Photocatalytic Arylation of Alkenes, Alkynes and Enones with Diazonium Salts

Carbon–carbon bond formation by sp–sp or sp–sp crosscoupling is a key transformation in organic synthesis. Many methods, typically involving transition metal catalysis, are known, and the recent recognition of Richard F. Heck, Ei-ichi Negishi and Akira Suzuki by the Royal Swedish Academy of Sciences (Stockholm, Sweden) when they were awarded the Nobel Prize in Chemistry (2010) underlines the importance of metal-catalyzed cross-coupling reactions. However, long before the triumph of the palladium-catalyzed cross-coupling reaction, such as the Heck (1972) and Sonogashira (1975) reactions, methods for arylation of alkenes and alkynes were known. The Meerwein arylation, developed in 1939, is a copper-catalyzed coupling of an aryl diazonium salt with unsaturated compounds. Even earlier, in 1896, an intramolecular variant of this reaction was reported, today known as the Pschorr reaction. A radical mechanism is discussed for both cases by reversible oxidation of copper(I) to copper(II). However, several drawbacks have prevented the broader application of these reactions in organic synthesis: the reaction yields are typically low (20–40%), high catalyst loadings are required (15–20 mol%), and side products are formed under the aqueous reaction conditions (Scheme 1). In addition to the reduction of aryl diazonium salts by copper(I) cations, several other methods exist giving access to aryl radicals. Amongst others, aryl radicals can be obtained by photoinduced electron transfer. Organometallic photocatalysts such as 2,2’-bipyridine (bpy)-containing ruthenium complexes (e.g. , [Ru(bpy)3] ) are known to undergo one-electron transfer reactions. Visible light-induced photoredox catalysis offers the possibility of initiating organic transformations with high selectivities under mild conditions, as demonstrated by MacMillan, Yoon, Stephenson and many others. Current reports describe the photocatalytic formation of carbon–carbon or carbon–heteroatom bonds. Recently, visible-light photocatalysis has entered the field of palladium-catalyzed cross-coupling reactions. In 2007, Akita reported the acceleration of copper-free Sonogashira-type reactions by adding a photocatalyst. Sanford et al. reported a merger of palladium-catalyzed C–H functionalization and visible-light photocatalysis. In their approach, aryl radicals are obtained from the photocatalytic reduction of aryl diazonium salts by the aid of [Ru(bpy)3] 2+ and, subsequently, used in palladium-catalyzed C–H arylation reactions. Direct C–H arylation of heteroarenes with aryl diazonium salts was achieved using eosin Y and visible light. [Ru(bpy)3] 2+ is the catalyst of choice for many photoredox reactions due to its unique photochemical properties : absorption of blue light (lmax=452 nm), high chemical stability, long lifetime of the photoexcited state, and high quantum yield of its formation. The catalyst is able to reduce aryl diazonium salts, such as para-bromophenyldiazonium tetrafluoroborate (1 f, E1/2red= +0.02 V), from the excited state (E1/2ox= 0.76 V at 293 K) and is therefore able to photochemically form highly reactive aryl radicals (4) that can subsequently be trapped by unsaturated compounds (2 ; Scheme 2). Combining the fields of photoredox catalysis and cross-coupling reactions, we report the intermolecular visible-light-mediated arylation of unsaturated compounds catalyzed by [Ru(bpy)3] 2+ or eosin Y as photocatalysts. The process is atom economic and efficient and therefore suitable to improve the classic Meerwein arylation protocol significantly. The reaction of phenyldiazonium tetrafluoroborate (1a) with styrene (2a) in the presence of [Ru(bpy)3] 2+ under inert atmosphere and irradiation with a blue high-power light-emitting diode (LED, lmax=455 15 nm, P=3 W) at ambient temperature gave stilbene (3a), which is the formal substitution product of a vinylic hydrogen atom by the aryl residue of the diazonium salt. This result is in contrast to the recently reported photocatalytic radical addition reactions of alkyl halides to olefins. Monitoring of the reaction kinetics revealed that the trans isomer is initially formed as the major product, but then Scheme 1. a) Classic Meerwein arylation protocol and b) the related improved photoredox process.