Metal Catalysis

TPAP – Tetra-n-propylammonium Perruthenate
The mild oxidation catalyst tetra-n-propylammonium perruthenate (TPAP) which we discovered in 1987 [1, 2, 3] has since become one of the principal reagents for the conversion of primary and secondary alcohols to their corresponding aldehydes and ketones.

More recently, we have used tetraalkylammonium salts or imidazolium ionic liquids in catalytic oxidations of alcohols with TPAP which allowed recovery and reuse of the oxidant; a concept that may find application in the recovery of other homogenous catalysts [4].

We have also reported on a convenient sequential oxidation-olefination protocol using TPAP as oxidant and phosphonium salts as olefin source. The oxidation reaction mixture was added directly to the phosphorane facilitating an efficient method for this transformation that avoids work-up of potentially sensitive aldehyde intermediates [5].

Polymer-supported perruthenate (PSP)
Considering our interest in supported reagents, the TPAP reagent is an ideal candidate for immobilisation onto solid support to enable facile work-up and purification of reactions and provide an opportunity for recycling of the spent reagent. Polymer-supported perruthenate (PSP) was easily generated by an ion exchange reaction of a commercially available Amberlyst resin, functionalised as the quaternary ammonium chloride, using an aqueous solution of potassium perruthenate. This novel reagent was shown to be effective for the stoichiometric oxidation of alcohols to their corresponding carbonyl compounds at room temperature and in high yields [6].

We have also used PSP in mild and selective oxidations of secondary hydroxylamines to give nitrones; in the presence of dipolarophiles isoxazolidines are obtained in one-pot processes in good yields [7].

A further important development of this process enabled the reaction to proceed catalytically, using atmospheric air or molecular oxygen as the co-oxidant in toluene [8, 9].

Nafion-TMS mediated Mukaiyama aldol reaction of silyl enol ethers with aldehydes, obtained from mild oxidation of alcohols with PSP yielded α,β-unsaturated ketones, which upon treatment with hydrazines allowed the clean synthesis of 4,5-dihydro-1H-pyrazoles [10].

The automated sequential application of PSP and polymer supported cyanoborohydride (PSCBH) in an oxidation-reductive amination procedure allowed the efficient transformation of simple alcohols into more complex amines which can be further derivatised by the use of polymer bound amino sulfonylpyridinium chlorides [11].

A new oxidation catalyst containing perruthenate immobilised within MCM-41 has been prepared and used in the clean oxidation of alcohols to carbonyl compounds with molecular oxygen [12].

1. Preparation and use of tetra-n-butylammonium perruthenate (TBAP reagent) and tetra-n-propylammonium perruthenate (TPAP reagent) as new catalytic oxidants for alcohols W.P. Griffiths, S.V. Ley, G.P. Whitecombe, A.D. White, J. Chem. Soc., Chem. Commun1987, 1625-1627

2. TPAP: tetra-n-propylammonium perruthenate, a mild and convenient oxidant for alcohols W.P. Griffith, S.V. Ley, Aldrichimica Acta, 199023, 13-14

3. Tetrapropylammonium perruthanate, Pr4N+RuO4- TPAP: a catalytic oxidant for organic synthesis S. V. Ley, S. P. Marsden, J. Norman, W. P. Griffith, Synthesis1994, 639-666

4. Tetra-n-propylammonium perruthenate: a case study in catalyst recovery and reuse involving tetraalkylammonium salts S.V. Ley, C. Ramarao, M.D. Smith, J. Chem. Soc., Chem. Commun2001, 2278-2279

5. A sequential tetra-n-propylammonium perruthenate-Wittig oxidation R.N. MacCoss, E.P. Balskus, S.V. Ley, Tetrahedron Lett. 2003, 44, 7779

6. Polymer supported perruthenate (PSP): a new oxidant for clean organic synthesisB. Hinzen, S. V. Ley, J. Chem. Soc., Perkin Trans. 11997, 1907-1908

7. Synthesis of isoxazolidines using polymer-supported perruthenate (PSP) B. Hinzen, S. V. Ley, J. Chem. Soc., Perkin Trans. 11998, 51, 1-2

8. Tetra-n-propylammonium perruthenate (TPAP)-catalysed oxidations of alcohols using molecular oxygen as a co-oxidant R. Lenz and S. V. Ley, J. Chem. Soc., Perkin Trans. 11997, 3291-3292

9. Polymer-supported perruthenate (PSP): clean oxidation of primary alcohols to carbonyl compounds using oxygen as cooxidant B. Hinzen, R. Lenz, S.V. Ley, Synthesis 1998, 977-979

10. Clean three step synthesis of 4,5- dihydro-1H-pyrazoles starting from alcohols using polymer supported reagentsF. Haunert, M. Bolli, S.V. Ley, J. Chem. Soc., Perkin Trans. 11998, 2235-2237

11. Use of polymer supported reagents for clean multi-step organic synthesis: preparation of amines and amine derivatives from alcohols for use in compound library generation S.V. Ley, M. Bolli, B. Hinzen, A-G. Gervois, B.J. Hall, J. Chem. Soc., Perkin Trans. 11998, 2239-2242

12. Modified mesoporous silicate MCM-41 materials: immobilised perruthenate: a new highly active hetergeneous oxidation catalyst for clean organic synthesis using molecular oxygen A. Bleloch, B.F.G. Johnson, S.V. Ley, A.J. Price, D.S. Shepherd, A.W. Thomas, J. Chem. Soc., Chem. Commun. 1999, 1907-1908