Continuous Flow Techniques in the Total Synthesis of Jaspine B: Part II

In this work, we report on the completion of the total synthesis of jaspine B from Garner's aldehyde using a Pd-catalyzed carbonylation strategy under continuous flow conditions. The target compound was synthesized from the key intermediate bicyclic aminolactone 5 via a sequence of Wittig olefination, DiBAl-H reduction, and hydrogenation, all implemented in flow microreactors. A particularly efficient transfer hydrogenation of the C ═ C double bond in alkene 8 was achieved by using formic acid as the hydrogen donor and palladium immobilized within a urea-based polymer support (UBPS). Furthermore, a multistep flow system was developed, enabling the direct integration of the hydrogenation of alkene 8 with the final carbamate 9 deprotection step. The methodology was successfully scaled for the preparation of lactol 6 intermediates, demonstrating the potential of continuous flow techniques for the streamlined synthesis of complex natural products.