Tryptamine Synthesis by Iron Porphyrin Catalyzed C−H Functionalization of Indoles with Diazoacetonitrile

Abstract

The functionalization of C À Hb onds with nonprecious metal catalysts is an important researcha rea for the development of efficient and sustainable processes.Herein, we describe the development of iron porphyrin catalyzedreactions of diazoacetonitrile with N-heterocycles yielding important precursors of tryptamines,a long with experimental mechanistic studies and proof-of-concept studies of an enzymatic process with YfeX enzyme.B yu sing readily available FeTPPCl, we achieved the highly efficient CÀHfunctionalization of indole and indazole heterocycles.T hese transformations feature mild reaction conditions,e xcellent yields with broad functional group tolerance,c an be conducted on gram scale,a nd thus provide au nique streamlined access to tryptamines.

Stoichiometric Photochemical Carbene Transfer by Bamford–Stevens Reaction

“…Noteworthy, under the present reaction conditions, the photochemical approach towards C−H functionalization of 7‐azaindole heterocycles is superior over currently available methods using specialized Rh II catalyst, excess amount of the expensive heterocycle and continuous‐addition techniques . Similarly, the direct C−H functionalization of indazole heterocylcles still remains a challenge in organic synthesis . When switching to the electron‐rich N ‐methyl pyrrole the product of C−H functionalization of the C 2 −H bond was obtained in moderate yield (Scheme ).…”

Diazoacetonitrile (N2CHCN): A Long Forgotten but Valuable Reagent for Organic Synthesis

“…Notably, no reaction was observed when blocking the 3‐position of the indole heterocycle or when using electron‐withdrawing protecting groups at the indole nitrogen. Control experiments indicate the participation of radicals in this reaction …”

Iron‐porphyrin Catalyzed Carbene Transfer Reactions – an Evolution from Biomimetic Catalysis towards Chemistry‐inspired Non‐natural Reactivities of Enzymes

“…Following an initial report on the C−H functionalization of indole heterocycles with donor‐acceptor diazoesters using iron complexes bearing a dinitrogen ligand, Fasan et al. and Koenigs together with Weissenborn reported on the C−H functionalization of protected and unprotected indole heterocycles using myoglobin, YfeX or Fe(III)TPPCl as catalyst, followed by a report by Arnold et al. on the same transformation using a P411 variant (Scheme a) .…”