Electrophilic double bonds

Ozonation ofAlkenes. The most common ozone reaction involves the cleavage of olefinic carbon—carbon double bonds. Electrophilic attack by ozone on carbon—carbon double bonds is concerted and stereospecific (54). The modified three-step Criegee mechanism involves a 1,3-dipolar cycloaddition of ozone to an olefinic double bond via a transitory TT-complex (3) to form an initial unstable ozonide, a 1,2,3-trioxolane or molozonide (4), where R is hydrogen or alkyl. The molozonide rearranges via a 1,3-cycloreversion to a carbonyl fragment (5) and a peroxidic dipolar ion or zwitterion (6). 

The mechanism of this new reaction is shown in Scheme 14. Coordination of the diene to palladium(II) makes the diene double bond electrophilic enough to be attacked by the allylsilane. The attack by the allylsilane takes place on the face of the diene opposite to that of the palladium (anti). This is the first example of an anti attack by an allylsilane on a 7T-(olefin)metal complex. Benzoquinone (BQ)-induced anti attack by chloride ion produces the product 58. 

Many aspects of the characteristics of the double-bonded functional groups have been reviewed in an impressive series of treatises, published over a period of more than 30 years. These reviews cover mostly the physicochemical aspects of double bonds electrophilic additions to carbon-carbon double bonds1, directing and activating effects of doubly bonded groups2 etc. 

The electron ejected from the monomer molecule attaches to the double bond of another monomer molecule, which leads to an anion-free radical. In essence, the irradiation produces cation, anion, and free radical, any of which can initiate the monomer unaffected by the irradiation. Which end of the initiator, i.e., cation, anion, or free radical, initiates the polymerization is dependent on the nature of the double bond (electrophilic or electrophobic) and the purity of the monomer [2]. In some monomers in extremely high purity, polymerization proceeds by all three polymerizations, i.e., cationic, anionic, and free radical, as depicted schematically in Figure 5.1. 

Hydrazoic acid adds readily to alkenes which are conjugated to powerful electron-withdrawing groups. Since such groups reduce the basicity of the carbon-carbon double bond, electrophilic attack by hydrazoic acid is more difficult, so that where reaction occurs it is likely to proceed by nucleophUic attack. The best known examples are the additions to a,/3-unsaturated carbonyl compounds and these are discussed subsequendy. 

An addition reaction is formally the reverse of an elimination reaction. We will see both electrophilic and nucleophilic additions in this section. There are few new generic classes of reactants to consider, and there are three new routes, but these are just the reverse of the elimination routes just covered. The new generic classes are discussed in much more detail in Chapter 5 and 6, but need to be introduced here. A carbon-carbon double bond can range from electrophilic to nucleophilic depending on what is attached to it (Fig. 4.33). Another way to make a double bond electrophilic is to replace one of its carbon atoms with an electronegative heteroatom like oxygen, C=0, a carbonyl. 

Examples of activated double bond electrophiles include a, 3-unsaturated carbonyl compounds, quinones, quinoneimines, quinonemethides and diiminoquinones as shown in Fig. 10.32B. These electrophilic intermediates are highly polarized and can react with nucleophiles in a 1,4-Michael-type addition at the more electrophilic or 3-oarbon of the activated double bond intermediate to the addition product (Fig. 10.32A). Specific examples of activated double bond electrophiles that have been proposed for the anticancer drug leflunamide, the food antioxidant butylated hydroxytoluene, acetaminophen, the antiandrogen flutamide, the anticonvulsant felbamate and the cytotoxic cyclophosphamide as shown in Fig. 10.32C. The bioinaotivation pathways for these electrophilic intermediate can involve either direct addition, with or without transferases, depending upon the degree of polarization and reactivity of the electrophilic intermediate (hard vs soft electrophiles). 

The oxazole ring exhibits rich and varied reactivity, which allows for functionalization at each ring atom other than oxygen. Oxazoles are weakly aromatic and, as such, display reactions characteristic of both aromatic substitutions and reactions of double bonds. Electrophilic aromatic substitutions—including bromination, nitration, and Friedel-Crafts reactions—preserve the aromatic character of the ring. On the other hand, additions across the C(4)-C(5) double bond that disrupt the aromatic nature of the ring are also known. 

However, in contrast to compounds with either isolated or cumulative double bonds, electrophilic addition reactions with alkenes that contain conjugated n-systems routinely produce products resulting from the interaction of both double bonds. While hydroboration appears to be an exception, with each double bond reacting separately (and the second more rapidly than the first), conjugated dienes, such as 1,3-butadiene (CH2=CH-CH=CH2), suffer addition across each double bond ( 1,2-addition ) as well as across the entire conjugated system ( 1,4-addition ). Commonly, the products ( 1,2-addition and 1,4-addition ) are formed concurrently. 

Synthesis of a chiral compormd from an achiral compound requires a prochiral substrate that is selectively transformed into one of the possible stereoisomers. Important prochiral substrates are, for example, alkenes with two different substituents at one of the two C-atoms forming the double bond. Electrophilic addition of a substitutent different from the three existing ones (the two different ones above and the double bond) creates a fourth different substituent and, thus, an asymmetric carbon atom. Another class of important prochiral substrates is carbonyl compounds, which form asymmetric compounds in nucleophilic addition reactions. As exemplified in Scheme 2.2.13, prochiral compounds are characterized by a plane of symmetry that divides the molecule into two enantiotopic halves that behave like mirror images. The side from which the fourth substituent is introduced determines which enantiomer is formed. In cases where the prochiral molecule already contains a center of chirality, the plane of symmetry in the prochiral molecules creates two diastereotopic halves. By introducing the additional substituent diasterom-ers are formed. 

The N-basicity of the commonly used amines (pyrrolidine > piperidine > morpholine) drops by 2-3 orders of magnitude as a consequence of electron pair delocalization in the corresponding enamines. This effect is most pronounced in morpholino enamines (see table below). Furthermore there is a tendency of the five-membered ring to form an energetically favorable exocyclic double bond. This causes a much higher reactivity of pyrroUdino enamines as compared to the piperidino analogues towards electrophiles (G.A. Cook, 1969). 

The electrophilicity of C = C double bonds conjugated with electron withdrawing groupings leads to a -synthons. This is an important example of the vinyiogous principle ... 

C—C double bonds may be protected against electrophiles by epoxidation and subsequent removal of the oxygen atom by treatment with zinc and sodium iodide in acetic acid (J.A. Edwards, 1972 W. Kndll, 1975). Halogenation has often been used for protection, too. The C—C double bond is here also easily regenerated with zinc (see p. 138, D.H.R. Barton, 1976). 

The resulting macrocyclic ligand was then metallated with nickel(II) acetate. Hydride abstraction by the strongly electrophilic trityl cation and proton elimination resulted in the formation of carbon-carbon double bonds (T.J. Truex, 1972). 

Glycosidic thiol groups can be introduced into glycosyl bromides by successive reactions with thiourea and aqueous sodium disulfite (D. Horton, 1963 M. Cemy, 1961, 1963). Such thiols are excellent nucleophiles in weakly basic media and add to electrophilic double bonds, e.g., of maleic esters, to give Michael adducts in high yields. Several chiral amphiphiles have thus been prepared without any need for chromatography (J.-H. Fuhrhop, 1986 A). 

Both steps m this general mechanism are based on precedent It is called elec trophilic addition because the reaction is triggered by the attack of an acid acting as an electrophile on the rr electrons of the double bond Using the two rr electrons to form a bond to an electrophile generates a carbocation as a reactive intermediate normally this IS the rate determining step... 

In general alkyl substituents increase the reactivity of a double bond toward elec trophilic addition Alkyl groups are electron releasing and the more electron rich a dou ble 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 formation rather than carbocation capture is rate determining... 

The regioselectivity of addition of HBr to alkenes under normal (electrophilic addi tion) conditions is controlled by the tendency of a proton to add to the double bond so as to produce the more stable carbocatwn Under free radical conditions the regioselec tivity IS governed by addition of a bromine atom to give the more stable alkyl radical Free radical addition of hydrogen bromide to the double bond can also be initiated photochemically either with or without added peroxides... 

We can consider the hydroboration step as though it involved borane (BH3) It sim phfies our mechanistic analysis and is at variance with reality only m matters of detail Borane is electrophilic it has a vacant 2p orbital and can accept a pair of electrons into that orbital The source of this electron pair is the rr bond of an alkene It is believed as shown m Figure 6 10 for the example of the hydroboration of 1 methylcyclopentene that the first step produces an unstable intermediate called a tt complex In this rr com plex boron and the two carbon atoms of the double bond are joined by a three center two electron bond by which we mean that three atoms share two electrons Three center two electron bonds are frequently encountered m boron chemistry The tt complex is formed by a transfer of electron density from the tt orbital of the alkene to the 2p orbital... 

You have just seen that cyclic halonmm ion intermediates are formed when sources of electrophilic halogen attack a double bond Likewise three membered oxygen containing rings are formed by the reaction of alkenes with sources of electrophilic oxygen... 

As shown m Table 6 4 electron releasing alkyl groups on the double bond increase the rate of epoxidation This suggests that the peroxy acid acts as an electrophilic reagent toward the alkene... 

The two dimers of (CH3)2C=CH2 are formed by the mechanism shown m Figure 6 16 In step 1 protonation of the double bond generates a small amount of tert butyl cation m equilibrium with the alkene The carbocation is an electrophile and attacks a second molecule of 2 methylpropene m step 2 forming a new carbon-carbon bond and generating a carbocation This new carbocation loses a proton m step 3 to form a mixture of 2 4 4 tnmethyl 1 pentene and 2 4 4 tnmethyl 2 pentene... 

Hydrogen bromide is unique among the hydrogen halides m that it can add to alkenes either by electrophilic or free radical addition Under photochemical conditions or m the presence of peroxides free radical addition is observed and HBr adds to the double bond with a regio selectivity opposite to that of Markovmkov s rule... 

Alkynes react with many of the same electrophilic reagents that add to the carbon-carbon double bond of alkenes Hydrogen halides for example add to alkynes to form alkenyl halides... 

The double bond m the alkenyl side chain undergoes addition reactions that are typical of alkenes when treated with electrophilic reagents... 

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... 

Normally carbon-carbon double bonds are attacked by electrophiles a carbon-carbon double bond that is conjugated to a carbonyl group is attacked by nucleophiles... 

Both parts of the Lapworth mechanism enol formation and enol halogenation are new to us Let s examine them m reverse order We can understand enol halogenation by analogy to halogen addition to alkenes An enol is a very reactive kind of alkene Its carbon-carbon double bond bears an electron releasing hydroxyl group which makes it electron rich and activates it toward attack by electrophiles... 

The diminished rr electron density m the double bond makes a p unsaturated aide hydes and ketones less reactive than alkenes toward electrophilic addition Electrophilic reagents—bromine and peroxy acids for example—react more slowly with the carbon-carbon double bond of a p unsaturated carbonyl compounds than with simple alkenes... 

Isopentenyl pyrophosphate and dimethylallyl pyrophosphate are structurally sim liar—both contain a double bond and a pyrophosphate ester unit—but the chemical reactivity expressed by each is different The principal site of reaction m dimethylallyl pyrophosphate is the carbon that bears the pyrophosphate group Pyrophosphate is a reasonably good leaving group m nucleophilic substitution reactions especially when as in dimethylallyl pyrophosphate it is located at an allylic carbon Isopentenyl pyrophosphate on the other hand does not have its leaving group attached to an allylic carbon and is far less reactive than dimethylallyl pyrophosphate toward nucleophilic reagents The principal site of reaction m isopentenyl pyrophosphate is the carbon-carbon double bond which like the double bonds of simple alkenes is reactive toward electrophiles... 

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