Synthetic Process Development of ( R )-(+)-1,2-Epoxy-5-hexene: An Important Chiral Building Block.

Herein, we describe two practical approaches to synthesize ( R )-(+)-1,2-epoxy-5-hexene from inexpensive and readily available raw materials and reagents. The first approach is a two-step sequence, involving an epoxidation with meta -chloroperoxybenzoic acid (mCPBA) and a chiral resolution with (salen)Co(II), producing ( R )-(+)-1,2-epoxy-5-hexene in 24-30% overall yield. The second approach utilizes readily available ( R )-epichlorohydrin as the starting material and features an epoxide ring-opening reaction with allylMgCl and the NaOH-mediated ring closure reaction. Development of this two-step process affords R -(+)-1,2-epoxy-5-hexene in overall isolated yields of 55-60% with an exceptional purity profile. Both approaches have been successfully demonstrated on 100-200 g scales.