Nucleophihc vinylic substitution

Nucleophihc substitution reactions in aqueous solution, 38, 161 Nucleophihc vinyhc substitution, 7, 1 Nucleophihc vinyhc substitution and vinyl cation intermediates in the reactions of vinyl iodonium salts, 37, 1... 

Recently, Bandini and co-workers [175] reported an intramolecular gold(I)-catalyzed asymmetric nucleophihc alkoxylation of allylic alcohols leading to vinyl-substituted six- and seven-membered heterocycles (Scheme 30a). Following this work, Aponick and Biannic [176] developed a synthesis of tetrahydrop5rans in high enantio- or diastereoselectivities (Scheme 30b). The configuration of the allylic alcohol controls efficiently the facial selectivity when the substrates include additional stereocenters. 

Such an intermediate can also stabilize itself by combining with a positive species. When it does, the reaction is nucleophihc addition to a C=C double bond (see Chapter 15). It is not surprising that with vinylic substrates addition and substitution often compete. For chloroquinones, where the charge is spread by resonance, tetrahedral intermediates have been isolated ... 

The synthesis of buprenorphine has a certain similarity to that of etorphine. After the Diels-Alder reaction of thebaine with methyl vinyl ketone, the double bond is hydrogenated. Then follows a Grignard reaction with t-butyhnagnesium chloride. For modification of the tertiary amine, this is demethylated with cyanogen bromide (von Braun reaction) and treated with cyclopropanecarbonyl chloride. Following reduction with lithium aluminium hydride, the aromatic methoxy-group is finally replaced by nucleophihc substitution under forcing conditions. 

Scheme 8.43. Aromatic substitution ortho and para to the phenolic hydroxyl via the Claisen rearrangement. Two pathways are shown. The first involves nucleophihc substitution (Sn2 and/or Sn2 ) at the oxygen of the phenol yielding an ether, which subsequently rearranges. The second involves a direct substitution of the vinyl gronp with a hydrogen on the aromatic ring.

SnI and Sn2 reactions occur only at sp hybridized carbon atoms. Now that we have learned about the mechanisms for nucleophihc substitution we can understand why vinyl halides and aryl halides, which have a halogen atom bonded to an sp hybridized C, do not undergo nucleophilic substitution by either the SnI or Sn2 mechanism. The discussion here centers on vinyl halides, but similar arguments hold for aryl hahdes as well. 

The generation of ethers through the formation of oxygen-carbon(sp ) bonds (Williamson approach) is rare due to the sluggish reactivity of vinyl and aryl halides in nucleophilic substitution. Furthermore, while nucleophihc substitution chemistry tends to work well for primary systems, significant amounts of elimination products are often observed with secondary alkyl hahdes, and tertiary substrates are typically unresponsive. As a result, a number of transition metal-catalyzed routes to the formation of ethers through the formation of oxygen-carbon(sp ) bonds have been developed. 

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