Addition reactions predicting regiochemistry

Markovnikov s rule is used to predict the regiochemistry of HX (electrophilic) addition reactions. The rule states that HX adds to an unsymmetrical alkene mainly in the direction that bonds H to the less substituted alkene carbon and X to the more substituted alkene carbon. 

Predicting the Products, Including Regiochemistry and Stereochemistry, Resulting from Addition Reactions of Alkenes... 

In 1869 Vladimir Markovnikov studied the regiochemistry of a large number of these addition reactions. On the basis of his observations, he postulated an empirical rule that can be used to predict the orientation of additions to alkenes ... 

Calculations have proven invaluable in understanding the many differences between la and lb. In addition, calculations have provided insight into the substituent effects on the ring expansion reactions of derivatives of lb. Finally, calculations have made predictions about the barriers to and regiochemistries of these reactions. Some of these predictions have been verified others await experimental test. 

Presumably, the oxidative cyclization of 3 commences with direct palladation at the a position, forming o-arylpalladium(II) complex 5 in a fashion analogous to a typical electrophilic aromatic substitution (this statement will be useful in predicting the regiochemistry of oxidative additions). Subsequently, in a manner akin to an intramolecular Heck reaction, intermediate 5 undergoes an intramolecular insertion onto the other benzene ring, furnishing 6. (i-Hydride elimination of 6 then results in carbazole 4. 

One general, and as yet unsolved problem, is understanding and predicting the regiochemistry of arylnitrenium ion addition to DNA bases. This reaction is complicated because phenylnitrenium ion has four potential sites of addition (Fig. 13.21) the nitrenium center as well as the ortho and para ring carbons. Likewise, DNA has numerous sites for electrophilic addition. In guanine bases alone, there is a possibility for addition to N7, 06, N2, or C8. 

The reactivity and orientation of nucleophilic attack on fluoroolefins are determined by the stability of the possible carbamon intermediates Fluoroolefins react regioselectively with nucleophiles so as to maximize the number of fluorines (3 to the electron-rich carbon in the transition state The reactivities increase in the order CF2=CF2 < CF2=CFCF3 CF2=C(CF3)2 and CF2=CF2 < CF2=CFC1 < CF2=CFBr, and nucleophdes attack exclusively at the CF2= end of these olefins [129,141] The regiochemistry of nucleophilic attack normally is predictable, but the product distribution arising from addition and addition-elimination pathways depends upon the olefin, nucleophile, and reaction conditions (equations 13-15) The various factors that control product distributions have been reviewed [142,143 144]... 

The effects of the cr—JT interaction on the ground-state properties of allyltrimethylmetal compounds are paralleled by the effect on reactivity towards electrophilic reagents. Mayr demonstrated that allyltrialkylsilanes, allyltrialkyl-germanes, and trialkylstannanes react with diphenylcarbenium ions at rates 105,5.6 x 105, and 109, respectively, relative to propene.158 The reaction rates were also found to be sensitive to the inductive effects of the other substituents attached to the metal. A theoretical evaluation of the factors determining the regiochemistry and stereochemistry of electrophilic addition to allylsilanes and other allyl systems is reported by Hehre et al.159 They predict a preference for electrophilic attack anti with respect to the silane substituent, a prediction that is supported by many experimental studies.82,160... 

Predict the products of additions, oxidations, reductions, and cleavages of alkynes, including the orientation of the reaction (regiochemistry) and the stereochemistry. 

Use radical stabilities to predict the regiochemistry of the radical addition chain reaction of HBr to propene (initiated by AIBN). 

Numerous examples of nucleophilic addition to n hydrocarbyl ligands exist.43 The regiochemistry of these additions to cationic metal complexes has been well studied and summarized by Davies, Green, and Mingos44 (DGM) as a set of rules. These rules can be used to predict where the nucleophile will add to a variety of tt-ligands when the reaction is under kinetic control. A summary of the rules follows. 

Dicyclopentadienyltitanium dichloride is possibly superior to titanium tetrachloride as a catalyst. Nickel(II) compounds are also active, but with these catalysts concurrent addition of the organomagnesium compounds to carbon-carbon multiple bonds causes complications. Examples of hydromagnesation by Grignard reagents are shown in Scheme 3.21. As is apparent from these reactions, addition to alkynes proceeds in syn fashion. The regiochemistry is also usually predictable, one regio-isomer is obtained mainly or exclusively. 

The addition of aldehydes and ketones to alkenes is a convenient high yield reaction for the synthesis of oxetanes. The regiochemistry shown by the addition process can usually be predicted on the basis of the better biradical formed by the addition of the oxygen of the excited carbonyl group to the alkene moiety. Such is the case with the photoaddition of... 

Thus, the regiochemistry of hydroboration is predicted by the same general rule that applies to all electrophilic additions to alkenes The reaction of an electrophile with a carbon-carbon double bond occurs preferentially via the transition state in which a partial positive charge develops on that carbon atom better able to accommodate it. Geometric constraints inherent in the cyclic transition state 60 require that the addition of borane to the alkene proceed so that both the boron and the hydrogen add from the same face of the double bond, a process called sy -addition. 

The nitration of very electron rich aromatic rings is diffusion controlled. Although the reactivity of NO2 is extremely high, these reactions sometimes show good selectivity in their regiochemistry of addition. Propose relative rates for the various steps in a plausible mechanism, and predict which steps are in equilibrium in order to account for the seeming lack of correlation with the reactivity-selectivity principle. 

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