Free-flow electrophoresis is an ideal tool for preparative separations in continuous microflow. With the approach presented herein for coupling free-flow electrophoresis and mass spectrometry it is now also possible to trace non-fluorescent compounds and identify them by means of mass spectrometry. The functionality of the method and its potential as an integrated separation unit for microflow synthesis is demonstrated by application to a multicomponent [3+2]-cycloannulation.

Four new σ bonds and two chiral centers are formed in a novel three‐component, one‐pot [3+2] cycloannulation process, which gives pyrrolobenzoxazoles directly in good yields and with excellent diastereoselectivity (see scheme, TMS=trimethylsilyl). The products could be converted into proline derivatives with full stereochemical control. A chiral scandium complex catalyzed the formation of the products with up to 83 % ee.

A novel 1,2-dinucleophile engages two imines in a sequential vinylogous Mannich-Mannich-Pictet-Spengler process to generate complex hexahydropyrrolo[3,2-c]quinolines in a one-pot operation. This methodology provides a rapid, highly modular, and flexible access toward a wide range of products and forms four new σ-bonds and chiral centers each. The diastereoselectivity may be inverted by fine-tuning of reaction conditions and the electronic nature of the imines.

The development of a direct and highly stereoselective synthesis of 2,3,5-substituted tetrahydrofurans has been accomplished through a combination of batch- and microchip-MS-experiments. This sequential transformation comprises a Lewis acid-mediated reaction of bis(silyl) dienediolate 1 and a broad range of aldehydes, furnishing products with three new σ-bonds and three stereogenic centers in a one-pot process with typically good yields and excellent stereoselectivity. Key steps which have been elucidated primarily with microchip-MS-experiments include a vinylogous aldol reaction and a Prins-type cyclization. Furthermore, a titanium BINOL complex is a powerful chiral catalyst for this process. The products were further converted into bi- and tricylic products by carbonyl-ene reactions, proceeding with excellent yields and diastereoselectivity.

The development of a direct and highly stereoselective synthesis of 2,3,5‐substituted tetrahydrofurans has been accomplished through a combination of batch‐ and microchip‐MS‐experiments. This sequential transformation comprises a Lewis acid‐mediated reaction of bis(silyl) dienediolate 1 and a broad range of aldehydes, furnishing products with three new σ‐bonds and three stereogenic centers in a one‐pot process with typically good yields and excellent stereoselectivity. Key steps which have been elucidated primarily with microchip‐MS‐experiments include a vinylogous aldol reaction and a Prins‐type cyclization. Furthermore, a titanium BINOL complex is a powerful chiral catalyst for this process. The products were further converted into bi‐ and tricylic products by carbonyl–ene reactions, proceeding with excellent yields and diastereoselectivity.