Electrophiles, reaction with allyl silane

While trifluoro and other halosilanes function by increased electrophilicity at silicon, nucleophilic reactivity of allylic silanes can be enhanced by formation of anionic adducts (silicates). Reaction of allylic silanes with aldehydes and ketones can... 

Reaction of allylic silanes with enantiomerically pure 1,3-dioxanes has been found to proceed with high enantioselectivity.70 The enantioselectivity is dependent on several reaction variables, including the Lewis acid and the solvent. The observed stereoselectivity appears to reflect differences in the precise structure of the electrophilic species that is generated. Mild Lewis acids tend to react with inversion of configuration at the reaction site, whereas very strong Lewis acids cause loss of enantioselectivity. These trends, and related effects of solvent and other experimental variables, determine the nature of the electrophile. With mild Lewis acids, a tight ion pair favors inversion, whereas stronger... 

The reaction of allyl silanes with aldehydes and ketones activated as electrophiles by Lewis acids is a very useful method for preparing homoallylic alcohols. Since allyl silanes are only modestly nucleophilic, strong electrophiles are needed to ensure a good reactivity match. 

Allylic silanes and stannanes react with various electrophiles with demetallation. These reactions can occur via several related mechanisms. Both types of reactants can deliver alkylic groups to electrophilic centers such as carbonyl and iminium. 

As with the silanes, the most useful synthetic procedures involve electrophilic attack on alkenyl and allylic stannanes. The stannanes are considerably more reactive than the corresponding silanes because there is more anionic character on carbon in the C-Sn bond and it is a weaker bond.156 The most useful reactions in terms of syntheses involve the Lewis acid-catalyzed addition of allylic stannanes to aldehydes.157 The reaction occurs with allylic transposition. 

There are, however, serious problems that must be overcome in the application of this reaction to synthesis. The product is a new carbocation that can react further. Repetitive addition to alkene molecules leads to polymerization. Indeed, this is the mechanism of acid-catalyzed polymerization of alkenes. There is also the possibility of rearrangement. A key requirement for adapting the reaction of carbocations with alkenes to the synthesis of small molecules is control of the reactivity of the newly formed carbocation intermediate. Synthetically useful carbocation-alkene reactions require a suitable termination step. We have already encountered one successful strategy in the reaction of alkenyl and allylic silanes and stannanes with electrophilic carbon (see Chapter 9). In those reactions, the silyl or stannyl substituent is eliminated and a stable alkene is formed. The increased reactivity of the silyl- and stannyl-substituted alkenes is also favorable to the synthetic utility of carbocation-alkene reactions because the reactants are more nucleophilic than the product alkenes. 

Allyl silanes react with a wide variety of electrophiles, rather like the ones that react with silyl enol ethers, provided they are activated, usually by a Lewis acid. Titanium tetrachloride is widely used but other successful Lewis acids include boron trifluoride, aluminium chloride, and trim ethyls ilyl tri-flate. Electrophiles include the humble proton generated from acetic add. The regiocontrol is complete. No reaction is observed at the other end of the allylic system. All our examples are on the allyl silane we prepared earlier in the chapter. 

The reaction with EtAlCb is a Lewis-acid-catalysed conjugate addition of the allyl silane on to the enone. Conjugate addition is preferred because the nucleophile (allyl silane) is tethered to the electrophile (enone) and the five-membered ring is easier to form than the alternative seven-membered ring. 

Scheme 9 demonstrates the further synthetic application of the thus obtained N,0-acetals. Substitution of the alkoxy or acyloxy group by nucleophiles like enol ethers, enol esters, enamines, other electron-rich olefins, CH-acidic compounds, electron-rich aromatics, isocyanides, trimethylsilyl cyanide, organometallics, vinyl and allyl silanes, hydroxy functions, or trialkylphosphites either catalyzed by Lewis acids or proton acids leads to the product of the amidoalkylation reaction (path a). In the presence of stereocenters as control elements, diasteroselective amidoalkylation reactions can be performed as shown in a large number of examples. On the other side, as Nyberg showed for the first time [196], elimination with formation of enecarbamates [208] and enamides [196,208,209] followed by reaction with electrophiles or nucleophiles (path b) also is possible. 

Crotyl silanes offer the possibility of diastereoselectivity in reactions with aldehydes in the same way as the corresponding boranes. The mechanism is completely different because crotyl trialkylsilanes react via an open transition state as the silicon is not Lewis acidic enough to bind the carbonyl oxygen of the electrophile. Instead, the aldehyde has to be activated by an additional Lewis acid or by conversion into a reactive oxonium ion by one of the methods described above. The stereoelectronic demands of the allylic silane system contribute to the success of this transformation. Addition takes place in an Se2 sense so that the electrophile is attached to the remote carbon on the opposite side of the n system to that originally occupied by silicon and the newly formed double bond is trans to minimize allylic strain. 

In the presence of a Lewis acid (such as Et2AlCl), allylsilanes react with electrophiles in a regiospecific manner. The intermediate (3-carbocation is stabilized by (a-Tc)-conjugation with the C-Si bond. The most important feature of this reaction is that the electrophile reacts with the terminus (y-carbon) of the allyl system, and the n-system is relocated adjacent to its original position. Even substituted allylic silanes can be acylated at the more hindered site. Because of this predictability and their high nucleophilicity, allylsilanes are valuable in many synthetic transformations. 

The most useful of all allyl anion equivalents are the allyl silanes.20 This is because it is easy to make them regioselectively, because they do not undergo allylic rearrangement (silicon does not do a [1,3] shift) and because their reactions with electrophiles are very well controlled addition always occurring at the opposite end to the silicon atom. Symmetrical allyl silanes can be made from allyl-lithiums or Grignards by displacement of chloride from silicon. A useful variant is to mix the halide with a metal, e.g. sodium, and Me3SiCl in the same reaction, rather after the style of the silicon acyloin reaction,21 as in the synthesis of the acetal 80. 

The Houk conformation for reactions ofalkenes with electrophiles Allyl silanes... 

We shall see in this section that allyl silanes can direct the transfer of chirality through Houk conformations without the need to form an enolate. The typical reaction of an allyl silane with an electrophile (chapter 12) is at the remote atom of the alkene with loss of the silyl group. This transfers, but does not create, chirality. So the allyl silane 152 reacts with formaldehyde and a Lewis acid to give the homoallylic alcohol 153 with no loss of ee. The silyl group has gone, the alkene is transposed, and the sense of the SE2 reaction is anti. All this is explained by the Houk conformation 154 with the C-Si bond able to interact with the alkene to raise the energy of the p-orbital and direct both the regio- and the stereoselectivity.25... 

To create new chirality we need a prochiral electrophile. Single enantiomers of functionalised allyl silanes 155 are made by kinetic resolution with a lipase.26 Reaction of 155 with an aldehyde and a Lewis acid gives the syn and anti homoallylic alcohols 156 and 157. 

Palladium-catalyzed hydrosilylation of 1,3-dienes is one of the important synthetic methods for allylic silanes, and considerable attention has been directed to the asymmetric synthesis of the latter by catalytic methods [9]. Optically active allyhc silanes have been used as chiral allylating reagents in S reactions with electrophiles, typically aldehydes [38,39]. In the presence of Pd catalysts the reaction with hydrosilanes containing electron-withdrawing atoms or substituents on sihcon usually proceeds in a 1,4-fashion giving allyHc silanes [40,41]. Asymmetric hydrosilylation of cyclopentadiene (29) forming optically active 3-silylcyclopentene (30) has been most extensively studied (Scheme 13). In the first report, hydrosilylation of cyclopentadiene (29) with methyldichlorosilane in the presence of 0.01 mol % of palladium-(l )-(S)-PPFA (15a) as a catalyst gave... 

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