Diastereoselective and Enantioselective Michael Addition Reactions of Ketones and Aldehydes to Nitro Olefins Catalyzed by C₂‐Symmetric Axially‐Unfixed Biaryl‐Based Organocatalysts Derived from Enantiopure α‐Proline

Abstract

A new class of axially‐unfixed biaryl‐based pyrrolidines with C2‐symmetry were designed and synthesized by using enantiopure α‐proline as a chiral source. These bifunctional organocatalys provided Michael adducts in high chemical yields (up to 99 %) and with excellent stereoselectivities (up to 99:1 dr and 96 % ee) in the direct Michael addition reactions of a variety of ketones and aldehydes to nitro olefins. The transition states were proposed to clarify the stereochemical course of the examined reactions.

Synthesis of Extended Bipyridine‐proline Chiral Catalysts and Resulting Effects on the Asymmetric Aldol Reactions of Bulkier Aldehyde Derivatives with Cyclohexanone

“…As compared to that of chiral phosphine and amine catalysts, chiral bipyridine catalysts have attracted great attention owing to their highly efficient stereocontrol and unique coordination capabilities . Noticeably, a lot of reports indicated that the installation of an axially unfixed bipyridine in the designed organocatalysts may afford them favorable conformational properties responsible for efficient chiral induction, and therefore the effect of the steric hindrance originating from reactant or catalyst itself could be minimized . Meanwhile, our preliminary work further testified that the ligands of 2,2′‐bipyridine are easy to be modified and readily combined with functional groups compared with other ligands in current reported, similarly, such as L ‐proline and L ‐phenylalanine as chiral amino acids.…”

“…Meanwhile, our preliminary work further testified that the ligands of 2,2′‐bipyridine are easy to be modified and readily combined with functional groups compared with other ligands in current reported, similarly, such as L ‐proline and L ‐phenylalanine as chiral amino acids. In 2013, Zhao et al . developed a new series of bifunctional organocatalysts based on 2,2′‐bipyridine skeleton using L ‐proline as chiral source for aldol reactions between p ‐nitrobenzaldehyde and cyclohexanone with moderate efficiency (up to 63 % yield) and excellent stereocontrol ( ee up to 80 % and dr up to 93 : 7) in aqueous media.…”

“…The present investigates were performed in a homogeneous media, and further elucidated the influences of larger molecules of aldehyde reactants on the reactive mechanism of asymmetric aldol reaction, while other report was carried out under a heterogeneous system, and explored the immobilization of bipyridine‐proline onto the mesoporous silicas and their recyclable catalytic performance in asymmetric aldol reaction. This work reported the synthesis of ( S )‐ N ‐(3′‐(naphthalene‐1‐sulfonamido)‐[2,2′‐bipyridin]‐3‐yl) pyrrolidine‐2‐carboxamide (abbreviated as Z 2 ) containing prolinamide, sulfonamide, and naphthyl group by condensation reaction, meanwhile, ( S )‐ N ‐(3′‐((4‐methylphenyl)sulfonamido)‐[2,2′‐bipyridin]‐3‐yl) pyrrolidine‐2‐carboxamide (abbreviated as Z 1 ) and (2 S ,2′ S )‐ N , N′ ‐([2, 2′‐bipyridine]‐3,3′‐diyl) bis(2‐amino‐3‐phenylpropanamide) (abbreviated as Z 3 ) were provided by our collaborator . The asymmetric aldol reaction performances of cyclohexanone with aromatic aldehydes catalyzed by Z 1 , Z 2 , and Z 3 were systematically demonstrated under various polar solvents, such as petroleum ether, anhydrous toluene, dichloromethane (CH 2 Cl 2 ), anhydrous ethanol (EtOH), dimethyl formamide (DMF), DMSO, and water …”

Recent Advances in Organocatalytic Methods for Asymmetric CC Bond Formation

“…These syn-selective transformations are performed under neat conditions and show moderate to very good yields and selectivities. [83] Ni, Headley et al successfully performed reactions of acetaldehyde 30 and nitroalkenes followed by a reduction to the corresponding primary alcohols. Moderate yields but very good enantioselectivity are observed in most examples.…”

Stereoselective conjugate addition of ketones to alkylidene malonates using thiourea‐sulfonamide organocatalyst

“…[1][2][3][4] Useful synthetic intermediates can be produced by selecting the combination of different Michael donors and acceptors. The organocatalytic reactions of Michael donors such as aldehydes and ketones with electron deficient Michael acceptors such as α,β-unsaturated aldehydes, 5,6 ketones, 7-10 sulfones, 11,12 and nitrostylenes [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] are well investigated. However, alkylidene malonates are rarely used as a Michael acceptor in organocatalysis despite their availability as a synthetic intermediate for access to remarkable pharmaceutical compounds.…”