The design and implementation of cascade reactions is a challenging facet of organic chemistry, yet one that can impart striking novelty, elegance, and efficiency to synthetic strategies. The application of cascade reactions to natural products synthesis represents a particularly demanding task, but the results can be both stunning and instructive. This Review highlights selected examples of cascade reactions in total synthesis, with particular emphasis on recent applications therein. The examples discussed herein illustrate the power of these processes in the construction of complex molecules and underscore their future potential in chemical synthesis.

Cascade reactions in total synthesis.

This Perspective illustrates the defining characteristics of free radical chemistry, beginning with its rich and storied history. Studies from our laboratory are discussed along with recent developments emanating from others in this burgeoning area. The practicality and chemoselectivity of radical reactions enable rapid access to molecules of relevance to drug discovery, agrochemistry, material science, and other disciplines. Thus, these reactive intermediates possess inherent translational potential, as they can be widely used to expedite scientific endeavors for the betterment of humankind.

Radicals: Reactive Intermediates with Translational Potential

Die Entwicklung und Umsetzung von Kaskadenreaktionen hat zu beachtlichen neuartigen, eleganten und effizienten Synthesestrategien gefuhrt. Als besonders anspruchsvoll erwies sich die Anwendung von Kaskadenreaktionen in der Naturstoffsynthese, doch gerade hier winken verbluffende und zugleich aufschlussreiche Ergebnisse als Belohnung. In diesem Aufsatz werden ausgewahlte Kaskadenreaktionen in der Totalsynthese erlautert, wobei neuere Anwendungen besonders hervorgehoben werden. Die erorterten Beispiele sollen die Leistungsfahigkeit dieser Prozesse beim Aufbau von komplexen Molekulstrukturen veranschaulichen und ihr Potenzial fur zukunftige chemische Synthesen verdeutlichen.

Kaskadenreaktionen in der Totalsynthese

Radical cyclizations and multicomponent radical cascades in solution were studied, which are initiated by intermolecular radical addition to C-C triple bond in alkynes as well as to related C?N triple bonds in nitriles and isonitriles. The reactions were arranged according to the atom that carries the unpaired electron in the attacking radical and cover main group IV-VI elements. The initial radical addition is highly regioselective and in reactions with substrates possessing several π systems, the alkyne moiety is usually attacked with high preference. This selectivity can be rationalized by the reversibility with which the initial radicaladdition occurs in many cases, in particular with Sn- and S centered radicals. Due to their high reactivity, vinyl radicals that are formed through radical attack at the alkyne moiety in enynes. Alkyl radicals resulting from radical addition to an alkene are far less reactive so that the competing dissociation and regeneration of the starting materials is often faster than the forward reaction steps.

Donna M. Rakiewicz

Papers

Radical-initiated polyolefinic cyclizations in linear triquinane synthesis. model studies and total synthesis of (±)-hirsutene