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.

Research and industrial interest in radical C–H activation/radical cross-coupling chemistry has continuously grown over the past few decades. These reactions offer fascinating and unconventional approaches toward connecting molecular fragments with high atom- and step-economy that are often complementary to traditional methods. Success in this area of research was made possible through the development of photocatalysis and first-row transition metal catalysis along with the use of peroxides as radical initiators. This Review provides a brief and concise overview of the current status and latest methodologies using radicals or radical cations as key intermediates produced via radical C–H activation. This Review includes radical addition, radical cascade cyclization, radical/radical cross-coupling, coupling of radicals with M–R groups, and coupling of radical cations with nucleophiles (Nu).

Recent Advances in Radical C-H Activation/Radical Cross-Coupling.

This review is focused on the use of solid Lewis acids to promote catalytic oxidations. While the concept of using Lewis acids to promote the reaction of organic substrates with oxidizing reagents is widely accepted in homogeneous catalysis, this concept has not become evident and generally used in heterogeneous catalysis until recent days. Certainly the development of new Lewis acid solids active and selective for catalytic oxidations is an urgent need and a challenging scientific target for some substrates especially using environmentally friendly oxidants. Since the replacement of current stoichiometric oxidations for the production of fine chemicals by environmentally benign catalytic oxidations is one of the major tasks in green chemistry, solid Lewis acids are called to play a crucial role to accomplish this goal. In the review, we will see the still important role that stoichiometric oxidations play in our daily life, and how they are being substituted by catalytic oxidations. At this point, three general mechanisms in which Lewis acids are involved will be described, and the material has been organized starting from homogeneous and ending with solid catalysts for heterogeneous oxidations. A bridge between the two will be established by presenting catalytic systems that can fill the gap between the two systems helping to rationalize the nature of the catalytic active sites in solid systems. This review is obviously focused on solid oxidation catalysts, and the core of the review is organized to show the evolution from the simplest strategy for heterogeneizing homogeneous catalysts, i.e., supporting the active species on large surface area solids, to the more elaborate ones in which the active sites are part of the solid structure. Given the importance of metallosilicates, and more specifically titanosilicates, as catalysts in commercial processes, special attention has been paid to these types of materials. Although sufficient references are provided to early seminal work, special emphasis has been given to most recent contributions to this area, particularly of the last 10 years. Patent literature has also been extensively covered in this review. Examples to illustrate the concepts have been selected among recent publications, and an effort has been made to present a series of commercial and near commercial processes based on catalytic oxidations. Finally, two * E-mail: acorma@itq.upv.es. 3837 Chem. Rev. 2002, 102, 3837−3892

Lewis acids as catalysts in oxidation reactions: from homogeneous to heterogeneous systems.

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

3.1. Carbon−Nitrogen Bond Formation 14 3.1.

Cerium(IV) ammonium nitrate--a versatile single-electron oxidant.

Organic synthesis using carbon centred radicals generated by one electron oxidants is of current interest. Although Mn(OAc)3 has received the most attention, it appears that cerium(IV) ammonium nitrate (CAN) would be a very useful reagent for the generation of radicals. The recent application of CAN in the construction of C–C bonds are highlighted in this review. CAN has been shown to mediate the facile oxidative addition of 1,3-dicarbonyl compounds to activated and unactivated alkenes leading to dihydrofurans and furanones. In most cases the reactions occur under milder conditions and the yields are superior when compared to Mn(OAc)3 mediated reactions. The results available thus far suggest that CAN offers cast potential in radical mediated organic synthesis.

Carbon–carbon bond forming reactions mediated by cerium(IV) reagents

A facile synthesis of optically active lactones using benzyl-3,6-anhydro glucofuranoside as chiral auxiliary

Novel crown ethers from 7-deoxycholic acid

Synthesis of Novel Receptors From 7-Deoxycholic Acid and Studies on Their Cation Binding Properties

Asymmetric synthesis of lactones 15a–16b, using the novel auxiliaries 1 and 2 readily available from D-glucose, is described.

Jaya Prabhakaran

Papers

Carbon–carbon bond forming reactions mediated by cerium(IV) reagents

A facile synthesis of optically active lactones using benzyl-3,6-anhydro glucofuranoside as chiral auxiliary

Novel crown ethers from 7-deoxycholic acid

Synthesis of Novel Receptors From 7-Deoxycholic Acid and Studies on Their Cation Binding Properties

Asymmetric induction using novel chiral auxiliaries derived from D-glucose