The oxyanion derived from hydroxyacrylate E-(5)
undergoes smooth intramolecular Michael addition to give the
trans-2,6-disubstituted tetrahydropyran (7) as the major
product of reaction. In contrast, the oxyanion obtained from isomer
Z-(5) cyclizes to give the
cis-2,6-disubstituted tetrahydropyran (6) as the major
product. Such chemistry has been extended to the enantioselective synthesis of
(+)-(6) the acquisition of which constitutes a formal total synthesis of
acid (+)-(2), a constituent of the glandular secretion from the civet cat
(Viverra civetta). Reductive amination of keto acrylate
(12) affords an intermediate amine which cyclizes,
in situ, to give the
cis-2,6-disubstituted piperidine (26). Analogous
treatment of compound (13) delivers the isomeric
trans-2,6-disubstituted piperidine (27) as the exclusive
product of reaction. Transition state structures have been proposed to account
for the diastereoselectivities observed in all of the cyclization reactions.
Highly Efficient Access to Strained Bicyclic Ketals via Gold-Catalyzed Cycloisomerization of Bis-homopropargylic Diols.
