The cationic ruthenium-hydride complex [(η 6 -C 6 H 6 )(PCy 3 )(CO)RuH] + BF 4 − was found to be a highly regioselective catalyst for the oxidative C-H coupling reaction of aryl-substituted amides and unactivated alkenes to give ortho-alkenylamide products. The kinetic and spectroscopic analyses support a mechanism involving a rapid vinyl C-H activation followed by a rate-limiting C-C bond formation steps.

A short and scalable synthesis of naamidine A, a marine alkaloid with a selective ability to inhibit epidermal growth factor receptor (EGFR)-dependent cellular proliferation, has been achieved. A key achievement in this synthesis was the development of a regioselective hydroamination of a monoprotected propargylguanidine to deliver N3-protected cyclic ene-guanidines. This permits the extension of this methodology to prepare N2-Acyl analogues in a fashion that obviates the troublesome acylation of the free 2-aminoimidazoles, which typically yields mixtures of N2- and N2,N2-diacylated products.

Recent efforts in designing expeditious catalytic synthesis of tetrasubstituted olefins have in part been stimulated by growing needs for developing generally applicable methods for tamoxifen analogs (anti-breast cancer drug) as well as for photo-responsive organic materials and molecular devices.[1] A number of different catalytic methods have been developed to synthesize tetrasubstituted olefins, including: Suzuki-type Pd-catalyzed coupling reactions,[2] Ni- and Rh-catalyzed exocyclization methods,[3] Ni- and Pd-catalyzed nucleophilic coupling reactions of alkynes[4] and of alkyne-to-arylboronic acids,[5] Ti-catalyzed tandem alkyne-epoxide-ethyl acetate coupling,[6] and the ring-closing olefin metathesis by using Grubbs catalyst.[7] Though catalytic conjugate addition of alkenes has been recognized as a potentially powerful synthetic methodology in forming tetrasubstituted olefins, generally applicable conjugate addition of simple olefins to α,β-unsaturated carbonyl compounds has been hampered by lack of reactivity of the olefin substrates and due to the formation of homocoupling and other byproducts. Chelate-assisted C–H insertion[8] and cross coupling methods[9] are among the most notable advances in catalytic coupling reaction of enones with simple alkenes. Ni-catalyzed conjugate addition and allylic substitution reactions of simple alkenes have also been reported recently.[10] We recently discovered that the cationic complex [(C6H6)(CO)(PCy3)RuH]+BF4− (1) is a highly effective catalyst precursor for the coupling reactions of arylketones and alkenes involving C–H activation.[11] Herein we report a novel catalytic synthesis of tetrasubstituted olefins from the intermolecular conjugate addition reaction of simple olefins to α,β-unsaturated carbonyl compounds.

The cationic complex [(pymox-Me2)RuCl2] + BF4-was found to be a highly effective catalyst for the C-H bond oxidation reaction of arylalkanes in water. For example, the treatment of ethylbenzene (1.0 mmol) with t-BuOOH (3.0 mmol) and 1.0 mol % of the Ru catalyst in water (3 mL) cleanly produced PhCOCH3 at room temperature. Both a large kinetic isotope effect (kH/kD = 14) and a relatively large Hammett value (ρ = -1.1) suggest a solvent-caged oxygen rebounding mechanism via a Ru(IV)-oxo intermediate species.Aqueous phase homogeneous catalysis has emerged as an important tool for attaining new "green" chemical technology in both industrial and fine chemical processes.1 Particular attention has been centered on the development of water-soluble metal catalysts for the C-H bond oxidation reactions, and in this regard, late transition metal complexes with nitrogen ligands have been shown to be effective for mediating catalytic oxidation of saturated hydrocarbons in protic media.2 A number of chemoselective allylic and propargylic C-H bond oxidation and oxidative coupling reactions of amines have recently been achieved by using water-soluble dirhodium 3 and ruthenium 4 catalysts, respectively. Fukuzumi reported an efficient C-H bond oxidation of arylalkanes mediated by CAN/[Ru(tpa)(H2O)2] + system in aqueous media.5 Li and co-workers devised a number of oxidative coupling reactions involving C-H bond activation in water.6 Surfacemodified heterogeneous ruthenium-hydroxo catalysts have also been found to mediate selective oxidation of benzylamines to arylamides in water.7 Despite these recent advances, only a few well-defined synthetic metal catalysts have been shown to mediate aerobic C-H bond oxidation reactions in the aqueous phase, and considerable controversies still persist on the issues of reaction mechanisms and the nature of reactive species.As part of an on-going effort to develop ruthenium-catalyzed C-H bond activation reactions, 8 we initially screened several chelating nitrogen ligands to synthesize water-soluble ruthenium catalysts. Thus, the treatment of [(COD)RuCl2]x with 1.2 equivalents of 4,4-NOT THE PUBLISHED VERSION; this is the author's final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation at the bottom of the page.Organic Letters, Vol 11, No. 7 (April 2, 2009): pg. 1567-1569. DOI. This article is © American Chemical Society and permission has been granted for this version to appear in e-Publications@Marquette. American Chemical Society does not grant permission for this article to be further copied/distributed or hosted elsewhere without the express permission from American Chemical Society.3 dimethyl-2-(2-pyridyl)oxazoline (pymox-Me2) ligand in 1,2-dichloroethane at 50 °C produced an orange-yellow colored complex (pymox-Me2)Ru(COD)Cl2 (1), which was isolated in 65% yield after recrystallization in n-hexanes/CH2Cl2 (Scheme 1). The treatment of 1 (0.4 mmol) with pymox-Me2 (1.9 mmol) in 1,2-dichloroethane at 100 °C led to the isolation of ...

A cascade silver(I)-catalyzed hydroamination/Michael addition sequence has been developed to deliver highly substituted bicyclic guanidines. This transformation gives rise to geometrically and constitutionally stable ene–guanidines and generates a remote stereocenter with moderate to high diastereoselectivity.

The cationic ruthenium-hydride complex [(C6H6)(PCy3)(CO)RuH]+BF4− (1) was found to be a highly effective catalyst for the intermolecular conjugate addition of simple alkenes to α,β-unsaturated carbonyl compounds to give (Z)-selective tetrasubstituted olefin products. The analogous coupling reaction of cinnamides with electron-deficient olefins led to the oxidative coupling of two olefinic C–H bonds in forming (E)-selective diene products. The intramolecular version of the coupling reaction efficiently produced indene and bicyclic fulvene derivatives. The empirical rate law for the coupling reaction of ethyl cinnamate with propene was determined as: rate = k[1]1[propene]0[cinnamate]−1. A negligible deuterium kinetic isotope effect (kH/kD = 1.1±0.1) was measured from both (E)-C6H5CH=C(CH3)CONHCH3 and (E)-C6H5CD=C(CH3)CONHCH3 with styrene. In contrast, a significant normal isotope effect (kH/kD = 1.7±0.1) was observed from the reaction of (E)-C6H5CH=C(CH3)CONHCH3 with styrene and styrene-d10. A pronounced carbon isotope effect was measured from the coupling reaction of (E)-C6H5CH=CHCO2Et with propene (13C(recovered)/13C(virgin) at Cβ = 1.019(6)), while a negligible carbon isotope effect (13C(recovered)/13C(virgin) at Cβ = 0.999(4)) was obtained from the reaction of (E)-C6H5CH=C(CH3)CONHCH3 with styrene. Hammett plots from the correlation of para-substituted p-X-C6H4CH=CHCO2Et (X = OCH3, CH3, H, F, Cl, CO2Me, CF3) with propene and from the treatment of (E)-C6H5CH=CHCO2Et with a series of para-substituted styrenes p-Y-C6H4CH=CH2 (Y = OCH3, CH3, H, F, Cl, CF3) gave the positive slopes for both cases (ρ = +1.1±0.1 and +1.5±0.1, respectively). Eyring analysis of the coupling reaction led to the thermodynamic parameters, Δ H‡ = 20±2 kcal mol−1 and S‡ = −42±5 e.u. Two separate mechanistic pathways for the coupling reaction have been proposed on the basis of these kinetic and spectroscopic studies.

The intramolecular hydroamination of a guanidine on an eneyne unit affords a guanidine-substituted diene capable of reacting with dienophiles. These substrates undergo [4+2]-cycloaddition reactions to generate a series of complex cyclic- and spirocyclic-guanidines. Select substrates can further undergo a ring opening-elimination cascade that ultimately reveals a vinyl-2-aminoimidazole. As such this cascade reaction may find application in the synthesis of oroidin-type natural products and their analogues

No abstract