Reaction mechanism stereochemistry studies

The study of the stereochemical course of organic reactions often leads to detailed insight into reaction mechanisms. Mechanistic postulates ftequently make distinctive predictions about the stereochemical outcome of the reaction. Throughout the chapters dealing with specific types of reactions, consideration will be given to the stereochemistry of a reaction and its relationship to the reaction mechanism. As an example, the bromination of alkenes can be cited. A very simple mechanism for bromination is given below ... 

The first three chapters discuss fundamental bonding theory, stereochemistry, and conformation, respectively. Chapter 4 discusses the means of study and description of reaction mechanisms. Chapter 9 focuses on aromaticity and aromatic stabilization and can be used at an earlier stage of a course if an instructor desires to do so. The other chapters discuss specific mechanistic types, including nucleophilic substitution, polar additions and eliminations, carbon acids and enolates, carbonyl chemistry, aromatic substitution, concerted reactions, free-radical reactions, and photochemistry. 

Isothermal studies at 370—420 K have been made of the kinetics of decomposition of [Co(NH3)6](N3)3, [Co(NH3)5(N3)](N3)2 and both cis-and frarcs-[Co(NH3)4(N3)2](N3) [1120]. Results are interpreted as indicating the operation of a common reaction mechanism which is not greatly influenced by either the constituents or the stereochemistry of the complex cation. The reactions of all four compounds may yield either CoN or Co(NH3)2(N3)2 as the residual product the alternative decompositions may be represented as... 

However, there is evidence that reactions of aluminium hydride produced in situ involve single-electron-transfer (SET) processesThe reactions described by Trost and Ghadiri have most likely not been studied in sufficient detail to permit an adequate description of the reaction mechanism to be given at this stage. It is, however, quite likely that the Grignard reactions catalyzed by copper(II) and nickel(II) complexes , as developed by julia - and by Masaki , do involve SET processes, although, if this is so, the preservation of stereochemistry in some of the examples described by these workers is quite remarkable. (In this context, the reader s attention is drawn to Reference 196, end of this section.)... 

Mechanistic studies have been designed to determine if the concerted cyclic TS provides a good representation of the reaction. A systematic study of all the E- and Z-decene isomers with maleic anhydride showed that the stereochemistry of the reaction could be accounted for by a concerted cyclic mechanism.19 The reaction is only moderately sensitive to electronic effects or solvent polarity. The p value for reaction of diethyl oxomalonate with a series of 1-arylcyclopentenes is —1.2, which would indicate that there is little charge development in the TS.20 The reaction shows a primary kinetic isotope effect indicative of C—H bond breaking in the rate-determining step.21 There is good agreement between measured isotope effects and those calculated on the basis of TS structure.22 These observations are consistent with a concerted process. 

Optically active sulfonium and selenonium salts are well known and the stereochemistry of the isomers has been studied.1 3 Optically active cyclic diaryl(alkoxy)-sulfonium salts 14, 15, and 16, stabilized by intramolecular sulfur-oxygen interaction, were synthesized in 2000 by reacting optically active spirosulfuranes with trimethyloxonium tetrafluoroborate.29 The absolute configurations were assigned on the basis of the reaction mechanism. The sulfonium salts were hydrolyzed in KHC03aq. to yield optically active sulfoxides in over 86% ee (Scheme 7). 

Applications of C13 NMR have included studies of molecular structure and stereochemistry, reaction mechanisms, and biochemical pathways amino acids, proteins, and nucleotides have been studied. For more on C13 NMR, see J. B. Stothers, Carbon-13 NMR Spectroscopy, Academic Press, 1972 G. C. Levy and G. L. Nelson, Carbon-13 Nuclear Magnetic Resonance for Organic Chemists, Wiley-Interscience, 1972. 

Although kinetic studies of bromination of methyl ( )-cinnamic acid and methyl (E)-fS-styrylphosphonate suggest analogous mechanisms for both reactions, the stereochemistry of the reactions indicates that product-forming steps of different character must be involved157. 

The quantitative prediction of the stereochemistry of a chemical reaction by strain energies requires knowledge of the reaction mechanism, i.e., the selective intermediates and/or transition states involved, and an accurate force field for the transient species. As discussed above, these are two demanding problems and so far there are no reports of studies in this area that have used molecular mechanics for quantitative predictions at the same level of accuracy as for conformational analyses. The application of empirical force field calculations to the design of asymmetric transformations clearly is a worthy task, and some examples of studies in this area have been discussed above. On the basis of two examples we will now discuss some general aspects highlighting the limitations of the qualitative considerations emerging horn molecular mechanics calculations for the interpretation and support of assumed reaction pathways. 

A stereochemical study of the synthesis of unsaturated 1,4-aminoalcohols via the reaction of unsaturated 1,4-alkoxyalcohols with chorosulfonyl isocyanate revealed a competition between an retentive mechanism and an SnI racemization mechanism, with the latter having a greater proportion with systems where the carbocation intermediate is more stable.254 An interrupted Nazarov reaction was observed, in which a nonconjugated alkene held near the dienone nucleus undergoes intramolecular trapping of the Nazarov cyclopentenyl cation intermediate.255 Cholesterol couples to 6-chloropurine under the conditions of the Mitsunobu reaction the stereochemistry and structural diversity of the products indicate that a homoallylic carbocation derived from cholesterol is the key intermediate.256 l-Siloxy-l,5-diynes undergo a Brpnsted acid-promoted 5-endo-dig cyclization with a ketenium ion and a vinyl cation proposed as intermediates.257... 

Thus, with compounds of type (a), the stereochemistry of substitution, insertion, and cleavage reactions can be studied (8, II), whereas with compounds of type (b), the mechanism of racemization and epimerization at the chiral metal atom can be investigated (II, 92). In the following sections, representative examples of both types of study will be given, from which it will become evident how optically active labels at metal centers in organo-transition-metal compounds contribute to the elucidation of the stereochemical course of reactions. 

In modern stereochemistry asymmetric reactions1-24 play an increasing role in the solution of problems involving chiral chemical compounds and in their preparation. Asymmetric reactions are useful in elucidating the structural features of chiral molecules and in the study of reaction mechanisms, including those of biochemical reactions. Their importance is further emphasized by the realization that all naturally occurring chiral chemical compounds stem from asymmetric syntheses. 

Thiazolylium and benzothiazolylium salts react normally with aqueous sodium borohy-dride yielding the corresponding thiazolidine or benzothiazoline. The mechanism and the stereochemistry of the reaction have been studied with thiazolylium salts chosen as models for thiamine, using borodeuteride/hydride and deuterium/protium oxide. The pathway described in Scheme 30 was suggested it involves the addition of a nucleophilic hydride at C-2 (50 -> 51), the addition of an electrophilic proton at C-5 (51 -> 52) and the addition of a second nucleophilic hydride at C-4 (52 — 53). 

Discussions and studies of reaction mechanisms attempt to analyse the way in which a compound A is transformed into a compound B. Varying degrees of sophistication are attached to the phrase reaction mechanism but the aim is generally to define the reaction in terms of elementary steps and stereochemistry. In solution chemistry, the structures of compounds A and B will be known and mechanistic information may be deduced from kinetic studies, solvent effects, stereochemistry, isotopic labelling, and other slight structural modifications. 

The stereochemistry of SO2 insertion into Fe, Mn, and W compounds has been investigated by several groups and shown to be in complete accord with the above mechanism. These studies have shown conclusively by NMR, CD, and X-ray methods that, in the cases studied, the SO2 insertion reaction proceeds with high stereospedfidty at both the metal (retention) and at carbon (inversion) 5i-i54) fo,- these systems... 

Another characteristic of modem coordination chemistry is the increasing reliance upon physicochemical methods unknown to Werner and his contemporaries. Simultaneously with an introduction of these newer techniques, emphasis shifted from preoccupation with qualitative studies of stmcture and stereochemistry to quantitative studies of thermodynamics, kinetics, and reaction mechanisms. Some areas of current research interest include unusual ligands, oxidation states and coordination numbers, solid-state chemistry, photochemistry, relationship between stmcture and reactivity, variable oxidation state, chelates, heteropoly complexes, organometalhc... 

The point has been made that the conditions of p-chloroethanol formation are not the same as used for the Wacker oxidation. Cu Pd chlorine-bridged dimers are likely reactants under higher [Cl ] reaction conditions, which may lead to a different reaction mechanism. However, a second stereochemical study also obtained results consistent with trans hydroxypaUadation. When cfr-l,2-dideuteroethene is oxidized in water with PdCl2 under a CO atmosphere, the product is tran5 -2,3-dideutero-jS-propiolactone (Scheme 37). The reaction conditions were, once again, not identical with standard Wacker process conditions, since the solvent was acetonitrile water, the temperature was —25°C, the bis-ethene PdCl2 complex was used, and there was no excess Cl present. Nevertheless, it is clear that, under many reaction conditions, a trans addition of water onto ethene coordinated to Pd is the favored reaction stereochemistry. 

These observations have led to the development of a trajectory-based model to rationalize the selectivity of the monooxygenase enzyme in Beauveria sulfurescens, and this may allow the regio- and stereochemistry of transformations on new (related) substrates to be predicted. Also of some assistance in predicting the stereochemical outcome of the reactions is the study of the mechanism, and this has been investigated and shown, at least in some cases, to proceed with inversion of stereochemistry. ... 

The mechanism of the reaction has been studied in basic, acidic, and neutral media. In basic medium, the reaction is a substitution of 87 2 type, the mechanism and stereochemistry of which have been reasonably well clarified. In asymmetric oxiranes, the attack by the nucleophile generally takes place with inversion on the less-substituted carbon atom (Eq. 297). 

This paper calls attention to the need for new ions in coordination chemistry—ions that would permit more detailed physico-chemical studies to be made, ions that would facilitate studies of less familiar metals and of less familiar coordination numbers, and ions that would help studies of chemical bonding and reaction mechanisms. Organometallic ions of the type RmM+ are such ions, and these form metal-chelate compounds of the type RmM Ch) . Three aspects of the chemistry of organometallic-chelate compounds are described (1) equilibria of compound formation ( ) kinetic and mechanistic studies of three types of reactions (a) reactions of the coordinated ligand, (b) substitution at the 4-, 5-, or 6-coordinate metal atom, and (c) reactions of the organic moiety and (3) studies of stereochemistry and chemical bonding. 

As noted earlier, the substitution of organometallic ions or pseudometal ions for a central metal ion has applications which are of interest to the physical-inorganic chemist. These applications are best indicated by looking at examples from three representative areas (1) the equilibria of complex formation (2) studies of reaction mechanisms and (3) problems of stereochemistry and chemical bonding. 

The stereochemistry of reactions is controlled by conformational and configurational stabilities of intermediate species in the transition state. Therefore, the stereochemical course of reactions must be discussed on the basis of the interemdiates and reaction mechanism that have been presumably clarified by electrochemically and organic chemically reasonable ways. However, on the contrary, it is also likely that a stereochemical result makes the mechanism more clear. In this sense, a stereochemical study can be useful as one method for analyzing the mechanism. 

Then we shall examine the stereochemistry of several reactions we have already studied—free-radical halogenation of alkanes, and electrophilic addition of halogens to alkenes- and see how stereochemistry can be used to get information about reaction mechanisms. In doing this, we shall take up ... 

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