A Synthetic and Computational Investigation into the Direct Synthesis of α-Hydroxymethylated Enones from β-Keto Phosphonates

Sarah J. Ryan; Christopher D. Thompson; David W. Lupton

doi:10.1071/CH09301

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A Synthetic and Computational Investigation into the Direct Synthesis of α-Hydroxymethylated Enones from β-Keto Phosphonates

Sarah J. Ryan ^A , Christopher D. Thompson ^A and David W. Lupton ^A ^B

+ Author Affiliations

- Author Affiliations

^A School of Chemistry, Monash University, Clayton, Vic. 3800, Australia.

^B Corresponding author. Email: david.lupton@sci.monash.edu.au

Australian Journal of Chemistry 62(7) 720-727 https://doi.org/10.1071/CH09301
Submitted: 20 May 2009 Accepted: 11 June 2009 Published: 13 July 2009

Abstract

The synthesis of a range of α-hydroxymethylated enones has been achieved using the Villiéras modification of the Horner–Wadsworth–Emmons (HWE) reaction. Scope, limitations, and mechanistic aspects of this reaction were investigated using a combination of synthetic and computational studies. These investigations support a Schlosser–Corey type reaction mechanism that is balanced between two pathways with the outcome influenced by the steric environment of the substrate.

Acknowledgements

The authors thank Yasmean Kalam for preliminary studies. The authors are grateful for the financial support of the Australian Research Council through the discovery program (DP0881137), Monash University through the ECR program and computing support from VPAC and APAC (NCI). D.W.L. acknowledges the provision of equipment from Roche Palo Alto.

References

^¶ The dihydroxymethylated derivative of phosphonate 2 (R = OEt) is indicated as an intermediate in the hydroxymethylation reported in Ref. [5a].

^† Intermediate 8a was prepared as described in the experimental section as a part of other optimization studies.

A Synthetic and Computational Investigation into the Direct Synthesis of α-Hydroxymethylated Enones from β-Keto Phosphonates

Abstract

Acknowledgements

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