The role of proton shuttling mechanisms in solvent-free and catalyst-free acetalization reactions of imines.

Proton transfer is central to the understanding of chemical processes. More so in addition reactions of the type NuH + E → Nu-EH taking place under solvent-free and catalyst-free conditions. Herein we show that the addition of alcohols or amines (the NuH component) to imine derivatives (the E component), in 1 : 1 ratio, under solvent-free and catalyst-free conditions, are efficient methods to access N,O and N,N-acetal derivatives. In addition, computational studies reveal that they are catalyzed reactions involving two or even three NuH molecules operating in a cooperative manner as H-bonded NuH(NuH)nNuH associates (many body effects) in the transition state through a concerted proton shuttling mechanism (addition of alcohols) or stepwise proton shuttling mechanism (addition of amines), thereby facilitating the key proton transfer step.

Organocatalysis by Networks of Cooperative Hydrogen Bonds: Enantioselective Direct Mannich Addition to Preformed Arylideneureas.

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.