Acid catalyzed, addition to alkenes

Now consider how we might make the carbonyl addition reaction easier.Two ways seem possible— we could make either the electrophile or the nucleophile stronger. Let s start with the acid-catalyzed reaction in which the carbonyl group is converted into a stronger electrophile. If we take as our model for the mechanism the acid-catalyzed additions to alkenes, a reasonable first step for hydration of a carbonyl would be protonation. But which end is protonated Again, there are two possiblities (Fig. 16.24). 

Additions of Si-H bonds to alkynes occur under similar conditions and with the same catalysts as hydrosilation of alkenes. Free radical addition to terminal alkynes gives cis products by a stereospecific terminal trans addition . Supported platinum catalysts give trans products by a terminal cis addition . Chloroplatinic acid catalyzed additions to terminal alkynes give mixtures of trans-1-alkenylsilanes and trans-2-alkenylsilanes in a ratio ranging from 1 1 to 1 5 depending on the substituents on silicon . Addition of SiH2Cl2 to CH2=CHC(CH3)3 gives trans-1-alkenyl- and bis(trans-l-alkenyl)silane products, but no (2-alkenyl)silane °. Internal alkynes react more slowly than terminal alkynes, and even reactions catalyzed by chloroplatinic acid require heat. 

Oxazines can also be synthesized by intramolecular addition of oximes to carbon-carbon double bonds. These reactions are not general nitrones and other products can be formed in competition with oxazines. There are examples of conjugate addition to activated alkenes <81TL2557, 91CPB2830> and of acid or Lewis acid-catalyzed addition to simple alkenes <88TL6805> or allenes <89JCS(P1)2415>. 3-Methyl-6-vinyl-5,6-dihydro-4//-1,2-oxazine was isolated in moderate yield from... 

Lewis Acid-catalyzed Addition to Epoxides. The Lewis acid-catalyzed addition of l,3-bis(silyl)propenes to epoxides has been studied for both inter- and intramolecular reactions. In the inter-molecular reaction, monosubstituted epoxides give higher yields (66-53%) than bis-substituted epoxides (33-19%) (eq 5). It is proposed that the epoxide opens in a Sn 1 fashion, followed by nucleophilic attack of the bis(silyl)propene on the resultant cation. This leads to a silicon-stabilized carbocation, which undergoes C O silyl migration 3uelding the final alkene. 

Acid catalyzed addition of alcohols to alkenes is sometimes used Indeed before Its use as a gasoline additive was curtailed billions of pounds of tert butyl methyl ether (MTBE) was prepared by the reaction... 

The formation of alcohols by acid-catalyzed addition of water to alkenes is a fundamental organic reaction. At the most rudimentary mechanistic level, it can be viewed as involving a carbocation intermediate. The alkene is protonated, and the carbocation is then captured by water. 

For those substrates more susceptible to nucleophilic attack (e.g., polyhalo alkenes and alkenes of the type C=C—Z), it is better to carry out the reaction in basic solution, where the attacking species is RO . The reactions with C=C—Z are of the Michael type, and OR goes to the side away from the Z. Since triple bonds are more susceptible to nucleophilic attack than double bonds, it might be expected that bases would catalyze addition to triple bonds particularly well. This is the case, and enol ethers and acetals can be produced by this reaction. Because enol ethers are more susceptible than triple bonds to electrophilic attack, the addition of alcohols to enol ethers can also be catalyzed by acids. " One utilization of this reaction involves the compound dihydropyran... 

Triple bonds can be monohydroborated to give vinylic boranes, which can be reduced with carboxylic acids to cis alkenes or oxidized and hydrolyzed to aldehydes or ketones. Terminal alkynes give aldehydes by this method, in contrast to the mercuric or acid-catalyzed addition of water discussed at 15-4. However, terminal alkynes give vinylic boranes (and hence aldehydes) only when treated with a hindered borane such as 47, 48, or catecholborane (p. 798)," or with BHBr2—SMe2. The reaction between terminal alkynes and BH3 produces 1,1-... 

An important cyclization procedure involves acid-catalyzed addition of diene-ketones such as 58, where one conjugated alkene adds to the other conjugated alkene to form cyclopentenones (59). This is called the Nazarov cyclization Cyclization can also give the nonconjugated five-membered ring. ... 

Although the reaction of ketones and other carbonyl compounds with electrophiles such as bromine leads to substitution rather than addition, the mechanism of the reaction is closely related to electrophilic additions to alkenes. An enol, enolate, or enolate equivalent derived from the carbonyl compound is the nucleophile, and the electrophilic attack by the halogen is analogous to that on alkenes. The reaction is completed by restoration of the carbonyl bond, rather than by addition of a nucleophile. The acid- and base-catalyzed halogenation of ketones, which is discussed briefly in Section 6.4 of Part A, provide the most-studied examples of the reaction from a mechanistic perspective. 

There are, however, serious problems that must be overcome in the application of this reaction to synthesis. The product is a new carbocation that can react further. Repetitive addition to alkene molecules leads to polymerization. Indeed, this is the mechanism of acid-catalyzed polymerization of alkenes. There is also the possibility of rearrangement. A key requirement for adapting the reaction of carbocations with alkenes to the synthesis of small molecules is control of the reactivity of the newly formed carbocation intermediate. Synthetically useful carbocation-alkene reactions require a suitable termination step. We have already encountered one successful strategy in the reaction of alkenyl and allylic silanes and stannanes with electrophilic carbon (see Chapter 9). In those reactions, the silyl or stannyl substituent is eliminated and a stable alkene is formed. The increased reactivity of the silyl- and stannyl-substituted alkenes is also favorable to the synthetic utility of carbocation-alkene reactions because the reactants are more nucleophilic than the product alkenes. 

The acid-catalyzed addition of water to the double bond of an alkene is a method for the preparation of low molecular weight alcohols that has its greatest utility in large-scale industrial processes. 

A formal asymmetric nucleophilic addition to carbonyl compounds is achieved by Trost and his co-workers in the allylic alkylation of acylals of alkenals. An excellent enantioselectivity is observed in this alkylation. The starting acylals are easily prepared by the Lewis-acid catalyzed addition of acid anhydrides to aldehydes, by use of Trost s ligand 118 (Scheme 13), where various carbon-centered nucleophiles are available (Scheme l4),101,101a-10lc Asymmetric synthesis of some natural products is achieved according to this procedure. 

Table 15. Lewis Acid Catalyzed Addition of Anhydrous Hydrogen Fluoride to Alkenes...

Addition to alkenes,2 The reagent (1) adds to unhindered alkenes to form anti-Markownikoff adducts the same reaction catalyzed by BF3 ethcrate gives the Markownikoff adduct. The products on oxidation with m-chloroperbenzoic acid give vinyl sulfones. 

The scope and limitations of the Lewis acid-catalyzed additions of alkyl chlorides to carbon-carbon double bonds were studied.51 Since Lewis acid systems are well-known initiators in carbocationic polymerizations of alkenes, the question arises as to what factors govern the two transformations. The prediction was that alkylation products are expected if the starting halides dissociate more rapidly than the addition products.55 In other words, addition is expected if the initial carbocation is better stabilized than the one formed from the dissociation of the addition product. This has been verified for the alkylation of a range of alkyl-and aryl-substituted alkenes and dienes with alkyl and aralkyl halides. Steric effects, however, must also be taken into account in certain cases, such as in the reactions of trityl chloride.51... 

Cationic polymerization of alkenes involves the formation of a reactive carbo-cationic species capable of inducing chain growth (propagation). The idea of the involvement of carbocations as intermediates in cationic polymerization was developed by Whitmore.5 Mechanistically, acid-catalyzed polymerization of alkenes can be considered in the context of electrophilic addition to the carbon-carbon double bond. Sufficient nucleophilicity and polarity of the alkene is necessary in its interaction with the initiating cationic species. The reactivity of alkenes in acid-catalyzed polymerization corresponds to the relative stability of the intermediate carbocations (tertiary > secondary > primary). Ethylene and propylene, consequently, are difficult to polymerize under acidic conditions. 

In a manner analogous to the acid-catalyzed addition of hydrogen peroxide, dialkyl peroxides are formed by the addition of alkyl hydroperoxides to alkenes (equation 23S).366... 

The peroxymercuration-demercuration of alkenes provides a more versatile approach to the corresponding hydroperoxides or dialkyl peroxides than direct acid-catalyzed addition (equation 239).372 374... 

Addition of Water Alkenes don t react with pure water, but in the presence of a strong acid catalyst such as sulfuric acid, a hydration reaction takes place to yield an alcohol. An -H from water adds to one carbon, and an -OH adds to the other. For example, nearly 300 million gallons of ethyl alcohol (ethanol) are produced each year in the United States by the acid-catalyzed addition of water to ethylene ... 

SE.3.1.2. Desymmetrization of gem-Dwarboxylates An equivalent of asymmetric carbonyl addition can be achieved by the alkylation of gem-dicarboxylates (Scheme 8E.17). The alkylation of gem-dicarboxylates, which are easily prepared by the Lewis acid-catalyzed addition of acid anhydrides to an aldehyde, converts the problem of differentiating the two enantiotopic 7t-faces of a carbonyl group into that of asymmetric substitution of either enantiotopic C-O bond of the gem-dicarboxylate. Although asymmetric induction may be derived from enantio-discrimination in the ionization step or in the alkene coordination step, the fast and reversible nature of alkene coordination suggests that the ionization step is more likely to be the source of enantio-discrimination. 

In addition to alkenes, functionalized alkenes can also be used as alkylating agents. Koltunov, Walspurger, and Sommer, have reported the alkylation of benzene with a,/3-unsaturated carboxamides in the presence of excess aluminum chloride [Eq. (5.72)]. The reaction takes place under mild conditions and gives the products in near-quantitative yields. Results with ortlro-dichlorobenzene and triflic acid are usually inferior. Triflic acid, however, can catalyze similar reactions of cyclic and open-chain unsaturated amines with benzene to give phenylalkylamines in excellent yields.180 The transformations are interpreted by invoking the involvement of dica-tionic intermediates 39 and 40. 

Acid-Catalyzed Synthesis. The acid-catalyzed reaction of alkenes with hydrogen sulfide to prepare thiols can be accomplished using a strong acid (sulfuric or phosphoric acid) catalyst. Thiols can also be prepared continuously over a variety of solid acid catalysts, such as zeolites, sulfonic acid-containing resin catalysts, or aluminas (22). The continuous process is utilized commercially to manufacture the more important thiols (23,24). The acid-catalyzed reaction is commonly classed as a Markownikoff addition. Examples of two important industrial processes are 2-methyl-2-propanethiol and 2-propanethiol, given in equations 1 and 2, respectively. 

Q In the presence of acid the double bond of the enol gets proton-ated. This step of the mechanism is identical to the first step of the mechanism for addition of the hydrogen halides and the acid-catalyzed addition of water to alkenes. The addition occurs so that the positive charge is located on the carbon that is bonded to the hydroxy group because this carbocation is stabilized by resonance. 

The mechanism of the formation of the tetrahydropyranyl ether (see Figure 23.1) is an acid-catalyzed addition of the alcohol to the double bond of the dihydropyran and is quite similar to the acid-catalyzed hydration of an alkene described in Section 11.3. Dihydropyran is especially reactive toward such an addition because the oxygen helps stabilize the carbocation that is initially produced in the reaction. The tetrahydropyranyl ether is inert toward bases and nucleophiles and serves to protect the alcohol from reagents with these properties. Although normal ethers are difficult to cleave, a tetrahydropyranyl ether is actually an acetal, and as such, it is readily cleaved under acidic conditions. (The mechanism for this cleavage is the reverse of that for acetal formation, shown in Figure 18.5 on page 776.)... 

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