Syntheses of Dihydroconduramines (±)-B-1, (±)-E-1, and (±)-F‑1 via Diastereoselective Epoxidation of N‑Protected 4‑Aminocyclohex-2-en-1-ols

Diastereoselective syntheses of dihydroconduramines
(±)-B-1,
(±)-E-1, and (±)-F-1 have been achieved from N-protected
4-aminocyclohex-2-en-1-ols via two complementary procedures for epoxidation
as the key step. Treatment of either trans- or cis-4-N-benzylaminocyclohex-2-en-1-ol with
Cl3CCO2H and then m-chloroperoxybenzoic
acid (m-CPBA) resulted in initial formation of the
corresponding ammonium species, followed by epoxidation on the face
syn to the ammonium moiety exclusively; chemoselective N-benzylation
then provided either (1RS,2SR,3RS,4RS)- or (1RS,2RS,3SR,4SR)-2,3-epoxy-4-N,N-dibenzylaminocyclohexan-1-ol, respectively.
Treatment of either trans- or cis-4-N,N-dibenzylaminocyclohex-2-en-1-ol
with m-CPBA resulted in initial formation of the
corresponding N-oxide, followed by epoxidation on
the face syn to the hydroxyl group exclusively; reduction then provided
either (1RS,2RS,3SR,4RS)- or an alternative route to (1RS,2RS,3SR,4SR)-2,3-epoxy-4-N,N-dibenzylaminocyclohexan-1-ol, respectively.
In all cases, SN2-type ring opening of these epoxides upon
treatment with aqueous H2SO4 proceeded by nucleophilic
attack with inversion at C(2) preferentially, distal to the in situ
formed ammonium moiety. Hydrogenolytic N-deprotection then gave the
corresponding dihydroconduramines (±)-B-1, (±)-E-1, and
(±)-F-1.