Overcoming Thermodynamically Driven Retro-Diels-Alder Reaction through a Cascade One-Pot Process Exemplified for a Bio-Based Platform Chemical

In this contribution, we describe a new approach to apply thermodynamically unfavored reactions in synthetic chemistry and to integrate them in cascade processes. By means of a new developed procedure for multi-step one-pot syntheses, we succeeded in nearly completely converting a thermodynamically labile Diels-Alder adduct, which strongly tends to react back, to the target product with high conversion of >99 % and in excellent yield by coupling with a rapid subsequent hydrogenation reaction. In detail, the process is based on the use of a rotating reaction vessel to form a thin product film of the thermodynamically labile Diels-Alder product from 2-methylfuran and maleic acid anhydride (as two bio-based raw materials), which then slowly dissolves into solution and is immediately converted by hydrogenation to the target product. Such a combination of Diels-Alder reaction and hydrogenation in a sequential one-pot process without by-product formation enables the efficient production of the product, which represents a valuable bio-based platform chemical. In addition, this process concept generally opens a perspective for the integration of thermodynamically unfavorable reaction steps in multi-step one-pot cascade processes while obtaining the desired target products in high yields.

Automated summary

In this article, a new approach is described for applying thermodynamically unfavored reactions in synthetic chemistry and integrating them in cascade processes. By using a rotating reaction vessel and a multi-step one-pot synthesis procedure, a thermodynamically labile Diels-Alder adduct was successfully converted to the target product with high conversion and excellent yield. This combination of Diels-Alder reaction and hydrogenation enables efficient production of a valuable bio-based platform chemical and opens new possibilities for integrating thermodynamically unfavorable reactions in multi-step one-pot cascade processes to obtain high yields of desired target products.