Vicinal difunctionalization electrophiles

The second group of reactions is called vicinal difunctionalization. They embrace the C2 and C3 positions of the furan ring simultaneously. Thus, complex 3 (X = O, R = R = R = H) reacts with benzaldehyde dimethyl acetal to give 4H-furanium cation (the product of electrophile addition at C4), which experiences further attack by the methoxide group with formation of the acetal 8 (950M2861). This reaction is possible in the presence of the Lewis acid (BF3—OEt2). Reaction with methyl vinyl ketone in methanol, when run in identical conditions. 

Usually, after an enolate ion is generated from an ocP-unsaturated ketone, it is converted to the P-alkylated product as shown above. But it is often possible to have the enolate react with some other electrophile (tandem vicinal difunctionalization), in some cases at the O and in other cases at the C. For example, if an alkyl halide R X is present (R = primary alkyl or allylic), and the solvent is 1,2-dime-thoxyethane, the enolate (66) can be alkylated directly. Thus, by this method, both the a and p positions of a ketone are alkylated in one synthetic operation (see also 15-23). 

A tanden anh-vicinal difunctionalization of alkynes, involving the addition of a lithium organotellurolate to an activated alkyne, with subsequent trapping of the vinyllithium intermediate with electrophiles, was recently reported and named electrotelluration. ... 

The two distinct bond-forming steps in tandem vicinal difunctionalization have been studied extensively. The first step consists of a nucleophilic addition to a ir-system the nucleophile is almost invariably an organometal. 1,4-Addition to an a, -unsaturated carbonyl substrate concomitantly generates a new cr-bond at the (3-carbon and an enolate ion. The second step constitutes C-functionalization of the enolate intermediate, forming a new o -bond between the nucleophilic a-carbon of the enolate and an electrophilic reagent. 

A similar but conceptually distinct approach to difunctionalization of terminal alkynes consists of sequential carboboration-palladium-catalyzed cross-coupling 137 equation (33) illustrates that this method also provides alkenes of high stereochemical purity by net syn Markovnikov addition. Benzyne-contain-ing molecules can act as highly activated substrates for vicinal difunctionalizations initiated by nucleophiles 138-140 thus, nucleophilic addition-electrophilic trapping can serve as an alternative to sequential directed metallation for the production of 1,2-disubstituted and 1,2,3-trisubstituted aromatic systems (equation 34).141... 

Alkynes can be transformed into alkenylstannanes by reaction with stannyl-cuprates. It is possible to trap the 1,2-dimetallic alkene species with various electrophiles. The analogous vicinal difunctionalization of alkynyl selenides " has also been reported. A route to trisubstituted alkenes from phenylthioacetylene"" starts with cuprate addition, but a 1,2-metal rearrangment is involved. Enamines are obtained from N-ethynyldiphenylamine. The alkenylcopper intermediate is also reactive toward many electrophiles. Silylcupration of functionalized alkynes may lead to cyclic products by virtue of intramolecular alkylation. ... 

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