An ew benzyne transformation is described that affords versatile biaryl structures without recourse to transition-metal catalysis or stoichiometric amounts of organometallic building blocks.Aryl sulfonamides add to benzyne upon fluoride activation, and then undergo an aryl Truce-Smiles rearrangement to affordb iaryls with sulfur dioxide extrusion. The reaction proceeds under simple reaction conditions and has excellent scope for the synthesis of sterically hindered atropisomeric biaryl amines.The biaryl motif is fundamental to chemistry,a si ti sw idely represented in natural products,m aterials,p harmaceuticals, and agrochemicals.Synthesis of these ubiquitous structures is often carried out using transition-metal catalysis and stoichiometric amounts of metallated arenes,w hich enable the coupling of two sp 2 -carbon centers via organometallic intermediates.[1] Thedrive for sustainable synthetic methods which avoid both the use of expensive and scarce transition metals, and the separate preparation of aryl metal reactants,h as stimulated efforts to develop metal-free biaryl syntheses. [2][3][4] Achieving the controlled union of two arene fragments without organometallic assistance is very challenging,a nd current methods are often forced to employ harsh reaction conditions and/or operationally complex protocols.R ecent examples include UV photochemistry to generate aryl cations from electron-rich arenes, [3a] oxidative coupling of electronrich arenes in the presence of strong Lewis acids, [3b-d] and base-mediated coupling of aryl iodides with simple arenes through electron transfer.[4] This latter approach has received significant attention in recent literature and uses the combination of an alkali metal base and an electron-rich ligand to generate aryl radicals through as ingle-electron transfer. Subsequent S Ar Hs ubstitution and oxidation lead to biaryl formation (Scheme 1a). Them ethod is impressively simple, but requires high temperatures,u pt o2 0-fold excess of the arene coupling partner,and produces regioisomeric mixtures of substituted biaryls.T he discovery of am ild, metal-free biaryl synthesis with broad substrate scope would therefore be as ignificant development in the field.We were interested in applying the reactive intermediate benzyne to this problem. Arynes are versatile intermediates in biaryl synthesis,with their addition to aryl organometallics being awell-described method, known since the earliest days of aryne chemistry. [5,6] Cross-coupling with simple arenes, however, in the absence of organometallic species,has rarely been reported as asynthetic method. [7] Given that arynes undergo smooth addition to heteroatom nucleophiles, [8] we wondered if this feature could be exploited in am etal-free biaryl synthesis through addition/ rearrangement chemistry.O ur synthetic plan is set out in Scheme 1b.S tarting with readily available aryl sulfonamides (1), addition of abenzyne [generated from a2-trimethylsilyl-(phenyl) triflate precursor upon treatment with fluoride] should give the ...
