Copper-Catalyzed Cycloaddition of Heterobicyclic Alkenes with Diaryl Disulfides to Synthesize Dihydrobenzo[b]thiophene Derivatives.

A novel copper-catalyzed cycloaddition of diaryl disulfides to heterobicyclic alkenes has been developed. The C-S and C-C bonds can be formed simultaneously on the C═C bond of the olefins via a single-step cycloaddition to afford a series of 2,3-dihydrobenzo[b]thiophene derivatives. This reaction exhibits excellent diastereoselectivity and relatively broad substrate scope. Various functional groups attached to the substrates are tolerated in this protocol to give the corresponding exo adducts in moderate yields.

Cobalt(II)-Catalyzed [4+2] Annulation of Picolinamides with Alkynes via C-H Bond Activation.

A cobalt(II)-catalyzed [4+2] annulation of picolinamides with alkynes via C-H bond activation has been developed. The operationally simple annulation reaction allows for the synthesis of acyl-substituted 1H-benzoquinoline bearing multiple aromatic rings (up to 96 % yield) without co-oxidant or other oxidation factors under mild conditions. Several control experiments were carried out. This practical [4+2] annulation provides an efficient route to access highly functionalized compounds.

Copper-catalyzed diastereoselective hydrothioetherification of oxa(aza)benzonorbornadienes.

A novel copper-catalyzed hydrothioetherification of oxa(aza)bicyclic alkenes with potassium thioacetate and aryl or alkyl iodides to synthesize unsymmetrical thioethers has been developed. Notably, the reaction with complete diastereoselectivity went through a syn-selective addition process to give exo-adducts. In addition, this protocol exhibited high efficiency and good functional group tolerance to afford the target thioethers in moderate to good yields. Based on the results of mechanistic investigations, a plausible mechanism was proposed.

ICl/AgNO3 Co-Catalyzed Radical Oxidation of Diaryl- and Alkylarylalkynes into 1,2-Diketones.

A novel ICl/AgNO3 co-catalyzed radical oxidation of diaryl- and alkylarylalkynes into 1,2-diketones is reported. The reaction proceeded smoothly under mild conditions and generated 1,2-diketones in moderate to good yields with a good tolerance of functional groups. Furthermore, the obtained C4-(1,2-diketoaryl)isoxazoles could react smoothly with 1,2-diaminobenzene to form C4-(3-arylquinoxalin-2-yl)isoxazoles. At last, a new one-pot strategy for the synthesis of quinoxalines from 1,2-diphenylethynes and 1,2-diaminobenzene is also reported.

Three-Component Cycloaddition To Synthesize Aziridines and 1,2,3-Triazolines.

An efficient three-component cycloaddition of oxa(aza)bicyclic alkenes/norbornene in the presence of NaN3 and arylsulfonyl chlorides was developed, affording the corresponding aziridine products in good yields (up to 82%) with moderate to good endo/exo selectivities (up to >99:1 endo/exo). Further studies showed that the cycloaddition of oxa(aza)bicyclic alkenes in the presence of NaN3 and chloroalkanes could afford the exo-cycloadduct 1,2,3-triazolines in good to excellent yields (up to 95%). Compared with the existing methodologies, the current protocol demands very simple and mild reaction conditions and is a metal-free catalyzed reaction. In addition, a plausible mechanism for the cycloaddition reaction was also proposed.

Palladium-Catalyzed syn-Stereocontrolled Ring Opening of Oxabicyclic Alkenes with Arylsulfonyl Hydrazides.

A novel palladium-catalyzed ring-opening reaction of oxabicyclic alkenes with arylsulfonyl hydrazides was first developed. In this work, we provide an efficient one-pot reaction to afford the corresponding cis-2-aryl-1,2-dihydronaphthalen-1-ols and 2-aryl-naphthalenes in moderate to excellent yields (up to 95%) under an open-air condition. Various types of functional groups attached to the substrates were tolerated well in this method. Among them, the cis-1,2-configuration of product 3ag was confirmed by X-ray crystallographic analysis. In addition, a plausible mechanism for ring opening was also proposed.

Iron-Catalyzed Transfer Hydrogenation in Aged N-Methyl-2-pyrrolidone: Reductive Ring-Opening of 3,5-Disubstituted Isoxazoles and Isoxazolines.

3,5-Disubstituted isoxazoles and isoxazolines undergo an iron-catalyzed reductive ring-opening in aged N-methyl-2-pyrrolidone (NMP). 5-Hydroxy-N-methyl-2-pyrrolidone generated in situ via a simple activation of commercial NMP acts as the hydrogen donor in the iron-catalyzed transfer hydrogenation reaction. It is the first example employing a combination of an iron catalyst and 5-hydroxy-N-methyl-2-pyrrolidone as reducing agents in a transfer hydrogenation reaction. The protocol is highly efficient for the synthesis of ß-enaminones and 1,3-diketones, providing a versatile route for the preparation of these 1,3-difunctional compounds bearing diversified substitution patterns.

Nickel-catalyzed syn-stereocontrolled ring-opening of oxa- and azabicyclic alkenes with dialkylzinc reagents.

A new nickel-catalyzed syn-stereocontrolled ring-opening of oxa- and azabicyclic alkenes with dialkylzinc reagents was developed, which afforded the corresponding cis-2-alkyl-1,2-dihydronaphthalen-1-ols and 1,2-alkyl amide derivatives in moderate to excellent yields (up to 99% yield) under mild conditions. In this work, we successfully avoided obtaining hydride addition byproducts arising from ß-hydride elimination on an ethyl nickel species. Furthermore, a plausible mechanism for the ring-opening reaction was also proposed.

Water-Promoted Ir-Catalyzed Ring-Opening of Oxa(aza)benzonorbornadienes with Fluoroalkylamines.

A highly effective water-promoted iridium-catalyzed ring-opening reaction of oxa(aza)benzonorbornadienes with fluoroalkylamines was developed for the synthesis of fluorinated trans-1,2-amino alcohol or diamine derivatives. Tetrabutylammonium iodide (TBAI) was necessary as an additive for excellent yields in the presence of [Ir(COD)Cl]2 catalyst. Fluorinated trans-1,2-amino alcohol or diamine derivatives could be obtained in good to excellent yields (up to 98%) under mild conditions within a shorter period. Another interesting finding was that the addition of water could greatly enhance the ring-opening reaction. In addition, a plausible mechanism for the ring-opening reaction was proposed.

Study on the mechanism of platinum(ii)-catalyzed asymmetric ring-opening addition of oxabicyclic alkenes with arylboronic acids.

The mechanism of an asymmetric ring-opening (ARO) addition of oxabicyclic alkenes catalyzed by a platinum(ii) catalyst was investigated by M06-2X/6-311G(d,p) using density functional theory (DFT). All the structures were optimized in the solvent model density (SMD) solvation model (solvation = the mixture of H2O/CH2Cl2 1 : 10, v/v) for consistence with experimental conditions. The overall mechanism is considered as a four-step reaction including transmetalation, carboplatinum, ß-oxygen elimination, and hydrolysis. The transmetalation and carboplatinum steps are multi-step processes, and both the regioselectivity and the enantioselectivity lie in the carboplatinum process. Based on the natural population analysis (NPA) and the orbital composition analysis of oxabicyclic alkenes, the preferable coordination site with a platinum(ii) center is considered as the bridging oxygen atom by exo-coordination because of the less steric hindrance and the stronger electronic effect. This coordination is thought of as origin of the regioselectivity and the enantioselectivity, which is different from that proposed previously. The Gibbs free energy profiles show that the rate-determining step involves the migration of an aryl group from the platinum(ii) center to one of the closer enantiotopic carbon atoms in an alkene of the oxabicyclic alkenes. The theoretically predicted enantiomeric excess (ee) value of 82% for this reaction is very close to the experimental ee value of 80%. It was found that the hydrogen bonds between the oxabicyclic alkenes and water molecules promotes the platinum(ii) catalyst leaving the reaction system effortlessly and entering the next catalysis recycle. In the overall catalytic cycle, the highest free energy barrier is 30.1 kcal mol-1 and the process releases an energy of 26.3 kcal mol-1. The results confirm that the Pt(ii)-catalyzed ARO reactions take place at mild experimental conditions, which is consistent with the experiment observations. Thus, this study is important for understanding the catalytic behavior of the transition metal platinum(ii) in an asymmetric ring-opening reaction.

Palladium-Catalyzed syn-Stereocontrolled Ring-Opening of Oxabicyclic Alkenes with Sodium Arylsulfinates.

Palladium-catalyzed syn-stereocontrolled ring-opening reactions of oxabenzonorbornadienes with a wide range of sodium arylsulfinates were investigated, affording the desired products in good to excellent yields under an air atmosphere. This protocol provides a low-cost new viable and convenient method toward the synthesis of cis-2-aryl-1,2-dihydronaphthalen-1-ol with good functional group tolerance. In addition, the cis configuration of 3da was established by X-ray diffraction analysis, and a plausible mechanism for the ring-opening reaction was proposed.

Iridium/Copper Co-catalyzed Anti-Stereoselective Ring Opening of Oxabenzonorbornadienes with Grignard Reagents.

Cooperative catalysis has been widely considered as one of the most powerful strategies to improve synthetic efficiency. A new iridium/copper cocatalyst was developed for the ring-opening reaction of oxabenzonorbornadienes with a wide variety of Grignard reagents, which afforded the corresponding anti-2-substituted 1,2-dihydronaphthalen-1-ols in high yields (up to 99% yield) under mild conditions. The effects of catalyst loading, Lewis acid, Grignard reagent loading, and reaction temperature on the yield were investigated. To the best of our knowledge, it represents the first example of ring-opening reactions of oxabicyclic alkenes with Grignard reagent nucleophiles in a trans-stereoselective manner.

Platinum-catalyzed asymmetric ring-opening reactions of oxabenzonorbornadienes with phenols.

A platinum(II)-catalyzed asymmetric ring opening of oxabenzonorbornadienes with phenols was developed, which afforded the corresponding cis-2-(un)substituted phenoxy-1,2-dihydronaphthalen-1-ol products rather than the trans ones in excellent yields (up to 99%) with moderate to good enantioselectivities (up to 87% ee) under mild conditions. In addition, the cis-configuration of product 2b was confirmed by X-ray diffraction analysis. Based on the results, a potential mechanism for the present catalytic reaction was proposed.

Iridium-Catalyzed Asymmetric Ring-Opening of Oxabenzonorbornadienes with N-Substituted Piperazine Nucleophiles.

Iridium-catalyzed asymmetric ring-opening of oxabenzonorbornadienes with N-substituted piperazines was described. The reaction afforded the corresponding ring-opening products in high yields and moderate enantioselectivities in the presence of 2.5 mol % [Ir(COD)Cl]2 and 5.0 mol % (S)-p-Tol-BINAP. The effects of various chiral bidentate ligands, catalyst loading, solvent, and temperature on the yield and enantioselectivity were also investigated. A plausible mechanism was proposed to account for the formation of the corresponding trans-ring opened products based on the X-ray structure of product 2i.

Nickel-catalyzed asymmetric ring opening of oxabenzonorbornadienes with arylboronic acids.

A new, versatile, and highly efficient nickel-catalyzed asymmetric ring-opening (ARO) reaction of oxabenzonorbornadienes with a wide variety of arylboronic acids has been developed, yielding cis-2-aryl-1,2-dihydronaphthalen-1-ols in high yields (up to 99%) with good to excellent enantioselectivities (up to 99% ee) under very mild conditions. The effects of various nickel precursors, chiral bidentate ligands, catalyst loadings, bases, solvents, and temperatures on the yield and enantioselectivity of the reaction were also investigated. A plausible mechanism was proposed to account for the formation of the corresponding cis-ring-opened products based on the X-ray structure of product 4b.

Platinum(II)-catalyzed asymmetric ring-opening addition of arylboronic acids to oxabenzonorbornadienes.

A new platinum(II)-catalyzed asymmetric ring-opening addition of arylboronic acids to oxabenzonorbornadienes was developed, which afforded the corresponding cis-2-aryl-1,2-dihydronaphthalen-1-ol products in high yields (up to 97%) with moderate to good enantioselectivities (up to 89% ee) under very mild conditions. The effects of various ligands, catalyst loading, bases, solvents, and temperatures on the yield and enantioselectivity of the reaction were also investigated. The cis configuration of product 2m was confirmed by X-ray diffraction analysis. A potential mechanism for the present catalytic reaction is proposed.

Platinum-catalyzed anti-stereocontrolled ring-opening of oxabicyclic alkenes with Grignard reagents.

A new platinum-catalyzed anti-stereocontrolled ring-opening of oxabicyclic alkenes with various Grignard reagents was reported, which afforded the corresponding anti-2-substituted-1,2-dihydronaphthalen-1-ol products with moderate to good yields in the presence of a catalytic amount of Pt(PPh3)4 (2.5 mol%) under mild conditions. The effects of catalyst loading, solvent and temperature on the yield were also investigated. Furthermore, the trans-configuration of the product 5i was confirmed by X-ray diffraction analysis.

Iridium-catalyzed asymmetric ring-opening reactions of azabenzonorbornadiene with carboxylic acid nucleophiles.

Iridium-catalyzed asymmetric ring-opening reaction of N-substituted azabenzonorbornadienes with various carboxylic acids has been developed. The ring-opening reaction offered trans-1,2-dihydronaphthalene products containing an allylic carboxylate moiety in moderate yields (up to 89 %) with high enantioselectivities (up to 96 %). The trans-configuration of the products was confirmed by X-ray crystallography.

Iridium-catalyzed asymmetric ring-opening of azabicyclic alkenes with alcohols.

A novel asymmetric ring-opening reaction of N-substituted azabenzonorbornadienes with a wide variety of substituted benzyl alcohols and the addition reaction of N-substituted azabenzonorbornadienes with thiols are reported, affording the corresponding 1,2-trans-alkoxyamino products in moderate yields with excellent enantioselectivities (up to 94% ee) and the corresponding thiol addition products in high yields with lower enantiomeric excesses (ee) in the presence of iridium catalyst, respectively. The effects of ligands, catalyst loading, solvents and additives, and temperature were also investigated. The anti-configuration of the product 3c was confirmed by X-ray crystal structure analysis. A possible mechanism for the present catalytic reaction is proposed.

Iridium-catalyzed asymmetric ring-opening of oxabenzonorbornadienes with phenols.

A novel iridium-catalyzed asymmetric ring-opening (ARO) reaction of oxabenzonorbornadienes with a variety of phenols was reported, which afforded the corresponding trans-2-phenoxy-1,2-dihydronaphthalen-1-ol products in high yields with moderate to excellent enantioselectivities (up to 98% ee) under mild conditions. The trans products are formed via the enantioselective cleavage of a bridgehead carbon-oxygen bond in 1 followed by S(N)2 nucleophilic attack by phenols. The effects of various bisphosphine ligands, Ag (I) salts, ammonium halides, bases, and solvents on the yield and enantioselectivity of the reaction were also investigated. The trans-configuration of the product 2a was confirmed by X-ray crystal structure analysis. A possible mechanism for the present catalytic reaction was proposed.