Fragmentation of Homoallylic Alkoxides. Thermolysis of potassium 2-substituted bicyclo [2.2.2]oct-5-en-2-alkoxides

Thermolysis of the potassium 2-substituted bicyclo [2.2.2]oct-5-en-2-alkoxides derived from alcohols 2–17 at 90–120° in hexamethylphosphoric triamide affords unsaturated ketones resulting from allylic bond cleavage. The mechanistic and synthetic aspects of this anionic fragmentation are discussed with reference to the formation of 1-(3′-cyclohexenyl)-2-alkanones 18–28 via initial heterolytic C(1), C(2)-bond cleavage in the substrate alkoxide and regioselective, intramolecular protonation of the resultant transient allylic anion.     

Stereochemical dependence of13C-shift and31P-13C-coupling in 3-substituted bicyclo[2.2.1]hept-5-en-2-yl- and bicyclo[2.2.2]oct-5-en-2-yl-phosphonates

Steric influences operating on¹³C-shifts and³¹P-¹³C-coupling constants have been investigated on phosphonates with a rigid framework.

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Stereochemische Abhängigkeit von¹³C-Verschiebungen und³¹P-¹³C-Kopplungskonstanten in 3-substituierten Bicyclo[2.2.1]hept-5-en-2-yl- und Bicyclo[2.2.2]oct-5-en-2-yl-phosphonaten

Zusammenfassung Der sterische Einfluß auf¹³C-Verschiebungen und³¹P-¹³C Kopplungskonstanten wurde an Phosphonaten mit starrer Struktur untersucht.

     

Epoxidation of 2-azabicyclo[2.2.1]hept-5-en-3-one

Epoxidation of 2-azabicyclo[2.2.1]hept-5-en-3-one has been performed in high yield with potassium hydrogen persulfate at pH 6, ¹H nmr data indicate an exo stereoconfiguration of the epoxide.     

2-Chlorobicyclo[2.2.1]hept-5-ene-2-carboxamide and 2-chlorobicyclo[2.2.1]heptane-2-carboxamide as precursors of bicyclo[2.2.1]hept-5-en-2-one and bicyclo[2.2.1]heptan-2-one: resolution,absolute configuration and hydrogen-bonding properties

The absolute configuration of bicyclo[2.2.1]heptan-2-one has not been correlated with a crystal structure of a chemical precursor. The only chemical correlation available had an ambiguity, which could have reversed the assignment. Herein, we report the resolution of 2-chlorobicyclo[2.2.1]hept-5-en-2-exo-carboxamide on a cellulose triacetate column and the crystal structures of the enantiomerically pure and racemic α-chloroamide. We found the absolute configuration (1R,2R,4R) for the (+)-enantiomer of the α-chloroamide. This compound was converted to (+)-bicyclo[2.2.1]hept-5-ene-2-one by base hydrolysis, and the 5,6-unsaturated compounds converted to the saturated congeners. This is the first unambiguous experimental determination of the absolute configuration of bicyclo[2.2.1]heptan-2-one and of bicyclo[2.2.1]hept-5-ene-2-one. The three crystal structures of 2-chlorobicyclo[2.2.1]hept-5-en-2-exo-carboxamide reported herein reveal H-bonded dimers, with two distinct orientations of the bicyclic portion relative to the carboxamide dimer. In the racemic crystal, each dimer is composed of two enantiomers, and the bicyclic portions have their bridge carbon atom (C-7) on opposite sides of the H-bonded carboxamide dimer moiety. In the enantiomerically pure crystals, the major dimer had both C-7 atoms on the same side of the carboxamide dimer moiety while the minor dimer had the C-7 atoms on opposite sides. The dimers are present in solution, and can be easily monitored.     

Microwave spectra and dipole moments of bicyclo [2.2.1]-hepta-7-one and bicyclo [2.2.1]hept-2-en-7-one

The microwave spectra of bicycle [2.2.1] hepta-7-one (I), bicyelo [2.2.1] hept-2-en-7-one (II), and exo-5,6-bisdeuteriobicyclo [2.2.1] hept-2-en-7-one (III) have been recorded in the region between 26.5 and 40.0 GHz. The rotational constants in the order A, B, C for the title compounds are 2773.24±0.31, 2301.74±0.04, and 2133.96±0.02 (I); 2979.22±0.08, 2418.60±0.01, and 2235.51±0.01 (II); and 2789.67±0.06, 2385.24±0.01, and 2150.60±0.01 (III). The rotational constants of four vibrationally excited states were also determined for (II). Quadratic Stark effect measurements on the 7₁₆ ← 6₁₅ transition of (I) gave ¦μ_a¦=2.99±0.03. Similar measurements on two 5 ← 4 and 4 ← 3 transitions of (II) gave ¦μ_a¦=2.88±0.03, ¦μ_b¦=0.39±0.03, ¦μ_c¦=0, and ¦μ_total¦=2.91±0.04.     

Synthesis and Epoxidation of 5-(2-Aminoethyl)bicyclo[2.2.1]hept-2-ene Derivatives

A number of derivatives of 5-(2-aminoethyl)bicyclo[2.2.1]hept-2-ene (85-90% of the endo isomer) were synthesized by reactions with p-nitrobenzenesulfonyl chloride, p-toluenesulfonyl chloride, benzoyl chloride, p-nitrobenzoyl chloride, benzyl isocyanate, m-tolyl isocyanate, phenyl isothiocyanate, and endic anhydride. By reactions of the resulting sulfon- and carboxamides with peroxyphthalic acid generated in situ from phthalic anhydride and 40-45% hydrogen peroxide the corresponding epoxy derivatives were obtained. These reactions were not accompanied by heterocyclization into azabrendane derivatives, which is typical of homologous N-(p-nitrophenylsulfonyl)-endo-5-aminomethylbicyclo[2.2.1]hept-2-ene.     

The Preparation of Optically Pure 7-Oxabicyclo [2.2.1]hept-2-ene Derivatives. The CD Spectrum of (+)-(1R)-7-Oxabicyclo [2.2.1]hept-5-en-2-one

(?)-1-Camphanoyloxyacrylonitrile (=(?)-1-cyanovinyl camphanate; 1 ) obtained from the commercially available (?)-camphanoyl chloride and 2-oxo-propiononitrile added to furan at 20° in the presence of Cu (BF₄)₂ · 6H₂O or ZnI₂ and gave a mixture of 2-cyano-7-oxabicyclo [2.2.1]hept-5-en-2-yl camphanates ( 2–5 ) from which isomer 5 could be obtained pure by crystallization. The latter was transformed into (+)-(1R)-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 6 ) in high yield and optical purity. Adducts 2–4 were recycled into 1 +furan by heating in toluene, and (?)-camphanic acid was recovered after saponification of 5 . The absolute configuration of 6 was deduced from its CD spectrum which showed two 1200-cm_?1 Franck-Condon series for its n→π transition.     

Synthesis of <Emphasis Type="Italic">para</Emphasis>-substituted bicyclo[2.2.1]hept-5-en-2-ylmethyl benzoates

para-Substituted bicyclo[2.2.1]hept-5-en-2-ylmethyl benzoates were synthesized by the Diels-Alder reaction of cyclopentadiene with the corresponding para-substituted allyl benzoates, and optimal reaction conditions were found. The product structure was confirmed by independent synthesis and IR and ¹H NMR spectroscopy.     

The Carbonyl Group as Homoconjugated Electron-Releasing Substituent. Regioselective electrophilic additions at bicyclo[2.2.1]hept-5-en-2-one,bicyclo[2.2.2]oct-5-en-2-one,and derivatives

In CHCl₃, CH₃CN, or AcOH, benzeneselenenyl chloride (PhSeCl), bromide (PhSeBr), and acetate (PhSeOAc), 2-nitrobenzenesulfenyl chloride (NO₂C₆H₄SCl), and 2,4-dinitrobenzenesulfenyl chloride ((NO₂)₂C₆H₃SCl) added to bicyclo[2.2.1]hept-5-en-2-one ( 5 ) in an. anti fashion with complete stereo- and regioselectivity, giving adducts 20–24 in which the chloride, bromide, or acetoxy substituent (X) occupies the endo position at C(6) and the Se- or S-substituent (E) the exo position at C(5), The addition 5 + (NO₂)₂C₆H₃SCl→ 24 was accompanied by the formation of (1RS, 2RS)-2-(2,4-dinitrophenylthio)cyclopent-3-ene-l-acetic acid ( 25 ). The latter was the major product in AcOH containing LiClO₄. The additions of PhSeCl and PhSeBr to bicyclo[2.2.2]oct-5-en-2-one ( 6 ) were less stereoselective (proportion of exo vs. endo mode of electrophilic attack was ca. 3:1) but highly regioselective gazing adducts 27/28 and 29/30 , respectively, the regioselectivity being the same as that of the electrophilic additions of 5 . The reaction of PhSeCl with a 4:1 mixture of 2-exo-chloro- and 2-endo-chlorobicyclo[2.2.1]hept-5-ene-2-carbonitriles ( 12 ) was slower than addition 5 + PhSeCl; it gave adducts 31/32 (4:1) in which the PhSe moiety occupies the exo position at C(6) and the Cl atom the endo position at C(5). The addition of PhSeCl to 2-chlorobicyclo[2.2.1]oct-5-ene-2-carbonitriles ( 13 ) was very slow and gave adducts with the same regioselectivity as 12 + PhSeCl, but opposite with that of reactions of the corresponding enones 5 and 6 . PhSeX (X = Cl, Br, OAc) added to 2-cyanobicyclo[2.2.1]hept-5-en-2-yl acetates ( 14 ) with the same regioselectivity as 12 + PhSeCl. The additions of PhSeCl, PhSeBr, NO₂C₆H₄SCl, and (NO₂)₂C₆H₃SCl to 2-(bicyclo[2.2.1]hept-5-en-2-ylidene)propanedinitrile ( 49 ) were not regioselective, showing that a dicyanomethylidene function is not like a carbonyl function when homoconjugated with a π system. The results are in agreement with predictions based on MO calculations suggesting that a carbonyl group homoconjugated with an electron-deficient centre can behave as an electron-donating, remote substituent because of favourable n(CO)?σC(1), C(2)?p(C(6) hyperconjugative interaction.     

The Homoconjugated Electron-Releasing Carbonyl Group of 1-Methylbicyclo[2.2.1]hept-5-en-2-one. Regioselective syntheses of 5-chloro- and 6-chloro-1-methylbicyclo[2.2.1]hept-5-en-2-one

Syntheses of (±)-2-exo-cyano-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl acetate ( 1 ) and of (±)-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 2 ) are reported. The additon of PhSeCl to 1 afforded (±)-5-endo-chloro-2-exo-cyano-1-methyl-6-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]hept-2-endo-yl acetate ( 6 ), whereas 2 added to PhSeCl with the opposite regioselectivity giving (±)-6-endo-chloro-1-methyl-5-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]heptan-2-one ( 7 ). These adducts were converted into 5-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 9 ) and 6-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 10 ), respectively.     

Synthesis of halomethyl-substituted bicyclo[2.2.1]hept-2-yl(meth)acrylates

Russian Journal of Applied Chemistry - Bicyclic esters, which are reactive monomers for the synthesis of new polymeric products and also of organic compounds, were synthesized by the reaction of...     

Facile Preparation of (±)-12-Epiprostaglandins from 7-Oxabicyclo[2.2.1]hept-5-en-2-one via an all-cis-formyllactone related to Corey lactone

The bicyclic monoselenoacetal 7 , easily obtained from (±)-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 6 ) via a radical addition-acyl migration sequence, was converted to racemic 12-epiprostaglandins 3 and 4 . The key intermediate was the all-cis-formyllactone 2b related to Corey lactone (see 12 ; Scheme 1). The presence of a (tert-butyl)-dimethylsilyl protective group for the 11-OH substituent (prostaglandin numbering) was found to be crucial in avoidingβ -elimination and epimerization during the Wittig-Horner reaction (Scheme 2). Epimerization at C(12) at the formyllactone stage (see 2b ) was also possible and gave the known precursor 1b of naturally occurring prostaglandins and analogs.     

Interconversion of bicyclo[2.2.1]hept-2-yne and 5-bicyclo[2.1.1]hexylidenecarbene

This work provides unambiguous results for the full equilibration of cycloalkyne 2 with its isomeric ring-contracted vinylidene 3 prior to their reaction with 2,3-dihydropyran (4), as evidenced by the products formed when 2 and 3 are produced directly from their precursors having bicyclo[2.2.1]heptyl and bicyclo[2.1.1]hexyl skeletons, respectively.     

Regioselective Radical Additions to 7-Oxabicyclo[2.2.1]hept-5-en-2-one

Radical addition to 7-oxabicylco[2.2.1]hept-5-en-2-one ( 1 ) was examined from a regiochemical point of view, and despite the small electronic anisotropy of the double bond, electrophilic radicals were found to add preferentially at C(5) with selectivities of up to 5:1. We also report the first case of an inversion of the regioselectivity of a radical reaction using Lewis acids.