Alkenes electrophiles, reactions with

The highly 7r-deficient character of the 1,2,4-triazine ring increases the nucle-ophilicity of the methyl group in methyl-1,2,4-triazine A-oxides in reactions with electrophilic alkenes and aldehydes. Thus treatment of the 6-methyl-3-phenyl-1,2,4-triazine 4-oxide 113 with l-(dimethylamino)-l-ethoxyethylene leads to the... 

Allyltitanium complexes derived from a chiral acetal have been reacted with carbonyl compounds and imines [63], While the chiral induction proved to be low with carbonyl compounds, high induction was observed with imines. This complex represents the first chiral homoenolate equivalent that reacts efficiently with imines. Finally, the reactions with electrophiles other than carbonyl compounds and imines, namely a proton source, NCS, and I2, furnished the corresponding alkene, chloro, and iodo derivatives in good yields [64]. 

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

The key success of these metal-catalyzed processes lies in the replacement of an unachievable carbozincation by an alternative carbometallation involving the transition metal catalyst, or another pathway such as an alkene-alkene (or alkyne) oxidative coupling promoted by a group IV transition metal complex, followed by transmetallation. An organozinc is ultimately produced and the latter can be functionalized by reaction with electrophiles. 

This dominance of sulfur in the reactions with electrophiles is well brought out in the addition of carbenes to the-two monocycles. Tire allylic sulfide (5,6-dihydro-2jF/- thiopyran) only affords the products of reaction at sulfur, while the vinylic sulfide (3,4-dihydro-2f/-thiopyran), in which the alkene is a little more nucleophilic due to the small interaction with the heteroatom, shows dichotomous behaviour. Dichlorocarbene affords the cyclopropane product (78) in 70% yield, but the stabilized ylide (76) is produced from bismethoxycar-bonylmethylide and (75). In fact it is possible that the initial reaction with dichlorocarbene is reaction at sulfur and subsequent rearrangement of this less stabilized ylide. Schemes 6 and 7 illustrate the results and proposed mechanisms (77JOC3365,64JOC2211). 

Reactions with electrophilic alkenes, ketones and ketenes 709... 

The chemistry of pyrrol-1-ylbenzylidene pentacarbonyl chromium, molybdenum and tungsten complexes was investigated. Reaction with electrophilic alkenes gives l-(phenylcyclo-propyl)pyrroles Under photolytic decarbonylation conditions 2 + 2 cycloaddition products were obtained with nucleophilic alkenes, cyclic dienes and imines. <950M2522>... 

The superbase metallation of alkenes in the allylic position followed by reaction with electrophiles is one of the best methods to access Z-alkenes with new functional groups. 

A more recent example of alkene metallation by superbase followed by reaction with electrophiles is the functionalization of isopulegol which can be performed without protection of the hydroxy group.81... 

As pointed out by Stork and coworkers in their definitive 1963 paper3, the reaction with electrophilic alkenes is especially successful since reaction at nitrogen is reversible. Reaction at the /2-carbon is (usually) rendered irreversible by, in the case of cyclohexanone enamines, internal proton transfer of the axial C-/2 proton to the anionic centre of the initially formed zwitterionic intermediate (34), under conditions of stereoelectronic control (Scheme 22). When this intramolecular proton transfer cannot occur in aprotic solvents, or when the product produced in protic solvents is a stronger carbon acid than adduct 35 (i.e. when Z = COR, N02), then carbon alkylation is also reversible and surprising changes in the regioselectivity of reaction may be observed (vide infra see also Section VI.D and Chapter 26). Cyclobutanes (36) and, in the case of a,/ -unsaturated... 

Again steric hindrance makes the reaction with electrophiles slower or difficult. Also in this case, the addition of Cu(I) salts is effective [16]. In the reactions with 1-substituted 1-stannylethene, cme-substitution is sometimes observed especially in the reaction of tins with electron-rich alkenes [69, 133-138]. This might be attributed to a participation of a Pd(0)-carbene species generated via a-elimination of regioisomeric Heck intermediate [136,139]. Cme-substitution is scarce when the electrophile is electron deficient (Scheme 29) [136,137]. Levin reported that zpso-selectivity in vinylation of a-stannylacrylate was restored by the addition of Cul [140]. 

Both electnm nchness and electnm accessibility tend to the prediction that a carbon-carbon double bond should be nucfrwpAjYir. That is. the chemistry of allcenes should involve reactiuns of the electron-rich double borsd with clcctron-poor roactants. Hiis is exactly what wc find The moot icupor-tanr. reaction of alkenes is their reaction with electrophiles. 

Acetylene, as is well known, is acidic enough to form acetylide salts with strong bases. A monoacetylide, HCsC M (M = metal), in reactions with electrophiles ( E ) yields a monosubstituted derivative of acetylene, HC=CE. The latter can undergo the same sequence of reactions to produce compounds of the type E C = CE. Consequently, acetylene can be regarded as a reagent equivalent to the synthons HC=C or C = C . If one further considers the possibilities for the transformation of the acetylenic fragment (for example, hydrogenation to the alkene or alkane, hydration to yield ketones, and other... 

Because a n bond is electron rich and much weaker than a a bond, alkenes undergo addition reactions with electrophiles (10.8). 

In Chapter 11 we continue our focus on organic molecules with electron-rich functional groups by examining alkynes, compounds that contain a carbon-carbon triple bond. Like alkenes, alkynes are nucleophiles with easily broken n bonds, and as such, they undergo addition reactions with electrophilic reagents. 

Is Cgo aromatic Although it is completely conjugated, it is not planar. Because of its curvature, it is not as stable as benzene. In fact, it undergoes addition reactions with electrophiles in much the same way as ordinary alkenes. Benzene, on the other hand, undergoes substitution reactions with electrophiles, which preserves the unusually stable benzene ring intact. These reactions are the subject of Chapter 18. 

Alkenes react with electrophiles such as HBr to 3ueld saturated addition products. The reaction occurs in two steps. The electrophile first adds to the alkene double bond to yield a carbocation intermediate, w hich reacts further to yield the addition product. 

C-Alkylations of hindered aldehyde enamines can be effected with a variety of alkylating agents, but only allylic and benzylic reagents are useful for alkylations of unhindered systems.Acyclic, homoan-nular and heteroannular dienamines undergo alkylation primarily at the a-positions. ° As discussed above, reactions of enamines with electrophiles containing sp -hybridized carbon atoms have numerous limitations. On the other hand, enamine reactions with electrophilic alkenes are highly useful and have received wide coverage in the literature. 

The Morita-Baylis-Hillman reaction and its aza-variant - the reaction of an electron-deficient alkene with an aldehyde (MBH) or an imine (aza-MBH) - provide a convenient route to highly functionalized allylic alcohols and amines. This reaction is catalyzed by simple amines or phosphines, which can react as a Michael donor with an electron-deficient alkene, generating an enolate intermediate. This intermediate in turn undergoes the aldol or Mannich reaction with electrophilic C=0 or C=N bonds, respectively, to deliver allylic alcohols and amines. 

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