Aerobic Oxidative Hydroxylation of Arylboronic Acids under Visible-Light Irradiation without Metal Catalysts or Additives.

Phenols are versatile synthetic intermediates and key structural motifs in many natural products and biologically active compounds. We herein report a visible-light-induced aerobic oxidative hydroxylation of arylboronic acids/pinacol esters using air as oxidant and without using any catalysts and base, etc., additives, providing a green entry to a variety of phenols in a highly efficient and concise fashion. This novel reaction is enabled by photoactivation of an electron donor-acceptor complex, in which THF serves as both the solvent and electron donor. DFT studies indicated that the oxidation process involves a concerted hydrogen abstraction transfer from THF and dehydroxylation of boronic acid undergoing spin crossover from triplet to singlet to produce an active peroxoboronic acid intermidiate. Salient merits of this chemistry include broad substrate scope and excellent functional group tolerance, gram-scale synthesis, and versatile late-stage functionalizations as well as the use of air, visible light, and catalyst- and additive-free conditions. This strategy introduces a novel photoreaction mode with the aid of a solvent, offering a succinct and environmentally sustainable route for synthesizing phenols. The strong practicability and highly efficient access to modifying complex biorelevant molecules bode well for the potential applications of this chemistry in pharmaceutical chemistry.

De novo design and synthesis of dipyridopurinone derivatives as visible-light photocatalysts in productive guanylation reactions.

Described here is the de novo design and synthesis of a series of 6H-dipyrido[1,2-e:2',1'-i]purin-6-ones (DPs) as a new class of visible-light photoredox catalysts (PCs). The synthesized DP1-5 showed their λ Abs(max) values in 433-477 nm, excited state redox potentials in 1.15-0.69 eV and -1.41 to -1.77 eV (vs. SCE), respectively. As a representative, DP4 enables the productive guanylation of various amines, including 1°, 2°, and 3°-alkyl primary amines, secondary amines, aryl and heteroaryl amines, amino-nitrile, amino acids and peptides as well as propynylamines and α-amino esters giving diversities in biologically important guanidines and cyclic guanidines. The photocatalytic efficacy of DP4 in the guanylation overmatched commonly used Ir and Ru polypyridyl complexes, and some organic PCs. Other salient merits of this method include broad substrate scope and functional group tolerance, gram-scale synthesis, and versatile late-stage derivatizations that led to a derivative 81 exhibiting 60-fold better anticancer activity against Ramos cells with the IC50 of 0.086 µM than that of clinical drug ibrutinib (5.1 µM).

Selective Removal of Aminoquinoline Auxiliary by IBX Oxidation.

8-Aminoquinoline (AQ) is a widely used bidentate auxiliary in metal-catalyzed directed C-H functionalization reactions. Herein, we report an efficient and chemoselective method to convert various N-quinolyl carboxamides to primary amides with the treatment of a stoichiometric amount of 2-iodoxybenzoic acid oxidant or the combination of a catalytic amount of 2-iodobenzoic acid and Oxone co-oxidant in mixed solvents of H2O and HFIP. Its unique compatibility with the Phth-protected α-amino acid (αAA) substrates enhances the overall synthetic utility of the AQ-directed palladium-catalyzed C-H functionalization strategy for synthesis of complex αAAs.

Acylamino-Directed Specific Sequential Difunctionalizations of Anilides via Metal-Free Relay Reactions for p-Oxygen and o-Nitrogen Incorporation.

Novel acylamino-directed relay disubstitutions realize the sequential difunctionalizations of anilides (1) under mild and metal-free conditions for the first time. This [bis(trifluoroacetoxy)iodo]benzene (PIFA) and BF3·Et2O promoted straightforward reaction produces a series of p-acetoxyl- or p-alkoxyl- o-nitro- N-arylamides (2), which are key scaffolds of various drugs, functional materials, and bioactive molecules. The flexibility with respect to the functional groups in these products affords this novel protocol excellent versatility for synthetic applications.

Selective Cleavage of Inert Aryl C-N Bonds in N-Aryl Amides.

A highly selective, IBX-promoted reaction has been developed for the oxidative cleavage of inert C(aryl)-N bonds on secondary amides while leaving the C(carbonyl)-N bond unchanged. This metal-free reaction proceeds under mild conditions (HFIP/H2O, 25 °C), providing facile access to various useful primary amides, some of which would be otherwise unattainable using conventional aminolysis and hydrolysis approaches.

Hypervalent Iodine(III)-Promoted Phenyl Transfer Reaction from Phenyl Hydrazides to Nitriles.

A useful transformation of nitriles to N-phenyl amides has been achieved through a novel intermolecular phenyl transfer reaction from phenyl hydrazides and N-addition to nitriles in the presence of PIFA under mild and solvent-free conditions. This cross-coupling reaction includes the oxidative cleavage of sp2 C-N bonds of phenyl hydrazides to form a phenyl radical and the subsequent N-addition to cyanos to form new sp2 C-N bonds and provides efficient access to various N-phenyl amides in moderate to good yields under mild reaction conditions.

Oxidation of ß-Ketoamides: The Synthesis of Vicinal Tricarbonyl Amides.

A facile and direct oxidative reaction for the synthesis of vicinal tricarbonyl amides in moderate to excellent yields (53-88%) was developed starting from readily available ß-ketoamides in the presence of phenyliodine(III) bis(trifluoroacetate). The resulting products possess significant synthetic potential, making this approach a valuable addition to the group of traditional methods already available for the preparation of these molecules.

Ammonium Acetate-Promoted One-Pot Tandem Aldol Condensation/Aza-Addition Reactions: Synthesis of 2,3,6,7-Tetrahydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-ones.

An efficient tandem intermolecular one-pot aldol condensation/aza-addition reaction of 2-methyl-3-carbamoylpyrroles and aldehydes was developed for the synthesis of 2,3,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-ones. The reaction proceeded using only 3.0 equiv of ammonium acetate promoter in green solvent poly(ethylene glycol)-400 at 100 °C to afford a series of pyrrolo[3,2-c]pyridinone derivatives in good to excellent yields.