Tandem Brook rearrangement/isomerization: Efficient and easy access to stereodefined fully substituted silyl enol ethers

Silyl enol ethers (SEE) are a key starting material for the synthesis of asymmetric quaternary carbon centers.[1] Nonetheless, if this building block has been used for decades,[2] it is still challenging nowadays to prepare selectively fully substituted SEE, solving both the problem of regio and stereo selectivity.

Several strategies to solve this problem were reported in the literature, using ketene intermediates,[3] chiral bases,[4] chiral auxiliaries,[5] tandem carbometallation/oxidation sequence,[6] or tandem metallation/carbamoyl transfer.[7] Nevertheless, if elegant stereoselective syntheses were described, a general, direct and easy approach for the preparation of the SEE of ketones or aldehydes remains undisclosed.

Inspired by the seminal report of Isao Kuwajima,[8] we report in the present work a tandem Brook rearrangement / Isomeriation sequence allowing the synthesis of fully substituted SEE, solving both the problems of region and stereo selectivity.

[1] Yamashita, Y.; Yasukawa, T.; Yoo, W.-J.; Kitanosono, T.; Kobayashi, S. Chem. Soc. Rev., 2018, 47, 4388

[2] (a) Brownbridge, P. Synthesis 1983, 1, 85. (b) Colvin, E. W. Silicon in Organic Synthesis; Butterworths: London, 1980; Chapter 17. (c) Weber, W. P. In Silicon Reagents for Organic Synthesis; Hafner, K., Lehn, J.-M., Rees, C. W., Schleyer, P. v. R., Trost, B. M., Zahradnik, R., Eds.; Springer-Verlag: New York, 1983; Chapters 12-16.

[3] Seebach, D.; Amstutz, R.; Laube, T.; Schweizer, B. W.; Dunitz, J. D. J. Am. Chem. Soc., 1985, 107, 5403

[4] Y. C. Qin, C. E. Stivala and A. Zakarian, Angew. Chem., Int. Ed.,2007, 46, 7466

[5] Kummer, Y. A.; Chain, W. J.; Morales, M. R.; Quiroga, O.; Myers, A. G. J. Am. Chem. Soc., 2008, 130, 13231

[6] Minko, Y.; Pasco, M.; Lercher, L.; Botoshansky, M.; Marek, I. Nature, 2012, 490, 522

[7] Haimov, E.; Nairoukh, Z.; Shterenberg, A.; Berkovitz, T.; Jamison, T. F.; Marek I. Angew. Chem. Int. Ed., 2016, 55, 5517

[8] Kato, M.; Mori, A.; Oshino, H.; Enda, J.; Kobayashi, K.; Kuwajima, I. J. Am. Chem. Soc., 1984, 106, 1773