Showing papers on "Double bond published in 2012"

Comparative study on the mechanism in photocatalytic degradation of different-type organic dyes on SnS2 and CdS

Abstract: The photocatalytic performances of the SnS 2 and the CdS under the irradiation of visible light were investigated by using different organic dyes as reactants. The photodegradation of organic dyes containing N N double bond on the SnS 2 followed a reduction mechanism with photoelectrons via the Sn IV /Sn II transition while the photodegradation of organic dyes containing N N double bond on the CdS and the photodegradation of organic dyes without N N double bond on either the SnS 2 or the CdS followed an oxidation mechanism with O 2 − and OH radicals. The SnS 2 exhibited much higher activity than the CdS during the photocatalytic degradation of organic dyes containing N N double bond, since the reduction of reactant molecules on the SnS 2 surface was much faster than the migration of either the O 2 − or the OH radicals. However, the SnS 2 displayed even lower activity than the CdS in the photocatalytic degradation of other organic dyes without N N double bond, since all these reactions followed the oxidation mechanism and the SnS 2 displayed a lower efficiency than the CdS in producing O 2 − or OH radicals due to the presence of the Sn IV /Sn II transition.

Direct C-H functionalization of enamides and enecarbamates by using visible-light photoredox catalysis.

Abstract: Direct C-H functionalization of various enamides and enecarbamates was realized through visible-light photoredox catalyzed reactions. Under the optimized conditions using [Ir(ppy)(2)(dtbbpy)PF(6)] as photocatalyst in combination with Na(2)HPO(4), enamides such as N-vinylpyrrolidinone could be easily functionalized by irradiation of the reaction mixture overnight in acetonitrile with visible light. The scope of the reaction with respect to enamide and enecarbamate substrates by using diethyl 2-bromomalonate for the alkylation reaction was explored, followed by an investigation of the scope of alkylating reagents used to react with the enamides and enecarbamates. The results indicated that reaction takes place with quite broad substrate scope, however, tertiary enamides with an internal C=C double bond in the E configuration could not be alkylated. Alkylation of N-vinyl tertiary enamides and enecarbamates gave monoalkylated products exclusively in the E configuration. Alkylation of N-vinyl secondary enamides gave doubly alkylated products. Double bond migration was observed in the reaction of electron-deficient bromides such as 3-bromoacetyl acetate with N-vinylpyrrolidinone. A mechanism is proposed for the reaction that is different from reported reactions of SOMOphiles with a nonfunctionalized C=C double bond. Further tests on the trifluoromethylation and arylation of enamides and enecarbamates under similar conditions showed that the reactions could serve as a mild, practical, and environmentally friendly approach to various functionalized enamides and enecarbamates.

Stereoselective Alkene Isomerization over One Position

Abstract: Although controlling both the position of the double bond and E:Z selectivity in alkene isomerization is difficult, 1 is a very efficient catalyst for selective mono-isomerization of a variety of multifunctional alkenes to afford >99.5% E-products. Many reactions are complete within 10 min at room temperature. Even sensitive enols and enamides susceptible to further reaction can be generated. Catalyst loadings in the 0.01–0.1 mol% range can be employed. E-to-Z isomerization of the product from diallyl ether was only <10–6 times as fast as its formation, showing the extremely high kinetic selectivity of 1.

Recent Advances in the Asymmetric Synthesis of α-(Trifluoromethyl)-Containing α-Amino Acids

Abstract: This review article provides a comprehensive update on the development of new methods for the asymmetric synthesis of α-(trifluoromethyl)-α-amino acids, covering the literature from 2006 to mid-February 2012. Most of the methods discussed are based on asymmetric additions across the carbon–nitrogen double bond of the imines derived from esters of 3,3,3-trifluoropyruvic acid. Medium to high levels of stereocontrol can be achieved using phenylglycinol-derived chiral auxiliaries attached to the nitrogen of the corresponding imines. Among the enantioselective approaches, impressive results were achieved through the application of the Strecker­ reaction using chiral thioureas, as well as chiral Bronsted acids, as organocatalysts. 1 Introduction 2 Stoichiometric Asymmetric Syntheses of α-(Trifluoromethyl)-α-amino Acids 3 Catalytic Asymmetric Syntheses of α-(Trifluoromethyl)-α-amino Acids 4 Miscellaneous 5 Conclusions

A stable germanone as the first isolated heavy ketone with a terminal oxygen atom

Abstract: Heavier analogues of ketones — containing a double bond between a group 14 element and oxygen — have so far not been isolated as stable compounds. Now, a stable monomeric germanone with a highly polarized Ge=O double bond has been isolated, stabilized by rigid bulky ligands.

Allylic Carbon–Carbon Double Bond Directed Pd-Catalyzed Oxidative ortho-Olefination of Arenes

Abstract: Pd-catalyzed selective ortho-olefination of arenes assisted by an allylic C–C double bond at room temperature using O2 as a terminal oxidant is described. A possible mechanism involving the initial coordination of allylic C═C bond to Pd followed by selective o-C–H bond metalation is proposed.

Palladium-catalyzed direct C-H arylation of enamides with simple arenes.

Abstract: The realm of transition-metal-catalyzed cross-coupling reactions has traditionally depended on prefunctionalized substrates for both reactivity and selectivity. The quest for improved atom economy and efficiency has brought forward revolutionary changes and important advances especially in the palladium-catalyzed direct C H functionalization where one or ideally both coupling partners could be replaced with simple arenes/alkenes. A vast majority of these tandem C H activation reactions are devoted on the synthesis of biaryl motifs. Direct oxidative coupling of unactivated arenes with olefins, the Fujiwara–Moritani reactions are comparatively under-explored in terms of the olefinic substrate scope and selectivity. Given the synthetic and economic potential of these reactions, development of new olefin functionalities that could be coupled with simple arenes is much warranted. Enamides are stable enamine surrogates and important synthetic intermediates having tunable reactivity and potential usage in various transformations. Development of effective and direct olefin functionalization of these compounds is highly desirable, because it provides access to multisubstituted amines and olefins, which are scaffolds that are pivotal in natural products as well as in molecular materials. Absolute stereocontrol of the double bond in these type of transformations is quite challenging, particularly when Z-enamides are required. Herein we present our results on the palladium-catalyzed direct arylation of enamides by using unactivated arenes through double C H functionalization. To our knowledge, this is the first report on the catalytic direct arylation of enamides and provides cost-effective and efficient access to highly substituted enamides with perfect Z selectivity. The initial screening studies were carried out using the enamide substrate 1 (Table 1, entry 1). Benzene was chosen as the model arene partner and used as the solvent, too. Sodium acetate was employed as a base and a stoichiometric amount of palladium acetate was used for the initial studies to avoid any side reactions that may happen with a terminal oxidant. Enamide 1 decomposed to the corresponding ketone under the reaction temperature of 80 8C (no reaction was observed at room temperature). We assumed that protecting the nitrogen atom of the enamide would increase the chemical stability of the enamide under the reaction conditions, and accordingly the N-methylated substrate 2 (Table 1, entry 2) was tested next. Significantly the substrate underwent a clean conversion and 59% of the desired arylated product 2a was isolated as a single stereoisomer (Z configuration as evidenced by NOESY, see the Supporting Information). The doubly acylated enimide 3 responded poorly under the reaction conditions (Table 1, entry 3). We reasoned that the electron density of the double bond is crucial for the coupling reaction and switched to the benzyl-protected substrate 4. Gratifyingly the product 4a was isolated in 91% yield in 26 h solely as the Z isomer (Table 1, entry 4, see the Supporting Information for the NMR proof for the Z configuration). Further increase of the electron density through a p-methoxy benzyl protection (enamide 5) did not alter the reaction profile (Table 1, entry 5). The carbonyl ligand on the nitrogen atom was also modified (enamide 6), but an E/Z mixture of the product 6a was isolated in a yield of 78% (Table 1, entry 6). Table 1: Effect of various nitrogen-protecting groups on the reactivity of enamides towards direct arylation.

N-Vinylcarbazole: An Additive for Free Radical Promoted Cationic Polymerization upon Visible Light

Abstract: N-Vinylcarbazole is proposed as an additive for epoxy ring-opening polymerization ROP upon visible light exposure. This compound can convert hardly oxidizable radicals to carbon centered radicals by an addition process onto the N-vinylcarbazole double bond. The generated radicals can be further easily oxidized by an iodonium salt thereby leading to efficient initiating cations for the ROP of epoxides. Different visible light photoinitiating systems have been investigated: Type I photoinitiators (derived from phosphine oxides) and dye/iodonium salt couples. The underlying chemical mechanisms are investigated by electron spin resonance (ESR) experiments.

Work-Function Decrease of Graphene Sheet Using Alkali Metal Carbonates

Abstract: A chemical approach was applied to decrease the work function of few-layer graphene. Li2CO3, K2CO3, Rb2CO3, and Cs2CO3 were used as n-doping materials. The sheet resistance of graphene doped with carbonate salt slightly increased from 1100 to 1700–2500 Ω/sq, and the transmittance of doped graphene with 0.1 M alkali metal at 550 nm decreased from 96.7 to 96.1–94% due to the formation of metal particles on the surface of graphene. A higher sheet resistance and lower transmittance were obtained at a higher concentration of alkali metal carbonate. The G peak in the Raman spectra was shifted to a lower wavenumber after alkali metal carbonate doping and the intensity ratio of the carbon double bond to the carbon single bond decreased with doping in the X-ray photoemission spectroscopy spectra, suggesting the charge transfer from metal ions to graphene sheets. Ultraviolet photoemission spectroscopy data showed that the work function of the graphene sheets decreased from 4.25 eV to 3.8, 3.7, 3.5, and 3.4 eV for g...

Alder-Ene Reaction: Aromaticity and Activation Strain Analysis

Abstract: We have computationally explored the trend in reactivity of the Alder-ene reactions between propene and a series of seven enophiles using density functional theory at M06-2X/def2-TZVPP. The reaction barrier decreases along the enophiles in the order H(2) C=CH(2) > HC≡CH > H(2) C=NH > H(2) C=CH(COOCH(3) ) > H(2) C=O > H(2) C=PH > H(2) C=S. Thus, barriers drop in particular, if third-period atoms become involved in the double bond of the enophile. Activation-strain analyses show that this trend in reactivity correlates with the activation strain associated with deforming reactants from their equilibrium structure to the geometry they adopt in the transition state. We discuss the origin of this trend and its relationship with the extent of synchronicity between H transfer from ene to enophile and the formation of the new C−C bond.

Stereospecific cross-coupling between alkenylboronates and alkyl halides catalyzed by iron-bisphosphine complexes.

Abstract: A stereospecific and high-yielding cross-coupling reaction between alkenylboron reagents and alkyl halides is described. The reaction has been achieved by using well-defined iron–bisphosphine complexes such as 1b FeCl2(3,5-t-Bu2-SciOPP), which was recently developed by the authors′ group. Various nonactivated alkyl bromides and chlorides possessing a base/nucleophile-sensitive functional group can participate in the cross-coupling, demonstrating its utility for stereoselective synthesis of functional molecules bearing a carbon–carbon double bond.

Differentiation of complex lipid isomers by radical-directed dissociation mass spectrometry

Abstract: Contemporary lipidomics protocols are dependent on conventional tandem mass spectrometry for lipid identification. This approach is extremely powerful for determining lipid class and identifying the number of carbons and the degree of unsaturation of any acyl-chain substituents. Such analyses are however, blind to isomeric variants arising from different carbon carbon bonding motifs within these chains including double bond position, chain branching, and cyclic structures. This limitation arises from the fact that conventional, low energy collision-induced dissociation of even-electron lipid ions does not give rise to product ions from intrachain fragmentation of the fatty acyl moieties. To overcome this limitation, we have applied radical-directed dissociation (RDD) to the study of lipids for the first time. In this approach, bifunctional molecules that contain a photocaged radical initiator and a lipid-adducting group, such as 4-iodoaniline and 4-iodobenzoic acid, are used to form noncovalent complexes (i.e., adduct ions) with a lipid during electrospray ionization. Laser irradiation of these complexes at UV wavelengths (266 nm) cleaves the carbon iodine bond to liberate a highly reactive phenyl radical. Subsequent activation of the nascent radical ions results in RDD with significant intrachain fragmentation of acyl moieties. This approach provides diagnostic fragments that are associated with the double bond position and the positions of chain branching in glycerophospholipids, sphingomyelins and triacylglycerols and thus can be used to differentiate isomeric lipids differing only in such motifs. RDD is demonstrated for well-defined lipid standards and also reveals lipid structural diversity in olive oil and human very-low density lipoprotein.

Intramolecular oxycyanation of alkenes by cooperative Pd/BPh3 catalysis.

Abstract: The cooperative catalysis by palladium and triphenylborane effects the intramolecular oxycyanation of alkenes through the cleavage of O-CN bonds and the subsequent insertion of double bonds. The use of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) as a ligand for palladium is essential for allowing the transformation to proceed with high chemo- and regioselectivity. Variously substituted dihydrobenzofurans with both a tetra-substituted carbon and cyano functionality are accessed by the newly developed methodology.

A Boron-Boron Triple Bond

Abstract: Although carbon readily forms double and even triple bonds, such bonds are much rarer between the heavier elements of the same group or between atoms of other main groups of the periodic system. Chemists have succeeded in creating some such molecules, such as double-bonded silicon compounds, although they are usually highly reactive. On page 1420 of this issue, Braunschweig et al. ( 1 ) report the synthesis of one such highly unusual chemical compound, which has a boron-boron triple bond.

Compositional Space Boundaries for Organic Compounds

Abstract: An upper elemental compositional boundary for fossil hydrocarbons has previously been established as double-bond equivalents (i.e., DBE = rings plus double bonds) not exceeding 90% of the number of carbons. For heteroatom-containing fossil compounds, the 90% rule still applies if each N atom is counted as a C atom. The 90% rule eliminates more than 10% of the possible elemental compositions at a given mass for fossil database molecules. However, some synthetic compounds can fall outside the upper boundary defined for naturally occurring compounds. Their inclusion defines an "absolute" upper boundary as DBE (rings plus double bonds to carbon) equal to carbon number plus one, and applies to all organic compounds including fullerenes and other molecules containing no hydrogen. Finally, the DBE definition can fail for molecules with particular atomic valences. Therefore, we also present a generalized DBE definition that includes atomic valence to enable calculation of the correct total number of rings, double bonds, and triple bonds for heteroatom-containing compounds.

Enantio- and Regioselective Epoxidation of Olefinic Double Bonds in Quinolones, Pyridones, and Amides Catalyzed by a Ruthenium Porphyrin Catalyst with a Hydrogen Bonding Site

Abstract: An array of differently substituted 3-alkenylquinolones was synthesized, and the enantio- and regioselectivity of their Ru-catalyzed epoxidation were studied. A precursor ruthenium(II) complex with a chiral tricyclic γ-lactam skeleton (octahydro-1H-4,7-methanoisoindol-1-one) was available by Sonogashira cross-coupling with a monobromo-substituted ruthenium(II) porphyrin. Enantioselective epoxidation reactions (60–83% yield, 85–98% ee) were achieved with this catalyst, and it was shown that the enantioselectivity depends critically on the presence of a two-point hydrogen bond interaction between the γ-lactam site of the catalyst and the δ-lactam (quinolone) site of the substrate. DFT calculations support the hypothesis that the reaction occurs via a hydrogen-bound transition state, in which the 3-alkenylquinolone adopts an s-trans conformation. The calculations further revealed that this transition state is preferred over a competing s-cis transition state because it exerts less strain in the rigid backbon...

Aerobic Palladium(II)‐Catalyzed 5‐endo‐trig Cyclization: An Entry into the Diastereoselective C‐2 Alkenylation of Indoles with Tri‐ and Tetrasubstituted Double Bonds

Abstract: The Mizoroki–Heck reaction, that is the palladium(0)-catalyzed alkenylation of prefunctionalized arenes (or alkenes), is now rivaled by oxidative palladium(II)-catalyzed processes (also referred to as Fujiwara–Moritani reactions) that involve C H bond activation. These related palladium catalyses proceed through the same C C bond-forming step, the migratory insertion of a C C double bond into the intermediate C(sp) Pd bond. Intermolecular coupling reactions are, however, limited to unhindered alkenes. If not functionalized with a directing group, dior even trisubstituted alkenes are usually not sufficiently reactive, 5] and the few successful oxidative coupling reactions are associated with selectivity problems (I)II and III, Scheme 1, upper). This situation changes in the intramolecular variant, in which those alkenes participate indeed in C C couplings. 6] We therefore had the idea to temporarily tether a trisubstituted alkene III with a synthetically useful functional group to an arene II (V)II and III, Scheme 1, upper). Intramolecular coupling (IV)V, Scheme 1, upper) would then be followed by the cleavage of the tether (I)IV, Scheme 1, upper). The net outcome of this three-step sequence is a C H bond alkenylation with complete control of the double bond geometry in the fully substituted alkene. For this, the planned ring closure onto the trigonal carbon atom would have to occur with endo selectivity, which is still the exception in oxidative palladium(II) catalysis. With our experience in intramolecular alkenylation (exo mode) 11] of indole C H bonds and exo cyclization of a,bunsaturated amides, we designed indole VIII with an alkene tethered to the indole nitrogen atom by an amide group (Scheme 1, lower). Its unprecedented endo ring closure would give the rare motif of 3H-pyrrolo[1,2a]indole-3-ones (VII)VIII, Scheme 1, lower). Subsequent ring-opening by cleavage of the amide linkage would provide a diastereocontrolled access to C-2 alkenylated indoles, which are hitherto not accessible by direct C H coupling with the requisite trisubstituted a,b-unsaturated acceptors (VII)VI, Scheme 1, lower). Herein, we show the realization of this strategy for several alkene substitution patterns and also for functionalized indole building blocks, for example, tryptophan und tryptamine. Our investigation began with the identification of suitable reaction conditions for the endo cyclization of a representative precursor (1!2, Table 1). Our previously elaborated aerobic oxidative setup in the presence of pivalic acid using Stoltz s Pd(OAc)2–L1 combination [11a,c,12, 16] afforded fully substituted 2 in reasonable yield (Table 1, entry 1). Variation of acid and solvent was only detrimental (Table 1, entries 2–4), and control experiments showed that all components of the Pd(OAc)2–L1–acid system are necessary for the reaction (Table 1, entries 5–7). It is worth mentioning that no exocyclic alkene regioisomer is formed because competing bhydride elimination pathways (b-H versus b’-H) are an issue in intermolecular coupling reactions of a-methyl-substituted a,b-unsaturated acceptors. In analogy to the seminal work of Stoltz and co-workers, we also tested several electronically modified pyridines (L2–L7, Figure 1). It emerged from this screening Scheme 1. Strategy for the diastereocontrolled formation of tetrasubstituted double bonds by “indirect” C H bond alkenylation of trisubstituted alkenes: Application to the C-2 alkenylation of indoles (FG and FG’= functional groups).

Using ambient ozone for assignment of double bond position in unsaturated lipids

Abstract: Unsaturated lipids deposited onto a range of materials are observed to react with the low concentrations of ozone present in normal laboratory air. Parent lipids and ozonolysis cleavage products are both detected directly from surfaces by desorption electrospray ionisation mass spectrometry (DESI-MS) with the resulting mass spectra providing clear evidence of the double bond position within these molecules. This serendipitous process has been coupled with thin-layer chromatography (TLC) to provide a simple but powerful approach for the detailed structural elucidation of lipids present in complex biological extracts. Lipid extracts from human lens were deposited onto normal phase TLC plates and then developed to separate components according to lipid class. Exposure of the developed plates to laboratory air for ca. 1 h prior to DESI-MS analysis gave rise to ozonolysis products allowing for the unambiguous identification of double bond positions in even low abundant, unsaturated lipids. In particular, the co-localization of intact unsaturated lactosylceramides (LacCer) with products from their oxidative cleavage provide the first evidence for the presence of three isomeric LacCer (d18:0/24:1) species in the ocular lens lipidome, i.e., variants with double bonds at the n-9, n-7 and n-5 positions.

Total Synthesis of (±)‐Merrilactone A

Abstract: This invention provides a total synthesis of Merrillactone and Merrilactone analogues having the structure wherein Z is O or >N-X, where X is H, straight or branched substituted or unsubstituted alkyl, alkenyl or alkynyl, or acyl, carbamoyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, aralkyl, amino, alkyl amino, or dialkyl amino; wherein each of R1 and R2 is H or R1 and R2 together are =O; wherein each of R3 and R4 is H or R3 and R4 together are =O; wherein each of R5 and R6 is, independently, H, alkyl, aralkyl, or aryl; wherein each of R7 and R8 is, independently, H or OR14, where R14 is alkyl or -C(O)-R15, where R15 is H, -CH2R16, -CHR16R16, -CR16R17R16, -OR16, alkenyl or alkynyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, aralkyl, amino, alkyl amino, or dialkyl amino, wherein each R16 is straight or branched, substituted or unsubstituted alkyl, alkenyl or alkynyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, aralkyl, or amino; and wherein R17 is straight or branched, unsubstituted alkyl, alkenyl or alkynyl, cycloalkyl, aryl, heterocycloalkyl, heteroaryl, aralkyl, or amino, or wherein R7 and R9 together are >O; wherein each of R9 and R10 is, independently, H, alkyl, OH, or OR13, where R13 is an alkyl, an acyl, or an amide, or R9 and R10 together are =CH2, or wherein R8 and R10 together are >O; wherein if one of R7 or R8 and one of R9 or R10 is absent, a double bond is formed as indicated by the broken line; and wherein each of R11 and R12 is, independently, H, OH, or OR13, where R13 is an alkyl, an acyl, or an amide, or R11 and R12 together are =O, or wherein R12 and R10 together are >O, including intermediates in the synthesis.

Mechanistic Insight into the NN Bond‐Cleavage of Azo‐Compounds that was Induced by an Al ? Al‐bonded Compound [L2−AlII ? AlIIL2−]

Abstract: An α-diimine-stabilized Al-Al-bonded compound [L(2-)Al(II)-Al(II)L(2-)] (L = [{(2,6-iPr(2)C(6)H(3))NC(Me)}(2)]; 1) consists of dianionic α-diimine ligands and sub-valent Al(2+) ions and thus could potentially behave as a multielectron reductant. The reactions of compound 1 with azo-compounds afforded phenylimido-bridged products [L(-)Al(III)(μ(2)-NPh)(μ(2)-NAr)Al(III)L(-)] (2-4). During the reaction, the dianionic ligands and Al(2+) ions were oxidized into monoanions and Al(3+), respectively, whilst the [NAr](2-) imides were produced by the four-electron reductive cleavage of the N=N double bond. Upon further reduction by Na, the monoanionic ligands in compound 2 were reduced to the dianion to give [(L(2-))(2)Al(III)(2)(μ(2)-NPh)(2)Na(2)(thf)(4)] (5). Interestingly, when asymmetric azo-compounds were used, the asymmetric adducts were isolated as the only products (compounds 3 and 4). DFT calculations indicated that the reaction was quite feasible in the singlet electronic state, but the final product with the triplet-state monoanionic ligands could result from an exothermic singlet-to-triplet conversion during the reaction process.

Reaction of arynes with carbon-heteroatom double bonds

Abstract: Recent achievements in the construction of heterocycles by the reaction of arynes with carbon-heteroatom double bonds are reviewed. Use of the Diels-Alder type, ionic, and radical mechanisms resulted in the formation of novel heterocycles containing oxygen, nitrogen, sulfur, and selenium atoms. Abstract This review focused on the application of nano-materials in heterocyclic chemistry. The main part of review is constituted by sections in which the reactions catalyzed by nanomaterials. In the last part of this review, emphasis is given to the heterocyclic supported nanomaterials and their importance in the catalysis. Abstract Aspergillides A, B, and C are cytotoxic macrolides produced by the marine-derived fungus Aspergillus ostianus strain TUF 01F313. The unique molecular architectures of the aspergillides featuring 14-membered marocyclic structures embedded with a tetrahydro- or dihydropyran unit have attracted significant attention from the synthetic chemistry community, and thereby various synthetic approaches to these structurally as well as pharmacologically intriguing molecules have been reported by as many as 12 research groups in the past 3 years. This review describes all of the syntheses disclosed to date, focusing mainly on the methodologies employed for the diastereoselective installation of the pyran ring systems.

Combined Oxypalladation/C ? H Functionalization: Palladium(II)-Catalyzed Intramolecular Oxidative Oxyarylation of Hydroxyalkenes

Abstract: Originating from the classic Wacker process,1 the palladium(II)-catalyzed oxidative difunctionalization of alkenes has emerged as an attractive strategy for the rapid generation of molecular complexity due to its ability to form multiple carbon–carbon/carbon–heteroatom bonds and stereogenic centers in a single step.2,3,4 This versatility, combined with the broad functional group compatibility and air- and moisture-tolerance, renders the Pd(II)-catalyzed oxidative difunctionalization a powerful tool for synthetic chemists. One of the most synthetically relevant transformations of this class is the Pd(II)-catalyzed oxidative carboetherification of hydroxyalkenes, which leads to a variety of interesting oxygenated heterocycles.5 Pioneered by Semmelhack,6 the oxidative carboetherification in the presence of CO or electronically biased olefins has been developed with wide application to complex molecule synthesis.7 Mechanistically such reactions are believed to proceed via a β-alkoxy-alkylpalladium(II) intermediate 1 generated from nucleophilic oxypalladation (Scheme 1). Compared to the more often reported carbon–heteroatom bond forming processes, the scope of oxidative carbon–carbon bond formation from 1 is still limited.8 It is both synthetically and mechanistically interesting to expand the scope of this type of transformation in order to access more structurally diverse molecules. Scheme 1 Scope of the Pd(II)/Pd(0) catalyzed oxidative carboetherification. Aiming to develop a viable method for the catalytic oxidative oxypalladation/arylation of unactivated hydroxyalkenes, we were inspired by the recent development in the field of Pd(II)-catalyzed directed arene C–H activation/C–C bond formation.9 Noting that 1 could undergo cyclopalladation with a proximate arene ring under similar condition (Scheme 1), we envisioned the possibility of merging the two Pd(II)-catalyzed transformations, namely the oxypalladation and C–H activation/C–C bond formation. The success of this strategy lies in the identification of a catalytic system efficient for both the oxypalladation and C–H functionalization steps, as well as the ability to avoid oxidation of the alcohol functional group.10 Herein we report a simple and mild Pd(II)-catalyzed method for the efficient construction of the tetrahydro-2H-indeno-[2,1-b]furan framework from acyclic hydroxyalkenes bearing unactivated arenes. We began our study by subjecting 4-methyl-3-phenylpent-4-en-1-ol (2a) to a catalytic amount of palladium acetate and a variety of different stoichiometric oxidants. Several common combinations for Pd(II)-catalyzed oxidative C–H activations such as Pd(II)/Cu(II), Pd(II)/Ag(I) and Pd(II)/PIDA were shown to be ineffective for this transformation (Table 1, entries 1–3).8,11 Simple Pd(OAc)2/pyridine/O2 (1 atm) system,12 however, was able to efficiently catalyze the desired transformation, affording 3a in moderate yield (entry 5). The use of bidentate pyridine-based ligands were found to significantly retard the reaction (entries 6, 7).13 Tuning the substituents on the pyridine ligand (entries 8–10) led to the identification of ethyl nicotinate14 as the optimal ligand. The ligand loading could also be lowered to 6 mol% without loss of yield (entry 12). Table 1 Representative optimization of the reaction conditions.a A variety of α-aryl-γ-hydroxyalkenes could be cyclized to the corresponding tetrahydro-2H-indeno-[2,1-b]furan derivatives using this Pd(II)-catalyzed intramolecular tandem oxypalladation/C–H activation protocol. Illustrative examples of the reaction scope are shown in Table 2. Both alkyl and aryl substituents on the carbon-carbon double bond were tolerated (3b, 3c), as well as tertiary alcohol nucleophile (3d). In addition, a wide range of electron-rich, -neutral and -deficient arenes were found to participate in the C–H activation process (3e–h, 3j). An aryl bromide-containing substrate afforded the desired product (3i) in modest yield, although additional quantities of copper(II) chloride proved to be necessary,15 this observed orthogonal reactivity relative to the Pd(0)-catalyzed cross-coupling chemistry is useful for the further elaboration of the arene ring. meta-Substituted arene (entry 10) cyclized to give a 3:1 mixture of regioisomers favoring the cleavage of the less hindered C–H bond (3j, 3j’). Finally it was found that a pyridyl group could also participate in the C–H activation process with functionalization solely at the 4-position (3k). Table 2 Pd(II)-catalyzed oxidative oxyarylation of hydroxyalkenes.a (1) Lactone 4 can be accessed by one step oxidation of the oxyarylation adduct 3a (eq. 1). The relative stereochemistry of 4 was confirmed by X-ray diffraction. Lactone 4 is also structurally related to a class of sulindac-derived biologically active molecules which have been used for “precancerous treatment.”16 To gain an insight into the reaction mechanism, deuterium labeling experiments were performed. The observed kinetic isotope effect for both intermolecular and intramolecular cases were found to be approximately 2.17 This observation is consistent with a reaction mechanism in which irreversible C–H bond cleavage is rate-limiting. Next, treating 2a with palladium acetate under an argon atmosphere in the presence of ethyl nicotinate also afforded cyclization product 3a (Scheme 2). The formation of 3a in the absence of external re-oxidant is consistent with the Pd(II)/Pd(0) catalytic cycle depicted in Scheme 1. Scheme 2 Oxyarylation in the absence of external oxidant. One of the most interesting aspects of the Pd(II)-catalyzed oxidative process is its orthogonal reactivity compared with Pd(0)-catalyzed transformations (Scheme 3). Treating hydroxyalkene 2i with a catalytic amount of palladium acetate and XPhos in the presence of K2CO3 afforded chroman derivative 5 by a classic Pd(0)-catalyzed C–O coupling.18 The alkene functional group remained intact. However, switching the base to NaOtBu resulted in the formation of cyclization product 3a via Pd(0)-catalyzed carboetherification of the alkene originally developed by Wolfe and co-workers.5 On the other hand, subjecting 2i to the standard conditions described in this work led to exclusive formation of 3i via the desired Pd(II)-catalyzed oxypalladation/C–H functionalization pathway. Dechlorinated material was not detected. This demonstrates the potential of diversified modification of a single compound containing multiple functional groups using different palladium catalyst systems. Scheme 3 Divergent Pd(II)-catalysis and Pd(0)-catalysis. In conclusion, we have developed an efficient protocol for the intramolecular oxidative oxyarylation of hydroxyalkenes using a Pd(II)-catalyzed tandem oxypalladation/C–H functionalization strategy. This methodology allows rapid access to tetrahydro-2H-indeno-[2,1-b]furan framework from simple acyclic hydroxyalkene bearing unactivated arenes or heteroarenes. Further mechanistic studies and application of this strategy to the synthesis of other heterocyclic systems are currently under investigation.

A New ONO3- Trianionic Pincer-Type Ligand for Generating Highly Nucleophilic Metal–Carbon Multiple Bonds

Abstract: Appending an amine to a C═C double bond drastically increases the nucleophilicity of the β-carbon atom of the alkene to form an enamine. In this report, we present the synthesis and characterization of a novel CF3–ONO3- trianionic pincer-type ligand, rationally designed to mimic enamines within a metal coordination sphere. Presented is a synthetic strategy to create enhanced nucleophilic tungsten–alkylidene and −alkylidyne complexes. Specifically, we present the synthesis and characterization of the new CF3–ONO3- trianionic pincer tungsten–alkylidene [CF3–ONO]W═CH(Et)(OtBu) (2) and −alkylidyne {MePPh3}{[CF3–ONO]W≡C(Et)(OtBu)} (3) complexes. Characterization involves a combination of multinuclear NMR spectroscopy, combustion analysis, DFT computations, and single crystal X-ray analysis for complexes 2 and 3. Exhibiting unique nucleophilic reactivity, 3 reacts with MeOTf to yield [CF3–ONO]W═C(Me)(Et)(OtBu) (4), but the bulkier Me3SiOTf silylates the tert-butoxide, which subsequently undergoes isobutylene ex...