Diastereomeric Reissert Compounds of Isoquinoline and 6,7-Dimethoxy-3,4-dihydroisoquinoline in Stereoselective Synthesis<sup>‖</sup>

Chiral acid chlorides were reacted with isoquinoline and 6,7-dimethoxy-3,4-dihydroisoquinoline to form diastereomeric Reissert compounds <b>8</b>−<b>11</b> and <b>18</b>−<b>21</b>, respectively. The best diastereoselectivity (80:20) was achieved in formation of the 9-phenylmenthyl derivative <b>20</b>. The diastereomers of 2-<i>l</i>-menthoxycarbonyl-1,2-dihydroisoquinaldonitriles (<i>S</i>)<i>-</i><b>8</b>/(<i>R</i>)<i>-</i><b>8</b>), formed in equal amounts, were inseparable. However, the individual diastereomers of 2-cholesteryloxycarbonyl-1,2-dihydroisoquinaldonitriles ((<i>R</i>)<i>-</i><b>11</b> and (<i>S</i>)<i>-</i><b>11</b>) and the 2-<i>l</i>-menthoxycarbonyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinaldonitriles ((<i>S</i>)<i>-</i><b>19</b>/(<i>R</i>)<i>-</i><b>19</b>)) were each readily purified. (<i>S</i>)<i>-</i><b>8</b>/(<i>R</i>)<i>-</i><b>8</b> (1:1) via the corresponding anions (NaH, −40 °C, DMF) with pivaldehyde yielded in 82:18 predominance the <i>S</i>-diastereomer of 1-isoquinolyl <i>tert</i>-butyl carbinyl <i>l</i>-menthyl carbonate ((<i>S</i>)<i>-</i><b>12</b>), which was obtained in pure form by a single recrystallization; hydrolysis produced 99% pure <i>S</i>-(−)-1-isoquinolyl <i>tert</i>-butyl carbinol [(<i>S</i>)<i>-</i><b>16</b>]. Reactions of the anions of diastereomeric Reissert compounds, either as mixtures or pure single species, with aromatic aldehydes and alkyl halides proceeded with at best modest selectivity (diastereomeric ratios up to 66:34 and 72:28, respectively). Therefore, it is concluded that the Reissert anions are either planar or rapidly inverting tetrahedral structures.