Concise Enantioselective Total Syntheses of (+)-Homochelidonine, (+)-Chelamidine, (+)-Chelidonine, (+)-Chelamine and (+)-Norchelidonine by a PdII-Catalyzed Ring-Opening Strategy

New enantioselective syntheses of the B/C hexahydrobenzo[c]phenanthridine alkaloids (+)‐homochelidonine, (+)‐chelamidine, (+)‐chelidonine, (+)‐chelamine, and (+)‐norchelidonine are described. Our rapid and convergent route to this class of natural products involved the development and application of a PdII‐catalyzed asymmetric ring‐opening reaction of a meso‐azabicyclic alkene with an aryl boronic acid as the key step. By screening a variety of functionalized ortho‐substituted aryl boronic acids, chiral ligands and reaction conditions we were able to prepare the requisite cis‐1‐amino‐2‐aryldihydronaphthalenes in high yield and in up to 90 % ee. Early attempts to complete the synthesis of (+)‐homochelidonine using an N‐Boc azabicyclic alkene are described in full. The successful route required a protecting group alteration followed by B ring formation and then stereoselective installation of the C‐11 syn‐hydroxy group by regioselective epoxide ring‐opening using a hydride source. Ring‐opening of the same epoxide intermediate with water ultimately led to the synthesis of (+)‐chelamidine. The same strategy was then used to synthesize the other structurally similar B/C hexahydrobenzo[c]phenanthridine alkaloids, (+)‐chelidonine, (+)‐chelamidine, and (+)‐norchelidonine. Five for the price of one: five natural products with one ring‐opening reaction. An efficient and highly convergent enantioselective synthesis of B/C hexahydrobenzo[c]phenanthridine alkaloids has been achieved. The approach relied on the development of a new and powerful desymmetrizing ring‐opening reaction of a meso‐azabicyclic alkene with an aryl boronic acid (MOM=methoxymethyl, Cbz=carbobenzyloxy).