Divergent Total Syntheses of C3 a-C7' Linked Diketopiperazine Alkaloids (+)-Asperazine and (+)-Pestalazine A Enabled by a Ni-Catalyzed Reductive Coupling of Tertiary Alkyl Chloride.

Short gram-scale asymmetric syntheses of asperazine, pestalazine A, and their unnatural congeners thereof, have been achieved in ≈10 steps by using readily accessible starting materials. The nickel-catalyzed reductive coupling protocol was utilized as a key step for the direct construction of C3a -C7' bond furnishing the diaryl-substituted quaternary carbon centers with remarkable steric hindrance. The streamlined access to this core structure of heterodimeric tryptophans under the mild reaction conditions, makes this strategy hold a great promise in the concise synthesis of other relevant oligomeric pyrroloindoline alkaloids with unique C3a-C7' linkages.