Bayesian optimization-driven parallel-screening of multiple parameters for the flow synthesis of biaryl compounds.

Traditional optimization methods using one variable at a time approach waste time and chemicals and assume that different parameters are independent from one another. Hence, a simpler, more practical, and rapid process for predicting reaction conditions that can be applied to several manufacturing environmentally sustainable processes is highly desirable. In this study, biaryl compounds were synthesized efficiently using an organic Brønsted acid catalyst in a flow system. Bayesian optimization-assisted multi-parameter screening, which employs one-hot encoding and appropriate acquisition function, rapidly predicted the suitable conditions for the synthesis of 2-amino-2'-hydroxy-biaryls (maximum yield of 96%). The established protocol was also applied in an optimization process for the efficient synthesis of 2,2'-dihydroxy biaryls (up to 97% yield). The optimized reaction conditions were successfully applied to gram-scale synthesis. We believe our algorithm can be beneficial as it can screen a reactor design without complicated quantification and descriptors.

Correction: Exploration of flow reaction conditions using machine-learning for enantioselective organocatalyzed Rauhut-Currier and [3+2] annulation sequence.

Correction for 'Exploration of flow reaction conditions using machine-learning for enantioselective organocatalyzed Rauhut-Currier and [3+2] annulation sequence' by Masaru Kondo et al., Chem. Commun., 2020, 56, 1259-1262, DOI: 10.1039/C9CC08526B.

Exploration of flow reaction conditions using machine-learning for enantioselective organocatalyzed Rauhut-Currier and [3+2] annulation sequence.

A highly atom-economical enantioselective organocatalyzed Rauhut-Currier and [3+2] annulation sequence has been established by using a flow system. Suitable flow conditions were explored through reaction screening of multiple parameters using machine learning. Eventually, functionalized chiral spirooxindole analogues were obtained in high yield with good ee as a single diastereomer within one minute.

Enantio- and Diastereoselective Betti/aza-Michael Sequence: Single Operated Preparation of Chiral 1,3-Disubstituted Isoindolines.

The first enantio- and diastereoselective Betti/intramolecular aza-Michael sequence carried out using a C3-symmetric chiral trisimidazoline organocatalyst is reported. The reaction of phenols and N-tosylimines bearing a Michael acceptor moiety afforded densely functionalized 1,3-disubstituted isoindolines bearing two stereogenic centers as single diastereomers in high yields (≤93%) and excellent enantioselectivities (≤99.9%).