Solution-Phase Parallel Synthesis of Novel Spirooxazolinoisoxazolines

摘要

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 β-elimination to form an α,β-unsaturated ester, (2) 1,3-dipolar cycloaddition with an oxime to form an isoxazoline ring, (3) reduction with NaBEU, 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.