Prediction of stereochemistry

Scheme 4.15 A highly flnt/-selective synthesis of haloallenes and prediction of stereochemistry of haloallenes by optical rotations with revised parameters.

The most successful examples of stereochemical control in electrophilic heteroatom cyclizations are those in which the substitution pattern constrains the substrate so that the two diastereofaces of the tt-system are significantly different. The most straightforward prediction of stereochemistry involves incorporating both the ir-system and the directing chiral center into a ring such that rotation about the vinylic bond that attaches the nucleophile to the double bond is highly restricted. Comparison of equations (1) and (2) illustrates this difference. For this reason, in the sections on cyclizations to form five- and six-membered rings, examples with constrained C=C—C bonds will be discussed separately. 

Dudding T, Houk KN (2004) Computational predictions of stereochemistry in asymmetric thiazolium- and triazolium-catalyzed benzoin condensations. Proc Natl Acad Sci U S A 101 5770-5775 Dwek RA (1996) Glycobiology toward understanding the function of sugars. Glycobiology. Chem Rev 96 683-720... 

The reactions described in this chapter demonstrate the diversity of reactions and products that are formed from reaction of a Grignard reagent with a prochiral or stereogenic center. Prediction of stereochemistry of the products is complicated by the dependence of the reaction parameters, such as nature of the Grignard reagent and substrate temperature, solvent and conditions and the effect of catalysts. 

Maturation of the petro-chemical industry, environmental pressures for "clean chemistry" and the explosive development of biotechnology have increased interest in the application of enzymatic processes to organic synthesis. Enzymatic processes play an increasing role in the generation of chiral pharmaceutical intermediates, water-soluble materials and biopolymers. One problem in the development of enzymatic reactions for organic synthesis is the prediction of the stereochemistry of reaction. Reliable models for prediction of stereochemistry are needed to broaden the application of enzymes to organic synthesis. 

Figure 11. Prediction of stereochemistry of reduction for 2-alkyl cyclohexanones by Jones cubic model. The direction of hydride delivery from NADH is indicated by the...

Formation of six-membered rings is the most common process in cation olefin cyclization. The initial cation is attacked by an olefin following Markovnikov s rule. Defined chairlike conformations in the transition state and the validity of the Stork Eschenmoser postulate9 allows the prediction of stereochemistry in a significant number of the cyclization products. 

Figure 4. Prediction of stereochemistry of boron enolates 9 and 10 using chair-type six-membered transition state based on the Zimmerman model.

Eaeh of the stereoselective reactions that were considered in Section 2.4 are discussed in more detail when the reaction is encountered in subsequent chapters. The key point for the present is that reaction mechanism determines stereochemical outcome. Knowledge about the mechanism allows the prediction of stereochemistry, and eonversely, information about stereochemistty provides insight into the mechanism. As we consider additional reactions, we will explore other examples of the relationships between mechanism and stereochemistry. 

Predictions of stereochemistry of hypothetical products of antarafacial [1,5] hydrogen shift. 

As an aid in the prediction of stereochemistry, organic chemists often use the guideline that diastereomers produce diastCTeomCTs. Replace the starting conpound in each of the two preceding exanples with one of its diastoeomers, and write the product of Sn2 displacement with the nucleophile shown. Are the resulting structures in accord with this rule ... 

The reaction between cyclopentadiene and methyl acrylate (14) catalyzed by BH3 has been studied and the results obtained used to develop a force field applicable to the prediction of stereochemistries of Lewis acid catalyzed reactions of chiral acrylates to dienes. This force field has been used in the study of several reactions involving bulky substituents. 

One attraction of electrocyclic ring closures for use in synthesis is related to fact that they proceed by means of clearly defined mechanisms. In a single step, one can form a ring and control relative or even absolute stereochemistry at multiple sites in a molecule leading to a rapid increase in complexity. Relative stereochemistry is controlled by orbital symmetry rules (Table 19.1), making the prediction of stereochemistry straightforward. The 7t-electron count always refers to the ring-open compound. 

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