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

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.