Site-Selective Rh-Catalyzed C-7 and C-6 Dual C–H Functionalization of Indolines: Synthesis of Functionalized Pyrrolocarbazoles

Abstract

A site-selective dual C-7 and C-6 C–H functionalization of indolines with azabenzonorbornadienes has been accomplished using Rh-catalysis. The reaction affords a potential route toward pyrrolocarbazoles with broad scope and functional group tolerance.

Recent Advances in Metal‐catalyzed Alkylation, Alkenylation and Alkynylation of Indole/indoline Benzenoid Nucleus

“…[32] Cui group reported the cyclization at the C7 and C6 positions of indolines using alkynes under Rh‐catalysis [32a] . While our group showed a one‐pot construction of pyrrolocarbazoles via Rh‐catalyzed site‐selective dual C−H activation of indolines at the C7 and C6 sites using azabenzonorbornadienes [32b] . Control experiments reveal that N ‐coordination is ideal for this reaction, while O ‐coordinating groups show no reaction.…”

Transition‐Metal‐Catalyzed Directing Group Assisted (Hetero)aryl C−H Functionalization: Construction of C−C/C‐Heteroatom Bonds

“…Shortly after this preliminary investigation, a follow-up study on pyrimidine directed synthesis of pyrrolocarbazoles was reported under Rh catalysis (Scheme 28). [89] Both protocols showed excellent functional group tolerance and a broad scope of 7-azabenzonorbornadienes as coupling components to deliver the desired adducts in good yields…”

Recent Advances in Retained and Dehydrogenative Dual Functionalization Chemistry

“…An oxidative coupling reaction of N-substituted arylamides (11) with disubstituted alkynes (12) using Pd(OAc) 2 catalyst by Huang and co-workers also proceeded under basic conditions to generate N-substituted isoquinolones (13) (Scheme 4). [7] The reaction firstly proceeds via an oxidative insertion into a CÀ H bond in deprotonated substrates (11-A) that are generated from the reaction of 11 and base, using activated Pd(II) species to form Pd(II) intermediates (11-B).…”

“…Regarding Rh-catalyzed dual functionalization, a site-selective Rh-catalyzed dual CÀ H functionalization of N-(pyrimidin-2yl) indolines (26) with 7-azabenzonorbornadienes (27) to furnish pyrrolocarbazoles (28) was developed by Punniyamurthy and co-workers (Scheme 8). [12] A plausible reaction mechanism for the Rh-catalyzed dual CÀ H functionalization is shown as follows: the 2-pyrimidine group undergoes C(7)À H activation to form rhodacycles (26-A). Coordination of the rhodium center in 26-A with 27 gives Rh complexes (26-B), and 26-B undergo migratory insertion to yield CÀ C bond formed Rh complexes (26-C).…”