthetic implications and possible utility of lithium enolates in Evans aldol additions are discussed.
authors.affiliation: Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University , Ithaca, New York 14853-1301, United States.
authors.forename: Evan H
authors.initials: EH
authors.lastname: Tallmadge
authors.affiliation: Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University , Ithaca, New York 14853-1301, United States.
authors.forename: Janis
authors.initials: J
authors.lastname: Jermaks
authors.affiliation: Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University , Ithaca, New York 14853-1301, United States.
authors.forename: David B
authors.initials: DB
authors.lastname: Collum
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D018360:Crystallography, X-Ray; D007700:Kinetics; D008094:Lithium / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000447:Aldehydes; D008094:Lithium