Primary Amine–2-Aminopyrimidine Chiral Organocatalysts for the Enantioselective Conjugate Addition of Branched Aldehydes to Maleimides

Chiral primary amines containing the (R,R)- and (S,S)-trans-cyclohexane-1,2-diamine scaffold and a pyrimidin-2-yl unit are synthesized and used as general organocatalysts for the Michael reaction of α-branched aldehydes to maleimides. The reaction takes place with 10 mol% organocatalyst loading and hexanedioic acid as cocatalyst in aqueous N,N-dimethylformamide at 10 °C affording the corresponding succinimides in good yields and enantioselectivities. DFT calculations support the stereochemical results and the role played by the solvents.

Bifunctional primary amine 2-aminobenzimidazole organocatalyst anchored to trans-cyclohexane-1,2-diamine in enantioselective conjugate additions of aldehydes

Bifunctional chiral primary amine 8 containing an (S,S)-trans-cyclohexane-1,2-diamine scaffold and a 2-benzimidazole unit is used as a general organocatalyst for the Michael addition of α,α-branched aldehydes to nitroalkenes and maleimides. The reactions take place, with 20 mol % of catalyst in dichloromethane at rt for nitroalkenes and with 15 mol % catalyst loading in toluene at 10 °C for maleimides, in good yields and enantioselectivities. DFT calculations demonstrate the bifunctional character of this organocatalyst activating the aldehyde by enamine formation and the Michael acceptor by double hydrogen bonding.