Aryl-aldehydes, activation

Kitamura and Noyori have reported mechanistic studies on the highly diastere-omeric dialkylzinc addition to aryl aldehydes in the presence of (-)-i-exo-(dimethylamino)isoborneol (DAIB) [33]. They stated that DAIB (a chiral (i-amino alcohol) formed a dimeric complex 57 with dialkylzinc. The dimeric complex is not reactive toward aldehydes but a monomeric complex 58, which exists through equilibrium with the dimer 57, reacts with aldehydes via bimetallic complex 59. The initially formed adduct 60 is transformed into tetramer 61 by reaction with either dialkylzinc or aldehydes and regenerates active intermediates. The high enantiomeric excess is attributed to the facial selectivity achieved by clear steric differentiation of complex 59, as shown in Scheme 1.22. 

Classical Aldol. Aldol reaction is an important reaction for creating carbon-carbon bonds. The condensation reactions of active methylene compounds such as acetophenone or cyclohexanone with aryl aldehydes under basic or acidic conditions gave good yields of aldols along with the dehydration compounds in water.237 The presence of surfactants led mainly to the dehydration reactions. The most common solvents for aldol reactions are ethanol, aqueous ethanol, and water.238 The two-phase system, aqueous sodium hydroxide-ether, has been found to be excellent for the condensation reactions of reactive aliphatic aldehydes.239... 

The readily prepared support was then used for dihydropyrimidine and chalcone synthesis (Scheme 7.29). Thus, the modified support was activated prior to reaction by treatment with tosyl chloride. Solutions of the appropriate acetophenones were then spotted onto the membrane and the support was submitted to microwave irradiation for 10 min [45]. In the next step, several aryl aldehydes were attached under microwave irradiation to form a set of corresponding chalcones through a Claisen-Schmidt condensation. 

Indeed the only conversion where biocatalysis should be seriously considered is the transformation of aldehydes into optically active cyanohydrins1 2. For example, the conversion of aryl aldehydes into the appropriate (R)-cyanohydrins using almond meal may be accomplished in quantitative yield and gives products... 

When the reaction with substituted benzaldehydes is conducted in the presence of ammonia, the a-amino carboxylic acids are formed [11], The corresponding reaction involving bromoform is less effective and, for optimum yields, the addition of lithium chloride, which enhances the activity of the carbonyl group, is required. In its absence, the overall yields are halved. The reaction of dichlorocarbene with ketones or aryl aldehydes in the presence of secondary amines produces a-aminoacetamides [12, 13] (see Section 7.6). 

Recent work [64] by Kiljunen and Kanerva has been directed towards the search for novel sources of (R)-oxynitrilases which may transform bulky aryl aldehydes. For this purpose whole cell preparations (called meal) from apple seeds and cherry, apricot and plum pips were tested for their (R)-cyanohydrin activity. In this study a comparison of almond and apple meal showed that they possess similar properties for the formation of the (R)-stereogenic centre. However, in certain cases higher enantioselectivity was observed using the apple meal preparation. Additionally, apple meal (R)-Hnl has also been applied to transform ketones into their corresponding cyanohydrins [65] thus creating a wider repertoire of substrates for this latest of (R)-Hnls. Thus it has only recently been shown that apple meal (R)-oxynitrilase is now an additional member of the (R)-Hnl family. 

The utility of the method was demonstrated with a variety of electron-rich and electron-poor aryl aldehydes, but the method was not suitable for aliphatic aldehydes. No racemization was observed in the copper-catalyzed oxidative amidation reaction when an optically active amine, (S)-valine methyl ester, was employed. 

Alkaline silver oxide is the most satisfactory reagent for oxidation of the aldehyde 3 to the acid 4.2 This reagent has been recommended for oxidation of aryl aldehydes (1,1012-1013), but only moderate yields have been reported for oxidation of a,/ -enals with Ag20.3 Apparently, the successful results in the oxidation of 3 are the result of the activating effect of the keto group. 

A 2 // -2 -o x o-1,4,2-oxazaphosphi nanc (71, X = H) can be added diastereoselec-tively to alkyl- or aryl-aldehydes or the corresponding aldimines to give alcohol [X = CH (OH)R1] or amine [X = CH (NHR2)R1] products in high yield 281 Nucleophilic and electrophilic activation strategies have been investigated to maximize the de. 

The thiazolium-catalyzed addition of an aldehyde-derived acyl anion with a receptor is a valuable synthetic tool leading to the synthesis of highly funtionalized products. Acyl anion receptors include Michael acceptor (Stetter reaction), aromatic aldehyde (benzoin reaction), ketone, nitroalkene, aziridine, activated imine. Recently, nucleophilic addition of acyl anions to unactivated imines has been explored <07CC852>. Treatment of aryl aldehydes with imines 146 in the presence of triazolium salt 147 (20 mol%) and triethylamine (20 mol%) provides the a-amino ketones 148 in good yields. However, this methodology does not work for 4-pyridylaldehyde and tert-buty laldehyde. 

Sulfur ylides, derived from benzyl bromides and an optically active alkyl sulfide, undergo base-promoted reactions with aryl aldehydes to produce optically active 1,2-diatyl epoxides.The reaction is illustrated by equation (17) and produces epoxides with optical purities in the range of 28-47% ee. The bicyclic sulfide shown in equation (17) was derived from (-t-)-camphor8ulfonic acid and produces the (RiO-enantiomer of the epoxide in excess. 

The method has been adapted to the formation of l)fs-diazoacetylalkanes from dibasic acid chlorides. Diazo ketones have been obtained from acyl chlorides containing a /Sj y-double bond, an ester group, and certain heterocyclic and aryl nuclei having alkyl, methoxyl, and nitro substituents. On the other hand, functional groups such as phenolic hydroxyl, arylamino, aldehyde, active methylene, and a,/S-unsaturated linkages may interfere. The method is ideal for application to complex molecules. 

Sonochemistry has been applied to acceleration of the Reformatsky reaction, Diels-Alder reactions, the arylation of active methylene compounds nucleophilic aromatic substitution of haloarenes, and to hydrostannation and tin hydride reduction. " Other sonochemical applications involve the reaction of benzyl chloride and nitrobenzene, a Sr I reaction in liquid ammonia at room temperature, and Knoevenagel condensation of aromatic aldehydes. lodination of aliphatic hydrocarbons can be accelerated, and oxyallyl cations have been prepared from ot,ot -diiodoketones using sonochemistry. Sonochemistry has been applied to the preparation of carbohydrate compounds.When sonochemistry is an important feature of a chemical reaction, this fact will be noted in the reactions presented in Chapters 10-19. 

The Gatterman aldehyde synthesis involves a Friedel-Crafts-type reaction on activated aromatic rings to afford aryl aldehydes (NoUer, 1966a). 

A decade later, Corey introduced an effective aluminum-diamine controller for Diels-Alder and aldol additions. The C2-symmetric stilbenediamine (stien) ligands are available in good yield from substituted benzils, which are in turn derived from benzoic acids, aryl aldehydes, or aryl bromides [48]. Formation of the active catalyst 3 is achieved by treatment of the bis(sulfonamide) with tri-methylaluminum recovery of the ligand was essentially quantitative. Acryloyl and crotonyl imides 4 are particularly effective dienophiles for this system, as shown in Scheme 4. 

Yamamoto has reported that the reactions of aldehydes less activated than chloral occur at 23 C using high pressures (10 kbar). The diastereoselectivity of the reactions of (5) and aryl aldehydes, however, is only 65-80% in favor of the anti diastereomer. 

Catalysts constituting a C2-symmetric 1,2-diamine have been used to hydrogenate a-aryl aldehydes to yield chiral alcohols, under dynamic kinetic resolution conditions. Hydrogenation of the carbonyl group of acylsilanes with 3 (presence of f-AmOK or NaBHr as activator) is apphcable to acquisition of a-silyl aUylc alcohols from conjugated acylsilanes. ... 

Avecia, a former part of the Zeneca Group, developed a range of cheap and highly active titanium- or vanadium-based salen catalysts called CACHy catalysts (Scheme 23). They are based on Jacobsen s salen technology, but they are much more reactive and can, for example, be used in concentrations as low as 0.1 mol% in the cyanation of aryl aldehydes. The catalysts show similar reactivity with alkyl aldehydes and ketones and are applicable to the synthesis of the commercially important mandelic acid derivatives. 

The reaction of 1 -trimethylsilylnaphthalene with pivaldehyde in the presence of 20 mol% Bu-P4 base proceeded smoothly at room temperature to give the alcohol in 91% yield. Other phosphazene bases with weaker basicities, such as Bu-P2 base and BEMP, showed no catalytic activity. As one of the conventional strong organic bases, DBU was found to be inactive. Caesium fluoride (CsF) was then examined as a fluoride anion donor, but no carbon-silicon bond cleavage was observed. Reactions with other aldehydes have been examined that with benzaldehyde was found to proceed somewhat slowly at room temperature. Other aryl aldehydes with electron-donating groups were also employed as electrophiles and the reactions proceeded smoothly at room temperature [57] (Table 5.5). 

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