Bicyclic systems from

These compounds have been prepared via oxidative addition reactions between the appropriate phosphate or phosphine and either a quinone or via displacement reactions with a suitable diol. Compounds 81 and 83 were prepared by such a displacement reaction between monocyclic pentaoxyphosphorane 317 and 3-fluorocatechol or catechol in toluene, respectively. This reaction takes advantage of the chelation effect of forming a bicyclic system from a monocyclic one <1997IC5730>. Compound 82 and compound 84 were synthesized via oxidation addition between tetrachloroquinone and the respective sulfur-containing cyclic phosphate or phosphine <1997IC5730>. Compound 93 was prepared from the phosphine 318 and the diol 319 in the presence of iV-chlorodiisopropylamine in an ether solution <1998IC93>. 

When the reaction of diethyl oxomalonate 381 was carried out with the free 5-methyl isothiosemicarbazide, triazine 281 was obtained in addition to its isomeric triazine 382. Reaction of 382 with phosphorus oxychloride gave 383, whose reaction with guanidine or benzamidine gave 384, which cyclized to 385. This represents (85JOC2293) the first example of a preparation of this bicyclic system from a 1,2,4-triazine. 

Recently, molecular orbital calculations (MP2/6-31G //RHF/6-31G level) which cover a series of bicyclic systems from the stable bicyclic compound 109 to the unknown 6,8-dioxabicyclo[5.1.0]octa-2,4-diene (2,3-epoxyoxepin, 120), as well as the two intermediate 8-oxa- (121) and 6-oxa- derivatives (122), were carried out58. These structures are interesting because the bicycle 120 is suggested as a transient intermediate in the metabolic oxidation of benzene leading to the muconaldehyde, which is responsible for the hema-totoxicity of benzene. 

Numerous methods of preparing bicyclic systems from monocyclic precursors have been reported and four general strategies can be identified. These are (i) intermolecular cyclization reactions which do not involve 1,3-dipolar cycloaddition reactions (ii) intermolecular 1,3-dipolar cycloaddition reactions (iii) nonoxidative intramolecular cyclizations and (iv) oxidative intramolecular cyclization reactions. These four general methodologies are now considered. 

More elaborate examples have been reported for example, the synthesis of bicyclic systems from two consecutive reverse Cope reactions have been demonstrated.18 Thus, upon treatment with sodium cyanoborohydride (pH 4), l,8-nonadien-5-one (53) underwent two consecutive reverse Cope reactions to yield the two epimeric N-oxides 54a and 54b. Reduction of these compounds with hexachlorodisilane gave indolizines 55a and 55b in 41% yield from 53. 

Fig. 8.49 AMI Protonation structures characteristics and corresponding heats of formation (AHf). Relative energies of the neutral species are indicated on the left (kcal/mol underline. AMI, italics. 3-21G optimized including ZPE). This stmcture has a boat conformation and may be disfavored in a bicyclic system (From Li et al. [72])...

The reaction has been carried out with differently substituted alkynol derivatives and oxygen-, nitrogen-, and carbon-centered nucleophiles and applied to the synthesis of enantiomerically pure [3.3.1]bicyclic systems from the chiral pool. The mechanism parallels the one proposed for the hydroalkoxylation/hydroarylation sequence. 

It is possible to prepare pyrimidines from other heteromonocyclic compounds by a variety of processes, or from fused heterobicyclic systems which already contain a pyrimidine ring by preferentially degrading the unwanted second ring. In the latter case, the bicyclic system may best be made from a pyrimidine in the first place, occasionally even from the self-same pyrimidine to which it reverts on degradation. Such syntheses may be of interest but are certainly not of any utility. 

The cycloaddition reaction of compound 6 with N-aryl- and N-aralkylazides 23 was also investigated (967(52)7183). Thiadiazabicyclo[3.1.0]hexene derivatives 25 were obtained from the labile triazoline intermediate 24 through nitrogen elimination. This bicyclic system underwent thermal transformation, producing thiadiazine dioxides 26 as the main product together with thiazete dioxides 27 and pyrazoles 28. 

Bicyclic isothiazole dioxides 81 (99JHC(36)161), on treatment with Ai-nucleo-philes such as benzylamine, afforded isothiazole dioxides 82a,b together with a minor amount of compounds 83. Alternatively, 82b could be obtained from 84 by reduction with 1,2-dimethylhydrazine and DBU. By using r-butylamine as the A-nucleophile, due to steric reasons, the formation of the isothiazole dioxide 85 could also be observed followed by transformation in the bicyclic system 86. 

When submitted to oxidation by a 2 per cent, solution of permanganate, pinononic acid, CgHj Og, melting at 128° to 129° C., the semi-carbazone of which melts at 204° C. Lastly the constitution of verbenone, as expressed by the above formula, is further confirmed by the fact that the bicyclic system is convertible into a monocyclic system by boiling with 25 per cent, sulphuric acid, with the formation of acetone and 3-methylcyclohexene-(2)-one-(l). This cyclohexenone has been characterised by its semi-carbazone (melting-point 198° C.) and by its conversion into y-acetobutyric acid (melting-point 36° C). The oily liquid, which did not react with sulphite, was submitted to benzoylation after dilution with pyridine. It thus gave rise to a benzoate from which was... 

In the course of studying the bromination reactions of the bicyclic systems we noticed that the reaction temperature has a dramatic influence on the product distribution. Increasing of the temperature gives non-rearranged reaction products (refs. 1,2). For this reason, we submitted 1 to high temperature bromination. To a solution of 1 in decalin at 150 C was added a hot solution of bromine in decalin in one portion. The colour of bromine disappeared immediately. After silica gel chromatography followed by fractional crystallization we isolated four products 2-6 in yields 8, 35, 37, and 9 % respectively. The structure of these compounds has been elucidated on the basis of spectral data by iH NMR and NMR experiments and by comparison with those reported in the literature. Symmetrical endo-c/5-isomer 6 has been observed for the first time. Studies concerning the mechanism of syn-addition show that the syn-adduct can arise either from direct... 

However, more recent work indicates that some bicyclic systems do indeed yield cyclic acetals from addition to carbene intermediates,<34,35>... 

Izquierdo et al. reported the enantioselective synthesis of 5-O-methylthioswainsonine 53 from a derivative a d-glucose as a single stereoisomer. Intramolecular alkylation of the tosylate precursor 52 created the bicyclic system in the final step of the synthesis as outlined in Equation (17) <1996TA2567>. 

A wide range of ring sizes have been synthesized, from the very small [1.1.0] fused ring systems to the macro-bicyclic systems. The reactivity and synthesis of the fused ring systems is reviewed first followed by the nonfused compounds. As the synthetic methods used to produce the various examples in this class of compounds were well reviewed in CHEC-II(1996), the synthetic methods section, Section 12.12.8, will outline selected types of compound within this group that have received more attention over the review period. 

Reaction of PTAD with a-angelica lactone gives the pyrazolotriazole 97 via an acyl ene reaction,152 and reaction with 4,4-diethyl-3,5-dimethyl-4//-pyrazole 2-oxide gives 98 after heating.153 A mesoionic bicyclic system 99 is proposed as a product from the reaction of DEAZD with triethylborane.154... 

---