CoTPP-catalyzed reaction of saturated bicyclic endoperoxides

Saturated bicyclic endoperoxides were exposed to CoTPP (Cobalt-meso-tetraphenylporphyrine) in chloroform, the peroxide bond was cleaved and a mixture of products arising from fragmentation and reduction obtained.     

Thermal and photochemical reactions of unsaturated bicyclic endoperoxides

Thermal, and especially photochemical, rearrangement of the endoperoxides (1) and (5)–(11) gives βγ-epoxycycloalkanones as primary products, accompanied by the expected syn-diepoxides.     

Synthesis and chemistry of unusual bicyclic endoperoxides containing the pyridazine ring

Inverse-Diels-Alder reaction of dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate with unsaturated bicyclic endoperoxides gave the bicyclic endoperoxides containing the pyridazine ring. The NEt(3) and CoTPP (TPP = tetraphenylporphyrin) catalyzed reaction of endoperoxide 8 resulted in the formation of hydroxy ketone 11 and cis-diol 9. Cleavage of the peroxide linkage in 8 with thiourea provided cis-diol 9. Oxidation of hydroxy ketone 11 and cis-diol 9 led to the phthalazine-5,8-dione 10. Furthermore, the various transformations of the other endoperoxides 19, 20, 22, 23, and 30 resulted in the formation of pyridazine derivatives.     

Polystyrene-supported N-methylthiourea: a convenient new reagent for the hydrogenolysis of bicyclic endoperoxides

The single-step preparation of a polystyrene-bound N-methylthiourea and its use for the hydrogenolysis of bicyclic endoperoxides is described.     

Kinetics of dissociative electron transfer to ascaridole and dihydroascaridole-model bicyclic endoperoxides of biological relevance

The homogeneous and heterogeneous electron transfer (ET) reduction of ascaridole (ASC) and dihydroascaridole (DASC), two bicyclic endoperoxides, chosen as convenient models of the bridged bicyclic endoperoxides found in biologically relevant systems, were studied in aprotic media by using electrochemical methods. ET is shown to follow a concerted dissociative mechanism that leads to the distonic radical anion, which is itself reduced in a second step by an overall two-electron process. The kinetics of homogeneous ET to these endoperoxides from an extensive series of radical anion electron donors were measured as a function of the driving force of electron transfer (deltaG(o)ET). The kinetics of heterogeneous ET were also studied by convolution analysis. Together, the heterogeneous and homogeneous ET kinetic data provide the best example of the parabolic nature of the activation-driving force relationship for a concerted dissociative ET described by Savéant; the data is particularly illustrative due to the low bond-dissociation enthalpy (BDE) of the O-O bond and hence small intrinsic barriers. Analysis of the data allowed the dissociative reduction potentials (E(o)diss) to be determined as -1.2 and -1.1 Vagainst SCE for ASC and DASC, respectively. Unusually low pre-exponential factors measured in temperature-dependent kinetic studies suggest that ET to these O-O bonded systems is nonadiabatic. Analysis of ET kinetics for ASC and DASC by the Savéant model with a modification for nonadiabaticity allowed the intrinsic free energy for ET to be determined. The use of this approach and estimates for the BDE provide approximations of the reorganization energies. We suggest the methodology described herein can be used to evaluate the extent of ET to other endoperoxides of biological relevance and to provide thermochemical data not otherwise available.     

Synthesis of antimalarial G-factors endoperoxides: relevant evidence of the formation of a biradical during the autoxidation step

In the search for new antimalarial endoperoxides related to G-factors series, using a methodology based on autoxidation of a dienol sytem, unexpected cyclic ether alcohols and hydroperoxides were obtained confirming the structure of the previously postulated biradical intermediate implicated in oxygen uptake. Antimalarial activities of PMB-endoperoxides are greatly enhanced when the peroxyhemiketal function is methylated for the G3 endoperoxide.     

Formation of bicyclic ethers from Lewis acid promoted cyclizations of cyclic oxonium ions

Oxacycles carrying a vinyl group and an acetal were extended with a cyclization terminator (vinyl silane or vinyl sulfide) by Suzuki coupling. Treatment with Lewis acid induced cyclization to provide bicyclic ethers in reasonable yields. In the case of the vinyl silane, an ene-like mechanism is preferred, whereas the thioenol ether enters into a Prins-type reaction channel. In one instance, the bicyclic compound was opened to give the ten-membered functionalized enone 24. [reaction: see text]     

Formation of 1-hydroxycyclopropanecarbonitrile ring in bicyclic systems

Reaction of α-methanesulfonyloxycycloalkanones with KCN in dimethylformamide is examined; this proceeds, with high yield, to give in some cases l-hydroxybicyclocarbonitriles and in other cases 2-cyanooxiranes. Open chain α-methanesulfonyloxyalkanones afford 2-cyanooxiranes.     

Formation of some bicyclic systems by radical ring-closure

The rates and stereochemistry of ring closure of the radicals ($\text{2}$), ($\text{9}$), ($\text{10}$), and ($\text{16}$) have been determined and rationalised.     

On the question of carbonyl oxide intermediates in the oxygen transfer by furan endoperoxides and bicyclic ozonides: intramolecular trapping experiments

On heating the furan endoperoxide ($\text{2}$) rearranges into the enol ester ($\text{4}$) and the bicyclic ozonide ($\text{3}$) affords instead the rearranged ozonide ($\text{7}$). The process ($\text{2}$) → ($\text{4}$) represents an intramolecular Baeyer-Villiger rearrangement presumably via the dioxirane (D-2), while the process ($\text{3}$) → ($\text{7}$) represents intramolecular trapping of the carbonyl oxide (C-3).     

Synthesis of endoperoxides derived from cyclooctatetraenes via singlet oxygenation

Cyclooctatetraene (1) reacted with photo-generated singlet oxygen to give the endoperoxide 7,8-dioxabicyclo[4.2.2]deca-2,4,9-triene (1a), which was further transformed to the cis-diepoxide 1b by catalytic rearrangement with Co-TTP to the unsaturated cis-diol 1c and the saturated cis-diol 1d by catalytic hydrogenation, to the saturated endoperoxide 1e by reaction with diimide, and to the epoxycyclooclatetraene If by deoxygenation with dimethylphosphine. Similarly, the methoxy-, phenyl- and methyl-substituted cyclooctatetraenes 3-5, respectively, gave the corresponding endoperoxides with the substituents located at the 1-position (3a, 5a), the 2-position (5b) and the 9-position (3b, 4a). Their structures were determined on the basis of their ¹H- and ¹³C-NMR data and by means of chemical transformation to the corresponding syn-diepoxides, i.e. 5,10-dioxatricyclo[7.1.0.0^4,6]deca-2,7-dienes. The formation of the endoperoxides is postulated to involve an electron transfer mechanism to give the radical cation of cyclooctatetraene and the superoxide ion. The latter couples into the homotropylium-type zwitterionic intermediate and subsequent cyclization leads to the endoperoxides.     

The Diastereoselective Formation of 1,2,4-Trioxanes and 1,3-Dioxolanes by the reaction of endoperoxides with chiral cyclohexanones

1,4-Diphenyl-2,3-dioxabicyclo[2.2.1]hept-5-ene ( 2 ), on treatment with a catalytic amount of trimethylsilyl trifluoromethanesulfonate (Me₃SiOTf) in CH₂Cl₂ at ?78°, reacts with excess (?)-menthone ( 10 ) to give (1S,2S,4′aS,5R,7′aS)-4′a,7′a-dihydro-2-isopropyl-5-methyl-6′,7′-diphenylspiro[cyclohexane-1,3′-[7′H]cyclopenta-[1,2,4]trioxine] ( 11 ) and its (1R,2S,4′aR,5R,7′aR)-diastereoisomer 12 in a 1:1 ratio and in 21% yield. Repeating the reaction with 1.1 equiv. of Me₃SiOTf with respect to 2 affords 11 , 12 , and (1S,2S,3′a.R,5R,6′aS)-3′a,6′a-dihydro-2-isopropyl-5-methyl-3′a-phenoxy-5′-phenylspiro[cyclohexane-l,2′-[4′H]cyclopenta[1,3]dioxole] ( 13 ) together with its(1R,2S,3′aS,5R,6′aR)-diastereoisomer 14 in a ratio of 3:3:3:1 and in 56% yield. (+)-Nopinone( 15 ) in excess reacts with 2 in the presence of 1.1 equiv. of Me₃SiOTf to give a pair of 1,2,4-trioxanes ( 16 and 17 ) analogous to 11 and 12 , and a pair of 1,3-dioxolanes ( 18 and 19 ) analogous to 13 and 14 , in a ratio of 8:2:3:3 and in 85% yield. (?)-Carvone and racemic 2-(tert-butyl)cyclohexanone under the same conditions behave like 15 and deliver pairs of diastereoisomeric trioxanes and dioxolanes. In general, catalytic amounts of Me₃SiOTf give rise to trioxanes, whereas 1.5 equiv. overwhelmingly engender dioxolanes. Adamantan-2-one combines with 2 giving only (4′aRS,7′aRS)-4′a,7′a-dihydro-6′.7′a-diphenylspiro[adamantane-2,3′-[7′H]cyclopenta[1,2,4]trioxine] in 98% yield regardless of the amount of Me3SiOTf used. The reaction of 1,4-dipheny 1-2,3-dioxabicyclo[2.2.2]oct-5-ene ( 32 ) with 10 and 1.1 equiv. of Me3SiOTf produces only the pair of trioxanes 33 and 34 homologous to 11 and 12 . Treatment of the (S,S)-diastereoisomer 33 with Zn and AcOH furnishes (1S,2S)-1,4-diphenylcyclohex-3-ene-1,2-diol. The crystal structures of 11 – 13 and 16 are obtained by X-ray analysis. The reaction courses of 10 and the other chiral cyclohexanones with prochiral endoperoxides 2 and 32 to give trioxanes are rationalized in terms of the respective enantiomeric silylperoxy cations which are completely differentiated by the si and re faces of the ketone function. The origin of the 1,3-dioxolanes is ascribed to 1,2 rearrangement of the corresponding trioxanes, which occurs with retention of configuration of the angular substituent.     

Isomerization of polyamide prepared from bicyclic oxalactam

Anionic solution polymerization of bicyclic oxalactam, 8-oxa-6-azabicyclo[3.2.1]octan-7-one (abbreviated as BOL), at 25°C yields the polyamide with both carbonyl and imino groups at the axial positions in the tetrahydropyran ring. On the other hand, the polyamide obtained by bulk anionic polymerization of BOL at 100°C has more complicated structures, probably due to the isomerizations and side reactions. The most frequent isomerization of the polyamide was the transfer of the carbonyl group adjacent to the tetrahydropyran ring from the equatorial to the axial position in the presence of base or acid catalyst at 25°C. Mechanisms are discussed from the viewpoint of the characteristic bonds in the polyBOL chain.     

Formation of bicyclic compounds in the reaction of 3-methyl-2,3-epoxysulfolane with thiocyanic acid

In the presence of an equivalent amount of sulfuric acid 3-methyl-2,3-epoxysulfolane reacts with sodium thiocyanate with primary opening of the oxy ring at the C₍₃₎-O bond to give, as the principal product, 5-methyl-3-oxo-2-oxa-4,8-dithiabicyclo[3.3.0]octane 8,8-dioxide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 331–335, March, 1985.     

Picosecond studies on the photodissociation dynamics of aromatic endoperoxides

Studies on various aromatic endoperoxides (POs) reveal a different photodynamic behavior despite similar excitation conditions and despite similar chromophore structures. Using picosecond laser pump-probe technique it was found that heterocoerdianthrone (HECD), dissolved in dichloromethane, is produced from photocycloreversion of its endoperoxide with a time constant of τ=40±10 ps. Since the lifetime of the photoreactive S₃ state is less than 3 ps, a two-step mechanism is expected. Photocleavage of the endoperoxide of anthradichromene (ADCPO) happens in 55±15 ps, whereas the endoperoxides of dimethylhomöocoerdianthrone (HOCDPO) and dimethoxyhomöocoerdianthrone (DMHDPO) photodissociate much faster. For their photodissociation we can state an upper time limit of 5 ps. The results of polarization and solvent dependent experiments demonstrate that the observed rise of signal is directly correlated with the formation of the parent compound in the ground state. The dynamics of the photodissociation of HECPO does not depend on polarity or viscosity of solvent. Therefore, an oxciplex configuration or an intermediate zwitterion cannot be involved in the photocycloreversion of aromatic endoperoxides. The model of a biradical mechanism must be claimed instead.     

Titanium-mediated synthesis of bicyclic cyclopropylamines from unsaturated nitriles

Here we report an easy synthesis of bicyclic primary cyclopropylamines directly from unsaturated nitriles. The described reaction involves Ti(II)-mediated intramolecular coupling of alkene and nitrile moieties.