Carbonyl compounds three-component reactions

A one pot samarium-catalyzed three-component reaction of aldehydes, amines, and nitroal-kanes leads to pyrroles. The reaction proceeds via imines, generated from the amine and carbonyl compound, followed by the Michael addition of the nitro compound (Eq. 10.10).12a In... 

Mercaptoacetic acid could be used as a versatile synthon for the synthesis of 17/,3//-thiazolo[3,4-tf]benzimidazole-type compounds <1996FA279, 1997FA673>. For instance, 2,3-diaminopyridine and 2-mercaptoacetic acid were reacted in a three-component reaction with a suitable carbonyl compound and provided the 17/,3//-thiazolo[3,4- ]-imidazo[4,5- ]pyridines 451 (Equation 212) <1994FA345>. 

It should be noted that carbonyl compounds, more often aldehydes, are usual second reagent in both the groups. Other building-blocks in these multicomponent processes, leading to the formation of five-, six-, and seven-membered heterocycles, can be numerous acids and their derivatives, p-dicarbonyl compounds or other CH-acids, isocyanides, etc. At this, three-component reactions of ABC and ABB types [32] are the most typical for aminoazole, although some four-component ABCC processes were also published. 

Reactions were conducted at 80°C and at different CO pressures with a reaction time of 29 to 30 minutes. Two different carbonyl compounds were produced by a three-component reaction setup. The yields were determined by GC analysis from the outlet flow. 

In parallel to the bismuth(III)-catalyzed three-component allylation reaction, we have reported the corresponding three-component bismuth(III)-catalyzed Mannich-type reaction. A major merit of the three-component reaction is indeed that many unique structures can be afforded rapidly when three or more reactants are combined in a single step to afford new compounds. The development of an efficient bismuth-catalyzed Mannich-type three-component reaction that combines an aldehyde, an amine, and a silyl enolate to give compounds with a (3-amino carbonyl core... 

Unlike amidines, the multicomponent reaction of a,(3-unsaturated ketones 96 (aliphatic [94] or aromatic [95, 96]) with carbonyl compounds 97 and ammonia, which are the synthetic precursors of amidines, yielded 1,2,5,6-tetrahydropyrimidines 98 instead of dihydroheterocycles. When R3 is not the same as R4 tetrahydropyrimidines 98 were mixtures of diastereomers A and B, in which the relative configurations of stereogenic centers were also established [95, 96]. In contrast to conventional mechanical shaking requiring about 48 h [95], sonicated reactions were completed within 90 min at room temperature and provided the target heterocycles in high yields and purities [96]. Ultrasonic irradiation also significantly expanded the possibilities of such three-component reactions (Scheme 3.29). 

One-electron oxidation systems can also generate radical species in non-chain processes. The manganese(III)-induced oxidation of C-H bonds of enolizable carbonyl compounds [74], which leads to the generation of electrophilic radicals, has found some applications in multicomponent reactions involving carbon monoxide. In the first transformation given in Scheme 6.49, a one-electron oxidation of ethyl acetoacetate by manganese triacetate, yields a radical, which then consecutively adds to 1-decene and CO to form an acyl radical [75]. The subsequent one-electron oxidation of an acyl radical to an acyl cation leads to a carboxylic acid. The formation of a y-lactone is due to the further oxidation of a carboxylic acid having an active C-H bond. As shown in the second equation, alkynes can also be used as substrates for similar three-component reactions, in which further oxidation is not observed [76]. 

In origin, the Mannich reaction is a three-component reaction between an eno-lizable CH-acidic carbonyl compound, an amine, and an aldehyde producing / -aminocarbonyl compounds. Such direct Mannich reactions can encompass severe selectivity problems since both the aldehyde and the CH-acidic substrate can often act as either nucleophile or electrophile. Aldol addition and condensation reactions can be additional competing processes. Therefore preformed electrophiles (imines, iminium salts, hydrazones) or nucleophiles (enolates, enamines, enol ethers), or both, are often used, which allows the assignment of a specific role to each car-... 

This three-component reaction between a carboxylic acid, a carbonyl compound such as a ketone or aldehyde, and an isocyanide, offers direct access to a-hydroxy carboxamides. 

The Hf(OTf)4-catalyzed Mannich-type reaction of imine with enol silyl ethers has been used as a means of access to 8-amino carbonyl compounds (Eq. 21) [23] this also was extended to a three-component reaction (Eq. 22). 

Three basic types of MCRs can take place.MCRs of type I are equilibria that form mixtures of reactants, intermediate products, and final products, whereas the reactants and intermediate products of MCRs of type II equilibrate, but their final products are in practice formed preferentially and irreversibly. MCRs of type III are sequences of irreversible subreactions from the reactants toward their final products. Usually, only rather low yields of products are formed by MCRs of type I. In 1850, StreckerP introduced the formation of a-amino-substituted alkyl cyanides 3 from ammonia, hydrogen cyanide, and the corresponding carbonyl compound 1, via the cationic intermediate 2 (Scheme 1). The introduction of the Strecker three-component reaction (S-3CR), an MCR of type I, heralded the beginning of MCR chemistry. 

In 1960, Hellmann and Opitz l realized that the majority of the previously discussed named reactions and other related processes are all a-aminoalkylations of nucleophilic compounds of sufficiently weak acids, corresponding to MCRs of type I, or they have secondary reactions of type II that are followed by the formation of heterocycles [the Hell-mann-Opitz three-component reaction (HO-3CR),t Scheme 2]. In 1921, Passerinih 47] jjj. troduced his three-component reaction (P-3CR), which involves the reaction of a carboxylic acid 7, a carbonyl compound 1, and an isocyanide 10, to form (via rearrangement of the first-formed product 11) an a-carboxy-substituted alkanamide 12 (Scheme 2). This was the first example of a MCR of type II that involved an isocyanide. 

HX=H20, HiSe, H2S2O3, HN3, H2NCN, HOCN, HSCN, RCO2H, RCOSH, ROCO2H, etc.) form the ions 8 and 9, which subsequently undergo an a-addition onto the unique divalent carbon of the isocyanide 10 (Scheme 2). The a-substituted adduct 13 then rearranges into its final product.t 1 Since 1962 this reaction has been called the Ugi four-component reaction (U-4CR).P 1 The U-4CR can formally be considered as the union of the HO-3CR and the P-3CR. Both of these three-component reactions have in common that they use carbonyl compounds and acids as reactants. 

In 1921 Passerini reported the synthesis of the a-acyloxycarboxamides (6a-e) according to the scheme below. The formation of a-acyloxycarboxamides by a three-component reaction of carboxylic acids (3), carbonyl compounds (4) and isocyanides (5) is the proper Passerini reaction. The reactions described in Sections 4.6.2.2-4.6.2.4 are closely related to the Passerini reaction we call them reactions of the Passerini type. ... 

Three-component condensation (3CC) of caiboxylic acids, C-isocyanides, and carbonyl compounds to afford a-acyloxycarboxamides. Also known as three-component reaction (3CR). C/i Ugi reaction. 

One-pot four-component reactions of carbonyl compounds, hydrazines, malononitrile, and P-ketoesters mediated by meglumine (13T9931), cetyltri-methylammonium chloride in aqueous medium (13SC1721), or in the absence of catalyst under ultrasound irradiation in water (13JHC1174) are versatile routes for the synthesis of pyrazole-fused 2-amino-3-carbonitrile-4f/-pyrans. Quinohnone-fiised 3-nitro-4H-pyrans result from the ZnCl2-cat-alyzed three-component reaction of 4-hydroxy-l-methylquinolin-2(lH)-one, nitroketene N,S-dimethyl acetal, and various aromatic aldehydes, in excellent yields (Scheme 14) (13TL3248). 

Kabachnik-Fields reaction is a three-component reaction between a carbonyl compound (ketone and aldehydes), an amine, and a dialkyl phosphite [144] to form a-aminoalkylphosphonates 79 (Scheme 12.26). It was first described in 1952 independently by Kabachnik [145] and Fields [ 146]. This reaction constitutes a general and effective method for the synthesis of a-amino phosphonates, which, in the last five decades, have danonstrated to be a kind of compounds of relevance. 

In the context of enantioselective nickel-catalysed multicomponent reactions, many excellent results have also been achieved. For example, three-component reactions between 1,3-dienes, carbonyl compounds... 

Synthesis of homoallylic alcohols through the reaction of organometallic allyl compounds with carbonyl compounds is one of the most important processes in organic synthesis. Sc(OTf)3-catalyzed allylation of aldehydes with tetraallyltin to prepare homoallylic alcohols has been reported. Recently, it was revealed that the addition of acetic anhydride to the reaction mixture dramatically increases the reaction s yields to more than 90% [10]. On the other hand, in the presence of a catalytic amount of Sc(OTf)3 (l-5mol%), benzoylhydrazines reacted with tetraallyltin to give the corresponding homoallylic hydrazines, which were readily converted to homoallylic amines (Scheme 12.6) [11]. Three-component reactions of aldehydes, benzoylhydrazine, and tetraallyltin also proceeded smoothly in the presence of a catalytic amount of Sc(OTf)3. 

Disconnection of TM 2.17a requires new knowledge. This stmcture corresponds to the Mannich base since the terf-amino group is present in the fl-posilion to the strong electron-withdrawing nitro group. The retra-Mannich type disconnection of two bonds leads to simple starting materials, piperidine, formaldehyde and 2-nitropropane. In the same scheme are proposed reaction conditions for the synthesis of TM 2.17. More details on the Mannich reaction are presented in Sects. 4. 4.2 and 6.1. Here it suffices to mention that this three-component reaction affords P-amino carbonyl compounds known as Mannich bases. 

Ye S, Gao K, Wu J (2010) Three-component reactions of 2-alkynylbenzaldoximes and a, P-unsaturated carbonyl compounds with bromine or iodine monochloride. Adv Synth Catal 352 1746-1751... 

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