Tryptamine Synthesis by Iron Porphyrin Catalyzed C–H Functionalization of Indoles with Diazoacetonitrile
Rene Koenigs developed a tryptamine synthesis by C–H functionalization of indoles with diazoacetonitrile.
Tryptamines are important endogenous signaling molecules that play a pivotal role in biochemical processes like the regulation of the sleep–wake rhythm. The closely related serotonin possesses key regulatory functions in the cardiovascular system and organ development and plays a central role as a neurotransmitter in the central nervous system. The synthesis of tryptamines is typically conducted following a classic route starting with a Mannich reaction of an indole heterocycle, followed by quaternization of the amine, nucleophilic substitution with highly toxic cyanide and final reduction. Professor Rene Koenigs (RWTH Aachen University, Germany) and co-workers previously reported on carbene transfer reactions of the underexplored and explosive diazoacetonitrile reagent. In a team effort with the groups of Junior Professor Martin J. Weissenborn (Leibniz Institute of Plant Biochemistry and Martin-Luther University Halle-Wittenberg, Germany) and Dr. Junming Ho (University of New South Wales, Sydney) iron porphyrin catalyzed reactions of diazoacetonitrile with N‐heterocycles were developed to synthesize important precursors of tryptamines.