Application of Electrocyclic Ring-Opening and Desymmetrizing Nucleophilic Trappings of <i>meso</i>-6,6-Dibromobicyclo[3.1.0]hexanes to Total Syntheses of Crinine and Haemanthamine Alkaloids

The thermally induced electrocyclic ring-opening of C₂-symmetric (<i>meso</i>) 6,6-dibromobicyclo[3.1.0]­hexanes such as <b>10</b> in the presence of the chiral, nonracemic 1°-amine <b>28</b> afforded a ca. 1:1 mixture of the diastereoisomeric and chromatographically separable 1-amino-2-bromo-2-cyclohexenes <b>37</b> (42%) and <b>38</b> (45%). Each of these was elaborated over 13 steps, including Suzuki–Miyaura cross-coupling, radical cyclization, and Pictet–Spengler reactions, into (−)- or (+)-crinane (<b>1</b> or <i>ent</i>-<b>1</b>, respectively). Variations on these protocols were applied to the total syntheses of (+)- and (−)-11-hydroxyvattitine [(+)- and (−)-<b>3</b>], (+)- and (−)-bulbispermine [(+)- and (−)-<b>4</b>], (+)- and (−)-haemanthamine [(+)- and (−)-<b>5</b>], (+)- and (−)-pretazettine [(+)- and (−)-<b>6</b>], and (+)- and (−)-tazettine [(+)- and (−)-<b>7</b>] as well as (±)-hamayne [(±)-<b>8</b>] and (±)-apohaemanthamine [(±)-<b>9</b>]. A number of these alkaloids were synthesized for the first time.