Syn-anti epimerization of aldols by aldolate dianions

Lizeng Peng a, Tao Zhang b, Tiansheng Mei b and Yulin Li *b
aLunan Pharmaceutical Co. Ltd., Linyi, 276003, P. R. China
bNational Laboratory of Applied Organic Chemistry, Institute of Organic Chemistry, Lanzhou University, Lanzhou, 730000, P. R. China. E-mail: liyl@lzu.edu.cn

Received (in Montpellier, France) 12th June 2003 , Accepted 28th July 2003

First published on 28th November 2003


Abstract

A proposed mechanism based on distal aldolate dianions is illustrated in this paper to explain the outcome of the directed aldol reaction when one uses more than 2 equivalents of base.


The aldol addition1 is a powerful and general method for stereocontrolled construction of carbon-carbon bonds. The most important stereochemical question in the directed aldol reaction concerns the formation of threo and/or erythro isomers of aldols or ketols.

One may use several mole equivalents of Li (or Na, Mg, etc.) enolates of the ketone and only 1 mole equivalent aldehyde to obtain the best yield of the desired condensation product. However, undesired products were usually obtained, along with the expected ones. One may explain the results through a rapid equilibration between the starting E- and Z-enolates based on the classic retro-aldol aldol process.1

During our studies on the total synthesis of brassinolide,2 we observed an interesting phenomenon, which we think can be well-explained through the formation of aldolated dianions, but not by the retro-aldol aldol process. A proposed mechanism is illustrated in Scheme 1 based on distal aldolate dianions3 when excess strong base was used during the aldol condensation.


The proposed mechanism based on the distal aldolate dianions.
Scheme 1 The proposed mechanism based on the distal aldolate dianions.

In summary, in our experiments syn- and anti-aldols were produced at the same time, whether the starting enolate was the Z- or E-enolate, in the directed aldol condensation when using an excess amount of strong base, as explained by the above-proposed mechanism.

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Grant No. 20072012).

References

  1. T. Mukaiyama, Org. React., 1982, 28, 203 CAS.
  2. L. Z. Peng, Y. L. Li and W. D. Z. Li, Tetrahedron Lett., 2003, 44, 3991 CrossRef CAS.
  3. For reports on the isomerization of aldols via an enol or enolate mechanism, see: (a) V. A. Martin, D. H. Murray, N. E. Pratt, Y. Zhao and K. F. Albizati, J. Am. Chem. Soc., 1990, 112, 6965 CrossRef CAS; (b) D. E. Ward, M. Sales and P. K. Sasmal, Org. Lett., 2001, 3, 3671 CrossRef CAS and references cited therein.

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