A rhodium-catalyzed three-component reaction of arylisocyanides, trifluorodiazoethane, and activated methylene isocyanides or azomethine ylides: an efficient synthesis of trifluoroethyl-substituted imidazoles

Abstract

A novel method for the synthesis of trifluoroethyl-substituted imidazoles is reported via a rhodium-catalyzed three-component reaction of isocyanides, 2,2,2-trifluorodiazoethane and activated methylene isocyanides or azomethine ylides.

2,2,2-Trifluorodiazoethane (CF3CHN2): A Long Journey since 1943

“…137 In 2019, Zhao continued this research by developing approaches to CF 3 -substituted imidazoles. 138 In particular, reaction between in situ generated CF 3 CHN 2 (1), phenyl isonitrile 494, and methylene-active isonitrile 495 gave trisubstitiuted imidazole 496 in 75% yield (Scheme 98). On the other hand, the reaction between CF 3 CHN 2 (1), phenyl isonitrile 494, and Shiff base of glycine 498 afforded the tetra-substituted imidazole 499 in 42% yield.…”

Trifluorodiazoethane: A versatile building block to access trifluoromethylated heterocycles

“…The synthesis of trifluoroethylated imidazoles 75 using trifluorodiazoethane was recently unveiled by Zhao's group (Scheme 36) [56]. This three‐component reaction of trifluorodiazoethane, isocyanides, and activated methylene isocyanides or azomethine ylides occurred in the presence of rhodium and silver catalysts.…”

Silver‐Catalyzed Three‐Component Coupling Reaction of Amines, 2‐Isocyanobenzaldehydes, and 2,2,2‐Trifluorodiazoethane and Synthesis of Trifluoromethyl‐Substituted Indolo[1,2‐c]quinazolines

“…Thus, development of efficient methods for the synthesis of trifluoromethyl‐substituted indolo[1,2‐ c ]quinazolines in the absence of transition metals is highly desired. As a continuation of our studies on the applications of diazo compounds [9,17] and isocyanides, [18] herein we report a silver‐catalyzed three‐component coupling reaction of amines, 2‐isocyanobenzaldehydes, and 2,2,2‐trifluorodiazoethane. This reaction provides an efficient method for the construction of CF 3 ‐containing dihydroquinazolines in a single step from readily available substrates under rather mild conditions.…”

“…Thus, various reagents and protocols for the trifluoromethylation of organic compounds have been developed over the past decades [3] . In this field, 2,2,2‐trifluorodiazoethane (CF 3 CHN 2 ) has emerged as particularly useful and versatile CF 3 ‐source in the preparation of various CF 3 ‐containing N ‐heterocycles such as pyrazolines, [4] pyrazoles, [5] triazoles, [6] tetrazoles, [7] pyridazines, [8] and imidazoles [9] . Obviously, it is of value to develop new synthetic strategies for the preparation of various new CF 3 ‐containing N ‐heterocycles employing 2,2,2‐trifluorodiazoethane as CF 3 ‐source.…”