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 C3asp3−C7′sp2 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. Highly efficient syntheses of bioactive alkaloids (+)‐asperazine and (+)‐pestalazine A were realized by means of Ni‐catalyzed reductive coupling between 7‐iodotryptophan and 3‐chlorocyclotryptophan derivatives. This key reaction secured the construction of C3a−C7′ bond and the associated sterically congested all‐carbon quaternary stereocenter in a single step. [ABSTRACT FROM AUTHOR]