A Nickel‐Bisdiamine Porous Organic Polymer as Heterogeneous Chiral Catalyst for Asymmetric Michael Addition to Aliphatic Nitroalkenes

Abstract

We report a polystyrene-incorporated chiral nickel(II)-bisdiamine complex, which is accessible on gram-scale. This metal complex functions as a heterogeneous catalyst for the enantioselective Michael addition between malonates and aliphatic nitroalkenes, and it provides yields and enantioselectivities on par with homogeneous catalysts. Good functional group tolerance is reported for this reaction. Upon recycling, the catalyst achieves significantly higher TONs than previously reported. We demonstrate scalability to multigram-scale, compatibility with continuous flow production (4.43 gram), and application to the synthesis of the blockbuster drug Pregabalin. Finally, a new tandem reaction is disclosed.

Porous organic polymers for light-driven organic transformations

“…Heterogeneous and chiral photocatalysts are the best choices owing to their good recyclability. [223][224][225] Although POPs have been extensively developed as heterogeneous chiral catalysts for organic synthesis, [226][227][228][229][230][231][232] research into asymmetric photocatalysis is still extremely scarce and remains in the early stages of development.…”

Asymmetric Michael Addition in Synthesis of β-Substituted GABA Derivatives

“…Final hydrolysis and decarboxylation of the γ-lactam (3R,4S)-62 with 6N HCl under reflux produced the (S)-Phenibut 24 as the hydrochloride salt in quantitative yield. Later, several heterogeneous catalysts incorporating chiral bis(cyclohexyldiamine)-based Ni(II) complexes were developed for the asymmetric Michael addition of malonates to both aromatic [66,67] and aliphatic [68][69][70] nitroalkenes. These catalysts demonstrated good activities, enantioselectivities, reusability, and applicability for the multistep sequential flow synthesis of the (S)-Pregabalin [69].…”

Recent developments in enantioselective nickel(ii)-catalyzed conjugate additions

“…In 2020, Kramer and Kegnaes reported the first incorporation of a chiral nickel( ii )–bisdiamine complex in a polystyrene porous organic polymer. 26 This was achieved through copolymerization of vinyl-functionalized nickel( ii )–bisdiamine complexes. Novel heterogeneous catalyst 7 was found to be a highly efficient promotor in the asymmetric Michael addition of dimethyl malonate to challenging aliphatic nitroalkenes.…”