Showing papers on "Substituent published in 2005"

1,2,3-triazole as a peptide surrogate in the rapid synthesis of HIV-1 protease inhibitors.

Abstract: Given the ubiquitous nature of the peptide linkage in biological molecules, replacement of the amide bond with isosteres in potential drug candidates has been a continual goal of many laboratories. Successful replacements will provide improved stability, lipophilicity, and absorption. Many surrogates have been introduced already, yet the synthesis of many of these isosteres in a combinatorial way is difficult and requires several steps. Thus, the discovery of new peptide surrogates with easier syntheses is an important achievement that could open new opportunities for the study of amide-containing molecules and the development of inhibitors with novel physicochemical properties. We have used the copper(i)-catalyzed azide–alkyne [3+2] cycloaddition as a straightforward reaction for the preparation of inhibitor libraries. Over 100 compounds were synthesized in microtiter plates and screened in situ. Two of these compounds—AB2 (pdb-1zp8) and AB3 (pdb-1zpA)—showed the best activity against wild type and mutant HIV-1 proteases (Table 1). AB2 and AB3, were then computationally docked by using AutoDock3. The docking simulation produced two conformations of approximately equal energy. One conformation placed the triazole in the position normally adopted by the peptide unit—between P2’ and P1’—in peptidomimetic compounds. Furthermore, the central nitrogen of the triazole was perfectly positioned to form a hydrogen bond with the water molecule normally found under the protease flaps. This water molecule also formed a hydrogen bond with the sulfonamide as seen in the crystallographic structure of amprenavir when bound to HIV-1 protease. The other conformation positioned the compounds in a similar place, but with the triazole rotated by 180 8. This allowed for a slightly better fit of the triazole substituent but sacrificed the hydrogen bond with the water molecule. In this work we have solved the ambiguity in binding conformation by solving the crystal structure of two inhibitors derived from a library of triazole compounds with HIV-1 protease. Interestingly, the two structures show that the triazole ring is an effective amide surrogate that retains all hydrogen bonds in the active site (Figure 1). HIV-1 protease (3 mgmL 1 in 0.025m sodium acetate pH 5.4, 10 mm dithiothreitol, 1 mm EDTA) was combined with inhibitor (32 mm in 50% (v/v) dimethylsulfoxide and 2-methylpentane2,4-diol) at 4 8C to give a 2:1 molar ratio of inhibitor to protein, and the mixture was centrifuged to remove the precipitate. The complex was crystallized by the hanging-drop vapor-diffusion method by mixing 9.6 mL of protease solution with 4 mL of crystallization buffer (1.34m ammonium sulfate, 0.1m sodium acetate, pH 4.8–5.4). Plates were sealed at 20 8C for one to two weeks. Data were collected from frozen crystals at the Argonne National Laboratory SER-CAT beamline 22-ID and with a Rigaku Table 1. Binding constants of 1,2,3-triazole compounds to HIV-1 protease.

Ab Initio Study of the Complexes of Halogen‐Containing Molecules RX (X=Cl, Br, and I) and NH3: Towards Understanding the Nature of Halogen Bonding and the Electron‐Accepting Propensities of Covalently Bonded Halogen Atoms

Abstract: Ab initio calculations have been performed on a series of complexes formed between halogen-containing molecules and ammonia to gain a deeper insight into the nature of halogen bonding. It appears that the dihalogen molecules form the strongest halogen-bonded complexes with ammonia, followed by HOX; the charge-transfer-type contribution has been demonstrated to dominate the halogen bonding in these complexes. For the complexes involving carbon-bound halogen molecules, our calculations clearly indicate that electrostatic interactions are mainly responsible for their binding energies. Whereas the halogen-bond strength is significantly enhanced by progressive fluorine substitution, the substitution of a hydrogen atom by a methyl group in the CH3X⋅⋅⋅NH3 complex weakened the halogen bonding. Moreover, remote substituent effects have also been noted in the complexes of halobenzenes with different para substituents. The influence of the hybridization state of the carbon atom bonded to the halogen atom has also been examined and the results reveal that halogen-bond strengths decrease in the order HCCX>H2CCHX≈OCHX≈C6H5X>CH3X. In addition, several excellent linear correlations have been established between the interaction energies and both the amount of charge transfer and the electrostatic potentials corresponding to an electron density of 0.002 au along the RX axis; these correlations provide good models with which to evaluate the electron-accepting abilities of the covalently bonded halogen atoms. Finally, some positively charged halogen-bonded systems have been investigated and the effect of the charge has been discussed.

Photophysical and electrochemical properties of 1,7-diaryl-substituted perylene diimides.

Abstract: Substituent effects on the photophysical and electrochemical properties of 1,7-diaryl-substituted perylene diimides (1,7-Ar2PDIs) have been carefully explored. Progressive red-shifts of the absorption and emission maxima were observed when the electron-donating ability of these substituents was increased. Linear Hammett correlations of 1/λmax versus σ+ were observed in both spectral analyses. The positive slopes of the Hammett plots suggested that the electronic transitions carry certain amounts of photoinduced intramolecular charge-transfer (PICT) character from the aryl substituents to the perylene diimide core which leads to the reduction of the electron density on the substituents. The substituent electronic effects originated mainly from the perturbation of the core PDI HOMO energy level by the substituents. This conclusion was supported by PM3 analyses and confirmed by cyclic voltammetry experiments. More interestingly, the Ph2NC6H4-substituted PDI, 4i, showed an unusual dual-band absorption that sp...

Cationic chalcone antibiotics. Design, synthesis, and mechanism of action.

Abstract: This paper describes how the introduction of “cationic” aliphatic amino groups in the chalcone scaffold results in potent antibacterial compounds. It is shown that the most favorable position for the aliphatic amino group is the 2-position of the B-ring, in particular in combination with a lipophilic substituent in the 5-position of the B-ring. We demonstrate that the compounds act by unselective disruption of cell membranes. Introduction of an additional aliphatic amino group in the A-ring results in compounds that are selective for bacterial membranes combined with a high antibacterial activity against both Gram-positive and -negative pathogens. The most potent compound in this study (78) has an MIC value of 2 μM against methicillin resistant Staphylococus aureus.

Catalytic Asymmetric Staudinger Reactions to Form β-Lactams: An Unanticipated Dependence of Diastereoselectivity on the Choice of the Nitrogen Substituent

Abstract: There are relatively few methods for the catalytic asymmetric synthesis of β-lactams, and those that have been reported are generally cis selective. This communication describes the first catalytic enantioselective Staudinger reactions that preferentially furnish trans β-lactams (trans = relationship of Ph to R1). The key to this method is the use of an N-triflyl protecting group for the imine. Along with serving as interesting targets in their own right, N-triflyl β-lactams readily react with nucleophiles to generate useful families of compounds, such as γ-amino alcohols and β-amino acids.

A Simple Iridium Catalyst with a Single Resolved Stereocenter for Enantioselective Allylic Amination. Catalyst Selection from Mechanistic Analysis

Abstract: A study of the relationship between the stereochemical elements of a phosphoramidite ligand and the stereoselectivity of iridium-catalyzed amination of allylic carbonates is reported. During catalyst activation, a complex of a phosphoramidite ligand possessing one axial chiral binaphtholate group and two resolved phenethyl substituents converts to a more reactive cyclometalated complex containing one distal chiral substituent at nitrogen, one substituent that becomes part of the metalacycle, and one unperturbed binaphtholate group. Systematic changes were made to the different stereochemical elements. Replacement of the distal chiral phenethyl substituent with a large achiral cycloalkyl group led to a catalyst that reacts with rates and enantioselectivities that are similar to those of the original catalyst with the phenethyl group. Studies of the reactions of diastereomeric ligands containing (R) or (S) binaphtholate groups on phosphorus, along with one (R)-phenethyl and one achiral cyclododecyl group on...

Substituent Effects on Redox Potentials and Optical Gap Energies of Molecule-like Au38(SPhX)24 Nanoparticles

Abstract: A molecule-like substituent effect on redox formal potentials in the nanoparticle series Au38(SPhX)24 has been discovered. Electron-withdrawing “X” substituents energetically favor reduction and disfavor oxidation, and give formal potentials that correlate with Hammett substituent constants. The ligand monolayer of the nanoparticles is shown, thereby, to play a strong role in determining electronic energies of the nanoparticle core and is more than simply a protecting or capping layer. The substituent effect does not, however, detectably change the HOMO−LUMO gap energy, being identical for the HOMO and LUMO levels and presumably inductive in nature.

Heteroatom‐Facilitated Lithiations

Abstract: Some 25 years have elapsed since the topic of metalation reactions was reviewed by Gilman and Morton. The intervening years have been notable for intensive explorations in this area, in part because many organolithium reagents are now commercially available. Specifically, research efforts have been characterized by the discovery of new functional groups that promote metalation, elaboration of novel heterocyclic and olefinic substrates as metalatable species, recognition of new types of lithiating agents, and the continuation of efforts to define accurately the mechanism of metalation. Accordingly, heteroatom-facilitated lithiation has become recognized as an increasingly important tool, not only in the elaboration of carbocyclic aromatic and heteroaromatic systems, but also in synthetic aliphatic chemistry. A few recent reviews have covered the topic in a more limited or less specific sense. It is the purpose of this chapter to survey and classify the vast accumulation of heteroatom-facilitated lithiations recorded since the first coverage in Organic Reactions. As outlined by Gilman and Morton, the terms “metalation” in general and “lithiation” in particular denote any replacement of a hydrogen atom by metal or lithium. In this review, however, lithiation is defined as the exchange of a hydrogen atom attached to an sp2-hybridized carbon atom by lithium to form a covalent lithium-carbon bond. More specifically, discussion is limited to those metalations that, through the influence of a heteroatom, are characterized by rate enhancement and regioselectivity. In fact, lithiation reactions of this type are noted for an extraordinarily high degree of regioselectivity, metalation generally occurring on the sp2-carbon atom closest to the heteroatom. Based on the relative position of the heteroatom, such lithiations are conveniently classified into two principal categories: alpha and beta (ortho) lithiations. In alpha lithiations the metalating agent deprotonates the sp2-carbon atom alpha to the heteroatom to form a carbonlithium bond. This sp2-carbon atom may be part of an olefinic or heteroaromatic π system. In beta lithiations the metalating agent is directed to deprotonate the sp2-carbon atom beta to the heteroatom-containing substituent. The sp2-carbon atom can be part of an aromatic or an olefinic π system. It should be noted that the designation “ortho metalation” is used specifically for the beta metalation of carbocyclic aromatic systems. This chapter surveys all systems in which alpha and beta lithiations have been observed, with the exception of ferrocenes. Keywords: lithiations; alpha lithiations; beta lithiations; scope; limitations; alpha activating atom; oxygen; sulfur; nitrogen; selenium; tellurium; halogens; beta-directing atom; substrates; enamines; vinyl isocyanides; formamides; pyrroles; indoles; pyrazoles; imidazoles; triazoles; tetrazoles; alkyl vinyl ethers; pyrazoles; pyridines; pyrimidines; furans; oxazolines; oxazoles; sulfides; sulfoxides; thiophenes; electron-withdrawing groups; vinyl halogens; amines; ethers; sulfones; amides; alcohols; ketones; experimental procedures

Organoboron compounds with an 8-hydroxyquinolato chelate and its derivatives: substituent effects on structures and luminescence.

Abstract: Four new luminescent organoboron complexes have been synthesized and fully characterized. These compounds are four-coordinate boron chelated by either 8-hydroxyquinolato (q) or functionalized 8-hydroxylquinolato ligands, including BPh2(5-(1-naphthyl)-q) (1), BPh2(5-(2-benzothienyl)-q) (2), B(2-benzothienyl)2q (3), and B(2-benzothienyl)2(2-Me-q) (4). All four compounds have a tetrahedral geometry as established by X-ray diffraction analyses. In solution, compounds 1-4 have an emission maximum at 534, 565, 501, and 496 nm, respectively, at room temperature. They emit similar colors in the solid states without red shifts of the emission band due to the lack of significant intermolecular interactions in the crystal lattices. The substituent group at C5 or C2 position of the 8-hydroxyquinolato ligand has been observed to have a significant impact on the emission energy and the emission quantum efficiency of the boron complexes. Molecular orbital calculations (Gaussian 98) showed that the electronic transition of 1 and 2 is a pi-pi* transition centered on the functionalized 8-hydroxyquinolato group and the electronic transition of 3 and 4 is an interligand charge transfer from the 2-benzothienyl ligand to the hydroxyquinolato ring. A double-layer electroluminescent device using 3 as the emitter has been fabricated, which produced a broad emission band with a significant contribution of exciplex emission.

Aqueous interfaces with hydrophobic room-temperature ionic liquids: a molecular dynamics study.

Abstract: We report a molecular dynamics study of the interface between water and (macroscopically) water-immiscible room-temperature ionic liquids "ILs", composed of PF6(-) anions and butyl- versus octyl-substituted methylimidazolium+ cations (noted BMI+ and OMI+). Because the parameters used to simulate the pure ILs were found to exaggerate the water/IL mixing, they have been modified by scaling down the atomic charges, leading to better agreement with the experiment. The comparison of [OMI][PF6] versus [BMI][PF6] ILs demonstrates the importance of the N-alkyl substituent on the extent of solvent mixing and on the nature of the interface. With the most hydrophobic [OMI][PF6] liquid, the "bulk" IL phase is dryer than with the [BMI][PF6] liquid. At the interface, the OMI+ cations retain direct contacts with the bulk IL, whereas the more hydrophilic PF6(-) anions gradually dilute in the local water micro-environment and are thus isolated from the "bulk" IL. The interfacial OMI+ cations are ordered with their imidazolium moiety pointing toward the aqueous side and their octyl chains toward the IL side of the interface. With the [BMI][PF6] liquid, the system gradually evolves from an IL-rich to a water-rich medium, leading to an ill-defined interfacial domain with high intersolvent mixing. As a result, the BMI+ cations are isotropically oriented "at the interface". Because the imidazolium cations are more hydrophobic than the PF6(-) anions, the charge distribution at the interface is heterogeneous, leading to a positive electrostatic potential at the interface with the two studied ILs. Mixing-demixing simulations on [BMI][PF6]/water mixtures are also reported, comparing Ewald versus reaction field treatments of electrostatics. Phase separation is very slow (at least 30 ns), in marked contrast with mixtures involving classical organic liquids, which separate in less than 0.5 ns at the microscopic level. The results allow us to better understand the specificity of the aqueous interfaces with hydrophobic ionic liquids, compared with classical organic solvents, which has important implications as far as the mechanism of liquid-liquid ion extraction is concerned.

Arylation Reactions: The Photo-SN1 Path via Phenyl Cation as an Alternative to Metal Catalysis

Abstract: Photo(sensitized) cleavage of benzenediazonium salts as well as, when an electron-donating substituent is present, of aryl chlorides, fluorides, mesylates, triflates, and phosphates leads to the corresponding phenyl cations in the triplet state. These otherwise unavailable intermediates add selectively to alkenes, alkynes, and (hetero)arenes, giving arylation products in a good yield. The reactions are photochemical alternatives of metal-catalyzed Heck and cross-coupling reactions and bear some mechanistic analogy with them.

Theoretical studies of stereoselectivities of intramolecular aldol cyclizations catalyzed by amino acids.

Abstract: The effects of different amino acid catalysts and substrate substituents on the stereoselectivity of the title reactions have been studied with the aid of density functional theory methods. Experimental data available in the literature have been compiled. B3LYP/6-31G(d) calculations match the general experimental trends and provide useful insights into the origins of the variations in stereoselectivities. Acyclic primary amino acids allow a greater conformational flexibility in the aldol transition states compared with proline. This makes them poorer enantioselective catalysts with triketone substrates with a methyl ketone side chain. The steric repulsion upon substitution at the terminal methyl group increases the energy difference between anti- and syn-chairs with primary amino acid catalysts and, consequently, the stereoselectivities. Proline, in contrast, is a poor catalyst for the latter reactions because the substituent's steric bulkiness raises the activation energy of the favored C−C bond-forming ...

Toward high-yielding supramolecular synthesis: Directed assembly of ditopic imidazoles/benzimidazoles and dicarboxylic acids into cocrystals via selective O-H...N hydrogen bonds

Abstract: The supramolecular reactions between symmetric ditopic imidazoles/benzimidazoles and a variety of aliphatic and aromatic dicarboxylic acids produced molecular cocrystals 1−8 in high yields. Despite variations in molecular shape and substituent groups on the ditopic bases, each structure contained infinite 1-D molecular chains held together by robust, primary O−H···N hydrogen bonds. Secondary C−H···O interactions existed within these motifs as well as between neighboring chains, and it seems that intra- and interchain interactions are of equal structural importance based upon an analysis of the metrics displayed by each set of interactions. This study demonstrates that neutral hydrogen-bond interactions between imidazole/benzimidazoles (acting as the acceptor sites) and carboxylic acids (acting as the donor sites) provide sufficient driving force for the directed assembly of a wide range of binary cocrystals.

Substituent effect of the coordinated pyridine in a series of pyrazolato bridged dinuclear diiron(II) complexes on the spin-crossover behavior

Abstract: Two series of pyrazolato bridged dinuclear NCS and NCBH3 diiron(II) complexes with various types of 3- or 4-substituted pyridines, [{Fe(NCS or NCBH3)(X-py)}2(mu-bpypz)2], were prepared and their variable-temperature magnetic susceptibilities were measured. There were found linear correlations of the spin-crossover temperatures Tc not only between the NCS and NCBH3 complexes with the corresponding substituted pyridines, but also between the Tc and the Hammett constants, supporting the electronic substituent effect of the coordinated pyridine rather than a steric effect. The ligand field and the interelectronic repulsion parameters together with the thermodynamic data and/or cooperativity factor were discussed in relation with their spin-crossover behavior.

A cobalt(III)-salen complex with an axial substituent in the diamine backbone: stereoselective recognition of amino alcohols.

Abstract: A cobalt(III)−salen complex (3) with an axial substituent on the diamine backbone has been synthesized. Crystal structure reveals that the axial substituent (p-nitrophenyl group) is positioned in close proximity to the metal binding site. The stereoselectivity of the cobalt complex for binding amino alcohols increases with increasing steric bulk of the amino alcohol from alaninol (2.9) to valinol (6.2) and t-leucinol (36.0).

Compound having s1p receptor binding potency and use thereof

Abstract: Compounds of the general formula (I); their salts, N-oxides and solvates; prodrugs thereof; and medicines comprising these. (I) [wherein each of the ring A and ring D is a substituted or unsubstituted cyclic group; each of E and G is a bonding group or a spacer whose main chain has 1 to 8 atoms; L is a hydrogen atom or substituent; X is a substituted or unsubstituted amino or substituted or unsubstituted heterocycle containing at least one nitrogen atom; and n is 0 to 3 with the proviso that when n is =2, multiple rings A may be identical with or different from each other]. The compounds of the general formula (I) have S1P receptor (especially EDG-1 and/or EDG-6) binding potency and are useful in the prevention and/or therapy for transplant rejection, autoimmune diseases, allergic disorders, etc.

Synthesis of Isocoumarins and α-Pyrones via Tandem Stille Reaction/Heterocyclization

Abstract: A general route to α-pyrones and 3-substituted isocoumarins from (Z)-iodovinylic acids 1a−f or 2-iodobenzoic acids 4a−c is described, including compounds bearing a substituent on the aromatic ring. Treatment of (Z)-β-iodovinylic acids 1a−f or 2-iodobenzoic acids 4a−c with various allenyltributyltin reagents in the presence of palladium acetate, triphenylphosphine, and tetrabutylammonium bromide in dimethylformamide provided good yields of the corresponding α-pyrones 3a−k or 3-substituted isocoumarins 5a−g via tandem Stille reaction and 6-endo-dig oxacyclization.

3-(dihydro(tetrahydro)isoquinolin-1-yl)quinolines

Abstract: A compound is provided which is useful as an active ingredient of an agricultural chemical having superior antimicrobial activity against various plant diseases and capable of controlling rice blast and so on at a low dose. A compound or salt thereof represented by the following general formula: (wherein, R 1 and R 2 represent a C 1 -C 6 alkyl group, aryl group, heteroaryl group, aralkyl group or R 1 and R 2 together represent a C 3 -C 10 cycloalkyl group, R 3 and R 4 represent a hydrogen atom, a C 1 -C 6 alkyl group or R 3 and R 4 together represent a C 3 -C 10 cycloalkyl group, R 5 represents a hydrogen atom, C 1 -C 6 alkyl group or acyl group, X represents a halogen atom, a C 1 -C 6 alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, aryl group, heteroaryl group, C 1 -C 6 alkoxy group, amino group, acyl group, cyano group or N-hydroxyalkaneimidoyl group, Y represents a substituent selected from the group consisting of a halogen atom, C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group and hydroxyl group, n represents an integer of 0 to 4, and m represents an integer of 0 to 6).

Catalytic [4+1] Cycloaddition of α,β-Unsaturated Carbonyl Compounds with Isocyanides

Abstract: The GaCl(3)-catalyzed [4+1] cycloaddition reactions of alpha,beta-unsaturated ketones with isocyanides leading to lactone derivatives are described. While some other Lewis acids also show catalytic activity, GaCl(3) was the most efficient catalyst. The reaction is significantly affected by the structure of both the isocyanides and the alpha,beta-unsaturated ketones. Aromatic isocyanides, especially sterically demanding ones and those bearing an electron-withdrawing group, can be used, but aliphatic isocyanides cannot. The bulkiness of substituents at the beta-position of acyclic alpha,beta-unsaturated ketones is an important factor for the reaction to proceed efficiently. Generally, the more the bulky substituent, the higher is the yield. The reaction of alpha,beta-unsaturated ketones bearing geminal substituents at the beta-position gave the corresponding products in high yields. In monosubstituted derivatives, the yields are relatively low. However, substrates having a bulky substituent, such as a tert-Bu group, at the beta-position give high yields. Bulkiness is also required in cyclic alpha,beta-unsaturated ketones, but the effect is small. In alkyl vinyl ketones, the reactivity decreased with the steric bulk of the alkyl group. In aryl vinyl ketones, the presence of an electron-donating group on the aromatic ring decreases the reactivity. The success of the catalysis can be attributed to the low affinity of GaCl(3) toward heteroatoms, compared with usual Lewis acids.

Evaluation of substituent effects on activity and enantioselectivity in the enzymatic reduction of aryl ketones

Abstract: The enzymatic reduction of a series of substituted aryl ketones catalyzed by 24 isolated recombinant ketoreductases was studied and the substituent effects on activity and enantioselectivity were evaluated. When comparing p- and m-substituted acetophenones, the substituent significantly affects the activity of some of the tested ketoreductases, while it has little effect on the activity of other ketoreductases. Most of the tested ketoreductases were highly enantioselective in the reduction of these aryl ketones. The electronic properties, steric factors, and the ability to form a hydrogen bond to the substituents at the ortho-position play a significant role in determining both the activity and enantioselectivity of the ketoreductase-catalyzed reductions. From an applicability point of view, both enantiomers of the product aryl alcohols could be prepared via reduction catalyzed by one or more of the ketoreductases in most cases.

Sulfur K-edge XAS and DFT Calculations on P450 Model Complexes: Effects of Hydrogen Bonding on Electronic Structure and Redox Potentials

Abstract: Hydrogen bonding (H-bonding) is generally thought to play an important role in tuning the electronic structure and reactivity of metal−sulfur sites in proteins. To develop a quantitative understanding of this effect, S K-edge X-ray absorption spectroscopy (XAS) has been employed to directly probe ligand−metal bond covalency, where it has been found that protein active sites are significantly less covalent than their related model complexes. Sulfur K-edge XAS data are reported here on a series of P450 model complexes with increasing H-bonding to the ligated thiolate from its substituent. The XAS spectroscopic results show a dramatic decrease in preedge intensity. DFT calculations reproduce these effects and show that the observed changes are in fact solely due to H-bonding and not from the inductive effect of the substituent on the thiolate. These calculations also indicate that the H-bonding interaction in these systems is mainly dipolar in nature. The −2.5 kcal/mol energy of the H-bonding interaction was...

Fast and regioselective Heck couplings with N-acyl-N-vinylamine derivatives.

Abstract: Highly regioselective Heck couplings of aryl triflates with N-acyl-N-vinylamines lacking an N-alkyl substituent were achieved with reaction times of approximately 1 h in yields ranging from 62 to 98% using 1.5 mol % of Pd2(dba)3, 3 mol % of DPPF, and diethylisopropylamine in dioxane. The efficiency of these cross-couplings were studied with several N-vinylamides and an example each of an N-vinylcarbamate and an N-vinylurea. The Heck coupling products easily underwent acidic hydrolysis to the corresponding aryl methyl ketone or in situ hydrogenation in the presence of (Ph3P)3RhCl under a hydrogen atmosphere to provide the N-acyl derivatives of pharmaceutically relevant benzylic amines. The coupling of a vinyl triflate and more interestingly a vinyl tosylate to N-vinyl acetamide was also studied affording a 2-acylamino-1,3-butadiene with the same high regioselectivity in preference for the α-isomer. This result suggests that Heck couplings of electron-rich alkenes with vinyl tosylates also follow a cationic...