Chiral Thiophosphoramidate‐Catalyzed Asymmetric Michael Addition of Ketones to Nitro Olefins

Abstract

A novel type of pyrrolidine-based chiral (thio)phosphoramidates was synthesized. Among them, compound (S,aR)-3d was proven to be an effective bifunctional organocatalyst for the asymmetric Michael addition of ketones to nitro olefins. The

C3‐Symmetric Proline‐Functionalized Organocatalysts: Enantioselective Michael Addition Reactions

“…( Table 4, Entries 1-16); whereas a high diastereoselectivity was observed for electron-rich nitroolefins (syn/anti up to 99:1), marginally less selectivity was observed for electrondeficient olefins (up to 94:6; Table 4, Entries 8,9,12,and 13). In the same vein, low enantioselectivity (ca.…”

“…Rather attenuated enantioselectivity was observed for nitroolefins substituted with aliphatic groups such as cyclohexyl and isobutyl (ca. [11] A wide variety of catalysts has been developed for this particular reaction based on readily available chiral amines, [12,13] due to the fact that the reaction affords enantiomerically enriched products with two contiguous stereocenters in a single step. For conjugate addition of cyclopentanone to β-nitrostyrenes substituted with electron-rich and poor substituents, both diastereoand enantioselectivities were found to be significantly less as compared to those for cyclohexanone (Table 4, Entries 17-19).…”

“…41 (s, 9 H), 2.61-2.72 (m, 6 H), 2.81-2.93 (m, 6 H), 3.16- 3.24 (m, 3 H),3.74 (d, J = 5.8 Hz, 6 H) ppm 13. C NMR (125 MHz, CDCl 3 ): δ = 15.5, 25.4, 29.4, 29.6, 46.2, 48.7, 55.0, 58.2.135.0 ppm.…”

Organocatalytic asymmetric Michael addition of aldehydes and ketones to nitroalkenes catalyzed by adamantoyl l-prolinamide

“…The aqueous phase was extracted with ethyl acetate. 65 The ethyl acetate extracts were pooled, washed with brine, dried over anhydrous Na 2 SO 4 , filtered off and the solvent was evaporated at low pressure to give a crude residue that was purified by column chromatography to give the pure Lprolineamide (7). …”

Highly Enantioselective Michael Addition of Acetone to Nitro Olefins Catalyzed by Chiral Bifunctional Primary Amine‐Thiophosphoramide Catalyst

“…[5] Most recently, we have developed (S,aR)-pyrrolidine thiophosphoramide 1 as an efficient organocatalyst for promoting the asymmetric Michael addition of cyclic ketones to nitro olefins. [6] It is believed that its high catalytic efficiency is attributable to its unique activation mode, arising from the thiophosphoramide moiety. This functionality serves as a hydrogen-bonding donor for the activation of nitro olefin substrates and formation of a well-controlled transition state.…”