title: Direct organocatalytic asymmetric heterodomino reactions: the Knoevenagel/Diels-Alder/epimerization sequence for the highly diastereoselective synthesis of symmetrical and nonsymmetrical synthons of benzoannelated centropolyquinanes.
abstract: Amino acids and amines have been used to catalyze three component hetero-domino Knoevenagel/Diels-Alder/epimerization reactions of readily available various precursor enones (1a-l), aldehydes (2a-p), and 1,3-indandione (3). The reaction provided excellent yields of highly substituted, symmetrical and nonsymmetrical spiro[cyclohexane-1,2'-indan]-1',3',4-triones (5) in a highly diastereoselective fashion with low to moderate enantioselectivity. The Knoevenagel condensation of arylaldehydes (2a-p) and 1,3-indandione (3) under organocatalysis provided arylidene-1,3-indandiones (17) in very good yields. We demonstrate for the first time amino acid- and amine-catalyzed epimerization reactions of trans-spiranes (6) to cis-spiranes (5). The mechanism of conversion of trans-spiranes (6) to cis-spiranes 5 was shown to proceed through a retro-Michael/Michael reaction rather than deprotonation/reprotonation by isolation of the morpholine enamine intermediate of cis-spirane (22). Prochiral cis-spiranes (5ab) and trans-spiranes (6ab) are excellent starting materials for the synthesis of benzoannelated centropolyquinanes. Under amino acid and amine catalysis, the topologically interesting dispirane 24 was prepared in moderate yields. Organocatalysis with pyrrolidine catalyzed a series of four reactions, namely the Michael/retro-Michael/Diels-Alder/epimerization reaction sequence to furnish cis-spirane 5ab in moderate yield from enone 1a and 1,3-indandione 3.
authors.affiliation: The Skaggs Institute for Chemical Biology and the Departments of Chemistry and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037.
authors.forename: D B
authors.initials: DB
authors.lastname: Ramachary
authors.forename: K
authors.initials: K
authors.lastname: Anebouselvy
authors.forename: Naidu S
authors.initials: NS
authors.lastname: Chowdari
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Barbas
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D002384:Catalysis; D008958:Models, Molecular; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D000475:Alkenes; D000588:Amines; D000596:Amino Acids; D013141:Spiro Compounds