Alkenes regioselective reactions

Dehydrohalogenation of alkyl halides (Sections 5 14-5 16) Strong bases cause a proton and a halide to be lost from adjacent carbons of an alkyl halide to yield an alkene Regioselectivity is in accord with the Zaitsev rule The order of halide reactivity is I > Br > Cl > F A concerted E2 reaction pathway is followed carbocations are not involved and rearrangements do not occur An anti coplanar arrangement of the proton being removed and the halide being lost characterizes the transition state... 

The overall result of the sequence hydroboration -I- oxidation is a regioselective and-Markownikoff-addition of water to an alkene. This reaction is an important method in organic synthesis, since it can be made stereoselective and even enantioselective. 

Regioselective reactions belong to the most important applications of homogeneous catalysis. An example is the hydroformylation of alkenes, which is a very important industrial reaction ... 

Formation of a titanacyclopentane via cyclic dimerization of ethylene was reported as early as 197644 (Scheme 17). In marked contrast with the corresponding Zr-promoted reactions discussed later in this chapter, the intramolecular version of the Ti-promoted alkene-alkene coupling reactions does not appear to have been well developed. Consequently, detailed aspects of pair -selectivity and regioselectivity still remain largely unknown. 

Although a fair number of examples of the Ti-promoted intermolecular alkyne-alkene coupling reactions are known, those that display high pair selectivity and regioselectivity are still relatively limited. Some representative examples are shown in Scheme 18 51 53>53a... 

Addition of (TMS)3SiH to a-chiral ( )-alkene 7 was found to take place with a complete Michael-type regioselectivity (Reaction 5.8) [26]. A complete syn stereoselectivity was observed for R = Me, and it was rationalized in terms of Felkin-Ahn transition state 8, which favours the syn product similar to nucleophilic addition. 

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. 

Asymmetric hydroboration.1 The key step in a synthesis of natural (+ )-hir-sutic add-C (1), based on an earlier synthesis of racemic 1, is an efficient asymmetric hydroboration of the meso-alkene 2. Reaction of 2 with (+ )-diisopinocampheyl-borane (90% ee) followed by oxidation provides the exo-alcohol 3 in 73% yield and in 92% optical purity. Ring expansion of the corresponding ketone with ethyl diazoacetate is not regioselective even in the presence of BF3 etherate or (C2H5)30+ BF4, but does afford the desired a-keto ester in the presence of SbCl5 (8, 500-501). Decarboxylation of the crude product gives (— )-4 in 90% ee after chromatography. 

The problem of selective hydrogenation of one double bond of a nonconjugated diene is essentially the same as that of competitive hydrogenation of alkene mixtures (see Section IV.A. 1). The less substituted double bond of the diene, consequently, can preferentially be hydrogenated under appropriate reaction conditions. The use of nonisomerizing catalysts, in general, is recommended to achieve such regioselective reaction. 

Borane, as a solution in tetrahydrofuran or generated in situ by the reaction of a metal hydride with boron trifluoride etherate, adds readily to alkenes to yield trialkylboranes. With a terminal alkene the reaction is highly (though not completely) regioselective and gives a primary trialkylborane, since the mode of addition results from the electrophilic character of the boron atom. 

Another approach for the ring expansion of epoxides uses low-valent iron complexes which open epoxides under reductive conditions, as reported by Hilt et al. [106]. The iron complexes are reduced and after coordination of the epoxide to the iron center an electron transfer initiates the radical-type ring opening of the epoxide. Under formal insertion of an alkene, regioselective formation of tetrahy-drofurans was observed (Scheme 9.46). The reaction is applicable to a broad range of acceptor-substituted alkenes bearing another double or triple bond system in conjugation with the inserted carbon-carbon double bond. 

The regioselective reaction of /ran.v-2-(/-butyldimethylsilyl)-3-vinyloxirane (13) with primary, secondary, and tertiary butyllithium has proceeded in a S 2 fashion and allowed the formation of a-silylated allylic alcohols with diastereomeric ratios of over (g) 7 1 in favour of the (Z)-alkenes (Scheme ll).72 A study of the effect of temperature, time, addition of salt, and polarity of the solvent on the diastereoselectivity of the reaction has been described. 

Preparatively, it is important that mineral acids, carboxylic acids, and terf-carbenium ions can be added to alkenes via carbenium ion intermediates. Because of their relatively low stability, primary carbenium ions form more slowly in the course of such reactions than the more stable secondary carbenium ions, and these form more slowly than the even more stable tertiary carbenium ions (Hammond postulate ). Therefore, mineral and carboxylic acids add to unsymmetrical alkenes regioselectively to give Markovnikov products (see Section 3.3.3 for an explanation of this term). In addition, these electrophiles add most rapidly to those alkenes from which tertiary carbenium ion intermediates can be derived. 

The hydromagnesiation of acetylenes, catalysed by titano- and zirconocenes is well known. A regioselective reaction occurs only if one of the substituents on the triple bond is silicon or an aryl group. Studies on its mechanism were reported by Sato.2 7 Cai has applied this reaction for the synthesis of a number of polysubstituted alkenes (Scheme p).28-28 -2 ... 

As shown in Scheme 42, selenoxides are crucial intermediates in the selenoxide elimination reactions. These are syn-eliminations which proceed via an intramolecular mechanism to yield alkenes as reaction products. The regioselectivities of these eliminations are dependent on the nature of the substituent Y in the / -position as shown in Scheme 44.286 The mild reaction conditions for these elimination reactions make them highly useful in organic synthesis and theoretical studies on this reaction have been carried out as well.286... 

You will recall from Chapter 31 that we divided phosphorus ylids into two categories, stabilized and un stabilized , in order to explain the stereochemistry of their alkene-forming reactions. Again, there is a similarity with sulfonium ylids the same sort of division is needed—this time to explain the different regioselectivities displayed by different sulfonium ylids. Firstly, an example. 

Chlorohydroxylation of alkenes.1 Anhydrous f-butyl hydroperoxide or di-f-butyl peroxide (1, 211-212) in the presence of TiCl4 effects chlorohydroxylation of alkenes. The reaction shows moderate to high regioselectivity as well as fair to good diastereo-selectivity when the substrate is substituted in the allylic or homoallylic position. Examples ... 

Thus, with electron-rich or electron-poor monosubstituted alkenes, the reaction with tri-fluoroacetonitrile oxide is more regioselective than with benzonitrile oxides. and the oxygen of the nitrile oxide adds to the substituted carbon. With other dipolarophiles, cyeloaddition is less regioselective. Competitive reactions include an electrophilic addition on the nitrile oxide, in particular with 1,1-disubstituted alkenes. and a further cyeloaddition which can occur when the dipolarophile is used in excess. ... 

As before, the reaction is best with monosubstituted alkenes regioselectivity is not high with 1,2-disubstituted alkenes, and the yields are less impressive (eqnation 12). ... 

Electronic effects on alkene regioselectivity in the Pauson-Khand reaction have also been observed. The regioselectivity observed in cycloadditions of norbomen-2-ones has been interpreted as arising from an electronic preference for attachment of the 5 C-S of the alkene to an alkyne carbon rather than cobalt in the bond-forming insertion step (equation 13). In these systems electronic and steric effects have been separated by carrying out identical reactions with the corresponding norbomen-2-ols, in which the... 

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