2 These bidentate organocatalysts preorganize and activate hydrogen-bond accepting substrates, leading to enhanced selectivities and reactivities among a large scope of organic reactions. Especially, bifunctional hydrogen-bond donor amide organocatalysts, such as ureas and squaramides, have attracted considerable attention in this field. Therefore, novel organocatalysts often employ the assembly of catalytic species, connected through multiple hydrogen bonds. Within enzymes, the catalytic activity is often governed by forming hydrogen-bond interactions with the substrate. 1 By creating enzyme-like catalytic sites, chemical transformations can occur with high proficiencies and selectivities. The use of non-covalent organocatalysts has emerged as a powerful catalytic method in asymmetric organic synthesis.
Thus, neither the electronegativity nor the often-suggested polarizability but the steric size of the chalcogen atom determines the amide's hydrogen-bond donor capability. The relative energies of the π* orbitals result from the overlap between the chalcogen np and carbon 2p atomic orbitals, which is set by the carbon-chalcogen equilibrium distance, a consequence of the Pauli repulsion between the two bonded atoms. This originates from the larger electronic density flow from the nitrogen lone pair of the NH 2 group towards the lower-lying π* C=S and π* C=Se orbitals than to the high-lying π* C=O orbital. Our quantum chemical investigations show that the NH 2 groups in thio- and selenoamides are more positively charged than in carboxamides. This phenomenon has been experimentally explored, particularly in organocatalysis, but a sound electronic explanation is lacking. The amino groups of thio- and selenoamides can act as stronger hydrogen-bond donors than of carboxamides, despite the lower electronegativity of S and Se.