Preparation of α- or β-trifluoromethylated vinylstannanes and their cross-coupling reactions

α- or β-Trifluoromethylated vinylstannanes 1, 2a, 3 and 4 were prepared form 1,1-bis(phenylthio)-2,2,3,3,3-pentafluoropropylbenzene (5) via several steps. The cross-coupling arylation reactions of 1–4 with aryl iodides bearing a bromo, methoxy, methyl, nitro or trifluoromethyl group on para- or meta-position of benzene ring afforded the corresponding coupling products in good yields. Compounds 1, 2a and 4 underwent the acylation reaction with various types of acyl chlorides to give the corresponding trifluoromethylated enone derivatives in good yields. Reduction of trifluoromethylated enone derivatives with LiAlH₄, followed by Fridel-Craft’s type of cyclization with AlCl₃ provided trifluoromethylated indene derivatives in good yields.     

Oxidative addition of N-halosuccinimides to palladium(0): the discovery of neutral palladium(II) imidate complexes, which enhance Stille coupling of allylic and benzylic halides

The Stille coupling of organostannanes and organohalides, mediated by air and moisture stable palladium(II) phosphine complexes containing succinimide or phthalimide (imidate) ligands, has been investigated. An efficient synthetic route to several palladium(II) complexes containing succinimide and phthalimide ligands, has been developed. cis-Bromobis(triphenylphosphine)(N-succinimide)palladium(II) [(Ph₃P)₂Pd(N-Succ)Br] is shown to mediate the Stille coupling of allylic and benzylic halides with alkenyl, aryl and allyl stannanes. In competition experiments between 4-nitrobromobenzene and benzyl bromide with a cis-stannylvinyl ester, (Ph₃P)₂Pd(N-Succ)Br preferentially cross-couples benzyl bromide, whereas with other commonly employed precatalysts 4-nitrobromobenzene undergoes preferential cross-coupling. Furthermore, preferential reaction of deactivated benzyl bromides over activated benzyl bromides is observed for the first time. The type of halide and presence of a succinimide ligand are essential for effective Stille coupling. The type of phosphine ligand is also shown to alter the catalytic activity of palladium(II) succinimide complexes.     

Synthesis of allyl phosphine oxides/boranes via Horner reaction of bis(diphenylphosphine)ethane monoxide reagent with an aldehyde

The Horner-Wittig addition-elimination reaction using bis(diphenylphosphine)ethane monoxide [DIPHOS(O)] with an aldehyde affords Z-allyl phosphine oxides/boranes. Alternatively, the stereoselective Lewis acid mediated intermolecular reduction of its γ-ketobisphosphoranes and stereoselective intramolecular reduction of γ-ketophosphine·borane derivatives followed by elimination of diphenylphosphinate affords E-allyl phosphine oxides/boranes with good to high selectivity. Allyl phosphine oxides are common intermediates in the synthesis of polyenes.     

Regioselective synthesis of 2,3-disubstituted 1-alkyl pyrrolo[2,3-b] quinoxalines through palladium-catalyzed Heck reaction of chalcones and evaluation of their anti-bacterial activities

The regioselective synthesis of 1-alkyl-2-aryl-3-acyl pyrrolo[2,3-b]quinoxalines through palladium-catalyzed Heck coupling reaction/heteroannulation was reported. The reaction of N-alkyl/benzyl-3-chloroquinoxaline-2-amines with chalcones catalyzed by Pd(OAc)₂ in the presence of KO^tBu, as the base, in DMSO afforded the desired products in good-to-high yields. The MIC and MBC determinations revealed that these compounds could be used in the future research works for the development of antibiotics.     

Recent advances in ionic liquids: green unconventional solvents of this century: part II

Abstract

In the second part of our paper, further recent developments of ionic liquids in selected name reactions of carbonyl chemistry such as Mannich, Reformatsky, Cannizaro, Streacker, Barbier, Pechmann, etc. are described.     

One-pot and regioselective synthesis of polysubstituted 3,4-dihydroquinazolines and 4,5-dihydro-3H-1,4-benzodiazepin-3-ones by sequential Ugi/Staudinger/aza-Wittig reaction

An efficient one-pot and regioselective synthesis of 3,4-dihydroquinazolines and 4,5-dihydro-3H-1,4-benzodiazepin-3-ones by Ugi/Staudinger/aza-Wittig sequence has been developed. The Ugi reactions of 2-azidobenzylamines, aldehydes, acids (or α-keto acids) and isocyanides produced the azide intermediates, which were then treated with tributylphosphine or triphenylphosphine to give polysubstituted 3,4-dihydroquinazolines or 4,5-dihydro-3H-1,4-benzodiazepin-3-ones in moderate to good yields by tandem Standinger/aza-Wittig reactions.     

Phase-Transfer-Catalyzed Michaelis-Becker Synthesis of Dialkyl Methyl Phosphonates

A liquid–liquid phase-transfer-catalyzed (PTC) Michaelis-Becker reaction was adopted in the preparation of dialkyl methyl phosphonate (R = Me, iPr, nBu, and iBu). This was performed by the reaction of an appropriate dialkyl hydrogen phosphonate with methyl iodide in the presence of benzyl triethyl ammonium chloride and sodium hydroxide as PTC and base, respectively. A liquid–liquid two-phase system (H₂O/CH₂Cl₂) introduced a suitable situation for the preparation of dialkyl methyl phosphonates with bulky alkyl groups (R = iPr, nBu, and iBu), but with R = Me, the hydrolysis of dimethyl hydrogen phosphonate (reagent) reduced the yield to 22%. In this case, a solid–liquid PTC-free system was successfully applied and yield of over 80% was obtained.     

Palladium bis(2,2,6,6-tetramethyl-3,5-heptanedionate) catalyzed Suzuki, Heck, Sonogashira, and cyanation reactions

Palladium bis(2,2,6,6-tetramethyl-3,5-heptanedionate): a structurally well-defined O-containing transition metal complex is reported as an efficient catalyst for Suzuki, Heck, and Sonogashira cross-coupling reactions. The protocol was also applied successfully for cyanation of aryl halides under milder operating conditions. The system tolerated the coupling of various aryl halides with alkenes, alkynes, and organoboronic acid along with the cyanation of aryl halides providing good to excellent yields of desired products.     

Preparation and characterization of Cu supported on 2-(1H-benzo[d]imidazol-2-yl)aniline-functionalized Fe3O4 nanoparticles as a novel magnetic catalyst for Ullmann and Suzuki cross-coupling reactions

Copper supported on 2-(1H-benzo[d]imidazol-2-yl)aniline (BIA)-functionalized Fe₃O₄ nanoparticles (Cu-BIA-Si-Fe₃O₄) as a novel magnetic catalyst was designed and used for the synthesis of new products via Ullmann and Suzuki cross-coupling reactions. The Ullmann reaction was performed by mixing arylboronic acid with aniline derivatives in dimethylsulfoxide solvent. Also, diaryls were synthesized via Suzuki C–C reactions between aryl halides and phenylboronic acid in the same solvent. The prepared materials and catalyst were characterized with various analytical techniques. The Cu-BIA-Si-Fe₃O₄ catalyst demonstrated catalytic efficiency with good to excellent yields for both types of reactions in comparison with commercial palladium catalysts. Also, the catalyst could be recovered by a simple filtration and retained its activity even after several cycles.     

A fully stereocontrolled total synthesis of (+)-leucascandrolide A

A highly stereocontrolled total synthesis of leucascandrolide A, a cytotoxic 18-membered macrolide from the calcareous sponge Leucascandra caveolata, starts out with a Jacobsen asymmetric hetero Diels-Alder reaction to configure the 2,6-cis-tetrahydropyran ring. All the remaining oxygenated stereocentres are introduced with high selectivity by relying on substrate-based control. An efficient endgame depends on two Mitsunobu reactions, the first to close the macrolactone with inversion at C17 and the second to attach the oxazole-containing side chain at C5, followed by Lindlar hydrogenation of the two alkynes to provide (+)-leucascandrolide A.     

Evidence of Kinetically Relevant Consistency in Thermal and Photo-Thermal HCOOH Decomposition over Pd/LaCrO3/C3N4 Composite

Photo-thermal catalysis has been an attractive alternative strategy to promote chemical reactions for years, however, how light cooperates with thermal energy is still unclear. We meet this demand by exploring reaction mechanism via pressure dependency studies as well as H/D exchange experiments with HCOOH decomposition as a probe over a palladium nanoparticle (Pd_n) and isolated Pd (Pd₁) decorated LaCrO₃/C₃N₄ composite catalyst, in which the H₂ formation rate shows a first-order dependence on HCOOH and inverse first-order dependence on CO partial pressures no matter the reaction was driven by thermal or photo-thermal energy. Additionally, negligible kinetic isotopic effects (KIEs: k_H/k_D) were determined under both dark and light conditions at 1.04 and 1.18 when the HCOOH was replaced by HCOOD. Besides, when the reactant HCOOH was further replaced by DCOOD, the KIE values of 1.55 (dark) and 1.92 (light) were obtained, which indicates that the HCOOH decomposition follows kinetically relevant (KR) of C−H bond rupture within HCOOH molecule under both thermal and photo-thermal reaction conditions and the catalytic surface was found to be densely covered by CO based on the pressure dependency studies as well as the in situ Fourier transform infrared spectroscopy (FTIR) analysis. Clearly, the HCOOH decomposition driven by thermal and photo-thermal energy follows the same reaction mechanism. Nevertheless, light induced hot electrons and the derived thermal effect do cause the enhancement of the reaction activity in some circumstances compared with bare thermal catalysis, which clarifies the confusion on cooperation mechanism of photo and thermal energies from the kinetic perspective. Hot electrons induced by photo-illumination was confirmed by in situ FTIR CO chemisorption with ∼10 cm⁻¹ redshift identified of the CO feature once light was introduced. Meanwhile, the photo thermal reaction system suffers from severe electron-hole re-combination at high reaction temperatures and make the thermal effect of photo irradiation dominant with respect to the effect at low reaction temperatures. This research provides insight to the mechanism on how photo-thermal reaction works and draws attention to the photo-thermal reaction process in boosting catalytic activity.     

An enantioselective organocatalyzed aza-MBH domino process: application to the facile synthesis of tetrahydropyridines

A chiral acid-base organocatalyst was found to promote an aza-MBH domino process between α,β-unsaturated carbonyl compounds and N-tosylimines to afford tetrahydropyridine derivatives with high enantioselectivity.     

A method for the synthesis of cyclopropanes by regiospecific and regioselective magnesium carbenoid 1,3-CH insertion as the key reactions

Addition reaction of two geometrical isomers of 1-chlorovinyl p-tolyl sulfoxides, derived from unsymmetrical ketones and chloromethyl p-tolyl sulfoxide, with lithium enolate of tert-butyl acetate gave single diastereomers of the adduct, respectively. Treatment of each diastereomer with i-PrMgCl resulted in the formation of magnesium carbenoid. Highly regiospecific 1,3-CH insertion reaction was found to take place from each magnesium carbenoid to afford cyclopropanes. On the other hand, when the unsymmetrical ketones bearing an oxygen- or a nitrogen-functional group on the α-carbon were used in this procedure, the regioselective 1,3-CH insertion reaction proceeded mainly. Stereochemistry of the adducts, reaction mechanism, and essence of the specificity and the selectivity are discussed.     

Competitive thermal ene reaction and Diels-Alder reactions of 2-[N-(alk-2-enyl)benzylamino]-3-vinylpyrido[1,2-a]pyrimidin-4(4H)-ones

Thermal reaction of 2-[N-(alk-2-enyl)benzylamino]-3-(2-substituted and 2,2-disubstituted)vinylpyrido[1,2-a]pyrimidin-4(4H)-ones gave azepine, the desired ene products, and/or pyran derivatives. The formation of the latter was responsible for the [4+2] cycloaddition reaction between the α,β-unsaturated ester carbonyl moiety as a diene part and the alkenylamino moiety as an ene one. The reaction features depended upon the kinds of substituents both on the vinyl and alkenyl counterparts; strongly electron-withdrawing substituents on the vinyl moiety or an electron-donating substituent on the alkenyl one changed the reaction feature from the ene reaction to the hetero Diels-Alder reaction.     

Synthesis of medium-sized carbocyclic ketones via the intramolecular B-alkyl Liebeskind-Srogl coupling reaction

Synthesis of medium-sized carbocyclic ketones via the intramolecular B-alkyl Liebeskind-Srogl coupling reaction is described. The sequence of hydroboration of ω-alkenyl thiol ester with 9-BBN and the Liebeskind-Srogl reaction results in the formation of medium-sized carbocyclic ketones with good yield.     

The perfluoroallylation of alkynes and transformation of the products

The addition of perfluoroallyl iodide to alkynes 1 initiated by AIBN in the absence of solvent 65 °C gave the corresponding 1:1 adducts (1,1,2,3,3-pentafluoro-5-iodopenta-1,4-dienes) 2. The reaction of 2 with boronic acids 3 and terminal alkynes 1 in the presence of catalytic palladium afforded the cross-coupling products 4 and 5, respectively.     

Variable Time Normalization Analysis: General Graphical Elucidation of Reaction Orders from Concentration Profiles

The recent technological evolution of reaction monitoring techniques has not been paralleled by the development of modern kinetic analyses. The analyses currently used disregard part of the data acquired, thus requiring an increased number of experiments to obtain sufficient kinetic information for a given chemical reaction. Herein, we present a simple graphical analysis method that takes advantage of the data‐rich results provided by modern reaction monitoring tools. This analysis uses a variable normalization of the time scale to enable the visual comparison of entire concentration reaction profiles. As a result, the order in each component of the reaction, as well as k_obs , is determined with just a few experiments using a simple and quick mathematical data treatment. This analysis facilitates the rapid extraction of relevant kinetic information and will be a valuable tool for the study of reaction mechanisms.     

Di(2-pyridyl)methylamine-palladium dichloride complex covalently anchored to a styrene-maleic anhydride co-polymer as recoverable catalyst for C-C cross-coupling reactions in water

A new polymer-supported di(2-pyridyl)methylamine-palladium dichloride complex covalently anchored to a styrene-alt-maleic anhydride co-polymer is prepared. This complex catalyzes Heck, Suzuki and Sonogashira cross-coupling reactions in neat water with similar efficiency than the monomeric complex. The turnover number (TON) of this polymer reaches up to 10⁴ for Heck reactions, whereas for Suzuki and Sonogashira couplings TONs up to 10⁵ are achieved. There is low leaching of palladium after filtration of the polymer and the activity remains almost constant after fourth and five reaction cycles especially in Sonogashira reactions. In the case of the Suzuki reaction Pd nanoparticles are dispersed into the polymer after the first cycle according to TEM images and 2.4% of Pd are found by ICP-OES in the corresponding filtrate. Alternatively, these palladium-catalyzed reactions can also be performed under microwave heating. These couplings take place with better efficiency with polymer-supported di(2-pyridyl)methylamine-palladium dichloride complex than with the polyurea-encapsulated Pd EnCat™ 40.     

Iodine-catalyzed tandem oxidative coupling reaction: A one-pot strategy for the synthesis of new coumarin-fused pyrroles

The simple and facile strategy for the synthesis of 2,3-disubstituted-chromeno[4,3-b]pyrrole-4(1H)-ones has been established. This method describes the Kornblum oxidation reaction of acetophenones, followed by the Knoevenagle treatment of the resulted (het)arylglyoxals with active methylene compounds and consequently iodine-activated Michael type reaction with 4-amino coumarin in a one-pot manner to afford disubstituted chromeno[4,3-b]pyrrole-4(1H)-one derivatives.     

3-Benzoylquinoxalin-2(1H)-one in the Kostanecki-Robinson Reaction. Synthesis and Structure of 2-Oxo-4-phenylpyrano[2,3-b]quinoxaline

3-Benzoylquinoxalin-2(1H)-one is cyclized with acetic anhydride in the presence of pyridine into 2-oxo-4-phenylpyrano[2,3-b]quinoxaline.