Molecular Editing of Pyrroles to Benzenes/Naphthalenes by N2O Deletion.

Molecular editing promises to facilitate the rapid diversification of complex molecular architectures by rapidly and conveniently altering core frameworks. This approach has the potential to accelerate both drug discovery and total synthesis. In this study, we present a novel protocol for the molecular editing of pyrroles. Initially, N-Boc pyrroles and alkynes are converted into N-bridged compounds through a Diels-Alder reaction. These compounds then undergo deprotection of the Boc group, nitrosylation, and cheletropic N2O extrusion to yield benzene or naphthalene products. By using benzyne as a substrate, this method can be conceptually viewed as a fusion of skeletal editing of the pyrrole ring and site-selective peripheral editing of the benzene ring. Furthermore, this proof-of-concept protocol has demonstrated its potential to transform the (hetero)arene motif from commercially available drugs, offering the possibility of generating new biologically active compounds.

Skeletal Editing of Benzene Motif: Photopromoted Transannulation for Synthesis of DNA-Encoded Seven-Membered Rings.

In this report, we present a photopromoted, metal-free transannulation of phenyl azides for the synthesis of DNA-encoded seven-membered rings. The transformation is efficiently achieved through a skeletal editing strategy targeting the benzene motif coupled with a Reversible Adsorption to Solid Support (RASS) strategy. A variety of valuable DNA-encoded seven-membered ring compounds, including DNA-encoded 3H-azepines, azepinones, and unnatural amino acids, are now accessible. Crucially, this DNA-compatible protocol can also be applied for the introduction of complex molecules, as exemplified by Lorcaserin and Betahistine. The selective conversion of readily available phenyl rings into high-value seven-membered rings offers a promising avenue for the construction of diversified and drug-like DNA-encoded library.

Radical C-H Sulfonation of Arenes: Its Applications on Bioactive and DNA-Encoded Molecules.

The photocatalyst-free electron donor-acceptor (EDA) complex photochemistry was deemed to expand the potential of photodriven radical chemistry. Here, we report a cross-coupling reaction of thianthrenium salt functionalized arenes and sodium sulfinates via a photopromoted single electron transfer (SET) process of an EDA complex. A series of biarylsulfones were obtained with high site-selectivity and reactivity. This mild and practical radical reaction could be applied on the bioactive and DNA-encoded molecules.

Rh(III)-Catalyzed ortho C-H functionalization of aromatic amides with bis(phenylsulfonyl)diazomethane and α-diazosulfones.

A Rh(III)-catalyzed migratory insertion of bis(phenylsulfonyl) carbene and α-sulfonyl carbenes into ortho C-H bonds of aryl amides has been developed. The products were obtained with moderate to excellent yields under mild reaction conditions. A reaction mechanism was proposed based on the control experiments and previous studies. Diverse desulfonylation transformations of the products were achieved.