Formal Synthesis of (−)-Cephalotaxine Based on a Tandem Hydroamination/Semipinacol Rearrangement Reaction

Traditionally, transition metal-catalyzed enantioselective transformations rely on chiral ligands tightly bound to the metal to induce asymmetric product distributions. Here we report high enantioselectivities conferred by a chiral counterion in a metal-catalyzed reaction. Two different transformations catalyzed by cationic gold(I) complexes generated products in 90 to 99% enantiomeric excess with the use of chiral binaphthol-derived phosphate anions. Furthermore, we show that the chiral counterion can be combined additively with chiral ligands to enable an asymmetric transformation that cannot be achieved by either method alone. This concept of relaying chiral information via an ion pair should be applicable to a vast number of metal-mediated processes.

In recent years, the concept of combining transition metal catalysis and organocatalysis has emerged as a promising strategy for developing new and valuable reactions, and has attracted considerable attention as it could potentially enable unprecedented transformations not currently possible by use of the transition metal complex or the organocatalyst alone. In this critical review, this strategy is illustrated with several recent outstanding examples, with the aim of shedding light on the synthetic utilities and potentials of this concept as a novel tool in organic synthesis (118 references).