Catalytic Oppenauer oxidation

Catalytic Oppenauer oxidations (Eq. 28) and Meerwein-Ponndorf-Verley reductions (Eq. 29) were studied in detail [232,234]. The gadolinium derivative, employed in situ without elimination of LiCl, was reported to be ten times more reactive in the MPV reduction of cyclohexanone as the standard reagent Al(OiPr)3 [235]. 

Most terpene-based citral (5) produced is based on the catalytic oxidative dehydrogenation of nerol (47) and geraniol (48), or by the Oppenauer oxidation of nerol and geraniol (123—125). 

The synthetic value of this reaction should be mentioned. Thus, current production of 5p-steroids from As-3(i-ols, readily available and cheap starting materials, requires a preliminary Oppenauer oxidation or fermentation to the A4-3-keto derivative followed by catalytic hydrogenation under alkaline conditions, as direct catalytic hydrogenation with both heterogeneous and homogeneous systems gives only the 5a isomer. 

The most common catalysts for the Meerwein-Ponndorf-Verley reduction and Oppenauer oxidation are Alm and Lnm isopropoxides, often in combination with 2-propanol as hydride donor and solvent. These alkoxide ligands are readily exchanged under formation of 2-propanol and the metal complexes of the substrate (Scheme 20.5). Therefore, the catalytic species is in fact a mixture of metal alkoxides. 

A major part of the work described in this section has been carried out with the aim of applying these silsesquioxane complexes of Ti, Zr and Hf in catalytic processes such as ethylene polymerization, olefin epoxidation and Oppenauer oxidation. These catalytic aspects have been highlighted in several recent review articles. 

Catalytic reduction of codeine gives dihydrocodeine and Oppenauer oxidation (a ketone such as acetone and an aluminum alkoxide, the ketone being reduced to an alcohol) gives hydrocodone. Hydrocodone can also be prepared directly from codeine with a metal catalyst, which isomerizes the allylic alcohol to a ketone. Codeine is prepared by methylation of morphine, which is isolated from the opium poppy. Hydrocodone is more potent than codeine. Acetaminophen is a mild analgesic and is discussed in Section 8. 

Nuttalline was isolated from Lupinus nuttallii L. (155). The tetracyclic structure of nuttalline was established by dehydration of deoxonuttalline (112), obtained from nuttalline (113) by reduction with sodium borohydride, and by catalytic reduction to sparteine (6) (Scheme 20). Oppenauer oxidation of nuttalline gives 2,4-dioxosparteine (125). The UV spectrum of this 1,3-diketone... 

One of the more benign ancillary activities of morphine lies in its activity in suppressing the cough reflex. Catalytic reduction of codeine (1-2) leads to the dihydro derivative (4-1). Oppenauer oxidation of the hydroxyl group leads to hydrocodone (4-2) [3], a compound used extensively in cough remedies it is of note, however, that this drug retains considerable opioid activity. 

Aluminum methoxide Al(OMe)3 is a solid which sublimes at 240 °C in vacuum. Aluminum isopropoxide melts in the range 120-140 °C to a viscous liquid which readily supercools. When first prepared, spectroscopic and X-ray evidence indicates a trimeric structure which slowly transforms to a tetramer in which the central Al is octahedrally coordinated and the three peripheral units are tetrahedral.162,153 Intramolecular exchange of terminal and bridging groups, which is rapid in the trimeric form, becomes very slow in the tetramer. There is MS and other evidence that the tetramer maintains its identity in the vapour phase.164 Al[OCH(CF3)2]3 is more volatile than Al[OCH(Me)2]3 and the vapour consists of monomers.165 Aluminum alkoxides, particularly Al(OPr )3, have useful catalytic applications in the synthetic chemistry of aldehydes, ketones and acetals, e.g. in the Tishchenko reaction of aldehydes, in Meerwein-Pondorf-Verley reduction and in Oppenauer oxidation. The mechanism is believed to involve hydride transfer between RjHCO ligands and coordinated R2C=0— A1 groups on the same Al atom.1... 

Kagan et al.39 have shown that alkoxides of metals belonging to the lantanides are able to promote Oppenauer oxidations in catalytic amounts. Thus, 10 mol% f-BuOSmF is able to induce the oxidation of a number of alcohols in variable yields in the presence of a variety of aldehydes and ketones as oxidants.393 Yb(0/-Pr)3 in a 5 mol% quantity is able to catalyze the oxidation of 1-phenylethanol to acetophenone in 98% yield with butan-2-one as oxidant.39b Other lantanides provided a lower yield. 

A number of zirconium compounds are able to catalyze Oppenauer oxidations. For example, zirconium dioxide, when properly conditioned, is able to promote the oxidation of alcohols in variable yields40 and it is reportedly superior than AI2O3. Other zirconium compounds able to induce Oppenauer oxidations in catalytic amounts include Cp2ZrH2,41 Cp2Zr(Oi-Pr)2,41b Zr(Oi-Bu)442 and Zr(0 -Pr)x on Si0242... 

Indium trichloride promotes catalytically the addition of alkynylstannanes to aldehydes (Table 25).42 Metallic indium also mediates the same Barbier-type coupling between alkynyl halides and aldehydes or ketones to give secondary or tertiary propargyl alcohols (Table 26). Secondary alcohols can be oxidized in situ according an Oppenauer process.395 Thus, alkynyl ketones have been prepared from aldehydes via an indium-mediated alkynylation reaction followed by an indium-mediated Oppenauer oxidation. They are also obtained via an indium-mediated alkynylation of the relevant acyl chlorides (Table 27).396... 

Lanthanide alkoxide complexes have been shown to promote a number of useful chemical reactions, whereby the complex is used catalytically or applied in stoichiometric amount. One such reactions is the Meerwein-Ponndorf-Verley reduction (MPV) or the Oppenauer oxidation, depending on which component is the desired product (Equation 6.5). If the alcohol is the desired product, the reaction is viewed as Meerwein-Ponndorf-Verley Reduction [43]. 

Table 1. The catalytic activity of arylboron compounds in the Oppenauer oxidation of (5)-perillyl alcohol. , OH...

Maruoka has successfully developed a highly accelerated Oppenauer oxidation [31,32] system using a bidentate aluminum catalyst [29]. This modified, catalytic system effectively oxidizes a variety of secondary alcohols to the corresponding ketones as shown in Sch. 9. For example, reaction of (2,7-dimethyl-l,8-biphenylene-dioxy)bis(dimethylaluminum) (8, 5 moI%) with carveol (14) at room temperature in the presence of 4-A molecular sieves, and subsequent treatment with pivalaldehyde (3 equiv.) at room temperature for 5 h yielded carvone (15) in 91 % yield. Under these oxidation conditions, cholesterol (16) was converted to 4-cholesten-3-one (17) in 75 % yield (91 % yield with 5 equiv. t-BuCHO). 

The tricyclic ring system containing the fully functionalized CD ring of taxol was prepared from (S)-(+)-carvone by T.K.M. Shing et al. The bicyclic a-hydroxy ketone (4-hydroxy-5-one) was isomerized by an Intramolecular redox reaction in the presence of catalytic amounts of aluminum isopropoxide. This example was a special case where both reactants were in the same molecule the ketone was the oxidant for the Oppenauer oxidation, whereas the secondary alcohol was the hydride donor for the MVP reduction. The conversion to the thermodynamically more stable 5-hydroxy-4-one proceeded in good yield. 

Peroxide intermediates are not fhe only species that enable oxidation of secondary alcohols. Oppenauer oxidation of secondary alcohols is of practical value, because only catalytic amounts of aluminum species are required and without aid from transition metals, which are usually more toxic. A new type of Oppenauer oxidation was recently discovered by Ooi and Maruoka [167]. This mefhod includes the use of bidentate aluminum catalyst which is also effective for MPV reduction (Scheme 6.144). The Oppenauer oxidation is the reverse of MPV reduction when pivalaldehyde is used as hydride-capturing agent, however, fhe reaction is virtually irreversible, giving the ketone in high yield. 

The most important side reaction in heterogeneously catalysed MPVO reactions is the acid-catalysed aldol condensation. Aldol products are usually observed during the Oppenauer oxidation of alcohols, when a surplus of ketone or aldehyde is used as the oxidizing agent and the solvent. The low amount of by-products formed when Ti-beta was used as the catalyst, demonstrates the advantage of the titanium system over Al-beta. This is probably caused by the much weaker Brpnsted acidity of the solvated titanium site [8] compared with the strong H -acidity of the aluminium site in Al-beta. As we have shown earlier Ti-beta has a high tolerance towards water, which further shows the catalytic potential of Ti-beta in MPVO reactions [9]. 

Meerwein-Ponndorf reduction. This method is the reverse of the Oppenauer oxidation. A ketone is reduced to an alcohol by treatment with an alcohol and a base. Engel38 was interested in the reduction of 3-ketosteroids of the 5/3-series to the axial 3/3-alcohol. a system present in the active cardiotonic steroids. After exploring catalytic reductions with limited success, he turned to the Meerwein-Ponndorf method using sec.-butyl alcohol and aluminum f-butoxide in refluxing absolute benzene. One interesting observation is that the reduction is complete in about 15 min furthermore, yields of 60% of the axial alcohol can be obtained if the reaction is stopped at this point. Prolonged reaction leads to an increase in the yield of the thermodynamically more stable equatorial alcohol. 

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