A Synthesis of C(16),C(18)-Bis-<i>epi</i>-cytochalasin D via Reformatsky Cyclization

2000-08-22T00:00:00Z (GMT) by E. Vedejs S. M. Duncan
Triene <b>5</b> has been prepared by the <i>E</i>-selective olefination of aldehyde <b>12</b> with the ylide <b>11</b>. Several alternative syntheses of <b>12</b> were evaluated, and the successful route involved conversion of <b>22</b> into the vinyl ether <b>23</b> by Petasis olefination, followed by Claisen rearrangement. Diels−Alder cycloaddition of <b>5</b> with <b>4</b> gave the adduct <b>6</b> in 77% yield, and Reformatsky cyclization under dilution conditions afforded <b>10</b> (67%). After conversion to enol silane <b>32</b>, oxidation with dimethyldioxirane produced <b>34</b>. Conversion to a key intermediate <b>38</b> using electrophilic selenenylation and selenoxide rearrangement, followed by enolate alkylation and deprotection, gave <b>43</b>. The X-ray crystal structure of <b>43</b> was determined to prove the stereochemistry.