Multicomponent Strategy to Pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine Derivatives under Microwave Irradiation.

A novel three-component reaction has been established that allows a flexible and practical approach to pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives from phenylglyoxal, ß-ketoamide, and 5-aminopyrazole with acetic acid as the solvent. Various dihydropyrazolo[3,4-b]pyrrolo[3,4-d]pyridin-6(3H)-one were isolated in moderate to good yields with broad functional group tolerance.

Visible-Light-Induced para-Difluoroalkylation of Aniline Derivatives.

Visible-light-induced, iridium catalyzed, para-selective C-H difluoroalkylation of aniline derivatives under mild reaction conditions is reported. Various substrates and bioactive compounds, such as precursors of vorinostat and chlorpropham, were all well tolerated. This protocol features a wide substrate scope, high regioselectivity, low catalyst usage, and operational simplicity.

Direct para-Selective C-H Amination of Iodobenzenes: Highly Efficient Approach for the Synthesis of Diarylamines.

Iodine(III)-mediated synthesis of 4-iodo-N-phenylaniline from iodobenzene has been achieved, and the reaction can proceed under mild conditions. A variety of functional groups were well tolerated, providing the corresponding products in moderate to good yields. The remaining iodine group provides an effective platform for converting the products into several valuable asymmetric diphenylamines. Most importantly, this reaction can be easily scaled up to the ten-gram scale, highlighting its synthetic utility. The mechanistic study revealed that the in situ generated aryl hypervalent iodine intermediate is the key factor to realize this para-selective C-H amination reaction.

Photoredox-Catalyst-Enabled para-Selective Trifluoromethylation of tert-Butyl Arylcarbamates.

The direct incorporation of a trifluoromethyl group on an aromatic ring using a radical pathway has been extensively investigated. However, the direct highly para-selective C-H trifluoromethylation of a class of arenes has not been achieved. In this study, we report a light-promoted 4,5-dichlorofluorescein (DCFS)-enabled para-selective C-H trifluoromethylation of arylcarbamates using Langlois reagent. The preliminary mechanistic study revealed that the activated organic photocatalyst coordinated with the arylcarbamate led to para-selective C-H trifluoromethylation. Ten-gram scale reaction performs well highlighting the synthetic importance of this new protocol.

Mixed methods to explore factors associated with the decline of patients in the methadone maintenance treatment program in Shanghai, China.

BACKGROUND: This study was to characterize the Methadone Maintenance Treatment (MMT) in Shanghai, China, and to explore factors associated with the decline of patients in MMT during 2005-2016. METHODS: Both qualitative and quantitative methods were used in this study. Based on the data from Shanghai Centers for Disease Control (CDC), we described the changes in the number of patients who received MMT, and new enrollment each year from 2005 to 2016. Focus groups were conducted with 22 patients, and in-depth interviews were conducted with 9 service providers. RESULTS: Quantitative data demonstrate that the number of new enrollment began to decline in 2009, and the number of patients receiving MMT began to decline in 2012. The main reasons for dropout include (1) discontinuing medication due to unknown reasons (25%), (2) criminal activities other than drug-related crimes (20%), (3) relapse to heroin use (16%), and (4) physical disease (10%). Qualitative assessment results indicate that the major reasons for the decline of patients in MMT are as follows: (1) the increase of Amphetamine-type stimulants (ATS) use in recent years, (2) limited knowledge about MMT in both patients and MMT staff, (3) complicated enrollment criteria, and (4) discrimination against drug use. CONCLUSION: Various reasons to explain the decline of patients in MMT in Shanghai, China, were identified. Government agencies, service providers, and other stakeholders need to work together and overcome identified barriers to support MMT programs in China.

Ruthenium-Catalyzed Carbonylation of Oxalyl Amide-Protected Benzylamines with Isocyanate as the Carbonyl Source.

An efficient synthesis of isoindolin-1-ones from oxalyl amide-protected benzylamines, through ruthenium-catalyzed intramolecular C(sp2)-H carbonylation, has been developed. Variously substituted benzylamines could be well tolerated in this new protocol, affording the corresponding products in moderate to excellent yields. This approach constitutes the first example of Ru(II)-catalyzed C(sp2)-H carbonylation with isocyanate as a novel commercially available carbonyl source.

Pd-Catalyzed regioselective sequential meta-, ortho-C-H functionalization of arenes: a predictable approach to the synthesis of polysubstituted ß-arylethylamines.

With the assistance of the same bidentate directing group, the first example of sequential, controllable C-H functionalization of ß-arylethylamines at different positions for the construction of polysubstituted arenes is reported. Pd-Catalyzed highly regioselective ortho-C-H functionalization reactions of meta-aryl substituted arylethylamines are performed, including alkynylation, iodination, acetoxylation and amination, which led to a concise approach to the synthesis of polysubstituted ß-arylethylamine derivatives.

Microwave-assisted synthesis of novel hetero[5]helicene-like molecules and coumarin derivatives.

A concise and efficient approach to design and synthesize hetero[5]helicene-like molecules and coumarin derivatives is reported. Intriguingly, using the same catalyst (silica sulfuric acid), and a different solvent and reaction temperature, the reaction selectively afforded hetero[5]helicene-like molecules 3 or coumarin derivatives 4. Product 4 has a highly planar geometry, and product 3 can be regarded as hetero[5]helicene-like because of its helical conformation.

An efficient one-pot synthesis of functionalized chromeno[4,3-b]pyridine derivatives under catalyst-free conditions.

A concise, efficient one-pot synthesis of functionalized chromeno[4,3-b]pyridine derivatives via a three-component reaction of 4-oxo-4H-chromene-3-carbaldehydes, malononitrile or cyanoacetates, and aromatic amines under catalyst-free conditions in an environmentally friendly medium (ethanol-water, 3:1 v/v) is described. This synthesis involves a group-assisted purification process, which avoids traditional recrystallization and chromatographic purification methods.

Pd-Catalyzed Coupling of γ-C(sp(3))-H Bonds of Oxalyl Amide-Protected Amino Acids with Heteroaryl and Aryl Iodides.

Pd-catalyzed regioselective coupling of γ-C(sp(3))-H bonds of oxalyl amide-protected amino acids with heteroaryl and aryl iodides is reported. A wide variety of iodides are tolerated, giving the corresponding products in moderate to good yields. Various oxalyl amide-protected amino acids were compatible in this C-H transformation, thus representing a practical method for constructing non-natural amino acid derivatives.

Multicomponent Strategy to Pyrazolo[3,4-e]indolizine Derivatives under Microwave Irradiation.

A simple and efficient one-pot construction of pyrazolo[3,4-e]indolizine derivatives via a diethylamine-catalyzed three-component domino reaction of arylglyoxals, cyclic 1,3-diones, and 5-aminopyrazoles under microwave irradiation is described. In this one-pot transformation, seven bonds and two new rings are efficiently formed. This synthesis was confirmed to follow the group-assisted-purification (GAP) chemistry process, which can avoid traditional recrystallization or chromatography purification methods.

Multicomponent strategy to indeno[2,1-c]pyridine and hydroisoquinoline derivatives through cleavage of carbon­carbon bond.

A concise and efficient three-component domino reaction has been developed for the synthesis of polyfunctionalized indenopyridine and hydroisoquinoline derivatives via the cleavage of a C­C bond under transition-metal-free conditions. This reaction provides facile access to complex nitrogen-containing heterocycles by simply mixing three common starting materials in EtOH in the presence of 20 mol % NaOH under microwave irradiation conditions.

Palladium-Catalyzed ortho-Olefination of Phenyl Acetic and Phenyl Propylacetic Esters via C-H Bond Activation.

A highly regioselective palladium-catalyzed ester-directed ortho-olefination of phenyl acetic and propionic esters with olefins via C-H bond activation has been developed. A wide variety of phenyl acetic and propionic esters were tolerated in this transformation, affording the corresponding olefinated aromatic compounds. The ortho-olefination of heterocyclic acetic and propionic esters also took place smoothly giving the products in good yields, thus proving the potential utility of this protocol in synthetic chemistry.

Palladium-Catalyzed Oxalyl Amide-Directed γ-Arylation of Aliphatic Amines.

A method for palladium-catalyzed oxalyl amide-directed arylation of α-unsubstituted aliphatic amines with aryl iodides has been developed. A wide variety of aryl iodides are tolerated in this transformation, affording various γ-arylpropylamine derivatives. Heterocyclic iodides can also be competent reagents in this γ-C(sp(3))-H bonds transformation.

Selective synthesis of polyfunctionalized pyrido[2,3-b]indoles by multicomponent domino reactions.

A series of novel polyfunctionalized pyrido[2,3-b]indoles were synthesized by three- or four-component domino reactions under microwave irradiation. This protocol has the advantages of readily available starting materials, short reaction times, high yields, easy workup, and high chemo- and regioselectivities.

An efficient three-component synthesis of highly functionalized tetrahydroacenaphtho[1,2-b]indolone derivatives catalyzed by L-proline.

An efficient and diastereoselective synthetic procedure for highly functionalized tetrahydroacenaphtho[1,2-b]indolone derivatives was successfully developed by the three-component reaction of acenaphthequinone, enaminones, and barbituric acid in the presence of a catalytic amount of L-proline. This method has the advantages of convenient operation, excellent yields, mild reaction conditions, and environmental friendliness.

Clean and efficient synthesis of isoxazole derivatives in aqueous media.

A series of 5-arylisoxazole derivatives were synthesized via the reaction of 3-(dimethyl-amino)-1-arylprop-2-en-1-ones with hydroxylamine hydrochloride in aqueous media without using any catalyst. This method has the advantages of easier work-up, mild reaction conditions, high yields, and an environmentally benign procedure.

Ultrasound-promoted one-pot, four-component synthesis of pyridin-2(1H)-one derivatives.

An efficient one-pot synthesis of 1,6-diamino-2-oxo-1,2,3,4-tetrahydro- pyridine-3,5-dicarbonitrile derivatives by four-component piperidine-catalyzed reactions of a ketone, malononitrile, ethyl cyanoacetate and hydrazine hydrate under ultrasound irradiation is described. This method provides several advantages such as shorter reaction times, excellent yields, and a simple workup procedure.

Microwave-assisted improved synthesis of pyrrolo[2,3,4-kl]acridine and dihydropyrrolo[2,3,4-kl]acridine derivatives catalyzed by silica sulfuric acid.

An improved synthesis of multifunctionalized pyrrolo[2,3,4-kl]acridine derivatives with different substituted patterns using silica sulfuric acid (SSA) as a heterogeneous catalyst under microwave irradiation conditions was developed. The reaction could be conducted by using readily available and inexpensive substrates within short periods of 12-15 min. under microwave irradiation. Compared with the conventional methods, the remarkable advantages of this method are milder reaction conditions, operational simplicity, higher yields, short reaction times, and an environmentally friendly procedure.

Ultrasound-promoted one-pot, three-component synthesis of spiro[indoline-3,1'-pyrazolo[1,2-b]phthalazine] derivatives.

A series of 3'-aminospiro[indoline-3,1'-pyrazolo[1,2-b]phthalazine]-2,5',10'-trione derivatives have been synthesized by a one-pot three-component reaction of isatin, malononitrile or ethyl cyanoacetate and phthalhydrazide catalyzed by piperidine under ultrasound irradiation. For comparison the reactions were carried out under both conventional and ultrasonic conditions. In general, improvement in rates and yields were observed when the reactions were carried out under sonication compared with classical conditions.