Alkenes stereoselective electrophilic addition

If the carbanion has even a short lifetime, 6 and 7 will assume the most favorable conformation before the attack of W. This is of course the same for both, and when W attacks, the same product will result from each. This will be one of two possible diastereomers, so the reaction will be stereoselective but since the cis and trans isomers do not give rise to different isomers, it will not be stereospecific. Unfortunately, this prediction has not been tested on open-chain alkenes. Except for Michael-type substrates, the stereochemistry of nucleophilic addition to double bonds has been studied only in cyclic systems, where only the cis isomer exists. In these cases, the reaction has been shown to be stereoselective with syn addition reported in some cases and anti addition in others." When the reaction is performed on a Michael-type substrate, C=C—Z, the hydrogen does not arrive at the carbon directly but only through a tautomeric equilibrium. The product naturally assumes the most thermodynamically stable configuration, without relation to the direction of original attack of Y. In one such case (the addition of EtOD and of Me3CSD to tra -MeCH=CHCOOEt) predominant anti addition was found there is evidence that the stereoselectivity here results from the final protonation of the enolate, and not from the initial attack. For obvious reasons, additions to triple bonds cannot be stereospecific. As with electrophilic additions, nucleophilic additions to triple bonds are usually stereoselective and anti, though syn addition and nonstereoselective addition have also been reported. 

The orientation of addition of an unsymmetrical adduct, HY or XY, to an unsymmetrically substituted alkene will be defined by the preferential formation of the more stabilised carbanion, as seen above (cf. preferential formation of the more stabilised carbocation in electrophilic addition, p. 184). There is little evidence available about stereoselectivity in such nucleophilic additions to acyclic alkenes. Nucleophilic addition also occurs with suitable alkynes, generally more readily than with the corresponding alkenes. 

When the same substituents are at each end of the double or triple bond, it is called symmetrical. Unsymmetrical means different substituents are at each end of the double or triple bond. Electrophilic addition of unsymmetrical reagents to unsymmetrical double or triple bonds follows Markovnikov s rule. According to Markovnikov s rule, addition of unsymmetrical reagents, e.g. HX, H2O or ROH, to an unsymmetrical alkene proceeds in a way that the hydrogen atom adds to the carbon that already has the most hydrogen atoms. The reaction is not stereoselective since it proceeds via a planar carbocation intermediate. However, when reaction proceeds via a cyclic carbocation intermediate, it produces regiospecific and stereospecific product (see below). A regioselective reaction is a reaction that can potentially yield two or more constitutional isomers, but actually produces only one isomer. A reaction in which one stereoisomer is formed predominantly is called a stereoselective reaction. 

In the case of electrophilic addition, the reactions of tricyclic dienes 1 with several electrophilic reagents have been investigated.1 7 Interestingly, some of these compounds undergo addition reactions with remarkable syn stereoselectivity. For example, the reaction of dimethyl tricy-clo[4.2.2.02,5]deca-3,9-diene-7,8-dicarboxylate with iodine azide solution, prepared in situ from an excess of sodium azide and iodine monochloride, in acetonitrile at — 5 C provided the. yyn-4-azido-3-iodo derivative 2 (Table 1) in 90% yield.1,2,4,6 The formation of the 5,>,n-4-azido-3-iodo derivative 2 is thought to be the first example of a syn addition of iodine azide to an alkene.1,2 The formation of the syn-product is best explained by the twist strain theory,8 according to which the syn transition structure A is favored over the an/7-coplanar transition structure B.1... 

We have expanded our collection of stereoselective reactions even more in the making of alkenes by the Wittig reaction (chapter 15), from acetylenes (chapter 16), by thermodynamic control in enone synthesis (chapters 18 and 19) and in sigmatropic rearrangements (chapter 35). We have seen that such E- or Z-alkenes can be transformed into three-dimensional stereochemistry by the Diels-Alder reaction (chapter 17), by electrophilic addition (chapters 23 and 30), by carbene insertion (chapter 30) and by cycloadditions to make four-membered rings (chapters 32 and 33). 

Although they really belong in Chapter 17 with other nucleophilic substitution reactions, we included the last few examples of epoxide-opening reactions here because they have many things in common with the reactions of bromonium ions. Now we are going to make the analogy work the other way when we look at the stereochemistry of the reactions of bromonium ions, and hence at the stereoselectivity of electrophilic additions to alkenes. We shall first remind you of an epoxide reaction from Chapter 17, where you saw this. 

Regio- and Stereoselectivity of the Addition Reactions Like proton-induced HAT additions [66-68], additions of carbocations to alkenes proceed with strict regioselectivity, the orientation being determined by the stabilities of the intermediate carbocations (Markovnikov rule). In this respect, carbocation additions differ from other electrophilic additions, as sulfenylations or selenylations, where the orientation is controlled by the nucleophilic attack at the bridged cationic intermediate (Scheme 13) [67, p. 860]. 

For electrophilic additions of halogens to alkenes, not only is the reaction rate strongly solvent-dependent [79-81] [cf. Eq. (5-29) in Section 5.3.2), but the stereochemical course may also be affected by the polarity of the medium [79, 386-388], For example, the stereoselectivity of bromine addition to cis- and trans -stilbene according to Eq. (5-140) has been found to be solvent-dependent, as shown in Table 5-23 [79, 386],... 

In addition to the 1,3-ally lie strain concept, Houk has employed a model for 7t-facial stereoselection of electrophilic additions to chiral alkenes, such as hydroboration, epoxidation, and dihydroxylation, with similar predictive success. ... 

Electron-deficient alkenes (e.g., NCHC=C(COOMe)2) can be aziridinated with 0-(aryl-sulfonyl)hydroxylamines <9lCOS(7)469>. The reaction is believed to involve a Michael addition followed by cyclization with expulsion of a sulfonate anion. Less electrophilic alkenes react in lower yield but with high stereoselectivity (Equation (2)). The chiral catalyst prepared from an optically active bisoxazoline and Cu(I)triflate is effective in promoting the enantioselective aziridination of alkenes <93JA5328>. The addition of nitrosyl chloride to alkenes, which are especially susceptible to... 

The mechanisms of dehalogenations have been reviewed by Miller and in a series of papers , the stereoselectivity of the dehalogenation of the stilbene dibromides with a wide variety of reagents has been discussed. The meso-stilbene dibromide always eliminates to give the thermodynamically more stable alkene, namely tra 5-stilbene which is product of apparent a t/-elimina-tion. However, the J/-stilbene dibromide gives both cis- and rm i-stilbenes, and the ratio of these products can provide useful mechanistic information. One-electron reductants, such as chromous ion, give rise to intermediate radical formation in which rotation about the Ca-Cg bond allows thermodynamic control of the reaction. Two-electron reductants, such as iodide ion in dimethyl formamide, induce highly stereoselective a i-elimination. In protic solvents, carbonium ion intermediates were proposed to explain the trend towards thermodynamic control. Miller has proposed a reaction mechanism which embraces elimination, substitution, and electrophilic addition to alkenes. 

Chamberlin AR, Mullholland RL, Kahn SD, Hehre WJ (1987) Modeling chemical reactivity. 7. The effect of a change in rate-limiting step on the stereoselectivity of electrophilic addition to allyhc alcohols and related chiral alkenes. J Am Chem Soc 109 672... 

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