Aldehydes amide reduction

Anhydrides are reduced with relative ease. McAlees and McCrindle 20) established the following increasing order of difficulty for various carbonyls acid chlorides > aldehydes, ketones > anhydrides > esters > carboxylic acids > amides. Reduction may proceed by 1,2-addilion of hydrogen or by cleavage of an oxygen-carbonyl bond. If 1,2-addition to the carbonyl occurs, as in the presence of strong protic acids over palladium, 1,1-diesters are formed by acylation 26). 

Reductive Amidation of Aldehydes. The reductive amidation of aldehydes using an organosilane as the reducing agent has been realized. Benzaldehyde reacts over a 74-hour period with triethylsilane and acetonitrile in 75% aqueous sulfuric acid at room temperature to produce an 80% isolated yield of N-benzylacetamide (Eq. 169).313 Octanal fails to react under the same conditions.313 Reductive amidation of aldehydes also occurs with the reagent combination Et3SiH/TFA/primary amide (Eq. 170).326... 

Silylformylation and hydroformylation reactions figured prominently in Ojima s approach to isoretronecanol and trachelanthamidine [40]. Thus, silylformylation of alkyne 70 proceeded smoothly to produce aldehyde 71 (Scheme 5.26). Reduction and protodesilylation provided allylic alcohol 72, which was protected to give 73. Hydroformylation in the presence of HC(OEt)3 led to a 2 1 mixture of 74 and 75. Deprotection and amide and amidal reduction then provided the target compounds. 

Table 3 Preparation of N -Protected Amino Aldehydes by Reduction of Ester and Amide Derivatives n o...

Scheme 9 Solid-Phase Synthesis of an a-Amino or Peptide Aldehyde by Reduction of the Corresponding Weinreb Amide LinkerN...

Many enzymes are both active and stable in carbon dioxide and have been used to conduct a number of reactions. Several different types of reactions have been examined, including hydrolysis (Lee et al., 1993 Randolph et al., 1985 Zheng and Tsao, 1996), oxidation (Hammond et al., 1985 Randolph et al., 1988), and esterification/transesterification (Kamihira et al., 1987 Nakamura et al., 1986 Rantakyla and Aaltonen, 1994), but there are other types of reactions that would make worthwhile investigations in carbon dioxide. These include preparation of amides, reduction of ketones, preparation of cyanohydrins from aldehydes, aldol reactions, hydroxylation reactions, and Baeyer-Villiger oxidation. 

The alkylation of ammonia, Gabriel synthesis, reduction of nitriles, reduction of amides, reduction of nitrocompounds, and reductive amination of aldehydes and ketones are methods commonly used for preparing amines. 

In the amide reduction scheme on p. 618, the step framed in green gives an iminium ion. Stopping the reaction here would therefore provide a way of making aldehydes from amides. Because these tetrahedral intermediates are rather more stable than those from ester reduction, this can often be achieved simply by carrying out the amide reduction, and quenching, at 0°C (-70 °C is usually needed to stop esters overreducing to alcohols). 

Reductions. This hydride is a strong reducing agent comparable to other lithium trialkylhydrides. It is superior to DIBAH for selective 1,2-reduction of enones. Reduction of ketones, esters, acid chlorides, and anhydrides proceeds at -78°. However, ketones can be reduced selectively in the presence of an ester. Esters are reduced to a mixture of an alcohol and an aldehyde. Complete reduction to an alcohol can be effected by reduction at -78° with 2 equiv. of 1 and then with excess sodium borohydride. Tertiary amides are reduced by 1 equiv. of the reagent to aldehydes in generally high yield. Selective reduction of primary halides in the presence of secondary halides is possible. 

The best way to prepare peptide aldehydes from the corresponding N -protected amino acids is by using a handle based on the Weinreb amide.f This commercial handle allows classical solid-phase elongation of peptides using protected Boc or Fmoc amino adds and, at the end of the synthesis, the peptide aldehyde is formed by reduction and concomitant cleavage from the resin with lithium aluminum hydride. Although the 4-hydro-xybenzoic acid handle also allows the preparation of peptide aldehydes by reduction of the resin-bound phenyl ester with lithium tri-tert-butoxyaluminum hydride, a noixture of the aldehyde and the alcohol is always formed. 

Finally, treatment of amides with phosphorus oxychloride gives Vilsmeier complexes, which are often formulated as A-alkylated imidoyl chlorides (59). Irrespective of their precise nature, it has been found that they can be converted very efficiently to aldehydes by reduction with zinc followed by aqueous work-up (Scheme 17). Although the method has only been used for benzaldehyde and a number of chlorinated and brominated analogs, the yields reported are consistently high (87-97%). ... 

This method is highly selective for unsaturated ketones and aldehydes, whereas reduction of a,p-un-saturated carboxylic acid derivatives, such as esters, amides and nitriles, is very sluggish. Thus, benz-ylideneacetone was selectively and cleanly reduced in the presence of methyl cinnamate, cinnamonitrile or cinnamamide. ... 

Selective reduction of aldehydes. This reduction can be effected with formic acid (1.25 equiv.) and triethylamine (1 equiv.) and a catalytic amount of RuCl2[P(C6H5)3]3 at 25° in THF. Under these conditions nitro, keto, ester, and r-amide groups are not reduced. The reduction of aldehydes, however, is sensitive to steric hindrance. Thus mesitaldehyde is reduced very slowly. 

The monomers are prepared by the homologation of N-protected amino acid aldehydes. Boc-protected amino aldehyde was synthesized in solution via Weinreb amide reduction with LiAlH4.Then, using a Wittig reaction, it was transformed into an olefin bearing an ethyl ester group, which was subsequently saponified. 

The equilibrium between the open and closed form of the aldehyde-amide formed from acylated derivatives of A pyrrolines (conkurchine series6) has been studied for the N-benzoyl (6) and the iV-acetyl (7) compounds.7 It appears that for the benzoyl derivative (6) the equilibrium is such that the open form is favoured, whereas for the acetyl derivative (7) the cyclic form predominates [there is an absence of C=0 aldehydic vibrations in the i.r. of (7)]. However, in both cases, reduction with sodium borohydride gave the two corresponding alcohol amides. 

Reduction of amides. A synthesis of /V-protected a-amino aldehydes involves reduction of morpholine amides. Defluorination of secondary o-fluorobenzamides at room temperature takes place before carbonyl group reduction. However, tertiary amides do not behave similarly. 

Amides. Reductive alkylation (with an aldehyde and NaBHa) followed by N-acylation and treatment with /-BuOK in THF constitutes a route to RCONHCH2R. ... 

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