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

Abstract

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.

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

“…Recent progress in photoredox catalysis [6][7][8], electrochemistry [9,10], and the use of transition-metal (TM) catalysts in radical cross-coupling reactions [11] have dramatically expanded the use of radicals in synthesis, leading to their strategic incorporation as "synthons" in modern organic chemistry, with complementary reactivity to more common polar reaction manifolds [12][13][14][15]. The utility of radicals has also been expanded through the recent development of transformations involving radical-polar crossover, which incorporate both radical and ionic bondforming steps into a single synthetic operation [16,17].…”

Selective preparative ‘oxidase phase’ in sesquiterpenoids: the radical approach

“…The impressive machinery of complexity as exemplified by the biosynthesis of terpenoids highlights the ability of Nature to perform highly selective transformations by utilizing enzymes and rather simple common scaffolds. 1 This divergent protocol empowered by the iterative use of primary metabolism reactions (IPP, DMAPP, and cationic reactions) produces carbocyclic frameworks (cyclase phase) that finally become oxidative enzymes (oxidase phase) (Fig. 1).…”