Bifunctional Guanidines as Hydrogen-Bond-Donating Catalysts

Abstract

Bicyclic guanidines, bearing 2-aminoquinazolin-4-one and 3-aminobenzothiadiazine-1,1-dioxide core structures, work as bifunctional amine catalysts, due to a double hydrogen-bond-donating ability of two guanidine N-H protons, which are capable of activating both nucleophile and electrophile simultaneously. In fact, these guanidine catalysts revealed to promote several asymmetric reactions such as hydrazination of active methylene compounds with azodicarboxylate and 1,3-proton migration of alkynoates to allenoates as well as the oxa-Michael addition and epoxidation of α,β-unsaturated amides and esters with better chemical yields and higher enantioselectivities than the corresponding thioureas. The catalytic mechanisms of these asymmetric reactions and their synthetic applications for biologically active molecules are also discussed in this chapter.

A Bifunctional N-Heterocyclic Carbene as a Noncovalent Organocatalyst for Enantioselective Aza-Michael Addition Reactions

“…However, the relatively weak basicity of tertiary amines (p K BH + ≈ 10 in DMSO) has limited the HOMO-raising activation to acidic nucleophiles. Bifunctional organocatalysts bearing a stronger basic site, such as amidine, guanidine, cyclopropenimine, and iminophosphorane, have been reported to be effective promoters of reactions involving less reactive nucleophiles . So far, synthetic applications using these strong bifunctional organocatalysts remain limited.…”