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

TL;DR

This paper describes a streamlined continuous flow synthesis of jaspine B, a complex natural product, using efficient chemical reactions in microreactors.

Contribution

The novel contribution is the development of a multistep continuous flow system for synthesizing jaspine B with efficient hydrogenation and scalable methods.

Findings

A Pd-catalyzed carbonylation strategy was successfully used in continuous flow for jaspine B synthesis.

Efficient transfer hydrogenation was achieved using formic acid and palladium immobilized on a urea-based polymer support.

A scalable multistep flow system integrated hydrogenation and deprotection steps for complex natural product synthesis.

Abstract

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.

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