Cobalt mediated cyclisations

1
Cobalt mediated cyclisations

• Multiple carbon-carbon bond forming reactions
  with high levels of regio-, and stereoselectivity
• The Pauson-Khand reaction
• Cobalt mediated 222 cycloadditions
• Intramolecular Nicholas reaction
• Other cyclisations and tandem reactions

2
The Pauson- Khand Reaction

• intermolecular version most limited, as
  olefins without strain scarcely react
• intramolecular version

3
The Pauson- Khand Reaction

• 1 dissociative loss of CO
• 2 addition of alkene
• 3 insertion of the alkene into the
• least hindered cobalt alkyne bond
• 4 CO insertion
• 5 reductive elimination
• 6 decomplexation

P.C. Magnus, C.Exon, P. Albaugh-Robertson,
Tetrahedron, 1985, 5861 Miquel A. Pericas et al,
Pure Appl. Chem., 2002, 74, 167 M. Yakamura, E.
Yakamura, J. Am. Chem. Soc., 2001, 123, 1703
4
(No Transcript)
5
Vinyl ethers, esters and halides in the PKR

• alkynes ketone or ester function is located at
  C-3
• alkenes 1,3 dienes

6
Vinyl ethers, esters and halides in the PKR

• Under mild conditions N-oxides techniques allow
  the employ of relatively sensitive vinyl ethers,
  regioselective
• Vinyl esters and halides

W. J. Kerr, M. Mc Laughlin, P. L. Pauson, S. M.
Robertson, Chem. Commun., 1999, 2171 W. J.
Kerr, M. Mc Laughlin, P. L. Pauson, S. M.
Robertson, J. Organomet. Chem., 2001, 630, 104
7
Regioselectivity of the intermolekular PKR

• Acyclic alkenes
• Allyl ethers and soft ligands at homoallylic
  position

8
Regioselectivity of the intermolecular PKR

• Monocyclic and fused bicyclic alkenes

D.C. Billington, W.J. Kerr, P.L. Pauson, C. F.
Farnocchi, J. Organomet. Chem., 1988, 356, 213
9
Regioselectivity of the intermolecular PKR
10
Regioselectivity of the intermolecular PKR
11
The intramolecular PKR

• Acyclic all-carbon Enynes

12
The intramolecular PKR

• Acyclic Heteroatom containing Enynes

13
Reaction conditions-acceleration of the PKR

• Dry state absorption conditions (DSAC)
• Adsorption of both complex and alkene on solid
  support such as silica,
• zeolite or alumina
• Especially beneficial for intramolekular
  PKR
• Polymer supported PKR
• Wang resin, Merrifield resin
• N-Oxides to promote loss of CO
• such as TMANO, NMO,
• acceleration of the reaction

W. A. Smit, A. S. Gybin, A. S. Shashkov, Y. T.
Strruchkov, L. G. Kyzmina, R. Caple, E.D.
Swanson, Tetrahedron Lett., 1986, 27, 1241
14

• other promoters sulfides and sulfoxides benefit
  especially the
  intermolekular PKR, Cy-NH2 enhances the yield of
  the intramolecular PKR
• Molecular sieves

15
The catalytic PKR

• stochiometric amounts to react with alkyne to
  give
• Catalytic versions
• early work
• Livinghouse (1998) Co2(CO)8 can catalyse the
  PKR
• (60-70 C) reagent must be extremely pure
• Improvement reductive decomplexation of stable
  alkyne complex

S. E. Gibson, A. Stevenazzi, Angew. Chem. Int.
Ed., 2003, 42, 1800 D. B. Belanger, T.
Livinghouse, Tetrahedron Lett., 1998, 39, 7641
16
The catalytic PKR

• Livinghouse photocemically induced catalytic PKR
• Additives

17
The catalytic PKR

• chiral phosphines
• other Co- sources

18
The catalytic PKR

• Heterogenous catalysts

19
The catalytic PKR

• Catalysis by other metals
• Titanium-catalysed variants
• Rhodium-catalysed variants

20
The catalytic PKR
21
Introducing Asymmetry in the PKR

• Transfering chirality from the substrate

A. Pal, A. Bhattachrjya, J. Org. Chem., 2001, 66,
9071 K. Subburaj, S. Okamoto, F. Sato, J. Org.
Chem., 2002, 67, 1024
22
Introducing Asymmetry in the PKR

• Using chiral auxiliaries

23
Introducing Asymmetry in the PKR

• chiral Promotors
• Improvement of the enantiomeric excess
  Substitution of CO by PPh3

24
More Literature

• E. W. Abel, F.G.A. Stone, G. Wilkinson,
  Comprehensive Organometallic Chemistry, 1996, 12,
  703 ff.
• J.Blanco-Urgoiti, L. Añorbe, L. Peréz-Serrano, G.
  Dominguez, J. Peréz-Castells,
• Chem. Soc. Rev., 2003, 33, 32
• O. Geis, H-G. Schmalz, Angew. Chem. Int. Ed.,
  1998, 37, 911
• When the Pauson-Khand and Pauson Khand type
  reactions go awry aphlethora of unexpected
  results
• L. V. R. Boñaga, M E. Krafft, Tetrahedron, 2004,
  60, 9795-9833
• K. M. Brummond, J. L. Kent, Tetrahedron, 2000,
  56, 3263