Asymmetric Hydride Transfer Research Articles

Asymmetric Total Synthesis of (-)-Aspidophylline A.

An asymmetric total synthesis of (-)-aspidophylline A has been accomplished. The key transformations include an asymmetric hydride transfer hydrogenation of an α,β-acetylenic ketone and a cationic gold(I)-catalyzed 6-exo-dig cyclization involving an alkynylindole/aminal formation cascade, which enables stereoselective establishment of the requisite quaternary carbon center.

ChemInform Abstract: Enantioselective Metal‐Free Hydrogenation Catalyzed by Chiral Frustrated Lewis Pairs

AbstractReview: 12 refs.

Enantioselective Metal‐Free Hydrogenation Catalyzed by Chiral Frustrated Lewis Pairs

Bulky Lewis acids and Lewis bases do not undergo neutralization to form classical Lewis acid–base adducts because of steric hindrance. The Lewis acids and Lewis bases involved in this phenomenon are termed “frustrated Lewis pairs” (FLPs). The synergy between the unquenched acid and base endows the Lewis pair with the ability to activate small molecules, in particular hydrogen. A milestone discovery in this field was reported by Stephan and co-workers in 2006, in which a phosphine–borane compound was reported to reversibly activate hydrogen under mild conditions. Since then, FLP chemistry has developed into a cutting-edge concept. Most of the reported FLPs, generally based on the strong Lewis acid B(C6F5)3 accompanied by a bulky amine or phosphine, may serve as hydrogenation catalysts. Recently, metal-free hydrogenation using FLP catalysts has been regarded as a promising application of FLP chemistry. FLP catalytic systems are able to hydrogenate a wide range of unsaturated substrates, such as imines, enamines, enol ethers, and heterocycles. Enantioselective hydrogenation, which is still dominated by transition-metal catalysts, plays a pivotal role in organic synthesis. Considering the increasingly stringent limits on the amount of metal impurities found in drug compounds, the development of an effective metal-free catalyst for enantioselective hydrogenation to synthesize chiral molecules is a longterm challenge. FLP-type enantioselective hydrogenation is a rational extension of this hydrogenation chemistry owing to its significant potential for the transition-metal-free synthesis of chiral molecules. However, FLP-type catalytic enantioselective hydrogenation has remained relatively unexplored. This strategy is hampered by the design and synthesis of an effective chiral borane reagent because this class of air-sensitive compound cannot be purified by the usual chromatography techniques. Another issue confronting researchers is that the stereoselectivity of borane connected to the chiral scaffold through a single s bond is difficult to control because two perfluorophenyl groups are necessary to keep enough Lewis acidity for H2 activation. To realize FLP-type catalytic enantioselective hydrogenation, four kinds of chiral FLP catalysts can be considered (Scheme 1), mode I: chiral B moiety, achiral N(P) moiety; mode II : achiral B moiety, chiral N(P) moiety; mode III : intramolecular chiral FLP; mode IV: chiral B moiety, chiral N(P) moiety. Great progress has been made in the rational design of chiral FLP catalysts based on modes I–III in recent years, but mode IV remains to be explored (Figure 1). In mode I, the chiral B H species resulting from H2 activation is expected to undergo an asymmetric hydride transfer to proScheme 1. Enantioselective metal-free hydrogenation by means of an FLP strategy.

AlIII–Calix[4]arene Catalysts for Asymmetric Meerwein–Ponndorf–Verley Reduction

Chiral AlIII-calixarene complexes were investigated as catalysts for the asymmetric Meerwein–Ponndorf–Verley (MPV) reduction reaction when using chiral and achiral secondary alcohols as reductants. The most enantioselective catalyst consisted of a new axially chiral vaulted-hemispherical calix[4]arene phosphite ligand, which attained an enantioselective excess of 99%. This ligand consists of two lower-rim hydroxyl groups, with the remaining two lower-rim oxygens directly connected to the phosphorus of the phosphite, which is derived from a chiral diol. The results emphasize the importance of the rigid calix[4]arene lower-rim substituents and point to a possible role of a lower-rim chiral pocket and Lewis-basic phosphorus lone pairs in enhancing asymmetric hydride transfer.

Hydrophilic pyrazine-based phosphane ligands: synthesis and application in asymmetric hydride transfer and H2-hydrogenation of acetophenone

Pyrazine-based hydrophilic phosphanes are useful ligands for the ruthenium- and rhodium-catalyzed hydrogenations of acetophenone under hydride transfer and dihydrogen conditions. The effect of alcohol additives on the catalytic, enantioselective aqueous hydrogenation of acetophenone is examined with the newly developed (R,R)-DAMPYPHOS as the ligand and Rh2(norbornadiene)2Cl2 as the catalyst precursor, giving rise to higher conversions (up to quantitative) and improved enantiomeric excesses (up to 95%) of the formed 1-phenylethanol.

Highly Enantioselective Synthesis of Tetrahydroquinolines via Cobalt(II)-Catalyzed Tandem 1,5-Hydride Transfer/Cyclization

A chiral catalyst prepared from N,N'-dioxide and Co(BF(4))(2)·6H(2)O was applied in the asymmetric hydride transfer initiated cyclization reaction, giving optically active tetrahydroquinolines in good yields with high enantioselectivities under mild reaction conditions. Meanwhile, in light of the absolute configuration of the product, a possible working model was proposed to explain the origin of the activation and asymmetric induction.

ChemInform Abstract: Evaluation of Ligands for Ketone Reduction by Asymmetric Hydride Transfer in Water by Multi‐Substrate Screening.

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Evaluation of Ligands for Ketone Reduction by Asymmetric Hydride Transfer in Water by Multi‐Substrate Screening

AbstractVarious ligands for the ruthenium‐catalyzed enantioselective reduction of ketones in water have been investigated. Multi‐substrate reactions have been carried out for the comparison of various proline amides and aminoalcohol ligands. Two sets of six aromatic ketones have been selected in order to evaluate the enantiomeric excesses of all the resulting alcohols by a single chromatographic analysis. The proline amide derivative prepared from (1R,2S)‐cis‐aminoindanol revealed as the best ligand for most of the ketones used in the multi‐substrate reductions. This ligand has been employed for the enantioselective reduction of a variety of other aromatic ketones and in all cases the enantiomeric excesses were improved compared to those obtained with phenylprolineamide used in our previous work.

Polishing a Diamond in the Rough: “Cu—H” Catalysis with Silanes

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Polishing a Diamond in the Rough: “CuH” Catalysis with Silanes

The value of a novel chemical transformation is often underappreciated at the time of its discovery. The reasons are doubtlessly manifold, but the "chemical zeitgeist" subtly determines how the new reaction will be received by the chemical community. The enantioselective reduction of carbonyls by copper-catalyzed hydrosilylation was certainly outshone by other asymmetric hydrogenation techniques. A seminal report at an early stage indicated the considerable potential of this catalytic process, yet it was disregarded for more than a decade. A refined mechanistic picture in connection with a plethora of new chiral ligands then led to copper-catalyzed 1,2- as well as 1,4-reductions of carbonyl compounds with excellent levels of enantioselection at high substrate-to-catalyst ratios and even more remarkable substrate-to-ligand ratios. The tide is turning for inexpensive copper catalysts in asymmetric hydride transfer reactions!

Cycloruthenated Compounds as Efficient Catalyst for Asymmetric Hydride Transfer Reaction

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Cycloruthenated compounds as efficient catalyst for asymmetric hydride transfer reaction

Abstract Cycloruthenated complexes obtained by direct C-H activation of enantiopure aromatic primary and secondary amines are efficient catalysts in asymmetric hydride transfer reaction. Reduction of acetophenone has been achieved rapidly with enantiomeric excesses (ee's) ranging from 38 to 89 %. The importance of Ru-C bond in the catalytic efficiency is highlighted.

Asymmetric Transfer Hydrogenation of Aromatic Ketones by Rh(I)/Bimorpholine Complexes.

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Asymmetric transfer hydrogenation of aromatic ketones by Rh(I)/bimorpholine complexes

The asymmetric hydride transfer reduction of aromatic ketones, using a [Rh(cod)Cl] 2 complex as a catalyst and (3 S,3′ S)-bimorpholine as a chiral ligand, was studied. By varying the amount of ligand, basic co-catalyst and temperature, high yields (>90%) and good enantiomeric excesses of the alcohols (ee up to 83%) were achieved.

Chiral hybrid silica: sol–gel heterogenisation of trans-(1 R,2 R)-diaminocyclohexane ligands for the rhodium catalysed enantioselective reduction of acetophenone

The synthesis of derivatives of trans-(1 R,2 R)-diaminocyclohexane with different substituents on the nitrogen atoms has been achieved. Rhodium complexes of these chiral ligands were evaluated as homogeneous catalysts for the asymmetric hydride transfer reduction (HTR) of acetophenone leading to moderate selectivities (ee=0–57%). The silylation of a bromo-aryl derivative was successfully performed by a Heck’s coupling reaction with vinyltriethoxysilane in the presence of a palladium catalyst. The immobilisation of this catalyst was then achieved by the sol–gel hydrolysis condensation. The resulting hybrid catalytic materials showed moderate selectivity, although much higher than the related homogeneous catalytic species.

Heterogeneous asymmetric catalysis

Abstract Examples of enantioselective catalysts, including homogeneous supported catalysts and biphasic liquid/liquid, are described and compared. In the case of asymmetric hydride transfer, polythiourea was proven to be more efficient for ruthenium-catalyzed reduction of arylketones, although the iridium complexes gave rise to higher ee when using amino sulfonamide bound to a polystyrene matrix. In the case of asymmetric reduction, the modification of the binap allows the formation of a polymer that could be used as a catalyst precursor and exhibits enantioselectivities as high as observed in solution, but easier to separate and recycle. Bisoxazoline bound to silica particules could also be used in copper-catalyzed asymmetric Diels-Alder reaction and cyclopropanation with selectivities similar to that obtained in solution.

Design of Molecular‐Imprinting Metal‐Complex Catalysts

AbstractFor Abstract see ChemInform Abstract in Full Text.

C2-Symmetric bimorpholines as chiral ligands in the asymmetric hydrogenation of ketones

2,2′-Bimorpholine and 3,3′-bimorpholine were used as chiral ligands in Rh-mediated asymmetric hydride transfer reduction of prochiral aromatic ketones affording corresponding alcohols with good ee (up to 75%).

Design of molecular-imprinting metal-complex catalysts

This article attempted to review novel metal-complex catalysts prepared by molecular-imprinting methods, presenting our work on recent catalyst design at surfaces. Molecular imprinting is a way to produce cavity with a particular molecule (template) by polymerization of organic and inorganic materials and removal of the template. The cavity with memory of the template provides shape-selective reaction space for the molecule which has similar shape to the template. Recently, the application to metal-complex catalysts has been achieved to exploit unique property different from homogeneous and simple supported metal-complex catalysts. Imprinting metal-complex catalysts prepared by using reaction intermediate or transition state analogues as templates for asymmetric hydride transfer reduction of ketones, aldol condensation, and shape-selective hydrogenation of simple alkenes without any functional groups are focused in the viewpoint of new approaches in design of shape-selective metal-complex catalysts.

Use of amino amides derived from proline as chiral ligands in the ruthenium(II)-catalyzed transfer hydrogenation reaction of ketones

We developed an efficient, easily available, and easy to use proline amide-based ruthenium(II) catalysts for the asymmetric hydride transfer reduction of prochiral ketones and e.e.s up to 98.8% have been measured.