C₂-Symmetric pyrrolidine-derived squaramides as recyclable organocatalysts for asymmetric Michael reactions

Abstract

Novel C-symmetric N,N'-bis-[(pyrrolidin-2-yl)methyl-squaramide] TFA salts bearing (R,R)- or (S,S)-1,2-di(pyridin-2-yl)ethane spacer groups were synthesized and applied, in combination with TEA, as efficient organocatalysts for asymmetric reactions between cyclohexanone derivatives and β-nitrostyrenes to afford the corresponding Michael adducts in high yields with good to excellent enantioselectivity. The catalytic procedure is readily scalable and recyclable over four times without a negative impact on the selectivity of the reaction. Some of the prepared compounds are valuable precursors to useful bioactive molecules.

Asymmetric Conjugate Addition of 3‐Hydroxychromen‐4‐Ones to Electron‐Deficient Olefins Catalyzed by Recyclable C2‐Symmetric Squaramide

“…As we proposed, with a 2‐fold excess of chromone 1 a , the reaction rate was noticeably lower than with an equimolar ratio of the reagents. Probably, the formation of an inactive associate of catalyst V with two molecules of chromone 1 a occurs, which reduces its activity and prevents nitrostyrene from effectively forming hydrogen bonds required for the asymmetric Michael reaction to occur [27] . The influence of the steric hindrance is confirmed by kinetic experiments in the presence of the acid additive (TFA, 2 mol%) which protonates one of the amino groups of catalyst V and does not impede to reagents contact.…”

“…These features give them an unambiguous advantage in the creation of modern technologies for the asymmetric synthesis of chiral biologically active substances. In addition C 2 ‐symmetric catalysts can be desymmetrized, for example, as a result of protonation or the formation of a hydrogen bond involving only one of two identical fragments, which makes it possible to regulate the properties of the catalyst to achieve the highest level of stereoinduction [27] …”

“…result of protonation or the formation of a hydrogen bond involving only one of two identical fragments, which makes it possible to regulate the properties of the catalyst to achieve the highest level of stereoinduction. [27] Apparently, bifunctional catalyst V deprotonates chromone 1 by the action of the tertiary amino group and simultaneously determines the geometry of active complex, forming strong hydrogen bonds with elec-tron-deficient olefin 2 or 4 by means of presenting NH-fragments, as described in plausible transition states TS1 and TS2 (Figure 5).…”

Сhiral and Racemic Fields Concept for Understanding of the Homochirality Origin, Asymmetric Catalysis, Chiral Superstructure Formation from Achiral Molecules, and B-Z DNA Conformational Transition

“…Symmetry 2019, 11, x FOR PEER REVIEW 18 Transition states of the reaction (16) on C2 organocatalyst 32.Therefore, asymmetric induction proceeds through the C1-symmetric (asymmetric) key intermediate in two-component reactions catalyzed by C2 organocatalysts. Another example in support of this conclusion is Michael's reaction (17) on novel C2-symmetric N,N'-bis-[(pyrrolidin-2 yl)methyl-squaramide] TFA ((R,R)-33 or (S,S)-33) salts[150].…”

Asymmetric Conjugate Additions of Carbonyl Compounds to Nitroalkenes under Solvent-Free Conditions Using Fluorous Diaminomethylenemalononitrile Organocatalyst

“…[1][2][3][4][5][6][7][8][9] Among several synthetic methods to obtain enantiomer-enriched, γ-nitro carbonyl compounds, asymmetric conjugate addition of carbonyl compounds to nitroalkenes using organocatalysts is one of the most convenient and environmentally benign methodologies. [10][11][12][13][14][15][16][17] Organocatalysis between carbonyl compounds and nitro alkenes has been reported by several research groups; however, due to obstacles faced by most previously reported organocatalysis, such as high catalyst loading or long reaction times, the development of organocatalysts for highly efficient asymmetric conjugate additions of carbonyl compounds to nitroalkenes still remains an area of research interest. Thiourea organocatalysts, which are represented by Takemoto catalysts, are excellent catalysts and are applied to remarkably important asymmetric reactions.…”