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Yet, benchmark methods for selective cross\u2010couplings rely on highly toxic heavy metal catalysts, which are unfavorable in the synthesis of pharmaceuticals. Metal\u2010free coupling reactions, on the other hand, may require harsh conditions and lack selectivity. We report a novel, metal\u2010free cross\u2010coupling reaction that involves the tethering of two phenyl groups by a temporary, traceless sulfonamide linker that directs a photochemical aryl fusion into a single coupling product. The perfect regio\u2010 and chemoselectivity of the reaction could be rationalized by a cyclic intermediate, which fragments into the biaryl and volatile side products. Using a flow reactor, we synthesized numerous substituted biaryl building blocks for important therapeutics in high yields, such as antibiotics, antitumor, neuroprotective and cholesterol\u2010lowering agents as well as antiarthritic non\u2010steroidal antiinflammatory drugs (NSAIDs). The new method was successfully employed in a total synthesis of cannabinol, an important analgesic and antiemetic therapeutic. We also report a metal\u2010free synthesis of key building blocks used for the preparation of sartans, antihypertensive agents that rank among the top blockbuster drugs worldwide. This safe and convenient protocol is a valuable alternative for the widely used metal\u2010dependent aryl cross\u2010coupling methods.<\/jats:p>","DOI":"10.1002\/anie.201805961","type":"journal-article","created":{"date-parts":[[2018,7,12]],"date-time":"2018-07-12T13:32:19Z","timestamp":1531402339000},"page":"14476-14481","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Metal\u2010Free Synthesis of Pharmaceutically Important Biaryls by Photosplicing"],"prefix":"10.1002","volume":"57","author":[{"given":"Florian","family":"Kloss","sequence":"first","affiliation":[{"name":"Department of Biomolecular Chemistry Leibniz Institute for Natural Product Research and Infection Biology, HKI  Beutenbergstrasse 11a 07745 Jena Germany"},{"name":"Transfer Group Antiinfectives Leibniz Institute for Natural Product Research and Infection Biology (HKI)  07745 Jena 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