Hydrogen bond donor-acceptor-donor organocatalysis for conjugate addition of benzylidene barbiturates via complementary DAD-ADA hydrogen bonding

A new class of hydrogen bond donor-acceptor-donor (HB-DAD) organocatalysts has been developed for conjugate addition of benzylidene barbiturates. HB-DAD organocatalyst 1a (featuring para-chloro-pyrimidine as the hydrogen bond acceptor (HBA), N-H as the hydrogen bond donor (HBD) and a trifluoroacetyl group as the electron withdrawing group (EWG)) is able to activate benzylidene barbiturates through complementary DAD-ADA hydrogen bonding. Using 1a in benzylidene barbiturate conjugate addition, good yields were achieved. The relative rate constant (krel= 2.9) of 1a in catalyzing the conjugate addition of benzylidene barbiturates and the binding constant (KA= 8936 (±723) M-1) of 1a with benzylidene barbiturates were determined by NMR and UV/Vis. spectroscopy studies. The excellent correlation (R2= 0.97) between the relative rate constant and binding affinity of 1a with benzylidene barbiturates provides support for the importance of DAD-ADA hydrogen bonding in organocatalysis. This journal is