Remote and selective cleavage of ω-alkenyl spiropentane derivatives

Jeffrey Bruffaerts, Technion, Haifa, Israel
Sukhdev Singh, Technion, Haifa, Israel
Ilan Marek, Technion, Haifa, Israel

Remote functionalization has becoming an emerging and increasingly popular concept in synthesis. Indeed, customizing a molecule on any desired position, even its least reactive, would represent a new pinnacle in organic chemistry, as virtually any derivative could be accessed in a versatile manner. In this context, a series of pioneering publications have highlighted the transition-metal assisted remote functionalization of alkenes through tandem reactions involving olefin isomerization or chain-walking process.[i]

In our research group, we have achieved so far distant activations of alkenes using a low-valent zirconocene-butene complex generated in situ, namely the Negishi reagent. More specifically, we have reported the remote cleavage of ω-alkenyl cyclopropanes[ii] in one-pot procedures involving successively zirconium-walk[iii] (migration of the metal on a hydrocarbon chain), selective ring-opening of a three-membered ring, followed by a double functionalization reaction.

In the present context, we hereby report the modulable and selective cleavage of ω-alkenyl spiropentane derivatives, which are chemically accessible starting from allenes. Using organozirconium chemistry, we have set divergent methodologies for the synthesis of vinylcyclopropane, diene and triene derivatives in good yields with excellent stereoselectivities. This work contributes to promote spiropentanes as versatile and useful intermediates in synthesis.

[i]. Selected examples: a) Grotjahn, D. B.,  Larsen, C. R., Gustafson, J. L., Nair R. &  Sharma, J. Am. Chem. Soc. 129, 9592-9593 (2007); b) Ohlmann, D. M., Gooßen, L. J. & Dierker, M. Chem. Eur. J. 17, 9508-9519 (2011); c) Kochi, T., Hamasaki, T., Aoyama, Y., Kawasaki, J. & Kakiuchi, F. J. Am. Chem. Soc. 134, 16544-16547 (2012); d) Mei, T. –S, Patel, H. H. & Sigman, M. S Nature 508, 340-344 (2014)

[ii]. Masarwa, A., Didier, D., Zabrodsky, T., Schinkel, M., Ackermann, L. & Marek, I. Nature 505, 199-203 (2014).

[iii]. Marek, I., Chinkov N. & Levin, A. Synlett 501-514 (2006).


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