Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

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.

Ionic liquids are solvents that consist entirely of ions. These nonvolatile and nonflammable solvents offer interesting opportunities for lanthanide and actinide chemistry. They can replace the organic phase in solvent extraction systems and can be used as nonaqueous electrolytes for electrodeposition of metals. Ionic liquids could find applications in the nuclear fuel cycle. Lanthanide coordination compounds or lanthanide-containing nanoparticles can be obtained via ionothermal or microwave-assisted synthesis in ionic liquids. Lanthanide-doped ionogels are a new type of luminescent hybrid materials. Ionic liquids can serve as solvents for lanthanide-mediated organic reactions, and there are several examples of high reactivity and selectivity.

Lanthanides and Actinides in Ionic Liquids

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.

Cerium(IV) ammonium nitrate (CAN) has recently emerged as a versatile reagent for oxidative electron transfer; the overwhelming number of reports serve as a testimony to the unparalleled utility of CAN in a variety of transformations of synthetic importance. Our recent work has uncovered novel carbon-carbon bond-forming reactions leading to the one-pot synthesis of dihydrofurans, tetrahydrofurans, and aminotetralins. In addition, we have developed a number of facile carbon-heteroatom bond-forming reactions by the CAN-mediated oxidative addition of soft anions to alkenes. A mechanistic rationale has been provided for the reactions explored. As might be expected of very powerful one-electron oxidants, the chemistry of cerium(IV) oxidation of organic molecules is dominated by radical and radical cation chemistry.

Recent advances in synthetic transformations mediated by cerium(IV) ammonium nitrate.

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

Radicals generated from dimedone and acetylacetone by CAN undergo addition to cyclic and acyclic alkenes to give dihydrofurans in good yields. In view of the experimental simplicity and higher yields of products formed CAN appears to be superior to the more commonly used Mn(OAc)3.

Facile synthesis of dihydrofurans by the cerium(IV) ammonium nitrate mediated oxidative addition of 1,3-dicarbonyl compounds to cyclic and acyclic alkenes. Relative superiority over the manganese(III) acetate mediated process

The oxidative addition of dimedone, acetylacetone and ethyl acetoacetate to cyclic and acyclic alkenes mediated by CAN gives dihydrofurans in good yields. Similar addition of the radical generated from dimethyl malonate to alkenes provides lactones. A comparative study of these reactions vis-a-vis those mediated by Mn(OAc)3 has shown that the former generally lead to higher yields of products. The milder reaction conditions, experimental simplicity, and the solubility of CAN in common organic solvents like methanol, acetonitrile and THF are other advantages. Thus it appears from this study that CAN is superior to the commonly used Mn(OAc)3.

Jessy Mathew

Papers

Recent advances in synthetic transformations mediated by cerium(IV) ammonium nitrate.

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

Facile synthesis of dihydrofurans by the cerium(IV) ammonium nitrate mediated oxidative addition of 1,3-dicarbonyl compounds to cyclic and acyclic alkenes. Relative superiority over the manganese(III) acetate mediated process

Oxidative addition of 1,3-dicarbonyl compounds to alkenes mediated by cerium(IV) ammonium nitrate and manganese(III) acetate: a comparative study

Synthesis of Spiroannulated Dihydrofurans by Cerium(IV) Ammonium Nitrate Mediated Addition Of 1,3-Dicarbonyl Compounds to Exocyclic Alkenes