Ring-fusion substituents

Artemisinic acid is a cw-fused decalin we can still deduce its shape from the steroid approach. Note that both hydrogens at the ring fusion are down, whereas we have been looking at systems where the ring fusion substituents are up. We shall need to change ring B rather than ring A. 

The oxazolo[3,4-a]azepinones 4, in which 5 7 ring fusion imparts considerable planarity and hence antiaromatic character on the ring system, undergo spontaneous dimerization.153 The mode of dimerization appears to depend on the nature and position of substituents. The unsubstituted system and the 9-chloro derivative 4 (R1 = Cl R2 = H) produce the exo.anti-dimers, e.g. 5, upon spray-vacuum pyrolysis at 300 C, whereas the 7-/ert-butyl, 7-bromo, 7-methyl, and 7,9-dichloro (4, R1 = R2 = Cl) compounds yield the exo,syn-dimcrs, e.g. 6. 

Some examples of IMDA reactions are given in Scheme 6.5. In Entry 1 the dienophilic portion bears a carbonyl substituent and cycloaddition occurs easily. Two stereoisomeric products are formed, but both have the cis ring fusion, which is the stereochemistry expected for an endo TS, with the major diastereomer being formed from the TS with an equatorial isopropyl group. 

Diaza-OTdo-hexaboranes [N2B4R4R 2] are the products of the fusion of rings NB2R2R. The mechanism of this cluster formation was investigated and in the case of the neopentyl substituent (R = CH2/Bu, R = /Bu) a tetracyclic molecule was identified as a possible intermediate in the ring fusion reaction.81,8111... 

PN and Parent Exo PX) have unsubstituted norbornenyl rings and differ from each other only in the stereochemistry of their ring fusion. These compounds have been elaborated by the incorporation of either a phenyl (tf>) or a carbomethoxy (C) group in the bridgehead (B) or vinyl (V) positions. Thus, the notation VN represents PN with a phenyl substituent at a vinyl position, while CBX represents PX with a carbomethoxy substituent at the bridgehead position. The isomerization and polymerization chemistry of these nine compounds (PN, PX, 4>BN, (jiVN, (jiVX, CBN, CBX, CVN, CVX) are the main concerns of our work. 

The ring-chain tautomerism of tetrahydro-l,3-oxazines is very sensitive to the stability differences, the substituents and the ring-fusion effect (Section IV,A). It also reveals a considerable stability difference in favor of the cis isomers. In the reactions of the cis- and trans-2-amino-l-cyclohexanols, as compared with the hydrindane analog systems, where the heteroatoms form an oxazolidine ring cis- or tra 5-fused with cyclohexane, the corresponding stability differences were again found to be in favor of the cis isomer (93JOC1967). 

An enormous number of different 1,3-dioxane structures have been reported since 1996 in Figure 3, mono-, bicyclic and spiro variants are presented, while Figure 4 contains examples of tricyclic structures with the 1,3-dioxane moiety. The conformations, bond lengths, bond and dihedral angles of the 1,3-dioxane rings are determined by the ring fusion, the attached substituents, and the presence of exocyclic double bonds. Thus, published structures are classified as either monocyclic (mono), spiro-substituted (spiro), bicyclic (bi), or tricyclic (tri). The well-known Meldrum s acid derivatives (M) have been most intensively studied. 

Dimerizations of alkenes bearing heteroaromatic substituents such as pyridine have been widely reported. 2-(/ -Styryl)quinoline (239), for example, yields on irradiation in the solid state a dimer which can be represented either as the head-to-head dimer (240) or the head-to-tail dimer (241).225 The stereochemistry of ring fusion in this and many other related dimers is not known. The structures of the dimers obtained by solid state photolysis of /3-2-furyl-, jg-2-thienyl-, and /9-3-pyridylacrylic acid have been interpreted in terms of crystal packing.226... 

In natural steroids, there are examples of the A/B ring fusion being trans or cis, or having unsaturation, either A4 or A5. In some compounds, notably the oestrogens, ring A can even be aromatic clearly there can then be no bridgehead substituent at C-10 and the normal C-10 methyl (C-19) must therefore be lost. All natural steroids have a trans B/C fusion, though cis forms can be... 

These reactions may show considerable selectivity. Corey and Chaykovsky19 give an example with the terpene carvone 80. The ylid 78 is made with NaH and reacts only with the enone and not with the unconjugated alkene. The product is one diastereoisomer 81 as the ylid has added to the opposite side of the ring to the only substituent. It also has retained the stereochemistry of the cis alkene but that is inevitable as 3/6 ring fusion must be cis. 

From the formula it is obvious that all the six-membered rings are transfused. This compels them to adopt a chair conformation and hence all the substituents at the ring fusion sites to occupy axial positions. Thus by knowing that the methyl group at position 19 is trans to the methoxy group it follows that the methoxy group must occupy an equatorial position. 

The effect of one substituent on the reactivity of another is generally similar to that observed in the corresponding polysubstituted benzenes. However, the partial bond fixation in an azole can lead to differential effects in the mutual interactions of substituents, similar to those found in naphthalene where the benzene ring fusion induces bond fixation. 

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