A cascade reaction, also known as a domino reaction or tandem reaction, is a chemical process that comprises at least two consecutive reactions such that each subsequent reaction occurs only in virtue of the chemical functionality formed in the previous step.[1] In cascade reactions, isolation of intermediates is not required, as each reaction composing the sequence occurs spontaneously. In the strictest definition of the term, the reaction conditions do not change among the consecutive steps of a cascade and no new reagents are added after the initial step.[1][2] By contrast, one-pot procedures similarly allow at least two reactions to be carried out consecutively without any isolation of intermediates, but do not preclude the addition of new reagents or the change of conditions after the first reaction. Thus, any cascade reaction is also a one-pot procedure, while the reverse does not hold true.[1] Although often composed solely of intramolecular transformations, cascade reactions can also occur intermolecularly, in which case they also fall under the category of multicomponent reactions.[3]
The main benefits of cascade sequences include high atom economy and reduction of waste generated by the several chemical processes, as well as of the time and work required to carry them out.[1][3][4] The efficiency and utility of a cascade reaction can be measured in terms of the number of bonds formed in the overall sequence, the degree of increase in the structural complexity via the process, and its applicability to broader classes of substrates.[2][5]
The earliest example of a cascade reaction is arguably the synthesis of tropinone reported in 1917 by Robinson.[6] Since then, the use of cascade reactions has proliferated in the area of total synthesis. Similarly, the development of cascade-driven organic methodology has also grown tremendously. This increased interest in cascade sequences is reflected by the numerous relevant review articles published in the past couple of decades.[1][2][3][4][5][7][8][9][10] A growing area of focus is the development of asymmetric catalysis of cascade processes by employing chiral organocatalysts or chiral transition-metal complexes.[3][7][10][11]
Classification of cascade reactions is sometimes difficult due to the diverse nature of the many steps in the transformation. K. C. Nicolaou labels the cascades as nucleophilic/electrophilic, radical, pericyclic or transition-metal-catalyzed, based on the mechanism of the steps involved. In the cases in which two or more classes of reaction are included in a cascade, the distinction becomes rather arbitrary and the process is labeled according to what can be arguably considered the “major theme”.[4] In order to highlight the remarkable synthetic utility of cascade reactions, the majority of the examples below come from the total syntheses of complex molecules.
- ^ a b c d e Tietze, L. F.; Beifuss, U. Angew. Chem. Int. Ed. 1993, 32, 131–163.
- ^ a b c Padwa, A.; Bur, S. K. Tetrahedron 2007, 63, 5341–5378.
- ^ a b c d Pellissier, H. Tetrahedron 2006, 62, 1619–1665.
- ^ a b c Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew. Chem. Int. Ed. 2006, 45, 7134–7186.
- ^ a b Tietze, L. F. Chem. Rev. 1996, 96, 115–136.
- ^ Robinson, R. J. Chem. Soc. Trans. 1917, 111, 762.
- ^ a b Pellissier, H. Tetrahedron 2006, 62, 2143–2173.
- ^ Wasilke, J. C.; Obrey, S. J.; Baker, R. T.; Bazan, G. C. Chem. Rev. 2005, 105, 1001–1020.
- ^ Chapman, C.; Frost, C. Synthesis (Stuttg). 2007, 2007, 1–21.
- ^ a b Enders, D.; Grondal, C.; Hüttl, M. R. M. Angew. Chem. Int. Ed. 2007, 46, 1570–1581.
- ^ Grondal, C.; Jeanty, M.; Enders, D. Nat. Chem. 2010, 2, 167–178.