Small-molecule H-bond donors in asymmetric catalysis.

Hydrogen bonding is responsible for the structure of much of the world around us. The unusual and complex properties of bulk water, the ability of proteins to fold into stable three-dimensional structures, the fidelity of DNA base pairing, and the binding of ligands to receptors are among the manifestations of this ubiquitous noncovalent interaction. In addition to its primacy as a structural determinant, hydrogen bonding plays a crucial functional role in catalysis. Hydrogen bonding to an electrophile serves to decrease the electron density of this species, activating it toward nucleophilic attack. This principle is employed frequently by Nature's catalysts, enzymes, for the acceleration of a wide range of chemical processes. Recently, organic chemists have begun to appreciate the tremendous potential offered by hydrogen bonding as a mechanism for electrophile activation in small-molecule, synthetic catalyst systems. In particular, chiral hydrogen-bond donors have emerged as a broadly applicable class of catalysts for enantioselective synthesis. This review documents these advances, emphasizing the structural and mechanistic features that contribute to high enantioselectivity in hydrogen-bond-mediated catalytic processes.

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Asymmetric catalysis by chiral hydrogen-bond donors.

Modern synthetic methods have revolutionized polymer chemistry through the development of new and powerful strategies for the controlled synthesis of complex polymer architectures. 1-5 Many of these developments were spawned by new classes of transition metal catalysts for the synthesis of new polyolefin microstructures, 5 the design of highly efficient families of “living” polymerization strategies for the synthesis of block, graft, and star polymers, 6-12 controlled methods for the synthesis of dendritic macromolecules, 3,13,14

Organocatalytic ring-opening polymerization.

The present critical review outlines the close relationship and mutual interplay between molecular recognition, active site considerations in enzyme catalysis involving anions, and organocatalysis utilizing explicit hydrogen bonding. These interconnections are generally not made although, as we demonstrate, they are quite apparent as exemplified with pertinent examples in the field of (thio)urea organocatalysis. Indeed, the concepts of anion binding or binding with negatively (partially) charged heteroatoms is key for designing new organocatalytic transformations. Utilizing anions through recognition with hydrogen-bonding organocatalysts is still in its infancy but bears great potential. In turn, the discovery and mechanistic elucidation of such reactions is likely to improve the understanding of enzyme active sites (108 references).

(Thio)urea organocatalysis—What can be learnt from anion recognition?

We synthesized a new class of bifunctional catalysts bearing a thiourea moiety and an amino group on a chiral scaffold. Among them, thiourea 1e bearing 3,5-bis(trifluoromethyl)benzene and dimethylamino groups was revealed to be highly efficient for the asymmetric Michael reaction of 1,3-dicarbonyl compounds to nitroolefins. Furthermore, we have developed a new synthetic route for (R)-(-)-baclofen and a chiral quaternary carbon center with high enantioselectivity by Michael reaction. In these reactions, we assumed that a thiourea moiety and an amino group of the catalyst activates a nitroolefin and a 1,3-dicarbonyl compound, respectively, to afford the Michael adduct with high enantio- and diastereoselectivity.

Enantio- and Diastereoselective Michael Reaction of 1,3-Dicarbonyl Compounds to Nitroolefins Catalyzed by a Bifunctional Thiourea

Enantioselective aza-Henry reaction catalyzed by a bifunctional organocatalyst.

The aza-Henry reaction of imines with nitroalkanes was promoted by chiral thiourea with an N,N-dimethylamino group to give β-nitroamines with good enantioselectivity. Various N-protected imines were examined as substrates. N-Phosphinoylimine gave the best result in terms of chemical yield and enantioselectivity (up to 91% yield, up to 76% ee).

Satoru Nakamura

Papers

Enantioselective aza-Henry reaction catalyzed by a bifunctional organocatalyst.

Enantioselective Aza‐Henry Reaction Catalyzed by a Bifunctional Organocatalyst.