Asymmetric 1,4-Michael Addition in Aqueous Medium Using Hydrophobic Chiral Organocatalysts

Abstract

Organic transformations exclusively in water as an environmentally friendly and safe medium have drawn significant interest in the recent years. Moreover, transition metal-free synthesis of enantiopure molecules in water will have a great deal of attention as the system will mimic the natural enzymatic reactions. In this work, a new set of proline-derived hydrophobic organocatalysts have been synthesized and utilized for asymmetric Michael reactions in water as the sole reaction medium. Among the various catalysts screened, the catalyst 1 is indeed efficient for stereoselective 1,4-conjugated Michael additions (dr: >97:3, ee up to >99.9%) resulting in high chemical yields (up to 95%) in a very short reaction time (1 h) at room temperature. This methodology provides a robust, green, and convenient protocol and can thus be an important addition to the arsenal of the asymmetric Michael addition reaction. Upon successful implementation, the present strategy also led to the formation of an optically active octahydroindole, the key component found in many natural products.

Amino Imidate Catalyzed Asymmetric Michael Reactions of Ketones and Nitroalkenes

“…The data agree with those reported in the literature. 15a Detected anti -isomer signal: δ = 4.02–3.97 (m, 1 H). 15b…”

Application of Proline-Derived (Thio)squaramide Organocatalysts in Asymmetric Diels–Alder and Conjugate Addition Reactions

“…16•TFA provided a higher, but only moderate enantiomer excess (51%) in a good yield (83%) in acetonitrile compared to squaramide 11•TFA (Table 4, entry 11 vs entry 12). To further improve the selectivity, higher catalyst loading (20 mol%) was applied but only the improvement of yields was achieved (Table 4, entries 13,14).…”

“…[7][8][9][10][11] Fülöp and coworkers successfully applied solid-supported proline-based catalysts in asymmetric Michael additions with excellent enantiomeric excess values (up to 95%). 12,13 Moreover, proline derivatives can be also applied in aldol, 3 Michael, 14 Mannich, 15 and Diels-Alder reactions, 2 etc. Considering the stereocontrol of the proline catalysts in asymmetric reactions, they can be divided into two main groups.…”

A triple cascade approach towards the diastereoselective synthesis of spiro trans-decalinol scaffolds

“…The first organocatalytic reaction of cyclohexanone and β-nitrostyrene for the synthesis of γ-nitroketone in the presence of l -proline was reported by Enders and co-workers in 79% yield and 97 : 3 dr. 10 Later on, many research groups explored bifunctional organocatalysts for the synthesis of various γ-nitroketones. 11,12 Although there are reports for organic transformations using pre-formed γ-nitrocarbonyls, 13 triple cascade reactions with γ-nitrocarbonyls as reaction intermediate are scarce. 14 In our continuing effort towards novel cascade reactions, 15 we envisioned that cyclohexanone, β-nitrostyrene and 2-arylidene-1,3-indanedione if exploited effectively could result in the formation of a spiro- trans -decalinol framework (Scheme 1).…”