title: Highly enantioselective synthesis of 2,6-disubstituted and 2,2,6-trisubstituted dihydropyrones: a one-step synthesis of (R)-(+)-hepialone and its analogues.
abstract: An efficient enantioselective approach to chiral dihydropyrones has been developed by the hetero-Diels-Alder (HDA) reactions of (E)-4-methoxy-2-trimethylsiloxy-penta-1,3-diene (diene 1) with aldehydes and pyruvates. It has been found that the readily accessible (R)-BINOL-Ti(OiPr)(4) (1.1:1) complex was a very effective catalyst for this reaction. Aromatic, heteroaromatic, conjugated, and aliphatic aldehydes afforded the corresponding products in moderate to high isolated yields (up to 99%) with excellent enantioselectivities (up to 99% ee). The first example of highly enantioselective synthesis of 2,2,6-trisubstituted dihydropyrones by the catalytic reaction of diene 1 with pyruvates was reported. The isolated intermediates indicated that this asymmetric HDA reaction proceeded in a Mukaiyama aldol pathway. On the basis of the absolute configurations of the products, a possible mechanism was proposed. Moreover, the catalytic system could be used to synthesize a series of enantioenriched beta-hydroxyketones 4. Finally, this methodology was successfully applied for the one-step synthesis of the important natural product (R)-(+)-Hepialone with 88% isolated yield and 94% enantioselectivity.
authors.affiliation: Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Yang
authors.forename: Deju
authors.initials: D
authors.lastname: Shang
authors.forename: Yanling
authors.initials: Y
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Du
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Feng
mesh_terms: D002384:Catalysis; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D011753:Pyrones; C511258:hepialone