Nucleophilic attack at silicon

The 2-(trimethylsilyl)ethoxymethyl group (SEM) can be removed by various fluoride sources, including TBAF, pyridinium fluoride, and HF.165 This deprotection involves nucleophilic attack at silicon, which triggers (3-elimination. 

R. A. Bassindale, P. G. Taylor, Reaction Mechanism of Nucleophilic Attack at Silicon, in The Chemistry of Organic Silicon Compounds (S. Patay, Z. Rappoport, eds.), p.839 ff, J. Wiley Sons, New York, 1989. 

The first cleavage reported is the displacement of platinum in silicon-platinum complexes by LiAlH and is believed to proceed by nucleophilic attack at silicon ... 

Therefore the polarity of the silicon-carbon bond is Si+C, and silicon-carbon bonds are generally observed to cleave in this direction, either via electrophilic attack at carbon, or nucleophilic attack at silicon. 

Further studies by Shiner and coworkers on the diastereomeric 4-(trimethylsilyl)-3-methyl-2-butyl brosylates 56 showed that solvolysis of one diastereomer gave mainly substitution products with a retained configuration68. A minor product is a cyclopropane resulting from nucleophilic attack at silicon in the ionic intermediate. From the stereochemistry of the cyclopropanes obtained it was deduced that the W conformation is favoured over the credo-sickle , as shown in Figures 3a and 3b. 

Addition to vinylsilanes is favoured over substitution by (i) the presence of bulky spectator ligands which hinder nucleophilic attack at silicon, and (ii) when the presence of electron-withdrawing groups on silicon lowers its leaving group ability. 

The results in Table 3 were explained as shown in Scheme 4. From the fact that no kinetic isotope effect was observed in the reaction of phenyl-substituted disilenes with alcohols (Table 1), it is assumed that the addition reactions of alcohols to phenyltrimethyl-disilene proceed by an initial attack of the alcoholic oxygen on silicon (nucleophilic attack at silicon), followed by fast proton transfer via a four-membered transition state. As shown in Scheme 4, the regioselectivity is explained in terms of the four-membered intermediate, where stabilization of the incipient silyl anion by the phenyl group is the major factor favoring the formation of 26 over 27. It is well known that a silyl anion is stabilized by aryl group(s)443. Thus, the product 26 predominates over 27. However, it should be mentioned that steric effects also favor attack at the less hindered SiMe2 end of the disilene, thus leading to 26. 

Kinetic studies show that hydrolysis of 1-organyl- and 1-alkoxysilatranes in neutral aqueous solutions is a first-order reaction catalyzed by the formed tris(2-hydroxyalkyl)amine13 294. As a rule, electron release and steric effects of the substituent X hinder the reaction. However, the hydrolytic stability of 1-methylsilatrane is just below that of 1-chloromethylsilatrane294. Successive introduction of methyl groups into the 3, 7 and 10 sites of the silatrane skeleton13,294 and substitution with ethyl group on C-459 retard sharply the hydrolysis rate. It was proposed294 that nucleophilic attack at silicon by water proceeds via formation of the four-centered intermediate 57 (equation 56). 

The second method122 uses a polar aprotic medium, such as DMF or N-methylpyrrol idone, a strong base, such as CsOH or KH, and r-BuOOH to facilitate nucleophilic attack at silicon sometimes, the presence of fluoride ion is advantageous. This protocol also cleaves sterically hindered alkoxysilanes. It provided a key step (equation 32) in a total synthesis123 of ( )-lupinine. 

The substitution occurs with retention of configuration at silicon. In contrast to the normal nucleophilic attack at silicon, it is relatively unaffected by steric hindrance and makes sterically crowded triorganochlorosilanes like tri-t-butylchlorosilane accessible29. 

Reaction mechanisms of nucleophilic attack at silicon A. R. Bassindale and P. G. Taylor... 

Pathways involving full ionization of the carbon-chlorine bond followed by migration of the alkyl group synchronously with nucleophilic attack at silicon or preceded by the attack have also have considered (109,110). 

The first reagent has a choice it can do either the Wittig or the Peterson reaction it prefers the Peterson reaction. This merely tells us that nucleophilic attack at silicon is faster than nucleophilic attack at phosphorus. The carbanion part of the ylid is next to silicon but it could be nowhere else. 

Scheme 8. Two possible mechanisms for nucleophilic attack at silicon with retention of configuration the fust two steps in a clockwise direction, starting at the top left represent the reaction that is zero order in NMI...

Heating dehydrates the hemiacetal-like compound the electrons on nitrogen push the OH group - t. Treatment with KOH in water does then cleave the C-Si bond by nucleophilic attack at silicon. JH would not be strong enough to remove a proton from an alkyne but attack on silicon is more rivourable because of the strong O-Si bond. 

A. R. Bassindale, P. G. Taylor, "Reaction mechanism of nucleophilic attack at silicon", in "The chemistry of organic silicon compounds" (Eds. S. Patai and Z. Rappoport), John Wiley Sons, 1989, p. 839. 

The chlorine cleavage is clearly established to be an electrophilic attack of Cl+ since no nucleophilic cleavage occurred by Cl". The reaction was explained as involving initial formation of cationic iron intermediates followed by a nucleophilic attack at silicon. Changes in ligands around the iron atom cause modifications in the electronic character of the leaving group and can thus modify the predominant stereochemistry. 

FIGURE 3. Parameters used in the correlation analysis of nucleophilic attack at silicon in an SN2-like process... 

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