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.
Synthesis of indazolo[5,4-b][1,6]naphthyridine and indazolo[6,7-b][1,6]naphthyridine derivatives
