Facile Construction of the 7,8‐Olefin Linkage in Vitamin D₃: A Practical Synthesis Benefiting the Vitamin D₃ Analog Study

Abstract

A facile procedure for construction of the 7,8‐olefin linkage in vitamin D₃ is described. Treatment of a mixture of A‐ring phosphine oxide and CD‐ring ketone in THF with lithium hexamethyldisilazide (LHMDS) at −20°C followed by gradual heating to 50°C gives the key intermediate of vitamin D₃ analogs in excellent yield. This simplified procedure makes possible small‐scale synthesis benefiting the vitamin D₃ analog study.

Keywords:

• Horner–Wittig olefination
• vitamin D₃
• vitamin D₃ analog

Acknowledgments

We thank Kunio Ogasawara, professor emeritus, Tohoku University, for his helpful suggestions.