Domino multicomponent reactions

Tietze L. F., Modi A. Multicomponent Domino Reactions for the Synthesis of Biologically Active Natural Products and Drugs Med. Res. Rev. 2000 20 304-322 Keywords Diels-Alder reactions... 

As a requisite for all domino reactions, the substrates used must have more than two functionalities of comparable reactivity. They can be situated in one or two molecules or, as in the case of multicomponent domino reactions, in at least three different molecules. For the design and performance of domino reactions it is of paramount importance that the functionalities react in a fixed chronological order to allow the formation of defined molecules. 

A very important development in multicomponent domino reactions is the enan-tioselective approach using organocatalysts which has been recently discussed in an excellent review by Yus and Ramon [2c]. The latest great success in this field stem from Enders and coworkers, presence of an enantiopure proline derivative to give polyfunctionalized cyclohexenes with 99% ee [111]. 

Gu Y, De Sousa R, Frapper P, Bachmann C, Barrault J, Jer me F (2009) Catalyst-free aqueous multicomponent domino reaction from formaldehyde and 1,3-dicarbonyls derivatives. Green Chem 11 1968-1972... 

Simon C, Peyronel JF, Rodriguez J (2001) A new multicomponent domino reaction of 1,3-dicarbonyl compounds One-pot access to polycyclic N/0-, N/S-, andN/N-aminals. Org Lett 3 2145-2148... 

Lieby-Muller F, Simon C, Constantieux T, Rodriguez J (2006) Current developments in Michael addition-based multicomponent domino reactions involving 1,3-dicarbonyls and derivatives. QSAR Comb Sci 25 432 38... 

Lieby-Muller E, Simon C, Imhof K, Constantieux T, Rodriguez J (2006) A multicomponent domino reaction and in situ aerobic oxidation sequence for the first one-pot synthesis of polycyclic benzimidazoles from 1,3-dicarbonyl derivatives. Synlett 1671-1674... 

Lieby-Muller F, Constantieux T, Rodriguez J (2005) Multicomponent domino reaction from beta-ketoamides highly efficient access to original polyfunctionalized 2,6-diazabicyclo 2.2.2 octane cores. J Am Chem Soc 127 17176-17177... 

Table 5 lndolo[2,3-a]carbazole synthesis by multicomponent domino reactions... 

This review is restricted only to sequences where initial and subsequent steps are catalyzed by palladium complexes. Furthermore, neither Pd-catalyzed unimolecular, parallel, nor multicomponent domino reactions will be treated in this overview. Reactions where identical functionalities are transformed by the same Pd-catalyzed step, i.e., multiple Pd-catalyzed reactions, will also not be covered. Hence, only those processes are within the scope of this review where an initially introduced Pd catalyst or precursor catalyzes related or significantly different reactions and where the sequence offers advantages over the stepwise conducted transformation. With respect... 

Efficient and elegant syntheses of complex organic molecules with multiple stereogenic centers continue to be important in both academic and industrial laboratories (Nicolaou et al. 2003, 2006). In particular, catalytic asymmetric multicomponent domino reactions, used in the course total syntheses of natural products and synthetic building blocks, are highly desirable (Nicolaou et al. 2003, 2006 Tietze and Beifuss 1993 Tietze 1996 Tietze and Haunert 2000 Wasilke et al. 2005 Ramon and Yus 2005 Guo and Ma 2006 Pellissier 2006 Pellisier 2006 Tietze... 

Marigo M, Schulte T, Franzen J, Jprgensen KA (2005b) Asymmetric multicomponent domino reactions and highly enantio selective conjugated addition of thiols to alpha,beta-unsaturated aldehydes. J Am Chem Soc 127 15710-15711... 

Tietze, L. F., Modi, A. Multicomponent domino reactions for the synthesis of biologically active natural products and drugs. Med. Res. Rev. 2000, 20, 304-322. 

Combining structural diversity and complexity with synthetic efficiency has led to an increased interest in multicomponent domino reactions. A multicomponent reaction is defined as a reaction in which more than two substrates, all present together, react with each other to form a product that is derived from all components in that system. Domino reactions as classified by Tietze [2b] are processes involving two or more bond-forming transformations, which take place under the same... 

Despite the wealth of opportunities for high-pressure applications in solid phase cycloaddition reactions and multicomponent domino reactions, only very few processes have been studied up until now. We hope that the results presented in this chapter will stimulate application of high pressure in combinational chemistry. 

Multicomponent Domino Reactions under Microwave Heating... 

Scheme 12.24 Multicomponent domino reactions of unsaturated carboxylic acids.

Tu and coworkers [56] synthesized new substituted 2,4-diaminopyridine-3,5-dicarbonitriles 92 under microwave irradiation and solvent-free conditions (Scheme 12.35). The multicomponent domino reaction of 2 mol of malononitrile... 

Scheme 12.38 Allylic esterification-based multicomponent domino reaction of enaminones.

Jerome and coworkers [81] reported multicomponent domino reactions of formaldehyde 69a, 1,3-dicarbonyl derivatives 146, and styrenes 113 (or indole derivatives) in water to afford a wide range of dihydropyrans 147 and C3-substituted indole derivatives in 22-82% yields (Scheme 12.57). The described multicomponent domino reactions exhibit a good substrate scope and provide direct access to a wide range of small organic skeletons traditionally produced through multistep processes. 

These reactions employ microwave heating and water as the reaction medium at 100 °C for 7-9 min. The mechanism for diastereoselectivity was confirmed by density functional theory (DFT) (B3LYP) calculations. Subsequently, new multicomponent domino reactions of Meldrum s acid 159, aromatic aldehydes 69, and electron-rich heteroaryl-amines 80 have been established for the synthesis of spiro pyrazolo[l,3]dioxanes-pyridine -4,6-diones and spirojisoxazolo [l,3]dioxanes-pyridine -4,6-diones 160 in aqueous solution under microwave irradiation (Scheme 12.64) [88]. A total of 26 examples were examined to show the broad substrate scope and high overall yields (76-93%). A new mechanism was proposed to explain the reaction process and the resulting chemo-, regio-, and stereoselectivity. 

Scheme 14.16 Bodwell s synthesis of cannabinol (108) using a multicomponent domino reaction (lEDDA, inverse electron demand Diels—Alder).

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