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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.

The title reaction was investigated by the use of ONIOM-RB3LYP calculations. A reaction system composed of alpha-chlorocyclohexanone, a methoxide ion and 8 MeOH solvent molecules was adopted. Two reaction channels, the semibenzilic acid mechanism (A) and cyclopropanone mechanism (B), were compared. B is found to be more favorable than A. The rate-determining step of B is the (MeOH)(3) addition transition state (TS3B) to the cyclopropanone intermediate. While TS3B involves a concerted function of MeO(-) addition and proton relays, it has a large activation energy. A new route was found, where the chloride ion evolved at the cyclopropane formation step (TS2B) works as a nucleophile to the cyclopropanone intermediate. Thus, a cyclopentane-carbonyl chloride intermediate is formed with a small activation energy. A new cyclopropanone mechanism is proposed.

1 Introduction 2 Experimental Background 3 Calculations of Grignard Reagents 4 Calculations of Model Grignard Reactions 5 A Comprehensive Computational Study of Grignard Reactions Keywords: Grignard reagent and Grignard reaction path geometries ; GAUSSIAN software of computational organic chemistry; RMgX addition to carbonyl compounds; Grignard reagent calculation; Intrinsic Reaction Coordinate (IRC); Grignard reaction by ab initio SCF MO theory; R1MgX dimer in Schlenk equilibrium and carbonyl group reactivity; polar four-center reaction and C–C bond formation

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.

Reaction of (Z)-2,3-bis(2-lithiophenyl)-2-butene (10) with selenium gave 12,13-dimethyldibenzo [d,h]-1,2,3-triselenonine (3) rather than either 11,12-dimethyldibenzo [c,g]-1,2-diselenocine (2) or 13,14-dimethyldibenzo [e,i]-1,2,3,4-tetraselenecine (4). Thermolysis and photolysis of 3 gave 5a,10a-dihydro-5a,10a-dimethyldibenzo-[b,f] seleno [3,2-b] selenophene (12) via extrusion of a selenium atom and a novel intramolecular addition of arylselenyls to a double bond. Ab initio molecular orbital calculations and X-ray structural analyses are made to elucidate the reaction mechanism

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.

The mechanism of stereoselective addition of Grignard reagents to carbonyl compounds has been investigated using B3LYP density functional theory calculations. The study of the reaction of methylmagnesium chloride and formaldehyde in dimethyl ether revealed a new reaction path involving carbonyl compound coordination to magnesium atoms in a dimeric Grignard reagent. The structure of the transition state for the addition step shows that an interaction between a vicinal-magnesium bonding alkyl group and C=O causes the C-C bond formation. The simplified mechanism shown by this model is in accord with the aggregation nature of Grignard reagents and their high reactivities toward carbonyl compounds. Concerted and four-centered formation of strong O-Mg and C-C bonds was suggested as a polar mechanism. When the alkyl group is bulky, C-C bond formation is blocked and the Mg-O bond formation takes precedence. A diradical is formed with the odd spins localized on the alkyl group and carbonyl moiety. Diradical formation and its recombination were suggested to be a single electron transfer (SET) process. The criteria for the concerted polar and stepwise SET processes were discussed in terms of precursor geometries and relative energies.

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.

The reaction of (E)-1-(phenylseleno)-2-(trimethylsilyl)ethene (1) and vinyl ketones 2a-d in the presence of a chiral Lewis acid prepared from TiCl(4), Ti(O(i)Pr)(4), (R)- or (S)-1,1'-binaphthol (BINOL), and MS4A gave enantiomerically enriched cis cyclopropane products 3a-d. The enantiomeric excess and chemical yield varied depending on the ratio of TiCl(4) and Ti(O(i)Pr)(4) to 1. Reproducible results (43-47% ee/33-41% yields) for cis-1-acetyl-2-[(phenylseleno)(trimethylsilyl)methyl]cyclopropane (3a) were obtained using 1.1 equiv of TiCl(4), 0.54-0.65 equiv of Ti(O(i)Pr)(4), and 1.65 equiv of BINOL. The observed enantioselectivity was explained by consideration of the structure of the postulated intermediates, alkoxy titanium-carbonyl complexes, via ab initio MO calculations.

Reaction of the Huisgen zwitterions, derived from triphenylphosphine and azodicarboxylates with activated alkenes has been studied. The reaction of various ethenetricarboxylates and diethyl azodicarboxylate with PPh3 gave pyrazolines efficiently. This pyrazoline synthesis is also applicable to 2-substituted acrylates such as trimethyl 2-phosphonoacrylate and methyl 2-(trifluoromethyl)acrylate. The possible reaction mechanism was discussed in comparison with the reaction of acetylenedicarboxylate and Huisgen zwitterions. The selective transformation of pyrazoline products have also been performed.

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 Cannizzaro reaction ("RX C") and the benzoin reaction ("RX B") were investigated by density functional theory calculations. Reaction models (benzaldehyde)2 + X(-) + (H2O)n [for X(-) = OH(-) (RX C) n = 8, and for X(-) = CN(-) (RX B) n = 8 or n = 14] were adopted. Three transition states (TSs) were obtained for RX C, and the rate-determining step was confirmed to be the hydride shift. The single electron transfer path was also obtained, which is supported by the C-O(-)CH[double bond, length as m-dash]O attraction. In RX B, seven TSs were obtained. The CC bond formation TS, TS4(B), was found to be the rate-determining step. However, the carbanion-formation TS (TS3(B)) and the CN(-) release TS (TS7(B)) are also of large activation free energies (DeltaG(double dagger)s). The result DeltaG(double dagger)(TS4(B))or = DeltaG(double dagger)(TS7(B)) approximately DeltaG(double dagger)(TS3(B)) was obtained with both n = 8 and n = 14 models. Proton relays along the linear hydrogen bonds are concerned with bond interchanges and promote well arranged and successive elementary processes in RXs C and B.

By the use of DFT calculations, the title rearrangement, Ph-NH-NH-Ph () --> H(2)N-C(6)H(4)-C(6)H(4)-NH(2) (2), was studied for the first time. Although it is a classical reaction (found in 1862), its mechanism is almost entirely unknown. There are three complexities associated with this mechanism. The first is the various rate orders for substituted hydrazobenzenes. The second is the product distribution. The third is the result of the kinetic isotope effect which is difficult to interpret. A reaction model, , (H(3)O(+))(2) and (H(2)O)(10) was used to trace the reaction path. Two hydronium ions were included, because there are two nitrogen atoms in . In the paths of the main reaction, (H(+))(2)-->H(+) + H(+), transient intermediates were found. Through their conversion, the second product, diphenyline (), was reached. For H(+), only the Claisen shift path was found, and the pi complex proposed by Dewar was not found. The absence is in accord with the kinetic result of Hammond and Shine. But the complex was revealed in the dimethoxyhydrazobenzene. Thus, while Dewar's pi complex was ruled out in 1950, it has been revived by the present calculations.

Reaction of (Z)-2,3-bis(2-lithiophenyl)-2-butene (10) with selenium gave 12,13-dimethyldibenzo [d,h]-1,2,3-triselenonine (3) rather than either 11,12-dimethyldibenzo [c,g]-1,2-diselenocine (2) or 13,14-dimethyldibenzo [e,i]-1,2,3,4-tetraselenecine (4). Thermolysis and photolysis of 3 gave 5a,10a-dihydro-5a,10a-dimethyldibenzo-[b,f] seleno [3,2-b] selenophene (12) via extrusion of a selenium atom and a novel intramolecular addition of arylselenyls to a double bond. Ab initio molecular orbital calculations and X-ray structural analyses are made to elucidate the reaction mechanism

A new Si surface modification with organic groups via hydrosilylation at room temperature is reported. A hydrogen-terminated Si (111) surface was reacted with activated alkynes such as propiolate esters, propiolic acid, but-3-yne-2-one, propiolonitrile and phenylacetylene at room temperature for 24–40 h to give modified surfaces. The coverage ratio was estimated to be 31–56% by XPS analysis. This surface modification method is mild, highly efficient and procedurally simple. The novel surfaces modified with various organic functional groups are expected to have interesting utilities.

Selected chemical transformations of a monocyclic thiepine 2,7-di-tert-butylthiepine 1 have been examined. Oxidation of the thiepine 1 gave the unstable thiepine 1-oxide 3, although further oxidation to form the thiepine 1,1-dioxide 4 did not proceed whilst S-methylation with methyl iodide–silver tetrafluoroborate gave rearranged aromatized compounds. In these electrophilic reactions at sulfur, the steric repulsion by two tert-butyl groups possibly causes the formation of the endo-sulfur coordinated species. Bromination gave either the ring-contracted thiophene 12, or the thiopyran 17, depending on the reaction conditions. The cycloaddition with tetracyanoethylene (TCNE) gave the [4 + 2] adduct 22.

Various 4- and 4,5-substituted 2,7-di-tert-butylthiepins such as 4-ethoxycarbonyl-(6), 4-formyl- (7), 4-hydroxymethyl- (8), 4-methyl- (12), 4-methy1-5-hydroxymethy1-(13), and 4,5-dimethyl derivatives (16), and so on, were synthesized by functional group transformation and some of their properties were examined.

Transformation de phenyl-5 styryl-2 isothiazoline-4thione-3 en β-methylthiostyryl-2 phenyl-5 thiazole sous l'action de Me 3 O•BF 4 . Etude RX du β-mesylstyryl-2 phenyl-5 thiazole. Mecanismes