Sulfoxide‐Directed Metal‐Free ortho‐Propargylation of Aromatics and Heteroaromatics

Abstract

What prompted you to investigate this topic/problem?Selective carbon-carbon bond formation to aromatic and heteroaromatic systems is ac rucial synthetic goal. The majority of "classical" and "cutting-edge" cross-couplings have one thing in common:t hey are mediated by platinium group metals (e.g.,R u, Rh, Pd and Pt). Unfortunately,t he supply of these metals is at risk and their use may become unsustainable. An important future course, therefore, involves the development of coupling reactions that do not involve the use of am etal. Such an approach has additional benefits as trace metal contamination in products arising from metal-catalysed processes is am ajor problem in industry.W e thus set out to develop innovative coupling processes that operate under metal-free conditions and that complement existing metalcatalysed cross-coupling technologies and may ultimately lead to their replacement.What is the most significant result of this study?Drawing inspiration from classical sulfoxide Pummerer chemistry, we have developed as trategy for metal-free cross-coupling that exploits as ulfoxide directing group on an aromatic ring. The sulfur atom of the directing group catches the nucleophilic coupling partner before delivering it to the aromatic ring. Thus, intermolecular carbon-sulfur bond formation is used to trigger intramolecular formation of the challenging carbon-carbon bond. Importantly, the directing effect of the sulfoxide is switched off after the coupling so over reaction cannot occur.U pon reoxidation, the directing group effect is restored. The "safety-catch" nature of the sulfoxide directing group has been illustrated in as elective, iterative double cross-coupling process.What future opportunities do you see (in the light of the results presented in this paper)?We are developing ap ortfolio of sulfoxide-directed, metal-free cross-couplings that exploit our strategy.Inparticular,werecognise the potential of developing metal-free couplings that correspond to dehydrogenative CÀH/CÀH-type couplings-arguably the most desirable class of cross-coupling process. The new technology can be used in the synthesis and modification of organic materials, chemosensors and bioactive targets.What other topics are you working on at the moment?We introduce and exploit new synthetic concepts for the efficient construction of molecules with important properties. For example, in addition to developing metal-free coupling technology,w ea re harnessing electron-transfer in new transformations, synthesising natural product-inspired antibacterial agents to address the global problem of resistance to antibiotics, exploring new catalytic processes using copper and iron, using chemical tools to interrogate biological systems, and synthesising new organic materials for applications in organic electronics and energy industries.Invited for the cover of this issue is the group of David J. Procter at the University of Manchester (UK). The image illustrates an ew,m etal-free direction for cross-coupling technology by taking signage from ...