Regiochemistry described

An exception to the regiochemistry described above (R binds to C) is shown in Scheme 6.55 [169]. The imine moiety does not insert into the Pd-alkyl bond but inserts into the Pd-acyl bond and the authors attribute this different behavior to the formation of a strong amide bond in the reaction with the acyl derivative. This thermodynamic driving force and the electrophilic character of the acyl carbon may explain the different regiochemistry observed. 

The term regiochemistry describes which alkene is formed—which region of the molecule reacts. In a few cases, there are no options—dehalogenation of 1,2-dibromides using zinc metal or iodide ion, for example (Figure 10.13). 

Regiochemistry (Section 6.8) A term describing the orientation of a reaction that occurs on an unsymmetrical substrate. 

Tamariz and coworkers [42] have described a versatile, efficient methodology for preparing N-substituted-4,5-dimethylene-2-oxazolidinones 42 (Figure 2.5) from a-diketones and isocyanates and have also studied their reactivity in Diels-Alder reactions. This is a method for synthesizing polycyclic heterocyclic compounds. Some of the reactions of diene 42 are summarized in Scheme 2.18. The nitrogen atom seems to control the regiochemistry of the reaction. 

As we leam addition reactions, we will be using two important terms to describe the regiochemistry Markovnikov and anti-Markovnikov. To use these terms properly, we must be able to recognize which carbon is more snbstituted. Consider the following example ... 

In addition to the regiochemistry, there is also special terminology used to describe the stereochemistry of a reaction. As an example, consider the following simple alkene ... 

Note Do not confnse the term anti with the term anti-Markovnikov. The term anti describes the stereochemistry, while the term anti-Markovnikov describes the regiochemistry. It is possible for an anh-Markovnikov reaction to be a syn addition. In fact, we will see snch an example very soon. 

Note that hydrozirconation of 2-vinylfuran gives only the internal product [86] (Scheme 8-16) which probably is the result of the combination of the effects described in this section (i) O-coordination, (ii) aromatic stabihzation, (iii) reduced steric effect of the flat furan ring, which favors the reverse expected regiochemistry in the hydrozirconation reaction of alkenes with [Cp2Zr(H)Cl] (1). 

The remarkably stable silaallene 133 described recently by West213,214 showed related behavior. Photolysis of 133 is reported to result in the C—H bond addition, across the Si=C bond, of a methyl group on the aromatic ring attached to the carbon end of the silaallene, resulting in the polycyclic compound 134. Alternatively, treatment of the silaallene with acid yields compound 135 by the nominal addition that occurs when one of the C—H bonds of an ortho r-Bu group of the supermesityl group attached to silicon adds to the ends of the Si=C bond with the opposite regiochemistry. 

As an alternative to hydrozirconation of acetylenic tellurides or selenides, Dabdoub and co-workers have more recently described the first additions of the Schwartz reagent (one equivalent) to acetylenic selenide salts 51 (Scheme 4.30) [52]. Subsequent alkylation at selenium produces 1,1-dimetallo intermediates 52, which are cleanly converted in a one-pot process to stereodefined products 53. It is noteworthy that ketene derivatives 52 are of ( )-geometry, the opposite regiochemistry to that which results from hydrozirconation of acetylenic tellurides (vide supra). This new route also avoids the mixtures of regio-isomers observed when seleno ethers are used as educts. The explanation for the stoichiometric use of Cp2Zr(H)Cl in these reactions, in contrast to the requirement for two equivalents with seleno ethers, may be based on cyclic intermediates 54, in which Li—Cl coordination provides an additional driving force. Curiously, attempted hydrozirconation of the corresponding telluride salt 55 under similar conditions was unsuccessful (Scheme 4.31) (Procedure 12, p. 143). 

This chapter describes our studies of electrophilic systems having adjacent, stable cationic centers. We have shown in a wide variety of systems that stable cationic centers (i.e., ammonium, pyridinium, and phosphonium groups) can enhance the reactivities of some electrophiles. This enhanced reactivity is evident by reactions with weak nucleophiles, but may also involve unusual rearrangements or regiochemistry in the conversions. Using this chemistry, reactive dicationic systems can be generated and studied. 

Due to the increased reactivity of the reaction in the presence of a Lewis acid, the reaction scope was extended to singly activated alkenes. Previous results had shown either no reaction or extremely poor yields. However, under the Lewis acid catalyzed conditions, acrylonitrile furnished a 1 1, endo/exo mixture of products. The addition of the catalyst gave unexpected regiochemistry in the reaction, which is analogous with results described in Grigg s metal catalyzed reactions. These observations in the reversal of regio- and stereocontrol of the reactions were rationalized by a reversal of the dominant, interacting frontier orbitals to a LUMO dipole-HOMO dipolarophile combination due to the ylide-catalyst complex. This complex resulted in a further withdrawal of electrons from the azomethine ylide. 

Mander s reagent (221) was also utilized to provide a nitrile CN triple bond as the 71 component for cycloaddition. Addition of Mander s reagent provided a superb yield of a single regioisomer 222. The regiochemistry obtained is consistent with addition of the HOMO of the dipole and the LUMO of the dipolarophile as described by Houk (Scheme 4.58). 

To verify the regiochemistry of the alkylation described above we reduced MFA with borane-methyl sulfide complex to provide 72 in 40% yield [Fig. (21)]. This compound was identical to the one prepared from the catechol 66 and 4-bromo-2-methyl-2-butene (73) using the chemistry reported in step 1 of Fig. (20), thereby conforming the assigned regiochemistry of compounds 68a-d. 

The A-benzenesulfonyl lmines of hexafluoroacetone readily react with nitrile oxides to give [3+2] adducts, apparently in a multistep reaction [ 151] (equation 36) Although only a few examples of [3+2] cycloaddition reactions of this type have been described so far, most 1,3-dipoles should react in this way with predictable regiochemistry [5 146,150 151]... 

As is evident from the resonance structures shown in Equation (1), additions to the parent pyrylium salt would be expected to occur at the 2-, 4-, or 6-positions, and the great bulk of the literature describes reactivity of this general type, although the effects of structure in terms of determining regiochemistry are significant. 

Another problem that occurs with eliminations is the regiochemistry of the reaction. As we saw in Chapter 9, most eliminations follow Zaitsev s rule and produce the more highly substituted alkene as the major product. However, a significant amount of the less highly substituted product is also formed. In addition, mixtures of ds and trans isomers are produced when possible, further complicating the product mixture. Because separating a mixture of such isomers is usually a difficult task, elimination reactions are often not the best way to prepare alkenes. (Other methods will be described in subsequent chapters.) However, if only one product can be formed, or if one is expected to greatly predominate in the reaction mixture, then these elimination reactions can be quite useful. 

These examples show that a synthesis must be carefully planned. The regiochemistry of each step must be considered as well as the compatibility of the substituents already on the ring with the reaction conditions. However, when completed, a cleverly crafted synthesis is a thing of beauty Chemists often describe such a synthesis as elegant. 

In some ways the reactions described in this chapter are simpler than those described in Chapter 11. The stereochemistry of the addition is not a concern here because there is no way to determine whether the addition occurs in a syn or an anti manner. Furthermore, the regiochemistry of these reactions is simple the nucleophile always adds to the carbon of the carbonyl group. 

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