Bicyclic derivatives

Thermolysis of pterodactylane (262) at 60 to 80 °C gave (263) and (264) in a 1 1 ratio (263) was not converted into (264) under the reaction conditions. Use of the deuteriated substrate (262b) gave products with the indicated labelling patterns. 

Goldstein and co-workers have initiated a careful study of the mechanistic possibilities involved in the thermal decomposition of bicyclo[2,2,0]hexene. Analysis of the products, greater than 97 % cyclohexa-1,3-diene, and strict first order kinetics (AH = 32.15 0.09kcalmol AS = 2.4 + 0.2e.u.) eliminated many pathways including those involving cis-hexa-l,3,5-triene. Use of the deuteriated substrate (269) 

Isomerization of bridgehead deuteriated Dewar benzene oxide (274) in tetra-chloroethylene gave the expected oxepin-benzene oxide mixture, demonstrating that the rearrangement occurs in straightforward fashion. The activation energy for the rearrangement was estimated to be 29 + 3 kcal mol  

A new synthesis of iV-substituted 1,2-dihydropyridines has used the relatively stable bicyclic isomer of 1,2-dihydropyridine (275) as a precursor. In this way a variety of substituents have been introduced by simple alkylation of (275) with the appropriate halides. Thermolysis, = 0.5 h for the R = Me at 120 °C, gave the dihydropyridines (276). 

Mundnich and Plieninger have studied the rearrangement of hexamethyl-Dewarbenzene to hexamethylbenzene using high pressure techniques. Large rate accelerations were found with AF = -34.6 2.5cm mol and AK = —22.5 1 cm mol The value found for the volume of activation was independent of solvent polarity and therefore not caused by solvent electrostriction by dipolar types of transition state. 

The as yet unobserved walk rearrangement of bicyclo[2,l,0]pentene has also been studied theoretically using optimized MINDO/2 calculations on the transition states (492) and (493), including configuration interaction for bond dissociation. The retention pathway, via (493), was calculated to be favoured over the inversion pathway, via (492), by 4.0kcalmol . This predicted pathway is Woodward-Hoffman forbidden. 

The thermal isomerization of 5-acetyl-5-methylbicyclo[2,l,0]pentane (494) has been the subject of a detailed kinetic study. Rates and activation parameters have been determined for all the processes. The exo-endo interconversion and the rearrangement to the cyclopentene (495) evidently do not involve a common intermediate. The activation parameters for the rearrangement to cyclopentenyl ketone, AH = 22.2 kcal mol and AS = - 33.0 cal K mol are indicative of a highly ordered transition state and suggest that the cyclopropyl-allylic rearrangement is an electrocyclic process. 

Thermal or photochemically induced rearrangement of the tricyclo[4,3,0,0 ]-nonadienes (496) gives the dihydroindenes (497). The thermal stabilities of the tricyclic dienes is in the order d c e b a. This ordering is largely explicable on the basis of steric effects. 

Dewar has applied the MINDO/3 method to a study of the thermal conversion of Dewar-benzene into benzene. The method gives an activation energy of 114.2 kJ mol , which is fairly close to the experimentally observed value of 96.2 kJ mol . The transition state has only symmetry. As a result, the HOMO/LUMO crossing occurs after the transition state. The charge distribution within the transition state shows that it tends towards a zwitterionic form and that either electron-attracting or -releasing substituents at the bridgehead should therefore facilitate the reaction. 

An approximate reaction surface for the thermal 1,3-sigmatropic rearrangement of bicyclo[3,2,0]hept-2-enes to norbornenes has been calculated using extended Huckel theory, The potential surfaces, calculated for bicyclo[3,2,0]heptene and 7-methylbicyclo[3,2,0]heptene, accommodate qualitatively the known experimental facts, but results of quantitative significance would require a dynamical approach. 

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Phototransformation of pyridazine 1,2-dioxides sharply contrasts with that of pyridazine 1-oxides. Pyridazine 1,2-dioxide derivatives give 3a,6a-dihydroisoxazolo[5,4- f]isoxazoles (53) through postulated bisiminoxyl radicals. 3,6-Diphenylpyridazine 1,2-dioxide gives, besides the corresponding bicyclic derivative (53), 3-phenylisoxazole (54) and 4,5-diphenyl-furoxan (55). The last two products can be explained by generation of the nitrile oxide from the intermediate (53) with subsequent dimerization to the furoxan (55 Scheme 18) (79T1267). 

Bicyclic derivatives Rate constants for nitrogen extrusion 78JA5122... 

Thermal cycli2alion of dienones enals, ynones, diones keloesters, etc, to monocyclic spirocycfc bicyclic derivatives, (ene reaction of unsalurated enol)... 

Thus, reduction of the bicyclic derivatives 25 (RR = CH2 RR = CH=C(Ph)) affords the corresponding 26a-type products, while hydrogenation of 2-ethoxy-3-acetylpyridine gives, along with the carbonyl group reduction product, the imine isomer 26b (R = Me, R = Et). These results were explained by the so-called internal strain effect, e.g., by steric repulsion between the nitrogen and oxygen lone pair in rotationally restricted bicyclic derivatives or between the 2 and 3 substituents. 

The isolated bicyclic derivatives induced very high stereoselectivity (ee s up to 99%) in the Pd catalyzed ally lie substitution reaction [85],... 

Diaza compound 669 condensed with bromobutyryl chloride under classical basic conditions gives bicyclic derivative 670. This compound can be further functionalized, for example, via classical enolate chemistry (Scheme 110)... 

In this chapter the emphasis will be placed on the cage compounds such as 1-boraadamantanes 5 and 7, 3-borahomoadamantanes 6, bicyclic derivatives 8, and other compounds with bridgehead boron atom. 

A similar transformation involving isocyanates instead of enamines has been reported. The imino thiadiazolidine 36 when reacted with methyl isocyanate affords a mixture of two compounds the bicyclic derivative 37 and the thiourea derivative 38 (Equation 10) <1997IJB399>. 

The thiadiazolopyrimidine derivative 39 reacts with ethoxycarbonyl isothiocyanate and carbon disulfide. In the former case the bicyclic derivative 40 is formed, and with the latter reagent the pyrimido dithiazole 41 is formed (Scheme 4) <2004JHC99>. 

Mason and coworkers10 studied the chiral bicyclic derivatives 2, 3, 33 and 34, having known absolute configuration. These molecules possess a planar s-cis diene chromophore and formally their chirality is due to the presence of the D or CH3 substituents, which rule out all the symmetry planes. However, it is interesting to point out a peculiar structural... 

Recent reports have emerged of several TRPV1 antagonists possessing a biaryl amide (14-16), urea (17), or urea isostere (18-20) scaffolds. Bicyclic derivatives 14-16 block capsaicin- or pH-stimulated calcium influx in FLIPR-based assays... 

In another example (Scheme 8), the intramolecular cycloaddition of an azido functionality onto an enone group afforded bicyclic derivatives with bridgehead iV atoms. The cyclopentenone derivative 28 afforded the indolizidinone 30 through the proposed compound 29 which might react through a diradical intermediate or through a betaine intermediate <2002TL5385>. 

Bicyclic derivatives. Polyhydroxylated carbo-bicyclic derivatives may be regarded as carbasugars with the rigid structure resulting from the presence of the additional carbocyclic ring. The most convenient way for construction of the bicyclic skeleton consists of the Diels-Alder reaction of properly functionalized trienes (intramolecular version) or dienes and olefins (intermolecular). 

The indirect cyclisation of bromoacetals via cobaloxime(I) complexes was first reported in 1985 [67], At that time the reactions were conducted in a divided cell in the presence of a base (40yo aqeous NaOH) and about 50% of chloropyridine cobaloximeflll) as catalyst precursor. It was recently found that the amount of catalyst can be reduced to 5% (turnover of ca. 50) and that the base is no longer necessary when the reactions are conducted in an undivided cell in the presence of a zinc anode [68, 69]. The method has now been applied with cobaloxime or Co[C2(DOXDOH)p ] to a variety of ethylenic and acetylenic compounds to prepare fused bicyclic derivatives (Table 7, entry 1). The cyclic product can be either saturated or unsaturated depending on the amount of catalyst used, the cathode potential, and the presence of a hydrogen donor, e.g., RSH (Table 7, entry 2). The electrochemical method was found with some model reactions to be more selective and more efficient than the chemical route using Zn as reductant [70]. 

A convenient preparation of dihydrobenzofurans has been achieved from the appropriately functionalized ort/ o-halophenol derivatives. Treatment of the aryl iodide (5)-33 with (TMS)3SiH and EtsB in the presence of air at room temperature, gave the aryl radical which cyclized in a 5-exo-trig mode and provided the bicyclic derivatives 34/35 as a 29 1 mixture of diastereoisomers in favour of 34 (Reaction 7.40) [51]. 

Table 3.7. THE ACTIVITY OF BICYCLIC DERIVATIVES OF GUANETHIDINE RGHjGHjNHGIiNHINHj...

Bicyclic derivatives of furazan A-oxide are prepared by nitrile oxide dimerization reaction. Dioxime 272 (R, R = Me) undergoes cyclization to the corresponding 4,4-tetramethylperhydrocycloocta[c]furazan A-oxide 273 (84% yield) by treatment with NaOCl/HaO/CHaCla at 0°C and then refuxing in toluene (equation 117). However, in the cases of sterically less hindered oximes 272 (R = H, Me R = H) only complex mixtures of oligomerization and cyclization products could be obtained ". Interestingly, the reaction of pyridyl oxime -274 with TsCl afforded 1,2,5-oxadiazole 275 as single product (equation 118). On the other hand, the reaction of Z-isomer of oxime 274 leads only to 0-tosylated oxime. ... 

Treatment of 3-formylchromone (95) and 4-amino-3-phenyl-5-triazolinethione (96) with KOH and TBAHSO4 in benzene also gave a bicyclic derivative (97) (Equation (34)) <87SC1851>. 4-Amino-3-triazolinethione (98) reacts with the diketoacetylene (99) in a similar manner to give (100) (Equation (35)) <92CHE222>. 

With respect to five-membered lactones fused to hexopyranose units, some approaches have been reported so far and the exploitation of their synthetic potential has led to the access of new carbohydrate derivatives. Bicyclic derivatives of this type are key intermediates in the synthesis of the epimer at C-3 of the sugar moiety contained in miharamycins [212, 213]. The latter are antibiotics known to inhibit strongly Pyricularia oryzae, which produces the rice blast disease. These compounds are also considered to be a potential bioterrorism agent (Scheme 42). Hence, the 3,3-spiroepoxide 176 was converted into the 3-C-cyanomethyl derivative 177, the hydrolysis of which led to spontaneous cyclization in the presence of... 

Bicyclic derivatives (133) of l,3-thiazol-4-imines have been prepared by treatment of (2-pyridylthio)acetonitrile with acid chlorides. The same compounds (133) are also formed from 5-acyl-2-mercaptopyridine, chloroacetonitrile, and acid chlorides. 

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