Synthesis domino

The rapid synthesis of heteroaromatic Hantzsch pyridines can be achieved by aromatization of the corresponding 1,4-DHP derivative under microwave-assisted conditions [51]. However, the domino synthesis of these derivatives has been reported in a domestic microwave oven [58,59] using bentonite clay and ammoniiun nitrate, the latter serving as both the source of ammonia and the oxidant, hi spite of some contradictory findings [51,58,59], this approach has been employed in the automated high-throughput parallel synthesis of pyridine libraries in a 96-well plate [59]. In each well, a mixture of an aldehyde, ethyl acetoacetate and a second 1,3-dicarbonyl compound was irradiated for 5 min in the presence of bentonite/ammonium nitrate. For some reactions, depending upon the specific 1,3-dicarbonyl compound used. 

Schemes Combinatorial domino synthesis of Hantzsch pyridines 21-23...

During the past few years, increasing numbers of reports have been published on the subject of domino reactions initiated by oxidation or reduction processes. This was in stark contrast to the period before our first comprehensive review of this topic was published in 1993 [1], when the use of this type of transformation was indeed rare. The benefits of employing oxidation or reduction processes in domino sequences are clear, as they offer easy access to reactive functionalities such as nucleophiles (e. g., alcohols and amines) or electrophiles (e. g., aldehydes or ketones), with their ability to participate in further reactions. For that reason, apart from combinations with photochemically induced, transition metal-catalyzed and enzymatically induced processes, all other possible constellations have been embedded in the concept of domino synthesis. 

Scheme 8.16. Multienzyme cocktail for the domino synthesis of precorrin-5 (8-61).

Scheme 10.13. Polyethylene glycol)-supported domino synthesis of 1,2,3,4-tetrahydroquinolines.

Scheme 10.15. Solid-state domino synthesis of pyrrole derivatives.

Scheme 10.19. Microwave-assisted solvent-free domino synthesis of nitrocyclohexanols.

Both natural and non-natural compounds with a 2ff,5ff-pyrano[4,3-fc]pyran-5-one skeleton are of interest in medicinal chemistry. Several natural products, such as the pyripyropenes, incorporate this bicyclic ring system. The group of Beifuss has described an efficient microwave-promoted domino synthesis of the 2ff,5H-pyr-ano[4,3-fo]pyran-5-one skeleton by condensation of a,/3-unsaturated aldehydes with 4-hydroxy-6-methyl-2]-f-pyran-2-one (Scheme 6.244) [428]. It is assumed that in the presence of an amino acid catalyst a Knoevenagel condensation occurs first, which is then followed by a 6jr-electron electrocyclization to the pyran ring. While the conventional thermal protocol required a reaction time of up to 25 h (refluxing ethyl... 

Without doubt, multicomponent reactions have become an attractive tool for the synthesis of biologically active molecules. In this regard, Jeong et al. reported an interesting domino synthesis of bicyclopentenones [50]. They employed a bimetallic system consisting of [Pd2(dba)3(CHCl3)] and... 

Sridharan V, Perumal PT, Avendano C, Menendez JC (2007) A new three-component domino synthesis of 1,4-dihydropyridines. Tetrahedron 63 4407 1413... 

Kumar A, Maurya RA (2008) Organocatalysed three-component domino synthesis of 1,4-dihydropyridines under solvent free conditions. Tetrahedron 64 3477-3482... 

Polysubstituted 1,3-oxazolidines were prepared in a one-pot diversity oriented four-component reaction (4-MCR), comprising two linked domino processes. Thus, domino synthesis of enol ethers 9 was followed by a sequential amine addition-cyclization sequence [74]. While strong microwave irradiation (900 W) of silica-gel absorbed conjugated alkynoates 9 and amines afforded tetrasubstituted pyrroles (via the skeletal rearrangement of 1,3-oxazolidines, see Sect. 2.1 and Scheme 5) [24], the use of milder microwave conditions (160 W power, 90 min) furnished 1,3-oxazolidines. Under these mild conditions the 1,3-oxazolidines did not rearrange to pyrroles and with respect to diastereoselectivity, the 1,3-oxazolidines were obtained as mixtures of syn/anti isomers. Overall, the formation of one C-C bond, one C-0 bond, two C - N bonds and a ring in this MCR required less than 3 hours and utilized simple and commercially available reagents (Scheme 26). 

Scheme 10.16. Solvent-free domino synthesis of flavanones.

Domino Synthesis of Spiro-Benzofuranones and Spiro-Benzoindolones... 

Jiang B, Cao L-J, Tu S-J et al (2009) Highly diastereoselective domino synthesis of 6-spirosubstituted pyrido[2, 3-d]pyrimidine derivatives in water. J Comb Chem 11 612-616... 

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