Synthesis of δ-oxo-1,1-bis(triflyl)alkanes and their acidities.

The reaction of 1,1-bis(triflyl)ethylene generated in situ with enolizable carbonyls yielded δ-oxo-1,1-bis(triflyl)alkane derivatives. Their acidities in both the gas and solution phases were determined.

Carbon acid induced Mukaiyama aldol type reaction of sterically hindered ketones.

1,1,3,3-Tetrakis(trifluoromethanesulfonyl)propane (Tf(2)CHCH(2)CHTf(2)) is one of the most effective Brønsted acid precatalysts for the Mukaiyama aldol type reactions of sterically hindered ketones. By using Tf(2)CHCH(2)CHTf(2) in a range from 0.5 to 2.0 mol %, the vinylogous Mukaiyama aldol reaction of alpha-substituted cyclohexanones with 2-silyloxyfurans smoothly proceeded to give the aldol products in excellent yield without the loss of diastereoselectivity. Under similar conditions, acyclic ketene silyl acetals also performed as nice nucleophiles toward sterically hindered ketones. These findings suggest that Tf(2)CHCH(2)CHTf(2) induced Mukaiyama aldol type reactions can overcome the steric hindrance between reaction sites.

Highly effective vinylogous Mukaiyama-Michael reaction catalyzed by silyl methide species generated from 1,1,3,3-tetrakis(trifluoromethanesulfonyl)propane.

Silyl methide species in situ generated from 1,1,3,3-tetrakis(trifluoromethanesulfonyl)propane (Tf(2)CHCH(2)CHTf(2)) performed as an excellent acid catalyst for the vinylogous Mukaiyama-Michael reaction of alpha,beta-unsaturated ketones with 2-silyloxyfurans. Notably, the required loading of Tf(2)CHCH(2)CHTf(2) to obtain the 1,4-adducts in reasonable yield was significantly low (from 0.05 to 1.0 mol %). This carbon acid-mediated VMM reaction provides a powerful synthetic methodology to construct highly substituted gamma-butenolide structure.

Novel defluorinative alkylation of trifluoroacetaldehyde N,O-acetal derivatives and its application to multi-component reaction.

The reaction of trifluoroacetaldehyde N,O-acetal derivatives with 2 molar equivalents of alkyllithium reagents proceeded viabeta-elimination of fluoride followed by alkyl transfer from excess alkyllithium to the generated ketene N,O-acetal intermediate at the beta-carbon of fluorine groups.

Direct alkylative Passerini reaction of aldehydes, isocyanides, and free aliphatic alcohols catalyzed by indium(III) triflate.

In(OTf)(3) was found to be a useful Lewis acid catalyst for direct alkylative Passerini reaction of aldehydes, isocyanides, and free aliphatic alcohols. In the present reaction, aromatic and alpha,beta-unsaturated aldehydes performed as nice substrates to give the corresponding alpha-alkoxy amide products in good yield.

Remarkable rate acceleration of intramolecular Diels-Alder reaction in ionic liquids.

The intramolecular Diels-Alder reaction of an ester-tethered 1,3,9-decatriene system was significantly accelerated in ionic liquids such as [emim]BF(4), [bmim]BF(4) and [bdmim]BF(4). Under the present conditions, the IMDA reaction proceeded smoothly without the use of Lewis acid catalysts to give cis-fused bicyclic lactones in good yield with high diastereoselectivity.

Tetrakis(trifluoromethanesulfonyl)propane: highly effective Brønsted acid catalyst for vinylogous Mukaiyama-Michael reaction of alpha,beta-enones with silyloxyfurans.

1,1,3,3-Tetrakis(trifluoromethanesulfonyl)propane was found as an excellent Brønsted acid catalyst for the Mukaiyama-Michael reaction of alpha,beta-enones with 2-silyloxyfurans; using beta,beta-disubstituted enones as a Michael acceptor, an excellent yield construction of quaternary carbon centers could be achieved; in addition, very low catalyst loading of Brønsted acid was used in a range from 0.05 to 1.0 mol%.

Synthesis, in vitro pharmacology, and pharmacokinetic profiles of 2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)-ethyl]-1-fluorocyclopropanecarboxylic acid and its 6-heptyl ester, a potent mGluR2 antagonist.

In this paper, we describe the synthesis of (+)-(1R( *),2R( *))-2-[(1S( *))-1-amino-1-carboxy-2-(9H-xanthen-9-yl)-ethyl]-1-fluorocyclopropanecarboxylic acid (+)-16a, a compound, that is, fluorinated at the alpha position of the carboxylic acid in the cyclopropane ring of a group II mGluRs antagonist, 1 (LY341495), using a previously reported stereoselective cyclopropanation reaction. The fluorinated compound (+)-16a exhibited almost the same affinity (IC(50)=3.49 nM) for mGluR2 as 1 but had a superior pharmacokinetic profile. Furthermore, a marked elevation of the plasma levels of (+)-16a was observed following the administration of a prodrug, (+)-17.

Intramolecular Diels-Alder reactions of ester-tethered 1,7,9-decatrienoates: bis[chloro(methyl)aluminum]trifluoromethanesulfonamide as a catalyst.

[reaction: see text] The intramolecular Diels-Alder reaction of 1,7,9-decatrienoate derivative with an ester tether is efficiently catalyzed by the bidentate Lewis acid, bis-aluminated trifluoromethanesulfonamide.

Palladium-catalyzed reaction of acylzirconocene chloride and stereoselective formation of bicyclo[3.3.0] compounds.

The acylzirconocene chloride complex as an acyl group donor reacts with omega-unsaturated alpha,beta-enones and -ynones under Pd-Me(2)Zn(Me(2)AlCl)-catalyzed conditions to give stereoselectively bicyclo[3.3.0] compounds through (i) formation of a Pd(II) intermediate by an oxidative addition of the Pd(0) catalyst to an enone function, (ii) cyclization of the Pd intermediate to an omega-unsaturated group, (iii) an acyl group transfer from zirconium to Pd metal, (iv) reductive elimination of the Pd metal, and (v) intramolecular cis-selective aldol reaction. [reaction: see text]

Zirconium-mediated intramolecular ester transfer reaction: synthesis of alpha-substituted gamma-aminobutyric acid (GABA) derivatives.

[reaction: see text]. The zirconium-mediated intramolecular ester transfer reaction of N-alkenyl carbamate derivatives proceeded to give alpha-substituted gamma-aminobutyric acid (GABA) derivatives in good to excellent yields. Quenching experiments of the reaction mixture with iodine or O2 indicated the presence of a cyclopropane intermediate. The resulting iodide was converted to 2-substituted pyrrolidine-3-carboxylate and/or alpha-alkylidene-gamma-aminobutyric acid derivatives in a stereospecific manner.

Radical cascade reaction with 1,4-dienes and 1,4-enynes using 2-(iodomethyl)cyclopropane-1,1-dicarboxylate as a homoallyl radical precursor: one-step synthesis of bicyclo[3.3.0]octane derivatives.

[reaction: see text] Radical cascade reaction with various 1,4-dienes and 1,4-enynes using dimethyl 2-(iodomethyl)cyclopropane-1,1-dicarboxylate as a homoallyl radical precursor smoothly proceeds through an iodine atom transfer mechanism to give functionalized bicyclo[3.3.0]octane derivatives in good yields.

Catalytic asymmetric synthesis of vicinal diamine derivatives through enantioselective N-allylation using chiral pi-allyl Pd-catalyst.

[reaction: see text] N-monoallylation of meso-vicinal diamine bistrisylamides using a chiral pi-allyl-Pd catalyst proceeded in an enantioselective manner (up to 90% ee) to give desymmetrization products in good yields. The product was converted to the known sigma-receptor agonist in short steps. In addition, the present catalytic asymmetric N-allylation was applied to kinetic resolution of racemic-diamide.

Diastereoselective Iodocarbocyclization Reaction of 2- or 3-Oxy-4-pentenylmalonate Derivatives.

1,2- Or 1,3-asymmetric induction in the iodocarbocyclization reaction of 4-pentenylmalonate derivatives having a stereogenic center at an allylic or a homoallylic position has been investigated. The iodocarbocyclization reactions of 3-oxy-4-pentenylmalonate derivatives proceeded with high cis-selectivity through stereoelectronic control of the oxygenated substituent at an allylic position. In the reaction of (S)-2-siloxy-4-pentenylmalonate, an excellent diastereoselectivity was achieved through the utilization of double stereodifferentiation with a chiral titanium catalyst. Furthermore, as an application of the present reaction, the asymmetric syntheses of cyclosarkomycin and a synthetic intermediate of brefeldin A from optically pure 2- and 3-oxy-4-pentenylmalonate derivatives are also described.

Regiocontrolled Iodoaminocyclization Reaction of an Ambident Nucleophile Mediated by Basic Metallic Reagent.

A new and general method of iodine-mediated cyclization reactions of allyl or homoallyl carbamates, ureas, and amides was found to give N-cyclized products as single regioisomers. The present reaction proceeded in good yield through regiocontrol (N-cyclization > O-cyclization) and the increase in the reactivity of an ambident nucleophile by a basic metallic reagent. The N-cyclization selectivity was remarkably affected by the additive employed. The iodoaminocyclization reaction of the homoallyl carbamates and ureas with a chiral center at the homoallylic position was found to proceed with high 1,3-cis- and 1,3-trans-selectivity, respectively.

Catalytic Asymmetric Iodocarbocyclization Reaction of 4-Alkenylmalonates and Its Application to Enantiotopic Group Selective Reaction.

The iodocarbocyclization reaction of 4-alkenylmalonate derivatives proceeded with excellent enantioselectivity (>/=95% ee) in the presence of 10-40 mol % of Ti(TADDOLate)(2). The Ti(TADDOLate)(2)-mediated catalytic asymmetric reaction was extended to the enantiotopic group selective reaction of bisalkenylated malonates, giving rise to trisubstituted cyclopentanoid compounds with both high diastereoselectivity (86-94% de) and excellent enantioselectivity (>/=95% ee). An efficient synthesis of (+)-boschnialactone from the product of the present reaction was also achieved.

Optically Active Axially Chiral Anilide and Maleimide Derivatives as New Chiral Reagents: Synthesis and Application to Asymmetric Diels-Alder Reaction.

New axially chiral N-acryl-N-allyl-o-tert-butylanilide and N-(o-tert-butylphenyl)-2-methylmaleimide with high optical purity and definite absolute configurations were prepared from o-tert-butylaniline and (S)-O-acetyl lactic acid or (R)-2-methylsuccinic acid, respectively. Iodine- or Lewis acid-mediated asymmetric Diels-Alder reaction of these axially chiral compounds with various dienes proceeded with high endo and diastereofacial selectivity.

Acylzirconocene Chloride as an "Unmasked" Acyl Anion.

Under mild conditions the acyl group of acylzirconocene chloride 1 formed from an alkene or alkyne and [(C5 H5 )2 ZrHCl] reacts as an "unmasked" acyl anion. The Lewis acid mediated reactions with aldehydes that yield α-ketol products in high yields demonstrate the versatility of this reagent for C-C coupling.