Palladium-Catalyzed Sonogashira-Coupling Conjoined C–H Activation: A Regioselective Tandem Strategy to Access Indolo- and Pyrrolo[1,2-a]quinolines

Abstract

An operationally simple approach for the regioselective tandem synthesis of indolo[1,2-a]quinolines 4a-v and pyrrolo[1,2-a]quinolines 5a-k from 1-(2-bromophenyl)-1H-indole/pyrrole/imidazole 1a-c, 2a,b by the palladium-catalyzed sequential C-C bond formation is described. The developed approach involves the palladium-catalyzed Sonogashira coupling followed by the intramolecular C-C bond formation via C-H activation, which leads to the formation of 6-endo-dig cyclized product. This synthetic methodology accommodates wide functional group variation on alkyne, which proves to be advantageous for the structural and biological activity assessments.

Synthesis of pyrrolo[1,2-a]quinolines and ullazines by visible light mediated one- and twofold annulation of N-arylpyrroles with arylalkynes

“…13 Several methods for the synthesis of fused nitrogen-containing heterocycles have been reported; many apply direct arylation reactions. These include palladium-catalyzed reactions, [14][15][16][17] 1,2-alkyl migration, 18 DDQ-mediated intramolecular cyclizations, 19 flash vacuum pyrolysis, 20 photosubstitution reactions, 21 and alkynecarbonyl metathesis. 22 Lautens et al reported a palladium catalyzed direct arylation of geminal dibromo-olefins with a boronic acid via tandem Suzuki-Miyura coupling reaction.…”

Recent Developments in the Cyclization of Alkynes and Nitrogen Compounds for the Synthesis of Indole Derivatives

“…Furthermore, the palladium‐catalyzed Sonogashira‐coupling followed by a carbon‐hydrogen activation involving 1‐(2‐bromophenyl)‐1 H ‐indole and terminal alkynes gave regioselectively the fused‐indolizines 108 (Scheme 79). [159] The corresponding products were formed in 41–80% yields by using PdCl 2 (PPh 3 ) 2 (5.0 mol %), LiCl (2.0 equiv) and NaOAc (3.0 equiv) in DMA at 120 0 C for 18–40 h. The results showed that the yields were influenced by the substituents at the terminal alkynes much more than by the indole substrates. In fact, the aryl alkynes bearing electron‐donating groups gave better yields than those bearing electron withdrawing groups and alkyl alkynes.…”

Efficient Synthesis of Helical Tetrasubstituted Alkenes as Potential Molecular Switches: A Two‐Component Palladium‐Catalyzed Triple Domino Process

“…As the yield of the domino process of 9 a was not satisfactory and to improve the efficiency of the whole reaction sequence we combined the carbopalladation/C À H activation domino process with the Sonogashira reaction to give a two-component triple domino process. [15][16][17] Pleasingly, reaction conditions similar to those employed for the Sonogashira reaction of 7 a and 8 d could be used for the domino transformations; the only changes required were a higher temperature and the use of DMF as the solvent. Under these reaction conditions a mixture of 7 b and 8 a gave the alkene 11 b in 67 % yield, and substrates 7 a and 8 d led to alkene 11 j in 77 % yield (Scheme 3).…”