Carbonyl compounds acid chlorides, reduction

Anions generated by cathodic reduction of carbonyl compounds, benzyl-chloride or activated double bonds can be trapped by addition to C02. With benzophenone the carbonate of benzilic acid was obtained (Eq. (134) ) 304 ... 

A particularly useful reaction has been the selective 1,2-reduction of a, P-unsaturated carbonyl compounds to aHyUc alcohols, accompHshed by NaBH ia the presence of lanthanide haUdes, especially cerium chloride. Initially appHed to ketones (33), it has been broadened to aldehydes (34) and acid chlorides (35). NaBH by itself gives mixtures of the saturated and unsaturated alcohols. 

Solid lithium aluminium hydride can be solublized in non-polar organic solvents with benzyltriethylammonium chloride. Initially, the catalytic effect of the lithium cation in the reduction of carbonyl compounds was emphasized [l-3], but this has since been refuted. A more recent evaluation of the use of quaternary ammonium aluminium hydrides shows that the purity of the lithium aluminium hydride and the dryness of the solvent are critical, but it has also been noted that trace amounts of water in the solid liquid system are beneficial to the reaction [4]. The quaternary ammonium aluminium hydrides have greater hydrolytic stability than the lithium salt the tetramethylammonium aluminium hydride is hydrolysed slowly in dilute aqueous acid and more lipophilic ammonium salts are more stable [4, 5]. 

Kinetic studies established that tetra-n-butylammonium borohydride in dichloromethane was a very effective reducing agent and that, by using stoichiometric amounts of the ammonium salt under homogeneous conditions, the relative case of reduction of various classes of carbonyl compounds was the same as that recorded for the sodium salt in a hydroxylic solvent, i.e. acid chlorides aldehydes > ketones esters. However, the reactivities, ranging from rapid reduction of acid chlorides at -780 C to incomplete reduction of esters at four days at 250 C, indicated the greater selectivity of the ammonium salts, compared with sodium borohydride [9], particularly as, under these conditions, conjugated C=C double bonds are not reduced. 

A more recent example, which involves an enantiomerically pure compound, reverts to the original lead by incorporating a hydroxyl group on the benzylic carbon. Preparation of this close relative of ibutilide (5-3) uses the same starting material. Acylation of w-dibutylamine with the acid chloride from the treatment of (6-1) with tert-butylcarbonyloxy chloride leads to the amide (6-2). Reduction of the carbonyl group in this compound with chloro-(+)-diisopropylcamphemyl borane (DIPCl) proceeds to afford the R alcohol (6-3) in high enantiomeric exess. 

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. 

Similar oxidative rearrangements to produce carbonyl compounds have been carried out with thallium(III) nitrate557 or peroxytrifluoroacetic acid-BF3.558 The Jones reagent (Cr03—H2S04) in the presence of a catalytic amount of Hg(II) is also effective.559 Chromyl chloride oxidation, when combined with reductive workup, is a simple, convenient one-step method to convert 2,2-disubstituted 1-alkenes to aldehydes.560,561... 

Reduction of carbonyl compounds.2 The reagent reduces aromatic and aliphatic ketones, aldehydes, and acid chlorides to alcohols in moderate to excellent yield in chloroform solution. The order of substrate reactivity is RCOCl>RCHO>R2CO. Only three of the eight hydrogens are transferred under the reaction conditions. 

In the reaction of CbSi" with acid chlorides, two trichlorosilyl groups are introduced (equation 14) this probably proceeds via a two-step mechanism. The first step involves reductive silylation and loss of the carbonyl group the second involves a halide displacement as above. These trichlorosilyl compounds may be further treated with Grignard... 

Acid-catalyzed addition of aliphatic, aromatic or heteroaromatic cyanohydrins to ethyl vinyl ether, n-butyl vinyl ether or dihydro-4//-pyran provides base stable, protected cyanohydrin derivatives. Phase transfer catalyzed alkylation of aliphatic cyanohydrins with allylic bromides gave a-substituted a-allyl-oxyacetonitrile. Carbonyl compounds react wiA cyanide under phase transfer catalysis to give cyanohydrin anions, which are trapped by an acyl chloride or ethyl chloroformate to give acyl- or alkoxycarbonyl-protected cyanohydrins respectively. The reduction of the carbonyl group of an acyl cyanide by NaBH4 under phase transfer conditions followed by esterification serves as an alternative route to aldehyde-derived cyanohydrin esters. ... 

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