Meerwein-Ponndorf-Verley reduction Aluminum isopropoxide

Butoxybis(dimethylamino)methane, 121 Dimethylformamide dimethyl acetal, 120 Trisdimethylaminomethane, 121 Marschalk reaction l,5-Diazabicyclo[4.3.0]nonene-5, 91 Meerwein-Ponndorf-Verley reduction Aluminum isopropoxide, 265 /-Butoxydiiodosamarium, 272 Dicyclopentadienyldihydridozirconium, 108... 

Isopropyl Alcohol and Aluminum Isopropoxide. This is called the Meerwein-Ponndorf-Verley reduction It is reversible, and the reverse reaction is known as the Oppenauer oxidation (see 19-3) ... 

In fact, a variation of this reaction has been utilized in the well-known Meerwein-Ponndorf-Verley reduction of carbonyl compounds (reverse of Oppenauer oxidation of alcohols) by aluminum isopropoxide The reaction involves a six-centered transition state, wherein the P-hydride is delivered into an incoming carbonyl group [Eq. (6.86)]. The stereochemistry of this reaction has been studied in detail. ... 

Cram s rule12fi or the more recent model of Felkin127 can be employed to predict the stereochemical outcome of such reactions. However, Meerwein-Ponndorf-Verley reductions present some of the few exceptions to the rule. For example, (-)-(R)-3-cyclohexyl-2-butanone is, in contrast to prediction, predominantly reduced by aluminum isopropoxide to the corresponding eryf/iro-product128. 

The reduction of the bicyclic terpcncs thujone and isothujone has also been studied with various reducing reagents and compared with the traditional Meerwein-Ponndorf-Verley conditions using aluminum isopropoxide in refluxing isopropanol for 4 hours (or alternatively. vec-bu-tanol). Control experiments show essential kinetic control (ca. 3% isomerization of thujones is observed prior to reduction)178. The less stable alcohol is preferentially formed in the Meerwein-Ponndorf-Verley reductions. 

Kinetically controlled conditions are not easily maintained in the Meerwein-Ponndorf-Verley reduction of less reactive a,/ -unsaturated or hindered ketones and the thermodynamically more stable equatorial alcohols become the major products. Thus, Meerwein-Ponndorf-Verley reduction of 5a-cholest-l-ene-3-one using aluminum isopropoxide in isopropanol is reduced to a 1 9 mixture of 3a- and 3/ -alcohols180 (see also ref 181) [d.r. [(3S)/(3/ )] 10 90. ... 

In many cases, bridged polycyclic ketones react relatively slowly in the Meerwein-Ponndorf-Verley reduction and the thermodynamic equilibrium is obtained using aluminum isopropoxide in boiling isopropanol. The equilibrium depends on the substituents (see refs 5, 183 and 184). 

Aluminum alkoxides, particularly those formed from secondary alcohols, have been of interest to synthetic chemists since the mid-1920s due to their catalytic activity. Examples of these trialkoxides include aluminum isopropoxide (AIP) and aluminum sec-butoxide (ASB). They are easily prepared at lab or plant scale and provide highly selective reductions and oxidations under mild conditions. These reductions are termed Meerwein-Ponndorf-Verley (MPV) reactions after the chemists (1-3) who first investigated their utility. Because a MPV reaction are accuratelybe described as an equilibrium process, the reverse reaction (oxidation) can also be exploited. These associated reactions are termed Oppenauer oxidations (4). Meerwein-Ponndorf-Verley reductions and Oppenauer oxidations as well as other reaction types and applications will be discussed, but first some background is provided concerning structure, preparation, and characterization of aluminum isopropoxide and related compounds. 

In a different vein and as already pointed out in Chapter 8 (Scheme 8.6), the Meerwein-Ponndorf-Verley reduction is the reverse of the Oppenauer oxidation of aldehydes and ketones, and it is only a change of solvent that dictates whether the reaction that occurs is an oxidation or a reduction.The same catalyst is used. Scheme 9.19 is the reverse of Scheme 8.6. Thus, it is now suggested that the carbonyl oxygen of cyclohexen-3-one displaces an isopropoxy group (2-propoxy [ OCH(CH3)2]) from the catalyst, aluminum isopropoxide [Al(0-iPr)3].Then, after intramolecular hydride transfer, propanone (acetone, CH3COCH3) is lost by displacement from aluminum by the solvent, 2-propanol (isopropanol [CH3CH(OH)CH3]), and finally, the cyclo-... 

Aluminum isopropoxide/aluminum chloroisopropoxide Modified Meerwein-Ponndorf-Verley reduction... 

It was noticed as early as 1925 that alkoxides of calcium, magnesium and particularly aluminum could catalyze the reduction of aldehydes by ethanol as shown in equation (65).242,243 Removal of very volatile acetaldehyde is easily achieved to drive the reaction to the right. In 1926, Ponndorf devised a method in which both aldehydes and ketones could be reduced to alcohols by adding excess alcohol and aluminum isopropoxide.244 Such reductions are today referred to as Meerwein-Ponndorf-Verley reactions. Although alkoxides of a number of metals, e.g. sodium, boron, tin, titanium and zirconium, have been used for these reactions, those of aluminum are by far the best. 

The classical Meerwein-Ponndorf-Verley (MPV) process, named after the independent originators, can be illustrated by the reduction of crotonaldehyde (43) by aluminum isopropoxide (44) in isopropyl alcohol (equation 24). Aluminum isopropoxide transfers hydride reversibly to a carbonyl acceptor. Acetone is formed as a volatile side product, which can be removed during reaction. The reaction of equation (24) is forced even further to the right by the use of excess isopropyl alcohol. MPV reactions have been reviewed.In the Oppenauer variant of this reaction an alcohol is oxidized to a ketone, and acetone is used as hydride acceptor in the presence of a strong base like r-butoxide. This reaction was originally developed for the selective oxidation of sterols. The synthetic aspects of this procedure have also been reviewed. ... 

The deviation from Cram s rule has been attributed to the cyclic nature of the transition state of the Meerwein-Ponndorf-Verley reaction129. The situation may be further complicated by hydride transfer from external aluminum isopropoxide units not involved in the cyclic six-mem-bered transition state49,5S-13°. These competitive mechanistic pathways (external vs internal hydride transfer) depend on the experimental conditions (concentrations of reactants etc.). These have also been observed in the reduction of cyclic 1,2-diones where an internal hydride transfer to the intermediate a-hydroxy ketones may be sterically hindered. In these cases the stereochemical outcome of Meerwein-Ponndorf-Verley reactions cannot be definitely predicted. 

One of the chemoselective and mild reactions for the reduction of aldehydes and ketones to primary and secondary alcohols, respectively, is the Meerwein-Ponndorf-Verley (MPV) reduction. The lifeblood reagent in this reaction is aluminum isopropoxide in isopropyl alcohol. In MPV reaction mechanism, after coordination of carbonyl oxygen to the aluminum center, the critical step is the hydride transfer from the a-position of the isopropoxide ligand to the carbonyl carbon atom through a six-mem-bered ring transition state, 37. Then in the next step, an aluminum adduct is formed by the coordination of reduced carbonyl and oxidized alcohol (supplied from the reaction solvent) to aluminum atom. The last step is the exchange of produced alcohol with solvent and detachment of oxidized alcohol which is drastically slow. This requires nearly stoichiometric quantities of aluminum alkoxide as catalyst to prevent reverse Oppenauer oxidation reaction and also to increase the time of reaction to reach complete conversion. Therefore, accelerating this reaction with the use of similar catalysts is always the subject of interest for some researchers. 

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