Sulfur-Directed α‑C(sp³)–H Amidation of Pyrrolidines with Dioxazolones under Rhodium Catalysis

Site-selective functionalization of saturated N-heterocycles such as pyrrolidines is a central topic in organic synthesis and drug discovery. We herein report the sulfur-assisted rhodium­(III)-catalyzed sp3 C–H amidation of pyrrolidines with dioxazolones as amidating agents. The amenability of the thioamide directing group is elucidated by a series of control experiments

Sulfur-Directed α‑C(sp³)–H Amidation of Pyrrolidines with Dioxazolones under Rhodium Catalysis

Site-selective functionalization of saturated N-heterocycles such as pyrrolidines is a central topic in organic synthesis and drug discovery. We herein report the sulfur-assisted rhodium­(III)-catalyzed sp3 C–H amidation of pyrrolidines with dioxazolones as amidating agents. The amenability of the thioamide directing group is elucidated by a series of control experiments

Transition-Metal-Free Alkylation and Acylation of Benzoxazinones with 1,4-Dihydropyridines

The direct functionalization of N-heterocycles is a vital transformation for the development of pharmaceuticals, functional materials, and other chemical entities. Herein, the transition-metal-free alkylation and acylation of C­(sp2)–H bonds in biologically relevant 2-benzoxazinones with 1,4-dihydropyridines as readily accessible radical surrogates is described. Excellent functional group compatibility and a broad substrate scope were attained. Gram-scale reaction and transformations of the synthesized adducts via Suzuki coupling with heteroaryl boronic acids demonstrated the synthetic potential of the developed protocol

Ruthenium(II)-Catalyzed Tandem C–H Allylation and [3 + 2] Dipolar Cycloaddition to Construct Bridged Tetracycles

The ruthenium­(II)-catalyzed tandem C–H allylation and intramolecular dipolar cycloaddition between azomethine imines and 2-methylidenetrimethylene carbonate is described herein. The initially formed β-substituted allyl fragment could trigger the exotype [3 + 2] cycloaddition with the polar azomethine group, resulting in the formation of bridged tetracycles bearing a hydroxymethylene group at a bridgehead carbon center. A wide substrate scope and broad functional group compatibility were observed. The gram-scale synthesis and synthetic transformations demonstrate the synthetic utility of this process

Transition-Metal-Free Alkylation and Acylation of Benzoxazinones with 1,4-Dihydropyridines

The direct functionalization of N-heterocycles is a vital transformation for the development of pharmaceuticals, functional materials, and other chemical entities. Herein, the transition-metal-free alkylation and acylation of C­(sp2)–H bonds in biologically relevant 2-benzoxazinones with 1,4-dihydropyridines as readily accessible radical surrogates is described. Excellent functional group compatibility and a broad substrate scope were attained. Gram-scale reaction and transformations of the synthesized adducts via Suzuki coupling with heteroaryl boronic acids demonstrated the synthetic potential of the developed protocol

Ruthenium(II)-Catalyzed Tandem C–H Allylation and [3 + 2] Dipolar Cycloaddition to Construct Bridged Tetracycles

The ruthenium­(II)-catalyzed tandem C–H allylation and intramolecular dipolar cycloaddition between azomethine imines and 2-methylidenetrimethylene carbonate is described herein. The initially formed β-substituted allyl fragment could trigger the exotype [3 + 2] cycloaddition with the polar azomethine group, resulting in the formation of bridged tetracycles bearing a hydroxymethylene group at a bridgehead carbon center. A wide substrate scope and broad functional group compatibility were observed. The gram-scale synthesis and synthetic transformations demonstrate the synthetic utility of this process

Solution Structure of a Sponge-Derived Cystine Knot Peptide and Its Notable Stability

A novel cystine knot peptide, asteropsin E (ASPE), was isolated from an <i>Asteropus</i> sp. marine sponge. The primary, secondary, and tertiary structures of ASPE were determined by high-resolution 2D NMR spectroscopy (900 MHz). With the exception of an <i>N</i>-terminal modification, ASPE shares properties with the previously reported asteropsins A–D, that is, the absence of basic residues, a highly acidic nature, conserved structurally important residues (including two <i>cis</i>-prolines), and a highly conserved tertiary structural framework. ASPE was found to be remarkably stable to gastrointestinal tract enzymes (chymotrypsin, elastase, pepsin, and trypsin) and to human plasma

Synthesis of Succinimide-Linked Indazol-3-ols Derived from Maleimides under Rh(III) Catalysis

The structural modification of N-aryl indazolols as tautomers of N-aryl indazolones has been established as a hot topic in pharmaceutics and medicinal chemistry. We herein disclose the rhodium­(III)-catalyzed 1,4-addition reaction of maleimides with N-aryl indazol-3-ols, which provides the succinimide-bearing indazol-3-ol scaffolds with complete regioselectivity and a good functional group tolerance. Notably, the versatility of this protocol is demonstrated by the use of drug-molecule-linked and fluorescence-probe-linked maleimides

Synthesis of Succinimide-Linked Indazol-3-ols Derived from Maleimides under Rh(III) Catalysis

The structural modification of N-aryl indazolols as tautomers of N-aryl indazolones has been established as a hot topic in pharmaceutics and medicinal chemistry. We herein disclose the rhodium­(III)-catalyzed 1,4-addition reaction of maleimides with N-aryl indazol-3-ols, which provides the succinimide-bearing indazol-3-ol scaffolds with complete regioselectivity and a good functional group tolerance. Notably, the versatility of this protocol is demonstrated by the use of drug-molecule-linked and fluorescence-probe-linked maleimides

Phthalazinone-Assisted C–H Amidation Using Dioxazolones Under Rh(III) Catalysis

The preparation of phthalazinone derivatives is pivotal for their utilization as pharmaceutical agents and other entities. Herein, we report the phthalazinone-assisted carbon–nitrogen bond forming reaction using dioxazolones as robust amidation sources under Rh­(III) catalysis. The broad functional group tolerance and complete site-selectivity are observed. Notably, a series of transformations of synthesized compounds into biologically relevant N-heterocycles demonstrates the applicability of the developed methodology