Radical Alliances: Solutions and Opportunities for Organic Synthesis

Abstract

The present account discusses in detail various mechanistic features of the degenerative radical addition‐transfer of xanthates and related thiocarbonylthio congeners and makes a comparison with the more classical Kharasch reactions to which it is similar in certain aspects. The xanthate group reacts reversibly with the ‘active’ radicals in the medium and is able to store them in a somewhat inactive form. This increases their effective lifetime in the medium and, at the same time, lowers their absolute concentration while regulating their relative concentration. These properties translate into a powerful carbon–carbon bond forming process, especially as regards intermolecular additions to electronically unbiased (‘unactivated’) alkenes. Most functional groups are tolerated, in particular polar functions that often require protection with other chemistries. This broad versatility is illustrated by examples where the xanthate addition to the alkene is combined with other, more classical reactions to provide a convergent, rapid access to a wide range of useful structures. Emphasis has been placed on the synthesis of open chain and more complex carbocycles, as well as on the transfer of chirality. These ‘radical alliances’ include organosilicon chemistry, the Diels–Alder cycloaddition and cheletropic extrusion of sulfur dioxide, the Claisen sigmatropic rearrangement, and the Horner–Wadsworth–Emmons (HWE) condensation.

A Convergent, Stereoselective Route to Trisubstituted Alkenyl Boronates

“…The -scission of intermediate radical 10 is in most cases slower than transfer of the xanthate group to give xanthate 11, but this is of no consequence since this transfer is reversible. 12 Radical 10 is continuously regenerated and ultimately collapses into the desired alkene 12. Many functional groups are tolerated, both on xanthate 9 and on activated allylic alcohol 8, allowing the synthesis of alkenes with numerous combinations of substituents and functionalities.…”

“…Radical processes have seldom been applied to the synthesis of alkenyl boronates . As part of our work on the unusual radical chemistry of dithiocarbonates (xanthates), we decided to exploit an earlier observation to develop a convergent, stereoselective approach to these important derivatives. One feature of radical intermediates is that β-scission by homolysis of carbon–oxygen bonds ( 1 → 2 , Scheme a) is generally a difficult process (i.e., very slow on radical reactions time scale) that is not normally observed .…”

“…By converting an allylic alcohol 6 into its fluoropyridoxy derivative 8 and taking advantage of the ability of xanthates 9 to mediate intermolecular additions even to electronically unbiased alkenes, an addition–fragmentation sequence can be accomplished to furnish alkene 12 . The β-scission of intermediate radical 10 is in most cases slower than transfer of the xanthate group to give xanthate 11 , but this is of no consequence since this transfer is reversible . Radical 10 is continuously regenerated and ultimately collapses into the desired alkene 12 and fluoropyridyloxy radical 13 , which ultimately evolves into fluoropyridinol 14 (for a mechanistic discussion, see ref ).…”

Discovery of the RAFT/MADIX Process: Mechanistic Insights and Polymer Chemistry Implications

“…The actual situation is somewhat more complex but does not change the essence of the argument (for instance, coproduct xanthate 59 can also participate in the process). The interested reader is directed to ref for a more detailed discussion.…”

Modular Approach to Substituted Pyridoazepinones

“…Following a longstanding interest in the synthesis of heterocyclic scaffolds in our group, we developed a few pathways to benzazepinones and N -alkyl-substituted pyridoazepinones (Scheme B). In this paper, we present a general and modular synthesis of N - unsubstituted pyridoazepinones.…”