Polycyclic polyenes

It will be seen that the aromatic energy of naphthalene (4dp) is double that of the monocyclic systems (2dp) naphthalene should therefore be a bicyclic aromatic system, and its chemistry is consistent with this. Phenyl-butadiene and [10]annulene are predicted to be similar in stability in practice [10]annulene is unstable because it cannot exist in a planar geometry, due to mutual interference by the central hydrogen atoms (18). The internal methylene derivative (19) of (18) is, however, stable, being almost planar. 

Another interesting way in which (18) can be obtained in a stable form is by triple union of nonatetraenyl and methyl, as indicated in Fig. 3.10(d). The third bond involves an inactive atom in the odd AH, i.e., one where the NBMO coefficient vanishes this union therefore makes no contribution to the first-order n energy [equation (3.23)]. The resulting bicyclic hydrocarbon, azulene, should therefore be in effect a monocyclic aromatic compound, the central bond playing no part in the aromatic system. Azulene is indeed much less stable than the isomeric naphthalene and the length of the central bond (1.48 A) is similar to that of single bonds in open-chain polyenes, e.g., the central bond in butadiene. 

This argument can be extended to other even, nonalternant cyclic polyenes in which there are two adjacent odd-numbered rings. Thus Fig. 3.11 

FIGURE 3.11. PMO analysis leading to the prediction that both pentalene and heptalene 

The PMO treatment can be extended to individual rings in polycyclic systems. Consider, for example, one of the terminal rings in anthracene (20). Anthracene can be constructed by union of methyl with the odd AH radical below in which the NBMO coefficients are as indicated. The n energies of union to the two bicyclic systems (21) and (22) and to (20) are a indicated. It will be seen that anthracene is more stable than (21) or (22), implying that that the terminal ring is aromatic. 

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TABLE 16. Experimentally determined structure parameters for small polycyclic polyenes (distances in A, angles in degrees)... 

Polycyclic systems. Dewar has extended his method to include the polycyclic polyenes. Fig. 21 illustrates the... 

The early Escherunoser-Stork results indicated, that stereoselective cyclizations may be achieved, if monocyclic olefins with 1,5-polyene side chains are used as substrates in acid treatment. This assumption has now been justified by many syntheses of polycyclic systems. A typical example synthesis is given with the last reaction. The cyclization of a trideca-3,7-dien-11-ynyl cyclopentenol leads in 70% yield to a 17-acetyl A-norsteroid with correct stereochemistry at all ring junctions. Ozonolysis of ring A and aldol condensation gave dl-progesterone (M.B. Gravestock, 1978 see p. 279f.). 

The organization of Part Two is according to structural type. The first section, Chapter Seven, is concerned with the synthesis of macrocyclic compounds. Syntheses of a number of heterocyclic target structures appear in Chapter Eight. Sesquiterpenoids and polycyclic higher isoprenoids are dealt with in Chapters Nine and Ten, respectively. The remainder of Part Two describes syntheses of prostanoids (Chapter Eleven) and biologically active acyclic polyenes including leukotrienes and other eicosanoids (Chapter Twelve). 

Polyene Cyclization. Perhaps the most synthetically useful of the carbo-cation alkylation reactions is the cyclization of polyenes having two or more double bonds positioned in such a way that successive bond-forming steps can occur. This process, called polyene cyclization, has proven to be an effective way of making polycyclic compounds containing six-membered and, in some cases, five-membered rings. The reaction proceeds through an electrophilic attack and requires that the double bonds that participate in the cyclization be properly positioned. For example, compound 1 is converted quantitatively to 2 on treatment with formic acid. The reaction is initiated by protonation and ionization of the allylic alcohol and is terminated by nucleophilic capture of the cyclized secondary carbocation. 

Polyene cyclizations are of substantial value in the synthesis of polycyclic terpene natural products. These syntheses resemble the processes by which the polycyclic compounds are assembled in nature. The most dramatic example of biosynthesis of a polycyclic skeleton from a polyene intermediate is the conversion of squalene oxide to the steroid lanosterol. In the biological reaction, an enzyme not only to induces the cationic cyclization but also holds the substrate in a conformation corresponding to stereochemistry of the polycyclic product.17 In this case, the cyclization is terminated by a series of rearrangements. 

Harring, S. R. Livinghouse, T. Polyene cascade cyclizations mediated by BF3CH3N02. An unusual efficient method for the direct, stereospecific synthesis of polycyclic... 

Many substituted thiophenes have also been electrochemically polymerised [19,54,399-405] (Table 4) as have thiophene dimers [21,37,55,251,400,406], trimers [21, 83,407], and tetramers [256,406], with the thiophene dimer giving rise to higher quality films than does the monomer [37, 395,408]. Several polycyclic monomers including a thiophene ring have also been polymerised [408-416], as have a series of compounds consisting of two thiophene rings linked by a polyene chain (Fig. 23c). The polymerisation of dithieno-thiophene (Fig. 23d) results in a polymer which shows remarkable similarity to polythiophene in its properties [409,410,414],... 

Some excellent examples of cationic polycyclizations, especially in the field of steroid synthesis, were described in Chapter 1. However, these polycyclizations can also be performed using a radical as initiator. Such reactions can be divided into those based on serial 6-mdo-trig cyclizations from polyene acyl precursors [92], radi-... 

It could be shown that the stereochemical outcome of such radical polycycliza-tions is influenced by the nature of the substituents (H, Me, C02R). For instance, as in the example 3-225, the all-( )-methyl-substituted polyene 3-228 also gave the corresponding all-trans-anti polycycle 3-229 in the presence of Bu3SnH and AIBN. However, the ester-substituted polyene 3-230 led to the cis-anti-cis-anti-cis tetracycle 3-231 under similar reaction conditions (Scheme 3.60). A certain degree of preorganization of the precursor is assumed to be the reason for this result [97]. 

This approach allows linear polyenes to be converted to functionalized polycyclic systems bearing up to six stereogenic centers. Another interesting use of the method deals with the synthesis of azapropellanes [45]. 

The largest contribution and variety in the family of polyenes is to be found in the group of bicyclic and polycyclic compounds. For this chapter we selected those compounds which represent the most important prototypes of different kinds of interaction, namely cyclopropyl-conjugation, spiroconjugation, hyperconjugation and homoconjugation. 

Linear and branched molecules, as well as some of the monocyclic ones, are identified only by their IUPAC names if their structure is immediately obvious. In the absence of accepted trivial or easy-to-read systematic names, larger polycyclic dienes and polyenes with rather unwieldy IUPAC names have been given numbers (4th column of the Table), which refer to the formula scheme following Table 1. 

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