Sulfonium-aided coupling of aromatic rings via sigmatropic rearrangement

Abstract

Biaryl synthesis continues to occupy a central role in chemical synthesis. From blockbuster drug molecules to organic electronics, biaryls present numerous possibilities and new applications continue to emerge. Transition-metal-catalyzed coupling reactions represent the gold standard for biaryl synthesis and the mechanistic steps, such as reductive elimination, are well established. Developing routes that exploit alternative mechanistic scenarios could give unprecedented biaryl structures and expand the portfolio of biaryl applications. We have developed metal-free C–H/C–H couplings of aryl sulfoxides with phenols to afford 2-hydroxy-2′-sulfanylbiaryls. This cascade strategy consists of an interrupted Pummerer reaction and [3,3] sigmatropic rearrangement. Our method enables the synthesis of intriguing aromatic molecules, including oligoarenes, enantioenriched dihetero[8]helicenes, and polyfluorobiaryls. From our successes in aryl sulfoxide/phenol couplings and a deeper understanding of sigmatropic rearrangements for biaryl synthesis, we have established related methods, such as aryl sulfoxide/aniline and aryl iodane/phenol couplings. Overall, our fundamental interests in underexplored reaction mechanisms have led to various methods for accessing important biaryl architectures.

Metal‐Free Arylation of Benzothiophenes at C4 by Activation as their Benzothiophene S‐Oxides

“…To further understand the mechanism and factors dictating reaction outcome and regioselectivity, the rearrangements and associated transition structures (TSs) of several benzothiophene S ‐oxides were studied using density functional theory (DFT) with the M06‐2X‐D3/def2‐QZVPP (SMD=CH 2 Cl 2 )//M06‐2X‐D3/6‐31+G(d,p) (SMD=CH 2 Cl 2 ) level of theory (Scheme 5). [10] In line with previous studies from our group [7a–b, 8e] and from others [8c,d,h,i, 11] we propose a mechanism involving initial activation of the sulfoxide moiety in benzothiophene S ‐oxides as the corresponding trifluoroacetate followed by addition of phenol to give aryloxysulfonium salt or sulfurane A ; use of anisole in place of phenol gave no reaction (see Supporting Information) thus underlining the importance of the free hydroxyl group in the phenol coupling partners.…”

Synthesis of 3-SCF2H-/3-SCF3-chromones via Interrupted Pummerer Reaction/Intramolecular Cyclization Mediated by Difluoromethyl or Trifluoromethyl Sulfoxide and Tf2O

“…Based on the above experimental results and previous reports, − a plausible mechanistic pathway for this reaction was postulated (Scheme ). First, the reactive electrophilic intermediate I , rather than the previously presumed analogous CHF 2 SOTf and BnOTf, , was generated from the reaction of difluoromethyl sulfoxide and Tf 2 O.…”

“…Given that sulfoxides have been verified to be versatile sulfur reagents in organic synthesis, − we conceived whether sulfoxide containing CF 2 H can be developed as a powerful difluoromethylthiolating agent for the construction of SCF 2 H substituted products. In the pioneering work of the Procter group, bench-stable trifluoromethyl sulfoxide has been synthesized and used as a trifluoromethylthiolating reagent for installing the SCF 3 group onto nucleophilic (hetero)­arenes through an interrupted Pummerer reaction (Scheme a) .…”

Construction of Cyclobutane‐Centered Tricyclic Caged Skeleton through a [5,5]‐Rearrangement Triggered Cascade

“…In the past few years, we have devoted to the development of sulfonium‐rearrangements and the rearrangement triggered dearomatization reactions [22–38] . In this line of work, a [5,5]‐rearrangement triggered dearomatization of aryl sulfoxides recently developed in our laboratory allows the introduction of allyl nitriles and various nucleophiles to arene rings, and thus providing value‐added alicyclic compounds ( Scheme 1 ,B ) [26] .…”