Double bonds, addition reactions

Addition to double bonds is not the only kind of reaction that converts an achiral molecule to a chiral one Other possibilities include substitution reactions such as the formation of 2 chlorobutane by free radical chlorination of butane Here again the prod uct IS chiral but racemic... 

Other nonpolymeric radical-initiated processes include oxidation, autoxidation of hydrocarbons, chlorination, bromination, and other additions to double bonds. The same types of initiators are generally used for initiating polymerization and nonpolymerization reactions. Radical reactions are extensively discussed in the chemical Hterature (3—15). 

Other limitations of the reaction are related to the regioselectivity of the aryl radical addition to double bond, which is mainly determined by steric and radical delocalization effects. Thus, methyl vinyl ketone gives the best results, and lower yields are observed when bulky substituents are present in the e-position of the alkene. However, the method represents complete positional selectivity because only the g-adduct radicals give reductive arylation products whereas the a-adduct radicals add to diazonium salts, because of the different nucleophilic character of the alkyl radical adduct. ... 

More useful for synthetic purposes, however, is the combination of the zinc-copper couple with methylene iodide to generate carbene-zinc iodide complex, which undergoes addition to double bonds exclusively to form cyclopropanes (7). The base-catalyzed generation of halocarbenes from haloforms (2) also provides a general route to 1,1-dihalocyclopropanes via carbene addition, as does the nonbasic generation of dihalocarbenes from phenyl(trihalomethyl)mercury compounds. Details of these reactions are given below. 

Photolytically generated carbene, as mentioned above, undergoes a variety of undiscriminated addition and insertion reactions and is therefore of limited synthetic utility. The discovery (3) of the generation of carbenes by the zinc-copper couple, however, makes carbene addition to double bonds synthetically useful. The iodo-methylzinc iodide complex is believed to function by electrophilic addition to the double bond in a three-center transition state giving essentially cis addition. Use of the... 

Predominant formation of s-products on reaction of A -acyliminium ions, containing an additional conjugated double bond, with propylzinc iodide likewise arises from A(1 3) strain as discussed133. 

The first step, as we have already seen (12-3), actually consists of two steps. The second step is very similar to the first step in electrophilic addition to double bonds (p. 970). There is a great deal of evidence for this mechanism (1) the rate is first order in substrate (2) bromine does not appear in the rate expression at all, ° a fact consistent with a rate-determining first step (3) the reaction rate is the same for bromination, chlorination, and iodination under the same conditions (4) the reaction shows an isotope effect and (5) the rate of the step 2-step 3 sequence has been independently measured (by starting with the enol) and found to be very fast. With basic catalysts the mechanism may be the same as that given above (since bases also catalyze formation of the enol), or the reaction may go directly through the enolate ion without formation of the enol ... 

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. 

Radical reactions used in synthesis include additions to double bonds, ring closure, and atom transfer reactions. Several sequences of tandem reactions have been developed that can close a series of rings, followed by introduction of a substituent. Allylic stannanes are prominent in reactions of this type. 

Also, the 1,4-dialkoxylation of acyclic 1,3-dienes was stereoselective. For example, the reaction of ( , )-2,4-hexadiene gave the d,l products 38 by a 1,4-syn addition. The double bond was exclusively of E configuration (equation 18). 

SECONDARY REACTIONS. The reactions of the free radicals include (1) abstractions (of H atoms, with preference for tertiary H, and of halogen atoms), (2) addition to double bonds, which are very efficient scavengers for radicals, (3) decompositions to give both small molecule products, such as CO2, and (4) chain scission and crosslinking of molecules. 

Addition to Double Bonds and Elimination Reactions. Both Lewis and Br nsted acidity of mineral surfaces can promote addition and elimination reactions (37). Equation 14 shows an example for an addition/elimination equilibrium catalyzed by Br nsted acidity ... 

Sulfenyl fluorides are extremely unstable and therefore only few perhalosulfenyl fluorides have so far been reported122. The formal addition of the elements of methanesulfenyl fluoride to carbon-carbon double bonds has been obtained123 by a one-pot reaction with dimethyl(methylthio)sulfonium tetrafluoroborate and triethylammonium tris(hydrofluo-ride). With this system also the addition to double bonds is highly stereoselective, at least... 

Usually, the formation of a new chiral centre involves the conversion of a prochiral sp carbon atom into one with sp hybridisation, the methods most generally used being the aldol and related condensations, pericyclic reactions (especially the Diels-Alder reaction), epoxidation, cyclopropanation and additions to double bonds (hydrogenation and hydroboration). Another possibility is the conversion of a prochiral sp carbon atom into a chiral centre, as for instance in the a-substitution (alkylation, halogenation, etc.) of a ketone. 

There is some information concerning the reaction of ozone with chemicals under aqueous conditions. The information available suggests that double-bond cleavage takes place, just as it does under nonaqueous conditions, except that ozonides are not formed. Instead, the zwitterionk intermediate reacts with water, producing an aldehyde and hydrogen peroxide. In addition to double-bond cleavage, a number of other oxidations are possible. Mudd et showed that the susceptibility of amino acids is in the order cysteine, tryptophan, methionine. 

The obvious disconnection in cyclopeptide alkaloids and indeed the strategy employed in most total syntheses of this type of compound is the formation of the aryl ether bond. Many groups chose to form the macrocyclic aryl ether by S Ar reaction. We decided to follow the inverse strategy, i.e., displacement of an allylic leaving group by a phenolate. In case of the natural cyclopeptide alkaloids, this would involve activation of yS-hydroxy-a-amino acids, which is likely to be accompanied by extensive elimination. Elimination is not possible when a-methylene- -hydroxy acids are used. Additionally, the double bond activates the leaving group and provides a handle for a possible later side chain attachment. 

As has been exemplified in this chapter, fluorinations with fluorine-18 can be classified into two categories (1) the nucleophilic reactions, which usually involve no-carrier-added [ F]fluoride of high-specific radioactivity as its Kf FIF-K complex and include substitutions in the aliphatic and the /lomoaromatic series and (2) the electrophilic reactions, which mainly use moderately low-specific radioactivity molecular [ F]fluorine, or other reagents prepared from it, such as acetyl [ F] hypofluorite, and include addition across double bonds, reactions with carbanions and especially fluorodehydrogenation and fluorodemetallation reactions. 

These reactions are examples of the preferred trans-diaxial opening of epoxides and the analogous trans-diaxial addition to double bonds. 

Carboethoxynitrene (19) can be generated in solution by base-catalyzed a-elimina-tion of 20 or upon photolysis of azide 13. The nitrene undergoes addition to double bonds and formal CH insertion reactions. ... 

Hydroboration-oxidation of alkenes preparation of alcohols Addition of water to alkenes by hydroboration-oxidation gives alcohols via anti-Markovnikov addition. This addition is opposite to the acid-catalysed addition of water. Hydrohoration is regioselective and syn stereospecific. In the addition reaction, borane bonds to the less substituted carbon, and hydrogen to the more substituted carbon of the double bond. For example, propene reacts with borane and THF complex, followed by oxidation with basic hydrogen peroxide (H2O2), to yield propanol. 

For reviews of the stereochemistry of carbene and carbenoid addition to double bonds, see Moss Set. Org. Transform. 1970, /, 35-88 Closs Top Stereochem. I960 3, 193 235. For a discussion of enantioselectivity in this reaction, see Nakamura Pure App. Ckem. 1978,50, 37. 

It would be very interesting to speculate on the behavior of the iso-electronic species NH and O atoms. From limited kinetic studies these appear to undergo addition to double bonds as well as abstraction type of reactions.21 22 However no definitive studies have been made on the existence of the insertion type of reaction which would be very much expected for both species, particularly for the O atom, in view of its fairly large electron affinity.8... 

Butene-2. The experimental results for the reaction of methylene with cis and trans butene-2 are summarized in Table III. In the liquid phase and in the gas phase at high pressures (>200 mm.) the major products are 1,2-dimethylcyclopropane (addition to double bond), pentane-2, and 2-methylbutene-2 (insertion products), and the steric configuration of the butene-2 is predominantly retained in the products... 

Another possible course of reaction of alkoxy radicals is addition to double bonds ... 

Next to nucleophilic displacement, the commonest mechanistic processes in enzymatic catalysis are addition to double bonds and elimination to form double bonds. These often involve addition of a nucleophile together with a proton to a highly polarized double bond such as C=O or C=N-. In other reactions, which are discussed in Section C,2, the nucleophile attacks one end of a C=C bond that is polarized by conjugation with C=0 or C=N. 

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