Stoichiometric Reduction Systems

The desire for a mild reducing reagent like borohydride which would be soluble in nonpolar media has led to the development of several ammonium borohydrides. 

The reducing power of tetralkylammonium borohydrides in dichloromethane is similar to that observed in water or alcohol. A convenient preparation of tetrabutyl-ammonium borohydride has recently been reported [11] and the utility of the reagent has been surveyed [12]. In dichloromethane solution, tetrabutylammonium borohydride readily reduces aldehydes, ketones and acid chlorides while reacting only very slowly with esters (see Table 12.2). 

Brandstrom and coworkers have shown that tetrabutylammonium borohydride in dichloromethane solution will react with alkyl halides (methyl iodide, ethyl bromide or 1,2-dichloroethane) to yield solutions of diborane (see Eq. 12.3). Although diborane cannot be distilled from these solutions and its presence is therefore not 

Several examples of reduction by tetrabutylammonium borohydride in the presence and absence of alkyl halide are recorded in Table 12.2. 

Tetrabutylammonium cyanoborohydride has also been used under noncataly tic conditions [ 13]. Inhexamethylphosphoric triamide (HMPA, HMPT), (n-C4H9)4N BH3CN reduces primary alkyl iodides to alkanes in high yield. Primary alkyl bromides are about half as reactive as the iodides and primary chlorides and tosylates are virtually inert, as are the cyano, nitro and carbonyl groups. 

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Metal-induced reductive dimerization of carbonyl compounds is a useful synthetic method for the formation of vicinally functionalized carbon-carbon bonds. For stoichiometric reductive dimerizations, low-valent metals such as aluminum amalgam, titanium, vanadium, zinc, and samarium have been employed. Alternatively, ternary systems consisting of catalytic amounts of a metal salt or metal complex, a chlorosilane, and a stoichiometric co-reductant provide a catalytic method for the formation of pinacols based on reversible redox couples.2 The homocoupling of aldehydes is effected by vanadium or titanium catalysts in the presence of Me3SiCl and Zn or A1 to give the 1,2-diol derivatives high selectivity for the /-isomer is observed in the case of secondary aliphatic or aromatic aldehydes. 

The use of organomagnesium reagents as terminal reductants in zirconocene-catalyzed diene reductive cyclization permits derivatization of the resulting bis(magnesiomethyl)cycloalkanes. However, the use of other stoichiometric reductants is likely to afford catalytic systems that exhibit complementary selectivity profiles. Molander reports the... 

Radical cyclizations catalyzed by 67a require the regeneration of the titanocene catalysts by a stoichiometric reductant, such as manganese. When 10 mol% of substituted cyclopentadienyltitanium complex 47e is applied instead truly catalytic cyclization sequences of epoxides 86 are possible (Fig. 25) [160]. Reductive radical generation from 86 promoted by titanocene chloride 67e and subsequent 5-exo cyclization of radical 86A generates a titanoxy cyclopentylalkyl radical 86B. Since the electron-poor titanocene chloride 67e reduces the tertiary radical 86B only sluggishly, its extended lifetime allows for a 1,5-SHi affording the bicyclic tetrahy-drofuran ring system 87. At the same time catalyst 67e is liberated. The reaction... 

One of the main issues with the use of magnesium and zinc as inexpensive co-reductants is their reactivity with alkyl halides. Also, additives such as TMSOTf are relatively expensive. In an attempt to address these limitations, Namy utilised mischmetal (La 33%, Ce 50%, Nd 12%, Pr 4%, Sm and other lanthanides 1%) as the stoichiometric reductant for the regeneration of the Sm(II).31,32 This reagent system provides an important alternative since it does not require the use of additives and mischmetal is relatively inexpensive. This system has been utilised successfully in Barbier and Reformatsky reactions, halide reductions and pinacol couplings (Scheme 7.7).31,32... 

The case considered here is relatively simple, but more complex behavior is frequently encountered the reduced form may have more than two stages of acidic dissociation and in addition the oxidized form may exhibit one or more acidic dissociations. There is also the possibility of basic dissociation occurring, but this can be readily treated as equivalent to an acidic ionization (cf. p. 362). The method of treatment given above can, however, be applied to any case, no matter how complex, and the following general rules have been derived which facilitate the analysis of pH-potential curves for oxidation-reduction systems of constant stoichiometric composition. ... 

In 1999, Cozzi and Umani-Ronchi described a diastereoselective intermolecular pinacol coupling of aromatic and aliphatic aldehydes in the presence of a catalytic quantity of TiCl4(THF)2/Schiff base (Eq. 3.38) [60]. Manganese is employed as the stoichiometric reductant with the Cozzi/Umani-Ronchi system, zinc generally affords a lower yield of the diol. The reaction is believed to proceed via a pathway analogous to that illustrated in Fig. 3-5. The observations of Cozzi and Umani-Ronchi that the Schiff base affects reaction diastereoselectivity and increases the reaction rate bode well for studies of asymmetric variants. In an initial investigation, these workers obtained 10% ee in a reductive dimerization of benzaldehyde (Eq. 3.39). 

One of the standard methods for the preparation of aldehydes involves the reduction of acid halides. A variety of stoichiometric reducing systems are available for this transfomiation, which include NaAlH(OBu-r)3, LiAlHfOBu-O.i, NaBHfOMe). Catalytic hydrogenation with H2 and Pd on carbon is also a popular method. In contrast, methods based on the radical reduction of acyl halides are synthetically less important. Radical reduction methods involve generation and subsequent hydrogen abstraction as key steps, which is complicated by decarbonylation of the intermediate acyl radicals. The first example in Scheme 4-1 shows that this competitive reaction is temperature dependent, where an acyl radical is generated from an acyl phenyl selenide via the abstraction of a phenylseleno group by tributyltin radical [5]. 

A variety of metal compounds as an oxidant have long been used for phenolic oxidation. These oxidants are widely used and are very effective for organic synthesis in a laboratory scale. However, they are no longer utilized in an industrial scale, because stoichiometric amounts of these metal compounds are often required. Accordingly, the corresponding oxidation-reduction systems must be constructed for each metal oxidation. In this section, phenolic oxidation using a variety of metal compounds will be described. 

In this chapter, reagents are classihed mainly into three categories (1) for catalytic oxidation of phenols, (2) for phenolic oxidation with nonmetallic compounds and (3) for phenohc oxidation with metallic compounds. In the 21st century, regardless of metallic or nonmetallic compounds, catalytic oxidation systems with high efficiency must be constructed. K stoichiometric amounts of reagents are employed, efficient oxidation-reduction systems should be invented. 

When a mixture of tetrachloromethane and benzaldehyde in DMF was treated, at room temperature, with a catalytic amount of lead(ll) bromide and a shght excess of aluminum as a stoichiometric reductant the coupled product was obtained in good yield (Scheme 13.69) [86]. Subsequent reductive 1,2-elimination of trichloromethyl carbinol by means of the Pb/Al bimetal system could be readily achieved by changing the reaction media. The mechanism of the Pb/Al bimetal redox system presumably involves lead(O) reduction of polyhalomethane to provide an organolead complex which then reacts wifh an aldehyde to give the couphng product. Regenerahon of lead(O) by reduchon of lead(ll) with aluminum metal would complete the catalyhc cycle. 

The H2-TPR profiles of differently loaded VPS catalysts in the range 200-1100°C, shown in Figure 3B, account for the stoichiometric reduction of V to in both VPS and bulk V2O5 systems. The H2-TPR pattern of the low VPS 2 catalyst (Fig. 3B, a) entails a very sharp... 

We have never succeeded in detecting by ESR the free radicals of important biological molcules such as lAA (indoleacetic acid) and NADH which are substrates for the peroxidase-oxidase reaction. When an electron acceptor such as ferric ion with o-phenanthroline is added to the peroxidase system, one can observe the stoichiometric reduction of iron (Figure 2) described in the following reactions (28). 

In contrast to the stoichiometric Fe-AcOH reduction system, O Dell and Nicholas have deseribed another reductive cyclization of o-nitro-substituted MBH acetates by carbon monoxide, using [Cp Fe(CO)2]2 as catalyst. ... 

Most of the nitro eompounds reactions reported to be promoted by iron carbonyl compounds are stoichiometric reductions to anilines, although some reactions affording azo-, azoxybenzenes or carbamates have also been reported (see Chapters 3 and 4). Catalytic reactions have been reported in only very few cases, and always with very low turnovers. This lack of stability of the catalytic systems appears to be due to the easy formation of iron oxides [229]. The last reaction can be partly retarded by adding the nitro compound slowly to the reaction mixture, but only about ten turnovers were anyway obtained even under these conditions [230]. 

The only iron systems for which some more mechanistic information are available are those involving the group of clusters [HFe3(CO)u], [Fe3(CO)n], and the radical anion [Fe3(CO)n]. The cluster [HFe3(CO)n] has been used as a stoichiometric reductant for nitro compounds in some cases [229, 243] and has also been proposed to be the active species when Fe3(CO)i2 and OH or F are used as reductants in a biphasic water/organic solvent system [236, 244-246]. 

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