1 Chapter 13 Silicon reagents  General features  Two other highly important properties of silicon  Reactions of organosilanes  1,2 rearrangements (Brook rearrangement)  Silicon as a protecting group for OH  Peterson olefination(Si-stabilised carbanions)  Silylenolethers  Alkylsilanes  Vinyl- or Alkenylsilanes  Allyl Silanes  Aryl Silanes

2 General Features Silicon is directly below carbon in the periodic table, and shows some similarity in bonding. It forms 4 bonds in neutral molecules and is tetrahedral. Silicon does not form very stable multiple bonds, as the large 3p orbital on silicon does not overlap well with the 2p orbital on carbon, oxygen or nitrogen. Carbon is more electronegative than silicon Silicon is a very versatile element, and you will find silicon reagents in 2 major roles; As protecting groups for OH In reactions for C-C and C=C bond formation

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4 Two other highly important properties of silicon Si-stabilised carbanions are important in the Peterson olefination reaction (see later)  Donation of the negative charge into a  * antigonding orbityal of an adjacent Si-C bond stabilises the anion.  This donation is rendered more effective due to silicon’s lower electronegativity compared to carbon. Therefore the  * antibonding orbital has a greater orbital coeffient on silicon. What this really means is that the antibonding orbital is a bit larger on the silicon side and leads to better overlap with the orbital containing the negative charge.  Stablisation of α-carbanions

5 Two other highly important properties of silicon  Stablisation of β-cations (  -effect of silicon ) CC CC Si + E.g allyl and vinyl silanes react with electrophiles via the following mechanisms

6  ipso-Substitution: a consequence of  -effect of silicon

7  Reaction of organosilanes ( Brook rearrangement ) When silylcarbinols are treated with base or active metals the silyl group is known to migrate from the C to a neighbouring O atom e.g. Brook rearrangement, generating silyl ethers

8 Various protecting groups are available and the resulting silyl ethers can be cleaved under a variety of conditions. Silyl protecting groups are typically put on under basic conditions  Reaction of organosilanes ( Silicon as a protecting group for OH )

9  The stability of the silyl ether towards cleavage depends on a number of factors:  Increasing steric bulk raises stability.  EWGs on silicon increase acid stability and decrease base stability and vice versa.  The ease of cleavage with F - parallels the ease of basic hydrolysis.  Reaction of organosilanes ( Silicon as a protecting group for OH ) With bulkier groups, such as TBDMS, it is possible to distinguish between primary and secondary alcohols.

10  Reaction of organosilanes ( Silicon as a protecting group for OH ) Deprotection: Selective deprotection

11  Reaction of organosilanes ( Peterson olefination )  Generation of Si-stabilised carbanions  Deprotonation with a strong base  Metal-halogen exchange  Addition of organometallics to vinyl silanes

12  Reaction of organosilanes ( Peterson olefination ) Key compounds are β-hydroxysilanes generated from the reaction of Si-stabilised carbanions with carbonyl compounds

13  Reaction of organosilanes ( Peterson olefination ) The next step is the elimination of OH and SiMe 3, which can generally be done in two ways. Each method is stereospecific. Acidic hydrolysis proceeds via an anti-elimination

14  Reaction of organosilanes ( Peterson olefination ) Basic conditions - syn elimination Therefore, in principle the Peterson olefination can be used to make single geometric isomers of alkenes. However, this is complicated by the difficulty in preparing pure diastereomers of the β-hydroxysilanes.

15 Example: The Peterson olefination is often less sterially demanding than the Wittig reaction W. Adam, C. M. Ortega-Schulte, Synlett, 2003, Recent Literature:

16 M. Iguchi, K. Tomioka, Org. Lett., 2002, 4, A. Barbero, Y. Blanco, C. Garcia, Synthesis, 2000,

17  Reaction of organosilanes ( Silyl Enol Ethers ) Some reactions of silyl enol ethers Preparation of silyl enol ethers Activated enolate

18 In the presence of a lewis acid

19  Genaration:  Silyl Enol Ethers: 2-Trimethylsilyloxybuta-1,3-dienes  Reaction:

20  Alkylsilanes Almost all acyclic Cl, Br, and I silanes react with all nucleophiles by an SN2 type mechanism leading to an inversion of configuration at the Si atom. In many cases the pentacovalent Si is thought to be an intermediate rather than a transition state.

21  Vinyl silanes Preparation using a variety of methods

22  Vinyl silanes The reactions of vinyl silanes: electrophilic substitution of the silyl group. This is highly regioselective and the substitution occurs with retention of alkene geometry.

23  Vinyl silanes

24  Allyl silanes  Preparation:  The reaction of allyl organometallic reagents with silylating agents.  The Wittig Reaction

25  The reactions of allyl silanes  Allyl silanes are more reactive than vinyl silanes and much more reactive than simple alkenes

26  The reactions of allyl silanes  Allyl silanes react with electrophiles with high regioselectivity. The electrophile attacks at the other end of the allylic system, and no bond rotation is required.

27  Allyl silanes react with a wide range of electrophiles in the presence of Lewis acids such as TiCl 4

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29  Aryl silanes

30 Exercise 4 Drawing the structures of the intermediate and the final products. Outline at least two kinds of enzymes or whole-cell systems used in the reduction of ketones to secondary alcohols.