Asymmetric Synthesis. 39. Synthesis of 2-(1-Aminoalkyl)piperidines <i>via</i> 2-Cyano-6-phenyl Oxazolopiperidine

The asymmetric synthesis of a series of 2-(1-aminoalkyl) piperidines using (−)-2-cyano-6-phenyloxazolopiperidine <b>1 </b>is described. LiAlH₄ reduction of <b>1</b> followed by hydrogenolysis led to the diamine <b>3</b>. The same strategy applied to C-2-methylated compound <b>7</b> afforded [(2<i>S</i>)-2-methylpiperidin-2-yl]methanamine (<b>9</b>). Addition of lithium derivatives to the cyano group of <b>1</b> resulted in the formation of an intermediate imino bicyclic system (<b>11a</b><b>−</b><b>c</b>) which could be diastereoselectively reduced to substituted diamino alcohols <b>13a</b><b>−</b><b>c</b>. The addition of an excess of PhLi to <b>1</b> in the presence of LiBr furnished disubstituted amine <b>19</b>, the precursor of diphenyl[(2<i>S</i>)-piperidin-2-yl]methanamine (<b>22</b>).