Scalable Formal Synthesis of (-)-Quinocarcin.
A scalable and unified strategy is described for the synthesis of (-)-quinocarcin, an important tetrahydroisoquinoline antitumor alkaloid. The strategy allows the practical formal synthesis of (-)-quinocarcin in 13 steps and 4.8% overall yield using N-phthaloyl-l-alanine as a chiral pool. It features the gram-scale and stereoselective synthesis of the tetrahydroisoquinoline moiety (AB ring) via Pd-catalyzed C(sp3)-H arylation and Pictet-Spengler condensation and a Cu(I)-catalyzed exo-selective [C + NC + CC] coupling reaction to generate the chiral pyrrolidine motif (D ring).