Highly enantioselective Michael addition of pyrazolin‐5‐ones to nitroolefins catalyzed by cinchona alkaloid derived 4‐methylbenzoylthioureas

Abstract

Cinchona alkaloid-derived 4-methyl/nitro benzoylthioureas were synthesized, which smoothly catalyzed the asymmetric Michael addition of pyrazolin-5-ones to nitroolefins. The results showed that electronic effects of substituents in the benzene ring of benzoylthioureas have subtle influences on their catalytic abilities and electron donating methyl group is favored than electron withdrawing nitro group. Preliminary Hartree-Fock calculations revealed that in the catalytic cycle, hydrogen bond energies of the complex formed with 4-methylbenzoylthioureas are about 0.19 to 1.56 kcal/mol higher than with the corresponding 4-nitrobenzoylthioureas. 4-Methylbenzoylthioureas were identified as the most effective catalysts that promoted asymmetric Michael addition of pyrazolin-5-ones to nitroolefins to give the S- or R-products with high enantioselectivities.

Regiodivergent Organocatalytic Reactions

“…Apart from this, they have various applications such as utilization in chiral ligands in the preparation of metal complexes, in NMR as chiral agents, resolving agents, chiral stationary phase in HPLC, electrolytic additives, and chiral solvating agents. They have been successfully used in various important asymmetric transformations such as the Mannich reaction [91][92][93], Michael addition [94][95][96], aza-Henry reactions [97,98], and epoxidation [99,100], in order to promote a highly enantio-and diastereoselective outcome.…”