Highly enantioselective Michael addition of ketones to nitroolefins catalyzed by (S)-pyrrolidine arenesulfonamide

A new type of catalyst for the asymmetric Michael addition reaction has been designed and synthesized. This catalyst, (S)-pyrrolidine arenesulfonamide 1, resulted in high yields (up to 93%), excellent diastereoselectivities (syn/anti ratio up to 99/1), and excellent enantioselectivities (ee up to 99%) for various cyclic ketones and nitroolefins.     

Enantioselective anti-Mannich reaction catalyzed by modularly designed organocatalysts

A highly stereoselective method for achieving the anti-Mannich reaction of aldehydes and ketones with ethyl (4-methoxyphenylimino)acetate was realized using the modularly designed organocatalysts (MDOs) self-assembled from cinchona alkaloid derivatives and (R)-pyrrolidien-3-carboxylic acid in the reaction media. The desired anti-Mannich products were obtained in good to excellent yields (up to 93%), excellent diastereoselectivities (up to 99:1 dr), and good to high enantioselectivities (up to 99% ee).     

Highly diastereo- and enantioselective direct aldol reactions by 4-tert-butyldimethylsiloxy-substituted organocatalysts derived from N-prolylsulfonamides in water

A new set of 4-tert-butyldimethylsiloxy-substituted organocatalysts derived from N-prolylsulfonamide has been designed and proved to be effective in catalyzing the direct aldol reactions of cyclic ketones with a series of aromatic aldehydes. Furthermore, to the best of our knowledge, there are no reports on the aldol reaction generating the products in very good yields (>99%) and with excellent diastereoselectivities up to >99:1 and enantioselectivities up to >99% by using lower catalyst loadings (only 3 mol %), without using any additives in a large amount of water under mild conditions.     

Chiral N-phosphoryl imines: design, synthesis and direct asymmetric addition reactions with diketones and diesters

Chiral N-phosphoryl imines derived from (S)-BINOL have been designed and synthesized in good to excellent chemical yields. These N-phosphoryl imines were found to react with diketones smoothly without the use of any bases. They can also serve as electrophiles for the reaction with diethyl malonate in the presence of potassium carbonate. Good yields (62%—quant) and excellent diastereoselectivities (up to 99:1 dr) have been achieved for 10 examples.     

Novel chiral ammonium ionic liquids as efficient organocatalysts for asymmetric Michael addition of aldehydes to nitroolefins

Two chiral ammonium ionic liquids 1a and 1b have been newly synthesized from commercially available (+)-cis-2-benzamidocyclohexanecarboxylic acid. These CILs have been demonstrated to be efficient organocatalysts for asymmetric Michael addition of aldehydes to nitroolefins with excellent yields (up to 99%), high enantioselectivities (up to 90%) and modest to high diastereoselectivities (syn/anti ratio up to 99/1).     

A new type of amino amide organocatalyzed enantioselective crossed aldol reaction of ketones with aromatic aldehydes

A new type of amino amide organocatalysts was designed and synthesized from commercially available amino acids in easy steps. Their catalytic activities were examined in enantioselective crossed aldol reaction of various acyclic and cyclic ketones with aromatic aldehydes to afford the corresponding chiral anti-aldol adducts with good to excellent chemical yields, diastereoselectivities and enantioselectivities (up to 99%, up to syn:anti?=?1:99, up to 97% ee).     

Enantioselective Ag(I)-catalyzed [3+2] cycloaddition of azomethine ylides using a chiral ferrocene-based phosphine–phosphoramidite ligand having a stereogenic P-center

A series of chiral ferrocene-based phosphine–phosphoramidite ligands (PPFAPhos) have been employed in the Ag(I)-catalyzed asymmetric [3+2] cycloaddition of azomethine ylides with dimethyl maleate. The results showed that the ligand with a stereogenic P-center in the phosphino moiety displayed the best diastereo- and enantioselectivities, in which up to 99% enantiomeric excesses and 99/1 endo/exo selectivities have been achieved.     

A chiral primary-tertiary-1,2-diamine as an efficient catalyst in asymmetric aldehyde–ketone or ketone–ketone aldol reactions

A novel chiral 1,2-diaminocyclohexane derivative, (1R,2R)-N¹-n-pentyl, N¹-benzyl-1,2-cyclohexanediamine, was designed, synthesized and applied as a catalyst in a number of aldol reactions between ketones and aryl aldehydes. Reactions between acetone and aryl aldehydes gave aldol products with moderate to good yields and with excellent enantioselectivity (up to yield 85%, ee 98%), while reactions between cyclohexanone and aryl aldehydes provided anti-β-hydroxyketone products with excellent yields, diastereoselectivity and with enantioselectivity (up to 82% yield, anti/syn ratio 99:1, ee 99%). The aldol reactions between acetone and isatins were investigated, which afforded excellent yields and enantioselectivity (up to 95% yield, 98% ee). The (R)- and (S)-isomers of convolutamydine A were obtained with 95% yield and 96% ee, and 95% yield and 94% ee, respectively.     

Organocatalytic asymmetric synthesis of 3(2H)-furanones with adjacent quaternary and tertiary stereocenters

An efficient stereoselective Michael addition of simple 3(2H)-furanones to α,β-unsaturated ketones has been described. The protocol provides a facile and efficient access to complex 3(2H)-furanones containing adjacent quaternary and tertiary stereocenters in high yields (up to 99%) with good diastereoselectivities (up to 86:14) and excellent enantioselectivities (up to 98% ee) under mild conditions.     

Effective and recyclable dendritic catalysts for the direct asymmetric Michael addition of aldehydes to nitrostyrenes

Direct catalytic enantio- and diastereoselective Michael addition reaction of aldehydes to nitrostyrenes is described using a series of recyclable chiral 2-trimethylsilanyloxy-methyl-pyrrolidine-based dendritic catalysts. Good yields (up to 82%), and high diastereoselectivities (up to syn/anti = 95/5) and enantioselectivities (up to 99% ee) have been obtained.     

Highly enantioselective 1,3-dipolar cycloaddition of imino esters with benzofuranone derivatives catalyzed by thiourea−quaternary ammonium salt

Highly enantioselective 1, 3-dipolar cycloaddition of 2-arylidene-benzofuran- 3(2H)-ones with imino esters catalyzed by thiourea?quaternary ammonium salts has been developed. This reaction provides efficient construction of a range of chiral spiro[benzofuran-2,3′-pyrrolidine] in high yields (up to 99%) and with good enantioselectivities (up to 99% ee) under mild conditions.     

Cinchona alkaloid derived squaramide catalyzed diastereo- and enantioselective Michael addition of isocyanoacetates to 2-enoylpyridines

An efficient organocatalytic diastereo- and enantioselective Michael addition of α-substituted isocyanoacetates to 2-enoylpyridines catalyzed by cinchona alkaloid-derived squaramide has been achieved, affording the corresponding adducts with two adjacent tertiary-quaternary stereocenters in excellent yields (up to 99%) and good to excellent stereoselectivities (up to >20:1 dr, up to 98% ee) under mild conditions.     

Asymmetric Michael addition reactions catalyzed by a novel upper-rim functionalized calix[4]squaramide organocatalyst

A novel upper-rim functionalized calix[4]squaramide organocatalyst bearing bis-squaramide and cyclohexanediamine scaffolds was designed and prepared to catalyse a serial of asymmetric Michael addition of 1,3-dicarbonyl compounds to α,β-unsaturated carbonyl compounds in high yields (up to 99 %) and good to excellent enantiomeric excesses (up to 99% ee). The comparative experiments indicated that the cooperative effect between calixarenes cavitives and chiral catalytic centers on this calix[4]squaramide catalyst could promote these reactions. Moreover, this strategy also provides valuable and easy access to chiral chromene, naphthoquinone and acetylacetone derivatives, which are important skeletons in biological and pharmaceutical compounds.     

Pt(IV)-catalyzed generation and [4+2]-cycloaddition reactions of o-quinone methides

Novel intermolecular and intramolecular generations of ortho-quinone methides and their formal [4+2]-cycloaddition reactions with olefins catalyzed by PtCl₄ and AuCl₃ under mild conditions have been developed. Good to excellent yields (up to 99%) and diastereoselectivity (up to >99:1) of the chromans were obtained. PtCl₄ was found to be effective and compatible with various functional groups present in the substrates. A mechanism accounting for its catalytic cycle is proposed and discussed.     

Highly enantioselective Michael/cyclization tandem reaction between dimedone and isatylidene malononitriles

A highly enantioselective Michael/cyclization tandem reaction between dimedone and isatylidene malononitriles has been developed. With 5?mol% of bifunctional organocatalyst C15, chiral spiro[2-amino-4H-pyran-oxindole] derivatives were obtained in excellent yields (97–99%) with excellent enantioselectivities (up to?>?99% ee).     

L-tert-Leucine derived urea-ammonium salts: Efficient bifunctional phase transfer catalysts for highly diastereo- and enantioselective aza-Henry reaction of isatin-derived N-Boc ketimines with α-aryl nitromethanes

An efficient way of aza-Henry reaction between isatin-derived N-Boc ketimines and α-aryl nitromethanes catalyzed by bifunctional phase transfer catalysts with a quaternary ammonium center derived from L-tert-Leucine has been developed. A series of 3-substituted 3-amino-oxindoles were constructed by this catalytic protocol in excellent yields (90–99%), with high enantioselectivities (83–95%) and diastereoselectivities (79:21–97:3). The asymmetric aza-Henry reaction of N-Boc amidosulfones and α-aryl nitromethanes were also investigated and gave the corresponding products in high to excellent yields (72–97%) with high enantioselectivities (up to 99%) and diastereoselectivities (up to >99:1).     

Aromatic l-prolinamide-catalyzed asymmetric Michael addition of aldehydes to nitroalkenes

Two chiral aromatic l-prolinamides were synthesized in high overall yield (95%) from N-Boc-l-proline and served as organocatalysts in asymmetric Michael reactions of aldehydes to nitroalkenes. Under the optimized reaction conditions, (S)-N-tritylpyrrolidine-2-carboxamide 4 was found to be a highly efficient organocatalyst for the Michael addition, and the corresponding Michael adducts were obtained in good yields (up to 94%), with excellent enantioselectivities (up to 99% ee) and diastereoselectivities (up to 99:1 dr).     

Chiral iminophosphoranes organocatalyzed asymmetric hydroxylation of 3-substituted oxindoles with oxaziridines

Enantioselective hydroxylation of N-protected 3-substituted oxindoles has been developed via chiral iminophosphorane catalysis with oxaziridines as oxidants. As such, a variety of optically active 3-substituted-3-hydroxy-2-oxindoles were obtained in excellent yields (91–99%) and moderate to excellent level of enantiomeric excess (up to 94% ee).     

4-Trifluoromethanesulfonamidyl prolinol tert-butyldiphenylsilyl ether as a highly efficient bifunctional organocatalyst for Michael addition of ketones and aldehydes to nitroolefins

4-Trifluoromethanesulfonamidyl prolinol tert-butyldiphenylsilyl ether bifunctional organocatalyst 3a is a highly efficient catalyst for the asymmetric Michael addition reactions of ketones and aldehydes to nitrostyrenes, leading to syn-selective adducts with excellent yields (>99%), high diastereoselectivities (up to 99:1 dr) and excellent enantioselectivities (up to 99% ee). Control experiments suggested that the trans-configuration relationship between the bulky group (-CH₂OTBDPS) and the sulfonamido group at the 4-position of the pyrrolidine ring was important to achieve high yield and stereoselectivity.     

Highly enantioselective Michael addition of <Emphasis Type="Italic">α,α</Emphasis>-disubstituted aldehydes to nitroolefins

A highly enantioselective Michael addition reaction of α,α-disubstituted aldehydes to β-nitrostyrenes has been developed. In the presence of rosin-based chiral primary amine-thiourea, γ-nitroaldehydes were afforded in excellent enantioselectivities (up to 99 % ee) with up to 99 % yield.