A practical and enantioselective palladium-catalyzed diboration of 1,1-disubstituted allenes is developed by employing a P-chiral monophosphorus ligand, BI-DIME. A series of diboronic esters containing a chiral tertiary boronic ester moiety are formed in excellent yields and ee’s with the palladium loading as low as 0.2 mol%. DFT calculations revealed a concerted mechanism of oxidative addition of bis(pinacolato)diboron and allene insertion, as well as a critical dispersion effect on the origins of the enantioselectivity. The method is successfully applied to the concise and enantioselective synthesis of brassinazole.

Asymmetric catalysis in flow has been attracting much attention very recently because of the potential advantages over its batchwise counterpart, such as high-throughput screening and synthesis, easy automation with the integration of on-demand reaction analysis, little or no reaction workup, and potential long-term use of the catalysts in the case of heterogeneous catalysis. Homogeneous asymmetric catalysis performed in a microreactor has demonstrated successful examples in fast catalyst screening, integrated inline/onlineanalysis, microflow photocatalysis, multistep transformation with unstable intermediates, and potential for lower catalyst loading or homogeneous catalyst recylcing. Since heterogeneous asymmetric catalysis serves as a better way than its homogeneous analogue for catalyst separation and recycling, this Review Article summarizes recent development via different catalyst immobilization methods, such as covalent support, a self-supported method, an adsorption method, and H-bonding, electrostatic or ionic interaction, and nonconventional media, as well. In addition, biocatalysis, including enzyme-catalyzed kinetic resolution and transformation, in flow will be discussed either in homogeneous or heterogeneous mode.Keywords: asymmetric catalysis; biocatalysis; continuous flow chemistry; heterogeneous; homogeneous; microreaction technology; solid-supported catalyst

A practical and enantioselective palladium-catalyzed diboration of 1,1-disubstituted allenes is developed by employing a P-chiral monophosphorus ligand, BI-DIME. A series of diboronic esters containing a chiral tertiary boronic ester moiety are formed in excellent yields and ee’s with the palladium loading as low as 0.2 mol%. DFT calculations revealed a concerted mechanism of oxidative addition of bis(pinacolato)diboron and allene insertion, as well as a critical dispersion effect on the origins of the enantioselectivity. The method is successfully applied to the concise and enantioselective synthesis of brassinazole.