Ley-Griffith oxidation

LEY - GRIFFITH Oxidation reagent Oxidation ol alcotwls to caitxnyl compounds with a pemjthenate catalyst and N-methylmorpholine - N-oxIde (NMO), In the presence of other functional gmups... 

LEY GRIFFITH Oxidation reagent Oxidation of alcohols to caitxsnyl compounds with a pemithenate catalyst and N-methylmofphoHne - N-oxide (NMO), in the presence of other functional groups... 

Schmidt et al. [74] prepared spirocyclic lactones by hydroformylation-acetalization of vinyl-tetrahydropyranes followed by Ley-Griffith oxidation (Scheme 5.82). Versatile building blocks were obtained after cleavage of the lactone ring, which were suitable for the synthesis of natural compounds such as pseudomonic acid A (C-glycoside). 

Other annellated tetrahydropyranes have been prepared by a hydroformylation-allylboration-hydroformylation sequence (Scheme 5.84) [76]. By treatment of an allyl amine derivative with syngas, a cascade reaction was initiated consisting of hydroformylation and hemiacetal formation, followed by a second hydroformylation-hemiacetal formation step. The product was converted via Ley-Griffith oxidation into the corresponding lactone. 

Oxidation of the alcohol 10-[3 -methoxy-2 -(methoxymethoxy)phenyl]decan-l-ol (7.19) with TPAP [(C3H7)4NRu04] afforded the aldehyde 10-[3 -methoxy-2 -(methoxymethoxy)phenyl] decan-1-al (7.20) in quantitative yield. The reagent TPAP is known as Ley-Griffith s reagent. 

S. V. Ley, J. Norman, W. P. Griffith, S. P. Marsden, Teterapropylammonium Perruthenate, Pr4N Ru04", TPAP A Catalytic Oxidation for Organic Synthesis, Synthesis 1 (1994) 639-666. 

Griffith, Ley et al.n discovered that, in variance with the instability and complex behaviour of perruthenate and ruthenate ions in aqueous solution, TPAP in organic media is quite stable and behaves as a very good oxidant for alcohols. Normally, it is employed in catalytic quantities in dry CH2CI2 with addition of TV-methylmorpholine /V-oxide (NMO) as the secondary oxidant. Catalytic TPAP in the presence of NMO is able to oxidize alcohols to adehydes and ketones under very mild conditions in substrates adorned by complex functionalities, and it has become one of the routine oxidants for alcohols in most Synthetic Organic Chemistry laboratories. 

A milestone in the routine employment of perruthenate in the oxidation of alcohols was established with the publication by Griffith, Ley et al. in 1987 on the catalytic use of tetra- -propylammonium perruthenate (TPAP).11 The presence of the tetra- -propylammonium cation renders this compound soluble in apolar media and allows the existence of a high concentration of perruthenate ion in organic solvents. The tetra- -propylammonium perruthenate is easily prepared and can be employed catalytically in CH2CI2 solution in the oxidation of alcohols to ketones and aldehydes, using /V-methyl morpholine A-oxide (NMO) as the secondary oxidant. 

Griffith, W., S. Ley, G. Whitcombe, and A. White (1987) Preparation and use of tetra-n-butylammonium per-ruthenate (TBAP reagent) and tetra-n-propylammonium per-ruthenate (TpAP reagent) as new catalytic oxidants for alcohols. Chemical Communications, 1625-1627. 

W. P. Griffith, S. V Ley, TPAP Tetra-n-Propylammonium Perruthenate, a Mild and Convenient Oxidant for Alcohols, Aldrichimica Acta 1990, 23, 13-19. 

R.A. Sheldon and J.K. Kochi, "Metal Catalysed Oxidations of Organic Compounds", Academic Press, New York, 1981 S.V. Ley, J. Norman, W.P. Griffith and S.P. Marsden, Synthesis, 1994, 639 M. Hudlicky, "Oxidations in Organic Chemistry", ACS, Washington, DC, 1990 and references cited therein. 

There are problems associated with the expensive disposal of toxic waste from metal-based oxidations of alcohols. Thus, the focus has been largely on catalytic reactions as typified by Ley and Griffith s tetrapropylammonium perruthenate oxidant (section 7.1.6). Completely metal-free oxidations have much potential for environment-friendly oxidations, particularly if the reagent can be recovered and recycled. The most common metal-free oxidation of alcohols are TEMPO/oxone or TEMPO/N-chlorosuccinimide oxidation, Dess-Martin periodane oxidation (section 7.1.5) and Swern oxidation (section 7.1.4) and its several variants. 

Ley, S. V., Norman, J., Griffith, W. P., Marsden, S. P. Tetrapropylammonium perruthenate, Pr4N Ru04, TPAP a catalytic oxidant for organic synthesis. Synthesis 1994, 639-666. 

The TPAP oxidation developed by Griffith and Ley [41] has proven to be a very important tool in organic synthesis. The polymer-supported perruthenate (PSP) version, first developed in the Ley group [42], enables the use of the reagent either stoichiometrically or catalytically in tandem with a co-oxidant. The power of PSP... 

Scheme 8.8. A representation of the oxidation of cnck>-bicyclo[2.2.1]heptan-2-ol to the corresponding ketone (bicyclo[2.2.1]heptan-2-one) with tetra-n-propylammoniumperruthenate (TPAP) in the presence of A-methylmorpholine A-oxide. Despite what is shown, all four ruthenium-oxygen (Ru-O) bonds in TPAP are equivalent and the process may actually involve a series of one-electron rather than two-electron redox steps. Curved arrows representing two-electron processes are used for convenience. The actual path is not yet known in detail (see Ley, S. V. Griffith, W. P. J. Chem.Soc. Chem. Commun., 1978,1625).

---