Chemists Close A Synthesis Gap For Terminal Alkenes

When selecting starting materials, synthetic organic chemists find many aspects of monosubstituted terminal alkenes attractive. Certain α-olefins, such as 1-hexene and 1-octene, are manufactured on a large scale, and the compounds are stable in the presence of many acids, bases, oxidants, and reductants. There are, however, few ways of functionalizing these alkenes enantioselectively because there’s not much reactivity difference between one face of the double bond and the other. Chemists at Boston College have addressed this gap in synthetic methodology by developing a strategy for turning terminal alkenes into chiral products (Nature 2013, DOI: 10.1038/nature12781). The first step in the one-pot cascade reaction, developed by James P. Morken, Scott N. Mlynarski, and Christopher H. Schuster, is a platinum-catalyzed enantioselective alkene diboration. The resulting diboration products are then cross-coupled with an aryl bromide or chloroalkene, thereby creating a C–C bond where the terminal C–B bond had been. The remaining C–B bond is chiral and can therefore be converted into chiral derivatives, such as alcohols or amines. The team demonstrated the usefulness of the strategy by synthesizing several medicinally relevant compounds, including the pain fighter and antiepileptic drug Lyrica (pregabalin).