Aldehydes aliphatic, reactions with

Bcnzaldehyde differs from aliphatic aldehydes in reactions with anions of lb in that formation of (Z)-isomers is favored only by a factor of 2-3, but again the selectivity can be reversed by the addition of HMPT. 

Reaction of RCHO with CJfCH=CHCH1Cl. This reaction can be regio-selective and f/ireo-selective when mediated by Sn and Al. The reaction of benz-aldehyde with cinnamyl chloride provides the anfi-homoallylic alcohol as the only detectable product. This diastereoselectivity obtains generally with aliphatic or aromatic aldehydes. The reaction with enals under the same conditions provides only the 1,2-adducts, again with anti-selectivity (equation I). The reaction of 2-phenylpropanal with 1 provides a mixture of homoallylic alcohols in the ratio 3 1, with anti-selectivity at the C—C bond formed in the reaction (equation II). 

The samarium(ll)-mediated Barbier reaction has been used as an alternative to the deprotonation chemistry to generate 2-alkyl-metallated oxazoles (Scheme 43). This reaction is very useful for the coupling of 2-iodomethyl oxazoles and aliphatic aldehydes. However, reactions with aromatic aldehydes gave mainly pinacol coupling products <20050L4099>. 

Primary amines cannot be usefully prepared, by reductive alkylation, from lower members of the aliphatic aldehydes and ammonia owing to side-reactions (for instance, formaldehyde and ammonia give hexamethylenetetramine). For aldehydes with more than five carbon atoms, however, conversion to the corresponding amine gives 60% yieldsEven better yields are reported for aromatic aldehydes, presumably because of the greater ease of imine formation With an excess of aromatic aldehyde the reaction with ammonia invariably leads to formation of the secondary amine but with aliphatic compounds a mixture of primary and secondary amines is generally obtained. Alternatively, secondary amines can be prepared directly from primary amines (equation 35). 

The carboline core is of high interest due to its presence in an array of compoimds, some of which are widely distributed in nature, including various plants, foodstuffs, marine creatures, insects, mammalians as well as human tissues and body fluids. Ghahremanzadeh et al. investigated the synthesis of a-carbolines, i.e., pyrido[2,3-b]indoles 169 (Scheme 94) in good yield via a four-component condensation reaction of indolin-2-one, 3-oxo-3-phenylpro-panenitrile, and various hydrazines and aldehydes in the presence of p-toluenesulfonic acid (p-TSA) at 140 °C in IL [BMlM][Br]. The reaction performed well with aromatic aldehydes, however, reaction with aliphatic aldehydes, for example, butanal or pentanal, complications such as incompletion of reaction, by-product formation, and difficulty in purifications arose, and the yield of the expected products were extremely poor. The authors claimed the methodology efficacious in terms of yield and product purity without p-TSA, only a trace of product was obtained even after 12 h. A similar reaction conducted in organic solvents afforded traces of tiie desired products [261]. 

A-Substituted pyrroles, furans and dialkylthiophenes undergo photosensitized [2 + 2] cycloaddition reactions with carbonyl compounds to give oxetanes. This is illustrated by the addition of furan and benzophenone to give the oxetane (138). The photochemical reaction of pyrroles with aliphatic aldehydes and ketones results in the regiospecific formation of 3-(l-hydroxyalkyl)pyrroles (e.g. 139). The intermediate oxetane undergoes rearrangement under the reaction conditions (79JOC2949). 

Paal-Knorr synthesis, 4, 118, 329 Pariser-Parr-Pople approach, 4, 157 PE spectroscopy, 4, 24, 188-189 photoaddition reactions with aliphatic aldehydes and ketones, 4, 232 photochemical reactions, 4, 67, 201-205 with aliphatic carbonyl compounds, 4, 268 with dimethyl acetylenedicarboxylate, 4, 268 Piloty synthesis, 4, 345 Piloty-Robinson synthesis, 4, 110-111 polymers, 273-274, 295, 301, 302 applications, 4, 376 polymethylation, 4, 224 N-protected, 4, 238 palladation, 4, 83 protonation, 4, 46, 47, 206 pyridazine synthesis from, 3, 52 pyridine complexes NMR, 4, 165... 

Cinnamic Acid.—The reaction, which takes place when an aldehyde (aliphatic or aromatic) acts on the sodium salt of an aliphatic acid in presence of the anhychide, is known as Perkin s reaction, and has a ery wide application. Accoid-ing to the result of Fittig s researches on the properties of the unsaturated acids described below, the reaction occurs in two steps. The aldeh) de forms first an additive compound with the acid, the aldehyde caibon attaching itself to the n-carbon ii.e.i nevt the carbovyl) of the acid. A saturated hydiOKy-acid is formed, which is stable, if the a-carbon is attached to only one atom of hydrogen, as in the case of isobutync acid,... 

The enamines of cyclic ketones, on reaction with aliphatic and aromatic aldehydes, give good yields of the 2-monoalkylidene derivative of the corresponding ketones (J28). The first step in the reaction appears to be the... 

Compound 40 has not yet been synthesized. However, there is a large body of synthetic data for nucleophilic substitution reactions with derivatives of 41 [synthesized from aliphatic and aromatic aldehydes, pyridine, and trimethylsilyl triflate (92S577)]. All of these experimental results reveal that the exclusive preference of pathway b is the most important feature of 41 (and also presumably of 40). 

Aliphatic, aromatic and vinylic aldehydes can be employed in this reaction with similar yields and enantioselectivities. When chiral aldehydes are utilized, excellent diastereoselectivity is obtained for matched cases, whereas mismatched cases yield products with moderate to good diastereoselectivity (Scheme 9.13a) [67]. The limitation of the methodology is that only terminal vinylepoxides can be obtained. 

The aldehyde structures and the tosylhydrazone salts were varied in an extensive study of scope and limitations, with use of both achiral and chiral sulfur ylides [73]. Aromatic aldehydes were excellent substrates in the reaction with benzaldehyde-derived ylides, whereas aliphatic aldehydes gave moderate yields and transxis ratios. 

With the chiral methyltitanium reagents 39, modified by the bidentate ligands A-sulfonyl-norephedrine 38, a pronounced enantioselectivity is observed in reactions with aromatic aldehydes. Considerably lower enantiosclcction is obtained with aliphatic aldehydes36. 

The lithium cnolate generated by deprotonation of 2-/m-butyl-6-methyl-l,3-dioxan-4-onc, readily available from polyhydroxybutyric acid (PHB), predominantly affords the diastereo-mers 7 when reacted with aldehydes. The diastereomeric ratios of aldol adducts 7/8, produced by reactions with aliphatic aldehydes, range from 87.5 12.5 to >99 1. Pure diastereoiners7are obtained by recrystallization in 25-74% yield116-118. Only marginal diastereoselectivities with respect to the carbinol center are obtained with aromatic aldehydes111-119. Benzoylation of the dioxanones 7, followed by reduction with lithium aluminum hydride, affords enan-tiomerically and diastereomerically pure triols 9 in >85% yield 11. ... 

The Pictet-Spengler reaction has mainly been investigated as a potential source of polycyclic heterocycles for combinatorial apphcations or in natural product synthesis [149]. Tryptophan or differently substituted tryptamines are the preferred substrates in a cyclocondensation that involves also aldehydes or activated ketones in the presence of an acid catalyst. Several versions of microwave-assisted Pictet-Spengler reactions have been reported in the hter-ature. Microwave irradiation allowed the use of mild Lewis acid catalysts such as Sc(OTf)3 in the reaction of tryptophan methyl esters 234 with different substituted aldehydes (aliphatic or aromatic) [150]. Under these conditions the reaction was carried out in a one-pot process without initial formation of the imine (Scheme 86). 

Anhydrides, both aliphatic and aromatic, as well as mixed anhydrides of carboxylic and carbonic acids, have been reduced to aldehydes in moderate yields with disodium tetracarbonylferrate Na2Fe(CO)4. Heating a carboxylic acid, presumably to form the anhydride, and then reaction with Na/EtOH leads to the aldehyde. 

In a related process, a-halo ethers can be prepared by treatment of aldehydes and ketones with an alcohol and HX. The reaction is applicable to aliphatic aldehydes and ketones and to primary and secondary alcohols. The addition of HX to an aldehyde or ketone gives tx-halo alcohols, which are usually unstable, though exceptions are known, especially with perfluoro and perchloro species. °... 

A particularly useful variation of this reaction uses cyanide rather than HCN. a-Amino nitriles can be prepared in one step by the treatment of an aldehyde or ketone with NaCN and NH4CI. This is called the Strecker synthesisand it is a special case of the Mannich reaction (16-15). Since the CN is easily hydrolyzed to the acid, this is a convenient method for the preparation of a-amino acids. The reaction has also been carried out with NH3-I-HCN and with NH4CN. Salts of primary and secondary amines can be used instead of NH to obtain N-substituted and N,N-disubstituted a-amino nitriles. Unlike 16-51, the Strecker synthesis is useful for aromatic as well as aliphatic ketones. As in 16-51, the Me3SiCN method has been used 64 is converted to the product with ammonia or an amine. ... 

There are actually three reactions called by the name Schmidt reaction, involving the addition of hydrazoic acid to carboxylic acids, aldehydes and ketones, and alcohols and alkenes. The most common is the reaction with carboxylic acids, illustrated above.Sulfuric acid is the most common catalyst, but Lewis acids have also been used. Good results are obtained for aliphatic R, especially for long chains. When R is aryl, the yields are variable, being best for sterically hindered compounds like mesi-toic acid. This method has the advantage over 18-13 and 18-14 that it is just one laboratory step from the acid to the amine, but conditions are more drastic. Under the acid conditions employed, the isocyanate is virtually never isolated. 

Diols (pinacols) can be synthesized by reduction of aldehydes and ketones with active metals such as sodium, magnesium, or aluminum. Aromatic ketones give better yields than aliphatic ones. The use of a Mg—Mgl2 mixture has been called the Gomberg-Bachmann pinacol synthesis. As with a number of other reactions involving sodium, there is a direct electron transfer here, converting the ketone or aldehyde to a ketyl, which dimerizes. 

Aliphatic or aromatic aldehydes RCHO can be transformed, in situ, via their iminium iodides, on reaction with enamines of ketones, to give /9-aminoketones. Thus, 4-methoxybenzaldehyde reacts with dimethylammonium chloride, triethyla-... 

Scheme 12.26 Asymmetric intramolecular Stetter reactions with aliphatic aldehydes...

Besides direct reduction, a one-pot reductive amination of aldehydes and ketones with a-picoline-borane in methanol, in water, and in neat conditions gives the corresponding amine products (Scheme 8.2).40 The synthesis of primary amines can be performed via the reductive amination of the corresponding carbonyl compounds with aqueous ammonia with soluble Rh-catalyst (Eq. 8.17).41 Up to an 86% yield and a 97% selectivity for benzylamines were obtained for the reaction of various benzaldehydes. The use of a bimetallic catalyst based on Rh/Ir is preferable for aliphatic aldehydes. 

The montmorillonite KlO-catalyzed aza-Diels-Alder reaction of Danishefsky s diene with aldimines, generated in situ from aliphatic aldehydes and p-anisidine, proceeded smoothly in H20 or in aqueous CH3CN to afford 2-substituted 2,3-dihydro-4-pyridones in excellent yields (Eq. 12.47).115 Also, complex [(PPh3)Ag(CBiiH6Br6)] was shown to be an effective and selective catalyst (0.1 mol% loading) for a hetero-Diels-Alder reaction with Danishefsky s diene and the reaction showed a striking dependence on the presence of trace amounts of... 

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