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Catalytic cyclization of allyl amides of ethenetricarboxylate leading to pyrrolidines has been examined. Reaction of allyl amides of ethenetricarboxylate with Sc(OTf) 3 (0.2 equiv) gave 4-hydroxymethyl-2-oxopyrrolidine derivatives as major products. The formation of hydroxymethylpyrrolidines may arise from participation of adventitious water in situ. Sc(OTf) 3 -catalyzed cyclization reactions of the allyl amides with TMSX (X = Cl, Br) proceeded efficiently to give halogenated 2-oxopyrrolidine derivatives. Sc(OTf) 3 -catalyzed cyclization reactions of the allyl ester with TMSX (X= Cl, Br) also proceeded to give halogenated 2-oxotetrahydrofuran derivatives.

Catalytic cyclization of amides of ethenetricarboxylate bearing ether and acetal groups has been examined. The reaction of the amides bearing cyclic ether and acetal groups in the presence of Lewis acid such as Sc(OTf)3 gave spirocyclic piperidine derivatives as major products. The cyclized products may be formed via intramolecular hydride transfer. The reaction mechanism was examined by the DFT calculations. The scope and limitations of the hydride transfer/cyclization reactions of amides of ethenetricarboxylates was investigated, and morpholine formation by intramolecular oxy-Michael addition was also found.

The Lewis acid promoted reactions of 2-substituted 2-propenyl amides and the 2-methylbuta-2,3-dienyl ester of ethenetricarboxylate have been examined. The reactions of 2-substituted 2-propenyl amides with AlCl3 gave 2-oxo-5,6-dehydropiperidines as the major products. The reaction of 2-methylbuta-2,3-dienyl ester with Lewis acids such as AlCl3 and SnCl4 gave 2-oxo-3,6-dihydropyran as the major product. The preference for six- over five-membered-ring formation was observed.

Lewis acid-promoted intramolecular reactions of allenyl ethenetricarboxylates and the corresponding amides have been examined. Reactions of allenyl ethenetricarboxylates and the amides with Lewis acids such as AlCl3, AlBr3 and ZnX2 (X = Cl, Br, I) gave 3,4-trans haloalkenyl five-membered heterocycles stereoselectively. The stereochemistry was determined by NOE experiments and reduction of the cyclized products. Various transformations of the haloalkenyl functionalized cyclic compounds have also been performed.

Lewis acid-promoted intramolecular reactions of alkenyl ethenetricarboxylates and the corresponding amides have been examined. Reaction of allyl ethenetricarboxylates and the amides with Lewis acids (1-2 equiv) such as TiCl4, TiBr4, AlCl3, and AlBr3 gave 3,4-trans-halogenomethyl 2-oxotetrahydrofuran and pyrrolidine derivatives stereoselectively in high yields. The stereochemistries were determined by NOE experiments. Reaction of alkyl-substituted allylic ethenetricarboxylates with Lewis acids gave chloro 2-oxotetrahydrofurans and pyrans. For some alkyl-substituted substrates, cationic intermediates may be formed under the reaction conditions, and rearranged products have been obtained.

The Lewis acid promoted reaction of 1,1-diarylallenes with ketone derivatives was examined. The tin(IV) chloride promoted reaction of diarylallenes with vinyl ketones gave indene derivatives through a conjugate addition/cyclization reaction. The reaction of diphenylallene with diethyl oxomalonate in the presence of one equivalent of tin(IV) chloride at –40 °C gave diethyl hydroxy(3-phenyl-1 H -inden-2-yl)malonate as the major product through a carbonyl addition/cyclization reaction, whereas the same reactants in the presence of 0.2 equivalents of tin(IV) chloride at 80 °C gave diethyl (3-phenyl-1 H -inden-2-yl)malonate. Diethyl hydroxy(3-phenyl-1 H -inden-2-yl)malonate was also converted into the latter product on heating at 80 °C in the presence of 0.2 equivalents of tin(IV) chloride.

The Lewis acid-promoted reaction of an ethenetricarboxylate derivative (1) with CF3-substituted propargyl alcohols has been examined. Reaction of γ-CF3 propargyl alcohols in the presence of zinc bromide gave five-membered CF3-containing tetrahydrofurans in 66–85% yield. The CF3 group activates alkyne as an electron-withdrawing group. On the other hand, reaction of γ-trifluoromethyl-α-aryl propargyl alcohols 2 with 1 in the presence of 1 equiv of SnCl4 gave cyclobutane derivatives 6 in 29–49% yield. Formation of cyclobutane 6a arises from the [2+2] cycloaddition between ethenetricarboxylate 1 and chloroallene 8, which is produced by the reaction of propargyl alcohol 2a and SnCl4.

Recent developments concerning the synthesis of methylenetetrahydrofurans and methylenepyrrolidines by one-pot formal [3+2] cycloadditions involving propargylic (and allylic) alcohols and amines with electrophilic alkenes are described. The synthetic methods provide powerful tools to prepare highly functionalized oxygen- and nitrogen-containing five-membered ring systems. The reactions can be effectively promoted by base, base/transition metals, and Lewis acids, depending on the substrates.

Oxygen-containing heterocyclic systems are important structures in organic chemistry because of their presence in many biologically active compounds. In this work, a Lewis acid-catalyzed cyclization of ethenetricarboxylate derivatives 1 with substituted propargyl alcohols to give methylenetetrahydrofurans was investigated. Reaction of 1 and gamma-silicon-substituted propargyl alcohols 4 with ZnBr2 at 80-110 degrees C led to (Z)-silicon-substituted products stereoselectively. Reaction of 1 and gamma-ester-substituted propargyl alcohol 7 in the presence of various Lewis acids gave ester-substituted methylenetetrahydrofurans stereoselectively. Interesting Lewis acid dependency on stereoselectivity for the reaction of 7 was found. Reaction of alpha-substituted propargyl alcohols also gave cyclized products.

The conjugate addition of amines is considered to be a useful reaction in synthetic organic chemistry. The reaction of reactive electrophilic olefins, ethenetricarboxylates, and aromatic amines with and without catalytic Lewis acids such as ZnCl2 and ZnBr2 at room temperature gave amine adducts in high yields. The products were converted to α-amino acid, dl -aspartic acid derivatives. Using Lewis acids such as Sc(OTf)3 and Zn(OTf)2 at higher temperature (40–80 °C), the reaction of ethenetricarboxylates and N-methylaniline gave an aromatic substitution product. A catalytic enantioselective conjugate addition using a chiral Lewis acid was also investigated. For example, the reaction of 1,1-diethyl 2-tert-butyl ethenetricarboxylate with N-methylaniline in the presence of chiral bisoxazoline-Cu(II) complex in THF at −20 °C for 17 h gave an amine adduct in 91% yield and 78% ee. On the other hand, the reaction with aniline and primary aniline derivatives gave adducts with almost no ee%.

A novel cyclization of 1,1-diethyl 2-tert-butyl ethenetricarboxylate (1a) in the presence of a Lewis acid afforded a 5,5-dimethyl-gamma-lactone derivative 2a. The reaction process has been shown to arise from formation by trapping of isobutylene generated in situ. Lewis acid-promoted intermolecular reactions of 1,1-diethyl 2-hydrogen ethenetricarboxylate (5) and various alkenes to afford highly functionalized gamma-lactones were also developed. [reaction: see text]

A novel cyclization reaction of ethenetricarboxylate derivative aromatic compounds in the presence of various Lewis acids gave benzo-annulated cyclic compounds such as oxindole and benzofuran derivatives via Friedel-Crafts intramolecular Michael addition in high yields. For example, the reaction of diethyl 2-[(N-methyl-N-phenylcarbamoyl)methylene]malonate (1a) in the presence of ZnCl2 at room temperature gave diethyl 2-(1-methyl-2-oxoindolin-3-yl)malonate (2a) in 98% yield. The reactions also proceeded with a catalytic amount of a Lewis acid such as AlCl3, ZnCl2, ZnBr2, Sc(OTf)3, or InBr3.

Depending on the functionality of the substrates used, either saturated or unsaturated six-membered ring products are obtained selectively.

Reactions of allenyl ethenetricarboxylates (I) and the corresponding amides (III) with Lewis acids, such as AlCl3, AlBr3 and ZnX2 (X = Cl, Br, I) afford 3,4-trans-haloalkenyl lactones (III) and lactams (IV)/(V).

The mechanism of the novel [2 + 1] cycloaddition reaction of 1-seleno-2-silylethenes has been investigated using DFT (density functional theory) calculations. This study revealed a remarkable reaction path; the silicon migration and cyclopropane ring closure occur concertedly with the aid of eight-membered cyclic Se–metal (in the Lewis acid) coordination. The transition state for the crucial silicon-shift and ring-closure steps was obtained. The structures show that a through-space Se–metal (Sn or Zn) interaction causes three-membered ring closure. Cyclopropane vs. cyclobutane product selectivity was elucidated by these calculations.

The reactions of (E)-1-(phenylseleno)-2-(trimethylsilyl)ethene (1a) and (E)-1-(phenylseleno)-2-(triethylsilyl)ethene (1b) with dimethyl 1,1-dicyanoethene-2,2-dicarboxylate (2) in the presence of SnCl4 in CH2Cl2 at −78 °C for 1 h exclusively afforded [2 + 2] cycloadducts 3a and 3b in 71% and 78% yields, respectively. The exclusive [2 + 2] selectivity in the reaction of 1 with 2 in the presence of SnCl4 is explained by destabilization of the proposed selenium-bridged intermediate that would lead to the [2 + 1] adduct by the presence of the two electron-withdrawing cyano groups. The reaction of 1a with 2 at 0 °C to room temperature in the presence of ZnBr2 gave a regioisomeric [2 + 2] cycloadduct 7a in low yield along with a corresponding desilylated cyclobutane 8 as the major product in moderate to good yield. The origin of the Lewis acid dependence of the regioselectivity was deduced from a theoretical comparison of stability of Lewis acid complexes.

Lewis acid-promoted intramolecular reactions of alkenyl ethenetricarboxylates and the corresponding amides have been examined. Reaction of allyl ethenetricarboxylates and the amides with Lewis acids (1–2 equiv) such as TiCl4, TiBr4, AlCl3, and AlBr3 gave 3,4-trans-halogenomethyl 2-oxotetrahydrofuran and pyrrolidine derivatives stereoselectively in high yields. The stereochemistries were determined by NOE experiments. Reaction of alkyl-substituted allylic ethenetricarboxylates with Lewis acids gave chloro 2-oxotetrahydrofurans and pyrans. For some alkyl-substituted substrates, cationic intermediates may be formed under the reaction conditions, and rearranged products have been obtained.

Lewis acid promoted treatment of ethenetricarboxylates and the nitrile (Ie) with arylallenes allows new access to indenes.

The reaction of (trimethylsilyl)vinyl selenide 1 and (trimethylsilyl)allenyl selenide 2 with vinyl ketones 3a-c in the presence of a Lewis acid gave cyclobutane derivatives stereoselectively. The reaction of 1 and 3a-c with SnCl 4 was quenched either with Et 3 N to give cyclobutanes 4a-c or with H 2 O to give acylsilanes 11a-c. The formation of both products is explained in terms of a zwitterionic intermediate. The cis relationship between the phenylseleno group and the carbonyl group of 4a-c is rationalized by consideration of a combination of secondary-orbital interactions and steric effects in the early stage of a intermediate formation

The reactions of 1-seleno-2-silylethenes 1 with highly electrophilic tricarbonyl-substitued olefins in the presence of Lewis acids have been investigated. The reaction of 1-(phenylseleno)-2-(trimethylsilyl)ethene (1a) with tris(alkoxycarbonyl) olefins 2 or 1,1-bis(alkoxycarbonyl)-2-acyl olefins 3 in the presence of ZnBr(2) at -30 degrees C gave cis-substituted cyclopropanes exclusively. The origin of the cis stereochemistry is ascribed to the synclinal addition path of the ZnBr(2)-coordinated electrophilic olefin to 1. Application of the highly functionalized selenium- and silicon-substituted cyclopropane products to the preparation of a useful synthetic intermediate 20 for the pyrethroid class of insecticides is also demonstrated.

Indenes are important core structures in organic chemistry. Few simple arylallenes have been used to construct indene skeletons by Friedel-Crafts reaction. Lewis acid catalyzed reaction of ethenetricarboxylates 1 and arylallenes has been examined in this study. The reaction of arylallenes and ethenetricarboxylate triesters with SnCl(4) gave indene derivatives efficiently, via a conjugate addition/Friedel-Crafts cyclization reaction. On the other hand, the reactions of 1,1-diethyl 2-hydrogen ethenetricarboxylate and arylallenes or alkylallenes with SnCl(4) at -78 degrees C or room temperature and subsequent treatment with Et(3)N gave gamma-lactones. The reactions of triethyl ethenetricarboxylate and 1,1-dialkylallenes with SnCl(4) at room temperature also gave gamma-lactones.

The Lewis acid-promoted reaction of an ethenetricarboxylate derivative (1) with CF3-substituted propargyl alcohols has been examined. Reaction of γ-CF3 propargyl alcohols in the presence of zinc bromide gave five-membered CF3-containing tetrahydrofurans in 66–85% yield. The CF3 group activates alkyne as an electron-withdrawing group. On the other hand, reaction of γ-trifluoromethyl-α-aryl propargyl alcohols 2 with 1 in the presence of 1 equiv of SnCl4 gave cyclobutane derivatives 6 in 29–49% yield. Formation of cyclobutane 6a arises from the [2+2] cycloaddition between ethenetricarboxylate 1 and chloroallene 8, which is produced by the reaction of propargyl alcohol 2a and SnCl4.

Recent developments concerning the synthesis of methylenetetrahydrofurans and methylenepyrrolidines by one-pot formal [3+2] cycloadditions involving propargylic (and allylic) alcohols and amines with electrophilic alkenes are described. The synthetic methods provide powerful tools to prepare highly functionalized oxygen- and nitrogen-containing five-membered ring systems. The reactions can be effectively promoted by base, base/transition metals, and Lewis acids, depending on the substrates.

Oxygen-containing heterocyclic systems are important structures in organic chemistry because of their presence in many biologically active compounds. In this work, a Lewis acid-catalyzed cyclization of ethenetricarboxylate derivatives 1 with substituted propargyl alcohols to give methylenetetrahydrofurans was investigated. Reaction of 1 and γ-silicon-substituted propargyl alcohols 4 with ZnBr2 at 80−110 °C led to (Z)-silicon-substituted products stereoselectively. Reaction of 1 and γ-ester-substituted propargyl alcohol 7 in the presence of various Lewis acids gave ester-substituted methylenetetrahydrofurans stereoselectively. Interesting Lewis acid dependency on stereoselectivity for the reaction of 7 was found. Reaction of α-substituted propargyl alcohols also gave cyclized products.

Lewis acid-catalyzed cyclization of various 2-(N-arylcarbamoyl)-methylenemalonates to give nitrogen-containing benzo-annelated heterocycles was investigated in terms of selectivity. Reaction of substrates with various alkyl groups on nitrogen proceeded to give oxindole derivatives. Cyclization reaction of diester-amides of MeO and halogen-substituted anilines in the presence of catalytic Lewis acid (ZnCl 2 , SnCl 4 , AlCl 3 , Zn(OTf) 2 , Sc(OTf) 3 , etc.) gave oxindoles in high yields. Interesting regioselectivity was observed for metahalogen substrates. Dimethoxyisoquinoline analogs were also obtained by this reaction using a catalytic Lewis acid.

A novel cyclization reaction of ethenetricarboxylate derivative aromatic compounds in the presence of various Lewis acids gave benzo-annulated cyclic compounds such as oxindole and benzofuran derivatives via Friedel–Crafts intramolecular Michael addition in high yields. For example, the reaction of diethyl 2-[(N-methyl-N-phenylcarbamoyl)methylene]malonate (1a) in the presence of ZnCl2 at room temperature gave diethyl 2-(1-methyl-2-oxoindolin-3-yl)malonate (2a) in 98% yield. The reactions also proceeded with a catalytic amount of a Lewis acid such as AlCl3, ZnCl2, ZnBr2, Sc(OTf)3, or InBr3.

Lewis acid and substituent dependency on the regioselectivity of hydrosilylation of propiolate esters 1a-c with tris(trimethylsilyl)silane (2a) was found. The reaction of methyl and ethyl propiolate esters and 2a without Lewis acid and in the presence of EtAlCl2 and Et2AlCl gave beta-silicon-substituted Z-alkenes 3 selectively. On the other hand, reaction in the presence of AlCl3 in dichloromethane gave alpha-silicon-substituted alkenes 4. In the case of trifluoroethyl propiolate ester 1c, reaction with aluminum chloride-based Lewis acids gave alpha-silicon-substituted alkenes 4 exclusively. Two competitive mechanisms, free-radical and ionic, are proposed as the source of the complementary regioselectivity displayed in these reactions. A transition state of the radical-forming step was obtained computationally. The reaction of various reactive acetylene substrates and 2a without Lewis acid and without solvent at room temperature gave beta-silicon-substituted Z-alkenes 3 selectively.

Lewis acid-promoted cyclizations of heteroatom-substituted enynes have been examined. The reaction of enynes 3 and 7 bearing silicon substituents on an alkyne afforded the halogenated five-membered γ-lactones 4 and γ-lactams 8 as the main products. The reaction of substrates 15 and 16 having 2-phosphonoacrylate instead of malonate also gave halogenated five-membered cyclic compounds 17 and 18 as the major products. The cyclized products are highly substituted and potentially useful for further synthetic transformations.

Lewis acid-promoted cyclizations of heteroatom-substituted enynes have been examined. The reaction of enynes 3 and 7 bearing silicon substituents on an alkyne afforded the halogenated five-membered γ-lactones 4 and γ-lactams 8 as the main products. The reaction of substrates 15 and 16 having 2-phosphonoacrylate instead of malonate also gave halogenated five-membered cyclic compounds 17 and 18 as the major products. The cyclized products are highly substituted and potentially useful for further synthetic transformations.

Reactions of enynes with three or two ester groups (1-4) in the presence of halogen-ligand Lewis acids gave cyclized products with halide incorporation (5-8) with high generality. The cyclization process was also analyzed in a theoretical study. Facile isomerization and dehydrohalogenation of five-membered products 5 and 8 by Al(2)O(3) or Et(3)N were also observed; this process introduces conjugated moieties into the products.

Stereoselective SnCl(4)-promoted [2 + 1] cycloaddition reactions of 1-seleno-2-silylethene 1 with 2-phosphonoacrylates 2 lead to highly functionalized cyclopropanephosphonate esters 3 in high yields. The cyclopropane products 3 are potentially versatile starting materials for biologically important compounds. Stereoselective synthesis of a novel functionalized alpha-aminophosphonic acid derivative, an analogue of (Z)-2,3-methanohomoserine 13, from the cycloadduct 3b was achieved. Stereoselectivity in the [2 + 1] cycloaddition was explained by consideration of the structure of the 2-SnCl(4) complex.

A novel cycloisomerization reaction of enynes 4 in the presence of ZnBr2 and THF (1 eq.) in CH2Cl2 at −40 °C gave exo-methylenic 1,3-dienes 5 in moderate to good yield.

The reactions of 1-seleno-2-silylethenes 1 with highly electrophilic tricarbonyl-substitued olefins in the presence of Lewis acids have been investigated. The reaction of 1-(phenylseleno)-2-(trimethylsilyl)ethene (1a) with tris(alkoxycarbonyl) olefins 2 or 1,1-bis(alkoxycarbonyl)-2-acyl olefins 3 in the presence of ZnBr(2) at -30 degrees C gave cis-substituted cyclopropanes exclusively. The origin of the cis stereochemistry is ascribed to the synclinal addition path of the ZnBr(2)-coordinated electrophilic olefin to 1. Application of the highly functionalized selenium- and silicon-substituted cyclopropane products to the preparation of a useful synthetic intermediate 20 for the pyrethroid class of insecticides is also demonstrated.

A novel cycloisomerization reaction of enynes 4 in the presence of ZnBr2 and THF (1 eq.) in CH2Cl2 at −40 °C gave exo-methylenic 1,3-dienes 5 in moderate to good yield.

Lewis acid-catalyzed cyclization of various 2-(N-arylcarbamoyl)-methylenemalonates to give nitrogen-containing benzo-annelated heterocycles was investigated in terms of selectivity. Reaction of substrates with various alkyl groups on nitrogen proceeded to give oxindole derivatives. Cyclization reaction of diester-amides of MeO and halogen-substituted anilines in the presence of catalytic Lewis acid (ZnCl 2 , SnCl 4 , AlCl 3 , Zn(OTf) 2 , Sc(OTf) 3 , etc.) gave oxindoles in high yields. Interesting regioselectivity was observed for metahalogen substrates. Dimethoxyisoquinoline analogs were also obtained by this reaction using a catalytic Lewis acid.