Intramolecular hydroacylation catalyzed by transition-metal is an efficient and straightforward strategy for the synthesis of various cyclic ketone derivatives. Especially, synthesis of five-membered ketones from 4-alkenals or 4-alkynals via hydroacylation have been widely studied and several enantioselective reactions have been reported.1 On the other hand, formation of six-membered rings via hydroacylation is quite difficult because of various side reactions (e.g. decarbonylation, olefin isomerization, etc.) and limited to only three reports until now.2 Herein, we report construction of optically active six-membered rings by Rh(I)-catalyzed intramolecular enantioselective hydroacylation of 4-allenals. During ongoing investigation of Rh(I)-catalyzed [6+2] cycloaddition of 4-allenals with multiple bonds,3 we found that cyclohexanone derivatives were produced through hydroacylation of 4-allenals depending on the reaction conditions. Hydroacylation of racemic 4-allenal 1 with 10 mol% [Rh((R)-DTBM-SEGPHOS)]BF4 and 4-fluorobenzonitrile in acetone at 45 °C afforded cyclohexanone 2 in 82% yield and 95% ee. A possible reaction mechanism for the formation of 2 is as follows: five-membered oxo-rhodacycle intermediate A would be formed from aldehyde and allene with Rh(I) complex followed by isomerization to seven-membered oxo-rhodacycle C via π-allylrhodium intermediate B, from which reductive elimination leads to give the cyclohexanone 2. In this reaction, racemic 4-allenal 1 was used as a substrate, nevertheless ketone product 2 was formed in high yield with high ee. This result suggests that the process is a dynamic kinetic resolution involving racemization of 1 during the reaction. Referrences 1. For a review, see: Willis, M. C. Chem. Rev. 2010, 110, 725. 2. (a) Gable, K. P.; Benz, G. A. Tetrahedron Lett. 1991, 32, 3473. (b) Nicolaou, K. C.; Gross, J. L.; Kerr, M. A. J. Heterocyclic Chem. 1996, 33, 735. (c) Takeishi, K.; Sugishima, K.; Sasaki, K.; Tanaka, K. Chem. Eur. J. 2004, 10, 5681. 3 (a) Oonishi, Y.; Hosotani, A.; Sato, Y. J. Am. Chem. Soc. 2011, 133, 10386. (b) Oonishi, Y.; Hosotani, A.; Sato, Y. Angew. Chem., Int. Ed. 2012, 51, 11548.

Rhodium(I)-catalyzed enantioselective intramolecular hydroacylation of 4-allenals

249th National Meeting (2015)

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