Manganese catalyzed C–H functionalization of indoles with alkynes to synthesize bis/trisubstituted indolylalkenes and carbazoles: the acid is the key to control selectivity

Abstract

The Mn-catalyzed C-H alkenylation reactions of indole with terminal- and internal-alkynes have been developed. In the presence of a catalytic amount of acid, the procedure efficiently affords bis/trisubstituted indolyl-alkenes in a highly regio- and stereo-selective manner. Without the addition of acid, the reaction undergoes a [2+2+2] cyclization process to give carbazoles with release of hydrogen gas. Notably, the directing pyrimidyl group can be readily removed. Experimental studies reveal that the reaction is initiated by a C-H activation step and the acid is the selectivity controller via a hydrogen transfer process.

C−H Functionalization of Indoles by 3d Transition‐Metal Catalysis

“…Lie and co‐workers reported the first example of Mn‐catalyzed syntheses of C‐2 alkenylated indoles employing MnBr(CO) 5 /DIPEA ( N,N ‐diisopropylethylamine) system. The authors have observed dramatic selectivity change by the addition of a catalytic amount of benzoic acid (Scheme ) . With the use of benzoic acid, selective alkenylation at C‐2 of indole was observed, whereas a [2+2+2] cyclization process occurred in the absence of acid.…”

“…The authors have observed dramatic selectivity change by the addition of a catalytic amount of benzoic acid (Scheme 9). [32] With the use of benzoic acid, selective alkenylation at C-2 of indole was observed, whereas a [2 + 2 + 2] cyclization process occurred in the absence of acid. This unified protocol tolerated a wide variety of indoles and alkynes.…”

Manganese‐Catalyzed C−H Olefination Reactions

“…Later on, Li and coworkers reported a Mn-catalyzed CÀ H alkenylation of indoles with alkynes in the presence of both base and acid (Scheme 3). [15] This reaction was applicable to a variety of alkynes including both terminal and internal ones, though the latter demonstrated relatively lower reactivity in some cases. Thus, various C2-alkenylated indoles were successfully accessed, which could be further transformed to useful functional heterocycles.…”

Air‐Stable Manganese(I)‐Catalyzed C−H Activation for Decarboxylative C−H/C−O Cleavages in Water

“…[6] In particular,m anganese catalysts are highly attractive because of their inexpensive and non-toxic nature.T hus,r ecent years have witnessed the emergence of organometallic CÀHactivation by user-friendly manganese(I) catalysts, [7] with key contributions by inter alia Kuninobu, [8] Wang, [9] Ackermann, [10] and Fairlamb, [11] among others. [12] Despite these major advances,t he manganese(I)catalyzed CÀHt ransformations were thus far largely limited to simple hydroarylation-based manifolds,w hile decarboxylative transformations have thus far proven elusive.C onsidering the remarkable recent advances in decarboxylative catalysis, [13] we became attracted to devising unprecedented manganese-catalyzed decarboxylative C À H/C À Otransformations,o nw hich we report herein. Notable features of our findings include 1) manganese(I)-catalyzed decarboxylative CÀHf unctionalizations,2 )robust organometallic CÀHa ctivation in H 2 Oa nd air, and 3) expedient CÀHa llylations on indoles,a renes and amino acids as well as synthetically meaningful ketimines ( Figure 1).…”