Synthesis of Tetrahydro-β-carbolines by a Manganese-Catalysed Oxidative Pictet-Spengler Reaction

Herein, an efficient and green procedure for the synthesis of tetrahydro-beta-carbolines via dehydrogenative coupling of alcohols with tryptamines is reported. The reaction was carried out under mild conditions in the presence of a catalytic amount of the (PNP)-P-iPr Mn catalyst and a weak base (Na2CO3). This method tolerated a variety of benzylic and aliphatic alcohol substrates with different functional groups and afforded diverse products in good to excellent isolated yields using tryptamines. Using this strategy, we successfully synthesised pharmaceutical molecules harman, harmaline, and harmine in a concise manner.

Automated summary

An efficient and green method for the synthesis of tetrahydro-beta-carbolines using a dehydrogenative coupling reaction between alcohols and tryptamines is reported. The reaction proceeds under mild conditions with the presence of a catalytic amount of (PNP)-P-iPr Mn catalyst and a weak base (Na2CO3). This strategy shows good tolerance towards various benzylic and aliphatic alcohol substrates with different functional groups, leading to diverse products in good to excellent yields.