Alkenes conjugate addition

In total, over the past six years, the chelating P,N-ligands have shown considerable promise in a variety of enantioselective processes, including transfer-hydrogenation and hydrosilylation of ketones, hydroboration of alkenes, conjugate addition to enones and Lewis-acid catalysed Diels-Alder reactions, in addition to those described above.128,341 It is anticipated that this list will continue to grow, and... 

Migration of a hydride ligand from Pd to a coordinated alkene (insertion of alkene) to form an alkyl ligand (alkylpalladium complex) (12) is a typical example of the a, /(-insertion of alkenes. In addition, many other un.saturated bonds such as in conjugated dienes, alkynes, CO2, and carbonyl groups, undergo the q, /(-insertion to Pd-X cr-bonds. The insertion of an internal alkyne to the Pd—C bond to form 13 can be understood as the c -carbopa-lladation of the alkyne. The insertion of butadiene into a Ph—Pd bond leads to the rr-allylpalladium complex 14. The insertion is usually highly stereospecific. 

In Grignard reactions, Mg(0) metal reacts with organic halides of. sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand. Pd(0) complexes react more easily with halides of carbons. In other words, alkenyl and aryl halides undergo facile oxidative additions to Pd(0) to form complexes 1 which have a Pd—C tr-bond as an initial step. Then mainly two transformations of these intermediate complexes are possible insertion and transmetallation. Unsaturated compounds such as alkenes. conjugated dienes, alkynes, and CO insert into the Pd—C bond. The final step of the reactions is reductive elimination or elimination of /J-hydro-gen. At the same time, the Pd(0) catalytic species is regenerated to start a new catalytic cycle. The transmetallation takes place with organometallic compounds of Li, Mg, Zn, B, Al, Sn, Si, Hg, etc., and the reaction terminates by reductive elimination. 

A particular kind of conjugate addition reaction earned the Nobel Prize in chemistry for Otto Diels and Kurt Alder of the University of Kiel (Germany) m 1950 The Diels-Alder reaction is the conjugate addition of an alkene to a diene Using 1 3 buta diene as a typical diene the Diels-Alder reaction may be represented by the general equation... 

Section 10 12 Conjugate addition of an alkene (the dienophile) to a conjugated diene gives a cyclohexene derivative in a process called the Diels-Alder reaction It is concerted and stereospecific substituents that are cis to each other on the dienophile remain cis m the product... 

Diels-Alder reaction (Section 10 12) Conjugate addition of an alkene to a conjugated diene to give a cyclohexene denva tive Diels-Alder reactions are extremely useful in synthesis... 

Although deprotonation of simple 1,3-dithiolanes at the 2 position is usually accompanied by cycloreversion to the alkene and dithiocarboxylate, this does not occur for the 2-ethoxycarbonyl compound 55. The anion of this is readily generated with LDA and undergoes conjugate addition to a,(3-unsaturated ketones, esters, and lactones to give, after deprotection, the a,8-diketoester products 56 (73TL2599). In this transformation 55 therefore acts as an equivalent of Et02C-C(0) . 

Enamines react with acceptor-substituted alkenes (Michael acceptors) in a conjugate addition reaction for example with o ,/3-unsaturated carbonyl compounds or nitriles such as acrylonitrile 8. With respect to the acceptor-substituted alkene the reaction is similar to a Michael addition ... 

The conjugate addition of a nucleophile to an a,fi-unsaturated aldehyde or ketone is caused by the same electronic factors that are responsible for direct addition. The electronegative oxygen atom of the a,/3-unsaturated carbonyl compound withdraws electrons from the /3 carbon, thereby making it electron-poor and more electrophilic than a typical alkene carbon. 

Synthetic polymers can be classified as either chain-growth polymen or step-growth polymers. Chain-growth polymers are prepared by chain-reaction polymerization of vinyl monomers in the presence of a radical, an anion, or a cation initiator. Radical polymerization is sometimes used, but alkenes such as 2-methylpropene that have electron-donating substituents on the double bond polymerize easily by a cationic route through carbocation intermediates. Similarly, monomers such as methyl -cyanoacrylate that have electron-withdrawing substituents on the double bond polymerize by an anionic, conjugate addition pathway. 

The effect of the solvent on the product distribution is observed in the conjugate addition of amines to 1-bromo-l-(phenylsulfonyl)alkenes (54) (equation 54)46. When the reaction is conducted in benzene at room temperature for 4 days, the adduct 55 is formed in good yield. On the other hand, the reaction in DMSO at 80-90 °C for 2.5 h affords 2-(phenylsulfonyl)aziridines (56) and no adduct (55) is isolated. 

Potential precursors to stereoselective INOC and ISOC reactions (e.g., 195 and 196, respectively) have been prepared via stereoselective conjugate additions of several allylic alcohols (e.g., 194,X = 0) and an allylic thiol (e.g., 194,X = S) to a chiral (E)-nitro alkene (e. g., 193) that was derived from (P)-2,3-isopropylidene... 

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... 

The catalytic enantioselective addition of vinylmetals to activated alkenes is a potentially versatile but undeveloped class of transformations. Compared to processes with arylmetals and, particularly alkylmetals, processes with the corresponding vinylic reagents are of higher synthetic utility but remain scarce, and the relatively few reported examples are Rh-catalysed conjugate additions. In this context, Hoveyda et al. reported very recently an efficient method for catalytic asymmetric allylic alkylations with vinylaluminum reagents that were prepared and used in Thus, stereoselective reactions... 

A second important reaction type considered in this chapter is conjugate addition, which involves addition of nucleophiles to electrophilic double or triple bonds. A crucial requirement for this reaction is an electron-withdrawing group (EWG) that can stabilize the negative charge on the intermediate. We focus on reactions between enolates and a,(3-unsaturated carbonyl compounds and other electrophilic alkenes such as nitroalkenes. 

More generally, many combinations of EWG substituents can serve as the anion-stabilizing and alkene-activating groups. Conjugate addition has the potential to form a bond a to one group and (3 to the other to form a a,y-disubstituted system. 

Scheme 2.23 provides some examples of conjugate addition reactions. Entry 1 illustrates the tendency for reaction to proceed through the more stable enolate. Entries 2 to 5 are typical examples of addition of doubly stabilized enolates to electrophilic alkenes. Entries 6 to 8 are cases of addition of nitroalkanes. Nitroalkanes are comparable in acidity to (i-ketocslcrs (see Table 1.1) and are often excellent nucleophiles for conjugate addition. Note that in Entry 8 fluoride ion is used as the base. Entry 9 is a case of adding a zinc enolate (Reformatsky reagent) to a nitroalkene. Entry 10 shows an enamine as the carbon nucleophile. All of these reactions were done under equilibrating conditions. 

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