Conformational lock in a Brønsted acid–Lewis base organocatalyst for the aza-Morita–Baylis–Hillman reaction

(S)-3-(N-Isopropyl-N-3-pyridinylaminomethyl)BINOL has been established as an efficient asymmetric bifunctional organocatalyst for the aza-MBH reaction. The acid–base functionalities cooperate in substrate activation and fixing of the organocatalyst conformation to promote the reaction with high enantiocontrol.     

Copper‐Complex‐Catalyzed Asymmetric Aerobic Oxidative Cross‐Coupling of 2‐Naphthols: Enantioselective Synthesis of 3,3′‐Substituted C1‐Symmetric BINOLs

A novel chiral 1,5‐N,N‐bidentate ligand based on a spirocyclic pyrrolidine oxazoline backbone was designed and prepared, and it coordinates CuBr in situ to form an unprecedented catalyst that enables efficient oxidative cross‐coupling of 2‐naphthols. Air serves as an external oxidant and generates a series of C₁‐symmetric chiral BINOL derivatives with high enantioselectivity (up to 99 % ee) and good yield (up to 87 %). This approach is tolerant of a broader substrates scope, particularly substrates bearing various 3‐ and 3′‐substituents. A preliminary investigation using one of the obtained C₁‐symmetric BINOL products was used as an organocatalyst, exhibiting better enantioselectivity than the previously reported organocatalyst, for the asymmetric α‐alkylation of amino esters.     

An efficient,recoverable fluorous organocatalyst for accelerating the DABCO-promoted Morita-Baylis-Hillman reaction

A convenient method for Morita-Baylis-Hillman reaction of arylaldehydes with methyl acrylate has been developed by using fluorous-tag organocatalyst 1-[4-(perfluorooctyl)phenyl]-3-phenylthiourea and DABCO at room temperature.The fiuorous, organocatalyst could be recovered from the reaction mixture by fiuorous solid-phase extraction(F-SPE) with excellent purity for direct reuse.     

The Brønsted Acid Catalyzed,Enantioselective Vinylogous Mannich Reaction

The first catalytic, enantioselective vinylogous Mannich reaction of acyclic silyl dienolates is reported. A second‐generation 2,2′‐dihydroxy‐1,1′‐binaphthyl (BINOL)‐based phosphoric acid has been developed and further optimized as an enantioselective organocatalyst. Upon protonation of the imines, chiral contact ion pairs are generated in situ and attacked highly diastereoselectively by the nucleophile. γ‐Substituted silyl dienolates that lead to more highly substituted Mannich products with a second stereogenic center in good diastereoselectivity have been employed in these reactions. The reaction path has been elucidated with NMR spectroscopy and mass spectrometry, which suggest that the protic reaction medium found to be optimal in these reactions serves to trap the cationic silicon species as silanol. A crystal structure of a phosphoric acid bound imine was obtained that provides insight into the binding mode and a rationale for the stereochemical course of the reaction.     

An efficient, recoverable fluorous organocatalyst for direct reductive amination of aldehydes

A commercially available perfluorooctyl aniline and phenyl isothiocyanate were reacted under mild conditions to give 1-[4-(perfluorooctyl)phenyl]-3-phenylthiourea as an analogue of thiourea-based organocatalyst. This fluorous organocatalyst was successfully employed to direct reductive amination of aldehydes. It could be readily separated from reaction product by fluorous solid phase extraction for direct use.     

Efficiency in isotetronic acid synthesis via a diamine-acid couple catalyzed ethyl pyruvate homoaldol reaction

[reaction: see text] L-proline failed to act as an organocatalyst in the homoaldol reaction of ethyl pyruvate; however, it reacted with the ester to give an azomethine ylide that in turn underwent 1,3-dipolar cycloaddition with a second molecule of pyruvate. Direct catalytic homoaldol reaction of ethyl pyruvate was performed using an (S)-(+)-1-(2-pyrrodinylmethyl)pyrrolidine/trifluoroacetic acid combination as organocatalyst. The use of polymer-supported reagents allowed for the lactonization of the aldol and isolation of the isotetronic acid derivative in hydroxy-free form.     

Simple and Efficient One-Step Synthesis of a Highly Enantioselective Catalyst 3,3′-Di(pyrrolidinylmethyl)-H8BINOL

A concise one-step synthetic method was developed to prepare (S)-3,3′-di(pyrrolidinylmethyl)-H₈BINOL via Mannich-type reaction. Under the optimal reaction conditions, the yield reached 83% (by recrystallization) and 93% (by column chromatography). This new procedure has reduced the molar ratio of pyrrolidine/paraformaldehyde/(S)-H₈BINOL from 58:58:1 to 3:3:1, which simplified the previously reported two-step reaction to a one-step reaction with no need for laborious operations such as cooling and solvent degassing, and avoided discharging a large amount of dioxane-containing waste water.     

(��)-1,1��-Binaphthalene-2,2��-diol-derived phosphoric diester: immobilization on polyethylene glycol support and application in the Pudovik reaction

(±)-1,1??-Binaphthalene-2,2??-diol (BINOL) was immobilized on polyethylene glycol (PEG) by means of triazole linkers, which were constructed by the [3+2] cycloaddition between azide and ethynyl fragments, preliminary incorporated into the molecules of these reactants. Treatment of these BINOL derivatives with phosphorus oxychloride leads to the corresponding PEG-immobilized 1,1??-binaphthalene-2,2??-diylphosphoric acids. The latter efficiently catalyze the Pudovik reaction and can be reused without loss of catalytic activity.     

Catalytic Strecker reaction: g-C3N4-anchored sulfonic acid organocatalyst for the synthesis of α-aminonitriles

Research on Chemical Intermediates - Efficient organocatalyst for enantioselective Strecker reaction was synthesized using g-C3N4 sheets (CN). CN-anchored sulfonic acid (CN-Bu-SO3H) was found to be...     

A novel hydrazide type organocatalyst for enantioselective Diels-Alder reactions

The development of a new class of hydrazide type organocatalyst, (4R,5R)-1,3-bis(isopropylamino)-4,5-dihenylimidazolidin-2-one 2a, for enantioselective Diels-Alder reactions between cyclopentadiene and α,β-unsaturated aldehydes are presented. The new organocatalyst 2a promoted the reaction, affording Diels-Alder adducts in good yields with good levels of enantioselectivity.     

Greener and practical synthesis of 4,4′-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol)s through a conventional heating and a mechanochemical procedure

A new catalytic application of 4,4′-trimethylenedipiperidine for the efficient synthesis of 4,4′-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol)s is developed. According to the principles of green chemistry, the reaction was performed by conventional and non-conventional processes: (a) in the refluxing ethanol using a catalytic amount of organocatalyst; (b) at room temperature in the presence of organocatalyst in a planetary ball mill under solvent-free conditions. The organocatalyst could be reused up to 10 runs, and a negligible reduction of catalytic activity was detected. A variety of substituted 4,4′-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol)s were obtained in good–to-excellent yields under eco-friendly conditions. 4,4′-Trimethylenedipiperidine is commercially available and easy to handle and storage, less toxic, non-flammable, as well as it shows high thermal stability and good solubility in water. The current methodology has merits including (a) wide substrate-scope and high yields of the desired products in the short reaction times, (b) avoiding the use of hazardous solvents and acidic and metal-containing catalysts, (c) minimize the generation of hazardous waste, and (d) simple workup process. Based on great potential as a promising organocatalyst, we hope it can be used as a greener alternative to piperidine for other organic transformations.     

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.     

α-羰基二硫缩烯酮的吲哚化反应

研究了BINOL酸催化α-羰基二硫缩烯酮的吲哚化反应,合成了12个β-吲哚基-β-乙硫基缩烯酮类化合物(3a~3l),其中3a,3d~3e,3g~3k为新化合物,其结构经~1H NMR,~(13)C NMR,IR和HR-MS表征。对反应条件进行了优化。结果表明:20 mol%BINOL酸为催化剂,3,3-二乙硫基苯丙烯酮与吲哚于85℃反应2.5 h,3-吲哚基-3-乙硫基苯丙烯酮收率85%。     

Immobilization of BINOL by cross-linking copolymerization of styryl derivatives with styrene, and applications in enantioselective Ti and Al Lewis acid mediated additions of Et2Zn and Me3SiCN to aldehydes and of diphenyl nitrone to enol ethers

The chiral ligand 1,1'-bi-2-naphthol (BINOL) has been succesfully immobilized on polystyrene. Several dendritic and non-dendritic BINOL derivatives (3, and 13-17), bearing at least two polymerizable styryl groups, were prepared and fully characterized. Suspension copolymerization of the MOM- or TIPS-protected cross-linking BINOL ligands (MOM = methyloxymethyl, TIPS = triisopropylsilyl) with styrene, cleavage of the protecting-groups, and loading with a Lewis-acid afforded catalytically active polystyrene-supported BINOLates. The polymer-bound BINOLs p-3, and p-13-p-16 were tested in the Ti-BINOLate-mediated addition of Et2Zn to PhCHO. The enantioselectivities (up to 93%) and conversions obtained with the polymer-bound catalysts were in most cases identical (within experimental error) to those obtained with the unsubstituted 1,1'-bi-2-naphthol and with the non-polymerized BINOL cross-linkers under homogeneous conditions. Special focus was put on the reusability of the supported catalyst: the polymer-beads were used in up to 20 consecutive catalytic runs, with the best polymers showing no or only minor loss of selectivity. BINOL-polymers p-17, obtained by copolymerization of a 3,3'-distyryl-substituted BINOL 17a with styrene, were used in the BINOL. AlMe-mediated cycloaddition of diphenyl nitrone with alkyl vinyl ethers. In all cases the exo/endo selectivity (> or =92:8) and the enantioselectivities with which the exo-cycloadducts were formed (> or =95%) correspond to those observed in the homogeneous reactions. A dendritically cross-linked BINOL-polymer was also employed in the Ti-BINOLate-mediated cyanosilylation of pivalaldehyde. The enantiopurity of the cyanohydrine obtained in the first run was as high as in the homogeneous reaction (72%); surprisingly the catalytic performance of the supported catalyst increased steadily during the first catalytic cycles to reach 83%. Thus, cross-linking BINOLs can be succesfully incorporated into a polystyrene matrix (without racemization!) to give polymer-bound BINOL ligands that give excellent performance over many catalytic cycles with catalytic activities comparable with those of soluble analogues.     

Development of axially chiral bis(arylthiourea)-based organocatalysts and their application in the enantioselective Henry reaction

Axially chiral bis(arylthiourea)-based organocatalyst 6b, prepared from (R)-(+)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2,2′-diamine, was found to be an effective chiral organocatalyst for the enantioselective Henry reaction of arylaldehydes with nitromethane to give the corresponding adducts in moderate enantioselectivities and good yields.     

Asymmetric [2 + 1] Cycloaddition Reactions of 1-Seleno-2-silylethene

The reaction of (E)-1-(phenylseleno)-2-(trimethylsilyl)ethene (1) and vinyl ketones 2a-d in the presence of a chiral Lewis acid prepared from TiCl(4), Ti(O(i)Pr)(4), (R)- or (S)-1,1'-binaphthol (BINOL), and MS4A gave enantiomerically enriched cis cyclopropane products 3a-d. The enantiomeric excess and chemical yield varied depending on the ratio of TiCl(4) and Ti(O(i)Pr)(4) to 1. Reproducible results (43-47% ee/33-41% yields) for cis-1-acetyl-2-[(phenylseleno)(trimethylsilyl)methyl]cyclopropane (3a) were obtained using 1.1 equiv of TiCl(4), 0.54-0.65 equiv of Ti(O(i)Pr)(4), and 1.65 equiv of BINOL. The observed enantioselectivity was explained by consideration of the structure of the postulated intermediates, alkoxy titanium-carbonyl complexes, via ab initio MO calculations.     

On-step synthesis of a bifunctional BINOL ligand for the highly enantioselective cyanation of aliphatic aldehydes

[reaction: see text] An efficient one-step synthesis of the optically active bifunctional BINOL ligand (S)-3 has been developed. It was found that (S)-3 in combination with Me2AlCl is a highly enantioselective catalyst for the addition of TMSCN to aliphatic aldehydes of diverse structures and is also among the most practical ones. A remarkable positive nonlinear effect was found for this chiral ligand.     

Diarylprolinol silyl ether as catalyst of an exo-selective, enantioselective Diels-Alder reaction

In combined use with CF3CO2H, 2-[bis(3,5-bis-trifluoromethylphenyl) triethylsiloxymethyl]pyrrolidine was found to be an effective organocatalyst of an exo-selective, enantioselective Diels-Alder reaction of alpha,beta-unsaturated aldehydes.     

Asymmetric alkyne addition to aldehydes catalyzed by Schiff bases made from 1,1′-bi-2-naphthol and chiral benzylic amines

Several 1,1′-bi-2-naphthol (BINOL)-based Schiff bases were prepared from the condensation of (R)-3,3′-diformyl BINOL with chiral benzylic amine derivatives. These compounds were used to catalyze the reaction of phenylacetylene with aldehydes in the presence of ZnEt₂ with up to 85% ee and 83% yield.     

Facile synthesis of chiral 2-amino-4-(indol-3-yl)-4H-chromene derivatives using thiourea as the catalyst

The enantioselective Friedel–Crafts alkylation of indoles with iminochromenes catalyzed by a bifunctional thiourea organocatalyst was investigated. This reaction afforded chiral functionalized 2-amino-4-(indol-3-yl)-4H-chromenes in good yields (up to 87% yield) and with moderate to good enantioselectivities (up to 86% ee).