An improved synthesis of a ketone catalyst for asymmetric epoxidation of olefins

An efficient synthesis of a ketone catalyst for asymmetric epoxidation of olefins from D-glucose in six steps is described.     

Nickel-catalyzed asymmetric alpha-arylation of ketone enolates

An atropisomeric dipyridyldiphosphine, P-Phos, can effect highly enantioselective Ni-catalyzed alpha-arylation of ketone enolates with aryl halides to install an all-carbon quaternary stereogenic center in up to 98% ee and excellent yields.     

Catalytic asymmetric vinylation of ketone enolates

[see reaction]. A protocol for the catalytic asymmetric vinylation of ketone enolates has been developed. Key to the success of this process was the development of new electron-rich chiral monodentate ligands.     

Palladium-catalyzed asymmetric allylic alkylation of ketone enolates

Palladium-catalyzed asymmetric allylic alkylation of nonstabilized ketone enolates to generate quaternary centers has been achieved in excellent yield and enantioselectivity. Optimized conditions consist of performing the reaction in the presence of two equivalents of LDA as base, one equivalent of trimethytin chloride as a Lewis acid, 1,2-dimethoxyethane as the solvent, and a catalytic amount of a chiral palladium complex formed from pi-allyl palladium chloride dimer 3 and cyclohexyldiamine derived chiral ligand 4. Linearly substituted, acyclic 1,3-dialkyl substituted, and unsubstituted allylic carbonates function well as electrophiles. A variety of alpha-tetralones, cyclohexanones, and cyclopentanones can be employed as nucleophiles. The absolute configuration generated is consistent with the current model in which steric factors control stereofacial differentiation. The quaternary substituted products available by this method are versatile substrates for further elaboration.     

Palladium-catalyzed arylation of ketone enolates: an expeditious entry to tamoxifen-related 1,2,2-triarylethanones

[reaction: see text]. After a rigorous study on the effect of several catalytic systems, a simple, high yielding procedure for the preparation of 1,2,2-triarylethanones, skeletal analogues of tamoxifen, is presented. Apart from the economic and environmental advantages involved, this palladium-catalyzed arylation of deoxybenzoin enolates features a lack of ortho-arylation side reactions. In addition, an alternative approach from acetophenones to the target triarylethanone system is also announced.     

Asymmetric allylic alkylation of ketone enolates: an asymmetric Claisen surrogate

[reaction: see text] The combination of catalytic palladium(0) and Trost ligand provides an effective catalyst for the rearrangement of allyl beta-ketoesters. The mechanism of the transformation involves formation of pi-allyl palladium intermediates which undergo enantioselective attack by ketone enolates. Decarboxylation of beta-ketocarboxylates allows regiospecific generation of enolates under extremely mild conditions.     

An improved rhodium-DIOP catalyst system for the homogeneous asymmetric hydrogenation of acetophenone

The asymmetric hydrogenation of acetophenone with an improved Rh-DIOP catalyst system was studied. Optical yields as high as 79% were obtained when a rhodium-DIOP-chloride catalyst system containing a tertiary hydroxyalkylamine promoter was used. The various factors governing the rates and selectivities are discussed.     

Palladium-catalysed arylation of sulfonamide stabilised enolates

α-Arylation of methanesulfonamides using palladium catalysis is described. For example, treatment of N-benzyl-N-methylmethanesulfonamide with catalytic Pd(OAc)₂ in the presence of sodium tert-butoxide, triphenylphosphine and toluene afforded N-benzyl-N-methylphenylmethanesulfonamide in 66% yield.     

An annulative approach to highly substituted indoles: unusual effect of phenolic additives on the success of the arylation of ketone enolates

A novel palladium-catalyzed arylation of ketone enolates with o-nitrohaloarenes was achieved through the addition of phenol additives. The mild reaction conditions employed allowed for the inclusion of a wide variety of functional groups in both substrates to be tolerated. The products of this reaction were then readily reductively cyclized to give highly substituted indoles in moderate to excellent overall yields.     

Kinetic cyanations of ketone enolates

Kinetic cyanations of ketone enolates using p-toluenesulfonyl cyanide provide efficient routes to β-ketonitriles.     

Towards a facile synthesis of triarylethanones: palladium-catalyzed arylation of ketone enolates under homogeneous and heterogeneous conditions

The palladium-catalyzed regioselective α-monoarylation of deoxybenzoins and α,α-diarylation of acetophenones provides general, efficient access to 1,2,2-triarylethanones. After a comprehensive search for suitable experimental conditions to optimize such transformations, both reactions are alternatively conducted by means of either commercially available polymer-anchored catalysts or a very simple homogeneous catalytic system, thus avoiding the use of complex ligands. In addition, the synthesis of deoxybenzoins employing polymer-supported fibrous palladium catalysts is reported for the first time, and the excellent catalyst recycling properties suggest applicability to industrial purposes.     

Practical synthesis of an L-fructose-derived ketone catalyst for asymmetric epoxidation of olefins

An L-fructose-derived ketone catalyst for asymmetric epoxidation of trans- and trisubstituted olefins was efficiently prepared from L-sorbose in five steps.     

N-Boc-L-valine-connected amidomonophosphane rhodium(I) catalyst for asymmetric arylation of N-tosylarylimines with arylboroxines

A catalytic asymmetric arylation of sterically tuned imines with arylboroxines was developed by using N-Boc-l-valine-connected amidomonophosphane rhodium(I) catalyst in n-PrOH. The TMS group used for the steric tuning of imines is convertible to other functionalities that are applicable as a key foothold for the carbon-carbon bond-forming coupling reactions.     

Radical trifluoromethylation of ketone Li enolates

It has generally been believed that highly basic Li enolates cannot be applied as substrates for radical trifluoromethylation due to defluorination of the α-CF₃ product. However, Li enolates can be in fact employed for radical trifluoromethylation. Moreover, the reaction is extremely fast and the minimum reaction time is only ∼1 s.     

Ruthenium-catalyzed decarboxylative allylation of nonstabilized ketone enolates

[reaction: see text] Bipyridyl(pentamethylcyclopentadienyl)ruthenium chloride is an efficient catalyst for the formal [3,3] rearrangement of allyl beta-ketoesters. The mechanism of the transformation involves formation of pi-allyl ruthenium intermediates, which are selectively attacked at the more substituted allyl terminus by freely diffusing enolates. Decarboxylation of beta-ketocarboxylates allows generation of enolates under extremely mild conditions.     

An improved lanthanum catalyst system for asymmetric amination: toward a practical asymmetric synthesis of AS-3201 (Ranirestat)

A catalytic asymmetric amination with a lanthanum/amide complex was significantly improved. The use of lanthanum nitrate hydrate in place of lanthanum triisopropoxide made the process reproducible, scalable, and cost-effective. The development of a ternary catalytic system of La/ligand/amine was a key to high ee and catalytic turnover. A 100 g scale reaction was performed to showcase a practical synthesis of a key intermediate for AS-3201, a highly potent aldose reductase inhibitor.     

Arynic condensation of ketone enolates—XIV: Condensation of aromatic α,β-unsaturated ketone enolates on arynes

Benzyne and 1-naphthyne (generated from the corresponding halogeno derivatives and the Complex Base NaNH₂-Bu^tONa) condense with α,β-unsaturated ketone enolates β-substituted by an aromatic ring and only enolisable in the α'-position, to lead to α-tetralones and/or indanones. The reaction path depends upon the nature of the ketone enolate and, less strongly, on the solvent. The reaction mechanism is discussed. These reactions constitute new simple and efficient syntheses of numerous α-tetralones and indanones.     

An unprecedented recyclable catalyst system for asymmetric hydroboration

Immobilised preformed chiral homogeneous catalysts were subjected to catalytic hydroboration of styrene with catecholborane and the activity, regio- and enantioselectivity observed were similar to those found when the corresponding homogeneous catalyst was used, remaining constant for several consecutive runs.