Three component condensation, synthesis alcohols

Prakash, G. K. S., Mandal, M., Schweizer, S., et al. (2002) Stereoselective synthesis of anti-CX-(difluoromethyl)-P-amino alcohols by boronic acid based three-component condensation. Stereoselective preparation of (2.V, 3 W) -d i (1norothreonine. J. Org. Chem., 67, 3718-3723. 

Gold nanoparticles on ZnO were used as a catalyst for the rapid one-pot three-component condensation of amines (106), aldehydes (107), and phenyl acetylene (20), affording the selective synthesis of propargylamines (108) at room temperature (Scheme 9.32) (Gonzalez-Bejar et al. 2013). Propargylic alcohols constitute important building blocks for many biologically active compounds and natural products. 

In the following year (2012), Rao Kolia and Lee extended the reaction for the synthesis of such biologically relevant 2-amino-4//-chromen-4-ylphosphonate derivatives (35) from the one-pot three-component condensation of substituted salicylaldehydes, malononitrile (or ethylcyanoacetate) and triethylphosphite in the presence of ethyle-nediamine diacetate (EDDA) as a catalyst in alcohol under room temperature conditions (Scheme 15). Recently, Brahmachari and Laskar (2014) have also developed an energy-efficient multicomponent one-pot procedure for the facile synthesis of a wide range of diverse (2-amino-3-cyano-4/f-chromen-4-yl)phosphonic acid diethyl esters at room temperature from the reaction of salicylaldehydes, malononitrile (or ethyl cyanoacetate) and triethylphosphite on the surface of a reusable heterogeneous MgO-nanocatalyst in aqueous ethanolic... 

Muller and co-workers reported the three-component one-pot synthesis of various pyrimidines through the in situ generation of unsaturated carbonyl compounds. The palladium catalyzed coupling of aryl halides bearing electron withdrawing substituents 7 with propargyl alcohols 8 produced unsaturated carbonyl compounds 9 after isomerization, which condensed with amidines 10 to form triaryl pyrimidines 11 . 

Albert S.C. Chun of the Hong Kong Polytechnic University reports (J. Org. Chem. 68 1589, 2003) two important transformations. The three-component (Mannich) condensation of 10 with 11 and 12 proceeds with high diastereoselectivity, to give the amino alcohol 13. Hydroboration of the alkyne 14 followed by transmetalation of the intermediate vinyl borane gives a zinc species, which under catalysis by the easily-prepared 3-naphthol 13 adds to aromatic and branched aldehydes with high . The product allylic alcohols are useful intermediates for organic synthesis. 

List gave the first examples of the proline-catalyzed direct asymmetric three-component Mannich reactions of ketones, aldehydes, and amines (Scheme 14) [35], This was the first organocatalytic asymmetric Mannich reaction. These reactions do not require enolate equivalents or preformed imine equivalent. Both a-substituted and a-unsubstituted aldehydes gave the corresponding p-amino ketones 40 in good to excellent yield and with enantiomeric excesses up to 91%. The aldol addition and condensation products were observed as side products in this reaction. The application of their reaction to the highly enantioselective synthesis of 1,2-amino alcohols was also presented [36]. A plausible mechanism of the proline-catalyzed three-component Mannich reaction is shown in Fig. 2. The ketone reacts with proline to give an enamine 41. In a second pre-equilib-... 

The Hantzsch pyridine synthesis is the condensation of two equivalents of a P-dicarbonyl compound such as ethylacetoacetate, one equivalent of an aldehyde, and one equivalent of a nitrogen donor such as ammonia (or ammonium acetate) in refluxing alcohol or acetic acid. The immediate resulted from this three-component coupling, 1,4-dihydropyridine 138, is then oxidized, driven by aromatization, to substituted pyridine 139. Saponification and decarboxylation of the 3,5-ester substituents then leads to symmetric 2,4,6-tri-substituted pyridine 140. 

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