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An Ir/spiro[4,4]-1,6-nonadiene-based phosphine-oxazoline ligand (SpinPHOX) complex-catalyzed double asymmetric hydrogenation of 3,6-dialkylidene-1,4-dimethylpiperazine-2,5-diones has been developed, providing efficient and practical access to a wide variety of chiral 3,6-disubstituted-2,5diketopiperazines in high yields with exclusive cis-diastereo-and excellent enantioselectivities (>99% de, up to 98% ee). The synthetic utilities of the protocol have been demonstrated in a gram scale synthesis of 6a and efficient construction of chiral products 8, 14, and 17 as well as a 2-butenyl-bridged bicyclic diketopiperazine 10 and hydroxydiketopiperazine 11. With an analogous achiral Ir catalyst, the hydrogenation of enantiopure monohydrogenated intermediate 7a gave cis-6a as the only product, indicating that the second-step hydrogenation of the titled transformation is a chiral substrate controlled process. The reaction profile study for asymmetric hydrogenation (AH) of 5a revealed that the concentration of the monohydrogenation intermediate 7a remained at a low level (<8%) during the course of hydrogenation. The hydrogenation of 5a to 6a proceeded significantly faster than that of its half-hydrogenated intermediate (S)-7a, indicating that the titled reaction involves primarily a processive mechanism, in which a single catalyst molecule performs consecutive hydrogenation of the two CC double bonds in substrate 5a without dissociation of the partially reduced 7a. The present protocol represents a rare example of asymmetric catalytic consecutive hydrogenation of heterocycles and provides an alternative way for efficient construction of cyclic dipeptides.