Palladium‐Catalyzed Migratory Insertion of Isocyanides into C(thiophene)–SMe Bonds: Access to Atom‐Transfer Reactions

Abstract

PdII‐catalyzed CN‐directed addition of isocyanides to C(sp2)–SMe bonds of thiophenes (generated in situ) effectively recycles the SMe activating group into thioimidate products. The catalytic sequence includes selective C(sp2)–SMe bond activation/migratory insertion of isocyanides into C(sp2)–PdIV and subsequent C(sp2)–SMe bond‐forming reductive elimination from imidoyl–PdIV–SMe complexes. Through these transition‐metal‐catalyzed addition reactions we have established isocyanides as a new template for atom‐transfer reactions. This groundbreaking research avoids the use of ancillary ligands that is a constant feature of all previously reported addition reactions with C–S bonds. This process proceeds through a high‐valent PdII/IV catalytic cycle, which – to the best of our knowledge – has not been previously reported in this regard. Isocyanide insertion into C(Ar)–S bonds through addition is also unprecedented. Finally, the resulting thioimidates were demonstrated to be convenient precursors for the synthesis of thieno[2,3‐c]pyrroles by targeting the recycled SMe group for the second time in a cascade reaction process.

Bond Forming Reactions Involving Isocyanides at Diiron Complexes

“…Similarly to CO, isocyanides can be incorporated into catalytic mechanisms based on oxidative addition, isocyanide insertion, and reductive elimination. This emerging strategy, based on CNR insertion into M-element bonds, offers tremendous opportunities for the synthesis of fine chemicals containing a nitrogen functionality, and is largely dominated by Pd-catalyzed or Pd-promoted reactions [17][18][19][20][21][22]. Considerable efforts have been made in order to expand the research field to other transition-metals, given the strong interest in replacing noble and rare metals with more abundant and sustainable transition metals, such as iron.…”

Recent Advances in Palladium-Catalyzed Isocyanide Insertions

“…An early example (2017) of such an imidoylative Liebeskind-Srogl coupling was performed in a one-pot fashion as depicted in Scheme 43 [81]. The thiophene 156 is formed via an S-demethylation/Thorpe-Ziegler cyclization [82], and is directly subjected to the imidoylative reaction conditions.…”

Recent Development in Palladium-Catalyzed Domino Reactions: Access to Materials and Biologically Important Carbo- and Heterocycles

“…The result of this reaction was the generation of a heterocyclic system in a multicomponent process where the palladium-catalyzed step did not promote such heterocyclization. 174 Scheme 114. Synthesis of thiochromenone derivatives.…”