Small Molecule Catalysts

Important early electrochemical characterizations of nitrosyl adducts of porphyrin complexes were performed by the Kadish group. Voltammetric studies of the nitrosyl adduct of Fe (TPP) demonstrated an electrochemically reversible reduction which was substantially positive to that of the parent Fe (TPP). The product of the reduction, a nitroxyl adduct formulated as Fe (TPP)(NO) , could be generated in situ and its absorbance spectra observed reduction of the dinitro-syl, Fe (TPP)(NO)2, who s formation is characterized by a positive 1/2 shift. Table 4.2, also forms the same product. Nevertheless, attempts to prepare the reduced nitrosyl product via bulk electrolysis were unsuccessful. Up to ten reducing equivalents were passed through a sample solution electrolytically, but the major species in solution remained the ferrous nitrosyl, i.e., the nitroxyl apparently decomposed via some unspecified reaction to regenerate the more stable nitrosyl. 

Electrocatalytic nitric oxide reductions were noted in the previously described studies by Meyer s group on nitrite reduction by water-soluble porphyrins. As NO is a proposed intermediate, it was used independently as a substrate to verify the assigned potential for the ferrous nitfosyl to nitroxyl transformation. Bettelheim et al. also investigated NO reduction by Fe(TMPyP) immobilized onto a GCE with a Nafion coating that repelled anions like nitrite from the electrode surface. Differential pulse voltammetry of this system obtained three distinct reduction waves at potentials ca. 0.5, -0.6, and —0.8 V, assigned using the mechanistic scheme of Meyer to sequential reductions of Ee (NO ), Ee (NO), and Ee (NO ). 

Similarly, Bedioui et al. used Ee(TPPS) immobilized in polyCpyrrole-alkylammonium) films to investigate the reversible reduction of [Ee (NO)] to [Fe (NO )] . They also examined similar reactivity with electropolymer-ized hemin, hematin, Fe(TMPyP), and Fe(TSPP). They found that a polymeric 

In an important series of papers, Ryan and coworkers performed extensive investigations into the effect of the porphyrin structure on the electrochem- 

Further investigation concentrated upon the reduction mechanism of the iron nitrosyl. Ryan et al. found that the electrochemical reduction of Fe(TPP)(NO) was highly reversible and, in the absence of excess NO, leads to a diamagnetic product (Fe(TPP)(NO) ) that they characterized by NMR, UV-Vis, and resonance Raman spectroscopy . The porphyrin vibrations for both Fe(TPP)(NO) and Fe(TPP)(NO) were consistent with low-spin ferrous complexes, thus the reduction is suggested to be ligand-based. Once generated, Fe(TPP)(NO) reacts slowly with proton sources such as phenols to ultimately regenerate Fe(TPP)(NO) in contrast, the two electron reduced product, Fe(TPP)(NO) , reacts rapidly with 

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An interesting case in the perspective of artificial enzymes for enantioselective synthesis is the recently described peptide dendrimer aldolases [36]. These dendrimers utilize the enamine type I aldolase mechanism, which is found in natural aldolases [37] and antibodies [21].These aldolase dendrimers, for example, L2Dl,have multiple N-terminal proline residues as found in catalytic aldolase peptides [38], and display catalytic activity in aqueous medium under conditions where the small molecule catalysts are inactive (Figure 3.8). As most enzyme models, these dendrimers remain very far from natural enzymes in terms ofboth activity and selectivity, and at present should only be considered in the perspective of fundamental studies. 

Galactose oxidase exhibits a surprisingly low specificity for the primary alcohol but is completely regioselective secondary alcohols are not substrates. This re-gioselectivity suggests potential synthetic applications (117) and has raised interest in the design of small molecule catalysts mimicking GO reactivity. 

Perhaps the most viable short-term use for dendritic macromolecules lies in their use as novel catalytic systems since it offers the possibility to combine the activity of small molecule catalysts with the isolation benefits of crosslinked polymeric systems. These potential advantages are intimately connected with the ability to control the number and nature of the surface functional groups. Unlike linear or crosslinked polymers where catalytic sites may be buried within the random coil structure, all the catalytic sites can be precisely located at the chain ends, or periphery, of the dendrimer. This maximizes the activity of each individual catalytic site and leads to activities approaching small molecule systems. However the well defined and monodisperse size of dendrimers permits their easy separation by ultrafiltration and leads to the recovery of catalyst-free products. The first examples of such dendrimer catalysts have recently been reported... 

These catalysts, their structures, modes of action, and uses, are discussed in the rest of the book. Both synthetic small-molecule catalysts as well as some of Nature s finest enzymes are discussed and the role of hydrogen bonding in catalysis is described in detail. 

The small-molecule catalysts are covered in Chapters 5 and 6. In Chapter 5, Joshua Payette and Hisashi Yamamoto discuss the importance of polar Bronsted-acid-type catalysts as well as cooperative effects in hydrogen bonding catalysis. Chapter 6 by Mike Kotke and Peter Schreiner is then devoted to the single most popular small-molecule catalyst types, the thiourea catalysts. Chapter 6, the longest of all chapters, also provides an excellent overview of the history and development of the field of small-molecule hydrogen bond catalysis. 

The asymmetric acylation reaction has proven utility in the synthesis of biologically relevant targets. This is demonstrated by the plethora of applications of lipases and esterases in total syntheses [ 1 ]. While these enzymes often display superb selectivities, their application to a broad class of substrates may be difficult and unpredictable [2]. To increase access to these materials in optically pure form, over the past decade several groups have developed small molecule catalysts for the asymmetric acylation reaction [3,4], In addition, these catalysts... 

The past decade has seen a large increase in the number of small molecule catalysts for asymmetric alcohol acylation. Representative members of virtually all... 

As a contemporary alternative to small molecule catalysts, directed evolution of a lipase to increase the enzyme s selectivity for a desired substrate has been demonstrated. Liebeton K, Zonta A, Schimossek K, Nardini M, Lang K, Dijkstra BW, Reetz MT, Jaeger K-E (2000) Chem Biol 7 709-718... 

Table 14 shows activation parameters of the intramolecular reactions of Michaelis complexes of which the hydrolyses of ABA(7) by poly(ABI-py) and poly(ABI-am) are the same systems as shown in Table 6 (35). Both the polymers and the low molecular weight analogues have the hydrophobic binding properties. The polymer catalysts show smaller AH values by 1 3 kcal MT1 and greater AS values by 6 10 eu, than those of the small molecule catalysts.

In this chapter, a brief overview of small-molecule activation by biological active sites and related small-molecule homogeneous catalysts has been provided. The six primary reactions, outlined in the introduction of this chapter (Section 4.5.1), are all carried out by enzyme active sites with remarkable efficiency and specificity. Importantly, all of the enzymes discussed in the preceding sections utilize readily available base metals in order to activate small molecules. This is a key requirement as we look to the needs and challenges of our energy future, which will require not only efficient catalysts, but also scalable and sustainable catalysts. Here, it is clear that there is a gap between what biology can enable and what has been achieved with small-molecule catalysts. While remarkable transformations have been reported for small-molecule catalysts that use noble metals, the documented examples of... 

Biological reactions are catalyzed by enzymes or ribozymes with efficiencies much greater than obtained from man-made small molecule catalysts. Many different interactions have been characterized that cause the modest rate accelerations for small molecule catalysts. By comparison, enzymes are mammoth catalysts and their size is clearly needed for the construction of an active site that enhances these individual stabilizing interactions and that favors additivity of several interactions. The chemical intuition that produces such generalizations has not led to a commonly accepted explanation for the rate acceleration achieved by any enzyme. Computational chemistry is an important tool which provides insight into important... 

Design of highly functional small-molecule catalysts and related reactions based on acid-base combination chemistry (particularly, synthesis of oxazolines and thiazolines and L-histidine-derived sulfonamide as a minimal artificial acylase for the kinetic resolution of racemic alcohols) 07SL686. 

This chemical guidance greatly reduces the number of possible combinations (but it is stUl in the tens of thousands). Finally, it may be necessary to deposit catalytic materials such as Pt, Pd, Ir, Ru, or Ni [59-61] or small molecule catalysts onto the surface of the electrode if the surface of the semiconductor itself has little catalytic activity. 

The products that were isolated possessed only slightly lower enantiomeric excess than those obtained with the corresponding small molecule catalyst. 

Realizing the high potential of both strong Br0nsted acids and weaker hydrogen bond donors as (chiral or achiral) small-molecule catalysts to activate electrophiles... 

Class II aldolase mimics (Scheme 10.4) were the first small-molecule catalysts that were reported for the direct intermolecular aldol reaction. These catalysts are characterized as bimetallic complexes that contain both Lewis acidic and Brpnsted basic sites. Shibasaki et al. first reported on the use of such a catalyst in the aldol reaction in 1997, demonstrating its potential with the reaction of various acetophenones 52 and aldehydes 53 (Scheme 10.13). Aldols 55 were obtained in good yields and enantioselectivities. A similar approach was used in the direct catalytic asymmetric aldol-Tishchenko reaction.Nevertheless, for the moment, this method does not provide access to true polypropionate fragments. ... 

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