Synthesis and chemical diversity analysis of bicyclo[3.3.1]non-3-en-2-ones

Functionalized bicyclo[3.3.1]non-3-en-2-ones are obtained from commercially available phenols by a hypervalent iodine oxidation, enone epoxidation, epoxide thiolysis, and intramolecular aldol reaction sequence. Reaction optimization studies identified room temperature as well as microwave-mediated procedures, providing moderate to good yields (57-88%) in the thiophenol-mediated epoxide opening and intramolecular aldol reaction. In addition, the isolation of a key intermediate and in situ NMR studies supported the mechanistic hypothesis. The bicyclic ring products occupy novel chemical space according to ChemGPS and Chemaxon chemical diversity and cheminformatics analyses.     

Oxy-cope rearrangements of bicyclo[3.2.0]heptenones. Synthesis of bicyclo[4.2.1]non-1(4)-en-6-ones and bicyclo[5.2. 1]dec-1(10)-en-5-ones

6-exo-Methylbicyclo[3.2.0]hepten-7-ones and their 2-alkylidene analogues are readily prepared from dialkyl squarates. These compounds undergo facial oxy-Cope ring expansions upon treatment with vinyllithium; the former leads to bicyclo[4.2. 1]non-1(4)-en-6-ones and the latter to the first examples of bicyclo[5.2.1]dec-1(10)-en-5-ones, compounds having exceptionally strained bridgehead double bonds. The transformations are controlled by the 6-exo-methyl group in the starting material along with the substituent at position-1 (bridgehead) which force attack of the lithium reagent from the concave face of the starting material, thus allowing the cyclopentenyl or alkylidene groups to participate in the sigmatropic event.     

Formation and trapping of 6-azabicyclo[3.2.2]non-5-ene,a strained bridgehead imine

Photolysis or flash vacuum pyrolysis of 1-bicyclo[3.2.1]octylazide $\text{9}$ yields 6-azabicyclo[3.2.2]non-5-ene $\text{10}$, a strained bridgehead imine, which could not be isolated but was trapped with methanol.     

A stereoselective synthetic route to 1,6-Dioxaspiro[4.4]non-3-en-2-ones from cyclopropyl alkyl ketones and alpha-ketoesters

[reaction: see text] The SnCl(4)-mediated reactions of cyclopropyl alkyl ketones with alpha-ketoesters afford a novel method for the synthesis of 1,6-dioxaspiro[4.4]non-3-en-2-ones with high stereoselectivities in moderate to good yields. This process is a sequential reaction involving a nucleophilic ring-opening reaction of the cyclopropane by H(2)O, an aldol-type reaction, and a cyclic transesterification mediated by Lewis acid.     

On the conformation of 8-substituted bicyclo [3.2.1] oct-6-en-3-ones

A series of 8-substituted bicyclo [3.2.1] oct-6-en-3-ones (of type i) possessing various R₁ and R₂ groups were prepared and characterized. The conformations of the possible isomers of 1-4 were assigned according to the following three methods: (a) NMR spectrum, (b) time averaged precise metal ion location within the Eu (dpm)₃-carbonylic compound complex, (c) UV spectra. Comparison of the chair and boat conformers by UV spectra showed that interactions between the double bonds and the carbonyl occurred in both cases, although to different extents, the ε being dependent on R₁ and R₂. The fore-mentioned interaction exists even in both series of the C₆C₇ dihydro derivatives.     

A bicyclo[3.2.0]hept-3-en-6-one approach to prostaglandin intermediates

[reaction:see text] The substituted cyclopentanic structures, 6-benzyloxymethyl-7-hydroxy-2-oxabicyclo [3.3.0]octan-3-one (1), a Corey lactone derivative, and 6-exo-benzyloxymethyl-2-oxabicyclo[3.3. 0]oct-7-en-3-one (2), have been obtained stereoselectively through the bicyclo[3.2.0]hept-3-en-6-one approach via 5-benzyloxymethyl-3-hydroxy-6-heptenoic acid, easily accessible from the inexpensive monoprotected cis-2-butene-1,4-diol.     

Use of cmr spectroscopy and photochemical transformations in structure assignments to bicyclo [3.2.0] hept-6-en-2-ones

Isomeric bicyclo [3.2.0] hept-6-en-2-ones, differing in the position of substituents at C_β and C_γ, can be distinguished by their photochemical behavior and by CMR spectroscopy.     

Dehydration of tertiary bicyclo[3.3.1]nonan-9-ol-2-ones. Rearrangement to cis-fused hexahydroinden-1-ones

Dehydrations of the anti-ketol 5 and its isomer 10 have been studied. In both cases the 1-hydrindenones 6 and 7 have been almost quantitatively obtained (1:1 ratio) through skeletal rearrangement of the kinetically favoured 9-methylene bicyclononane 9. This strongly supports the hypothesis of a stepwise rearrangement driven by the relative stabilities of the involved carbonium ions.     

Alkoxide-Accelerated [1,3] Sigmatropic Shift of Bicyclo[3.2.1]oct-6-en-2-ols to 8-endo-Hydroxybicyclo[3.3.0]oct-2-en-4-ones

Bicyclo[3.2.1]oct-6-en-2-ols 6 are shown to undergo [1,3] sigmatropic shift to afford 8-endo-hydroxy-bicyclo[3.3.0]oct-2-en-4-ones 8 under the influence of potassium hydride.     

An unusual rearrangement and addition of solvent during the photolysis of alkyl-substituted bicyclo[3.2.0 ]hept-6-en-2-ones in methanol

Conclusions During irradiation in methanol by light with 300 nm, 7-amyl- and 6-amylbicyclo[3.2.0]hept-6-en-2-ones rearrange into derivatives of bicyclo[2.2.1]heptene with the simultaneous addition of the solvent.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2760–2764, December, 1977.     

Electron impact mass spectra of some acridones substituted with hydroxyl,methoxyl, alkyl and alkenyl groups

Forty-four acridones were examined by mass Spectrometry. The fragmentations were studied, and included cleavage of the carbon? oxygen bond of methoxyl groups, cleavage of the carbon–carbon bonds of γ,γ-dimethylpyranyl groups, cleavage of isoprenyl groups and the formation of doubly charged molecular ions and daughter ions. The tendency for fission of carbon? oxygen bond in the methoxyl group for acridones is about 300 : 200 : 8 : 1 for the C(2), C(4), C(5) and C(6) positions, respectively. The isoprenyl group is very sensitive to its position in fragmentation, and mass Spectrometry can be a powerful aid in distinguishing between C(2)- and C(4)-isoprenyl isomers.     

Photochemical rearrangement of 8-oxabicyclo[3.2.1]oct-6-en-2-ones

Irradiation of 8-oxabicyclo[3.2.1]oct-6-en-2-ones results in a 1,3-acyl rearrangement. The initial photoproduct undergoes a subsequent reaction involving hydrogen transfer followed by intramolecular cycloaddition of a ketene intermediate.     

Reduction of bicyclo[3.2.0] hept-2-en-6-one and 7,7-dimethylbicyclo[3.2.0]hept-2-en-6-one using dehydrogenase enzymes and the fungus mortierella ramanniana

Bicyclo[3.2.0]hept-2-en-6-one (1) was reduced with an alcohol dehydrogenase from $\text{Thermoanaerobium brockii}$ and a whole cell system ($\text{M. ramanniana}$) with excellent substrate enantioselectivity: 7,7-dimethylbicyclo[3.2.0]hept-2-en-6-one (2) was similarly reduced using the 3α,20β-hydroxysteroid dehydrogenase from Streptomyces $\text{hydrogenans}$ while $\text{M. ramanniana}$ furnished both 6S-alcohols (4a), (6b) with high optical purity.     

Diels-Alder reactions of 4-triflyloxy-2,6,6-trimethyl-2,4-cyclohexadienone. An expedient methodology for the synthesis of bicyclo[2.2.2]oct-5-en-2-ones and bicyclo[2.2.2]octa-5,7-dien-2-ones

The synthesis of 4-triflyloxy-2,6,6-trimethyl-2,4-cyclohexadienone (13), bicyclo[2.2.2]octenones 1a-j and 15a-j, and bicyclo[2.2.2]octadienones 2a-f, 6a-d, and 11a-f is described. The 2,4-cyclohexadienones 4 and 13 were used for the first time as nondimerizing and easily accessible alternatives to 2,6,6-trimethyl-2,4-cyclohexadienone 12 in Diels-Alder reactions with acetylene derivatives 5a-d to prepare the adducts 6a-d and 11a-e in excellent yields. Compounds 11a-d were initially prepared by the alcoholysis of 6a-d to afford bicyclo[2.2.2]octene-2,5-diones 7a-dfollowed by treatment of 7a-d with N-phenyltriflimide in the presence of LHMDS at -78 degrees C. Diels-Alder reaction of 13 with an acetylene equivalent, phenyl vinyl sulfoxide, was also studied. A detailed study of the Diels-Alder reactions of various olefinic dienophiles 14a-j with 13 has been carried out to furnish cycloadducts 15a-j in high yields. Reductive removal of triflyloxy group of vinyl triflates 11a-f and 15a-j was performed in the presence of [Pd(PPh(3))(2)Cl(2)-Bu(3)N-HCO(2)H] to obtain the desired bicyclo[2.2.2]octadienones 2a-f and bicyclo[2.2.2]octenones 1a-j, respectively, in good overall yields.     

Conformations and reactions of bicyclo[3.2.1]oct-6-en-8-ylidene

Bicyclo[3.2.1]oct-6-en-8-ylidene (1) can assume either the conformation of "classical" carbene 1a or that of foiled carbene 1b in which the divalent carbon bends toward the double bond. Oxadiazoline precursors for the generation of 1 were prepared, followed by photochemical and thermal decomposition as well as flash vacuum pyrolysis (FVP) of a tosyl hydrazone sodium salt precursor, to give a number of rearrangement products. Matrix isolation experiments demonstrate the presence of a diazo intermediate and methyl acetate in all photochemical and thermal precursor reactions. The major product from rearrangements of "classical" bridged carbene 1a is bicyclo[3.3.0]octa-1,3-diene as a result of an alkyl shift, while dihydrosemibullvalene formed from a 1,3-C-H insertion. In contrast, thus far unknown strained bicyclo[4.2.0]octa-1,7-diene formed by a vinyl shift in foiled carbene 1b. The experimental results are corroborated by density functional theory (DFT), MP2, and G4 computations.     

Intramolecular [2+2] cycloaddition of homoallylketenes to bicyclo[2.1.1]hexan-5-ones

Intramolecular [2+2] cycloaddition of γ,δ-unsaturated ketenes derived from hex-5-enoyl chloride derivatives gave bicyclo[2.1.1]hexan-5-ones with complete regioselectivity.