Download Chapter 13 Silicon reagents

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
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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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Two other highly important properties of silicon
 Stablisation of α-carbanions
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.
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Two other highly important properties of silicon
 Stablisation of β-cations (b-effect of silicon )
C
+
Cb
Si
E.g allyl and vinyl silanes react with electrophiles via the following mechanisms
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 ipso-Substitution: a consequence of b-effect of silicon
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 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
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 Reaction of organosilanes (Silicon as a protecting
group for OH)
• 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
R
OH
TBSCl
Base
R
OTBS
Base = Et3N, imidazole
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 Reaction of organosilanes (Silicon as a protecting
group for OH)
 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.
With bulkier groups, such as TBDMS, it is possible to distinguish between primary
and secondary alcohols.
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Reaction of organosilanes (Silicon as a protecting group for OH)
Deprotection:
Selective deprotection
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 Reaction of organosilanes (Peterson olefination)
 Generation of Si-stabilised carbanions
Deprotonation with a strong base
Metal-halogen exchange
Addition of organometallics to vinyl silanes
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 Reaction of organosilanes (Peterson olefination)
• Key compounds are β-hydroxysilanes generated from the
reaction of Si-stabilised carbanions with carbonyl compounds
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 Reaction of organosilanes (Peterson olefination)
The next step is the elimination of OH and SiMe3, which can
generally be done in two ways. Each method is
stereospecific.
Acidic hydrolysis proceeds via
an anti-elimination
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 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.
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Example:
The Peterson olefination is often less sterially demanding than the Wittig reaction
Recent Literature:
W. Adam, C. M. Ortega-Schulte, Synlett, 2003, 414-416.
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M. Iguchi, K. Tomioka, Org. Lett., 2002, 4, 4329-4331.
A. Barbero, Y. Blanco, C. Garcia, Synthesis, 2000, 1223-1228.
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 Reaction of organosilanes (Silyl Enol Ethers )
• Preparation of silyl enol ethers
OSiMe3
1. Me2CuLi
2. Me3SiCl
O
OSiMe3
Et3SiH
Cat. (Ph3P)3RhCl
• Some reactions of silyl enol ethers
MeLi
PhCH2N+Me3F-
Activated
enolate
O
O Li+
OSiMe3
OSiMe3
O
Br
Me N+CH Ph
3
O
2
Me4Si
FSiMe3
I
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In the presence of a lewis acid
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
Silyl Enol Ethers: 2-Trimethylsilyloxybuta-1,3-dienes
Me3SiCl
NEt3
O
O
SiMe3
 Genaration:
OMe
OMe
Me3SiCl
NEt3
O
ZnCl2
OMe
Danishefsky's diene
O
SiMe3
OMe O
H
O
Via endo TS
+
O
Me3SiO
O
SiMe3
O
H
O
O
 Reaction:
H3O+
H
O
O
O
H
O
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 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.
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 Vinyl silanes
• Preparation using a variety of methods
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 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.
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 Vinyl silanes
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 Allyl silanes
 Preparation:
 The reaction of allyl organometallic reagents with silylating agents.
 The Wittig Reaction
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 The reactions of allyl silanes
 Allyl silanes are more reactive than vinyl silanes and much more reactive
than simple alkenes
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 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.
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 Allyl silanes react with a wide range of electrophiles in the presence of
Lewis acids such as TiCl4
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 Aryl silanes
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Exercise 4
• Drawing the structures of the intermediate and the final products.
H
Et3N/C6H6
1.
O
i) TBAF
ii) H2O
OTMS
2.
•
O
+
CO2Et
+ TMSCl
Ph
H
Outline at least two kinds of enzymes or whole-cell systems used in the
reduction of ketones to secondary alcohols.
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