An Alternative Route to Complex Allenes or Cyclooctatrienes via a Suzuki Cyclocarbopalladation Cascade.

The 4-exo-dig cyclocarbopalladation of vinyl bromides substituted with a triple or double bond resulted in impressive cascade reactions leading to different compounds under Suzuki cross-coupling conditions upon a slight modification of the starting material. When the starting compound carries a triple bond, a single cascade occurs providing a structure containing an allene, a tetrasubstituted cyclopropane, and a cyclobutene with complete stereoselectivity. When the related starting material possessing a double bond is reacted under the same conditions in the presence of various vinyl boronic esters or acids, an efficient 8π-electrocyclization provides tricyclic systems comprised of a cyclobutene unit, as well as a cyclooctatriene.

Cyclocarbopalladation/Stille Cascade: Stereoselective Access to Quaternary Functionalized Carbons.

Exploration of the 4-- cyclocarbopalladation in the discovery of new and original scaffolds afforded some unexpected results. The search for a way to produce seven-membered ring systems led to polycyclic molecules bearing a tetrasubstituted carbon. The triple bond that substitutes the cyclohexene ring on the starting compound is crucial for a high stereoselectivity.

Synthesis of Aromatic Rings Embedded in Polycyclic Scaffolds by Triyne Cycloaddition: Competition between Carbonylative and Non-Carbonylative Pathways.

Cycloadditions have emerged as some of the most useful reactions for the formation of polycyclic compounds. The carbonylative cycloaddition of triynes can lead to carbonylative and non-carbonylative competitive pathways, each leading to the formation of an aromatic ring. We report herein the one-pot synthesis of fully- and unsymmetrically-substituted tetracyclic 6,5,7,5-troponic and 6,5,6,5-benzenoid scaffolds using pre-organized triynes showing the competition between these two pathways.

Synthesis of Polyheterocyclic Tropones by [2 + 2 + 2 + 1] Carbonylative Cycloaddition of Triynes.

A direct synthesis of tropones (2,4,6-cycloheptatrienes) from simple preorganized triynes has been elaborated. This simple rhodium-catalyzed domino strategy allows one-pot access to fully substituted tropones in a 6-6-7-5 tetracyclic core in average to high yields.

Synthesis of Benzo[c]silole Derivatives Bearing a Tetrasubstituted Exocyclic C=C Double Bond by Palladium-Catalyzed Domino Reactions.

The synthesis of diversely substituted 2,3-dihydro-benzo[c]siloles through an unprecedented palladium-catalyzed domino sequence is reported, involving a cyclocarbopalladation of an internal silylalkyne. This reaction proceeds with complete stereoselectivity to lead to a fully substituted exocyclic C=C double bond. Notably, the overall domino sequence appears to be crucial to obtain the desired cyclic vinylsilanes.

Desymmetrizing Hydroformylation of Dihydromuconic Acid Diesters: Application to the Synthesis of (±)-Vindeburnol.

The desymmetrizing hydroformylation of internal alkenes derived from dihydromuconic acid is described. The study of this reaction afforded easy access to polyfunction aldehydes. After the evaluation of the reactivity of the dimethyl ester derivative with various primary amines, this methodology was used to design a rapid synthesis of (±)-vindeburnol from tryptamine in only two steps.

Aerobic Copper-Mediated Domino Three-Component Approach to 2-Aminobenzothiazole Derivatives.

An unprecedented three-component reaction involving a 2,2'-diaminodiaryl disulfide, copper cyanide, and an electrophile is described. This transformation is based on an oxidative copper-mediated S-cyanation as a key step and involves a cyanation/cyclization/acylation domino sequence enabling a rapid and efficient synthesis of diversely substituted 2-aminobenzothiazole derivatives. Notably, this reaction proceeds via an original mechanism involving an intermolecular migration of the acyl group.

Synthesis of Cyclooctatetraenes through a Palladium-Catalyzed Cascade Reaction.

Reported is a cascade reaction leading to fully substituted cyclooctatetraenes. This unexpected transformation likely proceeds through a unique 8π electrocyclization reaction of a ene triyne. DFT computations provide the mechanistic basis of this surprizing reaction.

Recent advances in the chemistry of organic thiocyanates.

Organic thiocyanates are important synthetic intermediates to access valuable sulfur-containing compounds. In this review the different methods for their preparation and their synthetic applications will be presented. The literature of the last 15 years will be covered, highlighting selected recent advances in the chemistry of this class of compounds.

Diastereoselective synthesis of novel aza-diketopiperazines via a domino cyclohydrocarbonylation/addition process.

Herein, we report an unprecedented, short and diastereo-selective synthesis of newly reported aza-diketopiperazine (aza-DKP) scaffolds starting from amino acids. The strategy is based on a Rh(I)-catalyzed hydroformylative cyclohydrocarbonylation of allyl-substituted aza-DKP, followed by a diastereoselective functionalization of the platform. This methodology allows the synthesis of novel bicyclic and tricyclic aza-DKP scaffolds incorporating six- or seven-membered rings, with potential applications in medicinal chemistry.

Cyclocarbopalladation/cross-coupling cascade reactions in sulfide series: access to sulfur heterocycles.

Cyclocarbopalladation/cross-coupling cascade reactions were applied for the first time in a sulfur series and represent an efficient route to access sulfur heterocycles. Stille or Suzuki-Miyaura cross-coupling was successfully used as the final reaction. The products are original benzothiolane and isothiochromane scaffolds with a stereodefined tetrasubstituted exocyclic double bond.

Fenestranes in synthesis: unique and highly inspiring scaffolds.

The scaffold of fenestranes is quite unique, as it contains four condensed cycles and a distorted tetracoordinated central carbon atom with bond angles greater than the regular 109°28". In this Minireview, a detailed overview on the developments regarding this compound class, including their synthesis, is given for the time period since 2006. In the past years, natural products that belong to the class of heterofenestranes have been isolated and their syntheses will also be discussed.

Synthesis of exotic polycycles such as cyclooctatrienes and fenestrenes with differential pro-apoptotic activities on human TRAIL-resistant metastatic cell lines.

New cyclooctatrienes were prepared by semihydrogenation of trienynes followed by 8π electrocyclization. Cyclooctatrienes and original fenestrenes previously reported were tested for their pro-apoptotic activities on two human cancer cell lines (THP-1 and SW620). Among the 20 new compounds tested, two compounds presented specific activities on the colon carcinomas TRAIL-resistant metastatic cell SW620, but a minor action on the monocytic leukemia THP-1 cell line.

Understanding the torquoselectivity in 8pi-electrocyclic cascade reactions: synthesis of fenestradienes versus cyclooctatrienes.

Unusual and novel polycyclic cyclooctatrienes, fenestradienes, and fenestrenes form readily from trienynes depending on the structure of the starting trienynes and the reaction conditions. The experimentally observed high torquoselectivities and complete diastereoselectivities of the 8pi-electrocyclization products have been thoroughly studied using density functional computations at B3PW91/6-31G(d,p). The different P- and M-helical topologies for the Mobius aromatic transition structures are the origin of the observed torquoselectivities in the cyclooctatrienes.

Synthesis of [4.6.4.6]fenestradienes and [4.6.4.6]fenestrenes based on an 8pi-6pi-cyclization-oxidation cascade.

Fenestranes are regarded as a particularly challenging synthetic targets, and only few syntheses have been reported in the recent past. These rare compounds of synthetic and theoretical interest are a class of tetracyclic skeletons, defined as doubly a,a'-bridged spiroalkanes. The reported results are focused on the synthesis of new and original [4.

A new pd-catalyzed cascade reaction for the synthesis of strained aromatic polycycles.

Two new palladium catalyzed cascade reactions involving a 4-exo-dig cyclocarbopalladation are described. These processes are shown to convert bromoenediynes and bromodienynes into strained aromatic compounds in a single step.

Cyclocarbopalladation involving an unusual 1,5-palladium vinyl to aryl shift as termination step: theoretical study of the mechanism.

A DFT/B3LYP model study has been carried out on the cyclocarbopalladation and on an unusual 1,5 vinyl to aryl palladium shift which are the two first steps of a cyclocarbopalladation-Stille coupling tandem reaction of various gamma-bromopropargylic-1,2 diols with alkenyls or alkynyl stannanes catalyzed by Pd(PPh(3))(4). From the calculations, the active intermediates in the catalytic process appear to bear a single phosphine ligand, the palladium(II) center keeping in all cases a square-planar coordination pattern either through intramolecular binding of the triple bond or via an intramolecular Pd..

Cyclocarbopalladation: sequential cyclization and C-h activation/Stille cross-coupling in the Pd-5-exo-dig reaction.

A new cyclization and C-H activation/Stille cross-coupling reaction on a nonactivated aromatic has been discovered. The reaction is regioselective and controlled by the stannylated reagent. Labeling experiments have been performed that provide evidence for a complete transfer of the deuterium through the coordination sphere of palladium.

Cyclocarbopalladation: 5-exo-dig cyclization versus direct Stille cross-coupling reaction. The influence of the alpha,beta-propargylic substitution.

Several bicyclic compounds bearing a 1,2-cyclopentanediol have been prepared from various anti- or syn-gamma-bromopropargylic diols and cis-dioxolanes under palladium(0) catalysis. The reaction proceeds through a 5-exo-dig cyclocarbopalladation. When the corresponding trans-dioxolanes are used, the only products isolated are obtained from a direct Stille cross-coupling reaction.

Cyclocarbopalladation: formation of bicyclic 1,2-cyclobutanediols through a rare 4-exo-dig cyclization.

[reaction: see text] Several bicyclic compounds bearing a strained 1,2-cyclobutanediol have been prepared from a gamma-bromopropargylic diol under palladium(0) catalysis. The reaction proceeds through a rare unfavored 4-exo-dig cyclocarbopalladation. In some cases, the first reaction is followed by a 6pi-electrocyclization leading to unusual strained tricyclic systems.

Cascade cyclization: an easy access to highly unsaturated polycyclic ring systems through a tandem stille/[4 + 2] reaction under mild conditions.

The synthesis of several polycyclic compounds 1a-c, 2, and 3 has been performed through a tandem Stille/[4 + 2] cascade reaction from cyclic bis(enoltrifluomethanesulfonate) 4a-c, 5, and 6, respectively. The reaction proceeds very efficiently in a one-pot operation at roomtemperature in DMF in the presence of a catalytic amount of Pd(CH(3)CN)(2)Cl(2) and LiCl.[reaction: see text]

General Method for the Preparation of Alkyne-Functionalized Oligopyridine Building Blocks.

A large series of alkyne-substituted oligopyridines based on 2,2'-bipyridine, 1,10-phenanthroline, 2,2':6',2"-terpyridine, or 1,8-naphthyridine substrates has been synthesized and fully characterized. The palladium(0)-catalyzed coupling of bromo- or chloro-substituted derivatives with (trimethylsilyl)acetylene proceeds readily in diisopropylamine under ambient conditions giving good yields of the corresponding alkyne-substituted substrates oligoPy(C&tbd1;C)SiMe(3). The terminal monoynes oligoPyC&tbd1;CH become available upon treatment with K(2)CO(3) in methanol.