Palladium-catalyzed nucleomethylation of alkynes for synthesis of methylated heteroaromatic compounds

Abstract

A novel palladium-catalyzed nucleomethylation of alkynes is developed, affording 3-methylindoles, 3-methylbenzofurans and 4-methylisoquinolines in moderate to excellent yields.

Three Component syn‐1,2‐Arylmethylation of Internal Alkynes**

“…The transformation is regio‐ as well stereoselective and offers access to methyl‐containing tetra‐substituted olefins (Figure 1D). Meanwhile, a directed intramolecular cyclative methylation of alkyne has led to substituted indoles [13] …”

“…Meanwhile, a directed intramolecular cyclative methylation of alkyne has led to substituted indoles. [13]…”

Palladium Catalyzed syn-1,2-ArylMethylation of Internal Alkynes

“…However, recently an intramolecular directed cyclative methylation of alkyne led to substituted indoles. 13 We herein uncover discussing a regioselective carbo-methylation of unsymmetrical alkynes (ynamide 11 and yne-acetates 12 ) when reacted with aryl iodides and methyl boronic acid under Pd-catalysis; the transformation has offered very high regioselectivity and functional group tolerance (Fig. 1D).…”

A General Protocol toward Synthesis of 3-Methylindoles Using Acenaphthoimidazolyidene-Ligated Oxazoline Palladacycle

“…In comparison with Fischer indole synthesis, transition metal catalysis via Pd chemistry is emerging as a powerful synthetic strategy for indoles. ,,, However, a convenient straightforward access to 3-methylindoles has been somewhat neglected to date. − Jørgensen et al first presented a route to synthesize 3-substituted indoles from 2-bromoiodobenzenes and allylamines at 140 °C . Recently Ye et al advanced relevant synthetic methodology via a Pd-mediated nucleomethylation of presynthesized 2-alkynylanilides with methylboronic acid . From the viewpoint of sustainable chemistry, however, these methods as practical protocols in industry are still seriously hampered by the following limitations: (1) high temperature and catalyst loading (>5 mol %), (2) substrates with narrow scopes or tedious preparations, and (3) poor activity for most of the inactive aryl chlorides (30–70%).…”

“…23 Recently Ye et al advanced relevant synthetic methodology via a Pd-mediated nucleomethylation of presynthesized 2-alkynylanilides with methylboronic acid. 26 From the viewpoint of sustainable chemistry, however, these methods as practical protocols in industry are still seriously hampered by the following limitations: (1) high temperature and catalyst loading (>5 mol %), (2) substrates with narrow scopes or tedious preparations, and (3) poor activity for most of the inactive aryl chlorides (30−70%). Consequently, the development of a new general, efficient approach to synthesize 3-methylindoles from simple substrates, especially o-dichloroarenes, is of great importance at the current time.…”