Self-terminating, oxidative radical cyclizations.

Tim Dreessen,Christian Plath,Lars Lietzau,Uta Wille,Arne Stademann,Christian Jargstorff

doi:10.3390/90600480

Tim Dreessen, Christian Plath + Show 4 more

Open Access

https://doi.org/10.3390/90600480

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Abstract

The recently discovered novel concept of self-terminating, oxidative radical cyclizations, through which alkynes can be converted into carbonyl compounds under very mild reaction conditions using O-centered inorganic and organic radicals as oxidants, is described

Highlights

During the past 20–30 years radical reactions became an important synthetic tool, especially for the synthesis of complicated, often polycyclic molecules
The finding of this novel oxidative radical cyclization cascade, which is initiated by addition of inorganic O-centered radicals and radical anions XOz to alkynes and terminated by release of an unreactive part of the entering radical, encouraged us to look for further radical species possessing similar properties: (i) The unpaired electron being located on average on an oxygen atom, and (ii) a relatively stable leaving group Xz, which is cleaved after the radical cyclization, taking the unpaired electron
We have shown that self-terminating, oxidative radical cyclizations are obviously not a special reaction for a few selected radicals, but are rather a very general concept, which can be applied to various different inorganic and organic O-centered radicals and even radical anions

Summary

Introduction

During the past 20–30 years radical reactions became an important synthetic tool, especially for the synthesis of complicated, often polycyclic molecules The success of this methodology is a result of (i) the mostly excellent stereoselectivities of these reactions [1], and (ii) the downright ease of radical generation and radical chain maintaining by using the combination of alkyl halides (or thiols, selenides, nitro compounds, etc.) with transition metal or non-metal hydrides (generally tin, mercury or silicon compounds) as radical precursors [2,3]. Our concept to approach this problem consisted of replacing the organic part in “ROz“ by an inorganic residue “X” (ROz → XOz), which does not contain carbon, but instead N, S or H Examples for this purpose are the nitrate radical, NO3z, the sulfate radical anion, SO4z−, and the hydroxyl radical, HOz, (with X = NO2, SO3−, H), respectively. Autoxidation processes with molecular oxygen, which is in its triplet ground state is an inorganic radical species, involve the formation of peroxyl and alkoxyl radicals as intermediates and are of significant importance for the industrial synthesis of several bulk chemicals, for example for the manufacture of phenol and acetone from cumene by the Hock process [16]

Results and Discussion

Inorganic Radicals

Other Oxygen-Centered Radicals

Some Mechanistic Considerations

Conclusions and Future Outlook