Vinylic carbon, nucleophilic displacement

Reactions which are apparently stereospecific occur in the nucleophilic displacement of vinylic iodide [31] in the electron-deficient alkenes E- and Z-24 shown in Scheme 9.14. With ethanolic toluenethiolate, the sole detectable product from the reaction of -24 is -25. However, -25 is also the sole detectable product from the reaction of Z-24. This stereoconvergence demands that the stereoisomers react through a common intermediate, and it was reasonably suggested that initial nucleophilic addition of the thiolate anion yields a resonance-stabilised carbanion (26) whose stereoisomerisation, again by rotation about a carbon-carbon single bond, is much faster than the loss of iodide to yield the substitution product ( fy). 

Thus, in the absence of nitrate, it is possible to obtain a chloroalkyl acetate as the main product.5353 b The most reasonable rationalization for these results is to include the formation of vinyl acetate and saturated ester as proceeding through a common /J-acetoxyalkylpalladium(II) intermediate. Depending on the conditions, the latter can decompose via /3-hydrogen elimination to vinyl acetate or via nucleophilic displacement at the a-carbon giving 1,2-disubstituted ethanes ... 

Mechanistically, this homobimetallic catalytic process can be described and rationalized as a Pd(0)-catalyzed deprotection of the phenyl allylether 97 furnishing phenolate 99 that now can enter the second Pd(II)-catalyzed cycle (Scheme 34). The destiny of the 7r-allyl-Pd complex is a carbonyl insertion to furnish, after nucleophilic displacement with methanol, but-3-enoic acid methyl ester and hydroiodic acid. The phenolate 99 cyclizes to give a vinyl-Pd species that inserts carbon monoxide followed by the attack of methanol. 

The clear-cut behavior in the opening of epoxides can sulfer some exceptions. Such abnormal reactions have been reported in the opening of epoxide 21 with vinylmagnesium bromide. In this case, the vinyl residue was introduced at C2 as expected but with retention of configuration this is because of preferential opening with the bromide ion followed by the displacement of the bromide atom with the carbon nucleophile [34]. 

The relative ease of the cyclization step from A to C may also be linked to the nucleophilic or coordinative ability of the heteroatom bound to the metal. The reaction of 7 with diphenylacetylene (Ph2C2) leads to the seven-membered derivatives 68 and 69 after prior isolation of the monoinsertion product 24, treatment with a silver salt, followed by the usual thermolytic conditions. This is another rare example of an intramolecular formation of a C-S bond within the coordination sphere of a transition metal and a novel, albeit limited to one alkyne, route to the rare family of dibenzo[bd] thiepins. With the closely related 8, which differs from 7 only by the tertiary amine unit in the metallacyclic framework instead of a thioether function, a carbocyclic product 71 is obtained (see under carbocycle reactions, next section). The formation of the seven-membered S-heterocycles is attributed to the good coordinative ability of the thioether group in 7. The S-atom remains close to the vinylic carbon function before the cyclization. With the poorly coordinating, readily displaced amine function in 8, the N-atom is detached from the metal and ultimately affords a spirocyclic product (see Scheme 18). 

Pd(II) compounds coordinate to alkenes to form rr-complexes. Roughly, a decrease in the electron density of alkenes by coordination to electrophilic Pd(II) permits attack by various nucleophiles on the coordinated alkenes. In contrast, electrophilic attack is commonly observed with uncomplexed alkenes. The attack of nucleophiles with concomitant formation of a carbon-palladium r-bond 1 is called the palladation of alkenes. This reaction is similar to the mercuration reaction. However, unlike the mercuration products, which are stable and isolable, the product 1 of the palladation is usually unstable and undergoes rapid decomposition. The palladation reaction is followed by two reactions. The elimination of H—Pd—Cl from 1 to form vinyl compounds 2 is one reaction path, resulting in nucleophilic substitution of the olefinic proton. When the displacement of the Pd in 1 with another nucleophile takes place, the nucleophilic addition of alkenes occurs to give 3. Depending on the reactants and conditions, either nucleophilic substitution of alkenes or nucleophilic addition to alkenes takes place. 

A nucleophilic mechanism can be applied in reductions with complex hydrides of highly fluori-nated aliphatic and alicyclic fluoroalkenes with electron-deficient C = C bonds the hydride anion adds as a strong nucleophilic agent to the more electrophilic carbon atom the intermediate anion can then lose a fluoride ion either from the original C = C bond, or from the allylic position finishing an SN2 displacement of the fluorine. Thus, the reductions of vinylic C-F bonds with hydrides proceed by a nucleophilic addition-elimination mechanism. Displacement of fluorine in highly fluorinated aromatic compounds proceeds by the same mechanism ... 

Acyclic stereocontrol remains a challenging problem in synthesis. While enan-tiomerically pure sulfoxides are valuable synthetic intermediates for enantiocon-trolled carbon-carbon bond formation by conjugate addition in cyclic cases, their usefulness for such alkylations in acyclic cases has not been firmly established. Moreover, most sulfoxide directed alkylation protocols utilize the valuable sulfur auxiliary just once, which limits the synthetic versatility of the process. Marino et al. have recently reported SN2 displacements of acyclic allylic mesyloxy vinyl sulfoxides with organocopper reagents (Scheme 10).33 In addition to the excellent observed stereoselectivities, the newly created chiral center is adjacent to a vinyl sulfoxide which should allow for subsequent chirality transfer operations. On treatment with organocopper nucleophiles, both sulfoxide diastereoisomers 40b and 43b underwent SN2 displacements with high Z selectivity to yield products 42b and 45b, respectively (Table 2). The oxidation state on the sulfur was varied... 

Nucleophilic attack on ( -alkene)Fp+ cations may be effected by heteroatom nucleophiles including amines, azide ion, cyanate ion (through N), alcohols, and thiols (Scheme 39). Carbon-based nucleophiles, such as the anions of active methylene compounds (malonic esters, /3-keto esters, cyanoac-etate), enamines, cyanide, cuprates, Grignard reagents, and ( l -allyl)Fe(Cp)(CO)2 complexes react similarly. In addition, several hydride sources, most notably NaBHsCN, deliver hydride ion to Fp(jj -alkene)+ complexes. Subjecting complexes of type (79) to Nal or NaBr in acetone, however, does not give nncleophilic attack, but instead results rehably in the displacement of the alkene from the iron residue. Cyclohexanone enolates or silyl enol ethers also may be added, and the iron alkyl complexes thus produced can give Robinson annulation-type products (Scheme 40). Vinyl ether-cationic Fp complexes as the electrophiles are nseful as vinyl cation equivalents. ... 

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