Substituted tetrahydroquinolines have attracted considerable attention from organic and medicinal chemists primarily because they display a wide range of pharmacological activities. Therefore, the development of new methodologies for the synthesis of this scaffold continues to be a very attractive field of research.<br/>In an endeavor to design an efficient route to highly substituted tetrahydroquinolines derivatives, herein, we wish to describe an efficient stereoselective protocol based on the organocatalytic conjugate addition followed by an intramolecular isocyanide based multicomponent reaction (MCR). Our strategy combines the stereocontrol nature of the organocatalytic approach with the diversity generating character of the multicomponent reactions.<br/>Therefore, this approach enables the rapid assembly of complex tetrahydroquinolines in good yield and high stereoselectivity over two steps. First, enantioriched hemiacetals are synthetized by an organocatalytic Michael addition. Then, this intermediate is employed in a Ugi-Smiles four-center three-component reaction (UGI-4C-3CR). In addition, shall be mentioned that other Michael donors could also be used - which highlight the versatility of this new protocol.

Diversity-oriented asymmetric synthesis of highly substituted tetrahydroquinoline

ACS Fall 2020 Virtual Meeting

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