Enzyme-Like Catalysis of the Nazarov Cyclization by Supramolecular Encapsulation

Journal Article · Mon Mar 29 04:00:00 EDT 2010 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/ja102633e· OSTI ID:1013063

Hastings, Courtney; Pluth, Michael; Bergman, Robert; Raymond, Kenneth

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.

• Research Organization: Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (US)
• Sponsoring Organization: Chemical Sciences Division
• DOE Contract Number: AC02-05CH11231
• OSTI ID: 1013063
• Report Number(s): LBNL-3969E
• Journal Information: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 20 Vol. 132; ISSN 0002-7863
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
ACCELERATION
ALCOHOLS
CATALYSIS
CYCLIZATION
DESIGN
ENCAPSULATION
ENZYMES
FUNCTIONALS
STABILIZATION
SUBSTRATES
SYNTHESIS