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, ...
Asymmetric hydrogenations are among the most practical methods for the synthesis of chiral building blocks at industrial scale. The selective reduction of an oxime to the corresponding chiral hydroxylamine derivative remains a challenging variant because of undesired cleavage of the weak nitrogen-oxygen bond. We report a robust cyclometalated iridium(III) complex bearing a chiral cyclopentadienyl ligand as an efficient catalyst for this reaction operating under highly acidic conditions. Valuable N-alkoxy amines can be accessed at room temperature with nondetected overreduction of the N‒O bond. Catalyst turnover numbers up to 4000 and enantiomeric ratios up to 98:2 are observed. The findings serve as a blueprint for the development of metal-catalyzed enantioselective hydrogenations of challenging substrates.
Ruthenium catalyzed transfer hydrogenation of 2-substituted dienes 1a-1i in the presence of paraformaldehyde results in reductive coupling at the 2-position to furnish products of hydroxymethylation 3a-3i, which embody all carbon quaternary centers. Reductive coupling of diene 1g to paraformaldehyde under standard conditions, but employing either deuterio-paraformaldehyde or d 8 -isopropanol, or both deuterio-paraformaldehyde corroborate a catalytic mechanism involving rapid and reversible diene hydrometallation with incomplete regioselectivity in advance of C-C coupling. These present method provides an alternative to the hydroformylation of conjugated dienes, for which efficient, regioselective catalytic systems remain undeveloped.Hydroformylation is the largest volume application of homogenous metal catalysis and the prototypical C-C bond forming hydrogenation. 1 Whereas alkene hydroformylation is well developed, the hydroformylation of conjugated dienes has proven especially challenging. 2 As part of a broad program aimed at the development of hydrogen-mediated C-C bond formations beyond hydroformylation, 3 one of the present authors reported ruthenium catalyzed reductive couplings of carbonyl compounds to various unsaturates, [4][5][6] NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript feedstock, was investigated. Here, we report that ruthenium catalyzed transfer hydrogenation of 2-substituted dienes in the presence of paraformaldehyde delivers products of reductive C-C coupling in good yield. Remarkably, and in contrast to prior work on diene-carbonyl reductive coupling, 4-8 conditions that promote interconversion of π-allyl A to the isomeric π-allyl B were identified, 9 enabling C-C coupling at the 2-position of the diene to furnish products incorporating all carbon quaternary centers.Initial studies focused on the reductive coupling of myrcene 1a to paraformaldehyde. Upon an assay of our previously disclosed conditions, 4a,b the catalyst prepared in situ from RuHCl(CO) (PPh 3 ) 3 and rac-BINAP was most effective, providing an 18% isolated yield of C-C coupling product. Surprisingly, this product appeared as an equimolar mixture of the anticipated adduct 2a and its regioisomer 3a, wherein coupling occurs at the substituted position of the diene to furnish the all carbon quaternary center. It was postulated that product 3a forms through isomerization of π-allyl isomer A to π-allyl B by way of reversible β-hydride elimination-diene hydrometallation. Based on this hypothesis, ruthenium catalysts that embody greater cationic character were assayed, as coordinative unsaturation should promote β-hydride elimination, potentially accelerating isomerization. Indeed, upon an assay of counterions, it was found that RuH(O 2 CC 7 F 15 )(CO)(dppb)(PPh 3 ), which is prepared in situ from RuH 2 (CO)(PPh 3 ) 3 and HO 2 CC 7 F 15 ,10 provides a 76% isolated yield of C-C coupling product as a 1:4 mixture of isomers 2a and 3a, respectively, in the presence of dppb.It was hypothesized that the ...
The chemoselective reduction of aldehydes and the tandem hydroformylation–hydrogenation of terminal alkenes are possible with a supramolecular catalyst that operates by a novel mechanism involving substrate activation by hydrogen bonding and subsequent metal–ligand bifunctional hydrogenation (see scheme).
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