Electrophilic substitution, stereospecificity

A short digression is in order at this juncture. The electrophilic substitution of a vinylsilane is a very useful process because it is generally both regio- and stereospecific. The carbon-silicon bond is strongly polarized due to the high electronegativity of carbon (2.35) relative to silicon (1.64).67b A unique and important conse-... 

The presence of chelating groups in those complexes is necessary to stabilize the intermediate aryl-palladium complex for isolation but it does not seem necessary to cause palladation. The chelating group does, however, tremendously accelerate the palladation. Aromatic compounds reactive to electrophilic substitution apparently undergo palladation with palladium acetate in acetic acid solution fairly readily at 100 °C or above. Of course, the arylpalladium acetates presumably formed, are not stable under these conditions, and they decompose very rapidly into biaryls and palladium metal 34,35,36) ag do aryl palladium salts prepared by the exchange route 24>. If the direct palladation is carried out in the presence of suitable olefins, arylation can be achieved, so far, however, only in poor yields, arid with concurrent loss of stereospecificity and formation of isomers and other side products 37.38). 

Scheme 6.1.5 Stereospecificity in the electrophilic substitution of an a-carbamoyloxy benzyllithium...

Scheme 6.1.10 Stereospecific electrophilic substitutions of a non-heterosubstituted benzyllithium...

Scheme 6.1.14 Stereospecific electrophilic substitutions of a cinnamyllithium 6.1.4.3 Rearrangements of stabilised or ganolithiums...

Electrophilic substitutions of alkenyl-, aryl-, and alkynylsilanes with heteroatom-stabilized cationic carbon species generated by the action of a Lewis or Brpnsted acid (acyl cation, oxocarbenium ion, etc.) provide powerful methods for carbon-carbon bond formation. Particularly, intramolecular reactions of alkenylsilanes with oxocarbenium and iminium ions are very valuable for stereoselective construction of cyclic ether and amine units.21-23 For example, the BFj OEt -promoted reaction of (E)- and (Z)-alkenylsilanes bearing an acetal moiety in the alkenyl ligand gives 2,6-disubstituted dihydropyrans in a stereospecific manner (Scheme l).23 Arylsilanes also can be utilized for a similar cyclization.24... 

The stereospecificity of deprotonation of ketone NA -dialkylhydrazones is less defined because of the problem of making unambiguous stereochemical assignments. However, based on the observed stereoselectivity of electrophilic substitutions on these anions, on chemical shift data and on analogies to enolate chemistry, it appears that ( )c—c stereochemistry again predominates, at least with LDA de-protonations. ... 

In the absence of Lewis acids, stereoselectivity is strongly dependent upon the geometry of the double bond in the allylstannane, both in simple thermal reactions (Scheme 28) and in pressure-induced reactions, as expected for a cyclic transition state. As well as being selective for the formation of the anti arrangement of substituents on the carbon chain, the overall electrophilic substitution in the thermal reaction of an ( )-allylstannane, is stereospecifically syn (Scheme 29), with a cyclic transition state (51),... 

Usually, the selectivities of both the individual steps - formation of the lithium intermediate and electrophilic substitution - cannot be monitored separately, and the product of the two selectivities is measured. Fortunately, it turned out, for most carbanion pairs and electrophilic reagents, that the substitution step is completely stereospecific (mostly retention, in some cases inversion), within the hmits of detection. Larger errors only may occur when the rates of... 

C.ii.e. Heck Reaction The cross-coupling between 5-iodoimidazoles and methyl acrylate has been appUed to complex structures as depicted for the preparation of (E S-(2-carbomethoxyvinyl)-l-(2,3,5-lri-0-acetyl-i eM-Z)-ribofuranosyl)imidazole-4-carboxamide 142 from the corresponding 5-iodoimidazole (Scheme 59). Acrylonitrile reacts in the same manner under Heck conditions to provide the ( )-5-cyanovinyl derivative. The C-glycosyl bond formation in the Heck coupling between the 3-iodopyrazolo[4,3-dlpyrimidine 143 and the ribofuranoid glycal 144 was regio- and stereospecific. The iodo substituent in the substrate was introduced by a simple electrophilic substitution. ... 

The highly impressive and remarkably stereospecific cobalt-catalysed diyne cooligomerization reaction, previously used to synthesize tricyclic systems, has now been applied to steroidal structures (Scheme 27), producing the shortest approach to the steroid nucleus, from an acyclic precursor, to date. Electrophilic substitution of the o-bis(trimethylsilyl)arene unit and the introduction of heteroatoms into the precursor (118) should expand the range of steroidal products considerably. 

Ketones can present a problem in specificity. Under basic conditions, they may react with two or more molecules of the electrophile to give a mixture of products. Furthermore, unsymmetric ketones may present a choice of two enolate sites so that control is necessary to direct to the desired one. Many alternatives have been developed for this problem. One solution is to incorporate a temporary group on one enolate site to render that site more acidic so that the electrophile will react there. The familiar p-ketoester reactions (acetoacetic ester synthesis) are widely used. For another alternative, the ketone is first converted to an imine (Section 6.2.3) or a dimethyl hydrazone, and the enolate of that derivative is used with electrophiles [28]. Stereospecificity of the addition is obtained by forming a derivative with (5)-l-amino-2-methoxymethyl-pyrrolidine (SAMP) as shown in Equation 7.15 [29]. Without derivati-zation, alkylation of unsymmetric ketones will occur mostly at the more substituted enolate site under reversible deprotonating conditions. Using a base such as EDA will give alkylation primarily at the least substituted enolate. 

As mentioned in Section 2, there have been many general calculations on the charge densities of aromatic heterocyclic systems, and these results have been used to make predictions about substitution patterns. In addition, studies of electrophilic substitutions of some heterocycles have used computational methods to predict not only the orientation but also the reactivity and stereospecificity of the substitution."... 

---