Synthesis of perfluorobicyclic ethers [2]. The electrochemical fluorination of α-cyclohexenyl-substituted carboxylic acid derivatives

The electrochemical fluorination of α-cyclohexenyl-substituted carboxylic esters [

; R′CH₃, C₂H₅, C₃H₇)] afforded both perfluoro(9-alkyl-7-oxa-bicyclo[4.3.0]nonane)s and perfluoro(8-alkoxy-9-alkyl-7-oxabicyclo[4.3.0]nonane)s in fairly good yields. As the driving force for the ring-closure in this fluorination, a mechanism which involves a resonance stabilized intermediate radical is proposed. Perfluoro(8-chloro-8-methoxy-9-ethyl-7-oxabicyclo[4.3.0]nonane) and perfluoro(8,8-dichloro-9-ethyl-7-oxabicyclo[4.3.0]nonane) were obtained by the controlled chlorination of perfluoro(8-methoxy-9-ethyl-7-oxabicyclo[4.3.0]nonane) with anhydrous aluminum chloride in low yields. Some new fused perfluorobicyclic ethers and a perfluoroacid fluoride obtained in this experiment have been characterized by infrared, mass and ¹⁹F nmr spectra and elemental analysis.     

Thermolytic transformations of polyfluoroorganic compounds

The reaction of α,α-dichlorooctafluoroethylbenzene with tetrafluoroethylene as a source of difluorocarbene has been studied. The copyrolysis of these compounds gave not only the expected products, decafluoro-α-methylstyrene and α-chloroheptafluorostyrene, but also noticeable amounts of perfluoro-1-methylindan and perfluoro-7-methylbicyclo[4.3.0]nona-1,4,6-triene along with perfluoro-3-methylindene and octafluorostyrene. It has been suggested that indan and the triene are formed with the participation of the C₆F₅CCICF₃ radical through sigmatropic shifts of fluorine atoms in the intermediate bicyclic compounds. The reaction of α,α-dichlorodecafluoropropylbenzene with tetrafluoroethylene afforded α-chloroheptafluorostyrene as the main product.     

Scope and applications of second generation palladium-catalyzed cycloalkenylation. Stereoselective total syntheses of isoiridomyrmecin, isodihydronepetalactone, and α-skytanthine

Functionalized bicyclo[3.2.1]octanes, -oxabicyclo-[4.3.0]nonanes, 3-azabicyclo[3.3.0]octanes, and 3-azabicyclo[4.3.0]nonanes were easily synthesized via a second generation palladium-catalyzed cycloalkenylation. Isoiridomyrmecin and isodihydronepetalactone, both of which feature a 3-oxabicyclo[4.3.0]nonane subunit, were stereoselectively synthesized via a second generation palladium-catalyzed cycloalkenylation as the key step. α-Skytanthine, a typical 3-azabicyclo[4.3.0]nonane alkaloid, was also constructed using the same catalytic cyclization protocol.     

Hydroxy lactones with the gem-dimethylcyclohexane system – Synthesis and antimicrobial activity

Two new lactones comprising the gem-dimethylcyclohexane ring: 2-chloro-5,5-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one and 2-bromo-5,5-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one as well as the already known 2-iodo-5,5-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one, were obtained from (6,6-dimethylcyclohex-2-en-1-yl)acetic acid. These lactones were used as substrates for the screening of biotransformation by whole cells of nine fungal strains (Fusarium species, Syncephalastrum racemosum and Cunninghamella japonica). Some of these microorganisms (mainly Fusarium species) transformed all three lactones during the hydrolytic dehalogenation into 2-hydroxy-5,5-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one. It is worth noting that two microorganisms (Fusarium culmorum and Fusarium scirpi) converted iodolactone with very high enantioselectivity (75.1% and 91.6%, respectively). The (+) isomer of hydroxy lactone was preferred. At the last step the hydroxy lactone obtained during biotransformation was examined for its biological activity against bacteria, yeasts and fungi. It was found that this compound inhibits growth of some tested microorganisms.     

Synthesis of key intermediates for a concise and convergent approach to the marine natural product eleutherobin

Synthesis of 1,6-syn-5,6-anti-2-methyl-5-isopropyl-bicyclo[4.3.0]-non-2-en-8-one in three steps from (rac)-phellandrene; and 1,6-syn-1-methyl-6-methoxy-3-aza-9-oxabicyclo[4.2.1]-non-7-en-4-one in five steps from 2-methoxy-5-methylfuran and tetrabromoacetone, provided these key intermediates for the construction of the skeleton of eleutherobin.     

Stereocontrolled transformation of nitrohexofuranoses into cyclopentylamines via 2-oxabicyclo[2.2.1]heptanes. Part 6: synthesis and incorporation into peptides of the first reported 2,3-dihydroxycyclopentanecarboxylic acid

Herein we report the intramolecular alkylation of nitronates of methyl-5-O-benzyl-3,6-deoxy-6-nitro-β-d-glucofuranoside and methyl-5-O-benzyl-3,6-deoxy-6-nitro-α-d-glucofuranoside into the corresponding 2-oxabicyclo[2.2.1]heptane derivatives. Similarly, methyl-3-O-benzyl-5-deoxy-5-nitromethyl-β-d-xylofuranoside and methyl-3-O-benzyl-5-deoxy-5-nitromethyl-α-d-xylofuranoside were cyclized to (1R,3R,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane and (1R,3S,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane, respectively. These 2-oxabicyclo[2.2.1]heptane derivatives were eventually transformed into enantiopure methyl (1S,2S,3R,4S,5R)-2-amino-2,3-dihydroxycyclopentanecarboxylate and this novel β-amino acid was incorporated into peptides.     

Copper(I)- and Copper(II)-catalyzed Diels-Alder Additions of α-Substituted Acrylonitrile to Furan. The Synthesis of 7-Oxa-bicyclo[2.2.1]hept-5-en-2-one

The difficult Diels-Alder additions of α-acetoxy- and α-chloroacrylonitrile to furan can be run at 20–35° and atmospheric pressure in the presence of CuCl. Cu(BF₄) · 6 H₂O, Cu(OOCCH₃)₂ · H₂O or cupric tartrate · 3H₂O. Under kinetic control, the exo-carbonitrile adducts 2 and 8 , respectively, are favoured. Saponification of the 2endo-acetoxy-7-oxabicyclo[2.2.1]hept-5-ene-2exo-carbonitrile ( 2 ) furnished the 7-oxabicyclo[2.2.1]hept-5-en-2-one ( 4 ). Basic hydrolysis of the adducts ( 8 + 9 ) of α-chloroacrylonitrile to furan and its 5exo, 6exo-isopropylidenedioxy derivatives did not give the corresponding ketones, the carboxamides 14 + 15 and 16 + 17 , respectively, were isolated.     

Substituierte 9-Oxabicyclo[4.2.1]- und 9-Oxabicyclo[3.3.1]nonane IV. endo,endo-2,5-Dihydroxy-9-oxabicyclo[4.2.1]nonan,endo, endo-, endo,exo- und exo,exo-2,6-Dihydroxy sowie endo,exo-2,7-Dihydroxy-9-oxabicyclo[3.3.1]nonan; Darstellung und Umwandlungsprodukte

The synthesis of the following compounds and reaction products thereof are described: endo, endo-2,5-dihydroxy-9-oxabicyclo[4.2.1]nonane ( 3–5 ), epimeric 2,6-dihydroxy-9-oxabicyclo[3.3.1]nonanes (endo, endo: 6–8 , exo, exo: 29–32 , and endo, exo: 43–45 ), and endo, exo 2,7-dihydroxy-9-oxabicyclo[3.3.1]nonane ( 46–50 ).     

Stereoselective synthesis of cyclic ethers via bromine assistedepoxide ring expansion

9-Oxabicyclo[6.1.O]non-4-ene reacts with bromine to give stereoselectively trans, trans-2,6-dibromo-9-oxabicyclo[3.3.1]nonane and trans, trans-2,5-dibromo-9-oxabicyclo[4.2.1]nonane.     

Pentafluorophenylation of Perfluorinated Benzocyclobutene,Indan, and Tetralin by Reaction with Pentafluorobenzene in SbF5

The reactivity of perfluorinated benzocyclobutene, indan, and tetralin in reaction with pentafluorobenzene in SbF₅ medium, and also the relative stability of generated therewith perfluoro-1-phenylbenzocycloalkenyl cations decrease with increasing alicyclic fragment in the benzocycloalkene. Treating the solutions of salts of the above cations with anhydrous HF results in the corresponding perfluoro-1-phenylbenzocycloalkenes, and the hydrolysis of salts furnishes their 1-hydroxy derivatives. In a reaction of 1-hydroxyperfluoro-1-phenylbenzocyclobutene, -indan, and -tetralin with SOCl₂ the hydroxy group is replaced by chlorine. Besides with indan and tetralin derivatives form respectively 7-pentafluorophenyloctafluoro-3-chlorobicyclo[4.3.0]hepta-1,4,6-triene and 7-pentafluorophenyldecafluoro-3-chlorobicyclo[4.4.0]octa-1,4,6-triene.     

Bifurcate, tandem ATRC reactions: towards 2-oxabicyclo[4.3.0]nonane core of eunicellins

Bifurcate, tandem ATRC reactions provide rapid access to 2-oxabicyclo[4.3.0]nonane ring system present in terpenes such as eunicellin.     

Conformational analysis of 7-alkyl-3-oxabicyclo-[3.3.1]nonanes and complexes with lanthanide shift reagents

The conformation of 3-oxabicyclo[3,3.1]nonane and of some of its 7α- and 7β-alkyl substituted derivatives has been studied with the use of ¹³C and ¹H NMR spectroscopy. A comparison is made with the carbocyclic analogues; it turns out that the replacement of the 3-methylene group by oxygen has no substantial influence on the conformational preferences. With the aid of ³J_HH coupling constants it is shown that the geometry of the cyclohexane rings is about the same as in the corresponding carbocyclic compounds. The results of calculations on the lanthanide induced shifts indicate that the tetrahydropyran ring is not flattened but probably somewhat puckered. The calculated location of Eu(III) in complexes of Eu(dpm)₃ with the 3-oxabicyclo [3.3.1]nonanes is compared with that in the complexes of the related compounds 2-oxaadamantane and 4-methyltetrahydropyran. The data indicate that the lanthanide ion coordinates “axially” to the latter compound.     

meta-Photoaddition reactions of 2-chloro-, 2,5-dichloro-, and 2-halo-5-isopropyl-tropones with 9,10-dicyanoanthracene

Photoreactions of 2-halotropones with the excited 9,10-dicyanoanthracene gave a meta-adduct and substitution products occurred at the C-2 position of troponoids. The mechanism of the meta-adduct was proved by the product analysis of the reaction of 3,7-dideuterio-2-bromo-5-isopropyltropone and 9,10-dicyanoanthracene. In the photoreaction of 2-chloro-5-isopropyltropone and 9,10-dicyanoanthracene in a mixed solvent of benzene and methanol, a benzaldehyde with a dibenzo-2-oxabicyclo[3.2.2]nonane system was obtained to support occurrence of an [8+4] cycloaddition reaction between them.     

Synthesis of cyclopropane-fused α-chlorolactones utilizing the nucleophilicity of cyclopropylmagnesium carbenoids

A novel method for the synthesis of cyclopropane-fused α-chloro-γ-lactones was developed utilizing the nucleophilicity of cyclopropylmagnesium carbenoids. Cyclopropylmagnesium carbenoids were generated from i-PrMgCl and 1-chlorocyclopropyl p-tolyl sulfoxides with a [(phenoxycarbonyl)oxy]methyl group at the 2-position of the cyclopropane ring. The resulting cyclopropylmagnesium carbenoids reacted with an intramolecular carbonate unit to give 1-chloro-3-oxabicyclo[3.1.0]hexan-2-ones in moderate to good yields. The asymmetric synthesis of 1-chloro-3-oxabicyclo[3.1.0]hexan-2-one was achieved using optically active dichloromethyl p-tolyl sulfoxide as a starting material.     

Highly efficient racemisation of a key intermediate of the antibiotic moxifloxacin

N-Chlorination by sodium dichloroisocyanurate and dehydrochlorination by TEA, followed by hydrogenation, allowed (1R,6S)-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane to be quantitatively racemised and the resulting trans-free cis racemate to be recycled into the resolution process to yield (1S,6R)-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane, a key intermediate of moxifloxacin.     

Cis-1-Phosphabicyclo[4.3.0]nonan

Cis-1-Phosphabicyclo[4.3.0]nonane cis-1-Phosphabicyclo[4.3.0]nonane has been synthesized by free-radical cyclization of 4-phophino-octa-1.7-diene. The bicyclic phosphine is characterized by reactions with CS₂, Ni(CO)₄, HSO₃F, CH₃I, H₂O₂, sulfur, and selenium, respectively. The determination of the relative configuration of the phosphine is done by a qualitative conformational analysis from the ¹³C n.m.r. data.     

Stereoselective synthesis of highly substituted 8-oxabicyclo[3.2.1]octanes and 2,7-dioxatricyclo[4.2.1.03,8]nonanes

The synthesis of new polyhydroxylated 8-oxabicyclo[3.2.1]octanes and 2,7-dioxatricyclo[4.2.1.0^3,8]nonanes is described. These structures is an interesting synthetic blocks for potential bioactive molecules. The precursor, 3-chloro-8-oxabicyclo[3.2.1]oct-6-ene-2,4-dione was obtained from reaction of tetrachlorocyclopropene with furan, then it was involved in carbonyl groups reduction and double bond oxidation, resulted in the formation of a polyhydroxylated derivatives, differently substituted at C-3 position, with five new stereocenters.Using intramolecular transannular hydroxycyclization, bicyclic epoxy diacetate was transformed into 2,7-dioxatricyclo[4.2.1.0^3,8]nonane in high yield through an alkoxide intermediate. Compounds thus obtained have a structure close to certain molecules with antitumor and glycosidase inhibitors activity.     

Formation of bicyclic adducts in the reactions of fluorinated 2,4-cyclohexadien-1-ones with 2-carboxyhenzenediazonium

Benzyne generated during the decomposition of 2-carboxybenzenediazonium interacts with 6-chloro-2,3,4,5,6-pentafluoro-2,4-cyclohexadien-1-one, 6-chloro-2,4,5,6-tetrafluoro-3-methoxy-2,4-cyclohexadien-1-one, 6-chloro-2,4,5,6-tetrafluoro-3-(pentafluorophenoxy)-2,4-cyclohexadien-1-one, and perfluoro-6-phenoxy-2,4-cyclohexadien-1-one to form [4+2]-cycloaddition products. The latter are easily converted to 1-naphthylacetic acid derivatives by the action of O- and N-nucleophiles.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1634–1637, September, 1994.This work was carried out with the financial support of the International Science Foundation (Project No. Ch₂-6713-0925).     

Synthesis of substituted 3-benzoyl-1,2,3,4-tetrahydropyridines by the addition of primary amines to 1,3,5-triphenyl-2-methylidene-1,5-pentanedione

1,3,5-Triphenyl-2-methylidene-1,5-pentanedione adds methyl- and cyclohexylamines to give, respectively, 1-methyl- and 1-cyclohexyl-3-benzoyl-4,6-diphenyl-1,2,3,4-tetrahydropyridines; 1-aza-3-benzoyl-4,6-diphenyl-7-oxabicyclo[4.3.0]nonane is obtained with ethanolamine.Communication 33 from the series Reactions of 1,5-Diketones. See [1] for communication 32.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 96–97, January, 1979.     

Synthesis of neodysiherbaine

The stereocontrolled synthesis of neodysiherbaine from diacetyl-l-arabinal is described. Key steps in the synthesis include the use of an asymmetric phase-transfer catalyzed glycine imine alkylation to introduce the α-amino acid function, and the RuO₄-mediated oxidative cyclization of a 1,5-diene to generate the 2,7-dioxabicyclo[4.3.0]nonane ring system.