The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.

C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals

The 3,3'-pyrrolidinyl-spirooxindole unit is a privileged heterocyclic motif that forms the core of a large family of alkaloid natural products with strong bioactivity profiles and interesting structural properties. Significant recent advances in the synthesis of this fused heterocyclic system have led to intense interest in the development of related compounds as potential medicinal agents or biological probes.

Pyrrolidinyl-spirooxindole natural products as inspirations for the development of potential therapeutic agents.

The substituted indole nucleus [indole is the acronym from indigo (the natural dye) and oleum (used for the isolation)] is a structural component of a vast number of biologically active natural and unnatural compounds. The synthesis and functionalization of indoles has been the object of research for over 100 years, and a variety of well-established classical methods are now available, to name a few of them, the Fisher indole synthesis, the Gassman synthesis of indoles from N-halo-anilines, the Madelung cyclization of N-acyl-o-toluidines, the Bischler indole synthesis, the Batcho-Leimgruber synthesis of indoles from o-nitrotoluenes and dimethylformamide acetals, and the reductive cyclization of o-nitrobenzyl ketones.1 In the last 40 years or so, however, palladiumcatalyzed reactions, generally tolerant of a wide range of functionalities and therefore applicable to complex molecules, have achieved an important place in the arsenal of the practicing organic chemist. Since the invention of an industrial process for the palladium-catalyzed production of acetaldehyde from ethylene in the presence of PdCl2 and CuCl2, an everincreasing number of organic transformations have been based on palladium catalysis. Almost every area of the organic synthesis has been deeply influenced by the profound potential of this versatile transition metal, modifying the way organic chemists design and realize synthetic processes.2,3 Because of its catalytic nature, palladium-catalyzed synthesis can provide access to fine chemicals, agrochemical and pharmaceutical intermediates, and active ingredients in fewer steps and with less waste than classical † In memory of Prof. Bianca Rosa Pietroni, a colleague and very close friend. * To whom correspondence should be addressed. Phone: + 39 (06) 4991-2785. Fax: + 30 (06) 4991-2780. E-mail: sandro.cacchi@ uniroma1.it. 2873 Chem. Rev. 2005, 105, 2873−2920

Synthesis and functionalization of indoles through palladium-catalyzed reactions

Construction of Spiro[pyrrolidine‐3,3′‐oxindoles] − Recent Applications to the Synthesis of Oxindole Alkaloids

Palladium-catalyzed carbonylation reactions of aromatic halides in the presence of various nucleophiles have undergone rapid development since the pioneering work of Heck and co-workers in 1974, such that nowadays a plethora of palladium catalysts are available for different carbonylative transformations. The carboxylic acid derivatives, aldehydes, and ketones prepared in this way are important intermediates in the manufacture of dyes, pharmaceuticals, agrochemicals, and other industrial products. In this Review, the recent academic developments in this area and the first industrial processes are summarized.

Palladium-catalyzed carbonylation reactions of aryl halides and related compounds.

Reactions and syntheses with organometallic compounds. 7. Synthesis of benzolactams by palladium-catalyzed amidation

Carbonylation d'halogenures de vinyle contenant une amine secondaire ou un alcool en presence de Pd(OAc) 2 /PPh 3 : obtention de lactames et lactones a 5, 6 ou 7 chainons portant un groupe α-methylene. Les pyrrolizidines et indolizidines sont obtenus a partir de pyrrolidines ou piperidines possedant un substituant halogenovinyl sur une chaine laterale en position 2

Palladium-catalyzed carbonylation. A new synthesis of α-methylene γ-, δ-, and ε-lactams and lactones including bicyclic lactams of pyrrolizidine and indolizidine skeletons

The reactions and syntheses with organometallic compounds. V. a new synthesis of indoles and isoquinolines by intramolecular palladium-catalyzed reactions of aryl halides with olefinic bonds

New synthesis of heterocycles by use of palladium catalyzed cycli zation of α-haloamide with internal double bond

Photoisomerisierung der Verbindung (I) liefert auser den "ublichen" Isomerisierungsprodukten (III) und (IV) auch das Umlagerungsprodukt (II).

Yoshio Ban

Papers

Reactions and syntheses with organometallic compounds. 7. Synthesis of benzolactams by palladium-catalyzed amidation

Palladium-catalyzed carbonylation. A new synthesis of α-methylene γ-, δ-, and ε-lactams and lactones including bicyclic lactams of pyrrolizidine and indolizidine skeletons

The reactions and syntheses with organometallic compounds. V. a new synthesis of indoles and isoquinolines by intramolecular palladium-catalyzed reactions of aryl halides with olefinic bonds

New synthesis of heterocycles by use of palladium catalyzed cycli zation of α-haloamide with internal double bond

Novel photoisomerization of 1-acylindoles to 3-acylindolenines. General entry to the total synthesis of Strychnos and Aspidosperma alkaloids