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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Solution-phase parallel synthesis of novel spirooxazolinoisoxazolines
Hao-Wei Shih1, Chih-Wei Guo, Kien-Hock Lo
1The Genomics Research Center, Academia Sinica, No 128, Academia Road Sec 2, Nankang District, Taipei 11529, Taiwan.
Abstract:
A practical and efficient solution-phase parallel synthesis of spirooxazolinoisoxazolines has been developed. Starting from methyl serine ester, the key steps are (1) acylation with concomitant beta-elimination to form an alpha,beta-unsaturated ester, (2) 1,3-dipolar cycloaddition with an oxime to form an isoxazoline ring, (3) reduction with NaBH(4), and (4) mesylation and in situ cyclization to form an oxazoline ring. All reaction steps and workup procedures were modified to allow the use of automated equipment including a synthesizer, a multifunctional liquid handler, and a vacuum centrifuge. Using this equipment, we synthesized a 100-membered library of spirooxazolinoisoxazoline in high yield, high purity, and excellent regioselectivity.
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