Cinchona alkaloid-derived quaternary ammonium salt combined with NaH: a facile catalyst system for the asymmetric trifluoromethylation of ketones

Enantioselective trifluoromethylation of aromatic ketones promoted by the cinchona alkaloid-derived ammonium bromide and sodium hydride was described. A series of trifluoromethyl-substituted aryl alcohols could be obtained in up to 82% ee with 98% yield under mild conditions. A possible catalytic cycle was also presented.     

Cinchona alkaloids/TMAF combination-catalyzed nucleophilic enantioselective trifluoromethylation of aryl ketones

The catalytic, nucleophilic enantioselective trifluoromethylation reaction of both acyclic and cyclic aryl ketones using the Ruppert-Prakash reagent is now at hand, with an operationally simple procedure, based on the combination of ammonium bromide of cinchona alkaloids with TMAF. The procedure is reliable and general. Trifluoromethyl-substituted tetrasubstituted aryl alcohols have been synthesized in up to 94% ee.     

Aluminum-catalyzed asymmetric alkylations of pyridyl-substituted alkynyl ketones with dialkylzinc reagents

Alkylations of pyridyl-substituted ynones with Et2Zn and Me2Zn, promoted by amino acid-based chiral ligands in the presence of Al-based alkoxides, afford tertiary propargyl alcohols efficiently in 57% to >98% ee. Two easily accessible chiral ligands are identified as optimal for reactions of the two dialkylzinc reagents. Catalytic alkylations with Et2Zn require a chiral ligand carrying two amino acid moieties (valine and phenylalanine) along with a p-trifluoromethylphenylamide C-terminus. In contrast, reactions with Me2Zn are most effectively promoted in the presence of a chiral ligand containing a single amino acid (benzyl cysteine), capped by an n-butylamide. Enantiomerically enriched tertiary alcohols bearing a pyridyl and an alkyne substituent can be functionalized in a variety of manners to furnish a wide range of difficult-to-access acyclic and heterocyclic structures; two noteworthy examples are Cu-catalyzed protocols for conversion of tertiary propargyl alcohols to enantiomerically enriched tetrasubstituted allenes and bicyclic amides that bear an N-substituted quaternary carbon stereogenic center. Mechanistic models that account for the trends and enantioselectivity levels are provided.     

Nucleophilic trifluoromethylation of carbonyl compounds and disulfides with trifluoromethane and silicon-containing bases

Provided that DMF (or another N,N-dialkylformamide) is present in the reaction medium, at least in a catalytic amount, fluoroform trifluoromethylates efficiently carbonyl compounds, even enolizable ones, when opposed to (TMS)(2)N(-) M(+), generated in situ from N(TMS)(3) and M(+) F(-) or RO(-) Na(+). When F(-) is used in a catalytic amount, silylated alpha-(trifluoromethyl)carbinols are obtained: in this case, the four-component system HCF(3)/N(TMS)(3)/catalytic F(-)/catalytic DMF behaves like the Ruppert's reagent, especially as far as nonenolizable carbonyl compounds are concerned (CF(3)SiMe(3) remains more efficient for enolizable carbonyl compounds). This process involves an adduct between DMF and (-)CF(3) which is the true trifluoromethylating agent. In the same way, fluoroform efficiently trifluoromethylates disulfides and diselenides when deprotonated with a strong base selected from t-BuOK or N(SiMe(3))(3)/Me(4)NF (or TBAT). t-BuOK is more adapted to the trifluoromethylation of aryl disulfides whereas N(SiMe(3))(3)/F(-) is well suited to that of aliphatic disulfides.     

Tributylphosphine-catalyzed reaction of ethanethiol with alkynyl ketones

A stereoselective and effective method for the synthesis of vinyl thioethers has been developed.This method is based on the Michael addition of ethanethiol to various alkynyl ketones using 10 mol%of tributylphosphine as catalyst.Most of alkynyl ketones react with ethanethiol in this system to yield mainly Z-isomer of vinyl thioether adducts,only in one case mainly E-isomer of vinyl thioether adducts was observed.     

Computational studies of cinchona alkaloid-catalyzed asymmetric Michael additions

Cinchona alkaloids exhibit remarkable catalytic activities in a wide range of organic transformations. This review summarizes the recent advances of computational studies in understanding the mechanism and origins of enantioselectivities in cinchona alkaloid-catalyzed asymmetric Michael additions. Key activation model and controlling factors of reactivity and selectivity are elucidated.     

N-alkylation of trimethylsilyl derivatives of isatin with halomethyl ketones

Trimethylsilyl derivative of isatin react with halomethyl ketones at the nitrogen atom in contrast to sodium salt of isatin, which reacts with these compounds at heterocyclic carbon atom. Institute for the Biological Protection of Vegetation, Academy of Sciences of Moldova, 2058, Moldova. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1345–1346, October, 1999.     

Triphenylphosphine-catalyzed isomerization of alkynyl ketones in aqueous solution

An efficient isomerization of alkynyl ketones to(E,E)-diene ketones was developed.The reaction catalyzed by 20 mol% triphenylphosphine in aqueous media gave the desired products in good yields.     

Room temperature asymmetric allylic trifluoromethylation of Morita-Baylis-Hillman carbonates

(DHQD)(2)PHAL-catalyzed asymmetric allylic trifluoromethylation of Morita-Baylis-Hillman adducts using a Rupert-Prakash reagent is reported. This transformation provided the S(N)2' trifluoromethylated products with good yields and excellent enantioselectivities at room temperature. It was also found that the reaction could be accelerated using acetonitrile as cosolvent.     

Rhodium-catalyzed novel trifluoromethylation at the alpha-position of alpha,beta-unsaturated ketones

Treatment of alpha,beta-unsaturated ketones with CF(3)I in the presence of Et(2)Zn and RhCl(PPh(3))(3) gave novel alpha-trifluoromethylation products in good yields. Hydrogen transfer from the ethyl group on the rhodium complex to the beta-position of the enone seems to play an important role in this reaction.     

Catalytic asymmetric vinylation of ketones

This communication describes the catalytic asymmetric 1,2-addition of vinylzinc reagents to aromatic, alpha,beta-unsaturated, and dialkyl ketones with enantioselectivities between 79 and 97% and with yields ranging from 84 to 98%. The products of these reactions are tertiary allylic alcohols with chiral quaternary centers that are useful in organic synthesis. The reaction involves hydrozirconation of a terminal alkyne, transmetalation to zinc, and addition to a ketone in the presence of a chiral titanium-based Lewis acid catalyst. The reactions proceed smoothly at room temperature in under 24 h.     

Rhodium(II) mediated cyclizations of diazo alkynyl ketones

The rhodium(II)-catalyzed reaction of -diazo ketones bearing tethered alkyne units represents a new and useful method for the construction of a variety of substituted cyclopentenones. The process proceeds by addition of the rhodium-stabilized carbenoid onto the acetylenic π-bond to give a vinyl carbenoid intermediate. The resulting rhodium complex undergoes a wide assortment of reactions including cyclopropanation, 1,2-hydrogen migration, CH-insertion, addition to tethered alkynes and ylide formation. The exact pathway followed is dependent on the specific metal/ligand employed and is also influenced by the nature of the solvent. Sulfonium ylide formation occurred both intra and intermolecularly when the reaction was carried out in the presence of a sulfide. In the case where an ether oxygen was present on the backbone of the vinyl carbenoid, cyclization afforded an oxonium ylide which underwent a [1,2] or [2,3]-sigmatropic shift to give a rearranged product. These cyclic metallocarbenoids were also found to interact with a neighboring carbonyl π-bond to produce carbonyl ylide dipoles that could be trapped with added dipolarophiles. The domino transformation was also performed intramolecularly by attaching an alkene directly to the carbonyl group. When 2-alkynyl-2-diazo-3-oxobutanoates were treated with a Rh(II)-catalyst, furo[3,4-c]furans were formed in excellent yield. The 1,5-electrocyclization process involved in furan formation has also been utilized to produce indeno[1,2-c]furans. Rotamer population was found to play a significant role in the cyclization of -diazo amide systems containing tethered alkynes. In this account, an overview of our work in this area is presented.     

Recent developments in asymmetric reduction of ketones with biocatalysts

Herein we review recent advances in the asymmetric reduction of ketones by biocatalysts. Included are discussions on recent developments in methodologies to control enantioselectivities of catalytic reactions, and examples of practical applications that reduce various types of ketones are also shown.     

Catalytic asymmetric cyanosilylation of ketones with chiral Lewis base

The development of broadly applicable and practical catalytic approaches for the enantioselective creation of quaternary stereocenters remains a highly desirable yet challenging goal. In this Communication, we describe a highly enantioselective cyanosilylation of acetal ketones (alpha,alpha-dialkoxy ketones) catalyzed by modified cinchona alkaloids. This reaction is the first highly enantioselective cyanosilylation of ketones catalyzed by an organic chiral Lewis base and is found to be highly efficient with acetal ketones bearing a broad range of alkyl, aryl, alkenyl, and alkynyl substituents. This new catalytic asymmetric reaction, coupled with the versatility of the acetal functionality, provides a broadly useful synthetic method for chiral building blocks bearing quaternary stereocenters. Acetal ketones, readily accessible but previously unexplored in asymmetric synthesis, demonstrate unusual reactivity and selectivity toward the nucleophilic cyanosilylation, thereby suggesting that they may be interesting substrates for other catalytic enantioselective reactions.     

Cinchona alkaloid derived ligands in catalytic asymmetric transfer hydrogenation

A collection of chiral quinuclidine ligands, derived from the Cinchona alkaloids quinine and quinidine, has been evaluated in the catalytic asymmetric transfer hydrogenation of aromatic ketones. It was fond that [IrCl(COD)]2 complexes of the diamines QCI-Amine and QCD-Amine gave the most active catalysts, capable of reducing a range of aromatic ketones with excellent conversions and good enantioselectivities (up to 95% ee). These are the best selectivities reported for ligands based on the quinuclidine core in an asymmetric transformation, and advocate that these ligands, commercially available in both pseudo-enantiomeric forms, will find practical use in this and other catalytic processes.     

Ni-ANIPE-enabled dynamic kinetic asymmetric addition of ketones with organoboronates

<正>The enantioenriched tertiary alcohols are among the most privileged skeletons in pharmaceuticals, natural products and agrochemicals. Therefore, tremendous effects have been devoted to constructing this chiral moiety, which constitutes the cornerstones in modern organic synthesis. Generally, the enantioselective nucleophilic addition of ketones functionality with the organometallics reagents represents one of the most reliable strategies to forge the tertiary carbon-oxygen bond.