A One-Pot Double C–H Activation Palladium Catalyzed Route to a Unique Class of Highly Functionalized Thienoisoquinolines

Abstract

The synthesis of a unique class of highly functionalized 3,4-thienoisoquinolines via an efficient palladium-catalyzed one-pot, regioselective double C-H activation is presented. This class of biologically relevant compounds has been prepared in five steps from commercially available starting materials with overall yields ranging from 27 to 62%. A masked carboxylic acid was used to direct C-H activation to the typically less reactive C4 position. Additionally, the carboxylic acid provides a synthetically useful handle for further functionalization.

Palladium‐Catalyzed Intermolecular Desulfinylative Cross‐Coupling of Heteroaromatic Sulfinates

“…Although a broad range of C2‐arylated heteroaromatics can be generated by decarboxylative cross‐coupling, the procedure suffers certain challenges. Nonetheless, decarboxylative couplings continue to attract significant attention,5a, 15 leading to the development of elegant advances employing copper and/or silver as co‐catalysts 13c,d. Developing an alternative to carboxylic acids with analogous yet complementary reactivity led us to investigate sulfinic acids.…”

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

“…The double CÀ H activation for the synthesis of thienoisoquinolines was applied to variety of substrates with EWG as well as EDG and received excellent yields (Scheme 135). [140] The above obtained products were subjected hydrolysis to get the corresponding acid derivatives. Subsequently, the acid was subjected to proto-decarboxylation to give the corresponding thiophene derivatives in good to excellent yields with very good substituent group tolerance (Scheme 136).…”

“…This protocol is similar to the one mentioned earlier from Wong and Forgione. [140] The agenda of this protocol is to utilize 3-(N-(2-bromobenzyl)arylsulfonamido)thiophene-2-carboxylates 249 for cyclization to obtain thienoisoquinolines. The scope of the reaction was examined on different aromatic sulfonamides containing electron donating groups as well as electron withdrawing groups (Scheme 144).…”

The First Glycosides with Pyrazolo[3,4-C]isoquinoline Aglycone Moiety. Synthesis and NMR Structure Investigation

“…Pyrrolo [3,4-c]-βcarboline-1,3-dienes III [8] have been studied as a new class of inhibitors of tyrosine kinases [11]. Thieno [3,4-c]isoquinoline IV, synthesis of which we carried out several years ago for the first time [9], have been studied as promising inhibitors NFkappaB receptor [12,13]. Therefore, the probability of new medicinal substances with the structure of condensed isoquinolines is very high, and the development of alternative methods of synthesis and functionalization azolo-and other condensed isoquinolines seems relevant, especially for medicinal chemistry.…”