Journal article

Synthesis of Alkyl Citrates (-)-CJ-13,981, (-)-CJ-13,982, and (-)-L-731,120 via a Cyclobutene Diester

Liselle Atkin, Zongjia Chen, Angus Robertson, Dayna Sturgess, Jonathan M White, Mark A Rizzacasa

Organic Letters | American Chemical Society | Published : 2018


An efficient and step-economic new approach to alkyl citrate natural products from a cyclobutene diester is presented. The key sequence involves a formal [2 + 2]-cycloaddition of a silylketene acetal with dimethylacetylene dicarboxylate to provide the cyclobutene diester 14 with 4.5:1 stereoselectivity. Exposure of diester 14 in acidic methanol effected a hydrolysis, intramolecular oxy-Michael reaction, and cyclobutanone methanolysis cascade to give the triester 15. Iodination and elimination then afforded a key alkyl citrate alkene intermediate, which was converted into the natural products (−)-CJ-13,982 (1), (−)-CJ-13,981 (2), and (−)-L-731,120 (3) via a cross-metathesis and subsequent red..

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Funding Acknowledgements

We thank the Australian Research Council Discovery Program and the University of Melbourne Faculty of Science Research Grant Support Scheme for funding. We also thank Circa Pty Ltd. for the generous gift of (S)-(+)-gamma-hydroxymethyl-gamma-butyrolactone.