The Peterson Olefination

1
The Peterson Olefination
Olefination chemistrys stepchild
2
Overview

• General mechanism
• Stereochemistry of alkylation
• ?-Silyl-carbanions
• Non-classical-Peterson-Olefination
• Nice reagents
• Comparison to other olefination methods

3
Concerted reaction pathway
4
Mechanism alkyl substituents
5
Alkyl substituents anti - elimination

• Normally ?-hydroxy-silanes can be isolated
• Stereochemistry of olefination can be directed by
  reaction conditions
• Treatment of anti- ?-hydroxy-silanes with acid
  gives E-double bonds

6
Alkyl substituents syn elimination

• Covalent bound cations (Li, Mg, Cr) stop the
  reaction at intermediate hydroxsilane
• Change to an ionic cations (Na, K) facilitates
  syn-elimination
• Treatment of anti- ?-hydroxy-silanes with base
  gives Z-double bonds

7
Approach models
L SiR3 MLPh SSH
Stepwise reaction1
Concerted reaction2
1 Bassindale et al., Perkin Trans.II, 1986,
593 2 Bassindale et al. J. Chem. Res. S., 1996, 34
T. Kawashima, R. Okazaki, Synlett, 1996, 600
8
Preparation of a-Silyl-carbanions 1

• Direct deprotonation
• Normally quite harsh conditions required
• silyl group stabilizes carbanion
• TMEDA (or HMPA) as additive necessary to achieve
  deprotonation
• Metal-Halogen exchange
• Usual Grignard-conditions applicable
• a-lithio-silanes available both from Li-metal and
  Li-organyls
• Problem Availability of a-halo-silanes

9
Preparation of a-Silyl-carbanions 2

• From Vinylsilanes
• Alkyllithiums add regioselectively at the
  ß-position (Tripenylvinylsilanes work best!)
• Reaction is susceptible to steric effects (both
  alkene termini)
• a-lithio-vinylsilanes1 are much less basic and
  provide access to allenes2

T.H.Chan, E.Chang., J.Org.Chem., 39, 3264
1 R.B.Miller, A.I.Al-Hassan, J.Org.Chem., 48,
4113-4116 2T.H.Chan et al. J.Org.Chem., 43, 1526
10
Preparation of a-Silyl-carbanions 3

• a- Silyl-Esters and a-Silyl-Ketones
• Direct silylation of ketones or esters
  problematic (O-Silylation!)
• Ways out use of bulky t-butylester or HMPA as
  (co-)solvent
• Indirect methods Cuprat-Addition to Acyl
  chlorides

T.Kaiho, S. Masamune, JOC, 47, 1612

• Direct silylation of ketones or esters
  problematic (O-Silylation!)
• Normally preference of the E-Isomer
• Exceptions Use of bulky Si-groups or use of HMPA
  as solvent
• a-Silyl-Lactones give good selectivities!

11
Preparation of a-Silyl-carbanions 4
a- Silyl-Thiols
D.J.Ager, Perkin Trans. I, 1986, 183

• Using method b) or c) disubstituted
  a-silyl-thioethers are accessible
• Silanols are isolable
• Silyl-Thiols (or product enol-thioethers) can be
  oxidized to sulfones subsequent
  Julia-Olefination possible!

12
Terminal Dienes

• Allylsilanes
• Problem Bidentate nucleophile ? gives preferably
  ?-TMS-alcohols
• WAYS OUT
• Di-TMS-Allylcompounds
• Ti-Complexes
• Chromium chemistry

T.H. Chan, J.S.Li., Chem. Comm. 1982, 969
M. Sato et al., T.L., 23, 4589 M. Sato et. al,
Chem. Comm. 1983, 921
Paterson et al., Synlett, 1995, 498-500
13
Non-classical Peterson olefinations

• C-C single bond is already present prior to
  olefination reaction
• Conversion of functional groups rather than
  disconnection

?-Silyl-ketones
Nozaki et al., JOC, 41, 2941
14
Non-classical Peterson olefinations

• Vinyl-silanes and ?-Silyl-epoxides
• Vinyl silanes can be oxidised to epoxides
• Nucleophilic opening of epoxides occurs at
  a-position

Cuifolini et al., JACS, 104, 2308
Kulkarni et al. JOC, 45, 4444
15
Useful reagents

• TMSCH2M(X)
• TMSCH2Cl commercially available (25g 43)
• Methylenation reagent for the tough cases
• Still sterically demanding, but less than Wittig!

Silver et al., T.L., 1973, 3497
W.C.Still, JACS, 101, 2493 (1979)

• Problems with easily enolizable ketones
• (a-silyl-carbanions are quite basic)

Ronald et al., JOC, 47, 2792 (1982)
16
Johnson modification

• Transmetallation to cerium!

Cohen et al. Tetrahedron, 50, 12793 (1994)

• Esters can be converted to Allylsilanes

Harmata et al. JOC, 1997, 62, 1578-1579

• Acyl silanes can be converted to Vinylsilanes

Fürstner et al. J. Organet. Chem, 414, 295 (1991)
17
Useful reagents

• Imine serves as protecting group for aldehyde
• Use of TES instead of TMS suppresses
  N-silylation during preparation

Corey et al. JACS, 102, 1439 (1980) Corey, E. J.,
Enders, D. Bock, M. G. T.L. 1976, 7
Colvin et al. Chem. Comm. 1973, 151 Aoyama, T.,
Shioiri, T., et al. Synlett, 1994, 107
Imam et al. T.L., 1977, 2613
18
Useful reagents

• Product ketene-thioacetal has a very broad
  chemical spectrum1
• Commercially available
• Always 1,2 addition useful for diene-synthesis

Brinkmeyer, R.S., T.L., 1979, 207

• Can be deprotonated with sec-butyllithium
• Stereochemistry of product?

1 Seebach, D., Synthesis, 1969, 17Seebach et
al., Synthesis, 1977, 357
19
Comparison

• PRO
• After work-up, TMS2O is a volatile byproduct
• Most atom-economical olefination method (TMSOH
  90g/mol)
• For alkyl substituents, double bond geometry can
  be tuned
• Unusual compounds obtainable

• LIMITATIONS
• Not the method of choice for coupling of large
  fragments
• Not all silyl-carbanions are easily obtainable
• Selectivity not always tunable
  (Electron-withdrawing substituents)
• Sometimes basicity of a-silyl-carbanions can be
  a problem

20
Literature

• Ager, D.J. Org. React., 38, 1-224 (1990)
• van Staden, F.L., Gravestock, D., Ager, D.J.,
  Chem. Soc. Rev, 2002, 31, 195-200
• Science of Synthesis, 2002, 4, 789-809
• and all references on the slides!