Aryl/heteroaryl aldehydes

Catalyst 5-Hydroxypentylammonium acetate (5-HPAA reusable task-specific ionic liquid) Keywords Alkyl/aryl/heteroaryl aldehydes, nitromethane, trialkylphosphites, 5-HPAA, solvent-free, room temperature, one-pot tandem Henry-Michael reaction, multicomponent reaction, terminal vinylphosphonates... 

Figure 6.106 Applications of Knoevenagel condensations to [ Clmalonic acid and aryl/ heteroaryl aldehydes...

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

Aryl- and heteroaryl aldehydes give 2-amino-2-oxazolines, which are otherwise relatively inaccessible.470,471... 

RCHO — RCH=CHC01CH3.1 Conversion of aldehydes to (E)-a,(3-unsat-urated esters can be effected by reaction with methyl bromoacetate and Bu,As (1 equiv.) catalyzed by zinc powder. This reaction proceeds with alkyl, aryl, and heteroaryl aldehydes. 

Tu and co-workers [106] also reported a novel and highly stereoselective four-component protocol reacting 2,6-diaminopyrimidine-4-one with an aryl aldehyde and a barbituric acid, resulting in the generation of new 6-spirosubstituted pyrido [2,3-rfjpyrimidines 62 as a mixture of two diastereoisomers in which the 5,7-cis isomer prevails. Water was used as the solvent and the reaction was run under microwave irradiation. The reaction did not proceed with aliphatic or heteroaryl aldehydes (Scheme 46). 

Hollingworth, G. J. Aldehydes Aryl and heteroaryl aldehydes, in Comp. Org. Funct. Group Trans, (eds. Katritzky, A. R., Meth-Cohn, 0.,Rees, C. W.), 3, 81-109, 733-856 (Pergamon, Oxford, New York, 1995). 

The alkylation chemistry of a considerable number of O-trimethylsilyl cyanohydrins derived from aryl and heteroaryl aldehydes has been reported by Hunig and coworkers. Tbe protected cyanohydrins are easily prepared by heating the aldehydes with trimethylsilyl cyanide in the presence of a Lewis acid. The use of dialkyl sulfates and tosylates as alkylating agents was so reported. Hata et alP failed to alkylate the anion of the adduct of trimethylsilyl cyanide and acetaldehyde, suggesting that the trimethylsilyl group is incompatible with the more basic anions derived from aliphatic aldehydes. Ficini et alP... 

The first report of catalyst-controlled Strecker reactions was based on a report by Inoue32 with the disclosure that cyclic dipeptide 55 could catalyze the asymmetric formation of cyanohydrins 5 from aldehydes 1. This group showed that the corresponding acyclic version of the catalyst did not possess any catalytic activity. The cyclic catalyst behaved best for aryl and heteroaryl aldehydes. 

Catalytic formylation of aryl, heteroaryl, and vinylic halides in the presence of an amine, carbon monoxide, and hydrogen using a palladium complex such as PdCljfPPh.O provides a convenient route to conjugated aldehydes in good to excellent yields (Eq. 59). The use of iodo substrates secures excellent yields. 

Further refinements from these workers led to a general synthesis of 5-aryl(heteroaryl)oxazoles 411 from aromatic and heterocyclic aldehydes using TosMIC and a resin-bound quaternary ammonium hydroxide. This approach greatly simplifies purification. The base and toluenesulfinic acid are removed by simple filtration to afford 411 in quite acceptable purity for biological screening. 

A one-pot sequential and cascade sequence involving the formation of allylic azides, from aryl/heteroaryl/vinyl halides, allene and sodium azide, by palladium catalyzed anion capture, and cyclization-anion capture, followed by 1,3-dipolar cycloaddition provided a variety of 1,2,3-triazoles in good yields <01T7729>. Reaction of a,P-acetylenic aldehydes 107 with sodium azide in dimethylsulfoxide followed by hydrolysis afforded 5-substituted-4-carbaldehyde-1,2,3-triazole derivatives 108 <01TL9117>. 

Azulenes undergo condensation reaations with aryl and heteroaryl aldehydes in the presence of mineral acids to give azulenium salts, which can react with nucleophiles to give a variety of 1-substituted derivatives, e.g. [82,125,128,129]. 

Kanai and colleagues developed an enantioselective synthesis of various 2-(2-hydroxyethyl)indole scaffolds via the amido-cupration of allenes followed by the asymmetric addition of carbonyl compounds. Treatment of allene 88 with a copper catalyst forms a stable and highly nucleophilic allyl-copper species, which then adds into benzaldehyde (89) to furnish indole 90. A range of carbonyl compounds are competent in the sequence, including aryl- and heteroaryl aldehydes, alkyl aldehydes, and aryl ketones. This is reported to be the first example of a combined catalytic indole generation and subsequent enantioselective addition of carbonyl compormds (14CS1585). 

A simple NHC, A,A -dimethylimidazolium iodide, catalyses a mild aroylation of 3,5-dichloro-2(l/f)pyrazinones (174) at the 2-position, using an aryl or heteroaryl aldehyde. ... 

Niralwad et al. (2010) also reported the synthesis of 2-arylbenzothiazoles using SSA as an efficient catalyst (Scheme 6.24). The method involved the reaction of 2-aminothiophenol and several snbstitnted aryl or heteroaryl aldehydes to afford the corresponding 2-arylbenzothiazole in good to excellent yields. The main advantages of the present synthetic protocol are mild, solvent-free conditions, an eco-friendly catalyst, and an easy reaction worknp procednre. 

Another highly efficient DYKAT was reported in 2009 by Shibasaki s group based on a barium-catalysed aldol/retro-aldol reaction.Thus, a-alkylidene-j9-hydroxy esters were obtained by reaction of aryl, heteroaryl, alkenyl and alkyl aldehydes with )S,y-unsaturated esters in both excellent enantio- and... 

A heterobimetallic Ga/cationic Yb/Schiff base complex as a Lewis acid/Lewis acid bifimctional catalyst catalyzes asymmetric a-addition of a-isocyanoacetamides to aryl, heteroaryl, alkenyl, and alkyl aldehydes (Scheme 6). The Schiff base derived from o-vanillin was suitable to utilize cationic rare earth metal triflates with good Lewis acidity in bimetallic Schiff base catalysis. 

Keywords 5,6-Diamino-l,3-dimethyluracils, aryl/cycloaryl/heteroaryl aldehydes, N-bromosuccinimide (NBS), 2,2 -azoisobutyronitrile (AIBN), aqueous acetonitrile, room temperature, condensation, ring closure, 8-substituted xanthines... 

Anderson and coworkers expanded the copper-catalyzed addition of trimethylsilyl nitronates to a broader range of imine substrates [49] Cu(OTf)2/t-Bu-BOX (13) catalyzed the addition of trimethylsilyl nitropropanate (163) to PMP-protected imines (167) derived from aryl, aliphatic, and heteroaryl aldehydes (Scheme 17.35). 

This methodology has been extended to kinetic resolution of azomethine imines (364) bearing a chiral center at the 5-position of the pyrazolidinone ring (Scheme 17.81) [111]. Modification of the chiral ligand to phosphaferrocene-oxazoline (366) proved optimal for kinetic resolution and allowed the catalyst loading to be lowered to 1 mol%. A number of aldehydes used to prepare azomethine imines are well tolerated, and azomethine imines with aryl, heteroaryl, and branched aliphatic substituents in the 5-position are resolved with high enantioselectivity. Unfortunately, kinetic resolution of C4-substituted azomethine imines is not efficient (s < 2). 

The domino Michael/aldol reaction of 3-halogeno-l,2-diones (273) (X = Cl, F) to a,fi-unsaturated aldehydes RCH=CHCH=0 (R = aryl, heteroaryl), catalysed by the prolinol derivatives (256), has been developed as a method for the construction of cyclopen- tanones (274) with four contiguous stereogenic centres (<94% ee, >20 1 dr)P ... 

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