Polystyrene-supported chiral Brønsted acids
for the catalytic production of enantiopure compounds in continuous flow
Chiral Brønsted acids are emerging as very powerful and versatile enantioselective organocatalysts. Ureas, thioureas, squaramides and phosphoric acids are, perhaps, the most popular, with many others being developed. Given the good results obtained in solution, some authors have studied their heterogenization with the aim of reusing and recycling these solid-supported catalysts. The most successful ones have led to the implementation of continuous flow processes. These latter cases are highlighted in this article.
ENANTIOSELECTIVE BRØNSTED ACID CATALYSIS
The activation of substrates through interaction with Brønsted acids is a time-honored strategy in catalysis. However, for many years asymmetric catalysis was restricted to Lewis acids bearing chiral ligands (1,2), whereas Brønsted acids were considered as simple proton sources, thus unable to induce any enantioselectivity. This scenario started to change when it was realized that simple H-bond donors were useful in molecular recognition (3). On the basis of these studies, a bridge was established to connect supramolecular chemistry with asymmetric catalysis and several authors reported the use of ureas and thioureas as effective H-bond donors that were able to promote enantioselective reactions (4-12). Other chiral Brønsted acids have followed this path, the most successful ones being probably squaramides (10,13-15) and phosphoric acids (16-23). Nowadays, this field constitutes one of the main pillars of enantioselective organocatalysis, complementing aminocatalysts, which require a carbonyl compound to be engaged in the catalytic process.
It is worth noting that, for the purpose of thi ...