Reduction aluminium alkoxides

The asymmetric reduction of prochiral ketones to their corresponding enantiomerically enriched alcohols is one of the most important molecular transformations in synthetic chemistry (20,21). The products are versatile intermediates for the synthesis of pharmaceuticals, biologically active compounds and fine chemicals (22,23). The racemic reversible reduction of carbonyls to carbinols with superstoichiometric amounts of aluminium alkoxides in alcohols was independently discovered by Meerwein, Ponndorf and Verley (MPV) in 1925 (21—26). Only in the early 1990s, first successful versions of catalytic... 

Finally, /i-hydrogen transfer is the key step in the Meerwein-Pondorf-Verley (MPV) reduction of ketones by alcohols, catalyzed by aluminium alkoxides and many other catalysts. In that case, competition is not an issue, since polymerization is usually not thermodynamically favourable. The accepted mechanism for this reaction is direct transfer of the hydride from alkoxide to ketone. 

Aluminium Alkoxides and Ketones Meerwein-Pondorf-Verley Reduction... 

Meerwein-Pondorf-Verley reduction, discovered in the 1920s, is the transfer hydrogenation of carbonyl compounds by alcohols, catalyzed by basic metal compounds (e.g., alkoxides) [56-58]. The same reaction viewed as oxidation of alcohols [59] is called Oppenauer oxidation. Suitable catalysts include homogeneous as well as heterogeneous systems, containing a wide variety of metals like Li, Mg, Ca, Al, Ti, 2r and lanthanides. The subject has been reviewed recently [22]. In this review we will concentrate on homogeneous catalysis by aluminium. Most aluminium alkoxides will catalyze MPV reduction. 

The procedure described in this experiment exemplifies a general method [225] for the reduction of propargylic alcohols to -allylic alcohols. The first step in the reaction is the formation of the aluminium alkoxide -C=C-C-OAlH3. Subsequently one of the three hydrogen atoms attached to aluminum is transferred to the triple bond with formation of a 5-membered cyclic aluminum compound. Hydrolysis affords the -allylic alcohol. In the present case an -enyne alcohol is formed. 

In this way, an aldehyde or ketone could be reduced to the corresponding alcohol after hydrolysis of the resulting aluminium alkoxide. This reaction is known as the Meerwein-Ponndorf-Verley reduction. 

The product is the racemic [(R)/(S)] alcohol since the free energies of the two diastereoisomeric transition states, resulting from hydride attack on the si-face of the ketone as shown (order of priorities O > R1 > R2, p. 16) or the re-face, are identical. The use of an aluminium alkoxide, derived from an optically pure secondary alcohol, to effect a stereoselective reaction (albeit in low ee%) was one of the first instances of an asymmetric reduction.48 Here (S)-( + )-butan-2-ol, in the form of the aluminium alkoxide, with 6-methylheptan-2-one was shown to give rise to two diastereoisomeric transition states [(5), (R,S) and (6), (S,S)] which lead to an excess of (S)-6-methylheptan-2-ol [derived from transition state (6)], as expected from a consideration of the relative steric interactions. Transition state (5) has a less favourable Me—Me and Et—Hex interaction and hence a higher free energy of activation it therefore represents the less favourable reaction pathway (see p. 15). 

Secondary alcohols may be oxidised to the corresponding ketones by the use of an aluminium alkoxide, frequently the t-butoxide, in the presence of a large excess of acetone (the Oppenauer oxidation). The reaction involves an initial alkoxy-exchange process followed by a hydride ion transfer from the so-formed aluminium alkoxide of the secondary alcohol by a mechanism analogous to that of the Meerwein-Ponndorf-Verley reduction (see Section 5.4.1, p. 520). 

In this case, propanone is the constituent of the reaction mixture that has the lowest boiling point. Hence, by continuously distilling it out of the system, the equilibrium may be effectively displaced to completion. The excess of propan-2-ol exchanges with the mixed aluminium alkoxide to liberate the reduction product. 

Aluminium alkoxides were anchored in the pores of siliceous MCM-41 type materials. The resulting catalysts were used in the hydrogen transfer reduction of a,p-unsaturated ketones to the corresponding allylic alcohols. The most active material is obtained by exposure of MCM-41 to a toluene solution of Al(OPr )3. With benzalacetone as a model substrate, optimum reaction conditions are cyclopentanol (hydride donor), toluene (solvent), and addition of 5A molecular sieve (water trapping). 

The Oppenauer oxidation with aluminium alkoxides provides an alternative method for the oxidation of secondary (and less commonly primary) alcohols. The reaction is the reverse of the Meerwein-Pondorff-Verley reduction (see Section 7.3). Typically aluminium triisopropoxide (or aluminium tri-tert-butoxide) is used, which serves to form the aluminium alkoxide of the alcohol. This is then oxidized through a cyclic transition state at the expense of acetone (or cyclohexanone or other carbonyl compound). By use of excess acetone, the equilibrium is forced to the right (6.45). 

Reductions of a similar type can be brought about by other metallic alkoxides, but aluminium alkoxide is particularly effective because it is soluble in both alcohols and hydrocarbons and, being a weak base, it shows little tendency to bring about wasteful condensation reactions of the carbonyl compounds. Reduction of... 

Alnminium alkoxides have long been used as catalysts for the reduction of aldehydes or ketones by secondary alcohols and recently lanthanide alkoxides were reported to act similarly in addition to catalysing the epoxidation of allylic alcohols with tert-butyl hydroperoxide. Aluminium alkoxides have also been used to catalyse the conversion of aldehydes to alkylesters (Tischtchenko reaction). A review gives a fascinating account of the use of heterometal alkoxides in asymmetric catalysis. 

The main drawback of the historic aluminium tri-isopropoxide-based catalytic systems is their low reactivity, the reduction of the carbonyl proceeding slowly even with an excess of catalyst . As mentioned in the introduction, many aluminium alkoxides are known to form aggregates and the observed low reactivity is in many cases correlated to the stability of the... 

Being more tolerant to impurities dian aluminium alkoxides, Sn(Oct)2 is widely used for the industrial production of PCL and PLAs mainly in bulk, within batch reactors. Any discussion on die industrial production of polymers has to integrate not only the polymerisation process, but also the monomer production. eCL is prepared by the Baeyer-Villiger oxidation of cyclohexanone (Renz et al, 1999 Rocca et al, 2003), which is produced by the catalytic oxidation of cyclohexane, itself resulting from the catalytic reduction of benzene, made available from oil, a non-renewable resource (Fig. 4.8). 

In the reduction of a carbonyl group, there is an initial transfer of a hydride ion by an SN2 mechanism when the complex (1) is formed. Since it has still three more hydrogen atoms, it reacts with three more molecules of ketone to give the alkoxide (2) Hydrolysis of the latter gives secondary alcohol, along with aluminium and lithium hydroxides. 

Complete control of the diastereoselectivity of the synthesis of 1,3-diols has been achieved by reagent selection in a one-pot tandem aldol-reduction sequence (see Scheme l). i Anti-selective method (a) employs titanium(IV) chloride at 5°C, followed by Ti(OPr )4, whereas method (b), using the tetrachloride with a base at -78 °C followed by lithium aluminium hydride, reverses the selectivity. A non-polar solvent is required (e.g. toluene or dichloromethane, not diethyl ether or THF), and at the lower temperature the titanium alkoxide cannot bring about the reduction of the aldol. Tertiary alkoxides also fail, indicating a similarity with the mechanism of Meerwein-Ponndorf reduction. 

Apart from aluminium, many other metals were tested in Meerwein-Ponndorf-Verley reductions and Oppenauer oxidations during the early years of research on hydride transfer from alkoxides.26 A consensus was... 

Thermolysis of tin and lead alkoxozirconates leads to the formation of metals. The mass-spectral data indicate the presence ofbarium and aluminium derivatives in the gas phase, but no preparative data are accessible for them. The major application of zirconium and hafnium alkoxides lies now in the sol-gel technology of zirconate-titanate and solid solutions Zr02-Y203 (see Section 10.3), Except in the synthesis of oxide materials, the alkoxides of zirconium and hafnium are traditionally used in the polymer chemistry, where they are applied as the components in catalysts [1278, 1269] and as additives to polymers, improving their characteristics [825, 1403] and so on. Already in 1930s Meerwein has proposed the use of zirconium alkoxides for the reduction of aldehydes intoprimary alcohols (Meerwein-Schmidt reaction) [1420],... 

Conversely, were nucleophilic attack of the alkoxide ion to occur at the carbonyl group of 31, then the species formed (35) should undergo Brook rearrangement to 36 with retention of configuration at silicon (Path A). Reduction of 36 with lithium aluminium hydride would then produce (S)-(—)-l-naphthyl phenyl methyl silane (37). 

Many soluble catalysts are known which will polymerize ethylene and butadiene. High activity soluble catalysts are employed commercially for diene polymerization but most soluble types are inefficient for olefin polymerization. A few are crystalline and of known structure such as blue (7r-C5H5)2TiCl. AlEtaCl [49] and red [(tt-CsHs )2TiAlEt2 ] 2 [50]. The complex (tt-CsHs )2TiCl2. AlEt2Cl polymerizes ethylene rapidly but decomposes quickly to the much less active blue trivalent titanium complex. Soluble catalysts are obtained from titanium alkoxides or acetyl acetonates with aluminium trialkyls and these polymerize ethylene and butadiene. Several active species have been identified, dependent on the temperature of formation and the Al/Ti ratio. Reduction to the trivalent state is slow and incomplete and maximum activity for ethylene polymerization occurs at about 25% reduction to Ti [51]. 

---