Pyrrolidine-HOBt: an oxytriazole catalyst for the enantioselective Michael addition of cyclohexanone to nitroolefins in water

Pyrrolidine-Oxadiazolone Conjugates as Organocatalysts in Asymmetric Michael Reaction

“…In effect, proline can function as bifunctional asymmetric catalyst and thereby became successful for facilitating stereoselective chemical transformations similar to enzymatic catalysis. Thus, the use of proline and the small molecules derived from it has been a major breakthrough in the field of organocatalysis to synthesize compounds with improved stereoselectivities. − Typically, the 1,4-Michael additions with proline as organocatalyst afford modest enantioselectivity; surprisingly though, homoproline is found to be ineffective. , Both proline and homoproline are bipolar molecules; the reactions usually require polar solvents like DMSO or alcohol because of their insoluble nature. The oxadiazolone ring is frequently employed as a bioisostere for a carboxylic acid for having similar p K a .…”

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

“…d and l forms of proline are inexpensive; besides this, proline has two functional groups, a carboxylic acid and an amine [thus, the reactions usually require polar solvents such as dimethyl sulfoxide (DMSO) or alcohol due to their insoluble nature], and plays a significant role in bi-functional asymmetric catalysis, which has become a successful strategy for facilitating chemical transformations similar to enzymatic catalysis. Thus, proline and its derivatives, to construct stereocenters in organic compounds with better selectivities, are one of the major milestones in the field of organocatalysis. − …”

“…The use of proline and proline derivatives as catalysts of multicomponent reactions performed in aqueous media has been summarized in a recent review . As an example, asymmetric Michael addition exclusively in water or brine has been reported albeit with very long reaction time and/or resulting in low enantioselectivities in many adducts. , In continuation of our studies and to improve on the enantioselectivity in water as a reaction medium in short reaction time, we here synthesized a set of new chiral proline-based compounds 1–5 (Figure ) as promising organocatalysts containing a bulky hydrophobic substituent at the 4-position and methylene-heterocycle at the 2-position (except cat. 4) of the pyrrolidine ring to examine the performance of these catalysts 1–5 in Michael addition between nitroolefins and carbonyl compounds solely in water medium.…”

Recent Advances in Asymmetric Organocatalyzed Conjugate Additions to Nitroalkenes

“…Thus, pyrrolidine 26 (10 mol %) containing a HOBt moiety ( Figure 4 ) promoted the Michael addition of cyclohexanone to aryl nitroolefins in water as solvent, providing the corresponding γ-nitrocarbonyl derivatives 46 in good yields (84–95%), with high diastereo- (91/9–96/4) and enantioselectivities (81–95%) irrespective of the substitution pattern on the nitroolefins. However, lower results were achieved with other ketones, such as tetrahydro- 4H -pyran-2-one, cyclopentenone or acetone [ 73 ]. Similar results were encountered when organocatalyst 36 (10 mol %) containing a oxyimide appendage ( Figure 5 ) was used in water for the Michael addition of cyclic ketones as pro-nucleophiles and aromatic trans -nitrostyrenes (86–95% yield, 91/9–97/3 dr , 85–96% ee ).…”