Hydroarylation Of Alkenes Research Articles

Addition of heterocycles to electron deficient olefins and alkynes catalyzed by gold(III)

A gold(III)-catalyzed hydroarylation of different olefins is reported here. AuCl 3 works as an excellent catalyst to mediate reactions between various heterocycles and electron deficient olefins and alkynes under mild conditions. This gold(III)-based method tolerates different functional groups such as aldehyde, carboxylic acid, nitrile, and is highly efficient. We have shown that some of these reactions complete in minutes at room temperature.

Trifluoroacetic Acid-Mediated Hydroarylation: Synthesis of Dihydrocoumarins and Dihydroquinolones

[reaction: see text] Trifluoroacetic acid mediates the hydroarylation of alkenes to afford dihydrocoumarins and dihydroquinolones in good yield. Intermolecular hydroarylation of cinnamic acids by phenols is particularly facile, which leads to the conclusion that previous reports of palladium-catalyzed hydroarylation of cinnamic acids in trifluoroacetic acid are erroneous.

Mechanistic analysis of hydroarylation catalysts.

Recently, two organometallic systems ([Ir(micro-acac-O)(acac-O,O)(acac-C(3))](2) and (Tp)Ru(CO)(Ph)(NCCH(3))) have been discovered that catalyze hydroarylation of unactivated olefins. Herein, we use density functional theory (B3LYP) to study the factors underlying this class of catalysts. In addition, we calculate the key steps for Rh, Pd, Os, and Pt with similar ligand sets. We previously showed there to be two key steps in the process: (i) insertion of a phenyl into the pi bond of a coordinating olefin, and (ii) C-H activation/hydrogen transfer of an unactivated benzene. An important discovery in these studies is that the barriers for these two steps are inversely correlated, complicating optimization of the overall process. However, herein we elucidate the causes of this inverse correlation, laying the foundation for the rational design of improved catalysts. Both steps are directly influenced by the accessibility of the higher 2-electron oxidation state, M(n) --> M(n+2). Systems with an easily accessible M(n+2) state activate C-H bonds easily but suffer from high energy insertions due to significant back-bonding. Conversely, systems without an easily accessible M(n+2) state have no debilitating back-bonding which makes insertion steps facile, but cannot effectively activate the C-H bond (leading instead to polymerization). The relationship between accessibility of the M(n+2) state and the amount of back-bonding in the coordinating olefin can be visualized by inspecting the hybridization of the coordinating olefin. Furthermore, we find a linear relation between this hybridization and the barrier to insertion. On the basis of these concepts, we suggest some modifications of the sigma framework expected to improve the rates beyond this linear correlation.

Synthesis and Structural Characterization of Novel Organometallic, Rh(III), Bis(acetylacetonate) Complexes

Recently, we reported the first catalytic, intermolecular, anti-Markovnikov, hydroarylation of unactivated olefins by a homogeneous, bis-chelating, O-donor Ir(III) complex,1 (acac)2Ir(R)(L), based on the simplest β-diketonate, acetylacetonate, acac. With the ultimate objective of designing more active catalysts for this potentially useful reaction by structure−function studies, we embarked on developing a rational synthesis of the bis-acac Rh(III) organometallic analogues to the Ir complex. While many tris-acac, late transition metal complexes are known, no rational syntheses of bis-acac, organometallic analogues have been reported. Herein, we report the synthesis and full characterization of the organometallic complex (acac)2Rh(Ph)(CH3OH), III, and related analogues. These complexes have all been found to be air and water stable.

Synthetic Applications of Palladium‐Catalyzed Hydroarylation and Related Systems

Synthetic organic chemists have recognized the hydroarylation of alkynes and alkenes as a versatile methodology. In the first part of this review, the regio- and stereochemistry of the hydroarylation of alkynes and the synthetic applications of this reaction in the synthesis of antiviral agents and steroid derivatives will be discussed. In the second part, applications of the hydroarylation of alkenes in the syntheses of epibatidine analogs, argemonine, retinoid X receptor (RXR), retinoic acid receptor (RAR) modulators and neurokinin (NK) receptor NK1 antagonists will be discussed. Emphasis will be placed on the application of Pd-catalyzed hydroarylation to the synthesis of biologically active compounds.

Mechanism of Ru(II)-catalyzed olefin insertion and C-H activation from quantum chemical studies.

The mechanism of catalytic hydroarylation of olefins by the homogeneous Ru(Tp)(CO)(Ph)(NCCH3) catalyst recently reported by Gunnoe et al. is characterized using quantum mechanics (density functional theory). The catalytic cycle features two key steps, 1,2-olefin insertion and C-H activation via an unusual mechanism, oxidative hydrogen migration. We find that these two key steps are competitive and that improving the rate of one step is detrimental to the rate of the other. The Ru catalyst has better balance and consequently higher activity than the previously explored Ir-based system.

Mechanism of homogeneous Ir(III) catalyzed regioselective arylation of olefins.

The mechanism of hydroarylation of olefins by a homogeneous Ph-Ir(acac)(2)(L) catalyst is elucidated by first principles quantum mechanical methods (DFT), with particular emphasis on activation of the catalyst, catalytic cycle, and interpretation of experimental observations. On the basis of this mechanism, we suggest new catalysts expected to have improved activity. Initiation of the catalyst from the inert trans-form into the active cis-form occurs through a dissociative pathway with a calculated DeltaH(0 K)() = 35.1 kcal/mol and DeltaG(298 K)() = 26.1 kcal/mol. The catalytic cycle features two key steps, 1,2-olefin insertion and C-H activation via a novel mechanism, oxidative hydrogen migration. The olefin insertion is found to be rate determining, with a calculated DeltaH(0 K)() = 27.0 kcal/mol and DeltaG(298 K)() = 29.3 kcal/mol. The activation energy increases with increased electron density on the coordinating olefin, as well as increased electron-donating character in the ligand system. The regioselectivity is shown to depend on the electronic and steric characteristics of the olefin, with steric bulk and electron withdrawing character favoring linear product formation. Activation of the C-H bond occurs in a concerted fashion through a novel transition structure best described as an oxidative hydrogen migration. The character of the transition structure is seven coordinate Ir(V), with a full bond formed between the migrating hydrogen and iridium. Several experimental observations are investigated and explained: (a) The nature of L influences the rate of the reaction through a ground-state effect. (b) The lack of beta-hydride products is due to kinetic factors, although beta-hydride elimination is calculated to be facile, all further reactions are kinetically inaccessible. (c) Inhibition by excess olefin is caused by competitive binding of olefin and aryl starting materials during the catalytic cycle in a statistical fashion. On the basis of this insertion-oxidative hydrogen transfer mechanism we suggest that electron-withdrawing substituents on the acac ligands, such as trifluoromethyl groups, are good modifications for catalysts with higher activity.

Novel bis-acac-O,O-Ir(III) catalyst for anti-Markovnikov, hydroarylation of olefins operates by arene CH activation.

A novel, thermally stable, homogeneous Ir catalyst for the anti-Markovnikov, hydroarylation of olefins is shown to operate by arene CH activation via the formation of a bisacac-O,O phenyl-Ir(III) species.

Stereocontrolled syntheses of epimeric 3-aryl-6-phenyl-1-oxa-7-azaspiro(4.5)decane NK-1 receptor antagonist precursors.

[structure: see text]. Complementary stereoselective syntheses of individual C3 epimers of the NK-1 receptor antagonist precursor 1 have been developed. Both diastereomers were derived from the common intermediate 3; introduction of the 3S stereocenter in 1a was achieved through hydrogenation of an arylated dihydrofuran, whereas the corresponding stereogenic center in 1b was installed using a stereo- and regioselective alkene hydroarylation.