Chemistry as a central science is facing a steadily increasing demand for new chemical entities. Innovative solutions, in all kinds of disciplines that depend on chemistry, require new molecules with specific properties, and their societal consequences are fundamental and pioneering. However, these molecules not only demand a realistic structural space but also their feasibility poses challenges to synthetic chemists. Nowadays the question of how to perform a synthesis has become most crucial. In particular multicomponent reactions are masterpieces of synthetic efficiency and reaction design. These one-pot processes consist of concatenations of elementary organic reactions under similar conditions.
See also the Thematic Series:
Multicomponent reactions II
Graphical Abstract
Scheme 1: Preparation of β-ketoenamides and subsequent cyclocondensation to 4-hydroxypyridines. a) Et2O, −40 ...
Scheme 2: Mechanistic rational for the formation of β-ketoenamides 16.
Scheme 3: Reaction of proline derivative 45 and formation of β-ketoenamide 47 and enolester 48.
Figure 1: 1H NMR spectra of 49 and the mixture of diastereoisomers 49 and 49’.
Scheme 4: Synthesis of pyrid-4-yl nonaflate 52.
Scheme 5: O-Methylation of pyridine derivatives 22 and 30 followed by desilylation.
Scheme 6: Formation of 5-alkoxypyrimidines from β-alkoxy-β-ketoenamides.
Graphical Abstract
Scheme 1: a) TBAD [(t-BuO2C−N=)2], PPh3, THF, −15 °C → rt, 49% (3a), 62% (3b); b) LiAlH4, Et2O–THF, 0 °C, 90%...
Figure 1: Model of the expected preferred conformation of imine 5a, as minimized using CSC Chem3D (MOPAC-PM3)....
Scheme 2: Possible explanation of diastereoselectivity in Ugi reactions of imines 5.
Graphical Abstract
Scheme 1: Povarov oxidation access to substituted quinolines.
Scheme 2: Tetrahydroquinoline oxidation.
Scheme 3: Synthesis of the Povarov adducts and their oxidation products.
Figure 1: Optimization of the reaction conditions for the preparation of quinoline 18.
Scheme 4: Oxidation of lactam-fused tetrahydroquinolines 20,20'.
Graphical Abstract
Figure 1: Two examples of bioactive pseudopeptides bearing a CF2H group.
Scheme 1: Synthesis of difluoromethyl-containing pseudopeptides (4a–m) by Ugi reaction and desulfanylation.
Scheme 2: The Ugi reaction of aniline, benzaldehyde, (isocyanomethyl)benzene with acetic acid, difluoroacetic...
Scheme 3: Synthesis of 2,2-difluoro-2-(phenylthio)acetic acid (2).
Graphical Abstract
Figure 1: Novel artificial RNases based on amino acids.
Scheme 1: Multicomponent approach to target molecules.
Scheme 2: Synthesis of starting diisocyanides 3a–3e.
Scheme 3: Synthesis of new aRNAses. Conditions: a. RCHO (3 eqiuv), BnNH2 (3 equiv), PhP(OH)2 (1 equiv), r.t.;...
Figure 2: Results of RT-qPCR of the TBEV RNA cleavage products in presence of 2.5 mM peptidomimetics 5a–g at ...
Figure 3: Results of RT-qPCR of the TBEV RNA cleavage products in the presence of 2.5 mM peptidomimetics afte...
Figure 4: Results of electrophoresis in 2% TBE-agarose gel with ethidium bromide of RT-qPCR products from Figure 3. (...
Graphical Abstract
Scheme 1: Selected resonance structures of azulene (1a) and structure of the sesquiterpene guaiazulene (1b).
Scheme 2: Synthesis of ynones by glyoxylation–decarbonylative Sonogashira coupling.
Scheme 3: Retrosynthetic analysis of N-heterocyclic substituted azulenes by a one-pot four-component approach....
Scheme 4: Three-component synthesis of azulenyl- and guaiazulenylynones 3 by glyoxylation–decarbonylative Son...
Scheme 5: Four-component synthesis of pyrimidylazulenes 5 by glyoxylation–decarbonylative Sonogashira couplin...
Scheme 6: Four-component synthesis of pyrazolylazulenes 7 by glyoxylation–decarbonylative Sonogashira couplin...
Graphical Abstract
Scheme 1: Synthesis of diverse dihydropyrimidine-related compounds.
Graphical Abstract
Scheme 1: Passerini reactions of α,β-unsaturated aldehyde 5.
Scheme 2: Passerini and Ugi reaction of saturated aldehyde 7.
Graphical Abstract
Scheme 1: Copper-catalyzed oxidative cyclization of alkenyl hydrazone.
Scheme 2: Pyrazolidinone 3a from Ugi adduct 2a.
Scheme 3: Attempted reactions of N-methyl hydrazones.
Scheme 4: Proposed mechanism.
Graphical Abstract
Scheme 1: Synthesis of substituted amides.
Scheme 2: Synthesis of ketocarbamates and imidazolones.
Scheme 3: Access to β-lactams.
Scheme 4: Access to β-lactams with increased structural diversity.
Scheme 5: Synthesis of imidazolinium salts.
Scheme 6: Access to the indenamine core.
Scheme 7: Synthesis of substituted tetrahydropyridines.
Scheme 8: Synthesis of more substituted tetrahydropyridines.
Scheme 9: Synthesis of chiral tetrahydropyridines.
Scheme 10: Preparation of α-aminonitrile by a catalyzed Strecker reaction.
Scheme 11: Synthesis of spiroacetals.
Scheme 12: Synthesis of masked 3-aminoindan-1-ones.
Scheme 13: Synthesis of homoallylic amines and α-aminoesters.
Scheme 14: Preparation of 1,2-dihydroisoquinolin-1-ylphosphonates.
Scheme 15: Pyrazole elaboration by cycloaddition of hydrazines with alkynones generated in situ.
Scheme 16: An alternative approach to pyrazoles involving hydrazine cycloaddition.
Scheme 17: Synthesis of pyrroles by cyclization of propargyl amines.
Scheme 18: Isoindolone and phthalazone synthesis by cyclization of acylhydrazides.
Scheme 19: Sultam synthesis by cyclization of sulfonamides.
Scheme 20: Synthesis of sulfonamides by aminosulfonylation of aryl iodides.
Scheme 21: Pyrrolidine synthesis by carbopalladation of allylamines.
Scheme 22: Synthesis of indoles through a sequential C–C coupling/desilylation–coupling/cyclization reaction.
Scheme 23: Synthesis of indoles by a site selective Pd/C catalyzed cross-coupling approach.
Scheme 24: Synthesis of isoindolin-1-one derivatives through a sequential Sonogashira coupling/carbonylation/h...
Scheme 25: Synthesis of pyrroles through an allylic amination/Sonogashira coupling/hydroamination reaction.
Scheme 26: Synthesis of indoles through a Sonogashira coupling/cyclofunctionalization reaction.
Scheme 27: Synthesis of indoles through a one-pot two-step Sonogashira coupling/cyclofunctionalization reactio...
Scheme 28: Synthesis of α-alkynylindoles through a Pd-catalyzed Sonogashira/double C–N coupling reaction.
Scheme 29: Synthesis of indoles through a Pd-catalyzed sequential alkenyl amination/C-arylation/N-arylation.
Scheme 30: Synthesis of N-aryl-2-benzylpyrrolidines through a sequential N-arylation/carboamination reaction.
Scheme 31: Synthesis of phenothiazine derivatives through a one-pot palladium-catalyzed double C–N arylation i...
Scheme 32: Synthesis of substituted imidazolidinones through a palladium-catalyzed three-component reaction of...
Scheme 33: Synthesis of 2,3-diarylated amines through a palladium-catalyzed four-component reaction involving ...
Scheme 34: Synthesis of rolipram involving a Pd-catalyzed three-component reaction.
Scheme 35: Synthesis of seven-membered ring lactams through a Pd-catalyzed amination/intramolecular cyclocarbo...
Graphical Abstract
Scheme 1: Concept of a Sonogashira–Glaser coupling sequence.
Scheme 2: Concept of a Sonogashira–Glaser cyclization synthesis of 2,5-di(hetero)arylthiophenes.
Scheme 3: Pseudo five-component Sonogashira–Glaser cyclization synthesis of symmetrical 2,5-di(hetero)arylthi...
Figure 1: Symmetrical 2,5-di(hetero)arylthiophenes 2 synthesized via the one-pot pseudo five-component Sonoga...
Graphical Abstract
Figure 1: Retrosynthetic scheme for (−)-julocrotine (1).
Scheme 1: Reactions and conditions: (a) DCC, NHS, DMF 80 °C, 18 h, 76%. (b) Ph(CH2)2Br, K2CO3, acetone, r.t.,...
Scheme 2: Reactions and conditions: (a) (CH2O)n, MeOH, r.t., 2 h then, RCOOH and t-BuNC, r.t., 18 h.
Scheme 3: Reactions and conditions: (a) (CH2O)n, MeOH, r.t., 2 h then, (S)-2-methylbutanoic acid and 7, r.t. ...
Graphical Abstract
Scheme 1: Microwave-assisted synthesis of 4 and 6.
Figure 1: ORTEP diagram of compound 6a.
Figure 2: ORTEP diagram of compound 5.
Figure 3: ORTEP diagram of compound 6e.
Figure 4: ORTEP diagram of compound 6g.
Scheme 2: A proposed mechanism to account for the formation of products 6. The factors that determine the nat...