Stability and Reactivity of Nicholas Carbocations

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Stability and Reactivity of Nicholas Carbocations

• Simon Meek
• 25 / 2 / 04

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Nicholas Carbocations
Experimetal evidence for charge delocalization
onto Co2(CO)6 moiety IR - Increase in carbonyl
stretching frequencies by 40-60 cm-1 relative
neutral complex. d(Co) ? ? (CO) 1H-NMR -
small downfield shift ?- alkyl groups 13C-NMR -
small downfield shift ?- alkyl groups
- resonances of CO ligands show small
shielding effects
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Isolation of Cations
K.M. Nicholas and R. Pettit, J. Organomet. Chem.,
1972, 44, C21
Asymmetric Propargylium Cations at Low
Temperatures
Padmana, S. Nicholas, K. M. J. Organomet. Chem.
1983, 268, 23.
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Depiction of Dicobalthexacarbonyl Systems
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Dynamic Behaviour
Schreiber et al., J. Am. Chem. Soc. 1987, 109,
5749
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Formation of Nicholas Carbocations
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Stability of Nicholas Carbocations
Schreiber et al., J. Am. Chem. Soc. 1987, 109,
5749
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Propargylium Cation Electrophilicity
Slightly less electrophilic -
dianisylmethylium ion Behave like
- Xanthylium ion
- Ferrocenylmethylium ion
Kuhn, O. Rau, D. Mayr, H. J. Am. Chem. Soc.
1998, 120, 900-907
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Reaction with nucleophiles

• Nucleophiles
• Hydride
• Nitrogen
• Oxygen
• Sulphur
• Fluoride

• 6. Carbon
• Alkenes
• Aromatics
• Enol derivatives
• (Syn selective for both E- Z- enolates)
• Ally metals

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Hydride
Hanaoka et al., J. Chem. Soc., Perkin Trans. 1
1995, 2849
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Nitrogen

• Azide
• Amines

Shunto, S., J. Med. Chem. 1998, 41, 3507.
Yeh, M. -C. P. Tetrahedron Lett. 1995, 36, 2823
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Oxygen
Martin, V. S. Tetrahedron Lett. 1995, 36, 3549.
Martin, V. S. Tetrahedron Lett. 1995, 36, 3549
Hanaoka, M. et al., Tetrahedron 2000, 56, 2203
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Sulfur
Went et al., J. Chem. Soc., Dalton Trans. 1993,
1857
Fluoride
Gree, Tetrahedron Lett. 1999, 40, 6399
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Carbon Alkenes
Krafft, J. Org. Chem., 1996, 61, 3912.
Tyrrell, J. Chem. Soc., Perkin Trans. 1 1998,
1427. Tyrrell, Tetrahedron Lett. 1997, 38, 685.
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Syntheis of Ingenane skeleton
Tanino et al., J. Org. Chem., 1997, 62, 3032
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Carbon Aromatics
Green, J. Chem. Soc., Chem. Commun. 1999, 2503
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Carbon Enol Derivatives (intermolecular)

• Reaction occurs through a synclinal transition
  state

Schreiber et al., J. Am. Chem. Soc. 1987, 109,
5749
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Carbon Chiral enol ethers (intermolecular)

• Facial selectivity - that expected of a
  noncoordinating electrophile
• Diastereoslectivity - synclinal transition state
  (syn isomer)
• Intermediate cations racemize faster than
  intermolecular alkylation
• Cations react with different rates (kinetic
  resolution)

Schreiber et al., J. Am. Chem. Soc. 1987, 109,
5749
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Intramolecular Reaction with Enolates

• Stereoselective
• (E) - cis-product
• (Z) - trans product
• Retention of ee suggests Nicholas Carbocation
• reacts faster than it racemizes (antarafacial
  migration)
• cf. Intermolecular addition

Carbery, Reignier, Miller and Harrity, J. Org.
Chem., 2003, 68, 4392.
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Enediyne Antibiotics
Magnus et al., J. Am. Chem. Soc., 1997, 119, 6739
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52 Cycloaddition reactions
Tanino, J. Am. Chem. Soc., 2000, 122, 6116.
Tanino, Org. Lett., 2002, 4, 2217
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Carbon Allyl

• Diastereoselectivity
• improves with steric bulk
• of both alkoxy group and
• remote propargylic moiety

• Syn form (benzyloxy and phenyl) most
• stable diastereomeric Nicholas carbocation
• Antarafacial migration of olefin ligand
• allows discrimination of enantio faces

Panek, Org. Lett., 2001, 3, 2439.
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Carbon Allyl
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Carbon Allyl
Diastereoselectivity explained by the
six-membered chelation transition state for allyl
metal additions to carbonyl compounds -
(E)- allyl boranes give the trans-dioxygenated
product - (Z)- allyl boranes give the
syn-dioxygenated product
Nicholas, J. Org. Chem., 1993, 58,
5587. Nicholas, J. Org. Chem., 1997, 62, 1737.
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Tandem use of Cobalt to Synthesize Trans-fused
5-5 ring system in ()-epoxydictymene
Schreiber, J. Am. Chem. Soc., 1997, 119, 4353
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Protecting group
Danishefsky, Org. Lett., 2004, 6, 413 Nicholas,
Tetrahedron Lett. 1971, 37, 3475
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Decomplexation of Cobalt

• Oxidative methods give parent alkyne
• Ferric nitrate
• Ceric ammonium nitrte or ceric sulphate
• Trimethylamine N-oxide
• N-morpholine N-oxide, often in conjuction with
  1,4-cyclohexandiene
• Tetrabutylammonium fluoride
• Sodium methanethiolate
• Pyridine
• Dimethylsulfoxide/water
• Reductive methods give alkenes
• Lithium in liquid ammonia
• Hydrogen over rhodium-charcoal catalyst
• Hydrogenation over Wilkinsons catalyst
• Tributyltin hydride
• Tributyltin hydride and NBS used in
  1,4-cyclohexadiene
• Triethylsilane or triphenylsilane- forms the
  vinylsilane

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References
Teobald, B. J., Tetrahedron., 2002, 58,
4133-4170 Nicholas, K. M., Acc. Chem. Res. 1987,
20, 207-214 Green, J. R., Curr. Org. Chem. 2001,
5, 809-826 Went, M. J. Adv. Organomet. Chem. ,
1997, 41, 69-125 Fletcher, A. J. Christie, S.
D. R., J. Chem. Soc., Perkin Trans.1 2000,
1657-1668 Caffyn, A. J. M. Nicholas, K. M.
Comprehensive Organometallic Chemistry II A
Review of the Literrature 1982-1994, 14 Volume
set Abel, E. W., Stone, F. G. A., Wilkinson, G.,
Eds. Pergamon Oxford, 1995 Vol. 12, pp
685-702, Chapter 7.1