A new organocatalyst derived from abietic acid and 4-hydroxy-l-proline for direct asymmetric aldol reactions in aqueous media

Enantioselective direct aldol reactions were carried out in aqueous media with a new organocatalyst that was derived from 4-hydroxy-l-proline and abietic acid via a simple and convenient synthetic protocol with a high overall yield (75%). The new organocatalyst was used for aldol reactions between substituted aromatic aldehydes and various ketones in the presence of several acid additives in aqueous media. The corresponding aldol products were obtained in high isolated yields (up to 99%) and with high anti-diastereoselectivities (up to 94%) and enantioselectivities (>99.9%). The catalyst loading can be efficiently reduced to only 1 mol %. The aldol reactions were found to be extremely fast which is very unusual in organocatalyzed reactions in water.     

Chiral quaternary alkylammonium ionic liquid [Pro-dabco][BF4]: as a recyclable and highly efficient organocatalyst for asymmetric Michael addition reactions

A novel series of chiral quaternary ammonium ionic liquids have been synthesized and shown to be very effective catalysts for the asymmetric Michael addition reactions of ketones and aldehydes to nitroolefins with excellent yields (up to 100%), diastereoselectivities (syn/anti = 99:1), and enantioselectivities (up to 97%). The catalytic system, an ionic liquid organocatalyst in [Bmim][BF₄], could be reused five times without a significant loss in catalytic activity or stereoselectivity.     

Achiral additives dramatically enhance enantioselectivities in the BINOL–Ti(IV) complex catalyzed aldol condensations of aldehydes with Chan’s diene

Achiral additives can dramatically enhance the enantioselectivities in the BINOL–Ti(IV) complex catalyzed aldol condensations of aldehydes with Chan’s diene. The best results were obtained by using 2.0 equiv of LiCl with respect to (S)-BINOL/Ti(Oi-Pr)₄ as the additive. In the presence of 4.0 mol % of LiCl and 2.0 mol % of BINOL/Ti(Oi-Pr)₄, all aldehydes tested gave δ-hydroxy-β-ketoesters as almost pure single enantiomers. Moreover, the present catalyst system was highly effective on reducing the catalyst loadings to 0.1 mol %.     

Asymmetric nitroaldol reaction catalyzed by copper–diamine complexes: selective construction of two contiguous stereogenic centers

Chiral copper(II) complexes of secondary bisamines derived from 1,2-diaminocyclohexane were successfully used in the diastereoselective nitroaldol reaction. The reactions were carried out in the presence of 10 mol % of the Cu(II) complex and 7.7 mol % of i-Pr₂NEt in 2-propanol at ?30 °C. Good to excellent yields, enantioselectivities of up to 99%, and moderate to excellent diastereoselectivities were obtained for both aromatic or aliphatic aldehydes and various prochiral nitrocompounds forming the corresponding β-nitroalcohols with two contiguous stereocenters.     

l-Proline amides catalyze direct asymmetric aldol reactions of aldehydes with methylthioacetone and fluoroacetone

Direct aldol reactions of aldehydes with methylthio- and fluoroacetone catalyzed by proline amides have been investigated. l-Prolinamide 5e was found to be the best catalyst. Under the optimized reaction conditions, a series of aromatic and aliphatic aldehydes reacted smoothly with methylthioacetone, to generate 1-methylthio-4-hydroxyketones 3 in good yields and with high regio- and enantioselectivities. Excellent enantioselectivities of up to 98% ee were observed for aromatic aldehydes and even higher enantioselectivities of >99% ee were observed for aliphatic aldehydes. Asymmetric direct aldol reactions of fluoroacetone with aldehydes in the presence of 20 mol % of 5e preferentially occurred at the fluoromethyl group, yielding products with high enantioselectivities (up to 98% ee).     

Recoverable Cinchona ammonium salts as organocatalysts in the enantioselective Michael addition of β-keto esters

Several dimeric Cinchona-alkaloid anthracenyldimethyl-derived ammonium salts, are used as organocatalysts in the enantioselective Michael addition reaction of cyclic β-keto esters to α,β-unsaturated carbonyl compounds, in the presence of diisopropylethylamine as a base (30 mol %), for the generation of enantiomerically enriched adducts bearing quaternary stereocenters. Quinine and quinidine-derived dimeric ammonium salts (1–10 mol %) afford the opposite and higher enantioselectivities of the corresponding adducts (up to 94% ee) in good yields (up to 98%). Substituted 2-alkoxycarbonyl-1-indanones are used as nucleophile precursors, as well as ethyl 2-oxocyclopentanecarboxylate and tert-butyl 2,5-dioxo-1-phenylpyrrolidine-3-carboxylate. These organocatalysts can be recovered at the end of the reaction by precipitation in ether and reused without any loss of activity.     

Highly enantioselective Michael additions of α-cyanoacetate with chalcones catalyzed by bifunctional cinchona-derived thiourea organocatalyst

The conjugate addition of ethyl α-cyanoacetate with chalcones has been developed. In the presence of cinchona alkaloid-derived thiourea organocatalyst 1i (10 mol %), ethyl α-cyanoacetate could react with various chalcones to afford Michael adducts with high yields (80–92%) and enantioselectivities (83–95% ee).     

Organocatalytic asymmetric addition of aliphatic thiols to nitro olefins and nitrodienes

The N-3,5-bis(trifluoromethyl)phenyl thiourea derivative of readily available chiral 1-benzyl-3-aminopyrrolidine was an effective organocatalyst for the asymmetric sulfa-Michael reaction. The adducts of aliphatic thiols to nitro olefins and nitrodienes were formed in good yields and with up to 87% ee in the presence of 2.5 mol % of the organocatalyst.     

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.     

Readily available (S)-proline-derived organocatalysts for the Lewis acid-mediated Lewis base-catalyzed stereoselective aldol reactions of activated thioesters

A set of enantiomerically pure Lewis bases containing different diphenyl phosphinyl oxide groups were easily synthesized in a straightforward procedure by reaction of readily available proline-based scaffolds and phosphinoyl chlorides. The newly synthesized derivatives were employed (0.1 mol equiv) as organocatalysts in the Lewis acid-mediated Lewis base-promoted direct stereoselective aldol reactions of activated thioesters with aromatic aldehydes, carried out in the presence of tetrachlorosilane and a tertiary amine. β-Hydroxy thioesters were obtained in moderate to high yields, with very high syn diastereoselectivities (dr up to >98:2), and fair enantioselectivities (ee up to 51%). Theoretical studies were performed in order to elucidate the origin of the stereoselection.     

Asymmetric synthesis of propargylic alcohols catalyzed by (−)-MITH

This investigation describes that in the presence of 2.5 mol % of (?)-2-exo-morpholinoisobornane-10-thiol (MITH) 1, catalytic asymmetric alkynylation of aldehydes gives enantioenriched propargylic alcohols with good enantioselectivities.     

Catalytic asymmetric cyano-phosphorylation of aldehydes using a YLi3tris(binaphthoxide) complex (YLB)

A highly enantioselective cyano-phosphorylation of aldehydes catalyzed by a YLi₃tris(binaphthoxide) complex YLB 1 is described. The slow addition of diethyl cyanophosphonate 4 to aldehydes 5 in the presence of YLB 1 (10 mol %), H₂O (30 mol %), tris(2,6-dimethoxyphenyl)phosphine oxide 3a (10 mol %), and BuLi (10 mol %) afforded cyanohydrin O-phosphates 6 in up to 98% yield and 97% ee. Mechanistic studies revealed that the addition of cyanide to aldehydes is irreversible and determines the enantioselectivity. The reaction mechanism is also discussed in detail.     

Planar chiral imidazolium salts based on [2.2]paracyclophane in the asymmetric rhodium-catalyzed 1,2-addition of arylboronic acids to aldehydes

A series of planar chiral imidazolium salts derived from [2.2]paracyclophane have been synthesized and characterized. By using these imidazolium salts as carbene precursors, the Rh-catalyzed 1,2-addition of arylboronic acids to aldehydes proceeded readily with low catalyst loadings (0.03–0.3 mol %) and gave a variety of chiral diarylmethanols in excellent yields and moderate enantioselectivities.     

A new chiral sulfonamide ligand based on tartaric acid: synthesis and application in the enantioselective addition of diethylzinc to aldehydes and ketones

A new sulfonamide ligand based on l-tartaric acid was synthesized and was employed as a chiral ligand in the enantioselective addition of diethylzinc to aldehydes, giving rise to the best enantiomeric excess up to 83% with 5 mol % of catalyst loading. Moreover, the addition of diethylzinc to ketones can also be achieved with good to excellent enantioselectivities by employing 7 mol % of the catalyst under mild conditions.     

Michael reaction of ketones and β-nitrostyrenes catalyzed by camphor-10-sulfonamide-based prolinamide

Novel camphor sulfonamide based organocatalysts were evaluated for their catalytic activity in the Michael reaction of ketones with nitroolefins. Reaction of ketones with β-nitrostyrenes in the presence of 20 mol % organocatalyst 1a and benzoic acid under solvent-free conditions at 0 °C provided the desired Michael adducts with high chemical yields (up to 97%) and excellent stereoselectivities (>99:1).     

A novel C3-symmetric prolinol-squaramide catalyst for the asymmetric reduction of ketones by borane

A novel C₃-symmetric prolinol-squaramide has been developed for the asymmetric reduction of ketones by borane. By using only 5 mol % catalyst 1a for the reaction, high yields and excellent enantioselectivities (up to 95% yield, 93% ee) were obtained. Moreover, 1a can be easily recovered by simple precipitation and re-used for four cycles without losing the selectivity.     

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.     

Asymmetric Michael addition of aldehydes to nitroolefins catalyzed by a pyrrolidine–pyrazole

An effective protocol for the stereoselective Michael addition of aldehydes to nitroolefins using pyrrolidine–pyrazole as an organocatalyst is described. The catalytic cycle was found to be productive in terms of yield and selectivity, when performed under solvent-free reaction conditions and employing 15 mol % of catalyst and 10 mol % of benzoic acid at room temperature.     

Linear polystyrene anchored l-proline,new recyclable organocatalysts for the aldol reaction in the presence of water

Two l-proline-based linear polystyrene anchored catalysts 1a and 1b have been synthesized efficiently. The catalytic activities and stereoselectivity of these readily tunable and amphiphilic organocatalysts were evaluated in the direct asymmetric aldol reaction of various aromatic aldehydes and ketones. By using 5 mol % of the catalysts, the corresponding products of the aldol reaction were obtained in good yields (up to 94%) and with excellent anti diastereoselectivities (up to 96:4) and enantioselectivities (up to 96% ee) in DMF in the presence of water. The yields of these reactions in a ketone/water mixture were lower than those in wet DMF (up to 76%). However, the stereoselectivity was comparable (up to 93:7 anti/syn ratio and 95% ee, respectively). In addition, catalysts 1a and 1b could be recovered by a simple precipitation and filtration process. They could also be re-used for at least five times without obvious loss of catalytic efficiency.     

Discovery of chiral catalysts by asymmetric activation for highly enantioselective diethylzinc addition to imines: using racemic and achiral diimines as effective activators

A library of chiral zinc complexes formed in situ by the combination of achiral and racemic diimines with 3,3′-di(3,5-ditrifluoromethylphenyl)-BINOL and diethylzinc were evaluated in the asymmetric addition of diethylzinc to N-acylimines. In the presence of 10 mol % of chiral ligand 4 and racemic diimine 5, high enantioselectivities of up to 97% ee and yields of up to 96% were achieved for a wide range of aromatic imines in dichloromethane at −30 °C.