Application of a C2-symmetric copper carbenoid in the enantioselective hydrosilylation of dialkyl and aryl-alkyl ketones

We report excellent reactivity and enantioselectivity of a C(2)-symmetric copper-bound N-heterocyclic carbene (NHC) in the hydrosilylation of a variety of structurally diverse ketones. This catalyst exhibits extraordinary enantioselctivity in the reduction of such challenging substrates as 2-butanone and 3-hexanone. Even at low catalyst loading (2.0 mol %), the reactions occur in under an hour at room temperature and often do not require purification beyond catalyst and solvent removal. The scope of this transformation was investigated in the reduction of 10 aryl-alkyl and alkyl-alkyl ketones.     

Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: highly enantioselective synthesis of valuable alcohols

In the presence of PhSiH(3) as the reductant, the combination of enantiomeric dipyridylphosphane ligands and Cu(OAc)(2)·H(2)O, which is an easy-to-handle and inexpensive copper salt, led to a remarkably practical and versatile chiral catalyst system. The stereoselective formation of a selection of synthetically interesting β-, γ- or δ-halo alcohols bearing high degrees of enantiopurity (up to 99.9% enantiomeric excess (ee)) was realized with a substrate-to-ligand molar ratio (S/L) of up to 10,000. The present protocol also allowed the hydrosilylation of a diverse spectrum of alkyl aryl ketones with excellent enantioselectivities (up to 98% ee) and exceedingly high turn-over rates (up to 50,000 S/L molar ratio in 50 min reaction time) in air, under very mild conditions, which offers great opportunities for the preparation of various physiologically active targets. The synthetic utility of the chiral products obtained was highlighted by the efficient conversion of optically enriched β-halo alcohols into the corresponding styrene oxide, β-amino alcohol, and β-azido alcohol, respectively.     

Pd-catalyzed selective hydrosilylation of aryl ketones and aldehydes

Pd salts in combination with triethylsilane as hydride source and DMF as solvent has been found to be excellent catalytic combination that selectively reduces aryl ketones and aldehydes under mild conditions to afford triethylsilyloxy compounds in excellent yields. Product selectivity to the respective benzyl alcohols can however be achieved when the reaction was performed in DMF/H₂O (4:1) as solvent system.     

Development of 4,4'-substituted-XylBINAP ligands for highly enantioselective hydrogenation of ketones

[reaction: see text] A family of 4,4'-substituted-xylBINAPs was synthesized in multistep sequences and characterized by NMR spectroscopy and mass spectrometry. Ru(diphosphine)(diamine)Cl(2) complexes based on these 4,4'-substituted-xylBINAPs and chiral diamines (DPEN and DAIPEN) were synthesized by treatment of [(benzene)RuCl(2)](2) with 4,4'-substituted-xylBINAP followed by chiral diamine, and characterized by (1)H and (31)P NMR spectroscopy and mass spectrometry. These Ru complexes were used for asymmetric hydrogenation of aromatic ketones in a highly enantioselective manner with complete conversion. With 0.1% catalyst loading, complete conversion and enantioselectivity greater than 99% were obtained for most of the aromatic ketones examined. These Ru catalysts thus gave the highest ee for asymmetric hydrogenation of aromatic ketones among all of the catalysts reported in the literature. A single-crystal X-ray diffraction study of Ru[(R)-L(4)()][(R,R)-DPEN]Cl(2) indicated that the 4-methyl group of the naphthyl ring and the methyl groups of the two xylyl moieties form a fence on the opposite side of the DPEN ligand of the Ru center. These three methyl groups will have significant repulsive interactions with the bulky aryl ring of the hydrogen-bonded aromatic ketone in the disfavored transition state. These results support our hypothesis of combining dual modes of enantiocontrol (i.e., the substituents on 4,4'-positions of the binaphthyl framework and the methyl groups on the bis(xylyl)phosphino moieties) to achieve higher stereoselectivity in the hydrogenation of aromatic ketones.     

P/S ligands derived from carbohydrates in Rh-catalyzed hydrosilylation of ketones

Reported is the synthesis of a number of diastereomerically pure cationic Rh(I)-complexes I starting from phosphinite thioglycosides. These complexes were used in the asymmetric hydrosilylation of prochiral ketones. The reactivity and enantioselectivity of the reaction was shown to be dependent on the pyranose ring, the substituent at the sulfur atom, the hydroxylic protective groups and most significantly on the alkene co-ligand.     

Asymmetric hydrosilylation of aryl ketones catalyzed by copper hydride complexed by nonracemic biphenyl bis-phosphine ligands

When complexed by selected ligands in either the BIPHEP or the SEGPHOS series, CuH is an extremely reactive catalyst capable of effecting asymmetric hydrosilylations of aromatic ketones at temperatures between -50 and -78 degrees C. Inexpensive silanes serve as stoichiometric sources of hydride. Substrate-to-ligand ratios exceeding 100000:1 have been documented. The level of induction is usually in the >90% ee category. The nature of the reagent has been investigated using spectroscopic and chemical means, although its composition remains unclear.     

Novel N,N,P-tridentate ligands for the highly enantioselective copper-catalyzed 1,4-addition of dialkylzincs to enones

Use of 0.25 mol % of the N, N, P-tridentate ligand containing the 2-quinolyl moiety ( 1 and 2) and 0.1 mol % of Cu(OTf) 2 enabled the enantioselective 1,4-addition of dialkylzincs to cyclic enones to produce 1,4-adducts in up to 99% ee.     

A new C2-symmetric chiral bisphosphine ligand containing a bioxazole backbone: highly enantioselective hydrosilylation of ketones

C₂-Symmetric (4S,4′S)-2,2′-bis(o-diphenylphosphinophenyl)-4,4′,5,5′-tetrahydro-4,4′-bi(1,3-oxazole) (1, Phos-Biox) has been designed and synthesized as a chiral ligand for metal-catalyzed reactions. The Phos-Biox 1 was found to be an efficient ligand for rhodium(I)-catalyzed asymmetric reduction of prochiral acetophenones with diphenylsilane to give optically active secondary alcohols of up to 97% ee.     

Highly enantioselective hydrosilylation of simple ketones catalyzed by rhodium complexes of P-chiral diphosphine ligands bearing tert-butylmethylphosphino groups

P-Chiral diphosphine ligands, (S,S)-1,2-bis(tert-butylmethylphosphino)ethane [(S,S)-t-Bu-BisP¹], (R,R)-bis(tert-butylmethylphosphino)methane [(R,R)-t-Bu-MiniPHOS], and (R,R)-2,3-bis(tert-butylmethylphosphino)quinoxaline [(R,R)-QuinoxP¹], were applied to the rhodium-catalyzed enantioselective hydrosilylation of simple ketones. The corresponding secondary alcohols were obtained in high yields with good to excellent enantiomeric excesses of up to 99%.     

Palladium-catalyzed oxidative coupling of trialkylamines with aryl iodides leading to alkyl aryl ketones

A new, simple method for selectively synthesizing alkyl aryl ketones has been developed by palladium-catalyzed oxidative coupling of trialkylamines with aryl iodides. In the presence of PdCl(2)(MeCN)(2), TBAB, and ZnO, a variety of aryl iodides underwent an oxidative coupling reaction with tertiary amines and water to afford the corresponding alkyl aryl ketones in moderate to excellent yields. It is noteworthy that this method is the first example of using trialkylamines as the carbonyl sources for constructing alkyl aryl ketone skeletons.     

Investigation of the addition of dialkyl(aryl)phosphine oxides to alkyl(aryl)vinyldialkoxysilanes

Conclusions Alkyl(aryl){2-[dialkyl(aryl)phosphoryl]ethyl}dialkoxysilanes were obtained as a result of addition of dialkyl(aryl)phosphine oxides to alkyl(aryl)vinyldialkoxysilanes.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 183–186, January, 1985.     

The application of chiral,non-racemic N-alkylephedrine and N,N-dialkylnorephedrine as ligands for the enantioselective aryl transfer reaction to aldehydes

The catalytic enantioselective arylation of several aldehydes using arylboronic acids as the source of transferable aryl groups is described; the reaction is found to proceed in excellent yields and high enantioselectivities (up to 96% ee) in the presence of a chiral amino alcohol derived from ephedrines and congeners.     

Chiral P,N‐ligands for the highly enantioselective addition of diethylzinc to aromatic aldehydes

A new sterically hindered chiral P,N‐ligand was synthesized and successfully applied to copper catalyzed asymmetric addition of diethylzinc to aromatic aldehydes. Various aromatic aldehydes can react smoothly to give the corresponding addition products with good to excellent enantioselectivities, which provides a readily accessible method for the preparation of chiral secondary alcohols.     

Cu(II)-catalyzed asymmetric hydrosilylation of diaryl- and aryl heteroaryl ketones: application in the enantioselective synthesis of orphenadrine and neobenodine

With certain amounts of sodium tert-butoxide and tert-butanol as additives, catalytic amounts of an inexpensive and easy-to-handle copper source Cu(OAc)(2)?H(2)O, a commercially available and air-stable non-racemic dipyridylphosphine ligand, as well as the stoichiometric desirable hydride donor polymethylhydrosiloxane (PMHS), formed a versatile in situ catalyst system for the enantioselective reduction of a broad spectrum of prochiral diaryl and aryl heteroarylketones in air, in high yields and with good to excellent enantioselectivities (up to 96?%). In particular, the practical viability of this process was evinced by its successful applications in the asymmetric synthesis of optically enriched potent antihistaminic drugs orphenadrine and neobenodine.     

Synthesis of functionalized dialkyl ketones from carboxylic acid derivatives and alkyl halides

Unsymmetrical dialkyl ketones can be directly prepared by the nickel-catalyzed reductive coupling of carboxylic acid chlorides or (2-pyridyl)thioesters with alkyl iodides or benzylic chlorides. A wide variety of functional groups are tolerated by this process, including common nitrogen protecting groups and C-B bonds. Even hindered ketones flanked by tertiary and secondary centers can be formed. The mechanism is proposed to involve the reaction of a (L)Ni(alkyl)(2) intermediate with the carboxylic acid derivative.     

Application of chiral mixed phosphorus/sulfur ligands to enantioselective rhodium-catalyzed dehydroamino acid hydrogenation and ketone hydrosilylation processes

Chiral mixed phosphorus/sulfur ligands 1-3 have been shown to be effective in enantioselective Rh-catalyzed dehydroamino acid hydrogenation and ketone hydrosilylation reactions (eqs 1, 2). After assaying the influence of the substituents at sulfur, the substituents on the ligand backbone, the relative stereochemistry within the ligand backbone, and the substituents at phosphorus, ligands 2c (R = 3,5-dimethylphenyl) and 3 were found to be optimal in the Rh-catalyzed hydrogenation of a variety of alpha-acylaminoacrylates in high enantioselectivity (89-97% ee). A similar optimization of the catalyst for the Rh-catalyzed hydrosilylation of ketones showed that ligand 3 afforded the highest enantioselectivities for a wide variety of aryl alkyl and dialkyl ketones (up to 99% ee). A model for asymmetric induction in the hydrogenation reaction is discussed in the context of existing models, based on the absolute stereochemistry of the products and the X-ray crystal structures of catalyst precursors and intermediates.