Application of Electrocyclic
Ring-Opening and Desymmetrizing
Nucleophilic Trappings of meso-6,6-Dibromobicyclo[3.1.0]hexanes
to Total Syntheses of Crinine and Haemanthamine Alkaloids
posted on 2019-02-06, 00:00authored byPing Lan, Martin G. Banwell, Anthony C. Willis
The
thermally induced electrocyclic ring-opening of C2-symmetric
(meso) 6,6-dibromobicyclo[3.1.0]hexanes
such as 10 in the presence of the chiral, nonracemic
1°-amine 28 afforded a ca. 1:1 mixture of the diastereoisomeric
and chromatographically separable 1-amino-2-bromo-2-cyclohexenes 37 (42%) and 38 (45%). Each of these was elaborated
over 13 steps, including Suzuki–Miyaura cross-coupling, radical
cyclization, and Pictet–Spengler reactions, into (−)-
or (+)-crinane (1 or ent-1, respectively). Variations on these protocols were applied to the
total syntheses of (+)- and (−)-11-hydroxyvattitine [(+)- and
(−)-3], (+)- and (−)-bulbispermine [(+)-
and (−)-4], (+)- and (−)-haemanthamine
[(+)- and (−)-5], (+)- and (−)-pretazettine
[(+)- and (−)-6], and (+)- and (−)-tazettine
[(+)- and (−)-7] as well as (±)-hamayne [(±)-8] and (±)-apohaemanthamine [(±)-9].
A number of these alkaloids were synthesized for the first time.