The Isomerization Mechanism

The isomerization mechanism is clearly established by labeling experiments. The rearrangement of a to c via a 7i-allyl hydride complex b in the coordination sphere of the metal is a key step in this cayalytic cycle (Scheme 54) [174, 175]. hi case of polyunsaturated derivatives, formation of a stable q" complexes (Scheme 55) is preferred over the rearrangement (a c). 

ABSTRACT The acid-catalysed epimerization reaction of bioactive indole alkaloids and their derivatives is reviewed. The three mechanisms, which have been proposed for the (J-carboline-type indole alkaloids, are discussed. Through recent developments, evidence for all three mechanisms has been obtained, which shows the complexity of the epimerization reaction. The epimerization seems to depend on structural features and reaction conditions making it difficult to define one universal mechanism. On the other hand, the isomerization mechanism of oxindole alkaloids has been widely accepted. The acid-catalysed epimerization reaction provides a powerful tool in selectively manipulating the stereochemistry at the epimeric centre and it can also have a marked effect on the pharmacology of any epimerizable compound. Therefore, examples of this reaction in die total synthesis of indole alkaloids are given and pharmacological activities of some C-3 epimeric diastereomers are compared. Finally, literature examples of acid-catalysed epimerization reactions are presented. 

The isomerization mechanism of oxindole alkaloids, in contrast, has never caused confusion. The mechanism, proposed independently by Wenkert and Seaton, has been accepted throughout the literature. 

Some further discussion of the differences in the isomerization mechanisms between the two molybdenum catalysts and the platinum catalysts must be made. A mechanism involving cyclic intermediates has been proposed for a number of catalysts including platinum supported on alumina.27 However, this is unlikely over the molybdenum catalysts which... 

The lipase-catalysed hydrolysis of methyl 2-fluoro-2-arylpropionates was proposed to proceed via a mechanism whereby, after ester hydrolysis, the enzyme facilitates the elimination of fluoride ion with the formation of a carbocation stabilized by the adjacent C02 group.230 Determination of the crystal structure of human sialidase Neu2, an enzyme that catalyses the hydrolysis of sialic acids, reveals a tyrosine residue that is positioned in the active site to stabilize the carbocation proposed as an intermediate in the hydrolysis.231 ll-Fluoro-all-frans-retinol is found to undergo isomerization to its 11 -cis form in the presence of visual cycle enzymes, in contrast to a previous study where no isomerization was reported.232 The result of the prior study was taken as evidence for a carbonium ion pathway in the isomerization. Although the authors of the present study do not rule out such a mechanism, they suggest that the isomerization mechanism remains unknown. Data obtained in a study of the oxidation of... 

The aim of this review is to describe the most interesting results characterizing the skeletal isomerization of n-butenes catalyzed by zeolitic and nonzeolitic molecular sieves and to discuss the state of the art of the isomerization mechanism, the nature and location of the active sites responsible for the selectivity for isobutylene, and the influence of the pore dimensions and pore structures of the molecular sieves. 

Nitrites exist as a mixture of the syn and anti forms, in dynamic equilibrium. The rate of configurational isomerisation in methyl nitrite has been determined by NMR complete line-shape analysis , and the following parameters were derived Ea = 11.1 kcal.mole S A = 2x10 sec (at 237° K) and AS = —3.5 eu (237 °K). The isomerization mechanism is believed to be intramolecular, involving partial delocalization of the N=0 double bond. 

Spectroscopic and isomerization properties are relevant for the isomerization mechanism, a major discussion point on azo compounds. It is not easy, there-... 

Electronic state calculations for azobenzene in early papers suffered from the inability of older methods to take into account the mixing of (n,7t ) and (7t,7C ) states. New calculations using ab-initio methods are successful, even in mastering donor/acceptor substituted azobenzenes. A survey of calculations in connection with the isomerization mechanism will be given in Section 1.6. 

The short pulse duration combined with the high photon density of ps-and fs-lasers have provided the means to study the properties of the excited states by emission and transient absorption measurements. Fluorescence of the lowest and higher excited states of azobenzene can be detected, but most work is being directed toward the dynamics of isomerization. Because questions about the isomerization mechanism are prominent in this field, this work will be discussed in Section 1.6 The Isomerization Mechanism. 

One feature of the data in Table 1.1 is that and < z- e not add up to unity. This is an indication that more than one potential surface is involved in the isomerization mechanism (see Section 1.6). The most unusual fact disclosed in Table 1.1, however, is that the quantum yields are wavelength dependent, is about twice as large for low-energy excitation of the... 

There are, however, azobenzenes that have wavelength-independent isomerization quantum yields and thus obey Kasha s rule. The structure of these molecules inhibits rotation. Rau and Liiddecke investigated azobenzeno-phane 9 and Rau the azobenzene capped crown ether 14, and these researchers found identical E,E —> E,Z, and E —> Z quantum yields respectively, regardless of which state was populated. The photoisomerization of azobenzenophanes and 13 could not be evaluated in the same way because the photoisomerization is intensity-dependent. A series of azobenzenes substituted in all ortho positions to the azo group has equal quantum yields for n —> n and k —> k excitation if the substituents are ethyl, isopropyl, tert.butyl, or phenyl. This provides clues for the elucidation of the isomerization mechanism (Section 1.6). 

Isomerization in the triplet manifold seems to be totally separate from the singlet route. Here also, however, isomerization quantum yields are reported that are dependent on the sensitizer s triplet energy.No implications for the isomerization mechanism have been discussed. 

The general statement of the isomerization mechanism, as given in the opening paragraph of this Section, is accepted at the present time as a mechanism of saccharinic acid formation. However, Nef s concept of the mode of isomerization of the original sugar to the intermediate a-dicarbonyl compound has undergone radical revision. 

It is possible that the isomerization mechanism involves the generation of (dimethoxyphos-phoryl)carbene which reacts with l,3-bis(trifluoro)benzene under thermodynamic control to give the cyclopropane 7. As proof, starting from the kinetic isomer 5, the transient phosphoryl-carbene was trapped by cyclohexane to yield the corresponding C-H insertion product. 

In any event, according to our present conclusion, further developed in this review, most of the isomerization mechanisms involve one single metal atom, the relative contributions of the bond shift and cyclic type reactions being regulated not by the number of surface metal atoms involved, but by... 

As for visual rhodopsins, spectroscopic studies of the protonated Schiff base of all-trans-retinal in solution are important for understanding the isomerization mechanism. We first reported the excited state dynamics of the protonated Schiff base of all-trans-retinal in methanol solution [81], and found that the kinetics is very similar to that of the ll-cis form (Fig. 4.6B). The only difference was that the lifetimes are 1.2-1.4 times longer in the all-trans form than in the ll-cis form [53,81], Slightly faster decay of the ll-cis form may be reflected by their molecular structures, namely the initial steric hindrance between C10-H and C13-CH3 in the ll-cis form (Fig. 4.3) that accelerates the fluorescence decay. Interestingly, it was found that the all-trans-locked 5-membered system, which prohibits both C11=C12 and 03=04 isomerizations, exhibits similar kinetics to those of the all-trans form in solution [82], These results are entirely different from those of the 11-cis-locked 5-membered system, in which the excited-state lifetime is 5-times longer (Fig. 4.6B,C) [53]. This suggests more complex excited-state dynamics for the all-trans form. Observation of the J-like state in protein [70-72] might be correlated with such properties of the protonated Schiff base of the all-trans form. 

This chapter has gathered together the current understanding of retinal photoisomerization in visual and archaeal rhodopsins mainly from the experimental point of view. Extensive studies by means of ultrafast spectroscopy of visual and archaeal rhodopsins have provided an answer to the question, What is the primary reaction in vision We now know that it is isomerization from 11-cis to all-trans form in visual rhodopsins and from all-trans to 13-cis form in archaeal rho-dopsin. Femtosecond spectroscopy of visual and archaeal rhodopsins eventually captured their excited states and, as a consequence, we now know that this unique photochemistry takes place in our eyes and in archaea. Such unique reactions are facilitated in the protein environment, and recent structural determinations have further improved our understanding on the basis of structure. In parallel, vibrational analysis of primary intermediates, such as resonance Raman and infrared spectroscopies, have provided insight into the isomerization mechanism. 

Due to constraints of space, I could not introduce many important theoretical studies here. Various important models have been proposed on the primary isomerization mechanism in rhodopsins, including the bicycle pedal model [101], sudden polarization [102], and the hula-twist model [103]. The finding of a conical intersection between the excited and ground states is also an important contribution [104]. Since the atomic structures of visual and archaeal rhodopsins are now available, theoretical investigations will become more important in the future. The combination of three methods - diffraction, spectroscopy, and theory - will lead to a real understanding of the isomerization mechanism in rhodopsins. 

The isomerization mechanism can be estimated from the structure of the compounds on the basis of the above-mentioned effect of the substituent on the mode of isomerization. Furthermore, the triplet lifetime and the efficiency of isomerization could be estimated for some olefinic compounds. 

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