Addition of Vinyl and Aryl Groups

Addition of Vinyl and Aryl Groups. The reaction of aromatic radicals, generated by decomposition of diazonium salts, with iminium salts in the presence of TiCE in aqueous media produces secondary amines (Eq. 11.53).91 The iminium salts are formed in situ from aromatic amines and aldehydes. 

Addition of vinyl and aryl groups Cope rearrangement Cross-dehydrogenative coupling Cycloaddition reaction... 

Chiral aminals 1,4-dihydropyridine-3-carboxaldehydes.1 The chiral aminal 2 prepared from pyridine-3-carboxylaldehyde and (S,S)-12 reacts with organocopper reagents in the presence of methyl chloroformate to give almost exclusively products of 1,4-addition, as expected from reactions of the free aldehyde.3 No products of 1,2-addition are formed, but 1,6-adducts are minor products in some cases. The 1,4-adducts are formed in 82-93% de (R-configuration). Addition of butyl and ethyl groups is best effected with lithium cuprates, but addition of methyl, vinyl, or aryl groups is best effected with organomagnesium cuprates. Under these conditions,... 

Kharasch and Tawney (1941) reported that copper salts catalyze 1,4-addi-tion of Grignard reagents to a,jS-unsaturated ketones. Gilman et al. (1952) first discovered that phenylcopper reacts with benzalacetophenone in a 1,4-addition. Subsequently House and associates (1966) have revealed the scope of the conjugate addition of cuprate complexes. Now alkyl, vinyl, and aryl groups can be introduced specifically at the p position of a,jS-unsaturated carbonyl compounds. Transfer of an allyl group from lithium diallylcuprate to 2-cyclohexenone is also known (House and Fischer, 1969). However, ethynyl, cyano, and hetero groups attached to the copper atom are difficult to transfer to electron-poor olefins. 

Palladium-Catalyzed Reactions. Numerous nucleophiles react with (l-bromovinyl)trimethylsilane in the presence of palladium complexes. The bromine has been substituted by phenylthio, vinyl, and aryl groups. This approach gives reasonable yields of the desired products. However, the substitution reactions sometimes lack regiospecificity. For example, a mixture of regioisomers was obtained in eq 6. Two mechanisms have been proposed for the formation of the -substituted product. One involves an elimination step to give trimethylsilylacetylene as an intermediate, which then undergoes catalyzed additions with the nucleophile at either the a- or positions. The other mechanism involves the formation of a pentacoordinated palladium intermediate, leading to the formation of isomeric products. ... 

Even if hundreds of chiral catalysts have been developed to promote the enantioselective addition of alkylzinc reagents to aldehydes with enantioselectivities over 90% ee, the addition of organozinc reagents to aldehydes is not a solved problem. For example, only very few studies on the addition of vinyl groups or acetylides and even arylzinc reagents to aldehydes have been published, in spite of the fact that the products of these reactions, chiral allylic, propargylic and aryl alcohols, are valuable chiral building blocks. 

The majority of the more important methods for the preparation of fluorinated compounds by substitution reactions have been reviewed in the previous sections. There are, however, some additional important synthetic procedures which should also be mentioned, mainly those concerned with the introduction of fluorine by substitution of functional groups containing boron, silicon and tin the reactions of organotin compounds are the most well-studied to date. These reactions are excellent synthetic methods for obtaining vinyl and aryl fluorides (sec also Section 1.1.1.1.). 

In a similar fashion, chromium tricarbonyl complexes of aryl ketones are exclusively alkylated and reduced from the exo face relative to the metal. For example, addition of vinyl magnesium chloride to the substituted tetralone complex (42) affords the alcohol (43) exclusively with an antirelationship between the incoming nucleophile and the chromium tricarbonyl group (Scheme 83). This was used in a synthesis of 11-epi-helioporin B. 2-Trimethylsilyl-substituted benzaldehyde complexes undergo an interesting... 

The discussion above emphasizes that the allyl-Ni reagents are quite selective for carbon halogen bonds, especially allyl, vinyl, and aryl halides. At the same time, modest reactivity as nucleophiles toward reactive carbonyl derivatives has been reported.Simple aldehydes, the more reactive ketones (such as cyclopentanone and benzoquinone), and certain epoxides will undergo 1,2-addition of the aUyl ligand to the carbonyl group. Esters, amides, and, most remarkably, acyl halides are inert toward the allyl Ni reagents under conditions where the reagents do not decompose thermally (<80 °C or so). 

A useful, although somewhat limited, method of preparing vinyl azides involves the addition of azide ion to vinyl halides with subsequent elimination of halide ion. This reaction is only possible when the halogen is located to a group which can effectively stabilize the intermediate carbanion. A number of alkyl and aryl substituted )3-chlorovinyl ketones (23) have been found to react in this way ". In many cases, however, the resulting /3-azidovinyl ketones (26) cannot... 

By extension to cross-coupling with vinyl and aryl triflates, the scope of the Stille reaction has been expanded greatly. Almost all functional groups are tolerated without the need for protection. The reactivity order of organic halides is I>Br>OTf>>Cl, but the order between Br and OTf can be reversed by addition of LiCl. By addition of LiCl (2 or 3 equiv) to provide a more reactive Pd-intermediate (vinyl-PdCIl versus vinyl-PdOTfL ) [25] and/or stable tin by-product (RjSnCl versus R3SnOTf), the reaction proceeds smoothly at ambient temperature. 

---