Iridium‐Catalyzed Regio‐ and Enantioselective Hydroarylation of Alkenyl Ethers by Olefin Isomerization

Iridium‐catalyzed hydroarylation of alkenyl ethers, such as allylic and homoallylic ethers, by C−H bond activation gave high yields of the corresponding addition products, where the aryl groups were selectively installed at the α‐carbon atom to the alkoxy group. The reaction involves an isomerization of the alkenyl ethers into the corresponding 1‐alkenyl ethers, which then undergo the regio‐ and enantioselective hydroarylation.     

Iridium-Catalyzed Regio- and Enantioselective Hydroarylation of Alkenyl Ethers by Olefin Isomerization

Iridium-catalyzed hydroarylation of alkenyl ethers, such as allylic and homoallylic ethers, by C−H bond activation gave high yields of the corresponding addition products, where the aryl groups were selectively installed at the α-carbon atom to the alkoxy group. The reaction involves an isomerization of the alkenyl ethers into the corresponding 1-alkenyl ethers, which then undergo the regio- and enantioselective hydroarylation.     

A Convergent Synthesis of Functionalized Alkenyl Halides through Cobalt(III)‐Catalyzed Three‐Component C−H Bond Addition

A Co^III‐catalyzed three‐component coupling of C(sp²)−H bonds, alkynes, and halogenating agents to give alkenyl halides is reported. This transformation proceeds with high regio‐ and diastereoselectivity, and is effective for a broad range of aryl and alkyl terminal alkynes. Diverse C−H bond partners also exhibit good reactivity for a range of heteroaryl and aryl systems as well as synthetically useful secondary and tertiary amide, urea, and pyrazole directing groups. This multicomponent transformation is also compatible with allenes in place of alkynes to furnish tetrasubstituted alkenyl halides, showcasing the first halo‐arylation of allenes.     

Highly stereoselective synthesis of aristeromycin through dihydroxylation of 4-aryl-1-azido-2-cyclopentenes

Dihydroxylation of 4-aryl-1-azido-2-cyclopentenes 6, in which an aryl group is used as a synthetic equivalent of CH(2)OH, was studied to improve the low to moderate stereoselectivity previously reported for cyclopentenes 3 possessing CH(2)X and nitrogen atom-containing groups. 2-Furyl, Ph, and p-MeOC(6)H(4) groups were chosen as the aryl groups. Compounds 6a-c possessing such aryl groups were prepared by CuCN-catalyzed reaction between 2-cyclopentene-1,4-diol monoacetate 9 and the corresponding Grignard reagents followed by substitution of the hydroxyl group with (PhO)(2)P(=O)N(3). The desired diols 7a-c were obtained with higher selectivities of >7:1 when dihydroxylation of 6a-c was carried out at 0 degrees C with OsO(4) (catalyst) and NMO in a mixed solvent of MeCN, THF, t-BuOH, and H(2)O. Among them, the furyl compound recorded the highest selectivity of 14:1. The furyl and azido groups on diol 7a were converted into hydroymethyl and adeninyl groups, respectively, to produce acetonide 2, which upon hydrolysis affords aristeromycin 1.     

Aryl transfer between Pd(II) centers or Pd(IV) intermediates in Pd-catalyzed domino reactions

A computational study has been performed to determine the mechanism of the key steps of Pd-catalyzed domino reactions in which C(sp2)-C(sp2) are formed from aryl and alkenyl halides. DFT calculations were done on model complexes of the proposed intermediates, with PH3 and H2O as ancillary ligands, to explore two possible mechanisms: the oxidative addition of aryl or alkenyl halides to palladacycles to give Pd(IV) intermediates, and the transmetalation-type reaction of aryl or alkenyl ligands between two Pd(II) centers, a palladacycle, and a Pd(II) complex formed by oxidative addition of aryl or alkenyl halides to Pd0. We have shown that oxidative addition of iodoethylene to Pd0 precursors is more favorable than oxidative addition to Pd(II) palladacycles, whereas transmetalation-type reactions between Pd(II) complexes are facile. Similar results were obtained with iodobenzene instead of iodoethylene and formamide as the ancillary ligand. These results suggest that Pd(IV) intermediates are not involved in these reactions.     

Lewis-acid-catalyzed rearrangement of arylvinylidenecyclopropanes: significant influence of substituents and electronic nature of aryl groups

Lewis-acid-catalyzed reactions of arylvinylidenecyclopropanes having three substituents at the corresponding cyclopropyl rings have been investigated thoroughly. The reaction products are highly dependent on the substituents at the corresponding cyclopropyl rings and the electronic nature of the aryl groups. For arylvinylidenecyclopropanes bearing two alkyl groups at the C-1 position (R1, R2, R3=aryl; R4=H; R5, R6=alkyl), naphthalene derivatives were formed in the presence of Lewis-acid Eu(OTf)3 in DCE at 40 degrees C. For arylvinylidenecyclopropanes in which R1, R2, R3=aryl and R4, R5=alkyl (syn/anti isomeric mixtures), the corresponding 6aH-benzo[c]fluorine derivatives were formed in the syn-configuration via a double intramolecular Friedel-Crafts reaction when all of the aryl groups do not have electron-withdrawing groups or the corresponding indene derivatives were obtained via an intramolecular Friedel-Crafts reaction as long as one electron-deficient aryl group was attached. For arylvinylidenecyclopropanes in which R1, R2, R3, R4=aryl and R5=alkyl or H, the corresponding indene derivatives were obtained exclusively via a sterically demanding intramolecular Friedel-Crafts reaction. Lewis-acid effects and mechanistic insights have been discussed on the basis of experimental investigations.     

Group IB organometallic chemistry: XXXV. Crystal and molecular structure of [Cu4(4-MeC6H4)-MeC-C(C6H4NMe2-2)2(C6H4NMe2-2)2], a tetranuclear organocopper compound containing bridging alkenyl and aryl groups

The crystal and molecular structure of the title compound has been determined by a single crystal X-ray diffraction study using standard Patterson and Fourier methods. The structure was refined by a block-diagonal least-square procedure to a finalR value of 0.16 for 3454 reflections. Crystals are monoclinic, space groupP2₁/c, witha 14.007(5), b 12.224(5), c 28.358(8)A?, β 99.60(1)°, andZ - 4.The molecule consists of a central rhombus-type core of copper atoms to which the alkenyl and aryl groups are bound in a bridging fashion (two electron-three center bonding). The two alkenyl and the two aryl groups each occupy adjoining edges of the Cu₄ core. The dimethylamino groups of the alkenyl ligand coordinate to copper, whereas those of the bridging aryl ligand are free. As a result the copper core is made up of copper atoms which are alternatingly two- and three-coordinate.The structure is discussed in terms of structural information now available for organocopper compounds. The geometry of the Cu₂C (bridge) moiety in organocopper cluster compounds as expected varies little with the nature of the bridging one-electron organo ligand (alkyl, alkenyl, alkynyl or aryl).     

Molecules with new topologies derived from hydrogen-bonded dimers of tetraurea calix[4]arenes

Tetraurea calix[4]arenes 2 have been synthesized in which two adjacent aryl urea residues are connected to a loop by an aliphatic chain -O-(CH(2))(n)-O-. The remaining urea residues have a bulky 3,5-di-tert-butylphenyl residue and an omega-alkenyloxyphenyl residue. Since this bulky residue cannot pass through the loop, only one homodimer (22) is formed in apolar solvents, for steric reasons, in which the two alkenyl residues penetrate the two macrocyclic loops. Covalent connection of these alkenyl groups by olefin metathesis followed by hydrogenation creates compounds 3, which consist of molecules with hitherto unknown topology. Their molecular structure was confirmed by (1)H NMR spectroscopy and ESIMS, and for one example by single-crystal X-ray analysis.     

Single‐Electron‐Transfer‐Induced Coupling of Arylzinc Reagents with Aryl and Alkenyl Halides

Arylzinc reagents, prepared from aryl halides/zinc powder or aryl Grignard reagents/zinc chloride, were found to undergo coupling with aryl and alkenyl halides without the aid of transition‐metal catalysis to give biaryls and styrene derivatives, respectively. In this context, we have already reported the corresponding reaction using aryl Grignard reagents instead of arylzinc reagents. Compared with the Grignard cross‐coupling, the present reaction features high functional‐group tolerance, whereby electrophilic groups such as alkoxycarbonyl and cyano groups are compatible as substituents on both the arylzinc reagents and the aryl halides. Aryl halides receive a single electron and thereby become activated as the corresponding anion radicals, which react with arylzinc reagents, thus leading to the cross‐coupling products.     

Application of vinyl tris(trimethylsilyl)germanes in Pd-catalyzed couplings

The oxidative treatment of vinyltris(trimethylsilyl)germanes with hydrogen peroxide (NaOH/H(2)O/THF) or tert-butyl peroxide (KH/THF) generates reactive germanol or germanoxane species that undergo Pd-catalyzed cross-couplings with aryl and alkenyl halides and aryl triflates in the presence of Pd(PPh(3))(4). Vinylgermanes having either a conjugated or isolated double bond serve as versatile transmetalation reagents. The E-germanes undergo coupling with retention of stereochemistry under aqueous and anhydrous conditions, while coupling of Z-germanes occurs with less stereoselectivity to produce a mixture of E/Z products.     

A short synthesis of highly substituted furans from alkenyl aryl ketones with dichloromethyl phenyl sulfoxide

Two-step synthesis of 2-aryl-5-(phenylsulfanyl)furans was achieved starting from alkenyl aryl ketones and dichloromethyl phenyl sulfoxide. The phenylsulfanyl group was successfully converted to other functional groups, via sulfinyl group, to give highly substituted 2-arylfurans in good overall yields.     

Nickel-catalyzed Suzuki-Miyaura reaction of aryl fluorides

Two protocols for the nickel-catalyzed cross-coupling of aryl fluorides with aryl boronic esters have been developed. The first employs metal fluoride cocatalysts, such as ZrF(4) and TiF(4), which enable Suzuki-Miyaura reactions of aryl fluorides bearing electron-withdrawing (ketones, esters, and CF(3)), aryl and alkenyl groups as well as those comprising fused aromatic rings, such as fluoronaphthalenes and fluoroquinolines. The second protocol employs aryl fluorides bearing ortho-directing groups, which facilitate the difficult C-F bond activation process via cyclometalation. N-heterocycles, such as pyridines, quinolines, pyrazoles, and oxazolines, can successfully promote cross-coupling with an array of organoboronic esters. A study into the substituent effects with respect to both coupling components has provided fundamental insights into the mechanism of the nickel-catalyzed cross-coupling of aryl fluorides.     

Intramolecular palladium-catalyzed direct arylation of alkenyl triflates

A catalyst generated from Pd(OAc)2 and dppp is effective for the direct intramolecular arylation of alkenyl triflates. Conjugated alkene-arene-containing carbocycles are produced in good yield. The process tolerates a variety of aryl substituents as well a simple heteroaryl groups. Electron-deficient aryl rings deliver faster reactions.     

Ruthenium-catalyzed functionalization of aryl carbon-oxygen bonds in aromatic ethers with organoboron compounds

The ruthenium-catalyzed reaction of aryl ethers having a carbonyl group at the ortho position to the ether group with organoboronates (R-B(OCH2CMe2CH2O), R = aryl, alkenyl, and alkyl) resulted in site-selective C-C bond formation. Among the transition metal complexes screened, the RuH2(CO)(PPh3)3 complex showed the highest activity. Several aromatic ketones having methoxy or phenoxy groups at the ortho position can also be used in this coupling reaction. A variety of arylboronates containing electron-donating (NMe2, OMe, methyl, and vinyl) and -withdrawing (F and CF3) groups reacted with methoxy ketones to give the corresponding coupling products in high yields.     

Cascade alkenyl amination/Heck reaction promoted by a bifunctional palladium catalyst: a novel one-pot synthesis of indoles from o-haloanilines and alkenyl halides

A novel approach for the synthesis of the important indole ring is described. Indoles are obtained from o-bromoanilines and alkenyl halides in a Pd-catalyzed cascade process that involves an alkenyl amination followed by an intramolecular Heck reaction. The overall process represents the first example of the participation of alkenyl amination reactions in Pd-catalyzed cascade reactions. Initially, the relative reactivity of aryl and alkenyl bromides and chlorides towards Pd-catalyzed amination was investigated. Competition experiments were carried out in the presence of primary and secondary amines, and these revealed the reactivity order alkenyl bromides > aryl bromides > alkenyl chlorides > aryl chlorides, as well as very high chemoselectivity; the more reactive halide was always favored. Thereafter, optimized reaction conditions for the sequential alkenyl amination/Heck cyclization to give indoles were investigated with the model reaction of o-bromoaniline with alpha-bromostyrene. An extensive screening of ligands, bases, and reaction conditions revealed that the [Pd2(dba)3]/DavePhos, NaOtBu, toluene combination at 100 degrees C were the optimized reaction conditions to carry out the cascade process (dba=dibenzylideneacetone, DavePhos=2-dicyclohexylphosphino-2'-N,N-dimethylaminobiphenyl). The reaction proceeds with aryl, alkyl, and functionalized substitutents in both starting reactants. The cyclization was also studied with N-substituted o-bromoanilines (which would give rise to N-substituted indoles); however, in this case, indole formation occurred only with 1-substituted-2-bromoalkenes. Finally, the application of this methodology to o-chloroanilines required further optimization. Although the catalyst based on DavePhos failed to promote the cascade process, a catalytic combination based on [Pd2(dba)3]/X-Phos promoted the formation of the indole ring also from the less reactive chloroanilines.     

Highly Stereoselective Cobalt(III)‐Catalyzed Three‐Component C−H Bond Addition Cascade

A highly stereoselective three‐component C(sp²)?H bond addition across alkene and polarized π‐bonds is reported for which Co^III catalysis was shown to be much more effective than Rh^III. The reaction proceeds at ambient temperature with both aryl and alkyl enones employed as efficient coupling partners. Moreover, the reaction exhibits extremely broad scope with respect to the aldehyde input; electron rich and poor aromatic, alkenyl, and branched and unbranched alkyl aldehydes all couple in good yield and with high diastereoselectivity. Multiple directing groups participate in this transformation, including pyrazole, pyridine, and imine functional groups. Both aromatic and alkenyl C(sp²)?H bonds undergo the three‐component addition cascade, and the alkenyl addition product can readily be converted into diastereomerically pure five‐membered lactones. Additionally, the first asymmetric reactions with Co^III‐catalyzed C?H functionalization are demonstrated with three‐component C?H bond addition cascades employing N‐tert‐butanesulfinyl imines. These examples represent the first transition metal catalyzed C?H bond additions to N‐tert‐butanesulfinyl imines, which are versatile and extensively used intermediates for the asymmetric synthesis of amines.     

Synthesis and cross-coupling reaction of alkenyl[(2-hydroxymethyl)phenyl]dimethylsilanes

Highly stable alkenyl[2-(hydroxymethyl)phenyl]dimethylsilanes are prepared by stereo- and regioselective hydrosilylation of alkynes catalyzed either by a platinum or ruthenium catalyst using protected [2-(hydroxymethyl)phenyl]dimethylsilanes. Cyclic silyl ether, 1,1-dimethyl-2-oxa-1-silaindan, also serves as a starting material for the alkenylsilanes by the ring-opening reaction with alkenyl Grignard reagents. The resulting alkenylsilanes undergo cross-coupling reaction with various aryl and alkenyl iodides under reaction conditions employing K₂CO₃ as a base at 35–50 °C in highly regio- and stereospecific manners. The reaction tolerates a diverse range of functional groups including silyl protections. The silicon residue is readily recovered and reused on a gram-scale synthesis. Intramolecular coordination of a proximal hydroxyl group is considered to efficiently form pentacoordinate silicates having a transferable group possibly at an axial position and, thus, responsible for the cross-coupling reaction under conditions significantly milder than those reported for the silicon-based reactions.     

Preparation and Characterization of Alkenyl Aryl Tetrafluoro‐λ6‐sulfanes

Substituted alkenyl aryl tetrafluoro‐λ⁶‐sulfanes have been prepared by the direct addition of readily accessible chlorotetrafluorosulfanyl arenes to primary alkynes. Substitution of an apical fluorine of the pentafluorosulfanyl group enables modulation of the reactivity of this little explored functional group while at the same time facilitating the direct investigation of aryl substituent effects on the aryl tetrafluorosulfanyl‐substituted products.     

MnI/AgI Relay Catalysis: Traceless Diazo‐Assisted C(sp2)–H/C(sp3)–H Coupling to β‐(Hetero)Aryl/Alkenyl Ketones

An unprecedented Mn^I/Ag^I‐relay‐catalyzed C(sp²)?H/C(sp³)?H coupling of (vinyl)arenes with α‐diazoketones is reported, wherein the diazo group was exploited as a traceless auxiliary for control of regioselectivity. Challenging β‐(hetero)aryl/alkenyl ketones were obtained through this operationally simple approach. The cascade process merges denitrogenation, carbene rearrangement, C?H activation, and hydroarylation/hydroalkenylation. The robustness of this method was demonstrated at preparative scale and applied to late‐stage diversification of natural products.     

Chemistry of metal hydrides : XXI. Insertion of acetylenes into palladium hydrides

trans-Pd(NO₃)H(PCy₃)₂ (I) when treated with Et₄NCl forms the hydride trans-PdClH(PCy₃)₂ which in turn reacts with AgPF₆ in acetonitrile to give trans-[PdH(CH₃CN)(PCy₃)₂]PF₆ (III). Both I and III react smoothly with acetylenes containing one electron-withdrawing group to give alkenyl products. The geometry of the resulting alkenyl ligand implies that cis addition has occurred and that the hydridic hydrogen adds to the acetylenic carbon containing the electron-withdrawing group.Acetylenes containing two electron-withdrawing groups give mixtures from which both alkenyl and zerovalent acetylene compounds can sometimes be isolated. In the presence of proton sponge, monosubstituted acetylenes still give alkenyl products while those substituted with two electron-withdrawing groups give the zerovalent products in good yield. The relevance of these results to an understanding of the nature of the migratory insertion reaction is discussed.