The Diels-Alder reaction: doomed to academic praise only?
The Diels-Alder reaction is universally acknowledged for its atom-efficient and simple access to molecular complexity. This textbook example of a green reaction forms one of the most efficient routes towards six-membered rings. However, a large gap is noticed between the relevance and versatility in the academic world, implying a small scale, and industrial use. Obviously, the current developed Diels-Alder procedures are failing to make their way into industry. This perspective paper will gave a critical overview of the most important bottlenecks of Diels-Alder reactions. Flow chemistry, a key research area for green engineering, is a powerful tool to facilitate a safe transfer of Diels Alder processes to the industrial environment.
A unique and powerful chemistry was discovered in 1928,(1) which has been studied vigorously ever since. The Diels-Alder (DA) reaction is a prominent type of pericyclic processes, that is, a reaction that takes place in a single step, without intermediates, via cyclic redistribution of bonding electrons. In this [4+2]cycloaddition, two new σ-bonds are introduced to form a six-membered ring. Typically, a mixture of endo- and exo-isomers is obtained. The endo products, however, are mostly obtained as the major products due to favourable secondary orbital interactions (2).
The DA reaction gained a strong position in organic synthesis at an astonishing speed. The widespread acknowledged utility rests on its broad scope and the ability to form six-membered rings and molecules which are otherwise difficultly accessible, such as bridged bicyclic compounds. However, a large gap is noticed between the relevance and versatility in the academic world, implying a small scale, and industrial use. Obviously, the current developed Diels-Alder procedures are failing to make their way into industry. The insurmountable bar ...