Rapid gas-liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide.

The enhanced reaction rate in the epoxidation of cyclohexene with air as an oxidant was discovered without any added catalyst utilizing a continuous flow reactor constructed with readily available stainless steel parts and devices. This continuous-flow process demonstrates a significant improvement in reaction time for highly selective epoxide production over the batch process due to the efficient mass transfer between the liquid phase and air. The flow process discovered was operated continuously with good operational stability, evaluated by a constant high yield of cyclohexene oxide, to obtain the desired product with high productivity.

A Synthetic Approach to Dimetalated Arenes Using Flow Microreactors and the Switchable Application to Chemoselective Cross-Coupling Reactions.

In spite of their potential utility, the chemistry of dimetalated arenes is still in its infancy because they are extremely difficult to synthesize. We report a novel method of synthesizing arenes bearing a boryl group and a metallic substituent, such as boryl, silyl, stannyl, or zincyl groups, in an integrated flow microreactor based on the generation and reactions of aryllithiums bearing a trialkyl borate moiety. The bimetallic arenes showed a remarkable chemoselectivity in palladium-catalyzed cross-coupling reactions. The selectivity was switched by the selection of the metal species that constitutes the dimetalated arenes as well as appropriate catalysts.

A Novel Approach to Functionalization of Aryl Azides through the Generation and Reaction of Organolithium Species Bearing Masked Azides in Flow Microreactors.

A novel straightforward method for aryl azides having functional groups based on generation and reactions of aryllithiums bearing a triazene group from polybromoarenes using flow microreactor systems was achieved. The present approach will serve as a powerful method in organolithium chemistry and open a new possibility in the synthesis of polyfunctional organic azides.

Three-component Ag-catalyzed enantioselective vinylogous mannich and Aza-Diels-Alder reactions with alkyl-substituted aldehydes.

Efficient protocols for three-component catalytic enantioselective vinylogous Mannich (VM) reactions of alkyl-substituted aldimines (including those bearing heteroatom-containing substituents) and readily available siloxyfurans are presented. High efficiency and stereoselectivity is achieved through the use of o-thiomethyl-p-methoxyaniline-derived aldimines. Reactions, performed under an atmosphere of air and in undistilled THF, can be promoted in the presence of as little as 1 mol % of easily accessible amino acid-based chiral ligands and commercially available AgOAc. The desired products are obtained in 44 to 92% yield, and in up to >98:<2 diastereomer and >99:<1 enantiomer ratio (>98% ee). Removal of the N-activating group is performed through a one-vessel oxidation/hydrolysis operation, which proceeds via a stable aza-quinone (characterized by X-ray crystallography). Evidence is presented indicating that reactions with chiral nonracemic aldehydes are subject to catalyst control: both substrate enantiomers react to afford the desired product diastereomers in high stereoselectivity. Aryl- and alkynyl-substituted o-thiomethyl-p-methoxyaniline-derived aldimines undergo Ag-catalyzed enantioselective VM reactions more efficiently and with higher selectivity than the corresponding o-anisidyl substrates. Additionally, Ag-catalyzed aza-Diels-Alder reactions of the alkyl-substituted aldimines bearing the structurally modified N-aryl unit afford enantiomerically enriched (up to 95% ee) products in up to 88% yield.