Convenient Access to 2,3-Disubstituted-cyclobut-2-en-1-ones under Suzuki Conditions and Their Synthetic Utility.

A regioselective synthesis of general applicability has been designed for the one-pot preparation of 2,3-disubstituted-cyclobutenones from iodoalkynes through cyclobutenylation, Suzuki CC coupling, and ketone formation. This one-pot methodology has been applied to the selective synthesis of an orally active cyclooxygenase II inhibitor. Furthermore, the obtained cyclobut-2-en-1-ones were used as synthons in several transformations, such as, the preparation of ß-lactams, phthalazines, cyclohexa-2,5-dien-1-ones, and cyclopent-3-en-1-ones.

Synthesis and Characterization of Stable Phosphorus Carbabetaines.

Phosphorus 1,3- and 1,4-carbabetaines with 'P(+)-C-C(-)' and 'P(+)-C-C-C(-)' structures, respectively, in which the carbanion moiety was significantly stabilized by two trifluoromethylsulfonyl groups, have been synthesized and characterized. Analysis of their X-ray crystal structures revealed that any attractive interactions between the anionic and cationic moieties were negligibly weak. This result was corroborated by using natural bond orbital (NBO) and Bader's quantum theory of atoms in molecules (QTAIM) models. In contrast, performing the same analysis of a known 1,3-carbabetaine equivalent, which can be drawn as a 'P(+)-C-C=C-O(-)' resonance structure, revealed pronounced charge-transfer interactions between the anionic and cationic moieties.

Divergence in Ynone Reactivity: Atypical Cyclization by 3,4-Difunctionalization versus Rare Bis(cyclization).

Functionalized ynones can be activated by Tf2 C=CH2 , which was generated in situ, to form zwitterionic species. These species were trapped in an intramolecular fashion by several nucleophiles to generate two major types of triflones in a divergent manner. Through fine-tuning of the reaction temperature, bis(triflyl)-6-membered- or (triflyl)-5-membered-fused-heterocycles were achieved in reasonable yields in a totally selective manner. In this way, bis(triflyl)flavones, bis(triflyl)thioflavones, bis(triflyl)selenoflavones, (triflyl)benzothienopyrans, (triflyl)benzoselenophenopyrans, (triflyl)vinyl aurones, and (triflyl)pyranoindoles were constructed. Conceivable mechanistic pathways were suggested on the basis of the isolation of several intermediates and the results from control experiments.

A Facile Synthesis of Blue Luminescent [7]Helicenocarbazoles Based on Gold-Catalyzed Rearrangement-Iodonium Migration and Suzuki-Miyaura Benzannulation Reactions.

New azahelicenes having interesting photophysical properties have been prepared in a four-step sequence. These [7]helicenocarbazoles are efficient blue luminophores, demonstrating the utility of gold catalysis in the preparation of advanced materials.

Gold-Catalyzed Divergent Ring-Closing Modes of Indole-Tethered Amino Allenynes.

Indole-tethered amino allenynes were chemodivergently cyclized for the controlled preparation of fused polycyclic indoles using gold catalysis. Double cyclization of terminal allenynes afforded hexacyclic 15 H-indolo[1,2,3-de]quinolino[3,2,1-ij]quinoxalines, in which allenynes bearing a substituted alkyne at the terminal end generated 12,13-dihydro-7 H-indolo[3,2-c]acridines, which are 5-membered cyclized adducts. Density functional theory calculations were performed to shed light on this difference in reactivity.

De Novo Synthesis of α-Hydroxy Ketones by Gallic Acid-Promoted Aerobic Coupling of Terminal Alkynes with Diazonium Salts.

An unprecedented metal-free direct preparation of unprotected α-hydroxy ketones from terminal alkynes under mild conditions with diazonium salts as the arene source and without the requirement of irradiation is described. The process is general and fully compatible with a wide variety of substitution in both reactants. Experimental and computational evidence strongly suggest the involvement of radical species in the transformation.

Allenols versus Allenones: Rhodium-Catalyzed Regiodivergent and Tunable Allene Reactivity with Triazoles.

2-Pyrrolines and 6-oxo-hexa-2,4-dienals have been prepared through the divergent reactions of 1-benzenesulfonyl-4-aryl-1,2,3-triazoles with functionalized allenes. The rhodium-catalyzed reactions between allenols and 1-benzenesulfonyl-4-aryl-1,2,3-triazoles yielded 2-pyrrolines. This transformation is compatible with the presence of aliphatic, aromatic, heterocyclic, amide, and halogen functional groups. Interestingly, a reactivity switch took place when the allene-tethered alcohol substrate was replaced by its ketone counterpart. When the rhodium-catalyzed reaction of 1-benzenesulfonyl-4-phenyl-1,2,3-triazole was performed with allenones, acyclic 6-oxo-hexa-2,4-dienals were stereoselectively formed as (2Z,4E) isomers.

Photoinduced Gold-Catalyzed Domino C(sp) Arylation/Oxyarylation of TMS-Terminated Alkynols with Arenediazonium Salts.

A selective and convenient synthesis of tri- and tetrasubstituted α,ß-unsaturated ketones, as well as 2,3-diarylbenzofurans has been developed with the aid of light and taking advantage of a cooperative gold/photoredox-catalyzed 2-fold arylation reaction of TMS-terminated alkynols. The reaction of 3-(trimethylsilyl)prop-2-yn-1-ols was competent to generate diarylated α,ß-unsaturated ketones; whereas the photoredox sequence involving 2-[(trimethylsilyl)ethynyl]phenol exclusively afforded 2,3-diarylbenzofurans. The reaction of terminal alkynes proceeded in poor yields while the use of bulkier silyl groups, such as TIPS, resulted unproductive. Apparently, the C(sp) arylation reaction is the first event on the domino bis-arylative sequence. These results could be explained through the intermediation of arylgold(III) species and several single electron transfer processes.

Cationic AuIII versus AuI : Catalyst-Controlled Divergent Reactivity of Alkyne-Tethered Lactams.

Switchable reactivity through cationic gold-based catalyst control built on the oxidation state, namely cationic AuIII versus AuI , has been achieved in the direct functionalization of 2-azetidinone-tethered alkynyl indoles.

Tunable Metal-Catalyzed Heterocyclization Reactions of Allenic Amino Alcohols: An Experimental and Theoretical Study.

Controlled preparation of 2,5-dihydro-1H-pyrroles, 3,6-dihydro-2H-pyrans, and pyrroles has been achieved through switchable chemo- and regioselectivity in the metal-catalyzed heterocyclization reactions of allenic amino alcohols. The gold-catalyzed cycloisomerization reaction of α-amino-ß-hydroxyallenes was effective as 5-endo cyclization by addition of amino functionality to the distal allene carbon to yield enantiopure 2,5-dihydro-1H-pyrroles, whereas their palladium-catalyzed cyclizative coupling reactions furnished 3,6-dihydro-2H-pyrans through a chemo- and regioselective 6-endo cycloetherification. Conversely, the gold-catalyzed heterocyclization reaction of ß-amino-γ-hydroxyallenes generated exclusively pyrrole derivatives. These results could be explained through a chemo- and regioselective 5-exo aminocyclization to the central allene carbon followed by aromatization. Chemo- and regioselectivity depend on both linker elongation as well as the type of catalyst. This behavior can be justified by means of density functional theory calculations.

Stereoselective synthesis of strained cage compounds via gold-catalyzed allene functionalization.

The diastereoselective synthesis of strained adducts that show cage-like structures has been accomplished directly from allenyl-ß-lactams through gold catalysis.

Metal-Catalyzed Cyclization Reactions of 2,3,4-Trien-1-ols: A Joint Experimental-Computational Study.

Controlled preparation of tri- and tetrasubstituted furans, as well as carbazoles has been achieved through chemo- and regioselective metal-catalyzed cyclization reactions of cumulenic alcohols. The gold- and palladium-catalyzed cycloisomerization reactions of cumulenols, including indole-tethered 2,3,4-trien-1-ols, to trisubstituted furans was effective, due to a 5-endo-dig oxycyclization by attack of the hydroxy group onto the central cumulene double bond. In contrast, palladium-catalyzed heterocyclization/coupling reactions with 3-bromoprop-1-enes furnished tetrasubstituted furans. Also studied was the palladium-catalyzed cyclization/coupling sequence involving protected indole-tethered 2,3,4-trien-1-ols and 3-bromoprop-1-enes that exclusively generated trisubstituted carbazole derivatives. These results could be explained through a selective 6-endo-dig cumulenic hydroarylation, followed by aromatization. DFT calculations were carried out to understand this difference in reactivity.

Direct Metal-Free Entry to Aminocyclobutenes or Aminocyclobutenols from Ynamides: Synthetic Applications.

The [2+2] cycloaddition of ynamides with the highly polarized reagent Tf2 C=CH2 has been developed to regioselectively afford bis(triflyl)aminocyclobutenes in the absence of catalyst under mild conditions. Incidentally, with the ynamides bearing electron-rich aromatic rings at the C-terminal, an interesting reactivity switch was observed; a cyclization/hydroxylation sequence yielded 2-amino-3-(triflyl)cyclobut-2-enols. Aminocyclobutene construction with addition of alcohols resulted in the formation of aminocyclobutenyl ethers through a cyclization/hydroalkoxylation process. Moreover, the utility of functionalized aminocyclobutenes as precursors for further elaboration was demonstrated with the preparation of α-amino-ß,γ-unsaturated ketones and 3-(triflyl)buta-1,3-dien-2-amines through 4 π-electrocyclic ring opening.

Iron-catalyzed domino indole fluorination/allenic aza-Claisen rearrangement.

The synthesis of 2-allenyl-2-substituted-3,3-difluoroindolines has been accomplished, taking advantage of the reaction between N-allenyl-indoles and Selectfluor under iron catalysis.

Metal-Free Allene-Based Synthesis of Enantiopure Fused Polycyclic Sultones.

The controlled metal-free preparation of fused δ-sultone derivatives has been developed starting from hydroxyallenynes. The use of 2-(3,3-diethyltriaz-1-enyl)-4-methylbenzene-1-sulfonyl chloride in a sulfonylation/rearrangement sequence gives access to 1,3-dien-2-yl arenesulfonates. These functionalized enynes suffered a direct cyclization/desaturation radical cascade, allowing the synthesis of a variety of enynyl [1,2]oxathiine 1,1-dioxides. Stereoselective cyclization of the readily formed core through intramolecular Diels-Alder reaction has also been demonstrated, affording ß-lactam- and glucofuranoside-fused δ-sultone polycycles. These selective reactions have been studied experimentally and additionally, their reaction mechanisms have been investigated computationally by means of density functional theory calculations.

Umbilical Hernia Repair: Analysis After 934 Procedures.

There is a lack of consensus about the surgical management of umbilical hernias. The aim of this study is to analyze the medium-term results of 934 umbilical hernia repairs. In this study, 934 patients with an umbilical hernia underwent surgery between 2004 and 2010, 599 (64.1%) of which were evaluated at least one year after the surgery. Complications, recurrence, and the reoperation rate were analyzed. Complications were observed in 5.7 per cent of the patients. With a mean follow-up time of 35.5 months, recurrence and reoperation rates were 3.8 per cent and 4.7 per cent, respectively. A higher percentage of female patients (60.9 % vs 29 %, P = 0.001) and a longer follow-up time (47.4 vs 35 months, P = 0.037) were observed in patients who developed a recurrence. No significant differences were observed between complications and the reoperation rate in patients who underwent Ventralex(®) preperitoneal mesh reinforcement and suture repair; however, a trend toward a higher recurrence rate was observed in patients with suture repair (6.5 % vs 3.2 %, P = 0.082). Suture repair had lower recurrence and reoperation rates in patients with umbilical hernias less than 1 cm. Suture repair is an appropriate procedure for small umbilical hernias; however, for larger umbilical hernias, mesh reinforcement should be considered.

An Alternative to Precious Metals: Hg(ClO4)2·3H2O as a Cheap and Water-Tolerant Catalyst for the Cycloisomerization of Allenols.

Hg(ClO4)2·3H2O, a cheap, water-tolerant, and stable salt, catalyzes the cycloisomerization reaction or α-allenols to 2,5-dihydrofurans in an efficient and selective manner. The reaction is general and can be applied to differently functionalized substrates, including alkyl-substituted, aryl-substituted, enantiopure, and tertiary allenols. In addition, density functional theory (DFT) calculations were performed to obtain insight into various aspects of the controlled reactivity of α-allenols under mercury catalysis. They suggest a dual activation of the allenol by the Hg complex that drives the reaction to the chemoselective formation of 2,5-dihydrofurans.

Gold as Catalyst for the Hydroarylation and Domino Hydroarylation/N1-C4 Cleavage of ß-Lactam-Tethered Allenyl Indoles.

Gold-catalyzed hydroarylation reaction of ß-lactam-tethered allenyl indoles gives azeto-oxepino[4,5-b]indol-2-ones, tetrahydroazeto-azocino[3,4-b]indol-2-ones, and hexahydroazeto-azepino[3,4-b]indol-2-ones with very high levels of stereo- and regioselectivity, the 7-exo and 8-endo carbocyclization modes by attack of the indole group toward either the internal or the terminal allene carbon, respectively, being favored. Hydroarylation across the central carbon of the allene moiety has not been detected. The controlled gold-catalyzed annulations allowed the formation of fused ß-lactams without harming the sensitive four-membered heterocycle. Besides, a novel gold-catalyzed domino process, namely, the allenic hydroarylation/N1-C4 ß-lactam bond breakage to afford dihydro-oxepino[4,5-b]indole-4-carboxamides, has been discovered.

Metal-free [3+2] cycloaddition of azides with Tf2C=CH2 for the regioselective preparation of elusive 4-(trifluoromethylsulfonyl)-1,2,3-triazoles.

1,2-Dipole Tf2C=CH2 is generated in situ and immediately reacts at room temperature with an azide to afford previously unknown 4-trifluoromethanesulfonyl 1,2,3-triazoles through a stepwise [3+2] cycloaddition reaction. Noteworthily, this mild and powerful uncatalyzed protocol is highly regio- and chemoselective.

Gallium-catalyzed domino arylation/oxycyclization of allenes with phenols.

The synthesis of dihydrobenzofuran-appended oxindoles has been accomplished taking advantage of an unprecedented reaction between allenols and phenols under metal catalysis.