We report the development of an open-source experimental design via Bayesian optimization platform for multiobjective reaction optimization. Using high-throughput experimentation (HTE) and virtual screening data sets containing highdimensional continuous and discrete variables, we optimized the performance of the platform by fine-tuning the algorithm components such as reaction encodings, surrogate model parameters, and initialization techniques. Having established the framework, we applied the optimizer to real-world test scenarios for the simultaneous optimization of the reaction yield and enantioselectivity in a Ni/photoredox-catalyzed enantioselective crosselectrophile coupling of styrene oxide with two different aryl iodide substrates. Starting with no previous experimental data, the Bayesian optimizer identified reaction conditions that surpassed the previously human-driven optimization campaigns within 15 and 24 experiments, for each substrate, among 1728 possible configurations available in each optimization. To make the platform more accessible to nonexperts, we developed a graphical user interface (GUI) that can be accessed online through a web-based application and incorporated features such as condition modification on the fly and data visualization. This web application does not require software installation, removing any programming barrier to use the platform, which enables chemists to integrate Bayesian optimization routines into their everyday laboratory practices.
Catalytic procedures are described for aminedirected borylation of aliphatic and aromatic tertiary amine boranes. Sequential double borylation is observed in cases where two or more C–H bonds are available that allow 5-center or 6-center intramolecular borylation. The HNTf2 catalyzed borylation of benzylamine boranes provides a practical means for the synthesis of ortho-substituted arylboronic acid derivatives, suitable for Suzuki-Miyaura cross-coupling applications.
Catalytic enantioselective and diastereoselective spiroketalizations with BINOL-derived chiral phosphoric acids are reported. The chiral catalyst can override the inherent preference for the formation of thermodynamic spiroketals, and highly selective formation of nonthermodynamic spiroketals could be achieved under the reaction conditions.
Designing efficient and green approaches to complex molecules is a challenge faced by any organization seeking to deliver modern pharmaceutical compounds to patients. The outcome of any route design effort, in terms of efficiency, is largely governed by the disconnections and synthetic strategies generated during the process of route scouting, coupled with the decisions made by the individuals responsible for the research. In this article, we delineate an approach, based on historical data, capable of quantifying the probable efficiency of a proposed synthesis prior to any research being conducted. This decisionmaking strategy can be used to both aid the decision-making process of innovators and to benchmark the outcome performance of the developed process, improving the efficiency of any manufacturing process developed. Through improved decision making and benchmarking, this approach could minimize the environmental impact of pharmaceutical production.
Three's a crowd: The combination of a Brønsted acid and a hydrogen‐bond donor cocatalyst was found to promote various ionic [2+4] cycloadditions under mild reaction conditions (see scheme; Ts=4‐toluenesulfonyl). Thiophosphoramides are the most effective cocatalysts because of the stronger counterion activation effect resulting from three, rather than two, hydrogen bonds involved in anion binding.
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