A Mixed‐Ligand Chiral Rhodium(II) Catalyst Enables the Enantioselective Total Synthesis of Piperarborenine B

Abstract

AbstractA novel, mixed‐ligand chiral rhodium(II) catalyst, Rh2(S‐NTTL)3(dCPA), has enabled the first enantioselective total synthesis of the natural product piperarborenine B. A crystal structure of Rh2(S‐NTTL)3(dCPA) reveals a “chiral crown” conformation with a bulky dicyclohexylphenyl acetate ligand and three N‐naphthalimido groups oriented on the same face of the catalyst. The natural product was prepared on large scale using rhodium‐catalyzed bicyclobutanation/ copper‐catalyzed homoconjugate addition chemistry in the key step. The route proceeds in ten steps with an 8 % overall yield and 92 % ee.