A Recyclable Electrochemical Reduction of Aldehydes and Ketones to Alcohols Using Water as the Hydrogen Source and Solvent.

There are several challenging problems such as the usage of combustible and hazardous hydrogen sources and severe environmental pollution in the conventional reduction of aldehydes/ketones to alcohols. We report here a practical, safe, and green electrochemical reduction, which solves these problems to a large extent. Through an undivided cell, Zn(+) and Sn(-) as the electrode, tetrabutylammonium chloride (TBAC) as the electrolyte, water as the solvent and hydrogen source, a wide range of aldehydes and ketones are converted into the corresponding alcohols in mild conditions. Furthermore, the electrolytes and water can be recycled, and reductive deuteration can be achieved by simply using D2O as the solvent. Finally, the reduction can be smoothly scaled up to a kilogram level.

Radical Three-Component Nitro Spiro-Cyclization of Unsaturated Sulfonamides/Amides to Access NO2-Featured 4-Azaspiro[4.5]decanes.

Free radical three-component nitration/spirocyclization of unsaturated sulfonamides/amides with tert-butyl nitrite was developed for the construction of diverse NO2-revised 4-azaspiro[4.5]decanes. This tandem system featured metal-free participation, simple operation, good selectivity/yields, and a green/low-cost O source. Meanwhile, one nitro-containing complex molecule and a scaled-up operation were performed well to test the synthetic potential of the cascade reaction. Isotopic labeling, radical inhibition experiments, and DFT analysis were carried out to gain insight into the reaction process.

Metal-free radical bicyclization/chloroalkylarylation of 1,6-enynes with chloroalkanes.

Free radical initiated bicyclization of 1,6-enynes with chloralkanes, is achieved via selective activation of the C(sp3)-H bond of the chloralkane, resulting in diverse polychlorinated/chlorinated polyheterocycles. Two kinds of transformations and a scaled-up experiment were performed to test the synthetic importance of the organic chlorides. Finally, a range of radical inhibition operations and radical clock tests were explored to support the reaction process.

A free radical nitration of olefins with NaNO2/I2O5.

We demonstrated herein an I2O5-mediated radical nitration of olefins with NaNO2. A variety of (E)-nitroolefins can be synthesized in high yields and chemoselectivity.

Photoinduced Tandem Cyanomethylation/Cyclization of Unsaturated Compounds: Access to Cyanomethylated 7- or 5-Membered N-Heterocycles.

A cyanomethylation/cyclization of aryl acetylenes/ethylenes with bromoacetonitrile was finished in a photopromoted condition, which offers an efficient and mild protocol for the preparation of cyanomethylated 7- or 5-membered N-heterocycles with good yields. Meanwhile, trichloroacetonitrile was also compatible with this radical pathway. In addition, a variety of single-crystal X-ray diffraction measurements, scaled-up operations to 1 mmol, functional group transformations of final products, light on/off experiments, and even radial inhibition studies were smoothly performed in this tandem system.

Nitro-Spirocyclization of Biaryl Ynones with tert-Butyl Nitrite: Access to NO2-Substituted Spiro[5,5]trienones.

A metal/peroxide-free involved simple cascade 6-exo-trig spirocyclization of tert-butyl nitrite with biaryl ynones has been finished, which resulted in various NO2-modified spiro[5,5]trienones with good regioselectivity/yields. A variety of scaled-up experiments, reduction/epoxidation operations, and mechanistic studies were performed to verify the merits and spirocyclization process of this radical system. Finally, the structure of the spirocycles was confirmed by single-crystal X-ray diffraction.

Palladium-catalyzed C(sp3)-H nitrooxylation of masked alcohols.

A palladium-catalyzed ß-C(sp3)-H nitrooxylation of aliphatic alcohols with AgNO2 is reported. An 8-formylquinoline-derived oxime is installed as an exo-type directing group for sp3 C-H activation and selectfluor acts as the oxidant. The reaction tolerates a variety of functional groups and shows good selectivity for ß-C-H nitrooxylation of alcohols.

Free Radical Promoted Trifluoromethylthiolation of Alkynes to Access SCF3-Containing Dibenzazepines or Dioxodibenzothiazepines.

Persulfate-promoted radical cascade trifluoromethylthiolation of aryl acetylenes with AgSCF3 provides a simple reaction system for the synthesis of SCF3-substituted dibenzazepines or dioxodibenzothiazepines with good Z/E selectivity. The single-crystal X-ray diffraction data confirms the structures of the final products. A series of scaled-up experiments, further transformations, and radical inhibition experiments were operated in the reaction system.

Advances in free-radical alkylation and arylation with organoboronic acids.

Organoboronic acids act as carbon-centered radical precursors that are widely utilized to construct diverse C-C bonds. This review summarizes the advances in this field. The content is divided into four parts according to the different categories of coupling partners with organoboronic acids. The reaction conditions as well as the mechanisms are demonstrated in each part.

Electrochemical Aerobic Oxidative Cleavage of (sp3)C-C(sp3)/H Bonds in Alkylarenes.

An electrochemistry-promoted oxidative cleavage of (sp3)C-C(sp3)/H bonds in alkylarenes was developed. Various aryl alkanes can be smoothly converted into ketones/aldehydes under aerobic conditions using a user-friendly undivided cell setup. The features of air as oxidant, scalability, and mild conditions make them attractive in synthetic organic chemistry.

Free Radical-Promoted Monochloroalkylarylation of Alkenes with Chloralkanes.

Free radical-initiated cascade cyclization of unactivated alkenes with chloralkanes, which undergoes selective activation of the α-C(sp3)-H bond of chloralkanes, provides a protocol for the synthesis of chlorinated heterocycles or polycyclic compounds. A series of radical inhibition experiments, radical capture operations, and radical clock tests were studied in this system.

Site-Specific Oxidation of (sp3)C-C(sp3)/H Bonds by NaNO2/HCl.

A site-specific oxidation of (sp3)C-C(sp3) and (sp3)C-H bonds in aryl alkanes by the use of NaNO2/HCl was explored. The method is chemical-oxidant-free, transition-metal-free, uses water as the solvent, and proceeds under mild conditions, making it valuable and attractive to synthetic organic chemistry.

Molecular Oxygen-Mediated Radical Alkylation of C(sp3)-H Bonds with Boronic Acids.

A direct and site-specific alkylation of (sp3)C-H bond with aliphatic boronic acid was achieved. By simply heating glycinates and amines together with alkylboronic acids under an oxygen atmosphere, a variety of unnatural α-amino acids and peptides could be obtained in good yields.

Free-Radical-Promoted Dehydrogenative Coupling of Polyfluorinated Alcohol with Quinone, Chromone, and Coumarin.

A free-radical-mediated dehydrogenative cross-coupling reaction of polyfluorinated alcohol with quinone, coumarin, and chromone was developed. It provides a sustainable and practical strategy for installation of fluorine atom into organic molecules by using polyfluorinated alcohols.

Free Radical Addition of Nitrile, Ketone, and Ester to Alkyne and the Selectivity Discussion.

A general and practical atom transfer radical addition (ATRA) of simple nitriles, ketones, and esters to alkynes was developed. It can allow an efficient access to a wide range of ß,γ-unsaturated nitriles, ketones, and esters. The unique chemoselectivity in this system is also discussed.

Atom-Transfer Radical Addition of Alcohols to Aliphatic Alkynes.

An intermolecular hydrogen bond-promoted atom-transfer radical addition of simple alcohols to aliphatic alkynes is demonstrated here. Through this strategy, a variety of allyl alcohols can be synthesized in high selectivity and yields. Furthermore, this work reveals the relationship between selectivity and the substrate.

A free radical alkylation of quinones with olefins.

We demonstrated herein an Fe(iii)-mediated radical alkylation of quinones. A wide range of bioactive molecules with quinone motifs can be rapidly synthesized by using readily available and inexpensive NaBH4/NaBD4 with alkenes at room temperature under open flask conditions.

Molecular Oxygen-Promoted General and Site-Specific Alkylation with Organoboronic Acid.

A general alkylating method using organoboronic acid under 1 atm of oxygen is developed. It allows a facile access to a wide range of functionalized molecules with privileged scaffolds in drugs and natural products such as oxindoles, quinolinones, chromones, naphthoquinones, coumarins, and quinolones. In contrast to previous alkylation approaches that generally requiring transition-metal catalysis and a stoichiometric chemical oxidant, the present strategy features metal-free, molecular oxygen as the terminal oxidant and site specificity.

A Fe(III)/NaBH4-Promoted Free-Radical Hydroheteroarylation of Alkenes.

A free-radical-mediated intermolecular hydroheteroarylation of simple alkenes was developed. Through simply mixing heteroarenes, alkenes, Fe(III), and NaBH4 at 0 °C together, a wide range of alkylated heteroarenes could be afforded in moderate to excellent yields within 1 h.

Molecular Oxygen-Mediated Minisci-Type Radical Alkylation of Heteroarenes with Boronic Acids.

The carbon-carbon bond formation via autoxidation of organoboronic acid using 1 atm of O2 is achieved in a simple, clean, and green fashion. The approach allows a technically facile and environmentally benign access to structurally diverse heteroaromatics with medicinally privileged scaffolds. The strategy also displays its practicality and sustainability in the resynthesis of marketed drugs Crestor and pyrimethamine.