Stereochemical control mechanisms

Let us recall that the origin of stereospecificity in the syndiospecific polymerisation of styrene lies in a chain end stereochemical control mechanism [52,70]. Key features of the stereoregulation mechanism are stereorigid rf coordination of the growing chain end and diastereoselective rj2 coordination of the styrene... 

Ewen, J.A. Elder, M.J. Jones, R.L. Haspeslagh, L. Atwood, J.L. Bott, S.G. Robinson, K. Metallocene/polypropylene structural relationships implications on polymerization and stereochemical control mechanisms. Macromol. Symp. 1991, 48, 253. 

The carbonyl and methylene regions were best simulated using Bernoullian statistical methods, supporting a chain-end stereochemical control mechanism. 

The sterlc defect shown In the Fischer projection formulae for structure I is a consequence of reversed enantioface selectivity in an enantiomorphic site stereochemical control mechanism. The defective stereochemical placement represents a monomer unit that has been accidentally enchained "backwards . A random distribution of mm defects in an otherwise stereoregular syndiotactic chain is the... 

A model assuming that Cp substituents distal to the bridge experience steric non-bonded contacts with the monomer methyl group, perhaps mediated by the chain end, accounts for the specificity of the chiral metallocenes that produce isotactic, atactic, syndiotactic, hemiisotactic, and random or block cotactic polypropylenes. The tacticities as well as the microstructures of these polymers are accomodated by these simple concepts, the geometry of the metallocene ligands, and by generally accepted fundamental aspects of the polymerization and stereochemical control mechanisms. 

The methods available for synthesis have advanced dramatically in the past half-century. Improvements have been made in selectivity of conditions, versatility of transformations, stereochemical control, and the efficiency of synthetic processes. The range of available reagents has expanded. Many reactions involve compounds of boron, silicon, sulfur, selenium, phosphorus, and tin. Catalysis, particularly by transition metal complexes, has also become a key part of organic synthesis. The mechanisms of catalytic reactions are characterized by catalytic cycles and require an understanding not only of the ultimate bond-forming and bond-breaking steps, but also of the mechanism for regeneration of the active catalytic species and the effect of products, by-products, and other reaction components in the catalytic cycle. 

It is apparent that steric bulk and stereochemical control of mechanism operates in the alkaline hydrolysis of methyl 8-acyl-1-naphthoates. The proximity and favourable orientation of the carbonyl group at the 8-position facilitates intramolecular catalysis from this group. However, the formation of the tetrahedral intermediate at the 8-acyl carbonyl group has distinct... 

Despite the uncertainties of mechanism and of the identity of reactive species, attempts have been made to analyze stereochemical control in asymmetric reductions in terms of a model of the transition state in which steric or other interactions can be assessed. These models could prove useful in suggesting modifications for improving the design of selective reducing agents or for predictive purposes. However, it should be kept in mind that there are only two possible outcomes in the direction of asymmetric induction at a prochiral unit undergoing reaction, and confidence in the predictive usefulness of a given model can only be obtained after a considerable number of examples have been examined. 

Cathodic cyclization reactions have supphed and continue to provide a fertile territory for the development and exploration of new reactions and the determination of reaction mechanism. Two areas that appear to merit additional exploration include the application of existing methodology to the synthesis of natural products, and, more significantly, a systematic assessment of the factors associated with the control of both relative and absolute stereochemistry. Until there is a solid foundation to which the non-electrochemist can confidently turn in evaluating the prospects for stereochemical control, it seems somewhat unlikely that electrochemically-based methods will see widespread use in organic synthesis. Fortunately, this comment can be viewed as a challenge and as a problem simply awaiting creative solution. 

Concerted mechanisms have also been considered to justify the high degree of stereoselectivity observed in many instances as, for example, in the cases shown in Scheme 3 [13,18-21], However, the high stereochemical control often observed in many ODPM rearrangements does not necessary imply that the reaction is taking place via concerted mechanisms. A stepwise process is also consistent with the stereochemical outcome of the reaction, where there are conformational or configurational restrictions to rapid C—C rotation. This subject has been extensively discussed and reviewed by Schuster [16]. 

Analysis of the poly(methyl methacrylate) sequences obtained by anionic polymerization was undertaken at the tetrad level in terms of two different schemes (10) one, a second-order Markov distribution (with four independent conditional probabilities, Pmmr Pmrr, Pmr Prrr) (44), the other, a two-state mechanism proposed by Coleman and Fox (122). In this latter scheme one supposes that the chain end may exist in two (or more) different states, depending on the different solvation of the ion pair, each state exerting a specific stereochemical control. A dynamic equilibrium exists between the different states so that the growing chain shows the effects of one or the other mechanism in successive segments. The deviation of the experimental data from the distribution calculated using either model is, however, very small, below experimental error, and, therefore, it is not possible to make a choice between the two models on the basis of statistical criteria only. 

The key issue for synthesis of pure stereoisomers, in either racemic or enantiomerically pure form, is that the configuration at newly created chiral centers must be controlled in some way. This may be accomplished in several ways. An existing functional group may control the approach of a reagent by coordination. An existing stereocenter may control reactant conformation, and thereby the direction of approach of a reagent. Whatever the detailed mechanism, the synthetic plan must include the means by which the required stereochemical control is to be achieved. When this cannot be done, the price to be paid is a separation of stereoisomers and the resulting reduction in overall yield. 

Type A Mechanism-controlled transformations, in which the stereochemical course is entirely determined by stereoelectronic, i.e., orbital controlled, factors. The transformations proceed with substituent-independent, unambiguous stereochemistry. Ideally, no stereoselection in the sense defined in Section 1. is possible. If the reaction works at all, it will follow the defined, predictable stereochemical pathway. Mechanism-controlled transformations are frequently used in ex-chiral-pool syntheses (see Section 2.2.). 

Cyclobutadienes represent very reactive alkenes that undergo both [2 + 2] as well as [4 + 2] cycloadditions. Both the cyclodimerizations, mixed [2 + 2] cycloadditions and Diels-Alder reactions of these reactive species have been reviewed (see Houben-Weyl, Vols. 4/4, p 231 and E 17 f, Section 10B). In most instances the initially formed cyclodimer is tricyclo[4.2.0.02-5]octa-3,7-diene (36) and has the all cis-syn configuration. This is attributed to the concerted [4n -I- 2n] cycloaddition mechanism in which stereochemical control is affected by secondary orbital interactions. 

Soluble Ziegler-Natta catalysts can exhibit unique stereochemical properties. Group IV metallocenes in combination with methylaluminoxanes produce isotactic polypropylene with two different isotactic microstructures. The usual enantio-morphic site control is characteristic of enantiomeric racemic titano- and zirco-nocene complexes (e.g., ethylene-bridged indenyl derivatives279,349). In contrast, achiral titanocenes (e.g., [Cp2TiPh2]) yield isotactic polypropylene with microstructure 49, which is consistent with a chain end control mechanism 279,349-351... 

Anionic ring-opening polymerization of l,2,3,4-tetramethyl-l,2,3,4-tetraphenylcyclo-tetrasilane is quite effectively initiated by butyllithium or silyl potassium initiators. The process resembles the anionic polymerization of other monomers where solvent effects play an important role. In THF, the reaction takes place very rapidly but mainly cyclic live- and six-membered oligomers are formed. Polymerization is very slow in nonpolar media (toluene, benzene) however, reactions are accelerated by the addition of small amounts of THF or crown ethers. The stereochemical control leading to the formation of syndiotactic, heterotactic or isotactic polymers is poor in all cases. In order to improve the stereoselectivity of the polymerization reaction, more sluggish initiators like silyl cuprates are very effective. A possible reaction mechanism is discussed elsewhere49,52. 

These two synthetic methods have, therefore, the built-in feature which limits them to the synthesis of aldoglycosyl nucleosides having a trans relationship between Cl and C2 substituents. From the practical point of view, however, in any successful synthesis of a D-ribofuranosyl analog of ribonucleosides, the /S configuration of the product is assured. In contrast, where the 2-acyloxy function is absent (as in poly-O-acyl-2-deoxyglycosyl halides), stereochemical controls of the condensation reaction, by the mechanisms involved in the trans rule, are lacking, and both the a and the /3 nucleoside should be formed.219... 

When the stereocontrol occurs by a chain end control mechanism, a stereochemical defect results in the stereochemistry of the defect being propagated along the chain until the next defect occurs (polymer 1 in Fig. 7). If a stereochemical defect occurs in a polymerization using an initiator that exhibits enantiomeric site control, the mistake will be rectified with the next incoming lactide unit (polymer 2 in Fig. 7). This is because it is the chirality of the metal centre which determines the PLA tacticity and not that of the last inserted lactide unit. 

The stereochemical control is achieved via a chain end control mechanism, enforced by the steric bulk of the ligand. The dinuclear complexes cannot control the stereochemistry, leading to atactic PLA, due to the lack of a single, hindered lactide coordination site. 

The effect of ionic liquid solvents on the stereochemical selectivity of allylation of 2-methoxycyclohexanone has been investigated, and found a higher selectivity (axial alcohol 34/equatorial alcohol 35) toward the chelation-controlled mechanism in ionic liquid than in conventional solvents such as water and THF. The use of 0.1 equiv. of indium, combined with Mn and TMSC1 (2 equiv. of each), results in the isolation of the desired products in good purity, with an overall conversion of 81% (Scheme 39).168... 

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