A Supramolecular Catalyst for Regioselective Hydroformylation of Unsaturated Carboxylic Acids

Abstract

Natural enzymes efficiently combine molecular recognition and catalysis in one functional assembly. Reactions within enzyme-substrate complexes have much higher rate constants than corresponding bimolecular reactions.[1] High degrees of regio-and stereoselectivity are achieved by orientation of the substrate and precise positioning of the reaction site in a favorable orientation relative to the catalytic center. Of particular importance for substrate binding by enzymes is the guanidine functional group of arginine. Over 70 % of enzyme substrates and cofactors are anions, and the guanidinium group forms strong ion pairs with oxoanions, such as carboxylates and phosphates.[2] Through multiple noncovalent interactions within the active site, enzymes can achieve astonishing levels of substrate selectivity. This specificity, however, can also be a problem. Very often, enzymes have a narrow substrate specificity and lack the generality required for synthetic applications.Homogeneous catalysis, especially with transition metals, is one of the key tools of modern synthetic chemistry. Traditionally, catalytic performance of an organometallic complex is tuned by variation of the steric bulk and electronic properties of the ligands. However, the emerging field of supramolecular catalysis seeks to produce efficient and selective catalysts by making use of specific molecular interactions and the principles of supramolecular chemistry. [3] Many research groups have attempted to combine noncovalent substrate binding and transition-metal catalysis, thereby aiming at enzymelike behavior. However, only a few examples of successful catalysts showing selectivity and rate enhancement in synthetically useful transformations have been reported to date. [4, 5] An early example came from Hayashi et al., who reported asymmetric hydrogenation of trisubstituted acrylic acids in the presence of a chiral (aminoalkyl)ferrocenylphosphine rhodium catalyst. The high enantioselectivity (greater than 97 % ee) is ascribed mainly to the attractive interaction between the amino group on the ferrocenylphosphine ligand and the carboxyl group of the substrate.[6] Very prominent results were recently achieved in the design of oxidation catalysts. Breslow and co-workers prepared metalloporphyrin catalysts with attached cyclodextrin groups. Steroid derivatives were bound by hydrophobic interactions, and their regioselective hydroxylation was achieved.[7] Crabtree, Brudvig, and co-workers have recently reported a catalyst containing a dinuclear manganese core and a ligand based on Kemps triacid. In this example, the carboxy group of the ligand can interact through hydrogen bonds with the carboxy group of the substrate, leading to specific substrate orientation and modified regioselectivity for oxidation. [8] Reactions that build molecular skeletons belong to the most important in organic synthesis. Hydroformylation of alkenes represents an ideal example of an atom-economic [9] CÀC bond-forming reaction and leads to products containing an aldehyde group, ...

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