The Birch reduction dearomatizes arenes into 1,4-cyclohexadienes. Despite substantial efforts devoted to avoiding ammonia and cryogenic conditions, the traditional, cumbersome, and dangerous proced...

Scalable Birch reduction with lithium and ethylenediamine in tetrahydrofuran.

A mature science, combining the art of the total synthesis of complex natural structures and the practicality of delivering highly diverged lead compounds for biological screening, is the constant aim of the organic chemistry community. Delivering natural lead compounds became easier during the last two decades, with the evolution of green chemistry and the concepts of atom economy and protecting-group-free synthesis dominating the field of total synthesis. In this new era, total synthesis is moving towards natural efficacy by utilizing both the biosynthetic knowledge of divergent synthesis and the latest developments in radical chemistry. This contemporary review highlights recent total syntheses that incorporate the best of both worlds.

Combining the best of both worlds: radical-based divergent total synthesis

Proposal for structural revision of several disubstituted tricycloalternarenes.

Abstract A synthesis of a δ‐ketohydroperoxide is described, addressing potential functional‐group compatibilities in these elusive species relevant to combustion and atmospheric chemistries. The hydroperoxide is installed via sulfonylhydrazine substitution, which was found to be more effective than displacement of secondary halides. As part of this protocol, it was observed that 1,2‐dimethoxyethane is an advantageous medium for the reaction, avoiding the formation of a tetrahydrofuran hydroperoxide side product. This discovery facilitated the multigram synthesis (6 steps, 41 % yield overall) and discrete characterization of the target δ‐ketohydroperoxide.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/chem.202202266

Multigram Synthesis of a Combustion‐Relevant δ‐Ketohydroperoxide through Sulfonylhydrazine Substitution

Synthesis of the 5/6 fused-spiro tricyclic framework of manginoid A

An enantioselective synthetic approach for preparing manginoids and guignardones, two types of biogenetically related meroterpenoids, is reported. This bioinspired and divergent synthesis employs an oxidative 1,3-dicarbonyl radical-initiated cyclization and cyclodehydration of the common precursor to forge the central ring of the manginoids and guignardones, respectively, at a late stage. Key synthetic steps include silica-gel-promoted semipinacol rearrangement to form the 6-oxabicyclo[3.2.1]octane skeleton and the Suzuki-Miyaura reaction of vinyl bromide to achieve fragment coupling. This synthesis protocol enables the asymmetric syntheses of four fungal meroterpenoids from commercially available materials.

Ai-Hong Su

Papers

Enantioselective Total Syntheses of Manginoids A and C and Guignardones A and C