Radical Aryl Migration from Boron to Carbon.

Radical aryl migration reactions represent a unique type of organic transformations that involve the intramolecular migration of an aryl group from a carbon or heteroatom to a C- or heteroatom-centered radical through a spirocyclic intermediate. Various elements, including N, O, Si, P, S, Sn, Ge, and Se, have been reported to participate in radical aryl migrations. However, radical aryl migration from a boron center has not been reported to date. In this communication, radical 1,5-aryl migration from boron to carbon in aryl boronate complexes is presented. C-radicals readily generated through radical addition onto alkenyl aryl boronate complexes are shown to engage in 1,5-aryl migration reactions to provide 4-aryl-alkylboronic esters. As boronate complexes can be generated in situ by the reaction of alkenylboronic acid esters with aryl lithium reagents, the aryl moiety is readily varied, providing access to a series of arylated products starting from the same alkenylboronic acid ester via divergent chemistry. Reactions proceed with high diastereoselectivity under mild conditions, and also the analogous 1,4-aryl shifts are feasible. The suggested mechanism is supported by DFT calculations.

1,n-Bisborylalkanes via Radical Boron Migration.

A systematic study of radical boron migration in diboronate complexes to form synthetically valuable 1,n-bisborylalkanes is reported. The boronate complexes are readily generated by reaction of commercial bis(pinacolato)diboron with alkyl Grignard compounds. C-radical generation at a defined position with respect to the diboron moiety is achieved either via intermolecular H-abstraction with a CF3-radical or via alkene perfluoroalkyl radical addition. It is shown that radical 1,2- and 1,4-boron migrations to provide geminal and 1,3-bisborylalkanes are efficient transformations. The 1,5-boron migration in the homologous series leading to 1,4-bisborylalkanes is also occurring, albeit with lower efficiency. Experimental results are supported by DFT calculations which also reveal the corresponding 1,3-boron migration in such diboronate complexes to be feasible.

Hydrogen Atom Transfer Induced Boron Retaining Coupling of Organoboronic Esters and Organolithium Reagents.

α-Functionalization of alkyl boronic esters and homologation of aryl boronic esters by regioselective radical C(sp3)-H activation in boron-ate complexes is reported. Reaction of commercial or readily accessed aryl boronic acid pinacol esters with alkyl lithium reagents provides boron-ate complexes. Selective α-C-H abstraction by in situ generated trifluoromethyl radicals leads to radical anions that undergo electron transfer oxidation followed by 1,2-aryl/alkyl migration from boron to carbon to give the α-arylated/alkylated alkyl boronic esters. The valuable boronic ester functionality remains in the products and the cheap trifluoromethyl iodide acts as the oxidant in these C-C couplings. The 1,2-alkyl migration from boron to carbon is highly stereospecific allowing access to stereoisomerically pure boronic esters.

Divergent Synthesis of CF3 -Substituted Allenyl Nitriles by Ligand-Controlled Radical 1,2- and 1,4-Addition to 1,3-Enynes.

A ligand-controlled system that enables regioselective trifluoromethylcyanation of 1,3-enynes has been identified, which provides access to a variety of CF3 -containing tri- and tetrasubstituted allenyl nitriles. We disclose that the involved propargylic radicals can be selectively trapped by (Box)CuII cyanide, while the tautomerized allenyl radicals are trapped by (phen)CuII cyanide (Box= bisoxazoline, phen=phenanthroline). In addition, the reaction features broad substrate scope and excellent functional group compatibility. Moreover, this protocol represents a novel regioselectivity-tunable functionalization of 1,3-enynes via radicals, which we believe will have great implications for the development of catalytic systems for selectivity control in radical and organometallic chemistry.

Enantioselective Decarboxylative Cyanation Employing Cooperative Photoredox Catalysis and Copper Catalysis.

The merger of photoredox catalysis with asymmetric copper catalysis have been realized to convert achiral carboxylic acids into enantiomerically enriched alkyl nitriles. Under mild reaction conditions, the reaction exhibits broad substrate scope, high yields and high enantioselectivities. Furthermore, the reaction can be scaled up to synthesize key chiral intermediates to bioactive compounds.

Asymmetric Copper-Catalyzed Intermolecular Aminoarylation of Styrenes: Efficient Access to Optical 2,2-Diarylethylamines.

We have developed a copper-catalyzed enantioselective intermolecular aminoarylation of alkenes using a novel N-fluoro-N-alkylsulfonamide as the amine reagent, which could react with the Cu(I) catalyst to release a related amino radical. After addition to styrene, the generated benzylic radical could couple with a chiral L*CuIIAr complex to achieve enantioselective arylation. Various optical 2,2-diarylethylamines were efficiently synthesized from simple styrenes with high enantioselectivity, and these products can serve as valuable synthons toward bioactive molecules' synthesis.

Asymmetric Cu-Catalyzed Intermolecular Trifluoromethylarylation of Styrenes: Enantioselective Arylation of Benzylic Radicals.

A novel asymmetric radical trifluoromethyl-arylation of alkenes has been developed, which provides an efficient approach to access chiral CF3-containing 1,1-diarylmethane derivatives with good to excellent enantioselectivity. Various vinyl arenes and aryl boronic acids are compatible with these conditions. The utility of the method is demonstrated by accessing modified bioactive molecules.

Enantioselective Copper-Catalyzed Intermolecular Amino- and Azidocyanation of Alkenes in a Radical Process.

Asymmetric copper-catalyzed intermolecular amino- and azidocyanation reactions of alkenes have been developed that proceed via a radical process in which a key benzylic radical intermediate is enantioselectively trapped by a chiral Box/CuII cyanide complex. A variety of enantiomerically enriched ß-amino/azido alkylnitriles were efficiently synthesized. The ß-azido alkylnitriles could be converted into a series of highly valuable optically active amine-based building blocks and bioactive compounds.

Enantioselective Copper-Catalyzed Intermolecular Cyanotrifluoromethylation of Alkenes via Radical Process.

A novel enantioselective copper-catalyzed intermolecular cyanotrifluoromethylation of alkenes has been developed, in which a variety of CF3-containing alkylnitriles are furnished with excellent enantiomeric excess. Preliminary mechanistic studies revealed (1) the reaction was initiated by a SET process between activated Togni's CF3+ reagent and a Cu(I) catalyst; (2) the released CF3 radical readily added to styrene to provide a benzylic radical, which was then trapped by a chiral Cu(II) cyanide species to deliver the desired alkylnitriles; (3) a low concentration of the CN anion was crucial to obtain high enantioselectivity.

Copper-catalyzed intermolecular trifluoromethylarylation of alkenes: mutual activation of arylboronic acid and CF3+ reagent.

A novel copper-catalyzed intermolecular trifluoromethylarylation of alkenes is developed using less active ether-type Togni's reagent under mild reaction conditions. Various alkenes and diverse arylboronic acids are compatible with these conditions. Preliminary mechanistic studies reveal that a mutual activation process between arylboronic acid and CF3(+) reagent is essential. In addition, the reaction might involve a rate-determining transmetalation, and the final aryl C-C bond is derived from reductive elimination of the aryl(alkyl)Cu(III) intermediate.

Carbon dots-based dual-emission ratiometric fluorescent sensors for fluorescence and visual detection of hypochlorite and Cu2.

Carbon dots (CDs) with blue emission were synthesized by solvothermal method using hydroquinone and 5-aminoisphthalic acid as precursors. The strong oxidation of ClO- caused the fluorescence quenching of CDs at 405 nm, and synchronously generated a new emission peak at 500 nm. Furthermore, upon the addition of Cu2+ to CDs-ClO- system, the green fluorescence at 500 nm was quenched, while the blue emission at 405 nm remained unchanged, due to the complexation between Cu2+ and the amino group on the CDs surface. Meanwhile, the fluorescence color of system changed from blue to bright green and then to dark blue by sequentially increasing the concentrations of ClO- and Cu2+. The fluorescence signal of F500/F405 exhibited a linear relationship with the concentration of ClO- and Cu2+ in a certain range, respectively. Thus, a ratiometric fluorescence sensor based on the obtained CDs were developed to sequentially detect ClO- and Cu2+ with detection limits of 0.40 µM and 0.31 µM, respectively. Additionally, the CDs were mixed with polyvinyl alcohol hydrogel to form test strips, which were successfully used for visual detection of ClO- and Cu2+. Satisfactory results were also obtained in the analysis of ClO- and Cu2+ in actual water samples.

Intramolecular Hydrogen Atom Transfer Induced 1,2-Migration of Boronate Complexes.

Radical α-C-H functionalization of alk-5-enyl boronic esters with concomitant functionalization of the alkene moiety is reported. These cascades comprise perfluoroalkyl radical addition to the alkene moiety of a boronate complex, intramolecular hydrogen atom transfer (HAT), single electron oxidation, and 1,2-alkyl/aryl migration. The boronate complexes are readily generated in situ by reaction of the alkenyl boronic esters with alkyl or aryl lithium reagents. Products are formed in a divergent approach by varying carbon radical precursors as well as alkyl/aryl lithium donors, and reactions proceed under mild conditions upon UV irradiation.

Enantioselective cyanation of benzylic C-H bonds via copper-catalyzed radical relay.

Direct methods for stereoselective functionalization of sp3-hybridized carbon-hydrogen [C(sp3)-H] bonds in complex organic molecules could facilitate much more efficient preparation of therapeutics and agrochemicals. Here, we report a copper-catalyzed radical relay pathway for enantioselective conversion of benzylic C-H bonds into benzylic nitriles. Hydrogen-atom abstraction affords an achiral benzylic radical that undergoes asymmetric C(sp3)-CN bond formation upon reaction with a chiral copper catalyst. The reactions proceed efficiently at room temperature with the benzylic substrate as limiting reagent, exhibit broad substrate scope with high enantioselectivity (typically 90 to 99% enantiomeric excess), and afford products that are key precursors to important bioactive molecules. Mechanistic studies provide evidence for diffusible organic radicals and highlight the difference between these reactions and C-H oxidations mediated by enzymes and other catalysts that operate via radical rebound pathways.

[Studies on chemical constituents from Polygonum macrophyllum].

OBJECTIVE: To study the chemical structures from Polygonum macrophyllum D. Don. METHODS: To isolate the constituents by reverse phase chromatography and characterize their structures by the analysis of chemical property and spectral data. RESULT: Six compounds were isolated from the 70% acetone extract from the complete herb of P. macrophyllum. Their structures were elucidated as (-)-epicatechin-5-O-beta-D-glucopyranoside (I), (+)-catechin-7-O-beta-D-glucopyranoside (II), 1-(3-O-beta-D-glucopyranosyl 4,5-dihydroxy-phenyl)-ethanone (III) (-)-epicatechin (IV), chlorogenic acid (V) and gallic acid (VI). CONCLUSION: Compounds I-VI were isolated from the plant for the first time.

[Toxicity of 50% ethanol salt powder of niclosamide on growth of silkworms].

OBJECTIVE: To observe the toxity of niclosamide on the growth of silkworms. METHODS: Mulberry leaves were soaked in the different concentrations of solution of 50% ethanol salt powder of niclosamide for 10 s or 3 min, and then the leaves were fed to silkworms. The death rates of silkworms and the weight of cocoons were observed. Normal feeding control groups were established. RESULTS: The death rates were 22.5%-85.0% and 56.0%-100% in the 10-s-soaked groups and 3-min groups, respectively, which were significantly higher than those in the control groups. CONCLUSION: The 50% ethanol salt powder of niclosamide has a toxity for silkworm. Therefore, we should properly handle the relationship between the Oncomelania snail control and silkworm breeding.

[Compliance of film-coated praziquantel tablets in schistosomiasis transmission-controlled areas].

OBJECTIVE: To observe the compliance of film-coated praziquantel tablets in the schistosomiasis transmission controlled areas, so as to provide the evidence for the establishment of chemotherapy intervention measures in these areas. METHODS: In the areas of schistosomiasis transmission controlled in Sichuan Province, 234 people were selected as film-coated praziquantel group (FCPG), and 203 people were selected as praziquantel group (PG). A questionnaire survey was implemented and the compliance of chemotherapy of the 2 groups was compared. RESULTS: In PG, all the people indicated that the praziquantel tablets has bad smell, 98.0% of the people had side-effects, such as nausea, headache, 69.5% thought the medicine was harmful to health subjectively, and 99.5% thought that it was too much dose of tablets for taking one time. In FCPG, all the people indicated that the film-coated praziquantel tablets had no bad smell, 18.8% of the people had side-effects, and 74.4% would like to choose film-coated praziquantel tablets. The rates of knowledge of praziquantel of PG and FCPG were 50.7% and 29.1%, respectively ( chi2 = 21.449, P = 0.01). CONCLUSIONS: The film-coated praziquantel tablets have no bad smell and lighter side-effects. The compliance of the film-coated praziquantel tablets is high in the areas of schistosomiasis transmission controlled, so the film-coated praziquantel tablets are worth to popularize and apply.

[One-stage urethroplasty with circumferential vascular pedicle preputial island flap for perineal hypospadias].

OBJECTIVE: To report the treatment of perineal hypospadias with one-stage urethroplasty with circumferential vascular pedicle preputial island flap. METHODS: A circumferential incision was made proximal to the corona and the urethral plate to correct chordee. A U-shaped skin incision was then made surrounding the meatus, and extended to the dorsal prepuce and parallel to the first incision. The tissue between the prepuce and dartos was dissected on the dorsum of penis to fix the prepuce as a neo urethra. After mobilizing the loop shaped skin flap through the button-hole of the pedicle, the internal and external sides of the loop were sutured to construct a new urethra. The catheter was removed 10-14 days (mean, 12.8 days) after operation. RESULTS: Since 1997, 22 patients with perineal hypospadias were treated. Primary healing was achieved in 18 cases (81.8%). Fistula happened in 4 patients. Among them, one case with meatal stenosis was treated with dilatation. Another 3 patients were reoperated. The neo urethral flap was 3.50-18.00 cm (mean, 9.43 cm) in length. All patients were followed up for more than 6 months. Good cosmetic appearance was achieved in 72.7% (16/22) of the patients. CONCLUSIONS: The circumferential vascular pedicle preputial island flap has advantages of good blood supply and autograft for new meatus, which allows the chordee correction and urethroplasty at one stage. It is a good method for the treatment of perineal hypospadias with severe chordee and penoscrotal transposition.