Enzyme-Like Catalysis of the Nazarov Cyclization by Supramolecular Encapsulation

• Published in: Journal of the American Chemical Society Vol. 132; no. 20
• Main Authors: Hastings, Courtney, Pluth, Michael, Bergman, Robert, Raymond, Kenneth
• Format: Journal Article
• Language: English
• Published: United States 29.03.2010
• Subjects: 37; ACCELERATION; ALCOHOLS; CATALYSIS; CYCLIZATION; DESIGN; ENCAPSULATION; ENZYMES; FUNCTIONALS; STABILIZATION; SUBSTRATES; SYNTHESIS
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja102633e

A primary goal in the design and synthesis of molecular hosts has been the selective recognition and binding of a variety of guests using non-covalent interactions. Supramolecular catalysis, which is the application of such hosts towards catalysis, has much in common with many enzymatic reactions, chiefly the use of both spatially appropriate binding pockets and precisely oriented functional groups to recognize and activate specific substrate molecules. Although there are now many examples which demonstrate how selective encapsulation in a host cavity can enhance the reactivity of a bound guest, all have failed to reach the degree of increased reactivity typical of enzymes. We now report the catalysis of the Nazarov cyclization by a self-assembled coordination cage, a carbon-carbon bond-forming reaction which proceeds under mild, aqueous conditions. The acceleration in this system is over a million-fold, and represents the first example of supramolecular catalysis that achieves the level of rate enhancement comparable to that observed in several enzymes. We explain the unprecedented degree of rate increase as due to the combination of (a) preorganization of the encapsulated substrate molecule, (b) stabilization of the transition state of the cyclization by constrictive binding, and (c) increase in the basicity of the complexed alcohol functionality.