Bifunctional 2,5-Diketopiperazines as Efficient Organocatalysts for the Enantioselective Conjugate Addition of Aldehydes to Nitroolefins

Four peptidomimics (3–6) containing the cis-DKP-1 or trans-DKP-2 scaffolds and either L-Pro or D-Pro were synthesized. DKP-1 and DKP-2 are bifunctional diketopiperazines formally derived from the head-to-tail cyclization of L-aspartic acid and either (R)- or (S)-2,3-diaminopropionic acid, which feature aminomethyl and carboxymethyl side arms in the 3- and 6-positions of the 2,5-piperazindione ring. Peptidomimics (3–6) were tested as organocatalysts in the conjugate addition of several aldehydes to β-nitrostyrene and (E)-2-(furan-2-yl)nitroethene with good to excellent diastereo- and enantioselectivities. Monte Carlo/Energy Minimization (MC/EM) conformational searches were performed on the four catalysts and their enamine derivatives with propanal to rationalize the observed stereoselectivity.