Compounds bicyclic

Bicyclic Compounds. Diethanolamine reacts with 1,1-difluoro-olefins to give 1 -aza-4,6-dioxabicyclo [3,3,0]octanes (478).  

The stereochemistry of methyl-substituted piperidine-2-carbinols (486) has been assigned by an n.m.r. and i.r. investigation of their oxazolopiperi-dine derivatives (487) 

Potassium methyIpyrrole-2-carboxyIate (488) reacts with styrene oxide in moist conditions to give (489), which is cyclized by polyphosphoric acid to (490). When cyclohexene oxide is used instead of styrene oxide the tricyclic compound (491) is formed.  

Ring opening of the oxazine (492) by palladium catalysis occurs with inversion of configuration to give (493), which is a key intermediate in the synthesis of the asymmetrically labelled compound (494) of biosynthetic importance.  

It could be expected that by using appropriate substrates free radical intramolecular addition could be used to synthesize bicyclic compounds and that the yields would be best in the CyS/Cy6 case. This is why we shall Hrst discuss examples involving the CyS/Cy6 case. 

An interesting reaction has been reported by Stork. Treatment of an unsaturated keto epoxide such as 264 with hydrazine in methanol gives the bicyclic compound 266 in 85% yield instead of the expected allylic alcohol from the Wharton reaction. A concerted mechanism and a free radical mechanism have been considered by Stork and, indeed, a free radical mechanism seems in accord with the other results described. This mechanism 

Examples of cyclization involving thiyl radicals leading to bicyclic compounds in the Cy5/Cy6 case have been also recorded. From the behavior of unsaturated aliphatic radicals one would expect to obtain a mixture of (Cy5) and (Cy6) products. In fact, the examples recorded and discussed in 

In conclusion, intramolecular free radical addition may be a useful method of synthesizing bridged cyclic compounds. From the examples of the Cy5/Cy6 case noted in this section, it may be concluded that a large preference for the (Cy 5) radical formation again exists and that, in some cases, a very high stereoselectivity in the last transfer step may be observed. The same stereoselectivity is often observed in cationic-induced cyclizations. 

More recently, Biichi has described the synthesis of dihydroagarofuran, an interesting fragrance of the oriental type, starting from (-)carvone the last step involves a selective Cy6 cyclization in a Cy6/Cy7 case (67% yield).  

This type of tautomerism can be seen in azapentalenes possessing at least one NH group. The factors, which influence the relative stabilities of NH tautomers, were summarized in four rules [78AHC(22)183]. 

Dipole moments and total energies for pyrazolo[l,5-b]-s,-triazole tautomeric forms 97a-97c were calculated using CNDO/2 and CNDO/S (76T341) the results predict the stability of tautomers in a 97a 97b 97c sequence. So far, no ab initio calculations or synthesis of 97 have been reported. For pyrazolo[3,2-c]-5-triazole 98 (76T341), the calculated dipole moments, electronic absorption, and proton chemical shifts are in a good 

The existence of pyrazolo[ 1,5-aJbenzimidazolc in form 101a in DMSO-c/6 has been established by 13C NMR spectroscopy (77ORM508). 

The couplings between the carbon atoms and the proton bonded to the pyrrole nitrogen atom observed for imidazo[l,2-b]pyrazolc 102 (77OM508) suggest the predominance of 102a. 

The tautomerism of 3-mcthyl-v-triazolo[4,3-a]bcnzi midazole 106 was established from the 13C-chemical shifts (in DMSO-d6) of the parent compound and its N-methylated derivatives (78BSF273). Tautomers 106a and 106b are both present in DMSO, whereas 106a is predominant in ethanol and 106b in dioxane (UV spectroscopy) (75JHC197). The interpolation of 13C-chemical shifts was suggested for calculations of tautomeric equilibrium constants. 

Ionization of an electron from the M—M bond of the long M4H6 isomers leads to the 2Aj M4Fk+ cation radicals which have significantly shorter central M—M bonds than in the neutral long-bond isomer (Table 20), contrary to the tentative expectation that this bond will be longer in the cation radicals. The extent of M—M bond shortening upon ionization increases from M = Si to M = Pb (Table 20). Ionization from the short-bond  

TABLE 20. Structures of group 14 analogs of bicyclo[1.1.0]butanes, of their cation radicals and of metallabicyclo[2.2.0]hexanes (pm, deg) 

Miriam Kami, Yitzhak Apeloig, Jurgen Kapp and Paul von R. Schleyer 

TABLE 21. Strain energies (kcalmol 1) of metallabicyclo[2.2.0]hexane (26), metallabicyclo[1.1.0]butane (25) and C-M4H8 (13) 

Metallabicyclo[2.2.0]hexanes 26 are considerably less strained than 25. The strain in MgHio, calculated by the homodesmotic equation 18, decreases in the order M = C Si Ge Sn Pb from ca 54 kcalmol-1 for M = C to 19 kcalmol-1 for M = Pb, very similar to the trend in the monocyclic M4H8 series (Table 21). Nagase and Kudo observed that the strain energy in polycyclic and polyhedral compounds (see below) is additive, e.g. it is twice as large in 26 than in the monocyclic M4H8194. 

If two heterocyclic rings are fused, additional mles are required. A parent ring is selected, and the other ring is considered fused on, as was observed for benzene fusion. Some mles are as follows  

COMMON RING SYSTEMS AND THE NAMING OF HETEROCYCLIC COMPOUNDS 

If both rings contain N, the larger ring is the parent. 

If both rings are of the same size, that with the most N atoms is the parent, or if the same number of N atoms is present, that fusion of the rings that gives the smallest numbers for N when the bicycle is numbered is chosen. 

If no N is present, O has priority over S over P, and then the above mles are applied. 

Now that we have dealt with both simple and complicated cycloalkanes (molecules containing a single ring), it is time to look briefly at molecules containing more than one ring. We have met such structures before, in both Chapter 2 (p. 85) and Chapter 3 

Bridged substitution (more than two carbons are shared if n = 0, the molecule is fused) 

FIGURE 5.47 Rings can share a single carbon (spiro), two carbons (fused bicycbc), or more than two carbons (bridged bicyclic). 

FIGURE 5.48 A two-dimensional picture of spiropentane is misleading. The two rings be in perpendicular planes. 

FIGURE 5.49 Some spiro compounds. Don t worry about the exotic names. 

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A major difficulty with the Diels-Alder reaction is its sensitivity to sterical hindrance. Tri- and tetrasubstituted olefins or dienes with bulky substituents at the terminal carbons react only very slowly. Therefore bicyclic compounds with polar reactions are more suitable for such target molecules, e.g. steroids. There exist, however, several exceptions, e. g. a reaction of a tetrasubstituted alkene with a 1,1-disubstituted diene to produce a cyclohexene intermediate containing three contiguous quaternary carbon atoms (S. Danishefsky, 1979). This reaction was assisted by large polarity differences between the electron rich diene and the electron deficient ene component. 

Synthesis by high-dilution techniques requires slow admixture of reagents ( 8-24 hrs) or very large volumes of solvents 100 1/mmol). Fast reactions can also be carried out in suitable flow cells (J.L. Dye, 1973). High dilution conditions have been used in the dilactam formation from l,8-diamino-3,6-dioxaoctane and 3,6-dioxaoctanedioyl dichloride in benzene. The amide groups were reduced with lithium aluminum hydride, and a second cyclization with the same dichloride was then carried out. The new bicyclic compound was reduced with diborane. This ligand envelops metal ions completely and is therefore called a cryptand (B. Dietrich, 1969). 

The 3-amino group brings a second nucleophilic center in these structures thus 2-imino-3-amino-4-methyl-4-thia201ine (409) reacts with methyl diloroformate to give the bicyclic compound (410) (Scheme 234). Other thiazolo-s-triazoles of the [3.2-l>] type have been obtained by... 

The bicyclic compound decahydronaphthalene, or bicyclo[4.4.0]decane, has two fused six-mem-bered rings. It exists in cis and trans forms (see Fig. 1.10), as determined by the configurations at the bridgehead carbon atoms. Both cis- and rran -decahydronaphthaiene can be constructed with two chair conformations. 

Methylpyridazine gives the pyridazine Reissert compound (105) with trimethylsilyl cyanide and freshly distilled benzoyl chloride. On the other hand, when pyridazine or 3-methylpyridazine reacts with undistilled benzoyl chloride the bicyclic compounds (106) are formed and these react with dimethyl acetylenedicarboxylate in anhydrous DMF to give pyrrolopyridazine derivatives (107 Scheme 30) (81JHC443). 

The possible structures for isothiazoles are discussed in Section 4.01.1, and attention in this chapter will be directed mainly towards the aromatic systems, as defined in Section 4.01.1. The saturated isothiazole 1,1-dioxides (5) are known as sultams, and bicyclic compounds of structure (6) are called isopenems. Isothiazoles readily coordinate to metals (76MI41703, 78MI41701, 79MI41700, 80MI41701). Coordination usually takes place through the nitrogen atom, but sulfur coordination can occur with soft metals such as cadmium or mercury. Some specific coordination complexes are discussed in later sections. 

The relation of rates of reduction with NaBH4 to variations in structure in a wide variety of monocyclic and bridged bicyclic compounds has also been discussed for example, a methyl a to a ketone slows the rate of reduction. Brown ° stated that reactions should not be discussed in terms of axial and equatorial attack, since the rates simply reflect differences in the energies of the possible transition states and not enough is known about the transition state to analyze it. He accepted th concepts of SAC and PDC, but preferred to call them steric strain contrpl and product stability control. ... 

The cyclic sulfur imides readily undergo condensation reactions in the presence of a base, e.g., pyridine. For example, the reaction of S7NH with sulfur halides, S Cla or SOCI2, produces the series (S7N)2Sx (x = 1, 2, 3, 5), or (S7N)2S0, respectively. The bicyclic compound S11N2 (6.6) is obtained by treatment of 1,3-S6(NH)2 with The reaction... 

The reaction of Me3SiNSNSiMc3 with TeCU is an especially fruitful source of chalcogen-nitrogen halides that contain both sulfur and tellurium. The initial product of this reaction is the bicyclic compound 8.17, which is obtained when the reaction is carried out in a 1 2 molar... 

The bicyclic compound 8.17 also serves as a source of the five-membered ring 8.20 upon reduction with SbPhs. In contrast to the related S or Se systems, 8.11a and 8.11b, both Cl substituents are attached covalently to Te in 8.20. Reaction of 8.20 with an excess of AsFs in SO2 produces the eight-membered cyclic [Tc2S2N4] dication, which exhibits a Te-Te bond length of 2.88 A (cf. 2.70 A for a Te-Te single bond) and no transannular S S bonding J... 

In contrast to the behaviour of 9.4a, the acyclic Te(IV) compound Cl2Te(NSO)2 can be isolated from the reaction of 9.4c with CI2 under mild conditions.Subsequent reaction of Cl2Te(NSO)2 with CI2 generates the bicyclic compound Cl6Tc2N2S (Section 8.10). 

Dehydrogenation of amino alcohols of type 40 affords even bicyclic compounds 41, the formation of which can be explained by nucleophilic attack of the hydroxyl group on the formed enamine salt (133,134). 

The bicyclic compound (76) gave carbon dioxide, the saturated amine (122), and the unsaturated lactam (123). 

The uses of an activation-numbering system for bicyclic compounds will be presented and the generalizations summarizing the reactivity... 

Tile existence of two annular tautomers in solution has been concluded from NMR spectroscopy for the cyclic A -acylbenzazoles 83 [82JPR(324)569]. Enamine and methylene imine tautomers have been described for condensed azolo-quinoxalines [93JHC782, 93JHC1463 95H2057] this type of tautomerism is discussed in detail for the [6.6]bicyclic compounds (see Section III,E,2). 

D. [5.6]Bicyclic Compounds Containing O and S in the Five-Membered Ring... 

Extension and revision of the von Baeyer system for naming polycyclic compounds (including bicyclic compounds), lUPAC recommendations for naming heterocycles 99PAC513. 

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