Synthesis of 1,2-Bis(trifluoromethylthio)arenes via Aryne Intermediates

Abstract

A general method for synthesis of 1,2-bis-trifluoromethylthioarenes has been developed. Arynes generated from silyl aryl triflates or halides react with bis(trifluoromethyl)disulfide to afford 1,2-bis-trifluoromethylthioarenes. Aryl, alkyl, ester, halide, and methoxy functionalities are compatible with reaction conditions. Use of bis(perfluoroaryl)-disulfides gave moderate yields of aryne disulfenylation or cyclization to fluorinated dibenzothiophenes.

Syntheses of 2-Aroyl Benzofurans through Cascade Annulation on Arynes

“…Finally, the present cascade reaction was employed for late-stage functionalization on the complex bioactive steroid estrone. The sterically crowded aryne precursor 7 , which was synthesized from estrone in 5 steps, was subjected to sulfonium salt 2n under standard reaction conditions at 60 °C to afford the corresponding product as a 7:3 ratio of the inseparable regioisomers 8a and 8b .…”

Copper-mediated 1,2-bis(trifluoromethylation) of arynes

“…Our approach is more operationally simple and general for synthesizing structurally diverse 1,2-bis(trifluoromethyl)arenes. Furthermore, aryne precursor 1w derived from estrone6 was successfully converted into the 1,2-bis(trifluoromethylated) derivative 2w (Scheme 3) demonstrating relevance of the current method to the modification of biologically active compounds.…”

“…Under Pd, Cu or Pt catalysis, arynes/hetarynes can insert into heteroatom–heteroatom bonds such as Si–Si, Sn–Sn and B–B bonds to provide 1,2-bis(functionalized) arenes with high synthetic utility (Scheme 1b). 5 However, such a method is not amenable to the preparation of bis-CF 3 products due to the fact that an infeasible aryne insertion to a “CF 3 –CF 3 ” bond would be required 6. We herein describe a new approach for 1,2-bis(functionalization) of arenes by reacting the aryne intermediate with an organometallic reagent twice, in this case [CuCF 3 ], thereby achieving an unpresented 1,2-bis(trifluoromethylation) of arynes (Scheme 1c).…”

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

“…Only trace of mono(trifluoromethylthiolated) product was detected, and most of the substrate 1a was not converted. To the best of our knowledge, the combination of bis(trifluoromethylthiolation) [36,[39][40][41] and cascade cycli- With the optimized reaction conditions in hand, we then set out to explore the substrate scope of N-[(3-aryl)propioloyl]indoles (Scheme 2). First, we explored the effect of the substitution on the indole ring.…”