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Organocatalysis by Networks of Cooperative Hydrogen Bonds: Enantioselective Direct Mannich Addition to Preformed Arylideneureas
Author(s) -
Lillo Victor J.,
Mansilla Javier,
Saá José M.
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201511555
Subject(s) - organocatalysis , enantioselective synthesis , chemistry , mannich reaction , catalysis , hydrogen bond , non covalent interactions , combinatorial chemistry , cyclohexane , organic chemistry , molecule
Abstract The concept of noncovalent organocatalysis by means of networks of cooperative hydrogen bonds (NCHB organocatalysis) has been explored. Arylideneureas were chosen as ideal substrates because of their powerful donor–acceptor properties. We have examined their uncatalyzed, direct Mannich reaction with acetoacetates in comparison with that catalyzed by a number of salan derivatives capable of providing a network of cooperative hydrogen bonds. Catalyst D [( R , R )‐ N , N ′‐bis(salicyl)cyclohexane‐1,2‐diamine] was found to drive the above direct Mannich reaction in an enantioselective manner, thereby allowing the synthesis of several Biginelli dihydropyrimidinones with high enantioselectivity. DFT calculations (B3LYP‐D‐PCM/6‐31+G*//B3LYP/6‐31+G*) revealed that the NCHB organocatalyst lowers the energy barrier of the reaction. The NCHB organocatalysts appear to function as biomimetic catalysts.