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% of overall yield. The second approach utilizes the 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 100-200g scales.