ß-Effect. Synthesis of Organosilanes. Alkylsilanes

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Ilene Melton
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1 Silicon Silicon is located in the periodic table immediately below carbon. It is tetravalent and forms tetrahedral compounds. Unlike carbon silicon does not form double bonds. There are also some important differences in bond strength: the silicon-silicon bond (230 kj mol -1 ) is weak in comparison to the carbon-carbon bond (356 kj mol -1 ) whereas the silicon-oxygen bond (368 kj mol -1 ) is stronger than the corresponding carbon-oxygen s-bond (336 kj mol -1 ). In general, bonds with electronegative elements are stronger with silicon than with carbon. In particular, the siliconfluorine bond is extremely strong (582 kj mol -1 ). In comparison, bonds to electropositive elements are weaker (i.e. triethylsilane (Et 3 SiH) is a reducing agent since the Si H bond is relatively weak (~323 kj mol -1 )). The carbon-silicon bond is strong enough for trialkyl silyl groups to survive a wide variety of synthetic transformations, but it is weak enough to be selectively cleaved when required using mild conditions. In particular, the hard nucleophilic fluoride group is used to remove silicon groups with the driving force for the transformation being the formation of strong Si F bonds. The bonds between silicon and other atoms are in general longer than the equivalent bonds between carbon and the corresponding atoms. For example, Si C bonds are 1.89Å whereas a typical C C bond is 1.54Å. The increased bond lengths between silicon and other atoms in comparison to the corresponding systems involving carbon enables hard nucleophiles (in particular F - ) to react at sterically hindered silicon centres. Silicon has a lower electronegativity value (1.8), c.f. carbon (2.5) and consequently, carbon-silicon bonds are polarised, rendering the silicon open to attack by nucleophiles. The most effective nucleophiles for silicon are those which are strongly electronegative and that upon reaction lead to the formation of strong bonds to silicon. A common source of fluoride ions is tetrabutylammonium fluoride (TBAF). This reagent is soluble in a wide range of commonly employed organic solvents. For example, silyl ethers can be cleaved by treatment with tetrabutylammonium fluoride. The mechanism involved appears to involve a simple S N 2 process, however, this is not the case. The reaction proceeds via a pentacovalent silicon centre. Two factors unique to silicon (in comparison to carbon) facilitate this process: i) the long silicon carbon bonds permit nucleophilic attack at what would appear to be a sterically congested silicon centre and ii) the vacant d-orbitals of silicon permit nucleophilic attack via geometric approaches not permitted by the bonding and anti-bonding orbitals of carbon. This nucleophilic substitution process is referred to as the S N 2-Si pathway and is an extremely rapid process. Almost all acyclic halosilanes (apart from fluorosilanes) react with nucleophiles by the S N 2-Si pathway and this leads to the inversion of configuration at silicon. In theory, the above reaction could proceed via an S N 1 pathway, (trialkylsilane cations are frequently observed in mass spectra), but this pathway is kinetically slower and leads to a 50:50 distribution of isomers.

2 ß-Effect The stabilisation of cations at the carbon atom in β-position to silicon is referred to as the β-effect of silicon. It is a result of the stabilisation of the positive charge by donation of electron density from the filled s-orbitals of the adjacent C H and C C bonds to the vacant p-orbital of silicon. Silicon is more electropositive in comparison to carbon and therefore the C Si bonds is an even more effective donor. In molecular orbital terms this can be described as the overlap between the vacant p-orbital on the carbon ß to the silicon atom and the filled s-orbital between the silicon atom and the a-carbon. Maximum stabilization only occurs if the vacant p-orbital and the s-orbital of the carbon-silicon bond are in the same plane. This can readily occur in acyclic systems but can be more difficult in cyclic systems. Another consequence of the β-effect is the preference for Ipso-Substitution displayed by aryl silanes in electrophilic aromatic substitution reactions. The only product formed in these reactions is the one resulting from direct substitution of the silyl group on the aromatic ring. Due to the β- effect the most stable Wheland intermediate in this reaction is ß to the silicon atom. Subsequent cleavage of the weakened C Si bond by a nucleophile therefore affords the ipso product. An alternative process can occur that would also involve the generation of a cation ß to silicon. However, this cation is not as stable as the vacant p-orbital is orthogonal to the C-Si bond and there cannot interact with it. Synthesis of Organosilanes Alkylsilanes Nucleophilic displacement of a Halogen from a Halosilane by an Organometallic Reagent

3 Grignard reagents and alkyl lithium systems can react with trimethylsilyl chloride to afford the corresponding tetrasubstituted silanes. The carbon-silicon bonds are sufficiently robust to withstand these reaction conditions and thus the trimethylsilyl group remains intact. Vinyl- or Alkenylsilanes Addition of Silanes to Multiple Bonds (Hydrosilation): Alkenes and alkynes can be converted into organosilanes by hydrosilation, typically involving the use of a catalyst such as hexachloroplatinic acid (H 2 PtCl 6 ). Silanes that possess either one or more halogen substituent are more reactive than trialkylsilanes. Nucleophilic displacement of a Halogen from a Halosilane by an Organometallic Reagent Alkynyl Silanes Terminal alkynes possess acidic protons (pka ~25) and are therefore removed by strong bases (Grignards, alkyl lithiums). If there are two alkynyl protons present one of them is protected ("masked") by trimethylsilylation. After the reaction the TMS protecting group can be readily cleaved by treatment with TBAF.

4 Alkynyl silanes can undergo electrophilic attack followed by elimination. The -effect of silicon determines the regiochemistry of the electrophile attack. Silicon-based Protecting Groups Silicon-based protecting groups are used extensively as a direct consequence of their versatility. They are formed efficiently by treatment of an halosilane with an alkoxide and the silicon group is easily removed by nucleophilic displacement with either fluoride or oxygen nucleophiles. The rate of removal is related to the steric bulk of the silicon-protecting group. The simplest protecting group is the trimethylsilyl (TMS) unit.trimethylsilylation can be carried out using TMS-Cl and base or other related reagents in which silicon is activated towards nucleophilic attack (e.g. N- Trimethylsilylimidazole (TMSI)). As it is the least sterically hindered silyl ether it is cleaved using water with either trace of acid or base. In general, the bulkier the alkyl substituents on the silicon the harsher the conditions required for removal of the protecting group. In use are the tertiary-butyldimethylsilyl (TBDMS) group, the triisopropylsilyl (TIPS) group and the tertiary-butyldiphenylsilyl (TBDPS). The bulkier the group the more difficult the formation of the silylether is. Imidazole is added to increase the reaction rate (nucleophilic catalysis). The TBDMS group is easily introduced by treating the alcohol with TBDMSCl in DMF in conjunction with imidazole. With bulkier groups it is possible to distinguish between primary and secondary alcohols. The most common deprotection procedure of sterically demanding Si-protecting groups involves flouride cleavage with TBAF (tetrabutylammonium fluoride) as reagent. Silyl Enol Ethers Silyl enol ethers are of enormous importance in organic chemistry as stable enolate equivalents. They are frequently employed in directed aldol reactions. Silyl enol ethers are produced classically by quenching enolate anions with TMS-Cl as electrophile.

5 The regiochemistry of enolate formation can be controlled using kinetic conditions (low temperature, strong, sterically demanding base) or thermodynamic conditions (weaker, "equilibrating" base, room or higher temperatures). Silyl enol ethers can also be prepared by either conjugate addition followed by trapping of the intermediate enolate ion with TMS-C. silylation or by direct hydrosilylation of a,ß-unsaturated ketones. Silyl enol ethers are relatively inert towards reaction with electrophiles. To achieve this reaction the silyl enol ether is first "activated" by conversion into a more reactive enolate (lithium enolate by reaction with methyl lithium or quaternary ammonium enolate with quaternary ammonium fluoride. Silyl enol ethers can also react with strong electrophiles if the electrophilicity of the alkylating agent is enhanced by the presence of a Lewis acid. Under such Lewis acid catalysis, electrophiles such as aldehydes and ketones may be added to trimethylsilyl enol ethers. This reaction is sometimes referred to as the Mukayama Aldol reaction.

Chapter 22 Carbonyl Alpha-Substitution Reactions

John E. McMurry www.cengage.com/chemistry/mcmurry Chapter 22 Carbonyl Alpha-Substitution Reactions The α Position The carbon next to the carbonyl group is designated as being in the α position Electrophilic