Alkyl/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... 

A number of microwave-assisted multicomponent methods for the synthesis of imidazoles have been reported [68-71 ]. The irradiation of a 1,2-diketone and aldehyde with ammonium acetate in acetic acid for 5 min at 180 °C in a single-mode reactor provides alkyl-, aryl-, and heteroaryl-substituted imidazoles 39 in excellent yield (Scheme 14) and this method has been used for the rapid and efficient preparation of two biologically active imidazoles, lepidiline B and trifenagrel [68]. 

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. 

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... 

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). 

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. 

A new, direct and chemoselective esterification of a-hydroxyacids was developed using a reversible covalent-binding strategy. By taking advantage of acetal chemistry, simple aldehydes can be used to catalyse efficiently the esterification of a-hydroxy carboxylic acids in the presence of -hydroxyacid moieties or other carboxylic acids in amounts equal to or in excess of the alcohols. A diverse array of a-aryl, a-alkyl, a-heteroaryl, and functionalized a-hydroxyacids were smoothly esterified with 1° and 2 alcohols catalysed by 10mol% salicylaldehyde (Scheme 1) furnishing the resultant... 

Shibasaki et al. also reported that similar Morita-Baylis-Hillman-type products were obtained via asymmetric aldol reaction of a p,y-unsaturated ester with aldehydes using a chiral barium catalyst system (Table 3) [25]. The desired products formed in good yields with high enantioselectivities after isomerization. Several aromatic- and alphatic aldehydes were tested, and in all cases high a-(E) selectivities and high enantioselectivities were observed. Several aryl, heteroaryl, alkenyl, and alkyl aldehydes can be used as substrates in this reaction. 

Recently, Sobhani and Honarmand have developed a new and convenient room temperature protocol for the synthesis of a series of terminal vinylphosphonates (20) from the three-component reaction of aryl/alkyl/heteroaryl aldehydes (18), triall lphosphites and nitro-methane (19) in good yields through a one-pot tandem Henty-Michael reaction followed by nitro-elimination in the presence of 5-hydro-jypenlylammonium acetate (5-HPAA) as a reusable task-specific ionic liquid (Scheme 8). Use of a reusable and cost-effective ionic liquid as an environmentally benign reaction media, mild reaction conditions and operational simplicity are the key features of the present protocol. 

CuCl- and Cu(OTf )2-catalyzed three-component coupling reaction of aryl, heteroaryl, and alkyl aldehydes with 2-aminopyridines and terminal alkynes to imida-zopyridine derivatives was reported by Chernyak and Gevorgyan (Scheme 8.58). 2-Aminoquinoline and 2-aminoisoquinoline also could act as coupling partners to form imidazoquinoline and imidazoisoquinoline frameworks in good yields. Alpi-dem and zolpidem were synthesized using this novel reaction in a highly efficient one-pot procedure [99]. 

Scheme 8.58 Three-component coupling reaction of aryl, heteroaryl, and alkyl aldehydes with 2-aminopyridines and terminal alkynes.

Iron(II) acetate in the presence of tricyclohexylphosphane as ligand is an efficient catalyst for the hydrosilylation of a variety of aryl, heteroaryl, alkyl, and a,P-unsaturated aldehydes to afford the corresponding primary alcohols (Scheme 4-327). Polymethyl-hydrosiloxane (PMHS) is employed as hydride source... 

An one-pot convenient method for the synthesis of a variety of 2,2 -dicyanoalkylphosphonates (557) by a tandem Knoevenagel-phospha-Michael reaction of triethyl phosphite (556) with aryl/heteroaryl/alkyl aldehydes (554) and malonitrile (555) in an aqueous micellar solution of sodium stearate,using surfactants, such as cetyltrimethylammonium bromide as a eationic mieelle and TritonX-100 as a neutral micelle at their critical micellar eoncentrations (CMC), has been described by Sobhani and Parizi (Scheme 138). ... 

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