Investigation of Lewis acid-catalyzed asymmetric aza-Diels-Alder reactions of 2H-azirines

Asymmetric Diels-Alder reactions with 2H-azirines as dienophiles have been studied. Diastereoselective reactions with an enantiopure azirine 1b, bearing a chiral auxiliary, gave substituted bi- and tricyclic tetrahydropyridines in high yield and stereoselectivity, under the influence of a Lewis acid. The novel enantioselective [4+2] cycloaddition reaction of 3-benzyl-2H-azirine carboxylate with cyclopentadiene was investigated with various chiral Lewis acid complexes and provided the corresponding tetrahydropyridines in moderate to low yield and enantioselectivity.     

Chiral Lewis acid-catalyzed enantioselective intramolecular carbonyl ene reactions of unsaturated alpha-keto esters

[reaction: see text] Chiral Lewis acid-promoted highly enantioselective intramolecular carbonyl ene reactions of unsaturated alpha-keto esters have been investigated. In the presence of chiral Lewis acids such as [Sc((R,R)-Ph-pybox)](OTf)(3) and [Cu((S,S)-Ph-box)](OTf)(2), several unsaturated alpha-keto esters underwent carbonyl ene reactions in CH(2)Cl(2) at room temperature to give monocyclic products in good yield and excellent enantioselectivity.     

Lewis acid-catalyzed reactions on polystyrene

The action of aluminium halides upon polystyrene was studied as a function of the nature of the reaction medium and of the concentration of catalyst. It was demonstrated that polystyrene undergoes crosslinking, the extent of which is particularly important in chlorinated aliphatic solvents and at high catalyst concentrations. In additions, phenyl rings of the polymer are alkylated and halogenated by the solvent or catalyst. Infrared spectroscopic investigation of the structure of the products indicated that in most cases crosslinking was connected with the formation of 1,4-disubstituted, and eventually 1,2,4-trisubstituted benzenes. In carbon tetrachloride medium, meta substitution was also detected. In products obtained when polystyrene was treated with high amounts of the Lewis acid in CCl₄ medium degrees of substitution even higher than three were probable.     

Chiral ruthenium Lewis acid-catalyzed nitrile oxide cycloadditions

The synthesis of the chiral ligand (R,R)-BIPHOP-F is detailed. Its coordination to a cationic cyclopentadienyl ruthenium fragment generates [Ru (acetone)(R,R)-BIPHOP-F)Cp][SbF₆], a transition metal Lewis acid that catalyzes the [3+2] dipolar cycloaddition reaction between aryl nitrile oxides and α,β-unsaturated aldehydes to give chiral 2-isoxazolines with yields of 43-98% and asymmetric purity of 60-93% ee. The stereochemistry of the major enantiomer is S, consistent with an approach of the nitrile oxide to the C_α-Si face of the enal in the anti-s-trans conformation in the catalyst site.     

Development of fluorous Lewis acid-catalyzed reactions

Organic synthetic methodology in the 21st century aims to conform to the principles of green sustainable chemistry (GSC) and we may expect that in the future, the realization of GSC will be an important objective for chemical industries. An important aim of synthetic organic chemistry is to implement waste-free and environmentally-benign industrial processes using Lewis acids as versatile as aluminum chloride. A key technological objective of our work in this area has been to achieve a "catalyst recycling system that utilizes the high activity and structural features of fluorous Lewis acid catalysts". Thus, we have developed a series of novel fluorous Lewis acid catalysts, namely the ytterbium(III), scandium(III), tin(IV) or hafnium(IV) bis(perfluoroalkanesulfonyl)amides or tris(perfluoro- alkanesulfonyl)methides. Our catalysts are recyclable and effective for acylations of alcohols and aromatics, Baeyer-Villiger reactions, direct esterifications and transesterifications in a fluorous biphasic system (FBS), in supercritical carbon dioxide and on fluorous silica gel supports.     

Pipecolic acid-catalyzed direct asymmetric mannich reactions

[STRUCTURE: SEE TEXT] Mannich reactions between aldehydes and N-p-methoxyphenyl-protected alpha-imino ethyl glyoxylate have been performed using (S)-pipecolic acid as catalyst. The reactions give both syn- and anti-products (dr=1.4-2:1) with high enantioselectivities (>98% ee). In contrast, (S)-proline-catalyzed reactions give mainly syn-products with high enantioselectivities. Computational studies reveal that the energetic preference between the transition structures involving the s-cis-enamine and the s-trans-enamine is smaller for the pipecolic acid as compared to proline, yielding the (2S,3R)-anti and the (2S,3S)-syn Mannich product in nearly equal amounts.     

Chiral phosphoric acid-catalyzed asymmetric transfer hydrogenation of quinazolinones

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Lewis acid-catalyzed tri- and difluoromethylation reactions of aldehydes

The first Lewis acid-catalyzed trifluoromethylation reactions of aldehydes with Me3SiCF3 under TiF4/DMF, Ti(O iPr)4/DMF and Cu(OAc)2/dppp/toluene conditions are described. We have successfully applied this methodology to the difluoromethylation of aldehydes using Me3SiCF2SePh, Me3SiCF2P(O)OEt2 and Me3SiCF2SPh.     

Lewis acid-catalyzed Mannich type reactions with potassium organotrifluoroborates

Three-component Lewis acid-catalyzed Mannich type reactions using potassium organotrifluoroborates (aryl, vinyl, and allyl reagents) has been developed as an extension of the standard Petasis reaction.     

Lewis acid-catalyzed asymmetric hydroxymethylation of silicon enolates in aqueous media

Asymmetric hydroxymethylation of silicon enolates with formaldehyde in aqueous media has been achieved using praseodymium triflate and a chiral crown ether. Formaldehyde aqueous solution can be directly used for the reactions, and a water/THF mixture was found to be the best solvent system. This is the first example of catalytic asymmetric hydroxymethylation of silicon enolates.     

Lewis acid-catalyzed reactions of donor-acceptor cyclopropanes with furan derivatives

Lewis acid-catalyzed reactions of dialkyl 2-arylcyclopropane-1,1-dicarboxylates with 2,5-dimethylfuran were found to give products of [3+2]-cycloaddition to C(2)-C(3) bond, which contain reactive vinyl ether moiety. These adducts can be further transformed into various products depending on the Lewis acid, the nucleophilicity of aryl group in starting cyclopropane and the ratio of reagents. The vinyl ether moiety can attack the appropriate nucleophilic center in intramolecular or intermolecular mode or can undergo cycloaddition to the second equivalent of donor-acceptor cyclopropane. Alternatively, 2,5-diphenylfuran formed Friedel-Crafts products only when reacted with donor-acceptor cyclopropanes.     

Lewis acid-catalyzed Prins-type reactions of methylenecyclopropylcarbinols with aldehydes and aldimines

Lewis acid-catalyzed Prins-type reactions of methylenecyclopropylcarbinols with aldehydes and aldimines proceeded smoothly to give the corresponding 3-oxa-bicyclo[3.1.0]hexane units via 5-exo cyclization in good to high total yields.     

Cascade dearomatization of N-substituted tryptophols via Lewis acid-catalyzed Michael reactions

Lewis acid-catalyzed cascade dearomatization of N-substituted tryptophols via Michael addition reaction was developed. The generality of the method has been demonstrated by the synthesis of versatile furoindoline derivatives with a quaternary carbon center in good yields.     

Chiral Lewis acid-catalyzed highly enantioselective [4 + 3] cycloaddition reactions of nitrogen-stabilized oxyallyl cations derived from allenamides

A chiral Lewis acid-catalyzed highly enantioselective [4 + 3] cycloaddition reaction of allenamide-derived nitrogen-stabilized chiral oxyallyl cations is described here. The use of bisoxazoline ligand and CuOTf2 provides high enantioselectivity, especially with [SbF6]- as the counteranion.     

Non-linear effects in acyclic amino acid-catalyzed direct asymmetric aldol reactions

Non-linear effects were observed in acyclic amino acid-catalyzed direct asymmetric intermolecular aldol reactions. The non-linear effects are due to the equilibrium solid-liquid phase behavior of amino acids. The results suggest that the phase behavior of amino acids linked to asymmetric catalysis may have implications to the evolution of homochirality.     

Lewis acid-catalyzed reactions of mono-aryl group substituted methylenecyclopropanes with diethyl ketomalonate

Mono-aryl group substituted methylenecyclopropanes (MCPs) 1 react with diethyl ketomalonate 2a, an activated ketone, to give the corresponding 7-hydroxy-5-oxa-spiro[2,4]heptan-6-one derivatives 6 with syn-configuration in moderate yields in the presence of water under the catalysis of Lewis acids such as Sc(OTf)₃, Yb(OTf)₃ or In(OTf)₃ at room temperature. The reaction mechanism has been discussed on the basis of an ¹⁸O-labeling experiment.     

Alpha'-hydroxy enones as achiral templates for Lewis acid-catalyzed enantioselective Diels-Alder reactions

alpha'-Hydroxy enones react with dienes in the presence of (S,S)-[Cu(tBu-box)](OTf)2 or (S,S)-[Cu(tBu-box)](SbF6)2 (2 to 10 mol %) to afford the corresponding Diels-Alder adducts in high yield and selectivity. Isomeric ratios (regioselectivity, endo/exo or cis/trans) of up to >99:1 and ee values of up to >99% are obtained. Significantly, difficult dienes such as isoprene, 2,3-dimethyl butadiene and piperylene behave satisfactorily. Subsequent oxidative cleavage of the ketol in the resulting cycloadducts by treatment with cerium ammonium nitrate (CAN) yields the corresponding enantiopure carboxylic acids. Alternatively, carbonyl addition and subsequent diol cleavage with CAN produces the corresponding ketone adducts.     

Lewis acid-catalyzed ring-opening reactions of methylenecyclopropanes with alcoholic or acidic nucleophiles

[reaction: see text] Methylenecyclopropanes can react with various nucleophiles such as alcohols, phenols, carboxylic acids, and thiols to give the corresponding homoallylic esters or ethers in good yields with good stereoselectivities in the presence of Lewis acids.     

Lewis acid-catalyzed asymmetric diels-alder reactions using chiral sulfoxide ligands: chiral 2-(arylsulfinylmethyl)-1,3-oxazoline derivatives

New chiral sulfoxide-1,3-oxazoline ligands have been developed as chiral ligands for Lewis acid-catalyzed asymmetric Diels-Alder reactions. The use of chiral sulfinyl 1,3-oxazoline ligands in copper(II)-catalyzed asymmetric Diels-Alder reactions provided an endo cycloadduct as a major product with moderate enantioselectivity. A rationale is proposed for the mechanism of the asymmetric induction.