Acid-catalyzed intramolecular ring-opening reactions of cyclopropanated oxabenzonorbornadienes with alcohol nucleophiles

An investigation of intramolecular ring-opening reactions of various cyclopropanated oxabenzonorbornadienes (CPOBDs) with alcohol nucleophiles is reported, which forms two regioisomeric products in good yields. The effect of various tether lengths was explored, wherein increasing the alcohol tether length to 4 or 5 carbons exclusively generated Type 3 products in good yield, while C-1-hydroxymethyl substituted CPOBD formed a 1,3,5-cycloheptatriene derivative in excellent yield. Electron donating arene and electron withdrawing C-5-bridgehead substituents formed Type 3 major products, whereas electron withdrawing arenes and electron donating C-5 substituents preferentially afforded Type 2 compounds. A mechanism is also proposed for the formation of both regioisomeric products.     

Tricyclic-isoxazolidine analogues via intramolecular 1,3-dipolar cycloaddition reactions of nitrones

The tricyclic-isoxazolidine analogues tetrahydrothiochromenoisoxazoles, hexahydroisoxazolequinolines and tetrahydroisoxazolepyranopyridines were prepared by an intramolecular 1,3-dipolar cycloaddition reaction of a nitrone with an alkene. For N-alkylated hexahydroisoxazolequinolines, reduction of the reaction time from two days to 40 min was achieved using microwave heating. The cyclization to form tetrahydroisoxazolepyranopyridines only proceeded when the alkene was substituted with an electron withdrawing group.     

Reactions of carbamyl radicals: intramolecular hydrogen abstraction reactions

ω-Phenylalkyl-N-methylcarbarnyl radicals undergo intermolecular addition to 3,3-dinethylbut-l-ene in preference to intramolecular hydrogen abstraction. Methyl N-(ω-phenylalkyl) carbanyl radicals and methyl N-pentylcarbamyi radicals readily abstract hydrogen through a six membered transition state or a seven membered transition state if the hydrogen is beniylic. The selectivities are interpreted in terms of the electrophilicity of the radical and the stereo-electronic requirements of hydrogen abstraction reactions.     

Reactivity of pseudobases from pyridinium salts competition between hydrogen transfer and ring-opening reactions

The reactions of 3-cyano-1-methylpyridinium iodide (1a) and l-benzyl-3-cyanopyridinium chloride (1b) in aqueous NaOH have been studied over a range of concentrations from N 0.5 to N 2.5 with respect to the hydroxide ion, and with the concentrations of the reactants at different ratios. It has been found that the intermediate, not isolable pseudobases can undergo, depending on the experimental conditions, two competitive reaction channels, namely, a redox process leading to the dihydropyridines 3–5 and pyridones 2,6, and a ring-opening reaction leading to the pentadienenitrile 7, 2-imino-3-pyridinecarbaldehyde 8, and 2-(aryl)alkylamino-3-pyridinecarbaldehyde 9.     

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.     

Electron impact induced intramolecular hydrogen transfer reactions in polymethylene glycol di-p-toluenesulfonates

The mechanisms of formation of the ionized acid and the protonated acid fragments in the electron impact induced fragmentation of the title compounds were investigated. The well known mechanisms of hydrogen transfer through mono- and bicyclic transition states that occur in the molecular ions of carboxylic esters are not the main pathways giving rise to these fragments. The major component of the m/z 172 peak corresponding formally to ionized p-toluenesulfonic acid in fact has a different structure; its formation involves a complex mechanism including a double hydrogen transfer reaction.     

Selective ring-opening reactions of

The reactivity of strained [1]ferrocenophanes, [Fe(eta-C5H4)2ERx] (ERx = SiMe2, 1a: SiMePh, 1b; SnR2, 1c), towards boron halides has been investigated and has been shown to provide a facile pathway to ferrocene derivatives functionalized with Lewis acidic boron centers. The boron halides RBX2 (R = Cl, Ph, fc; X = Cl, Br) (fc = Fe(eta-C5H4)2) lead to selective cleavage of the Si-Cp bonds in 1a and 1b to give, depending on the reaction stoichiometry, functionalized mono- or diferrocenylboranes RnB [(eta-C5H4)Fe(eta-C5H4SiMe2Cl)](3-n) (2a: R = Cl, n = 2; 2b: R = Cl, n = 1; 2c: R = Ph, n = 1) and RnB[(eta-C5H4)Fe(eta-C5H4SiMePhCl)](3-n) (2d: R = Cl, n = 2) in high yields. Compounds 2a-d were characterized by multinuclear NMR spectroscopy, mass spectrometry, and by single-crystal X-ray diffraction (for 2b). Most likely due to steric constraints, a triferrocenylborane was not obtained even from the reaction of BCl3 with an excess of 1a, whereas facile formation of the diferrocenylphenylborane 2c from PhBCl2 and two equivalents of 1a was observed. Selective hydrolysis of the B-Cl bonds of chlorodiferrocenylborane 2b in the presence of trace amounts of water led to the silylated tetranuclear ferrocene complex [(ClMe2Sifc)2B-O-B(fcSiMe2Cl)2] (3) without cleavage of the Si-Cl bonds. The structure of 3 was confirmed by an X-ray diffraction study. Studies of the reactivity of the higher Group 14 homologue of 1a and 1b, the tin-bridged [1]ferrocenophane 1c, revealed that facile addition of B-Cl bonds occurs across the Sn-Cp bonds to yield the 1-stannyl-1'-borylferrocenes [(ClMes2Sn)fc(BClR)] (4a: R = Cl; 4b: R = Ph; Mes = 2,4,6-Me3C6H2). The new synthetic methodology can be extended to bifunctional Lewis acids such as the bis(boryl)ferrocene 1,1'-fc(BBr2)2, which affords the linear boron-bridged ferrocene trimer 1,1'-[fc[B(Br)fcSiMe2Br]2] 5 in 54% isolated yield. In order to incorporate the functionalized ferrocenylboranes into polymer structures, compound 2c was reduced with Li[BEt3H] to give the silicon-hydride functionalized species [PhB[(eta-C5H4)Fe(eta-C5H4SiMe2H)]2] (6), which was then used as a capping reagent in the transition metal catalyzed polymerization of 1a. This process leads to the incorporation of the ferrocenylborane unit into the main chain of a poly(ferrocenylsilane) to afford [PhB-[(fcSiMe2)(n-1)fcSiMe2H]2] (7).     

The role of intramolecular hydrogen bonds in nucleophilic addition reactions of ketenaminals

Quantum-chemical calculations of the geometries and electronic structures of molecules of ketenaminals 3-(diaminomethylene)-2,4-pentanedione and dimethyl-2-(diaminomethylene)-malonate and calculations of the structures of intermediates in the reaction of the nucleophilic addition of the ketenaminals to the acetonitrile molecule are performed by B3LYP/6-31+G** method. Two possible scenarios of the process are shown, depending on the mutual orientation of reacting molecules. The nucleophilic addition proceeds in two stages. It is found that the rate-limiting stage of the process is the transfer of the proton of the intramolecular hydrogen bond in a ketenaminal molecule. The experimentally observed faster reaction of pyrimidine formation for the 3-(diaminomethylene)-2,4-pentanedione molecule relative to that for dimethyl-2-(diaminomethylene)-malonate is explained by the hydrogen bond being stronger and the barrier of proton transfer from the aminogroup to the ketogroup oxygen falling upon nucleophilic attack in the former molecule.     

Quantum chemical investigation of low-temperature intramolecular hydrogen transfer reactions of hydrocarbons

The B3LYP functional was evaluated as a method to calculate reaction barriers and structure-reactivity relationships for intramolecular hydrogen transfer reactions involving peroxy radicals. Nine different basis sets as well as five other MO/DFT and hybrid methods were used in comparing three reactions to available experimental data. It was shown that B3LYP/6-311+G(d,p) offers a good compromise between speed and accuracy for studies in which thermodynamic and kinetic data of many reactions are required. Sixteen reactions were studied to develop structure-reactivity relationships to correlate the activation energy with the heat of reaction. As long as no structural heterogeneities were present in the transition state ring, a simple Evans-Polanyí relationship was shown to capture the activation energy as a function of heat of reaction for reactions in the 1,5-hydrogen shift family. For peroxy radicals undergoing self-abstraction of a hydrogen atom in the 1,5-position, the activation energy was calculated as E(a) (kcal mol(-1)) = 6.3 + Delta H(rxn) (kcal mol(-1)). For reactions with a carbonyl group embedded in the ring of the transition state, the activation energy of peroxy radicals undergoing self-abstraction was correlated as E(a) (kcal mol(-1)) = 18.1 + 0.74 Delta H(rxn) (kcal mol(-1)). The impact of the size of the transition state ring on the activation energy and pre-exponential factor was also probed, and it was shown that these effects can be described using simple nonlinear and linear fits, respectively.     

Lewis acid catalyzed ring-opening reactions of methylenecyclopropanes with diphenylphosphine oxide in the presence of sulfur or selenium

Methylenecyclopropanes undergo an interesting Lewis acid-catalyzed ring-opening reaction with diphenylphosphine oxide in the presence of sulfur or selenium upon heating at 85 degrees C in 1,2-dichloroethane to give the corresponding homoallylic thiol or selenol derivatives in good to high yields.     

A practical synthetic route to functionalized THBCs and oxygenated analogues via intramolecular Friedel-Crafts reactions

A practical catalytic approach to the synthesis of 4-substituted 1,2,3,4-tetrahydro-beta-carbolines (THBCs, 1) and 1,2,3,9-tetrahydropyrano[3,4-b]indoles (2) via InBr3-catalyzed intramolecular Friedel-Crafts (F-C) cyclization is described. The use of cross-metathesis reaction represents a direct route to the cyclization precursors and the use of InBr3 (5 mol%) allowed polycyclic indole compounds to be isolated in high yields under mild reaction conditions (rt, DCM, minutes). Finally, efforts toward the development of a stereocontrolled version of the present cyclization are presented, highlighting [salenAlCl] and bimetallic [(salenAlCl)2-InBr3] system as promising chiral Lewis acids (ee up to 60%).     

Tunnel effects on inter- and intramolecular hydrogen transfer reactions of transient dihydro- and hexahydrocarbazoles

We examine inter- and intramolecular hydrogen-transfer processes in two related metastable dihydrocarbazoles in nonpolar solvents of different viscosity and compare them with similar transfer processes in transient hexahydrocarbazoles. N-ethyldiphenylamine (A′) and N-ethyl-2,6-dimethyldiphenylamine (A) photocyclize in their triplet states, yielding the triplet states of the zwitterionic dihydrocarbazoles ³Z′* and ³Z*, respectively, which subsequently relax to their metastable singlet ground states ¹Z′ and ¹Z′. In spite of their similarity, the two transients ¹Z′ and ¹Z stabilize by completely different pathways: the unsubstituted transient ¹Z′ is converted into N-ethylcarbazole (C) and an N-ethyltetrahydrocarbazole (THC) by a bimolecular disproportionation reaction. The methylsubstituted intermediate ¹Z is converted into a stable dihydrocarbazole (D) by a sigmatropic, intramolecular [1,8]-H-shift and by an intermolecular, mutual hydrogen-exchange reaction within the encounter complex ¹(ZZ) which yields two molecules of D. The rates of the intra- and of the intermolecular transfer reaction of ¹Z are governed by tunnel effects. The rate of the intramolecular tunnel process does not depend on solvent friction and becomes temperature independent at low temperatures. The rate of the intermolecular, reaction-controlled exchange reaction ¹(ZZ) → 2 ¹D becomes also temperature independent if the solvent is fluid enough. In more viscous solvents the reaction becomes diffusion controlled and, therefore, strongly temperature dependent. The intermolecular disproportionation reaction 2 ¹Z′ → C + THC is also reaction controlled but no tunnel effects are observed.     

Isomerization of n-hexyl and s-octyl radicals by 1,5 and 1,4 intramolecular hydrogen atom transfer reactions

n-Hexyl and s-octyl radical isomerizations by intramolecular hydrogen atom shift have been studied in the presence of high methyl radical concentration where isomerized alkyl radicals reacted predominantly by combination and disproportionation reactions with methyl radicals. By assuming the rate coefficient of 1-hexyl radical recombination to be equal to that of ethyl self-combination, the rate coefficient of log(k₁/s^?1) = (9.5 ± 0.3) – (11.6 ± 0.3) kcal mol^?1/RT ln 10 has been derived for the 6sp isomerization of n-hexyl radicals, 1-hexyl → 2-hexyl (1). Investigation of s-octyl radical isomerization was complicated by fast interconversion between 3-octyl, 2-octyl, and 4-octyl radicals. Use of the methyl trapping technique and systematic variation of methyl radical concentration made possible the determination of log(k₂/s^?1) = (9.4 ± 0.7) ? (11.2 ± 1.0) kcal mol^?1/RT ln 10 for the 6ss isomerization of 3-octyl and the estimation of log(k₃/s^?1) = 10.5–17 kcal mol^?1/RT ln 10 for the 5ss isomerization of 2-octyl radicals, where 3-octyl → 2-octyl (2), and 2-octyl → 4-octyl (3).     

Photochemical intramolecular nitrene insertion of 6-azidouridine derivatives

A highly efficient intramolecular nitrene insertion was observed upon irradiation of 6-azidouridine derivatives. The N⁶,2′-cyclo structure of the product was determined unequivocally by X-ray crystallography.     

Photochemical reactions of 7-aminocoumarins

The photochemical reactions of 4-methyl-7-diethylaminocoumarin with the dimethyl ester of acetylenedicarboxylic acid, diethyl ester of maleic acid, and N-phenylmaleimide in the presence of oxygen and acetophenone give products of the heterocyclization at C(₆) and C(₈) of coumarin fragment with participation of the diethylamino group. The stereochemical structure of the compounds synthesized was demonstrated using PMR spectroscopy. A mechanism was proposed for this reaction involving the formation of an -amino radical and its addition to the acetylene or olefin, accompanied by attack on the aromatic ring with subsequent aromatization.See [1] for Communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 30–36, January, 1989.