Organosilicon Flashcards
What is the electronegativity of Si?
Si - χ1.8
Electropositive wrt C (χ2.5) & B (χ2)
What are some general reactions organosilicon compounds undergo?
SN2 or via a silicon-ate intermediate (5-coordinate intermediate with -ve charge)
Substitution α- to the Si via prior attack at Si
What is the C-Si bond size compared to C-C?
C-Si is longer by 25%
Si in Me3Si is less hindered
What is the significance in the bond strength of Si bonds?
Si-F is a very strong bond
Si-O is a strong bond
These are driving forces
How does substitution α- to Si occur?
What group migrates when there is substitution α- to Si?
The group most able to stabilise a -ve charge migrates
How do Si atoms stabilise β-carbocations?
C-Si bond polarity and hyperconjugation
Polarity gives slight -ve charge to the C
Hyperconjugation with p-orbital lowers lp on Si
What does Si stabilising β-carbocations drive?
Vinyl- and allylsilane chemistry
Vinyl silanes undergo direct electrophilic substitution
Allyl silanes undergo electrophillic substitution with allylic transposition
What is a common reaction between vinyl silanes and electrophiles?
Direct electrophilic substitution occurs
How do allyl silanes react with electrophiles?
Electrophilic substitution with allylic transposition
How do Si stablise α-carbanions?
Electropositivity and hyperconjugation
Hyperconj has the -ve charge donated into Si σ* orbital as electropositive
What happens when you react a silicon subsituted alkane/alkene with a strong base?
Deprotonates C which is α to the Si group
How can TMS be used as a protecting group?
R-OH + TMSCl → R-OTMS + HCl
In pyridine
Not a good protecting group as easily cleaved
How can TBS be used as a protecting group?
R-OH + imidazole + t-BuMe2Si-Cl → R-OTBDMS
Imidazole is nucleophllic catalyst - attacks Si to kick off the Cl, then O attacks the Si
Good protecting group - resistant to basic conditions, only cleavable with acid or fluoride & regioselective for 1º alcohol
How can a protecting group be removed with F- or methanolysis?
Can be under basic or acidic cond
If acidic: protonates O, then MeOH attacks Si
If base: MeO- directly attacks the Si
What groups can TBS protect?
1º alcohol
What is TMSCl used for?
In-situ trap for alkoxides
E.g. Si modified acyloin reaction - the chlorosilane removes basic alkoxides to prevent side reactions such as Clasien/Dieckmann
What is the Si-modified acyloin reaction used for?
Generating small ring compounds with no side products
What is the Brook rearrangment?
Silyl carbinols + Et2NH ⇒ R-OTMS
1,2-anionic migration of a silyl group from carbon to oxygen
Catalytic amount of a base
How can acylsilanes undergo the Brook rearrangement?
Acylsilane + NaCN → R-C(OTMS)-CN
Still goes via 1,2-rearrangement
What is the structure of sinyl enol ethers?
Used as a precursor for specific enolates, generated at a particular site not necessarily governed by the acidity of the enolisable α-protons
What routes can be used to synthesise silyl enol ethers?
From ketones - can use kinetic or thermo control
From enones - R2CuLi then TMSCl, alternatively Li in NH3(l) and t-BuOH then TMSCl
How can silyl enol ethers be synthesised from ketones under kinetic control?
LDA @ -78ºC, then TMSCl to make the sinyl enol ether
Then can add MeLi then MeI
How can thermodynamic silyl enol ethers be synthesised?
TMSCl and Et3N @ 130ºC to make the sinyl enol ether
Then can add MeLi and MeI to form ketone
How can you convert a hydrogen α to a ketone be replaced for an R group?
Convert to sinol ethyl ether - use thermo or kinetic conditions to get wanted product
Thermo - adds R to least substitued side
Kinetic - adds R to more substituted side
Then add MeLi and R-I
How are sinyl enol ethers synthesised from enones?
Either: R2CuLi followed by TMSCl
Or: Li in NH3 (l) then t-BuOH followed by TMSCl
What can be added to a silyl enol ether to make an enolate?
MeLi
What is the reactivity of silyl enol ethers and enolates with 3º-alkyl halides?
Enolates don’t react with 3º-alkyl halides
TMS enol ethers react with 3º-alkyl halides via a SN1-like mechanism
How do TMS enol ethers react with 3º-alkyl halides?
Use TiCl4 as a catalyst
Forms R3C+-TiCl5
How can you add a bulkyl tertiary R group to a ketone?
Form a silyl enol ether using thermo or kinetic control then adding MeLi
Followed by adding the 3º-alkyl halide version of the bulkyl group
How do silyl enol ethers react with π-electrophiles?
Adds electrophile to alkene
E.g. Eschenmoser’s salt, Chloroalkyl ether & TiCl4
How can you add -CH2OH to a C α to a carbonyl?
Make a silyl enol ether
Then react with benzyl chloromethyl ether to make a protected alcohol
Then H2 and Pd/C to remove -CH2Ph
How can you add -CH2NMe2 to a C α to a ketone?
Convert to a silyl enol ether
Then add Eschenmoser’s salt CH2=N+Me2 I-
How can you add =CH2 to a C α to a ketone?
Convert to a silyl enol ether
Then add Eschenmoser’s salt CH2=N+Me2 I- to add -CH2NMe2
Then react with m-CPBA/MeI to make alkene
How can a silyl enol ether be used to add a -OH to the C α to a ketone?
Make into a silyl enol ether
Then add m-CPBA which can then be hydrolysed
How can a halide atom be added to a C atom α to a ketone?
Make a silyl enol ether
Then add X2
How are silyl enol ethers used as EWG for diels-alder reactions?
Enone reacted with TMSCl and Et3N
Produces diene with protected -OTMS which cna then react in Diels-Alder reaction
-OTMS can be removed using acid or F-
What is Danishefsky’s diene and how does it react?
What is a silyl ketene acetal?
Equivalent of silyl enol ethers but for esters
What is the Ireland-Clasien rearrangement?
Allyl ester → silyl ketene acetal → hydrolysed to γ,δ-unsaturated acids (extended carboxylic acid with an alkene at opposite side)
Uses LDA (-78ºC) then TMSCl
What is the selectivity of the Ireland-Clasien rearrangment?
High-stereoselectivity as 6-membered chair TS
E- only gives anti product
Z - only gives syn product
What is the conformation for the Ireland-Clasien rearrangment?
What routes can be used to make vinyl silanes?
Silyation of organometallics - from alkynes or alkenes
Shapiro reaction - from ketones
How can vinyl silanes be made from silylation of organometallics?
Alkynes: BuLi then R3Si-Cl to R-≡-SiR3, followed by H2 Pd/C to made Z-alkene and UV to E-alkene
Alkenes: vinyl bromide to grignard followed by TMS
What is the shapiro reaction?
Ketone to vinyl silane
Reagents: ArSO2NHNH2 then 2BuLi followed by TMSCl
How do vinyl silanes react with electrophiles?
Via β-carbocation intermediates
Stereospecific due to orbital overlap
What is the orbital overlap for vinyl silane reaction with electrophiles?
What is the stereospecificity of a desilyation reaction?
E alkene to E
Z to Z
As requires sufficient overlap in elimination step
How do vinyl silanes react with Cl2 or Br2?
Anti addition of the halide then the alkoxide/F- induced anti elimination
So reverses stereochem
How can you reverse the E/Z of an alkene with a halide?
Anti addition of Cl2/Br2 to vinyl silane, then alkoxide/F- anti elimination
Gives a vinyl halide
How do vinyl silanes react with C-electrophiles?
Si-accelerated Friedel-Crafts reaction
How can you add a carbonyl (ketone or acyl) to a vinyl group?
Make a vinyl silane and then add RCOCl and AlCl3
Si-accelerated Friedel-Crafts reaction
How can an aryl silane be prepared?
Organometallic reacted with chlorosilane (R3Si-Cl)
Can either use bromoaryl with grignard or 2Li
How do arylsilanes react with electrophiles?
Ipso substitution of silane (electrophile replaces silane)
How are epoxy silanes prepared?
Either: Si varient of Darzens - uses s-BuLi then aldehyde
Epoxidation of vinyl silanes - uses mCPBA
Epoxide deprotonation - silylation using a base + TMSCl
What is the difference between n and s-BuLi?
n-BuLi is more nucleophillic but less basic, less regioselective
sec-BuLi is more basic and less nucleophillic, more regioselective
How are epoxy silanes used to mask carbonyls?
Can be cleaved easily with acidic hydrolysis to form enone which is in eqm with the carbonyl
What is an allyl silane?
How are allyl silanes prepared?
Silyation of organometallics (bromo allyl then Mg/Li and TMSCl)
Wittig olefination - using ketone with select R groups, and phosphonium with -TMS
What is the Wittig olefination?
Aldehyde/ketone + triphenyl phosphonium ylide (wittig reagent) → Alkene + Ph3P=O
Wittig reagent preapred from 1º alkyl halide + PPh3 → phosphonium salt, then phosphonium salt + BuLi → wittig reagent
Why is the Wittig olefination useful for creating allyl silanes?
Carbonyl can have different R-groups to add different groups
How do allyl silanes react?
React with electrophiles via β-carbocation to Si stabilisation
Results in transposition of double bond and loss of TMSCl
How do acetal alkenes react with lewis acids?
How can allyl silanes be used in diels-alder reactions?
Attached to diene - can then transpose the double bond formed in the DA reaction
Can use acid or TBAF and H2O
How are olefins formed from hydroxy silanes?
Acidic or basic (NaH) conditions
Driven by strong Si-O bond
Under base: O- can attack Si, syn elimination produces olefin and NaO-SiMe3
Under acid: X- attacks Si and anti-eliminates H2O, produces olefin and H2O + XSiMe3
What types of olefins formed from hydroxy silanes?
Acidic - goes via anti elimination
Base - goes via syn elimination
What is the peterson olefination?
α-silylcarbanions (from organometallic) + ketone/aldehyde → β-hydroxy silane → alkene
How do epoxysilanes react with Bu2CuLi and H2O?
When reacting an aldehyde + amine + allyl silane react what occurs first?
imine forms and then the allyl silane attacks the reactive C
How do -SiCl3 compounds react with KF, H2O2 with KHCO3?
-SiCl3 → -OH (retention of configuration)
-O-OH attacks Si, puts -ve on Si
