title: Lewis base activation of Lewis acids: catalytic, enantioselective vinylogous aldol addition reactions.
abstract: The generality of Lewis base catalyzed, Lewis acid mediated, enantioselective vinylogous aldol addition reactions has been investigated. The combination of silicon tetrachloride and chiral phosphoramides is a competent catalyst for highly selective additions of a variety of alpha,beta-unsaturated ketone-, 1,3-diketone-, and alpha,beta-unsaturated amide-derived dienolates to aldehydes. These reactions provided high levels of gamma-site selectivity for a variety of substitution patterns on the dienyl unit. Both ketone- and morpholine amide-derived dienol ethers afforded high enantio- and diastereoselectivity in the addition to conjugated aldehydes. Although alpha,beta-unsaturated ketone-derived dienolate did not react with aliphatic aldehydes, alpha,beta-unsaturated amide-derived dienolates underwent addition at reasonable rates affording high yields of vinylogous aldol product. The enantioselectivities achieved with the morpholine derived-dienolate in the addition to aliphatic aldehydes was the highest afforded to date with the silicon tetrachloride-chiral phosphoramide system. Furthermore, the ability to cleanly convert the morpholine amide to a methyl ketone was demonstrated.
authors.affiliation: Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, IL 61801, USA. denmark@scs.uiuc.edu
authors.forename: Scott E
authors.initials: SE
authors.lastname: Denmark
authors.forename: John R
authors.initials: JR
authors.lastname: Heemstra
mesh_terms: D000143:Acids / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry*; D000468:Alkalies / Q000737:chemistry*; D002384:Catalysis; D004987:Ethers; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D013237:Stereoisomerism
chemical_list: D000143:Acids; D000447:Aldehydes; D000468:Alkalies; D004987:Ethers