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 Lewis acid-catalyzed asymmetric Baylis-Hillman reactions

An effective chiral Lewis acid-catalyzed asymmetric Baylis-Hillman reaction is described. Good to high enantioselectivities were obtained using 3 mol % chiral catalyst. Novel camphor-derived dimerized ligands were prepared from the condensation of (+)-ketopinic acid with the corresponding diamines and hydrazine under acidic conditions. When alpha-naphthyl acrylate was used as a Michael acceptor, the reaction is complete within 20 min with high stereoselectivity and in reasonable chemical yields.     

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 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.     

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.     

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.     

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.     

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.     

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.     

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 Meyer-Schuster reactions: methodology for the olefination of aldehydes and ketones

In principle, the most efficient and atom-economical means of converting an aldehyde or ketone into the homologated α,β-unsaturated ester is through addition/rearrangement sequences involving acetylenic π-bonds (Scheme 1). Implementation of such a strategy for the synthesis of α,β-unsaturated esters is presented: addition of ethoxyacetylene followed by scandium(III) triflate-catalyzed Meyer-Schuster rearrangement reaction. Stereoselectivities range from good to excellent in the formation of disubstituted α,β-unsaturated esters from aldehydes (Table 3). The two-stage olefination of even the most hindered ketones proceeds with near perfect efficiency (Table 4).     

Stereoselective Lewis acid-catalyzed alpha-acylvinyl additions

Silyloxyallenes derived from alpha-hydroxypropargylsilanes undergo efficient addition to aldehydes with catalytic amounts of Lewis acids. The allenes are accessed from the corresponding propargylsilanes in a base-catalyzed 1,2-Brook rearrangement/SE2' process. Enantioenriched propargylsilanes are synthesized by a new zinc-promoted addition of alkynes to acylsilanes in up to 74% ee. This work demonstrates that conversion to the silyloxyallenes occurs with minimal erosion in optical activity. The use of a chiral chromium(III) Lewis acid effects the catalytic asymmetric addition of racemic silyloxyallenes to aromatic aldehydes in up to 92% ee. The overall reaction is broad in scope and accommodates a wide variety of aromatic and aliphatic substituents on both the propargylsilane and aldehyde.     

Lewis acid-catalyzed enantioselective hydroxylation reactions of oxindoles and beta-keto esters using DBFOX ligand

The first catalytic enantioselective hydroxylation reaction of both 3-aryl and 3-alkyl-2-oxindoles using the DBFOX-Zn(II) complex, leading to pharmaceutically important chiral 3-hydroxy-2-oxindoles was described. The structure of oxidant was found to play an important role to increase the enantioselectivity. The methodology has successfully applied to the highly enantioselective hydroxylation of beta-keto esters using the DBFOX-Ni(II) complex.     

Enantioselective Lewis acid-catalyzed Mukaiyama-Michael reactions of acyclic enones. Catalysis by allo-threonine-derived oxazaborolidinones

allo-Threonine-derived O-aroyl-B-phenyl-N-tosyl-1,3,2-oxazaborolidin-5-ones 1g,n catalyze the asymmetric Mukaiyama-Michael reaction of acyclic enones with a trimethylsilyl ketene S,O-acetal in high enantioselectivity. A range of alkenyl methyl ketones is successfully employed as Michael acceptors affording ee values of 85-90% by using 10 mol % of the catalyst. The use of 2,6-diisopropylphenol and tert-butyl methyl ether as additives is found to be essential to achieve high enantioselectivity in these reactions. The effects of the additives are discussed in terms of the retardation of an Si(+)-catalyzed racemic pathway, which seriously deteriorates the enantioselectivity of asymmetric Mukaiyama-Michael reactions. A working model for asymmetric induction is proposed based on correlation between catalyst structures and enantioselectivities.     

Lewis acid-catalyzed rearrangement of multi-substituted arylvinylidenecyclopropanes

An interesting rearrangement of arylvinylidenecyclopropanes having three substituents at the 1- and 2-positions of the corresponding cyclopropane catalyzed by Lewis acids to give 6aH-benzo[c]fluorine derivatives via a double intramolecular Friedel-Crafts reaction or to give an indene derivative via an intramolecular Friedel-Crafts reaction is described.     

Lewis acid-catalyzed nucleophilic ring-opening/intramolecular Conia-ene reactions of methylenecyclopropane 1,1-diesters with propargyl alcohols

We presented a Lewis acid-catalyzed nucleophilic ring opening of methylenecyclopropane (MCP) 1,1-diesters with propargyl alcohols. Unlike the proximal-bond cleavage mode observed in cases of unactivated MCPs, the intrinsic characteristic of MCP 1,1-diesters gave a regiospecific distal-bond cleavage under attack of propargyl alcohols as nucleophiles. By combining a subsequent intramolecular Conia-ene reaction, 3,5-dimethylenetetrahydropyrans could be obtained in either a stepwise or a one-pot strategy.     

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.     

Asymmetric Lewis acid-catalyzed Diels-Alder reactions of alpha,beta-unsaturated ketones and alpha,beta-unsaturated acid chlorides

[reaction: see text] Conformational analysis, van der Waals attractions, and transition structure calculations are combined to design an asymmetric Lewis acid-catalyzed Diels-Alder reaction for simple acyclic alpha,beta-unsaturated ketones and alpha,beta-unsaturated acid chlorides, giving up to 83 and 92% ee, respectively. The two-point-binding chiral recognition mechanism, Lewis acid-Lewis base coordination with boron and a van der Waals attraction with the naphthyl group, uses the inherent enone unit of simple alpha,beta-unsaturated carbonyl compounds, ending the need for auxiliary oxygen binding sites on the dienophile.