Chiral 1,2,3-Triazolium Salt Catalyzed Asymmetric Mono- and Dialkylation of 2,5-Diketopiperazines with the Construction of Tetrasubstituted Carbon Centers

Novel asymmetric mono- and dialkylation reactions of a-substituted 2,5-diketopiperazines catalyzed by new chiral spirocyclic-amide-derived triazolium organocatalysts have been developed, resulting in a range of enantioenriched 2,5-diketopiperazine derivatives containing one or two tetrasubstituted carbon stereocenters. The reactions feature high yields (up to 98%), and excellent cis-diastereo- and enantioselectivides (up to >20:1 dr, >99% ee), and they provide a new asymmetric synthetic approach to important pinctionalized 2,5-diketopiperazine skeletons. Furthermore, a possible reaction mechanism was proposed based on both control experiments and extensive DFT calculations.

Automated summary

Novel asymmetric mono- and dialkylation reactions of α-substituted 2,5-diketopiperazines catalyzed by new chiral spirocyclic-amide-derived triazolium organocatalysts have been developed, leading to enantioenriched products and providing a new synthetic approach.