Molecular complexes substrate-catalyst

One of the major difficulties in Forlani s proposal of the molecular complex substrate-catalyst mechanism, to explain the fourth-order kinetics, is the assumption that this complex needs an additional molecule of amine to decompose to products. The formation of molecular complexes between dinitrohalobenzenes and certain amines (especially aromatic amines) has been widely studied, and their involvement in SwAr reaction has been discussed in Section II.E. The equilibrium constants for the formation of those complexes were calculated in several cases, and they were included in the kinetic expressions when pertinent. But in all cases, the complex was assumed to be in the reaction pathway, and no need of an additional amine molecule was invoked by the several authors who studied those reactions. 

That the formation of molecular complexes (especially EDA complexes) can catalyse the decomposition of the cr-adduct has been discussed in Section n.E. Another possibility is that the substrate and catalyst (nucleophile or added base) form a complex which is then attacked by a new molecule of the nucleophile in this context catalysis need no longer be associated with proton removal. Thus, Ryzhakov and collaborators183 have recently shown that the N-oxides of 4-chloropyridine and 4-chloroquinoline act as jt-donors toward tetracyanoethylene and that the reactions of these substrates with pyridine and quinoline are strongly catalysed by the jr-acceptor. Similarly, the formation of a Meisenheimer complex between 1,3,5-trinitrobenzene and l,8-diazabicyclo[5,4,0]undec-7-ene in toluene has been assumed to take place via an association complex to explain the observed second-order in tertiary amine184. 

A new assumption to be discussed in this section is that the fourth-order kinetics in SatAr by amines in aprotic solvents is due to the formation of the substrate-catalyst molecular complex. Since 1982, Forlani and coworkers149 have advocated a model in which the third order in amine is an effect of the substrate-nucleophile interaction on a rapidly established equilibrium preceding the substitution process, as is shown in Scheme 15 for the reaction of 4-fluoro-2,4-dinitrobenzene (FDNB) with aniline (An), where K measures the equilibrium constant for ... 

Forlani and coworkers184 determined that the magnitude of k was found to increase linearly with nucleophile concentration for the reaction of picryl fluoride with 2-hydroxypyridine in chlorobenzene, and k E/k D = 1.5 for mono-deutero-2-hydroxypiridine was observed184. Since isotope effects are usually small in S/yAr in apolar solvents1 the authors attributed the isotope effect to the formation of a substrate-catalyst molecular complex. They obtained a value of k E/kp, D = 1-75 for the ratio of the association constants, hAd- When the substrate was picryl chloride, the slight increase of k with nucleophile concentration was interpreted in terms of Scheme 6 giving a value of K = 2.9 1 identical with that for the fluoro-substrate (3.0 1). 

In some of Forlani s works, such as the reactions of l-halogeno-2,4,6-trinitrobenzene with 2-hydroxypyridine123,125, a substrate-catalyst molecular complex was assumed, but the kinetic law showed the regular second order in amine. Rather interestingly in this scheme, the authors assume that the molecular complex can lead to the formation of products following a second order in nucleophile kinetics, while in the reactions with amines it was presumed that the complex was not on the reaction coordinate, and that an additional molecule of amine was required (the authors needed to include this additional molecule to account for the third order in amine rate law). 

A 3D-structure of the substrate-catalyst complex, which was supported by molecular modeling, revealed that the large group of the imine is directed away from the catalyst. This complex of the catalyst with the Z imine, and a solution structure of the organocatalyst, are shown in Figure 5.1 [12]. This explains the broad substrate tolerance which is independent of steric or electronic properties. A further important hypothesis is that addition of HCN occurs over the diaminocyclohexane framework in 10a this led to the prediction that a more bulky amino acid/amide portion should give a further improved catalyst. This conclusion led to (model-driven) optimization which resulted in the improved and highly enantioselective Strecker catalyst 10b (for preparative results with this catalyst see Scheme 5.8 and related text) [12]. 

In microporous supports or zeolites, catalyst immobilization is possible by steric inclusion or entrapment of the active transition metal complex. As catalyst retention requires the encapsulation of a relatively large complex into cages only accessible through windows of molecular dimensions, the term ship-in-a-bottle has been coined for this methodology. Intrinsically, the size of the window not only determines the retention of the complex, but also limits the substrate size that can be used. The sensitivity to diffusion limitations of zeolite-based catalysis remains unchanged with the ship-in-a-bottle approach. In many cases, complex deformation upon heterogenization may occur. 

The form of the activated complexes [48, 49] is substantially different in homogeneous and heterogeneous reactions. In a homogeneous reaction, the catalyst forms a molecular complex between the substrate that is recognized by its molecular... 

The enantioselective step is the oxidative addition of H2 to the square diastereomeric substrate complexes that are in rapid dissociative equilibrium. The major enantiomer of the product arises from the minor substrate-catalyst diastereomer, this isomer cannot always be detected since it reacts much more rapidly with H2 than the major diastereomer. Molecular modelling suggests that the principal enantiodifferentiating interactions are between the enamide ester function and the nearest arene substituent of the chiral diphosphine.12 The large increase in reaction rate for the minor diastereomer arises from the increased stability of the corresponding dihydro intermediate, that is, the enantioselective step is under product control. 

Hawkins et al. described a simple and efficient catalyst for the Diels-Alder reaction based on a chiral alkyldichloroborane (Eq. 15) [16]. A molecular complex between methyl crotonate and the chiral catalyst have been isolated for the first time. A study of the crystal structure of the complex enabled the authors to propose a model predicting the approach of the diene on one of the faces of the methyl crotonate, because the other face is protected by n-n donor-acceptor interactions. This secondary attractive substrate-catalyst interaction is the basis of the stereocontrol. 

In all cases the catalyst favored the phenyl derivative chemoselectivity was in the 80-90% range. The (3-CD unit selectively incorporates the phenyl ring and this assists the transport of the substrate from the organic into the aqueous phase. Formation of such a host/guest molecular complex keeps the alkene double bond at a suitable distance to interact with the Rh-phosphine catalyst. Both effects increase the rate of hydrogenation of 4-phenyl 1-butene. 

---