Highly enantioselective aldehyde-nitroolefin Michael addition reactions catalyzed by recyclable fluorous (S) diphenylpyrrolinol silyl ether

A recyclable and reusable (S) diphenylpyrrolinol silyl ether I organocatalyst bearing a n-C₈F₁₇ fluorous tag has been demonstrated for promoting the asymmetric Michael addition reactions of a wide range of aldehydes with both aryl and alkyl-substituted nitroolefins and excellent levels of enantio- and diastereoselectivities are achieved. The catalyst I can be conveniently recovered by fluorous solid-phase extraction and subsequently reused (up to eight cycles) without significant loss of its catalytic activity and stereoselectivity for the process.     

Highly enantioselective Michael additions in water catalyzed by a PS-supported pyrrolidine

The development of a highly efficient, polymer-supported organocatalyst for the Michael addition of ketones to nitroolefins is described. A 1,2,3-triazole ring, constructed through a click 1,3-cycloaddition, plays the double role of grafting the chiral pyrrolidine monomer onto the polystyrene backbone and of providing a structural element, complementary to pyrrolidine, key to high catalytic activity and enantioselectivity. Optimal operation in water and full recyclability make the triazole linker attractive for the immobilization of organocatalysts.     

A recyclable fluorous (S)-pyrrolidine sulfonamide promoted direct, highly enantioselective Michael addition of ketones and aldehydes to nitroolefins in water

[reaction: see text] A recycle and reusable fluorous (S)-pyrrolidine sulfonamide organocatalyst has been developed for promoting highly enantio- and diastereoselective Michael addition reactions of ketones and aldehydes with nitroolefins in water. The organocatalyst is conveniently recovered from the reaction mixtures by fluorous solid-phase extraction and can be subsequently reused (up to six cycles) without a significant loss of catalytic activity and stereoselectivity.     

Highly efficient asymmetric aldol reaction in brine using a fluorous sulfonamide organocatalyst

A fluorous organocatalyst promotes direct asymmetric aldol reactions of aromatic aldehydes with ketones in brine to afford the corresponding anti-aldol products in high yield with up to 96% ee. Fluorous organocatalyst can be readily recovered by solid phase extraction using fluorous silica gel and reused without purification.     

Highly enantioselective direct aldol reaction catalyzed by organic molecules

We have demonstrated that a new class of l-proline-based organic compounds catalyzed the direct aldol reaction between aldehydes and acetone to provide beta-hydroxy ketones in good yields. The reaction is efficient, and 5-10 mol % of the catalyst and excellent enantioselectivities (97-99% ee) were obtained in both aromatic and aliphatic aldehydes. The presence of a gem-diphenyl group at the beta-carbon is necessary for high enantioselectivity.     

Highly enantioselective mukaiyama aldol reactions catalyzed by a chiral oxazaborolidinium ion: total synthesis of (-)-inthomycin C

A cationic oxazaborolidinium-catalyzed asymmetric Mukaiyama aldol reaction of (1-methoxy-2-methyl-propenyloxy)-trimethylsilane with various aldehydes including α,β-disubstituted acroleins has been developed in high yields and enantioselectivities. The synthetic utility of this methodology was demonstrated in the first short synthesis of naturally occurring inthomycin C in high enantiopurity.     

Highly diastereo- and enantioselective direct aldol reactions of aldehydes and ketones catalyzed by siloxyproline in the presence of water

Proline-based organocatalysts have been developed for a highly enantioselective, direct aldol reaction of aldehydes and ketones in the presence of water. While several surfactant-proline combined catalysts have proved effective, proline derivatives with a hydrophobic moiety such as trans-siloxy-L-proline and cis-siloxy-D-proline, both of which are easily prepared from the same commercially available 4-hydroxy-L-proline, have been found to be the most effective organocatalysts examined in this study, affording the aldol product with excellent diastereo- and enantioselectivities, these two catalysts generating opposite enantiomers. Water affects the selectivity, and poor results are obtained under neat reaction conditions or in dry organic solvents. More than three equivalents of water are required for the best diastereo- and enantioselectivities, while three equivalents is the recommended amount from a synthetic point of view. The reaction proceeds in the organic phase, and also proceeds in the presence of a large amount of water. The large-scale preparation of aldols with the minimal use of an organic solvent, including in the purification step, is described.     

Highly diastereo- and enantioselective direct aldol reactions of cycloketones with aldehydes catalyzed by a trans-4-tert-butyldimethylsiloxy-l-proline amide

An organocatalyst derived from trans-4-hydroxy-l-proline and (1S,2S)-1,2-diphenyl-2-aminoethanol catalyzes the direct aldol reactions of cycloketones with a wide scope of aldehydes in high yields and with excellent diastereoselectivities of up to >99:1 and enantioselectivities of up to >99% ee.     

Highly stereoselective direct aldol reactions catalyzed by a bifunctional chiral diamine

The enantioselective organocatalytic direct aldol reactions of ketones with various aldehydes were developed by using chiral 1,2-cyclohexanediamine (DACH) based multifunctional ligands via a noncovalent catalysis mechanism. By using a catalyst, we also obtained functionalized 3-alkyl-3-hydroxyindolin-2-ones in high yields and with good to excellent enantioselectivities.     

Highly enantioselective direct aldol reaction catalyzed by cinchona derived primary amines

Highly enantioselective aldol reactions of aldehydes with cyclic ketones catalyzed by a primary amine derived from cinchonine are reported. Aromatic aldehydes reacted with various cyclic ketones cleanly to afford the anti-aldol adducts in up to 99% yield, with good diastereoselectivities (up to 9 : 1) and excellent enantioselectivities (up to 99% ee).     

Highly enantioselective carbonyl-ene reactions catalyzed by a hindered silyl-salen-cobalt complex

We report here the enantioselective carbonyl-ene reactions of various 1,1-disubstituted and trisubstituted alkenes with ethyl glyoxylate. The reactions are catalyzed by a new Co-salen complex, in which bulky triisobutylsilyl (TIBS) substituents occupy the positions ortho to the phenolic oxygens. This complex catalyzes the reactions under nearly ideal conditions - at room temperature and using catalyst loadings as low as 0.1 mol % - and provides the chiral, homoallylic alcohol products in excellent yields, enantioselectivities, and diastereoselectivities.     

Asymmetric aldol reactions catalyzed by tryptophan in water

Tryptophan was shown to be able to catalyze direct aldol reactions between various cyclic ketones and aromatic aldehydes in water with high enantioselectivity.     

Highly enantioselective phenylacetylene additions to ketones catalyzed by (S)-BINOL-Ti complex

The readily available and inexpensive (S)-BINOL ligand in combination with Ti(O(i)Pr)(4) is an effective chiral catalyst for the catalytic asymmetric addition of alkynylzinc to unactivated simple ketones. Good to excellent enantioselectivities were achieved. No previous case has been reported successfully using BINOL to catalyze the addition of phenylacetylene to unactivated ketones, and thus the utility of BINOL in asymmetric catalysis is expanded.     

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.     

Highly enantioselective azadiene Diels-Alder reactions catalyzed by chiral N-heterocyclic carbenes

Highly enantioselective, N-heterocyclic carbene (NHC)-catalyzed aza-Diels-Alder reactions are described. A novel chiral triazolium salt based on the cis-1,2-aminoindanol platform serves as an efficient precatalyst for the NHC-catalyzed redox generation of enolate dienophiles that undergo LUMOdiene-controlled Diels-Alder reactions with N-sulfonyl-alpha,beta-unsaturated imines in good yields and with exceptional diastereo- and enantioselectivities (>99% ee). In contrast to uncatalyzed variants, this organocatalytic process proceeds at room temperature without stoichiometric reagents, producing synthetically valuable, enantiomerically pure cis-3,4-disubstituted dihydropyridinone products.     

Highly exo-selective and enantioselective cycloaddition reactions of nitrones catalyzed by a chiral binaphthyldiimine-Ni(II) complex

[reaction: see text] Significant levels of exo-selectivity (exo:endo = >99:1 to 86:14) and enantioselectivity (95-82% ee) were obtained in the 1,3-dipolar cycloadditions of a number of nitrones with 3-(2-alkenoyl)-2-thiazolidinethiones, using the chiral binaphthyldiimine-Ni(II) complex (5-20 mol %), which was easily prepared form N,N'-bis(3,5-dichrolo-2-hydroxybenzylidene)-1,1'-binaphthyl-2,2'-diamine and Ni(ClO4)2 x 6H2O in CHCl3 in the presence of 4 A molecular sieves, as a chiral Lewis acid catalyst.