Brønsted acid‐catalyzed Reactions of Unprotected N‐heterocycles with Aryl/Aryl Diazoalkanes

Abstract

The chemoselective C−H functionalization of unprotected N‐heterocycles is a challenging task in organic synthesis. Herein, we report on a Brønsted‐acid catalyzed reaction of aryl/aryl diazoalkanes with unprotected N‐heterocycles to selectively allow for C−H functionalization at the C3‐position under mild reaction conditions and short reaction time without the need of protecting groups. The general applicability of this method was further expanded towards protected indole and unprotected pyrrole heterocycles.

Visible-light-mediated radical reactions of indoles withpara-quinone methides using eosin Y as an organophotoredox catalyst

“…8 The decarboxylative C-3 benzylation of indole-3-acetic acid was another direct method reported for the synthesis of indolyldiarylmethanes. 9 In addition, indolyldiarylmethanes could be accessed through other methods, which include the 3-component coupling reaction of indoles with aldehydes and boronic acids, 10 nucleophilic substitution reactions involving a labile leaving group, 11 acid mediated coupling of aliphatic amines/nitrosoarenes to indoles, 12 tandem hydroformylation/Fischer indole synthesis from olefins, 13 reactions involving the aza-fulvene intermediate, 14 C(sp 3 )–H arylation of diarylmethane via deprotonative-cross-coupling processes, 15 coupling reactions under heterogeneous catalysis, 16 etc .…”

Acid‐Catalyzed Carbene Transfer from Diazo Compounds: Carbocation versus Carbene as Key Intermediate

“…The terminal nitrogen of diazo compounds can be activated by the Pier's borane HB(C 6 F 5 ) 2 [9] and by the intramolecular P−O−B frustrated Lewis pair (FLP) of t Bu 2 POBcat [10] via 1,1‐addition reactions. Brønsted acids can also be used to catalyze the C−H functionalization of N ‐heterocycles with diazo compounds [11] …”

“…Brønsted acids can also be used to catalyze the CÀ H functionalization of N-heterocycles with diazo compounds. [11] According to recent experimental and DFT studies, it is generally believed [12] that the diazo C=N bond can be activated by Lewis acids to form neutral carbene-like intermediates [8,9,13] for further carbene transfer reactions (Scheme 1B). Such belief is also related to the fact that diazo compounds are well-known carbene precursors upon thermolysis or photolysis.…”