Bischler-Napieralski reaction catalyst

Formation of amide 163 from 158 and 3,4-dimethoxyphenylethylamine 133, followed by a Bischler-Napieralski reaction and transfer-hydrogenation of the formed imine 164 with the ruthenium catalyst (S,S)-122 (Scheme 5.32) gave the enantion-pure epi-emetine analogue 161 (> 98% ee) and the enantioenriched diastereomer 162 (80% ee). 

The synthesis of hydrastine (61) by Falck and Manna demonstrate that the amide product of the Passerini reaction could be used in a subsequent Bischler-Napieralski reaction as a method to produce isoquinolines. In their report, carboxybenzaldehyde derivative 62 was condensed with isonitrile 63 in 71% yield to provide amide 64. Cyclization (POCI3/CH3CN), reduction of the dihydroisoquinoline (Adam s catalyst/H2), and reductive alkylation with formaldehyde gave a diastereomeric mixture of a- and p-hydrastines in 58% overall yield from Passerini product 64. 

One application of this reaction was in the synthesis of yohimban 11.17 (Scheme 11.6). The cycloaddition precursor 11.14 could be easily built up from tryptamine 11.13 and the cyclization employed a nickel/phosphite catalyst system. Selective reduction of the less-hindered alkene, protio-desilylation and a Bischler-Napieralski reaction gave the desired pentacyclic system 11.16. Reduction of the remaining alkene gave yohimban 11.17... 

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