Cascade Multicomponent Synthesis of Indoles, Pyrazoles, and Pyridazinones by Functionalization of Alkenes

Abstract

The development of multicomponent reactions for indole synthesis is demanding and has hardly been explored. The present study describes the development of a novel multicomponent, cascade approach for indole synthesis. Various substituted indole derivatives were obtained from simple reagents, such as unfunctionalized alkenes, diazonium salts, and sodium triflinate, by using an established straightforward and regioselective method. The method is based on the radical trifluoromethylation of alkenes as an entry into Fischer indole synthesis. Besides indole synthesis, the application of the multicomponent cascade reaction to the synthesis of pyrazoles and pyridazinones is described.

Intermolecular radical carboamination of alkenes

“…It should be pointed out that an Ag/H 2 O 2 -mediated radical cascade comprising alkenes, aryldiazonium salts and sodium triflinate as reaction partners to afford indoles was reported by the Antonchick group, in which diazo compounds of type 160 were also suggested as intermediates. 95 The MacMillan group reported an enantioselective 3+2 coupling of the N-protected b-amino aldehyde 163 and various activated alkenes to access multi-substituted pyrrolidines 164 with moderate to high diastereoselectivity and high enantioselectivity (Scheme 36). 96 N-Bocylated cinnamyl amine also engages in this cascade to afford multi-substituted pyrrolidines 182 with good diastereoselectivity.…”

CF3SO2X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF3SO2Na

“…Amino- and azotrifluoromethylation of alkenes: Alkene trifluoromethylation was applied to the construction of indole, pyrazole and pyridazinone moieties via a multicomponent cascade reaction developed by Antonchick and Matcha in 2014 [ 31 ]. The method was based on the reaction between simple alkenes, sodium triflinate and diazonium salts.…”

Renaissance of 1,2,5‐Oxadiazolyl Diazonium Salts: Synthesis and Reactivity

“…Azo coupling reaction of aryl diazonium salts with azide anion and aromatic amines results in substituted azides and triazenes formation . Other methods with the retention of the dinitrogen functionality include cycloaddition or cyclocondensation approaches leading to various 5‐ and 6‐membered heterocyclic scaffolds . Along with these two general modes of reactivity, aromatic ipso ‐substitutions with an irreversible loss of dinitrogen as a stable leaving group has been investigated.…”