Combinatorial tetrahydroquinoline

Dihydropyridines such as 56 have recently been reported to undergo Lewis acid-catalyzed multicomponent reactions with anilines and aldehydes to form pyrido-fused tetrahydroquinolines 58 (Equation 2) <2005JC033>. A wide variety of dihydropyridines, aldehydes, and anilines are tolerated, and the reaction proceeds well on numerous solid supports allowing the reaction to be performed combinatorially. 

M., Khadem, S., Leek, D. M., Arya, P. (2006) Part 1. Modular approach to obtaining diverse tetrahydroquinoline-derived polycyclic skeletons for use in high-throughput generation of natural-product-hke chemical probes. Journal of Combinatorial Chemistry, 8, 715-734. 

Polymeric catalysts. A very useful modification of the catalyst is obtained by ligand exchange with a (polyallyl)triflamide, forming polymer-bound scandium triflamide bistriflate. The catalyst has been used in the combinatorial synthesis of a tetrahydroquinoline library from anilines, aldehydes, and alkenes. A related catalyst prepared from ScClj-bHjO and Nafion is effective in several useful synthetic reactions, including allylation, Diels-Alder reaction, and Friedel-Crafts acylation. ... 

The three component condensation employing aldehydes, anilines and electron-rich olefins leading to substituted tetrahydroquinolines 93 constitutes an attractive approach for combinatorial and parallel synthesis (Scheme 3.6.13). 

A powerful tool to synthesize easily minute amounts of organic compounds on demand by using both ionic liquids droplets as microreactors and electrowetting as a fluidic motor has been described. These droplets can be moved, divided and combined on an open digital microfluidic lab-on-a-chip system [60]. This has been demonstrated with BTS ILs used as reaction media and supports, properly functionalized to perform the Grieco s multicomponent synthesis of tetrahydroquinolines (Fig. 5.5-3). It is assumed that this original concept should impact many areas, notably combinatorial chemistry, parallel synthesis, optimization of protocols, synthesis of dangerous products and embedded chemistry in a portable device. 

---