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.

Palladium-catalyzed alkynylation.

Selective cleavages of carbon-carbon bonds catalyzed by transition-metal complexes have been shown to be increasingly versatile tools for organic synthesis allowing for complementary synthetic strategies Numerous examples of transition-metal catalyzed C-C bond activations of three- and four-membered ring systems have been reported These strained rings have been shown to engage in a variety of new ring-opening rearrangements and cycloaddition reactions leading to valuable structures Besides strain-driven transformations, other facilitating strategies to enforce the C-C bond activation of unstrained molecules have been developed as well While the variety of different transformations is less abundant, they concentrate on chelation-assisted reactions using appropriate permanent or transient directing groups In particular, the cleavage and subsequent functionalization of the C-CN bonds and decarbonylation processes operating by an excision of carbon monoxide from ketone derivatives have witnessed a large progress

Catalytic C-C Bond Activations via Oxidative Addition to Transition Metals.

Insofar as one of the fundamental objectives of organic synthesis is the construction of complex molecules from simpler ones, the importance of synthetic efficiency becomes immediately apparent and has been well-recognized.1 The increase in molecular complexity2 that necessarily accompanies the course of a synthesis provides a guide (and a measure) of synthetic efficiency. As a goal, one would like to optimally match the change in molecular complexity at each step with reactions of comparable synthetic complexity. Thus, the creation of many bonds, rings, and stereocenters in a single transformation is a necessary (though not sufficient) condition for high synthetic efficiency. The ultimate, perfect match would constitute single-step syntheses. More realistically, especially in view of the desire for general synthetic methods, the combination of mulScott E. Denmark was born in New York in 1953. He obtained an S.B. degree from MIT in 1975 and carried out research with Daniel Kemp and Richard Holm. His graduate studies at the ETH-Zurich with Albert Eschenmoser culminated with the D. Sc. Tech. degree in 1980. That same year he joined the faculty of the University of Illinois at UrbanasChampaign and was promoted to full professor in 1987. In 1991 he was named the Reynold C. Fuson Professor of Chemistry. His research interests are primarily in the invention of new synthetic reactions, structure and reactivity of organoelement reagents, and the origin of stereocontrol in fundamental carbon−carbon bond forming reactions.

Tandem [4+2]/[3+2] Cycloadditions of Nitroalkenes.

I. Introduction 1485II. Scope of This Review 1485III. Transformations of Cyclobutane Derivatives inOrganic Syntheses1486A. Ring-Opening Reactions 1486B. Ring-Contraction Reactions 1493C. Ring-Expansion Reactions 14951. Five-Membered Rings 14952. Six-Membered Rings 15093. Seven-Membered Rings 15174. Eight-Membered Rings 15215. Nine-Membered Rings 1523IV. Transformations of Cyclobutane Derivatives inNatural Product Syntheses1524A. Ring-Opening Reactions 1524B. Ring-Expansion Reactions 15261. Five-Membered Rings 15262. Six-Membered Rings 15293. Seven-Membered Rings 15324. Eight-Membered Rings 1533V. Conclusion 1534VI. Acknowledgments 1534VII. References 1534

The application of cyclobutane derivatives in organic synthesis.

Par chauffage de derives de cyclobutenone, formation de vinyl-cetenes; ces derniers se combinent avec des alcyne-1yl-ethers, -sulfures et -amines selon un processus de cycloaddition [2+2] regioselective. Preparation de methylthio-3-, methoxy-3 et methylamino-3 phenols

A regiocontrolled annulation approach to highly substituted aromatic compounds

Synthese a partir de t-butyldimethylsiloxy-8 (=R-8) methoxy-1 methyl-5 octene-4yne-1 et de methoxymethoxymethyl-3 (=R'-3) methyl-2 cyclobutene-2one-1 via la cyclisation de l'acide R-3 R'-6 hydroxy-2 methoxy-4 methyl-5 benzoique

Total synthesis of mycophenolic acid

A [4 + 4] annulation approach to eight-membered carbocyclic compounds

Laser photochemistry: trapping of quinone-olefin preoxetane intermediates with molecular oxygen and chemistry of the resulting 1,2,4-trioxanes

A hydroxymethyl anion equivalent: tributyl[(methoxymethoxy)methyl]stannane



intermediate: (tributylstannyl)methanol




reactant: Boron trifluoride etherate (13.0 mL, 0.106 mol)




product: tributyl[(methoxymethoxy)methyl]stannane





Keywords:

addition, to CO;
metalation reactions, tin;
protection, oxygen;
assay methods, for butyllithium, with 2-butanol, menthol, 2-pentanol, or 2-propanol, 1,10-phenanthroline indicator;
boron trifluoride etherate;
dichloromethane (methylene chloride);
diisopropylamine;
dimethoxymethane, purification;
tetrahydrofuran;
tributyltin hydride, preparation;
organotin compounds, highly toxic;
tin alkyls;
tributyl[(methoxymethoxy)methyl]stannane, potential poison;
(tributylstannyl)methanol, potential poison;
flasks, alkaline washed

Stephen K. Gee

Papers

A regiocontrolled annulation approach to highly substituted aromatic compounds

Total synthesis of mycophenolic acid

A [4 + 4] annulation approach to eight-membered carbocyclic compounds

Laser photochemistry: trapping of quinone-olefin preoxetane intermediates with molecular oxygen and chemistry of the resulting 1,2,4-trioxanes

A Hydroxymethyl Anion Equivalent: Tributyl[(Methoxymethoxy)Methyl]Stannane