A new transition-metal-free route for the direct trifluoromethylthiolation and trifluoromethylsulfoxidation of electron-rich aromatics with CF3SO2Na in the presence of PCl3 was developed. Notably, PCl3 was used as a reducing and chlorination reagent. The transition-metal-free protocol utilized cheap and readily available reagents and exhibited good atom economy; therefore, it will serve as an alternative and practical strategy for the trifluoromethylthiolation and trifluoromethylsulfoxidation of electron-rich aromatics.

A novel triphenylphosphine-mediated direct trifluoromethylthiolation of indole derivatives using trifluoromethanesulfonyl chloride as the SCF3 source was developed. Sodium iodide facilitated this transformation by generating iodine in situ which was found to accelerate this transformation. The use of a transition metal-free protocol, readily available reagents, and mild reaction conditions allowed this protocol to be easily scaled up.

A new method for phosphine-mediated difluoromethylthiolation of indole derivatives and other electron-rich aromatics including pyrroles, pyrazolones, indolizine, and 1,3,5-trimethoxybenzene was developed using difluoromethanesulfonyl chloride. The additive n-Bu4NI was demonstrated to facilitate this reaction by generating iodine in situ, which could promote this transformation. The use of a transition-metal-free protocol, readily available reagents, and mild reaction conditions makes this protocol more practical than traditional methods.

A novel transition metal-free route for the direct trifluoromethylthiolation of electron-rich aromatics using CF3SO2Na in the presence of PhPCl2 was developed. More specifically, PhPCl2 was used as both a reducing and a chlorinating reagent for the first time in this CF3SO2Na-based trifluoromethylthiolation reaction. The absence of transition metals and the use of cheap and readily available reagents render this method an alternative and practical strategy for the trifluoromethylthiolation of electron-rich aromatics.Download high-res image (153KB)Download full-size image

Triphenylphosphine-mediated metal-free trifluoromethylthiolation and difluoromethylthiolation of thiols by CF3SO2Cl and CHF2SO2Cl to synthesize trifluoromethyl disulfides and difluoromethyl disulfides, respectively, was achieved at room temperature. Iodine generated in situ from iodide facilitated this reaction via the formation of iodotriphenylphosphonium iodide which could serve as a reducing agent in this transformation. Readily available reagents and mild reaction conditions without transition-metals allow this protocol to be more practical than traditional methods.Download high-res image (133KB)Download full-size image

A four-component, 1,4-addition Ugi reaction using cyclic α,β-unsaturated ketones, carboxylic acids, amines, and isocyanides was developed for the first time. By combining this reaction with Michael addition, nucleophilic substitution, and C–N bond formation reactions, bicyclic and tricyclic scaffolds with pyridinone and quinolinone moieties, two basic units among a variety of natural products and pharmaceuticals, were constructed.

Iodine-catalyzed thiolation of electron-rich aromatics, including substituted anisole, thioanisole, phenol, toluene, and naphthalene, using sulfonyl hydrazides as sulfenylation reagents was carried out. Sulfonothioates, the products of decomposition of sulfonyl hydrazides in the presence of iodine, are proposed as the major sulfenylation species in this transformation.

Iodine-catalysed regioselective sulfenylation of flavonoid derivatives with sulfonyl hydrazides was developed. Various flavonoid thioethers were obtained in moderate to good yield. The thiolation could be conveniently directed to C-8 for flavone, flavonol, dihydroflavone, and isoflavone derivatives or to C-7 for aurone derivatives by employing the isopropyl ethers of flavonoids bearing free OH groups at the C-5 or C-4 positions.

•Transition-metal-free thiolation of pyrazolones and benzofurans was achieved.•Aryl sulfonyl chlorides were used as sulfenylation reagents.•Triphenylphosphine was used as a reducing agent.•Potassium iodide was found to facilitate the transformation.An efficient, transition-metal-free method to synthesize pyrazolone thioethers as well as 2-aryl and 3-aryl benzofuran thioethers by employing aryl sulfonyl chlorides as sulfenylation reagents in the presence of triphenylphosphine was developed. Potassium iodide was found to facilitate the transformation for the first time by generating more reactive sulfenyl iodide in situ from sulfenyl chloride.

A mild method was developed for the direct C–H iodination of 1,3-azoles catalysed by CuBr2. Compared with the traditional metalation/iodination sequences carried out with nBuLi or TMPLi (TMP = 2,2,6,6-tetramethylpiperidino), a relatively weaker base, LiOtBu, was used in the presence of 1,10-phenanthroline. Five series of 1,3-azoles, including benzoxazole, benzothiozole, N-methyl-benzoimidazole, 5-phenyloxazole and 2-phenyl-1,3,4-oxadiazole were tested and afforded the corresponding iodination products.

An efficient, metal-free protocol used to synthesize aryl benzo[b]furan thioethers based on the I2-catalyzed cross-coupling of benzo[b]furans as well as the electrophilic cyclization of 2-alkynylphenol derivatives with aryl sulfonyl hydrazides was developed. Various 2-aryl and 3-aryl benzo[b]furan thioethers were obtained in moderate to good yields.

Aryl pyrazolone thioethers were synthesized via the I2-catalysed cross-coupling of pyrazolones with aryl sulphonyl hydrazides in the presence of p-toluenesulphonic acid, which has been proposed to promote the reaction by facilitating the decomposition of sulphonyl hydrazides.

A novel triphenylphosphine-mediated direct trifluoromethylthiolation of indole derivatives using trifluoromethanesulfonyl chloride as the SCF3 source was developed. Sodium iodide facilitated this transformation by generating iodine in situ which was found to accelerate this transformation. The use of a transition metal-free protocol, readily available reagents, and mild reaction conditions allowed this protocol to be easily scaled up.

A new method for phosphine-mediated difluoromethylthiolation of indole derivatives and other electron-rich aromatics including pyrroles, pyrazolones, indolizine, and 1,3,5-trimethoxybenzene was developed using difluoromethanesulfonyl chloride. The additive n-Bu4NI was demonstrated to facilitate this reaction by generating iodine in situ, which could promote this transformation. The use of a transition-metal-free protocol, readily available reagents, and mild reaction conditions makes this protocol more practical than traditional methods.

Aryl pyrazolone thioethers were synthesized via the I2-catalysed cross-coupling of pyrazolones with aryl sulphonyl hydrazides in the presence of p-toluenesulphonic acid, which has been proposed to promote the reaction by facilitating the decomposition of sulphonyl hydrazides.

Iodine-catalysed regioselective sulfenylation of flavonoid derivatives with sulfonyl hydrazides was developed. Various flavonoid thioethers were obtained in moderate to good yield. The thiolation could be conveniently directed to C-8 for flavone, flavonol, dihydroflavone, and isoflavone derivatives or to C-7 for aurone derivatives by employing the isopropyl ethers of flavonoids bearing free OH groups at the C-5 or C-4 positions.

Iodine-catalyzed thiolation of electron-rich aromatics, including substituted anisole, thioanisole, phenol, toluene, and naphthalene, using sulfonyl hydrazides as sulfenylation reagents was carried out. Sulfonothioates, the products of decomposition of sulfonyl hydrazides in the presence of iodine, are proposed as the major sulfenylation species in this transformation.