Reductions with aluminium alkoxides

Aldehydes and ketones can be reduced smoothly to the corresponding alcohols by aluminium alkoxldes. The most satisfactory alkoxlde for general use Is aluminium tsopropoxide  

The undermentioned reductions may be carried out by simple adaptations to the procedures chloral to trichloroethyl alcohol m-nitroacetophenono of a-methyl-3-nitrobenzyl alcohol and o-nitrobenzaldehyde to o-nitroben l alcohol. 

The above reversible equation indicates that one mol of aluminium tsopropoxide will reduce directly three mols of the carbonyl compound. It is generally desirable to use excess of the reductant except for aromatic aldehydes for the latter side reactions (e.g., 2RCHO----- RCOOCHjR Tischenko re- 

The following mechanism of the reaction has been suggested it includes the coordination of the carbonyl compound with the aluminium atom in aluminlura tsopropoxide and the transfer of a hydride ion  

The reagent is conveniently stored as a solution in isopropyl alcohol. The molten (or sobd) alkoxide is weighed out after distillation into a glass-stoppered bottle or flask and is dissolved in sufficient dry isopropyl alcohol to give a one molar solution. This solution may be kept without appreciable deterioration provided the glass stopper is sealed with paraffin wax or cellophane tape. Crystals of aluminium isopropoxide separate on standing, but these may be redissolved by warming the mixture to 65-70°. 

The above reversible equation indicates that one mol of aluminium iso- 

For many reductions it is not necessary to distil the reagent. Dilute the dark solution, prepared as above to the point marked with an asterisk, to 1 litre with dry isopropyl alcohol this gives an approximately one molar solution. Alternatively, prepare the quantity necessary for the reduction, using the appropriate proportions of the reagents. 

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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). 

It is noteworthy that in some cases reduction with metal alkoxides, including aluminium isopropoxide, involves free-radical intermediates (single electron transfer (SET) mechanism). ... 

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. 

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... 

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. 

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). 

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]. 

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). 

All of these reactions may be repeated starting with methyl (2/ ,3f )-3-hydroxy-2-methylbutanoate (9a) which is obtained, as shown in Scheme 2, by the double deprotonation of methyl 3-hydroxybutanoate (2b) using lithium di-isopropylamide (LDA) to give the alkoxide-enolate (8) and alkylation with a methyl halide in THF at —After reduction with lithium aluminium hydride, tosyla-tion of the alcohol group and nucleophilic attack by lithium chloride, the (2f ,3f )-l-chloro-2-methyl-3-butanol (10) is available for the sequential metallation reactions and conversion to 1,4-diols or lactones. 

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... 

The main feature of the Meerwein-Ponndorf-Verley reaction pathway involves the coordination of both reactants to the Lewis-acid metal eentre and hydride transfer from the alcohol to the earbonyl group. Aluminium or titanium alkoxides are usually effective homogeneous catalysts. With tin-Beta catalyst, cyclohexanone reduction with 2-butanol led selectively to cyclohexanol at 100 °C. Ketone conversion was >95%, whereas silicon-Beta, Sn02/Si02 and SnCl4 -5H20 were inaetive under the same experimental conditions. Therefore, the activity is likely due to tetrahedral tin in the zeolite framework, and not to extra-framework tin or to leached tin. ... 

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. 

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). 

The reaction of tosylhydrazones of a -unsaturated enones with sodium boro-hydride in alcoholic solution leads not to reduction, but instead to elimination according to Scheme 35, to provide a synthesis of allyl ethers in good yields. Potassium carbonate or sodium alkoxides can replace borohydride as the base in this sequence. trans-A y ethyl ethers (74) may be synthesized stereoselectively by the addition of aluminium hydrides to 1-alkynes and subsequent reaction of the vinyl alane formed (Scheme 36). This route complements the same authors ... 

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