A Biaryl-Cyclohexenone Photoelectrocyclization/Dearomatization Sequence to Substituted Terpenes.

Described here is the development of sequential cross-coupling, photoelectrocyclizations, and reductive dearomatizations of biaryl cyclohexenones as a means of synthesizing terpene skeletons. This methodology promises to provide insight that will enable us and others to use this approach to generate a variety of biologically active small molecules, including members of the abietane and morphinan skeletons.

Asymmetric Rubottom-Type Oxidation Catalyzed by Chiral Calcium Phosphates.

Invited for the cover of this issue is the group of Jon C. Antilla at Zhejiang Sci-Tech University. The image depicts asymmetric Rubottom-type oxidation catalyzed by chiral calcium phosphates. Read the full text of the article at 10.1002/chem.202203720.

Asymmetric Rubottom-Type Oxidation Catalyzed by Chiral Calcium Phosphates.

A highly efficient catalytic asymmetric Rubottom-type oxidation is described. Using meta-chloroperbenzoic acid (m-CPBA) as the oxidant and chiral calcium phosphate as the catalyst, the facile transformation enables direct hydroxylation of N-Boc oxindoles and ß-ketoesters in high yields (up to 99 %) and in a highly enantioenriched fashion (up to >99 % ee). The application of the established method was demonstrated by the synthesis of a pharmaceutically important 3-hydroxyoxindole with excellent enantiocontrol.

Chiral Calcium Phosphate-Catalyzed Enantioselective Amination of 3-Aryl-2-oxindoles with Dibenzyl Azodicarboxylate.

A chiral calcium phosphate-catalyzed enantioselective amination of 2-oxindoles with dibenzyl azodicarboxylate has been developed, affording the products in consistently high yields and excellent enantioselectivity. This synthetic method features low catalyst loading and a high catalytic efficiency. Moreover, the practical value of this process is well demonstrated by a scale-up experiment and a trial of catalyst recovery and reuse.

Chiral Calcium Phosphate Catalyzed Enantioselective Amination of 3-Aryl-2-benzofuranones.

A 4-tert-butyl-phenyl substituted (R)-[H8]-BINOL chiral calcium phosphate catalyzed enantioselective amination of 3-aryl-2-benzofuranones with dibenzyl azodicarboxylate is described. The catalyst loading of the reaction is 1 mol %. This transformation is facile and has a high degree atom economy, which gave products with good yields and high enantioselectivities (79% to 99%). This reaction has excellent ee and a broad substrate scope with mild reaction conditions.

Palladium-Catalyzed Serendipitous Synthesis of Arylglyoxylic Amides from Arylglyoxylates and N,N-Dialkylamides in the Presence of Halopyridines.

A palladium-catalyzed synthesis of arylglyoxylic amides by the reaction of arylglyoxylates and N,N-dialkylamides in the presence of a 2,3-dihalopyridine has been realized for the first time. An anticipated 2,3-diaroylpyridine did not form in this reaction. The current study unveils an unprecedented role of 2,3-dihalopyridine toward this amidation. Our mechanistic study reveals that the arylglyoxylate could react with halopyridine to form a traceless activated pyridyl ester of arylglyoxylic acid, which upon subsequent reaction with amino surrogate, N,N-dialkylamides could form the arylglyoxylic amides.

Formation of amides, their intramolecular reactions for the synthesis of N-heterocycles, and preparation of a marketed drug, sildenafil: a comprehensive coverage.

A unified approach to the tandem preparation of diverse nitrogen heterocycles via decarboxylative acylation of ortho-substituted amines with α-oxocarboxylic acids and subsequent intramolecular cyclizations has been developed. The key features of this work include: the first example of transition-metal-free decarboxylative amidation of α-oxocarboxylic acids with ortho-substituted amines, realization of intramolecular cyclization of amides employing nucleophiles that have previously been unexplored, mechanistic investigation of an unprecedented K2S2O8 promoted amide formation and its subsequent intramolecular cyclizations, and application to the synthesis of a best-selling marketed drug.

Implications of dynamic imine chemistry for the sustainable synthesis of nitrogen heterocycles via transimination followed by intramolecular cyclisation.

An exploration of a tandem approach to the sustainable synthesis of N-heterocycles from readily available N-aryl benzylamines or imines and ortho-substituted anilines is described, which demonstrates, for the first time, an important synthetic application of dynamic imine chemistry. The key features to the successful development of this protocol include the utilisation of N-aryl benzylamines as imine precursors in transimination, the occurrence of transimination in acetonitrile in the absence of any catalysts, an intramolecular nucleophilic addition occurring in the newly formed imine causing irreversible transimination, and the tandem event occurring under green conditions.

Sulfate Radical Anion (SO4(•-)) Mediated C(sp(3))-H Nitrogenation/Oxygenation in N-Aryl Benzylic Amines Expanded the Scope for the Synthesis of Benzamidine/Oxazine Heterocycles.

A transition-metal-free, K2S2O8-mediated intramolecular oxidative nitrogenation/oxygenation of C(sp(3))-H in N-aryl benzylic amines followed by oxidation at the benzylic center has been developed for the synthesis of benzamidine/benzoxazine heterocycles, providing an expedient access to quinazolin-4(3H)-ones, N-aryl-2-arylbenzimidazoles, and 4H-3,1-benzoxazin-4-ones. A considerable amount of work dealing with the mechanistic study to understand the crucial intramolecular cyclization step largely favors an iminium ion as the key intermediate.

Transition-metal-free tandem oxidative removal of benzylic methylene group by C-C and C-N bond cleavage followed by intramolecular new aryl C-N bond formation under radical conditions.

A novel tandem oxidative conversion of 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepines to phenazines has been achieved under transition-metal-free, mild conditions using K2S2O8 or DDQ as the oxidizing agent. The transformation proceeds through oxidative removal of a benzylic methylene group by C-C and C-N bond cleavage followed by a new aryl C-N bond formation under radical conditions.