Palladium-Catalyzed C-H Functionalization and Flame-Retardant Properties of Isophosphinolines.

C-H activation is a powerful strategy for forming C-C bonds without the need for prefunctionalization. In this paper, we present a general, direct, and regioselective palladium-catalyzed functionalization of a phosphorus heterocycle, 2-phenyl-1-isophosphinoline 2-oxide. The mild reaction conditions enabled the introduction of various functionalized alkenes.

Ru(II)-Catalyzed Enantioselective Transfer Hydrogenation of α-Ketophosphonates: Straightforward Access to Valuable Chiral α-Hydroxy Phosphonates.

Asymmetric transfer hydrogenation (ATH) is arguably one of the most powerful tools for the synthesis of chiral compounds. Despite tremendous advances in this field, the reduction of α-ketophosphonates remains largely unexplored. Herein, we report an efficient Ru-catalyzed ATH on a broad range of α-ketophosphonates.

Access to 2-Fluorinated Aziridine-2-phosphonates from ,-Halofluorinated -Iminophosphonates-Spectroscopic and Theoretical Studies.

The efficient one-pot halofluorination of a -enaminophosphonate/-iminophosphonate tautomeric mixture resulting in ,-halofluorinated -iminophosphonates is reported. Subsequent imine reduction gave the corresponding -aminophosphonates as a racemic mixture or with high diastereoselectivity. The proposed protocol is the first example of a synthesis of -inactivated aziridines substituted by a fluorine and phosphonate moiety on the same carbon atom.

Beyond the Limits of Atropochirality: Design of Highly Conformationally Restrained Biaryls with Bridgehead Phosphine Oxide.

In the last three decades, reacting sterically congested ortho-substituted arenes to form atropochiral biaryls is an appealing venture and a challenging subject that has garnered significant attention. Therefore, there is interest in developing methods to prepare these compounds. In this study, an efficient approach to produce a new class 2,2' disubstituted biaryls bridgehead phosphine oxides with an unusual topology and exceptional conformational stability is presented.

New Approaches toward Building C -P bond: A Two-Decade Overview.

Since the review of Savignac, the past 20 years have seen significant progresses on the synthesis of alkynylphosphorus compounds considerably expanding the original and rather limited organic toolbox. This comprehensive review explores the latest and potentially greener methodologies using sustainable catalysis or direct metal-free couplings from stable and easy to handle precursors. Recent progress and mechanistic insights for metal-catalyzed reactions with a particular emphasis on copper, palladium, nickel and silver catalytic systems, photocatalytic and metal-free reactions are detailed covering most of the publications related to this field since 2000 until March 2022.

Gold-Catalyzed Access to Isophosphinoline 2-Oxides.

Gold(I)-catalyzed reactions of electron-poor alkynes are still a challenging process. A straightforward synthesis of phosphorus-based heterocycles, namely, 2-phenyl 1-isophosphinoline 2-oxides , is reported. The reaction used PPhAuCl precatalyst in combination with triflic acid under microwave activation and afforded isophosphinoline 2-oxides in moderate to quantitative yields through a fully regioselective 6-endo-dig hydroarylation cyclization, paving the way toward an effective synthesis of phosphorus heterocycles.

Diversity-Oriented Synthesis toward Aryl- and Phosphoryl-Functionalized Imidazo[1,2-]pyridines.

We report herein an efficient synthesis of diversely polysubstituted imidazo[1,2-]pyridines, a family of aza-heterocycles endowed with numerous biological properties, through a sequence involving two consecutive palladium-catalyzed cross-coupling reactions. First, we demonstrated that a Hirao coupling occurred straightforwardly in high yields at positions 3, 5, and 6 of imidazopyridine derivatives, giving access to a wide variety of substituted phosphonates, phosphinates, and phosphine oxides. In a second step, direct CH-arylation of phosphorylimidazopyridines with aryl halides was found to be effective and fully selective, leading to 3-aryl-substituted imidazopyridines in moderate to high yields depending on steric hindrance.

Golden Face of Phosphine: Cascade Reaction to Bridgehead Methanophosphocines by Intramolecular Double Hydroarylation.

Reported herein is the first example of a gold-catalyzed cyclization of bis(arylmethyl)ethynylphosphine oxides. This represents an original approach to bridgehead methanophosphocines 1, eight-membered heterocycles. Gold catalyst in combination with triflic acid activates alkyne and induces a double hydroarylation.

Transition-Metal-Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation: Sustainable Chemistry to Access Bioactive Molecules.

Over the last few decades, the development of new and highly efficient synthetic methods to obtain chiral compounds has become an increasingly important and challenging research area in modern synthetic organic chemistry. In this account, we review recent work from our laboratory toward the synthesis of valuable chiral building blocks through transition-metal-catalyzed asymmetric hydrogenation and transfer hydrogenation of C=O, C=N and C=C bonds. Application to the synthesis of biologically relevant products is also described.

Synthesis and Antiproliferative and Metabolic Evaluations of Novel Securinine Derivatives.

New securinine analogues have been prepared by semisynthesis. Two series were developed using either Suzuki or Sonogashira cross coupling reactions. The in vitro cytotoxicity of the compounds was assayed against HCT-116 colon cancer cells.

Synthesis and biological evaluation of new securinine analogues as potential anticancer agents.

A series of new securinine analogues was prepared by Heck reaction from readily accessible securinine and commercially available iodoarenes. The in vitro cytotoxicity of the prepared compounds was assayed against a panel of four cancer cell lines: A375, A549, HCT-116 and HL-60 showing promising growth inhibition with excellent IC50 values in the nanomolar range. The plasmatic stability of the most potent analogue was also investigated demonstrating that they might serve as valuable leads for the development of anticancer drugs.

Efficient Synthesis of Differentiated syn-1,2-Diol Derivatives by Asymmetric Transfer Hydrogenation-Dynamic Kinetic Resolution of α-Alkoxy-Substituted β-Ketoesters.

Asymmetric transfer hydrogenation was applied to a wide range of racemic aryl α-alkoxy-β-ketoesters in the presence of well-defined, commercially available, chiral catalyst Ru(II) -(N-p-toluenesulfonyl-1,2-diphenylethylenediamine) and a 5:2 mixture of formic acid and triethylamine as the hydrogen source. Under these conditions, dynamic kinetic resolution was efficiently promoted to provide the corresponding syn α-alkoxy-β-hydroxyesters derived from substituted aromatic and heteroaromatic aldehydes with a high level of diastereoselectivity (diastereomeric ratio (d.r.

Enantioselective ruthenium(II)/Xyl-SunPhos/Daipen-catalyzed hydrogenation of γ-ketoamides.

A series of γ-hydroxy amides were synthesized with high enantioselectivities (up to 99%) using asymmetric hydrogenation of the corresponding γ-ketoamides in the presence of Ru-Xyl-SunPhos-Daipen catalyst providing key building blocks for a variety of naturally occurring and biologically active compounds.

Enantioselective rhodium-catalyzed synthesis of α-chloromethylene-γ-butyrolactams from N-allylic alkynamides.

The first enantioselective cycloisomerization with intramolecular halogen migration of various 1,6-enynes promoted by a cationic Rh-Synphos catalyst is reported. This method provides an efficient route to enantiomerically enriched γ-butyrolactam derivatives, which are important core scaffolds found in numerous natural products and biologically active molecules. Good yields and enantiomeric excesses up to 96% are achieved.

Enantioselective synthesis of 1-aryl-tetrahydroisoquinolines through iridium catalyzed asymmetric hydrogenation.

Asymmetric hydrogenation of 1-aryl-3,4-dihydroisoquinolines using the [IrCODCl](2)/(R)-3,5-diMe-Synphos catalyst is reported. Under mild reaction conditions, this atom-economical process provides easy access to a variety of enantioenriched 1-aryl-1,2,3,4-tetrahydroisoquinoline derivatives, which are important pharmacophores found in several pharmaceutical drug candidates, in high yields and enantiomeric excesses up to 99% after a single crystallization.

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.

Ru-catalyzed highly chemo- and enantioselective hydrogenation of γ-halo-γ,δ-unsaturated-β-keto esters under neutral conditions.

Finely-tuned ruthenium-catalyzed highly chemoselective and enantioselective hydrogenation of γ-halo-γ,δ-unsaturated-β-keto esters at the carbonyl group was achieved under neutral reaction conditions (ee up to 97%). Both olefin and alkenyl halogen moieties, which are labile under hydrogenation conditions, remained untouched during the reaction.

Ruthenium-catalyzed enantioselective hydrogenation of aryl-pyridyl ketones.

Various substituted aryl-pyridyl ketones were hydrogenated in the presence of Ru-XylSunPhos-Daipen bifunctional catalytic system with enantiomeric excesses up to 99.5%. Upon introduction of a readily removable ortho-bromo atom to the phenyl ring, enantiomerically enriched 4-chlorophenylpyridylmethanol was obtained by hydrogenation method with 97.

Efficient enantioselective synthesis of 3-aminochroman derivatives through ruthenium-Synphos catalyzed asymmetric hydrogenation.

A highly enantioselective asymmetric hydrogenation of various trisubstituted enamides derived from chroman-3-ones promoted by cationic Ru-Synphos catalysts is reported. This atom-economical and clean method provides an efficient route to optically active 3-aminochroman derivatives, which are important pharmacophores found in numerous drug candidates, in high chemical yields and enantiomeric excesses up to 96%.

Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-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,β-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.

(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,β-unsaturated carbonyl compounds at room temperature.

Highly diastereo- and enantioselective synthesis of monodifferentiated syn-1,2-diol derivatives through asymmetric transfer hydrogenation via dynamic kinetic resolution.

The first enantio- and diastereoselective approach to alpha-alkoxy-substituted syn-beta-hydroxyesters through highly efficient catalytic asymmetric transfer hydrogenation via dynamic kinetic resolution reactions from the corresponding racemic beta-ketoesters is described. In this atom-economical process, two contiguous stereogenic centers are generated simultaneously with an excellent diastereoselectivity (up to 99/1) and enantioselectivity (up to 99%), allowing a rapid access to a wide variety of aromatic and heteroaromatic monodifferentiated syn-1,2-diols.