Enantioselective Construction of the Biologically Important Cyclopenta[1,4]diazepine Framework Enabled by Asymmetric Catalysis by Chiral Spiro‐Phosphoric Acid

Abstract A chiral spiro‐phosphoric‐acid‐catalyzed asymmetric approach for constructing the biologically important cyclopenta[1,4]diazepine scaffold with high enantioselectivity (up to 98:2 er) has been established through the use of three‐component tandem reactions of cyclopentane‐1,3‐dione, 1,2‐phenylenediamine, and isatins under mild reaction conditions. Among a series of chiral phosphoric acids, spiro‐phosphoric acid exhibited the highest catalytic activity on controlling the enantioselectivity of the three‐component tandem reaction. This reaction represents the first catalytic asymmetric construction of chiral cyclopenta[1,4]diazepine frameworks with structural diversity. The approach also constitutes the first systematic investigation on this catalytic asymmetric three‐component reaction, which will enrich the fields of both organocatalysis and catalytic asymmetric multicomponent reactions.