Electrophilic addition regioselectivity

HOMe/H + i i "TT MeO H Electrophilic addition (regioselective inter alia)... 

The regioselectivity of electrophilic addition is governed by the ability of an aro matic ring to stabilize an adjacent carbocation This is clearly seen m the addition of hydrogen chloride to mdene Only a single chloride is formed... 

Section 11 16 Addition reactions to alkenylbenzenes occur at the double bond of the alkenyl substituent and the regioselectivity of electrophilic addition is governed by carbocation formation at the benzylic carbon See Table 11 2... 

Electrophilic addition (Section 11 16) An aryl group stabilizes a benzylic carbocation and con trols the regioselectivity of addition to a double bond involving the benzylic carbon Markovni kov s rule is obeyed... 

The effects of a- vs. P-fluonnation imply that fluoroolefms normally react regioselectively with electrophiles to minimize the number of fluorines p to the electron-deficient carbon in the transition state. Diverse types of electrophilic additions follow this rule (equations 6-8, for example), although there aie exceptions, especially for ionic addiPons of halomethanes to fluoroolefins [124]... 

In general, alkyl substituents increase the reactivity of a double bond toward electrophilic addition. Alkyl groups are electron-releasing, and the more electron-rich a double bond, the better it can share its tt electrons with an electrophile. Along with the observed regioselectivity of addition, this supports the idea that carbocation fonrration, rather than carbocation capture, is rate-detenrrining. 

The regioselectivity of addition of HBr to alkenes under nonnal (electrophilic addition) conditions is controlled by the tendency of a proton to add to the double bond so as to produce the more stable carbocation. Under free-radical conditions the regioselectivity is governed by addition of a bromine atom to give the more stable alkyl radical. 

Scheme 11 Opposite regioselectivities of the electrophilic additions to enam-ines and their onium ions...

A more complete discussion of the mechanism of addition of hydrogen halides to alkenes is given in Chapter 6 of Part A. In particular, the question of whether or not discrete carbocations are involved is considered there. Even when a carbocation is not involved, the regioselectivity of electrophilic addition is the result of attack of the electrophile at the more electron-rich carbon of the double bond. Alkyl substituents increase the electron density of the terminal carbon by hyperconjugation (see Part A, Section 1.1.8). 

The regioselectivity and stereoselectivity of electrophilic additions to 2-benzyl-3-azabicyclo[2.2.1]hept-5-en-3-one are quite dependent on the specific electrophile. Discuss the factors that could influence the differing selectivity patterns that are observed. 

The addition of hydrogen halide to alkene is another classical electrophilic addition of alkene. Although normally such reactions are carried out under anhydrous conditions, occasionally aqueous conditions have been used.25 However, some difference in regioselectivity (Markovnikov and anti-Markovnikov addition) was observed. The addition product formed in an organic solvent with dry HBr gives exclusively the 1-Br derivative whereas with aq. HBr, 2-Br derivative is formed. The difference in the products formed by the two methods is believed to be due primarily to the difference in the solvents and not to the presence of any peroxide in the olefin.26... 

When the pyrrolo[l,2-c]oxazole 269 was treated with trimethyl orthoformate in the presence of BF3 Et20, in dichloromethane at — 78 °C, a mixture of compounds was obtained from which the expected 5-dimethoxymethyl derivative, 270, was isolated in poor yield (12%) with another dimethoxylated compound 271 (23%). The formation of 271 could be explained by the addition of the formyl cation equivalent at C-7, followed by the protonation at C-6 of the resulting enamide 272 leading to the electrophilic iV-acyliminium ion 273 (Scheme 40). The regioselectivity of this electrophilic addition of trimethylorthoformate to the silyloxypyrrole 269 at C-7, in a non-vinylogous manner, is unusual <1999TL2525>. 

As already commented in the introduction of this chapter, regardless of its substitution pattern, the main trends of allenylidene reactivity are governed by the electron deficient character of the C and Cy carbon atoms of the cumulenic chain, the Cp being a nucleophilic center [9-15]. Thus, as occurs with their allcarbon substituted counterparts, electrophilic additions on 7i-donor-substituted allenylidene complexes are expected to take place selectively at Cp, while nucleophiles can add to both C and Cy atoms. However, the extensive 71-conjugation present in these molecules results in a reduced reactivity of the cumulenic chain and, in some cases, in marked differences in the regioselectivity of the nucleophilic additions when compared to the all-carbon substituted allenylidenes. In the following subsections updated reactivity studies on 7i-donor-substituted allenylidene complexes are presented by Periodic Group. 

In contrast, electrophilic additions to the double bond of acetal 70 (derived from 64 ) gave adduct mixtures 71/72 with regioselectivities opposite to those of reactions 64 + EX — 68 + 69, 72 being the major adducts. Tests were carried out to confirm that adducts 68 + 69 and 71+72 were formed under conditions of kinetic control. Acetal 70 was obtained optically pure via resolution of lactol 73 by medium pressure chromatographic (silica gel) separation of the diastereomeric acetals 74 derived from (-)-menthol. ... 

The synthesis and chemistry of metal complexes of thiophenes have been reported including the electrophilic additions to osmium-thiophene complexes <9902988> and nucleophilic additions to ruthenium-thiophene complexes <99JOMC242>. The selectivity for the insertion of ruthenium into 3-substituted thiophenes was studied <99CC1793>. For example, treatment of 3-acetylthiophene (84) with Ru(cod)(cot) led to a regioselective 1,2-insertion of ruthenium giving thiaruthenacycle 85. 

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. 

Electrophilic addition to terminal alkynes (unsymmetrical) is regioselective and follows Markovnikov s rule. Hydrogen halides can be added to alkynes just like alkenes, to form first the vinyl halide, and then the geminal alkyl dihalide. The addition of HX to an alkyne can be stopped after the first... 

The normal course of reaction of alkenes involves addition of Lewis acids (electrophiles) yielding an intermediate carbocation which is trapped by a weak nucleophile [114]. The most common electrophilic addition reactions are summarized in Ligure 6.1. If the olefin is unsymmetrically substituted, the question of regioselectivity arises. We begin by examining the effects on the olefin n system of three classes of substituents as... 

---