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The direct utilization of simple and abundant feedstocks in carbon‐carbon bond‐forming reactions to embellish sp3‐enriched chemical space is highly desirable. Herein, we report a novel photochemical deoxygenative hydroalkylation of unactivated alkenes with readily available carboxylic acid derivatives. The reaction displays broad functional group tolerance, accommodating carboxylic acid‐, alcohol‐, ester‐, ketone‐, amide‐, silane‐, and boronic ester groups, as well as nitrile‐containing substrates. The reaction is operationally simple, mild, and water‐tolerant, and can be carried out on multigram‐scale, which highlights the utility of the method to prepare value‐added compounds in a practical and scalable manner. The synthetic application of the developed method is further exemplified through the synthesis of suberanilic acid, a precursor of vorinostat, a drug used for the treatment of cutaneous T‐cell lymphoma. A novel mechanistic approach was identified using thiol as a nucleophilic catalyst, which forms a key intermediate for this transformation. Furthermore, electrochemical studies, quantum yield, and mechanistic experiments were conducted to support a proposed catalytic cycle for the transformation. [ABSTRACT FROM AUTHOR]

The direct methylation of N‐heterocycles is an important transformation for the advancement of pharmaceuticals, agrochemicals, functional materials, and other chemical entities. Herein, the unprecedented C(sp2)‐H methylation of iminoamido heterocycles as nucleoside base analogues is described. Notably, trimethylsulfoxonium salt was employed as a methylating agent under aqueous conditions. A wide substrate scope and excellent level of functional‐group tolerance were attained. Moreover, this method can be readily applied to the site‐selective methylation of azauracil nucleosides. The feasibility of gram‐scale reactions and various transformations of the products highlight the synthetic potential of the developed method. Combined deuterium‐labeling experiments aided the elucidation of a plausible reaction mechanism. [ABSTRACT FROM AUTHOR]

Rhodium(III)‐catalyzed hydroxymethylation followed by intramolecular annulation of azobenzenes using paraformaldehyde as a valuable C1‐feedstock is described. The method is readily extended to the coupling reaction between azobenzenes and trifluoroacetaldehyde. This transformation efficiently produces a range of C3‐unsubstituted and C3‐trifluoromethylated (2H)‐indazoles, which are important targets in the development of novel bioactive compounds. Excellent chemoselectivity and functional group tolerance were observed. The synthetic transformation of C3‐unsubstituted (2H)‐indazoles highlights the utility of the developed method. [ABSTRACT FROM AUTHOR]

The rhodium(iii)-catalyzed cross-coupling reaction of 8-methylquinolines with a range of allylic alcohols in water is described. This approach leads to the synthesis of various γ-quinolinyl carbonyl compounds, which are synthetically useful precursors for the construction of bioactive tetrahydroquinoline and azasteroid derivatives. [ABSTRACT FROM AUTHOR]

Nonenzymatic reactions, though critical in natural product biosynthesis, are significantly challenging to control. Adding 3% NaI to the culture medium of Penicillium janczewskii significantly increased pseurotin D ( 1 ) production and decreased pseurotin A ( 2 ) production. Previously, 1 and 2 were suggested to be produced via a nonenzymatic reaction, where the epoxide at C-10 undergoes S N 2 ( 2 ) or S N 2' ( 1 ) reactions. We confirmed that 1 was isolated as a 1:1 mixture of C-13 epimers by spectral elucidation via CP3 analysis aided by selective excitation NMR methods, which supported that 1 was produced through a nonenzymatic S N 2' reaction. We propose that NaI increased the ratio of 1 by causing steric hindrance at the C-11 position of the transient intermediate, which makes C-13 more preferred in the S N 2/S N 2' competition.

The direct utilization of simple and abundant feedstocks in carbon-carbon bond-forming reactions to embellish sp 3 -enriched chemical space is highly desirable. Herein, we report a novel photochemical deoxygenative hydroalkylation of unactivated alkenes with readily available carboxylic acid derivatives. The reaction displays broad functional group tolerance, accommodating carboxylic acid-, alcohol-, ester-, ketone-, amide-, silane-, and boronic ester groups, as well as nitrile-containing substrates. The reaction is operationally simple, mild, and water-tolerant, and can be carried out on multigram-scale, which highlights the utility of the method to prepare value-added compounds in a practical and scalable manner. The synthetic application of the developed method is further exemplified through the synthesis of suberanilic acid, a precursor of vorinostat, a drug used for the treatment of cutaneous T-cell lymphoma. A novel mechanistic approach was identified using thiol as a nucleophilic catalyst, which forms a key intermediate for this transformation. Furthermore, electrochemical studies, quantum yield, and mechanistic experiments were conducted to support a proposed catalytic cycle for the transformation., (© 2023 Wiley-VCH GmbH.)

The direct methylation of N-heterocycles is an important transformation for the advancement of pharmaceuticals, agrochemicals, functional materials, and other chemical entities. Herein, the unprecedented C(sp 2 )-H methylation of iminoamido heterocycles as nucleoside base analogues is described. Notably, trimethylsulfoxonium salt was employed as a methylating agent under aqueous conditions. A wide substrate scope and excellent level of functional-group tolerance were attained. Moreover, this method can be readily applied to the site-selective methylation of azauracil nucleosides. The feasibility of gram-scale reactions and various transformations of the products highlight the synthetic potential of the developed method. Combined deuterium-labeling experiments aided the elucidation of a plausible reaction mechanism., (© 2020 Wiley-VCH GmbH.)

The rhodium(III)-catalyzed C-H functionalization followed by intramolecular annulation reactions between azobenzenes and sulfoxonium ylides is described. This protocol leads to the efficient formation of 3-acyl (2 H)-indazoles with a range of substrate scope. A high level of chemoselectivity and functional group tolerance of this transformation were also observed.

The rhodium(iii)-catalyzed cross-coupling reaction of 8-methylquinolines with a range of allylic alcohols in water is described. This approach leads to the synthesis of various γ-quinolinyl carbonyl compounds, which are synthetically useful precursors for the construction of bioactive tetrahydroquinoline and azasteroid derivatives.