New Cationic Olefin Cyclization−Pinacol Reactions. Ring-Expanding Cyclopentane Annulations That Directly Install Useful Functionality in the Cyclopentane Ring

2002-08-08T00:00:00Z (GMT) by Larry E. Overman John P. Wolfe
Two new tandem cationic olefin cyclization−pinacol reactions that provide cyclopentane-fused cycloalkanone products are described. Treatment of <i>cis</i>-1-[2-alkenyl-2-(triethylsiloxy)cycloalkyl]but-3-en-2-ol derivatives <b>21</b>−<b>24</b> with triflic anhydride at −78 °C affords cycloalkanones <b>31</b>−<b>34</b> in 54−90% yields with diastereoselectivities of typically >20:1. In this unusual transformation, the starting cycloalkanone is ring-expanded and fused to a 2-alkenylcyclopentane fragment. Reaction of <i>cis</i>-(2-siloxy-2-alkenylcycloalkyl)pyrrolidin-1-ylethanones <b>15</b>−<b>17</b> with triflic anhydride and 2,6-di-<i>tert</i>-butyl-4-methylpyridine (DTBMP) at −20 to +65 °C followed by hydrolysis of the intermediate iminium salts <b>64</b> with aqueous KHCO<sub>3</sub> affords cycloalkanediones <b>46</b>−<b>48</b> in moderate yield and high diastereoselectivity (>20:1). These are the first examples of ring-expanding cyclopentane annulations that directly introduce a carbon side chain or carbonyl functionality at the cyclopentane C2 position. The high diastereoselectivities observed in these reactions are believed to arise from reaction through highly organized cyclic transition states.