Project description:Salens are a class of important ligands and have been widely applied in asymmetric catalytic organic reactions. Enlarged salen-like ligands containing flexible chains were synthesized from L-phenylalanine, ethane/propanediamines, and salicylaldehydes, and successfully utilized in the scandium-catalyzed enantioselective Michael addition of indoles and enones (2-cinnamoylpyridine 1-oxides). The catalytic system demonstrates excellent reactivity and stereoselective control over electron-rich indole substrates with up to 99% yield and 99% enantiomeric excess. The enlarged Salen ligands with flexible and rigid combined linkers fit their coordination with large rare earth elements. Their coordination abilities were tuned by the electronic effect of substituents on their salicylaldehyde moiety, facilitating the construction of excellent chiral environments in the scandium(III)-catalyzed asymmetric Michael addition of indoles to 2-cinnamoylpyridine 1-oxides.
Project description:A number of upper rim-functionalized calix[4]thiourea cyclohexanediamine derivatives have been designed, synthesized and used as catalysts for enantioselective Michael addition reactions between nitroolefins and acetylacetone. The optimal catalyst 2 with a mono-thiourea group exhibited good performance in the presence of water/toluene (v/v = 1:2). Under the optimal reaction conditions, high yields of up to 99% and moderate to good enantioselectivities up to 94% ee were achieved. Detailed experiments clearly showed that the upper rim-functionalized hydrophobic calixarene scaffold played an important role in cooperation with the catalytic center to the good reactivities and enantioselectivities.
Project description:A highly stereoselective one-pot procedure involving an enantioselective Michael addition promoted by low loading of an amino-squaramide catalyst followed by an achiral base catalyzed domino Michael-Knoevenagel-type 1,2-addition sequence provides efficient access to fully substituted cyclohexanes bearing five contiguous stereogenic centers in good yields (68-86%) and excellent stereoselectivities (>30 : 1 dr and 96-99% ee).
Project description:In this paper, the organocatalytic asymmetric 1,4-Michael addition reaction of azadienes and α-thiocyanoindanones was investigated. A series of chiral benzofuran compounds containing thiocyano group and quaternary carbon center were synthesized in moderate yields with good enantioselectivities (up to 90:10 er) and high diastereoselectivities (up to >95:5 dr). This is the first case of 1,4-Michael addition reaction using α-thiocyanoindanones to obtain a series of chiral thiocyano compounds and further broaden the scope of application of azadiene substrates. In addition, a possible reaction mechanism is also described in the article.
Project description:Chiral derivatives of γ-aminobutyric acid are widely used as medicines and can be obtained by organocatalytic Michael additions. We show here the stereoselective synthesis of 4-methylpregabalin stereoisomers using a Michael addition of dimethyl malonate to a racemic nitroalkene. The key step of the synthesis operates as a kinetic resolution with a chiral squaramide catalyst. Furthermore, specific organocatalysts can provide respective stereoisomers of the key Michael adduct in up to 99:1 er.
Project description:Only a few studies on the use of halogen bonding in catalysis have been published so far. Herein, (benz)imidazolium-based halogen bond donors are used as catalysts in a Michael addition reaction. The most potent catalyst, a rigid atropisomer featuring two iodobenzimidazolium moieties, provided a rate acceleration versus a reference compound of ca. 50.
Project description:We developed self-assembled peptides containing a partial amyloid β protein sequence and a metal-coordination site. The amyloid fibril-copper complexes exhibited excellent reactivity and moderate enantioselectivity in Michael addition reactions with 2-azachalcone and dimethylmalonate. The catalytic amyloids were characterized using various measurements to confirm their amyloid-like nanofibre structures.
Project description:An asymmetric sulfa-Michael addition of alkyl thiols to enone diesters is reported. The reaction is catalyzed by a bifunctional triaryliminophosphorane-thiourea organocatalyst and provides a range of α-sulfaketones in high yields and enantioselectivities. Leveraging the gem-diester functional handle via a subsequent diastereotopic group discrimination generates functionalized lactones with three contiguous stereocenters.
Project description:Cage catalysis continues to create significant interest, yet catalyst function remains poorly understood. Herein, we report mechanistic insights into coordination-cage-catalyzed Michael addition using kinetic and computational methods. The study has been enabled by the detection of identifiable catalyst intermediates, which allow the evolution of different cage species to be monitored and modeled alongside reactants and products. The investigations show that the overall acceleration results from two distinct effects. First, the cage reaction shows a thousand-fold increase in the rate constant for the turnover-limiting C-C bond-forming step compared to a reference state. Computational modeling and experimental analysis of activation parameters indicate that this stems from a significant reduction in entropy, suggesting substrate coencapsulation. Second, the cage markedly acidifies the bound pronucleophile, shifting this equilibrium by up to 6 orders of magnitude. The combination of these two factors results in accelerations up to 109 relative to bulk-phase reference reactions. We also show that the catalyst can fundamentally alter the reaction mechanism, leading to intermediates and products that are not observable outside of the cage. Collectively, the results show that cage catalysis can proceed with very high activity and unique selectivity by harnessing a series of individually weak noncovalent interactions.
Project description:Organophosphorus compounds are the core structure of many active natural products. The synthesis of these compounds is generally achieved by metal catalysis requiring specifically functionalized substrates or harsh conditions. Herein, we disclose the phospha-Michael addition reaction of biphenyphosphine oxide with various substituted β-nitrostyrenes or benzylidene malononitriles. This biocatalytic strategy provides a direct route for the synthesis of C-P bonds with good functional group compatibility and simple and practical operation. Under the optimal conditions (styrene (0.5 mmol), biphenyphosphine oxide (0.5 mmol), Novozym 435 (300 U), and EtOH (1 mL)), lipase leads to the formation of organophosphorus compounds in yields up to 94% at room temperature. Furthermore, we confirm the role of the catalytic triad of lipase in this phospha-Michael addition reaction. This new biocatalytic system will have broad applications in organic synthesis.