Orientations transition states

The metalloalkyne complex Ru ( )-CH=CH(CH2)4C CH Cl(CO)(P,Pr3)2 exhibits behavior similar to that of cyclohexylacetylene (Scheme 10).40 Thus, it reacts with OsHCl(CO)(P Pr3)2 to give the hydride-vinylidene derivative (P Pr3)2 (CO)ClRu ( )-CH=CH(CH2)4CH=C OsHCl(CO)(P,Pr3)2, which evolves in toluene into the heterodinuclear-pi-bisalkenyl complex (P Pr3)2(CO)ClRu (is)-CH=CH(CH2)4CH=CH-( ) OsCl(CO)(P,Pr3)2. Kinetic measurements between 303 and 343 K yield first-order rate constants, which afford activation parameters ofAH = 22.1 1.5, kcal-mol-1 andAS = -6.1 2.3 cal-K 1-mol 1. The slightly negative value of the activation entropy suggests that the insertion of the vinylidene ligand into the Os—H bond is an intramolecular process, which occurs by a concerted mechanism with a geometrically highly oriented transition state. 

Reactions.—Carbonyls. Mechanism. Additional evidence is appearing that 1,2-oxaphosphetans are formed directly from ylides and carbonyl compounds. Further studies on the kinetics of the reactions of phenacylidenetriphenyl-phosphoranes with substituted benzaldehydes in non-polar aprotic solvents and in glycols support the concept of a highly oriented transition state of low polarity. n.m.r. spectroscopy on solutions in which ylides and carbonyl compounds had been allowed to react at — 70 °C showed the presence of only... 

A 3D representation (see 356) of transition state 352 is shown for the specific condensation of benzal-dehyde (R = Ph) with the ( )-enolate of 2-butanone (R = r2 = Me). A similar 3D drawing (357) is shown for the opposite orientation (transition state 353). These are crude representations of the transition state, but they show the pseudo-axial and pseudo-equatorial interactions of the phenyl and methyl groups for the condensation of benzaldehyde with the thermodynamic enolate of 2-butanone. Transition states 352 and 353 represent the generalized reaction with a (Z)-enolate with an aldehyde for two different orientations. For the... 

The rate equations for the formation of a number of peroxo-complexes of vana-dium(v), together with the related kinetic parameters, are given in Table 9. The large negative values of AS are ascribed to a highly oriented transition state (linked to the different natures of the c/j-double-bonded oxygens and the rest in the VOa unit)... 

In diethyl ether, the complexed reagent attacks quite slowly and leads via a late, product-orientated transition state to 136 with low selectivity, while the bulky and highly reactive TM E DA (tetramethylethylenediamine) reagent proceeds via an early transition state at the less hindered m-carbonyl, giving rise to 137 [52]. 

Sequences such as the above allow the formulation of rate laws but do not reveal molecular details such as the nature of the transition states involved. Molecular orbital analyses can help, as in Ref. 270 it is expected, for example, that increased strength of the metal—CO bond means decreased C=0 bond strength, which should facilitate process XVIII-55. The complexity of the situation is indicated in Fig. XVIII-24, however, which shows catalytic activity to go through a maximum with increasing heat of chemisorption of CO. Temperature-programmed reaction studies show the presence of more than one kind of site [99,1(K),283], and ESDIAD data show both the location and the orientation of adsorbed CO (on Pt) to vary with coverage [284]. 

Wheland intermediate (see below) as its model for the transition state. In this form it is illustrated by the case mentioned above, that of nitration of the phenyltrimethylammonium ion. For this case the transition state for -nitration is represented by (v) and that for p-substitution by (vi). It is argued that electrostatic repulsions in the former are smaller than in the latter, so that m-nitration is favoured, though it is associated rvith deactivation. Similar descriptions can be given for the gross effects of other substituents upon orientation. 

The model adopted by Ri and Eyring is not now acceptable, but some of the more recent treatments of electrostatic effects are quite close to their method in principle. In dealing with polar substituents some authors have concentrated on the interaction of the substituent with the electrophile whilst others have considered the interaction of the substituent with the charge on the ring in the transition state. An example of the latter method was mentioned above ( 7.2.1), and both will be encountered later ( 9.1.2). They are really attempts to explain the nature of the inductive effect, and an important question which they raise is that of the relative importance of localisation and electrostatic phenomena in determining orientation and state of activation in electrophilic substitutions. 

The electrostatic interaction of the charge on the orienting substituent and the charge on the ring, or the ring positions in the transition state. 

The stereochemical outcome of these reactions can be explained by considering the transition-state geometry. For example, applying the Houk model (495) to akyhc alcohols and their derivatives, the smallest substituent at the preexisting chiral center is oriented "inside" over the face of the transition-state ring and the oxygen atom "outside" (483). 

Enby 6 is an example of a stereospecific elimination reaction of an alkyl halide in which the transition state requires die proton and bromide ion that are lost to be in an anti orientation with respect to each odier. The diastereomeric threo- and e/ytAra-l-bromo-1,2-diphenyl-propanes undergo )3-elimination to produce stereoisomeric products. Enby 7 is an example of a pyrolytic elimination requiring a syn orientation of die proton that is removed and the nitrogen atom of the amine oxide group. The elimination proceeds through a cyclic transition state in which the proton is transferred to die oxygen of die amine oxide group. 

We have previously seen (Scheme 2.9, enby 6), that the dehydrohalogenation of alkyl halides is a stereospecific reaction involving an anti orientation of the proton and the halide leaving group in the transition state. The elimination reaction is also moderately stereoselective (Scheme 2.10, enby 1) in the sense that the more stable of the two alkene isomers is formed preferentially. Both isomers are formed by anti elimination processes, but these processes involve stereochemically distinct hydrogens. Base-catalyzed elimination of 2-iodobutane affords three times as much -2-butene as Z-2-butene. 

Various structural factors have been considered in interpreting this result The most generally satisfactory approach is based on a transition>state model, advanced by Felkin and co-woricers, in which the largest group is oriented perpendiculariy to the carbonyl group. Nucleophilic addition to the carbonyl groi occurs from the opposite side. ... 

STO-3G calculations find the corresponding transition state to be more stable than other possible conformations by several kilocalories per raole. The origin of the preference for this transition-state conformation is believed to be a stabilization of the C=0 LUMO by the a orbital of the perpendicularly oriented substituent. 

Another stereochemical feature of the Diels-Alder reaction is addressed by the Alder rule. The empirical observation is that if two isomeric adducts are possible, the one that has an unsaturated substituent(s) on the alkene oriented toward the newly formed cyclohexene double bond is the preferred product. The two alternative transition states are referred to as the endo and exo transition states ... 

How do orbital symmetry requirements relate to [4tc - - 2tc] and other cycloaddition reactions Let us constmct a correlation diagram for the addition of butadiene and ethylene to give cyclohexene. For concerted addition to occur, the diene must adopt an s-cis conformation. Because the electrons that are involved are the n electrons in both the diene and dienophile, it is expected that the reaction must occur via a face-to-face rather than edge-to-edge orientation. When this orientation of the reacting complex and transition state is adopted, it can be seen that a plane of symmetry perpendicular to the planes of the... 

In 6j5-hydroxy-19-iodo steroids (Figure 12-2) the orientation of the reacting centers O—CH2—I resembles the arrangement in the transition state of an S 2 displacement reaction and consequently the activation energy for the transition (3) (4) is low. It has been suggested that the conformation... 

C-alkylation of secondary and tertiary aromatic amines by hexafluoroacetone or methyl trifluoropyruvate is performed under mild conditions [172] (equation 147) The reaction of phenylhydrazme with hexafluoroacetone leads selectively to the product of the C-hydroxyalkylation at the ortho position of the aromatic ring The change from the para orientation characteristic for anilines is apparently a consequence of a cyclic transition state arising from the initial N hydroxy alky lation at the primary amino group [173] (equation 148)... 

The reactions of pyrrolidinocyelohexenes with acid have also been Considered from a stereochemical point of view. Deuteration of the 2-methylcyclohexanone enamine gave di-2-deuterio-6-methylcyclohexanone under conditions where ds-4-/-butyI-6-methyIpyrrolidinocycIohexene was not deuterated (2J4). This experiment supported the postulate of Williamson (2JS), which called for the axial attack of an electrophile and axial orientation of the 6 substituent on an aminocyclohexene in the transition state of such enamine reactions. These geometric requirements explain the more difficult alkylation of a cyclohexanone enamine on carbon 2, when it is substituted at the 6 position, as compared with the unsubstituted case. 

Destabilization of the ES complex can involve structural strain, desolvation, or electrostatic effects. Destabilization by strain or distortion is usually just a consequence of the fact (noted previously) that the enzyme is designed to bind the transition state more strongly than the substrate. When the substrate binds, the imperfect nature of the fit results in distortion or strain in the substrate, the enzyme, or both. This means that the amino acid residues that make up the active site are oriented to coordinate the transition-state structure precisely, but will interact with the substrate or product less effectively. 

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