Palladium‐Catalyzed Amination of Aryl Sulfides with Anilines

A combination of a palladium–NHC catalyst and potassium hexamethyldisilazide enables the amination of aryl sulfides with anilines to afford a wide variety of diarylamines. The reaction conditions are versatile enough for the reaction of even bulky ortho‐substituted aryl sulfides. This amination can be applied to the modular synthesis of N‐aryl carbazoles from the corresponding ortho‐bromothioanisoles. As aryl sulfoxides undergo extended Pummerer reactions to afford ortho‐substituted aryl sulfides, the Pummerer products are thus useful substrates for the amination to culminate in efficient syntheses of a 2‐anilinobenzothiophene and an indole as proof‐of‐principle of the utility of the extended Pummerer reaction/amination cascade.     

Radical Cyclization Reactions via Manganese(III) Acetate Leading to 2‐Thienyl‐Substituted Dihydrofuran Compounds

The 2‐thienyl‐substituted 4,5‐dihydrofuran derivatives 3 – 8 were obtained by the radical cyclization reaction of 1,3‐dicarbonyl compounds 1a – 1f with 2‐thienyl‐substituted conjugated alkenes 2a – 2e by using [Mn(OAc)₃] (Tables 1–5). In this study, reactions of 1,3‐dicarbonyl compounds 1a – 1e with alkenes 2a – 2c gave 4,5‐dihydrofuran derivatives 3 – 5 in high yields (Tables 1–3). Also the cyclic alkenes 2d and 2e gave the dihydrobenzofuran compounds, i.e., 6 and 7 in good yields (Table 4). Interestingly, the reaction of benzoylacetone (=1‐phenylbutane‐1,3‐dione; 1f ) with some alkenes gave two products due to generation of two stable carbocation intermediates (Table 5).     

Trinuclear Non‐Heme Iron Complexes Based on 4‐Substituted 2,6‐Diacylpyridine Ligands as Catalysts in Aerobic Allylic Oxidations

Taking the regio‐ and chemoselectivities of our iron complex precursors with pyridine core in aerobic oxidations into account, we envisioned a more effective influence on catalytic properties by the introduction of different substituents in 4‐position of the pyridine moiety. The synthesis of these novel 4‐substituted (pyridine‐2,6‐diyl)dipropanoic acids 4 is described. Analogously to the unsubstituted derivative, ligands 4 reacted with Fe(ClO₄)₃ to form trinuclear Fe₃(μ₃‐O) complexes 3 , which were tested in the aerobic Gif‐type oxidation of α‐pinene to myrtenol, verbenone, myrtenal, and pinene oxide. The electronic nature of the substituents was found to slightly effect the ratio of allylic oxidation/epoxidation, whereas its influence on the oxidation preference of secondary to primary C? H bonds is negligible as compared to the unsubstituted complex.     

Synthesis of 3‐Acyl‐4‐alkenylpyrrolidines by Platinum‐Catalyzed Hydrative Cyclization of Allenynes

A series of nitrogen‐tethered allenynes (‘5‐aza‐1,2‐dien‐7‐ynes’) 1 were transformed to the corresponding 3‐acyl‐4‐alkenylpyrrolidines 3 when treated with a catalytic amount of PtCl₂ in MeOH at 70°. Initial Pt‐promoted cyclization forms a nonclassical carbocationic intermediate. In contrast to the cycloisomerization in toluene, which produced the bicyclic cyclobutenes 2 , the intermediate is intercepted by addition of an oxygen nucleophile to achieve the formal hydrative cyclization.     

Synthesis of 3‐Carbamoyl β‐Lactams via Manganese(III)‐Promoted Cyclization of N‐Alkenylmalonamides

Manganese(III)‐promoted cyclization of N‐alkenylmalonamides (=N‐alkenylpropanediamides) gave 3‐(aryl/(alkylamino)carbonyl) β‐lactams as well as 3‐(aryl/(alkylamino)thiocarbonyl) β‐lactams. The relative configuration of the obtained products was unambiguously determined by X‐ray crystallography. The proposed method is very useful for the one‐pot synthesis of a number of 3‐(aryl/(alkylamino)carbonyl) β‐lactams, especially those containing an amino(thiocarbonyl) moiety, which are not selectively accessible by other methods.     

Enantioselective Oxidation of Secondary Alcohols Catalyzed by Soluble Chiral Polymeric [N′,N′‐Bis(salicylidene)ethane‐1,2‐diaminato(2−)]manganese(III) ([MnIII(salen)]) Type Complexes in a Biphasic System

The polymeric [N′,N′‐bis(salicylidene)ethane‐1,2‐diaminato(2?)]manganese(III) ([Mn^III(salen)]) type complexes 1 and 2 were successfully applied to the oxidative kinetic resolution of secondary alcohols. The reaction proceeded readily at room temperature with excellent enantioselectivities of up to 99.9% ee. A variety of substrates, including aromatic and aliphatic alcohols, could be tolerated. The polymeric catalysts could easily be recovered and recycled.     

Pronounced Catalytic Activity of Manganese(III)–Schiff Base Complexes in the Oxidation of Alcohols by Tetrabutylammonium Peroxomonosulfate

A novel and practical catalytic method for efficient and highly selective oxidation of a wide range of benzylic, allylic, aliphatic, primary, and secondary alcohols to the corresponding aldehydes and ketones using tetrabutylammonium peroxomonosulfate catalyzed by tetradentate Schiff base–Mn^III complexes has been developed. Electron‐deficient and hindered alcohols required longer reaction times for oxidation in this catalytic system. The electron‐poor and hindered salicylidene ring of the ligand enhanced the catalytic activity and stability of Mn catalysts. The desired turnover numbers obtained in the oxidation reactions indicated the high efficiency and relative stability of these simple Schiff base complexes in this catalytic system.     

Oxidation of Stereo‐regular Poly(styrene‐co‐4‐methylstyrene) by Cobalt(II) Acetate Tetrahydrate/Sodium Bromide Catalyst

Chemical modification on the stereo‐regular poly(styrene‐co‐4‐methylstyrene) (sPS‐PMS) was attempted in this study. Metallocene copolymerization of styrene (St) and 4‐methylstyrene (MSt) was performed by using η⁵‐pentamethylcyclopentadienyl‐titanium(IV)tributoxide (Cp*Ti(OBu)₃)/methylaluminoxane (MAO)/tri‐iso‐butylaluminum (TIBA) catalyst in the bulk state. Cobalt(II) catalyst was then applied to oxidize the benzylic methyl group on the MSt units of the resulting sPS‐PMS copolymer. Both aldehyde and carboxylic acid in the oxidized products were resolved by the FTIR and ¹H NMR. The oxidized sPS‐PMSs exhibit a low and a high‐temperature T_g and T_m corresponding to the transitions in the amorphous and the crystalline regions. Hydrogen‐bond and polar interactions between the aldehyde and carboxylic acids tend to interrupt the regular chain packing of the oxidized sPS‐PMS, resulting in the lowering of T_m with oxidation level. The oxidized sPS‐PMS showed better adhesion to glass fiber than pure sPS‐PMS copolymer as evaluated from the respective SEM fractured micrographs.     

Copper‐Catalyzed Ritter‐Type Reaction of Unactivated Alkenes with Dichloramine‐T

It was shown that dichloramine‐T ( 1 ) reacted with cyclohexene in acetonitrile to give N¹‐(2‐chlorocyclohexyl) amidine 2a and N‐(2‐chlorocyclohexyl)acetamide ( 3 ) via the competitive addition of acetonitrile and N‐chloro‐N‐tosylamino anion to cyclohexenechloronium ion. This reaction can be catalyzed by Cu(OAc)₂, primarily affording 2a . Furthermore, the resulting 2a can be cyclized to benzimidazol 14a in good yield by treating with KOH in dioxane.     

Pd‐NHC‐Catalyzed Alkynylation of General Aryl Sulfides with Alkynyl Grignard Reagents

Cross‐coupling reactions of unactivated aryl sulfides with alkynylmagnesium chloride have been invented to afford 1‐aryl‐1‐alkynes with the aid of a palladium/N‐heterocyclic carbene complex. This reaction has by far the widest scope of all transformations utilizing aryl sulfides and alkynes, while known cross‐coupling alkynylations of aryl‐sulfur electrophiles require activated azaaryl sulfides, thiolactams, or arenesulfonyl chlorides. The alkynylation of aryl sulfides is compatible with typical protecting functional groups. The alkynylation is applied to the synthesis of benzofuran‐based fluorescent molecules by taking advantage of characteristic organosulfur chemistry.     

Synthesis and Cytotoxicity of 6‐Pyrrolidinyl‐2‐(2‐Substituted Phenyl)‐4‐Quinazolinones

In our continuing search for potential anticancer candidates, 2‐(3‐methoxyphenyl)‐6‐pyrrolidinyl‐4‐quinazolinone ( JJC‐1 ) was selected as the lead compound. Starting 5‐pyrrolidinyl‐2‐aminobenzamide was prepared using standard methodology from 5‐chloro‐2‐nitrobenzoic acid by reaction with SOCl₂, NH₃, pyrrolidine, and H₂. The starting benzamide then was reacted with 2‐substituted benzaldehyde or benzoyl chloride in N,N‐dimethylacetamide (DMAC) in the presence of NaHSO₃ at 150 °C. Thermal cyclodehydration/dehydrogenation gave the target 6‐pyrrolidinyl‐2‐(2‐substituted phenyl)‐4‐quinazolinones ( 15–22 ). These target compounds were assayed for their cytotoxicity in vitro against six cancer cell lines, including human monocytic leukemia cells (U937), mouse monocytic leukemia cells (WEHI‐3), human hepatoma cells (HepG2, Hep3B) and human lung carcinoma cells (A549, CH27). Most of them exhibited significant cytotoxic effect toward U937 and WEHI‐3 cells, with EC₅₀ values ranging from 0.30 to 10.10 μM. Compound 19 was investigated further for its action mechanisms. Preliminary findings indicated that compound 19 induced G2/M arrest and apoptosis on U937 cells.     

Sodium Iodide (NaI)‐Catalyzed Cross‐Coupling for C−S Bond Formation via Oxidative Dehydrogenation: Cheap,Direct Access to Unsymmetrical Aryl Sulfides

A simple and practical NaI‐catalyzed direct C−H sulfenylation of arenes has been developed under air. In this reaction, aryl sulfides were obtained in moderate to excellent yields with high regioselectivity from readily available aromatic compounds and aryl/alkyl thiols, even on gram scale. To demonstrate the practicability of this reaction, two bioactive compound skeletons were synthesized in good yields. This method can also be used to late‐stage modification of curcumin.     

Stepwise Mechanism of Hydroxide Ion Catalyzed Cyclization of Uridine 3′‐Thiophosphates

Diastereoisomeric isopropyl‐, 2‐ethoxyethyl‐, 2,2‐dichloroethyl‐ and 2,2,2‐trichloroethyl uridine 3′‐thiomonophosphates, 1a – 1d , respectively, have been synthesized, and their hydrolyses in aqueous alkali at 25° have been followed by HPLC. According to the time‐dependent product distributions obtained, the alkyl phosphorothioates 1a – 1d undergo cleavage to uridine 2′‐ and 3′‐thiophosphates, 7a and 7b , respectively, via a uridine 2′,3′‐cyclic thiophosphate ( 6 ). The rate of the hydroxide ion‐catalyzed cyclization of both (R_P)‐ and (S_P)‐diastereoisomer is highly dependent on the polar nature of the leaving group, the β_lg values being ?1.23±0.03 and ?1.24±0.03, respectively. Brønsted dependence of the second‐order rate constants (k_OH [dm³ mol^?1 s^?1]) on the pK_a values of the leaving alcohols shows a convex breakpoint on going from alkyl esters 1a – 1d to aryl esters studied earlier. This may be considered as a strong evidence for a stepwise mechanism, where the formation and breakdown of the phosphorane intermediate is the rate‐limiting step with aryl and alkyl esters, respectively.     

Potassium Thiocyanate‐Promoted One‐Pot Synthesis of (1,3‐Diaryl‐2,5‐dioxoimidazolidin‐4‐ylidene)acetates from Aryl Isocyanates and Alkyl Propiolates. Short Communication

The reaction of aryl isocyanates and alkyl propiolates (=alkyl prop‐2‐ynoates) in the presence of potassium thiocyanate (KSCN) led to geometric isomers of alkyl 2‐(1,3‐diaryl‐2,5‐dioxoimidazolidin‐4‐ylidene)acetates in moderate‐to‐good yields.     

A Novel and Regiospecific Synthesis of 1‐Aryl‐1H‐benzotriazoles via Copper(I)‐Catalyzed Intramolecular Cyclization Reaction

1‐Aryl‐1H‐benzotriazole derivatives were synthesized via intramolecular cyclization of easily obtained triazenes, using CuI as the catalyst, DMSO as the solvent, t‐BuONa as the base, and 1,10‐phenanthroline as the ligand, in up to 97% yield. The synthesis is regiospecific and functional group‐tolerant.     

Synthesis of Monospiro‐2‐amino‐4H‐pyran Derivatives Catalyzed by Propane‐1‐sulfonic Acid‐Modified Magnetic Hydroxyapatite Nanoparticles

Various monospiro‐2‐amino‐4H‐pyran derivatives have been synthesized in high yields (via three‐component coupling of ninhydrin or different isatins with malononitrile and 1,3‐dicarbonyl compounds) in the presence of catalytic amount of propane‐1‐sulfonic acid‐modified magnetic hydroxyapatite nanoparticles in H₂O. Due to easy magnetic removal of nanocatalyst and applying of H₂O as solvent, this protocol enhanced product purity, and promised economic as well as environmental benefits, exemplifying a waste‐free chemistry. More importantly, the catalyst could be easily recycled for more than five times without loss of activity.     

C1‐Symmetric Bicyclo[2.2.2]octa‐2,5‐diene (bod*) Ligands in Rhodium‐Catalyzed Asymmetric 1,4‐Addition of Arylboronic Acids to Enones and 1,2‐Addition to N‐[(4‐Nitrophenyl)sulfonyl]imines

A set of ten C₁‐symmetric chiral bicyclo[2.2.2]octa‐2,5‐dienes (bod*) 2 (Fig. 1) were tested as ligands in Rh‐catalyzed arylation reactions. The 1,4‐addition of arylboronic acids to cyclohex‐2‐en‐1‐one, cyclopent‐2‐en‐1‐one, and tert‐butyl cinnamate proceeded smoothly with excellent enantioselectivities (up to 99% ee; Tables 1–3). The challenging 1,2‐addition of triphenylboroxine to N‐[(4‐nitrophenyl)sulfonyl]imines yielded the product in high yield and in good enantioselectivity (up to 92% ee; Table 4). Generally, the use of C₁‐symmetric chiral bod* ligands bearing bulky substituents resulted in lower enantioselectivities, whereas several electron‐poor and electron‐rich bod* ligands gave higher enantioselectivities than the benchmark ligands reported in literature.     

Synthesis of 9,9‐Disubstituted 9H‐Pyrrolo[1,2‐a]indoles by Hydriodic Acid‐Catalyzed Cyclization of 1‐[2‐(1‐Aryl(or methyl)ethenyl)phenyl]‐1H‐pyrroles

A novel method is reported for the synthesis of 9,9‐disubstituted 9H‐pyrrolo[1,2‐a]indoles. Cyclization of 1‐[2‐(1‐aryl(or methyl)ethenyl)phenyl]‐1H‐pyrroles, which can be easily prepared from 2‐(1‐aryl(or methyl)ethenyl)anilines, proceeds smoothly, in general, at 0° in the presence of a catalytic (or an equimolar) amount of HI in MeCN to provide the desired products.