Alkoxyl Radicals as O-Synthons in Self-Terminating Radical Oxygenations: An Experimental and Theoretical Study

Abstract

Alkoxyl radicals 9 (XO^•), generated by photolysis of thiocarbamates 8, were found to initiate and undergo self-terminating radical oxygenations, in which alkynes are transformed into ketones. With this result, we have shown that every major class of organic O-centered radicals can act as O-atom synthon in this sequence, demonstrating the generality of this novel concept in radical chemistry. Theoretical investigations of the terminating homolytic scission of the O-X bond reveal that resonance stabilization in the cleaved radical X^• (e.g. benzyl, allyl) both lowers the activation barrier, ΔE^‡ , and increases the exothermicity, whereas radical stabilization by inductive effects (as in tert-butyl) only reduces ΔE^‡ , compared to non-stabilized radicals. The experimental results indicate that the final homolytic bond scission is not the only crucial step in this mechanism, but that generation of XO^• as well as the initial radical addition to the alkyne triple bond must be of similar importance.

Key words

radicals - alkynes - oxidations - photochemistry - computational chemistry

References

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3

To our knowledge, rate data for the addition of alkoxyl radicals to alkynes have not been determined so far.

11

Because of the strong transannular interactions, cycloalkyne 1 had proven to be a very suitable trial horse for studying self-terminating radical oxygenations.^4-8

13

The up-scaling of photochemical reactions is normally not straight forward, because, in contrast to thermal reactions, generally a non-linear increase of both irradiation time and solvent amount is required. We have found earlier that the best way to accomplish photo-induced, self-terminating radical oxygenations on preparative scales is by accordingly increasing the amount of reaction flasks containing up to 10 mM of reactants (alkyne and radical precursor), irradiating them simultaneously and combining them for work-up.⁸

14

No attempt was made to separate 5 and 6. Earlier work has shown that the products are formed with a ratio of 5:6 = 3:1.^4a

18

Steric repulsion by the bulky methyl substituents may be the reason for the slightly longer O-X bond in the tert-butyl substituted radical 12.

19

A comparable result was found for the reverse addition of a methyl radical to the oxygen atom in formaldehyde, calculated at the G3MP2//B3LYP/SVP level of theory.^16a

21

BHandHLYP calculations performed with the cc-pVDZ, aug-cc-pVDZ and cc-pVTZ basis set, respectively, resulted in comparable results for ΔE^‡ and ΔE than obtained with the 6-311G** basis set. MP2 calculations with these basis sets generally reflected the results of the B3LYP method.