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

Transition-metal-catalyzed addition of heteroatom-hydrogen bonds to alkynes.

Synthesis of Heterocycles via Palladium π-Olefin and π-Alkyne Chemistry

Update 1 of: Synthesis and Functionalization of Indoles Through Palladium-Catalyzed Reactions

The catalytic isomerization of propargylic alcohols promoted by transition-metals represents a straightforward and appealing route to synthetically useful α,β-unsaturated carbonyl compounds. Three different reaction pathways are known for these atom-economical transformations: (i) the so-called Meyer–Schuster and Rupe rearrangements, in which a formal 1,3- or 1,2-shift of the hydroxyl group takes place, and (ii) the redox-type isomerization, which involves a simultaneous oxidation of the alcohol unit and reduction of the CC bond. In this Perspective article an overview of the different metal catalysts presently available to promote these isomerization reactions, their mechanisms of action as well as relevant synthetic applications, is provided.

Metal-catalyzed transformations of propargylic alcohols into α,β-unsaturated carbonyl compounds: from the Meyer–Schuster and Rupe rearrangements to redox isomerizations

Palladium-catalyzed heteroannulation with acetylenic carbinols as synthons-synthesis of quinolines and 2,3-dihydro-4(1H)-quinolones

o -Iodoanilides 4 reacted with terminal acetylenic carbinols 5 under palladium-catalyzed conditions to yield o -substituted anilides 6 . Most of the anilides 6 could be cyclized with NaOEt/EtOH to 2-arylquinolines 2 . o -Iodoanilines 7 reacted with carbinols 5 leading to 8 which on palladium(II) assisted cyclisation afforded substituted quinolines 2 . An excellent synthesis of the alkaloid dubamine (2n) is reported. Also, the anilides 6 on acid-catalyzed rearrangement, deprotection and cyclisation led to the 2-aryl-2, 3-dihydro-4(1H)-quinolones 16 .

Palladium‐Catalyzed Heteroannulation with Acetylenic Carbinols as Synthons — Synthesis of Quinolines and 2,3‐Dihydro‐4(1H)‐quinolones.

In the title compound, oxonium 5-amino-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-sulfonate hydrate, H3O(+)-C4H4N3O5S(-)-H2O, the sulfonate group is in the anionic form and charge balance is provided by an oxonium cation, H3O(+) Screw-related molecules overlap significantly and are hydrogen bonded to form a zigzag chain of the uracil skeleton along the direction of the c screw axis The partially stacked bases and their glide-related equivalents run parallel to the a axis to form hydrophobic zones separated by hydrophilic zones built up by a network of hydrogen bonds

Oxonium 5-aminouracil-6-sulfonate hydrate.

The compound, 1-(ethoxymethyl)-6-(phenylselenyl)-5-ethyl uracil, crystallizes in the monoclinic space group P21/n with unit cell parameters a = 5.304(1), b = 21.261(4), c = 13.996(4) A, β = 94.30(2)°, and Z = 4. The acyclic chain C1′, O4′, C4′, C5′ is in fully extended form and nearly perpendicular to the uracil base. The molecules are held together by van der Waal's forces.

1-(Ethoxymethyl)-6-(phenylselenyl)-5-ethyl uracil: a nucleoside analog

In the title compound, C14H19IN2O8, an almost planar heterocyclic base is oriented anti with respect to the puckered sugar moiety. The sugar pucker is C2′-endo/C3′-exo, the N-glycosidic torsion angle is 166.4 (4)° and the conformation of O5′ is +sc. The mol­ecules are linked by hydrogen bonds of the types N—H⋯O and O—H⋯O.

M. De

Papers

Palladium-catalyzed heteroannulation with acetylenic carbinols as synthons-synthesis of quinolines and 2,3-dihydro-4(1H)-quinolones

Palladium‐Catalyzed Heteroannulation with Acetylenic Carbinols as Synthons — Synthesis of Quinolines and 2,3‐Dihydro‐4(1H)‐quinolones.

Oxonium 5-aminouracil-6-sulfonate hydrate.

1-(Ethoxymethyl)-6-(phenylselenyl)-5-ethyl uracil: a nucleoside analog

Ethyl 3-(2'-deoxyuridin-5-yl)-3-hydroxy-2-iodopropanoate, a nucleoside analogue.