Photochemistry of β-γ-Unsaturated Spirolactones
, Pablo Wessig and Torsten Linker *Round 1
Reviewer 1 Report
In their manuscript, the authors report a new unexpected photochemical di-pi-methane rearrangement of spirolactone in which the carboxyl function is involved in the rearrangement. In such reactions a high degree of molecular complexity is generated. They are therefore interesting for application to organic synthesis. A computational investigation was performed and a reasonable mechanism is suggested. Furthermore, Paternò-Büchi reactions of the same cyclohexadiene spirolactones with benzaldehyde and benzophenone have been observed. One may argue that the yields are low which is in part due to the photochemical reactivity of the primary photoproducts as it is discussed by the authors. This is a typical problem which can be resolved by a systematic study or continuous flow conditions (see for example: DOI: 10.1021/jo050705p in connection with DOI: 10.1002/anie.200250507). But this is beyond the subject of the present study. I recommend publication of the manuscript in Photochem.
Author Response
We thank Reviewer 1 for the very fast and positive evaluation of our manuscript.
Indeed, we believe that flow techniques might improve the yields and we are aware of the important work of Prof. Booker-Milburn. Because we don't have such equipment in our group, this might be interesting for future collaborations.
However, we added one sentence on page 6 (highlighted in green) regarding the flow technique, and we hope that we could improve our revised manuscript.
Reviewer 2 Report
In this manuscript, Linker and coworkers describe photochemical reactions of spirolactones at a 1,4-cyclohexadiene core. The work is done carefully and described clearly. It is an original contribution to classic organic photochemistry, something that one sees quite rarely these days. The yields are modest but and each new photochemical reaction of such simple substrates is conceptually interestingthe observed products result from a rather complex non-trivial cascade.
For reactions with aldehydes and ketones, one has to wonder where the excitation is and whether the aldehyde/ketone or the spirolactone that is excited. Even simply showing the overlay of absorption spectra would be quite informative.
Some of the 3-exo closure/reopening cascades resemble similar sequences in reactions of 1,4-cyclohexadienes with alkynes (see, J. Am. Chem. Soc. 2005, 127, 4270-4285. http://pubs.acs.org/doi/full/10.1021/ja043803l). It would be interesting, perhaps, to test reactivity of the new spirolactones towards these classic targets as well.
Yields of bimolecular photochemical reactions often depend strongly on the concentrations. It would be interesting to explore this deeper or, at least, clearly specify the range of concentrations and explain why these concentrations were chosen.
Author Response
We thank Reviewer 2 for the very fast and positive evaluation of our manuscript.
The question of excitation is an important issue and thus we measured new UV spectra (page 8, highlighted in green) as suggested. Indeed, benzaldehyde and benzophenone show n-pi* absorption bands at 286 and 339 nm in accordance to literature. Thus, irradiation with UV-B light fits well, whereas sole spirolactone 11a (230 nm) does not react under such conditions.
We thank Reviewer 2 for the suggestion of reactions of spirolactones with alkynes, we were not aware of this interesting work of Prof. Alabugin. However, a disadvantage for our substrates might be, that "simple" 1,4-cyclohexadiene was used in 100 fold excess because it can be easily removed after the reaction. In our reactions the spirolactone is the "more expensive" substrate and we used the carbonyl compounds in excess.
We investigated the concentration dependence in the photoreactions of sole spirolactones (Table 1) and discussed this in the manuscript. For reactions with carbonyl compounds, we altered the ratio from 1:1 to 3:1 (Scheme 6). If we use even more carbonyl compound, the amount of side products 24 and 25 (Scheme 6) increases too much. To our opinion, the main problem is the easy polymerization of our spirolactones, reducing the yields remarkably, and we discussed this in the manuscript. This problem might be resolved by flow techniques, e.g. developed by Prof. Booker-Milburn, because of the shorter contact time of substrates with light. We don't have such equipment, but it might be attractive for future work. Additionally, we added one sentence on page 6 (highlighted in green) regarding this topic and hope that the question of concentrations is clearer now.
We believe that we could improve our revised manuscript due to the helpful suggestions of Reviewer 2 and our additional comments on flow techniques and the measured UV spectra (Figure 6) and hope that Reviewer 2 can agree that the manuscript is now suitable for a publication in Photochem.
