Lewis acids carbonyl compound reduction

A popular two-step protocol for the deoxygenation of carbonyl compounds is the Mozingo reaction in which the aldehyde or ketone is transformed to a dithioacetal in the presence of a Lewis acid and then reductive desulphurization is carried out with Raney The reaction is mild, efficient and particularly convenient for small-scale... 

On the other hand, trialkylhydrosilanes are capable of reducing carbonyl compounds and some activated olefins in the presence of Brc nsted or Lewis acids. Apparently, coordination of carbonyl oxygen to acid is important to activate electrophilic carbons. We thought that pentacoordinate hydridosilicates should be a good hydride transfer reagent because of the intrinsic nucleophilicity, while the significant Lewis acid character of the silicon center should activate the substrate carbonyl compounds. Reduction of carbonyl compounds with pentacoordinate hydridosilicates are expected to proceed without any additives and thus very interesting from both mechanistic and practical point of view. 

Compared to monodentate Lewis acid (19), bidentate Lewis acid (17) resulted in higher electrophilic activation of carbonyl compounds. For example, in the presence of Lewis acid (17), BusSnH reduction of acetophenone smoothly proceeded at —78 °C to give phenylethanol in 91% yield. A similar reaction with Lewis acid (19) gave phenylethanol in only 9% yield (Scheme 6.43). 

The synthesis of the right-wing sector, compound 4, commences with the prochiral diol 26 (see Scheme 4). The latter substance is known and can be conveniently prepared in two steps from diethyl malonate via C-allylation, followed by reduction of the two ethoxy-carbonyl functions. Exposure of 26 to benzaldehyde and a catalytic amount of camphorsulfonic acid (CSA) under dehydrating conditions accomplishes the simultaneous protection of both hydroxyl groups in the form of a benzylidene acetal (see intermediate 32, Scheme 4). Interestingly, when benzylidene acetal 32 is treated with lithium aluminum hydride and aluminum trichloride (1 4) in ether at 25 °C, a Lewis acid induced reduction takes place to give... 

This reaction sequence of conjugate reduction followed by aldol reaction is known as the reductive aldol reaction. In certain instances, reductive elimination from the M-TM-enolate species may occur to furnish M-enolate, which itself may participate in the aldol reaction (Scheme 3). This detour may be described as the background path or stepwise path in one-pot. Indeed, it has been reported that certain cationic Rh complexes such as [Rh(COD)(DPPB)] (COD = 1,5-cyclooctadiene, DPPB = diphenylphosphinobutane) catalyze the aldol reactions of silyl enol ethers and carbonyl compounds by serving as Lewis acids [5-8]. 

The practical applications of NaBH4 reductions on mineral surfaces for in situ generated SchifFs bases have been successfully demonstrated. The solid-state reductive amination of carbonyl compounds on various inorganic solid supports such as alumina, clay, silica etc. and especially on K 10 clay surface rapidly afford secondary and tertiary amines [126]. Clay behaves as a Lewis acid and also provides water from its interlayers thus enhancing the reducing ability of NaBH4 [22],... 

Reduction of a., -unsaturated carbonyl compounds. Hydrosilanes, particularly (QH,)2SiH2, in the presence of Pd(0), and a Lewis acid, particularly ZnCl2, can effect selective conjugate reduction of unsaturated ketones, aldehydes, and carboxylic acid derivatives. Chloroform is the solvent of choice. In addition, 1 equiv. of water is required. Experiments with D,0 and (C6H,),SiD2 indicate that... 

Reduction of aldehydes and ketones.4 In the presence of hydrogen chloride (or a Lewis acid), the reagent reduces carbonyl compounds to alcohols in high yield and with high stereoselectivity. However, the reduction of hindered ketones requires a strong Lewis acid (A1C13). Aldehydes are reduced so much more readily than ketones that selective reductions are possible. The reagent is also useful for reduction of a,/5-cnals to allylic alcohols. 

A solvent-free reductive amination of carbonyl compounds using sodium borohydride supported on moist montmorillonite K10 clay also was facilitated by microwave irradiation (Scheme 8) [54]. Clay served the dual purpose of a Lewis acid and provided water from its interlayers to enhance the reducing ability of NaBH4. 

For a-bromo ketones and related compounds, enhancement of the enantioselectivities has been achieved by the addition of simple Lewis acids (e.g., BF3, Cp2TiCl2, or magnesium salts, which presumably form Lewis acid-Lewis base complexes with the carbonyl functions of the substrates).2627 The stereochemical effect of some Lewis acid additives on the reduction of a racemic a-bromo ester, namely ethyl 2-bromo-2-phenylpropanoate, is summarized in Scheme 27.2. 

If, for example, the mild Lewis acid LiAlH4—it is mildly acidic because its acidic moiety is Li+—is used as a hydride donor, the diastereoselectivity of the reduction of a-chiral carbonyl compounds with a heteroatom in the a position can be controlled by... 

There is a second effect. In the transition state in which the stronger Lewis acid complexes the carbonyl oxygen, the carbonyl group is a better electrophile. Therefore, it becomes a better hydride acceptor for Brown s chloroborane than in the hydride transfer from Alpine-Borane. Reductions with Alpine-Borane can actually be so slow that decomposition of this reagent into a-pincnc and 9-BBN takes place as a competing side reaction. The presence of this 9-BBN is problematic because it reduces the carbonyl compound competitively and of course without enantiocontrol. 

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