Aldehydes acyl derivative reduction

One of the more difficult partial reductions to accomplish is the conversion of a carboxylic acid derivative to an aldehyde without over-reduction to the alcohol. Aldehydes are inherently more reactive than acids or esters so the challenge is to stop the reduction at the aldehyde stage. Several approaches have been used to achieve this objective. One is to replace some of the hydrogens in a group III hydride with more bulky groups, thus modifying reactivity by steric factors. Lithium tr i - / - b u to x y a I u m i n u m hydride is an example of this approach.42 Sodium tri-t-butoxyaluminum hydride can also be used to reduce acyl chlorides to aldehydes without over-reduction to the alcohol.43 The excellent solubility of sodium bis(2-methoxyethoxy)aluminum hydride makes it a useful reagent for selective... 

Alkenylthiophenes and alkenylbenzo[6]thiophenes are most readily obtained by dehydration of the corresponding alkanols, obtained by reduction of the appropriate acyl derivatives (equation 12 Sections 3.14.2.4, 3.15.9.2.3). Allyl derivatives can be obtained by coupling a suitable allyl halide with the appropriate thienyllithium derivatives (Section 3.14.2.4). An unusual direct synthesis of 3-vinylthiophenes by ring closure of a-mercapto-aldehydes or -ketones with 1,3-butadienyl-l-triphenylphosphonium salts (386) gives satisfactory yields (equation 13) (75CJC3526). 

The anion derived from sulfone 4 coupled readily to aldehyde 3 (Scheme 17.7) to give a mixture of P hydroxysulfones that could be converted to a 2.5 1 mixture of the olefins 2 and 32, after acylation and reductive desulfonylation. Unfortunately, problems were subsequently encountered during the attempted removal of the acetal unit from 2 and 32 with pyridinium p-toluenesulfonate in propanol and acetonitrile. Apparently, silyl ether cleavage competed with the desired deacetalation process. Notwithstanding this, the C(24),C(26) diol was isolated pure in 33% yield, along with 28% yield of recovered starting material. This diol... 

Papaverine has been synthesized from the oxazole (19), obtained from the 2-lithio-derivative of 5-(3,4-dimethoxyphenyl)oxazole with veratric aldehyde, by catalytic reduction to the acyl-/ -phenylethylamine followed by Bischler-... 

Aryl -a-aminopropionic acids are obtained by reduction of azlactones with phosphorus and 50% aqueous hydriodic acid in glacial acetic acid. Many other reducing agents have been used. Reviews of this synthesis and related reactions have been made. The azlactones are conveniently prepared in good yields from aromatic aldehydes and N-acyl derivatives of glycine. Potassium carbonate has been found to be a superior catalyst for this condensation. Ketones cannot be substituted for the aromatic aldehydes. ... 

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. 

The poly-N-alkyl- and hexa-N-acyl derivatives of neomycin and paromomycin fail to show activity, but the hexa-N-methane-sulfonates and -sulfina-tes are claimed to be active and less toxic. 6 - and 6" -N alkyl- and N-alkylaryl-neomycins and -paromomycins have been prepared from the Schiffs bases by reduction with NaBH4 Some of the alkylaryl compounds show a slightly improved activity the alkyl derivatives are ineffective. The hexa-N-benzylneomydns prepared from neomycin, aromatic aldehydes and NaBH4, as well as the corresponding paromomycins, synthesized by means of catalytic reduction of the Schiffs bases, have reduced antibacterial activity. The Schiffs bases of paromomycin show in vitro the same activity as the parent compoimd, obviously because of the ease of hydrolysis. 

Reduction of Acyl Derivatives to Aldehydes. Aroyl chlorides and bromides give modest yields of aryl aldehydes when refluxed in diethyl ether with triethylsilane and Aluminum Chloride. Better yields of both alkyl and aryl aldehydes are obtained from mixtures of acyl chlorides or bromides and triethylsilane by using a small amount of 10% Palladium on Carbon catalyst (eq 7). This same combination of triethylsilane and catalyst can effect the reduction of ethyl thiol esters to aldehydes, even in sensitive polyfunctional compounds (eq 8). ... 

In the reduction of an acyl derivative, Pd undergoes oxidative addition inserting between the acyl group and X. Hydrogen or a substituted hydride adds to the palladium(II) followed by reductive elimination to regenerate Pd(0) and release the aldehyde (Eq. 1 Scheme 1). 

The reductions of ketones, aldehydes, carboxylic acids and acyl derivatives are fundamental reactions in organic synthesis and the use of aqueous media has allowed high regio- and stereoselective processes to be performed under mild conditions. 

Carboxylic acids and their acyl derivatives are relatively difficult to reduce. These reactions require strong reducing agents. In this section, we will review some of these reductions, which we studied earher as methods to synthesize alcohols and aldehydes. 

Aside from the outstanding and reliable diastereoselectivity, two more advantageous features helped the method to success the easy, one-step preparation of various N-acylated derivatives from the parent oxazolidinones and the cleavage of the auxiliary by hydrolysis, transamidation to the Weinreb amide, esterification, and reduction, as outlined in Section 4.1. A typical Evans aldol procedure with phenylalanine-derived oxazolidinone (S)-47, including the preparation of propionic imide 73 and cleavage of the auxiliary, is shown in Scheme 4.47. Typically, the boron aldolate resulting from the addition to the aldehyde has to be cleaved by an oxidative work-up. The hydrolysis of the aldol adduct 211 occurs without detectable epimerization that liberates diastereomerically and enantiomerically pure carboxylic acid 212 besides the auxiliary (S)-47 [110]. 

The aldehyde intermediate can be isolated if 1 equivalent of diisobutvl-aluminum hydride (D1BAH) is used as the reducing agent instead of LiAlH4. The reaction has to be carried out at -78 °C to avoid further reduction to the alcohol. Such partial reductions of carboxylic acid derivatives to aldehydes also occur in numerous biological pathways, although the substrate is either a thioester or acyl phosphate rather than an ester. 

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