Copper-catalyzed γ-selective and stereospecific allylic alkylation of ketene silyl acetals

Copper-catalyzed allylic alkylation of ketene silyl acetals proceeded with excellent γ-E-selectivity. Efficient α-to-γ chirality transfer with anti-selectivity occurred in the reaction of enantioenriched secondary allylic phosphates, affording enantioenriched β-branched γ,δ-unsaturated esters. Excellent functional group compatibility was observed.     

Highly enantioselective intermolecular Stetter reactions of β-aryl acceptors: α-ketoester moiety as handle for activation and synthetic manipulations

The use of β,γ-unsaturated-α-ketoesters in the intermolecular Stetter reaction furnishes 1,2,5-tricarbonyl compounds in high yield and excellent enantioselectivity. The α,δ-diketoesters generated using this methodology serve as useful synthetic building blocks via chemo- and diastereoselective transformations.     

Highly diastereo- and enantioselective one-pot Michael-Aldol reactions of α,β-unsaturated aldehydes with imidazole derivatives

Highly diastereo- and enantioselective one-pot Michael-Aldol reactions of α,β-unsaturated aldehydes with imidazole derivatives have been developed. The cascade reactions products could be obtained with three stereocenters in high yields and excellent diastereo- and enantioselectivities.     

New synthetic methods for α,β -unsaturated ketones,aldehydes, esters and lactones by the palladium-catalyzed reactions of silyl enol ethers,ketene silyl acetals,and enol acetates with allyl carbonates

Silyl enol ethers and ketene silyl acetals derived from ketones, aldehydes, esters and lactones are converted into α,β-unsaturated ketones, aldehydes, esters and lactones by treatment with allyl carbonates in high yields using the palladium—bis(diphenylphosphino)ethane (dppe) complex as catalyst. Phosphine-free palladium catalyst instead of the palladium—phosphine complex gives a higher selectivity for the preparation of cyclopentenone, cyclooctenone, dienones, α,β-unsaturated esters and lactones. As a solvent, the use of nitriles such as acetonitrile is essential. In other solvents, allylation takes place. Enol acetates derived from ketones are converted into α,β-unsaturated ketones by reaction with allyl carbonate in acetonitrile using the palladium complex and tributyltin methoxide as bimetallic catalysts.     

Synthesis of α,α-disubstituted α-amino esters: nucleophilic addition to iminium salts generated from amino ketene silyl acetals

Alkoxycarbonyl iminium species are prepared easily by the oxidation of tetrasubstituted amino ketene silyl acetals, and subsequent nucleophilic addition of Grignard reagents to the iminium salts gives α,α-disubstituted α-amino ester derivatives in moderate to good yields, in which aryl and ethynyl substituents are readily introduced.     

Highly efficient asymmetric Mannich reaction of dialkyl α-diazomethylphosphonates with N-carbamoyl imines catalyzed by chiral Brønsted acids

An efficient method involving the first use of chiral phosphoric acids as catalysts in the asymmetric Mannich reaction of dialkyl diazomethylphosphonates and N-carbamoyl imines is developed. With only 0.1 mol % catalyst 1f, the reaction proceeded smoothly and produced the corresponding β-amino-α-diazophosphonate with up to 97% yield and >99% ee.     

Enantioselective allylic substitutions using ketene silyl acetals catalyzed by a palladium–chiral amidine complex

Enantioselective allylic substitutions using ketene silyl acetals 3 as a nucleophile have been explored. In the asymmetric reactions of 1,3-diphenylprop-2-enyl pivalate 2 catalyzed by the Pd(0)–chiral amidine 1 complex, excellent levels of stereocontrol are achieved along with good conversions, demonstrating that ketene silyl acetals are able to expand the scope of asymmetric allylic alkylations. The present asymmetric reactions should proceed via nucleophilic attack at the allyl terminus trans to the diphenylphosphinyl group of the amidine on the side opposite to palladium.     

Synthesis of multi-substituted cyclobutenes: Cyclic strategy for [2 + 2] cycloaddition of ketene silyl acetals with propiolates

Cyclic ketene silyl acetals were utilized for [2 + 2] cycloaddition with propiolates to prevent an undesired electrocyclic ring opening reaction. Trimethylaluminum catalyzed this cycloaddition to afford the cyclobutene derivatives in high yields. The advantage of this reaction was highlighted by the successful application of β-substituted propiolates to afford the multi-substituted cyclobutenes. Furthermore, we applied this methodology to the late stage functionalization of natural product artemisinin.     

Reaction of a chlorovinylcarbene with ketenealkyl silyl acetals. Synthesis of new α- and β-allenic carboxylates.

The reaction of ketenealkylsilylacetals with 1,1-dimethyl-2,2,3-trichlorocyclopropane in the presence of methyllithium leads to cyclopropane compounds, which, when treated with tetrabutylammonium fluoride give α- or β-allenic carboxylates.     

Highly enantioselective organocatalytic α-amination reactions of aryl oxindoles: developing designer multifunctional alkaloid catalysts

An enantioselective α-amination of aryl oxindoles catalyzed by a dimeric quinidine has been developed. The reaction is general, broad in substrate scope, and affords the desired products in good yields with good to excellent enantioselectivities. This study provides the first examples of a general organocatalytic method for the creation of nitrogen-containing, tetrasubstituted chiral centers at C(3) of various aryl oxindoles. Furthermore, new catalysts and insights into structural elements of the catalysts that significantly influence enantioselectivities are disclosed.     

Highly diastereo- and enantioselective organocatalytic michael addition of α-ketoamides to nitroalkenes

The first organocatalytic enantio- and diastereoselective conjugate addition of α-ketoamides to nitroalkenes has been achieved using a bifunctional amino thiourea catalyst. In this new approach, the substrate amide proton plays a critical role in the formation of the Michael anti-adducts in high yields and high stereoselectivities. To illustrate the high synthetic potential of this methodology, the diastereo- and enantioselective synthesis of a hexasubstituted cyclohexane via a Michael-Michael-Henry cascade reaction is described.     

Reductive aminopropylation of ketene silyl (thio)acetals leading to the synthesis of δ-amino esters

In the presence of silica gel or titanium tetrachloride, ketene silyl acetals or ketene silyl thioacetals underwent 1,4-addition with α,β unsaturated aldimines which possess a large triphenylmethyl group at the imino nitrogens followed by reduction with sodium cyanoborohydride to give aminopropylated products, δ-amino esters, in good yields.     

Rearrangement of N-tert-butanesulfinyl α-halo imines with alkoxides to N-tert-butanesulfinyl 2-amino acetals as precursors of N-protected and N-unprotected α-amino carbonyl compounds

Reaction of N-tert-butanesulfinyl α-halo imines with alkoxides afforded new N-tert-butanesulfinyl 2-amino acetals in good to excellent yield. These N-tert-butanesulfinyl 2-amino acetals are convenient precursors for the TMSOTf-promoted synthesis of the corresponding N-protected α-amino aldehydes and ketones, as well as for the HCl-promoted synthesis of 2-amino acetal hydrochlorides and α-amino ketone and α-amino aldehyde hydrochlorides in high yield. Via this method, an asymmetric synthesis of (S)-cathinone hydrochloride (er 94:6) was achieved.     

Diastereoselectivity in theLewis acid mediated aldol reaction of chiral α, β-epoxyaldehydes with a ketene silyl acetal

Summary The Lewis acid mediated aldol reaction of chiral , -cis andtrans epoxyaldehydes1 and2 withtert-butyl ketene silyl acetal proceeds mainly withanti diastereofacial preference. The best results were obtained forcis epoxyaldehyde1 in the presence of catalytic amounts of BiCl₃·1.5 eq. ZnI₂ (anti:syn 13:1), whereas the poorest stereoselectivity was observed when an excess of LiClO₄ was used (anti:syn 1:1). The more stable epoxyaldehyde conformers were determined and the diastereofacial preference was found to be in agreement with a nucleophilic attack on the energetically more favoured conformers.

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Diastereoselektivität derLewis-Säure-katalysierten Aldolreaction zwischen chiralen , -Epoxyaldehyden und einem Ketensilylacetal

Zusammenfassung DieLewis-Säure-katalysierte Aldolreaktion der chiralen , -cis- und -trans-Epoxyaldehyde1 und2 mittert-Butylketensilylacetal verläuft stereoselektivanti. Die besten Ergebnisse wurden für dencis-Epoxyaldehyd1 in Gegenwart katalytischer Mengen BiCl3·1.5 eq. Znl₂ erhalten (anti:syn 13:1). Die geringste Stereoselektivität trat auf, wenn LiClO₄ im Überschuß eingesetzt wurde (anti:syn 1:1). Das beobachtete Verhalten steht mit einem nucleophilen Angriff am energetisch günstigeren Konformeren im Einklang.

     

Cinchona-based primary amine-catalyzed enantioselective aza-Michael reactions of pyrroles with α,β-unsaturated aldehydes

The cinchona-based primary amine-catalyzed enantioselective aza-Michael reaction of α,β-unsaturated aldehydes with 4,5-dihalo-1H-pyrrole-2-carbonitriles as the N-centered heteroaromatic nucleophile, followed by chemoselective reduction provided the corresponding chiral aza-Michael products in good yields and with excellent enantioselectivities (90–97% ee).