S₈-Catalyzed triple cleavage of bromodifluoro compounds for the assembly of N-containing heterocycles

Abstract

An unprecedented S8-catalyzed selective triple-cleavage of bromodifluoroacetamides is disclosed for the first time.

Recent Advances in the Synthesis of Heterocycles via Reactions Involving Elemental Sulfur

“…In term of redox balance, the global transformation is only a simple condensation with removal of a water and an ethanol molecules without change in oxidation states of any atom. It could be possible that, as in the previous case, [166] highly nucleophilic polysulfide generated in situ from the reaction of sulfur with 2-aminopyridine, acted as nucleophilic catalyst.…”

“…Elemental sulfur (in 20 mol % as S 8 or 160 mol % as atomic sulfur) was found to promote the condensation of anilines o-substituted by a cyclizable group (such as NH 2 , OH, SH) 394 with α-bromo-α,α-difluoro acetamides/acetates 395 to provide the corresponding benzazole-2-yl carboxamides or carboxylates 396 (Scheme 149). [166] The reactions proceeded at high temperature for o-phenylenediamines (130°C for 16 h), whereas o-aminothiophenols reacted under milder conditions (90°C, 12 h). High nucleophilicity of polysulfide, generated in situ from the reaction of sulfur with Na 2 CO 3 at elevated temperature, was inarguably responsible for this condensation with triple dehydrohalogenation via cascade of nucleophilic substitution and addition/elimination steps.…”

Chlorodifluoromethane as a C1 Synthon in the Assembly of N-Containing Compounds

“…Our design is based on our recent discovery in which ethyl bromodifluoroacetate (BrCF 2 COOEt) (Ma et al., 2018b, Deng et al., 2019) could act as a C1 source and formylating reagent with amines via quadruple cleavage under basic conditions (Ma et al., 2018a, Ma et al., 2018c, Ma et al., 2018d); we postulated that the quadruple cleavage of ClCF 2 H could also be occurred under the similar sets since it is known that difluorocarbene could be readily accessible from ClCF 2 H under basic conditions. Moreover, compared with BrCF 2 COOEt, ClCF 2 H is obviously much cheaper and more atomic economical.…”

Synthesis of Polycyclic Furan and Chromene Derivatives via Cascade Reactions Enabled by Cleavage of Multiple C(sp3)−F Bonds

“…Compared with more activated aromatic [21][22][23][24][25] or vinylic analogues, [26][27][28][29][30][31][32][33] selective aliphatic C(sp 3 )À F functionalization of unreactive perfluoroalkyl substance with multiple CÀ F bonds attached remote to π-system is relatively uncommon. [34][35][36][37][38][39][40][41][42][43][44][45][46][47] The successful realization of this challenging issue is complicated by several apparent factors (Scheme 1A). First, the high strength and activation barrier of CÀ F bond (BDE CÀ F = 500 � 50 kJ/ mol) result in chemical robustness of fluorocarbon in terms of thermodynamic stability and kinetic inertness.…”

“…bond formation and precise retention of partially fluorinated scaffold, although most of the advances focus on the manipulation of single C−F bond. Compared with more activated aromatic [21–25] or vinylic analogues, [26–33] selective aliphatic C( sp 3 )−F functionalization of unreactive perfluoroalkyl substance with multiple C−F bonds attached remote to π‐system is relatively uncommon [34–47] . The successful realization of this challenging issue is complicated by several apparent factors (Scheme 1A).…”