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The application of parallel synthesis to lead optimization programs in drug discovery has been an ongoing challenge since the first reports of library synthesis. A number of approaches to the application of parallel array synthesis to lead optimization have been attempted over the years, ranging from widespread deployment by (and support of) individual medicinal chemists to centralization as a service by an expert core team. This manuscript describes our experience with the latter approach, which was undertaken as part of a larger initiative to optimize drug discovery. In particular, we highlight how concepts taken from the manufacturing sector can be applied to drug discovery and parallel synthesis to improve the timeliness and thus the impact of arrays on drug discovery.

Organic transformations mediated by photoredox catalysis have been at the forefront of reaction discovery. Recently, it has been demonstrated that binuclear Au­(I) bisphosphine complexes, such as [Au2(μ-dppm)2]­X2, are capable of mediating electron transfer to nonactivated bromoalkanes for the generation of a variety of alkyl radicals. The transfer reactions of bromine, derived from nonactivated bromoalkanes, are largely unknown. Therefore, we propose that unique metal-based mechanistic pathways are at play, as this binuclear gold catalyst has been known to produce Au­(III) Lewis acid intermediates. The scope and proposed mechanistic overview for the formal bromine atom transfer reaction of nonactivated bromoalkanes mediated by photoredox Au­(I) catalysis is presented. The methodology presented afforded good yields and a broad scope which include examples using bromoalkanes and iodoarenes.

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