General asymmetric hydrogenation of 2-alkyl- and 2-aryl-substituted quinoxaline derivatives catalyzed by iridium-difluorphos: unusual halide effect and synthetic application.

A general asymmetric hydrogenation of a wide range of 2-alkyl- and 2-aryl-substituted quinoxaline derivatives catalyzed by an iridium-difluorphos complex has been developed. Under mild reaction conditions, the corresponding biologically relevant 2-substituted-1,2,3,4-tetrahydroquinoxaline units were obtained in high yields and good to excellent enantioselectivities up to 95%. With a catalyst ratio of S/C = 1000 and on a gram scale, the catalytic activity of the Ir-difluorphos complex was maintained showing its potential value. Finally, we demonstrated the application of our process in the synthesis of compound (S)-9, which is an inhibitor of cholesteryl ester transfer protein (CETP).

Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,ß-unsaturated ketones with DIFLUORPHOS and SYNPHOS analogues.

Applications of electron-deficient DIFLUORPHOS and SYNPHOS analogues in the rhodium-catalyzed asymmetric conjugate addition of boronic acids to α,ß-unsaturated ketones afford the 1,4-addition adducts in yields up to 92% and with 99% ee. Particularly, a Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to nonsubstituted maleimide substrates using the (R)-3,5-diCF(3)-SYNPHOS ligand is also reported. This protocol provides access to various enantioenriched 3-substituted succinimide units of biological interest, in high yields and good to excellent ee up to 93%, which could be upgraded up to 99% ee, after a single crystallization.

Efficient route to atropisomeric ligands--application to the synthesis of MeOBIPHEP analogues.

A highly efficient Pd-catalyzed P-C coupling reaction of easily accessible atropisomeric bisphosphane is described in the presence of various electron-poor aromatic iodides. The reactions are conducted in the presence of a Pd(II)/dppf catalyst in acetonitrile at 80 °C. The reaction conditions are compatible with several electron-withdrawing groups such as esters, cyano, chloro, and trifluoromethyl groups and lead to atropisomeric MeOBIPHEP derivatives in good to excellent yields and high enantiomeric purities.

(R)-3,5-diCF3-SYNPHOS and (R)-p-CF3-SYNPHOS, electron-poor diphosphines for efficient room temperature Rh-catalyzed asymmetric conjugate addition of arylboronic acids.

Two new atropisomeric electron-poor chiral diphosphine ligand analogues of SYNPHOS were prepared, and their electronic properties are described. These two ligands afforded high performance for the Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,ß-unsaturated carbonyl compounds at room temperature.

Ruthenium chloride as an efficient catalytic precursor for hydroarylation reactions via C-H bond activation.

A very simple and efficient catalytic system for the hydroarylation of olefins by aromatic ketones and Michael acceptors using simple and inexpensive ruthenium trichloride as a ruthenium source is described. These very mild conditions (dioxane at 80 degrees C) appeared to be highly compatible, tolerant, and selective toward various functional groups, and the ease of the protocol is highly convenient for synthetic purposes.

Rhodium-catalyzed functionalization of sterically hindered alkenes.

For the first time the rhodium-catalyzed 1,4-addition of organoboranes to hindered Baylis-Hillman adducts, trisubstituted alkenes, affording highly functionalized alkenes, via addition of the organoboranes and hydroxyelimination, is reported. Moreover, preliminary results have shown that, thanks to the use of a monosubstituted chiral diene ligand, enantio-enriched products were easily accessible, while chiral phosphane ligands were completely inappropriate in this reaction.

Room-temperature rhodium-catalyzed asymmetric 1,4-addition of potassium trifluoro(organo)borates.

For the first time the room-temperature rhodium-catalyzed asymmetric 1,4-addition of potassium aryltrifluoroborates to alpha,beta-unsaturated substrates is described. Thanks to the use of a chiral diene as ligand for rhodium and triethylamine as base, to facilitate transmetalation of the boron species, high yields and enantioselectivities were generally achieved. Moreover, the use of such tetravalent boron species offers some improvements compared to the use of boronic acids in term of stability and ease of purification.

C-C bond formation via C-H bond activation using an in situ-generated ruthenium catalyst.

We report here our full results concerning the possibility of generating in situ from a stable and readily available ruthenium(II) source a highly active ruthenium catalyst for C-H bond activation. The versatility of this catalytic system has been demonstrated, as it offers the possibility of modifying the electronic and steric properties of the catalyst by fine-tuning of the ligands, allowing functionalization of various substrates. Aromatic ketones and imines could be easily functionalized by the reaction with either vinylsilanes or styrenes, depending on the electronic and steric nature of the ligand. Moreover, variable-temperature NMR experiments and the isolation of a ruthenium intermediate complex provided some insights into the generation of the active catalytic ruthenium species in this reaction.

Rhodium-catalyzed formation of stereocontrolled trisubstituted alkenes from Baylis-Hillman adducts.

Efficient and general conditions for the formation of stereodefined trisubstituted alkenes by using the rhodium-catalyzed reaction of unactivated Baylis-Hillman adducts with either organoboronic acids or potassium trifluoro(organo)borates are reported (see scheme).We report here efficient and general conditions for the formation of stereodefined trisubstituted alkenes using the rhodium-catalyzed reaction of unactivated Baylis-Hillman adducts with either organoboronic acids and potassium trifluoro(organo)borates. The use of the [{Rh(cod)OH}(2)] precursor gave very fast coupling reactions under low catalyst loading, very mild reaction conditions (from room temperature up to 50 degrees C) and without the need of additional phosphane ligands. Based on the new reaction conditions, the reaction, originally limited to Baylis-Hillman adducts derived from esters, could be extended to a large variety of Baylis-Hillman adducts, bearing either keto, cyano or amido functionalities. Moreover, the reaction of Baylis-Hillman adducts bearing esters functionality was improved and could be conducted at lower temperature using lower catalyst loading.

Asymmetric Pauson-Khand-type reaction mediated by Rh(I) catalyst at ambient temperature.

An efficient asymmetric PKR mediated by Rh(I) catalyst at ambient temperature was developed. The reaction utilizing a Rh(I) catalyst bearing a (R)-3,5-diMeC4H4-BINAP ligand at 18-20 degrees C under a reduced partial pressure of CO (0.1 atm) provided PKR products in high chemical yield as well as high enantioselectivity.

Sterically hindered benzophenones via rhodium-catalyzed oxidative arylation of aldehydes.

Efficient cross-coupling, allowing a straightforward access to congested benzophenones, between aromatic aldehydes and potassium aryltrifluoroborates, is described in the presence of a rhodium/tri-tert-butylphosphane catalyst system and acetone as cosolvent. The use of the stable phosphonium salts of tri-tert-butylphosphane prevented the use of highly oxidizable tri-tert-butylphosphane and allowed a careful control of the stoichiometry with the rhodium.

Anti-Markovnikov hydroarylation of styrenes catalyzed by an in situ generated ruthenium complex.

An efficient and practical catalytic system for the anti-Markovnikov ruthenium-catalyzed hydroarylation of styrenes with acetophenone, allowing a straightforward access to bibenzyl backbones, is described for the first time: this process, involving regioselective C-H bond activation, is complementary to a Friedel-Crafts type reaction giving the branched adduct.

Heterogeneous gold catalysts for efficient access to functionalized lactones.

A novel class of heterogeneous gold catalysts supported on zeolite beta-NH4+ was prepared by the deposition-precipitation method. This new class of catalyst showed interesting catalytic activities for the intramolecular cycloisomerization of gamma-acetylenic carboxylic acids leading to functionalized gamma-alkylidene gamma-butyrolactones. Analysis of the supported gold species with in situ X-ray photoelectron spectroscopy (in situ XPS) suggests that cationic Au (possibly AuIII) can play an important role in such reactions. The high discrepancy in catalyst stability in favor of the Au supported on the zeolite system over bulk Au2O3 is explained by 1) the size of the particles and 2) the reversibility of the redox deactivating process (AuIII-->AuI) in the presence of oxygen for the supported system. The efficiency of this system allowed reaction under mild heterogeneous conditions. The potential for catalyst recycling was also highlighted.

Ruthenium-SYNPHOS-catalyzed asymmetric hydrogenations: an entry to highly stereoselective synthesis of the C15-C30 subunit of dolabelide A.

An efficient construction of the C15-C30 segment of the cytotoxic macrolide dolabelide A is described. The synthesis relies on ruthenium-SYNPHOS-mediated asymmetric hydrogenation reactions of beta-keto esters to generate the C19, C21, and C27 hydroxyl-bearing stereocenters with very high levels of enantio- and diastereoselectivity.

Cycloisomerization of 1,n-enynes: challenging metal-catalyzed rearrangements and mechanistic insights.

Metal-catalyzed cycloisomerization reactions of 1,n-enynes have appeared as conceptually and chemically highly attractive processes as they contribute to the highly demanded search for atom economy and allow the discovery of new reactions. Since the pioneering studies with palladium by the research group of Barry Trost in the mid-1980s, several other metals have been identified as excellent catalysts for the rearrangement of enyne skeletons. Moreover, the behavior of 1,n-enynes may be influenced by other functional groups such as alcohols, aldehydes, ethers, alkenes, or alkynes, thus enhancing the molecular complexity of the synthesized products. Apart from the intrinsic rearrangements of 1,n-enynes, several tandem reactions incorporating intramolecular trapping agents or intermolecular partners have been discovered. This Review aims to highlight the main contributions in this field of catalysis and to propose and comment on the mechanistic insights of the recent discoveries.