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Synthesis of (±)-Hippolachnin A
Collaborative Total Synthesis: Routes to (±)-Hippolachnin A Enabled by Quadricyclane Cycloaddition and Late-Stage C–H Oxidation.
J. Am. Chem. Soc. 2016;
18 April 2016 (online)
Key wordscollaborative total synthesis - quadricyclane [2+2] cycloaddition - (±)-hippolachnin - C–H oxidation
In this work, the authors combine their independently elaborated routes into a unique collaborative total synthesis of (±)-hippolachnin A. The convergent synthesis relies on a [2+2] quadricyclane cycloaddition, followed by ring-opening metathesis and allylic C–H oxidation.
Thermal [2+2] cycloaddition of acyl chloride A and quadricyclane B generated cyclobutane C after treatment with sodium hydroxide in moderate yield and excellent diastereoselectivity. Ring-opening metathesis catalyzed by Grubbs I under an ethylene atmosphere gave carboxylic acid D. A late stage C–H oxidation of bicycle D gave lactone F, which was converted in three further steps into (±)-hippolachnin A.