Nucleophilic conjugate addition to alkenes

You Will soe a few mechanisms in thla ch er where we have written an intramolecular deprotonatipn. This saves writing two steps—pnotonation of the enoiate and deprotonation of N here)—but puite possibly this is not the actual mechanism by which the proton transfer takes place. Any proton wilt do, as will any base—do not take the arrows here too literally. 

The essential requirement for these reactions is a conjugating substituent that is about as anion-stabilizing as a carbonyl group. One we have seen before is cyanide and we shall look first at conjugated nitriles. The simplest is acrylonitrile. This compound adds amines readily. 

The amine first attacks the alkene in a typical conjugate addition to make a stable anion. Notice that the nucleophile must attack the far end of the alkene to do this—attack next to the electron-withdrawing group would not work. 

The anion can have its charge drawn on the nitrogen atom but it is really delocalized over the two neighbouring carbon atoms and is very like an enoiate. Do not be put off by the odd appearance of the enoiate . The dot between the two double bonds is a reminder that there is a linear sp carbon atom at this point 

Protonation at carbon restores the cyanide and gives the product— an amino-nitrile. The whole process adds a 2-cyano-ethyl group to the amine and is known industrially as cyanoethylation. 

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In contrast to a, -ethylenic ketones or even a, -ethylenic sulfones, a, ) -ethylenic sulfoxides generally are not sufficiently electrophilic to undergo successful nucleophilic j8-addition . a-Carbonyl-a, j8-ethylenic sulfoxides, however, are potent, doubly activated alkenes which undergo rapid and complete -addition of various types of nucleophiles even at — 78 °C. A brief account summarizing this area is available . The stereochemical outcome of such asymmetric conjugate additions to enantiomerically pure 2-sulfmyl 2-cycloalkenones and 2-sulfinyl-2-alkenolides has been rationalized in terms of a metal-chelated intermediate in which a metal ion locks the -carbonyl sulfoxide into a rigid conformation (36 cf. 33). In this fixed conformation, one diastereoface of the cyclic n... 

In contrast to the well documented conjugate addition of carbon nucleophiles to activated alkenes, similar intermolecular attempts with activated alkynes with non-cuprate reactants are typically non-productive due to competing multiple addition processes.87 6 However, protic intramolecular conjugate additions of ketones as shown for the syntheses of griseofulvin and hirsutic acid,222 are successful. Recently, several aprotic intramolecular conjugate additions to activated alkynes have been reported, as... 

Boron—nitrogen coordination polymers, with ferrocene, 6, 208 Boron nucleophiles, in conjugate additions asymmetric 1,4-additions, 10, 388 mechanisms, 10, 384 to nitroolehns, 10, 388 to a,/3-unsaturated amides, 10, 386 to a,/3-unsaturated esters, 10, 386 to a,/3-unsaturated ketones, 10, 384 Boron-silicon bonds, addition to alkenes, 10, 760 to alkynes, 10, 758 to allenes, 10, 760 to carbenoids, 10, 766 to 1,3-dienes, 10, 762 to isocyanides, 10, 765... 

We are going to extend this idea now and show that other groups besides the carbonyl group can promote nucleophilic addition to alkenes and then extend the idea further into the reactions of allylic and aromatic compounds. First of all we are going to look at other conjugating electron-withdrawing groups. 

Nucleophilic substitution at saturated carbon 20 Electrophilic addition to alkenes 22 Electrophilic aromatic substitution 29 Conjugate Michael addition of enolates 39 Radicals... 

In contrast to HBr, the acids HC1 and HI do not undergo free-radical addition to alkenes, even in the presence of peroxides or O2. Abstraction of H- from HC1 is too endothermic, and addition of I- to an alkene is too endothermic. However, thiols (RSH) add to alkenes by a free-radical mechanism exactly analogous to the addition of HBr. The initiator is usually AIBN or (BzO)2- The alkene may be electron-rich or electron-poor. Note that the conjugate addition of thiols to electron-poor alkenes can occur either by a free-radical mechanism or by a polar, nucleophilic mechanism. 

Equation 8.69 demonstrates addition to the y position of the t al lyl complex and represents simply the reverse of nucleophilic addition to [Fe(alkene)]+ reagents (see equations 8.39 and 8.40).97 The synthetic utility of this reaction is illustrated in equation 8.70, where the iron complex undergoes conjugate addition to the a,(3-unsaturated diester. The resulting r 2-n ligand then undergoes... 

The double bond can be restored after a conjugate addition to an electrophilic alkene if the enolate intermediate 110 is trapped as a silyl enol ether 111 and then combined with a sulfur or selenium electrophile which is later eliminated. Organocuprates are ideal nucleophiles for this process as the intermediate enolate can be trapped as a silyl enol ether and reacted directly with PhSCl or PhSeCl. 

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