Ring Syntheses by Transformation of Other Rings

Ring Syntheses by Transformation of Other Heterocyclic Systems... 

RING SYNTHESES BY TRANSFORMATION OF OTHER HETEROCYCLIC SYSTEMS 85... 

These consider ring syntheses from non-heterocyclic compounds first, followed by transformation of other heterocyclics. Syntheses in which no new heterocyclic ring is formed are dealt with primarily in the appropriate reactivity section, but with cross-referencing when necessary. Ring syntheses from acyclic precursors are dealt with as logically as possible according to the number and nature of the new ring bonds formed in the process. 

There have been no reports of 1,2,3-oxadiazoles synthesized by transformation of another ring since the last survey <1996CHEC-II(4)165> other than those involving cyclization of substituents attached to benzene (Section 5.03.9). 

Pyrrole syntheses have been organized systematically into intramolecular and intermolecular approaches as well as by the location of the new bonds that describe the pyrrole ring forming step (two examples are illustrated below). Multi-component reactions appear at the end of the section on intermolecular approaches. The final section includes pyrrole syntheses that arise from transformations of other heterocycles. 

Many ring syntheses of oxepines and hydrogenated oxepines by the transformation of other rings are based on pericyclic reactions <88S569>. Below are presented various synthetic methods, which are classified by the nature and size of the starting ring. 

Pyridine ring syntheses (48) can be classified into essentially two categories ring synthesis from nonheterocyclic compounds, and synthesis from other ring systems. The synthesis of pyridine derivatives by transformations on the pyridine ring atoms and side-chain atoms have been considered in the previous section. 

If the cycloaddition and cycloreversion steps occurred under the same conditions, an equilibrium would establish and a mixture of reactant and product olefins be obtained, which is a severe limitation to its synthetic use. In many cases, however, the two steps can very well be separated, with the cycloreversion under totally different conditions often showing pronounced regioselectivity, e.g. for thermodynamic reasons (product vs. reactant stability), and this type of olefin metathesis has been successfully applied to organic synthesis. In fact, this aspect of the synthetic application of four-membered ring compounds has recently aroused considerable attention, as it leads the way to their transformation into other useful intermediates. For example aza[18]annulene (371) could be synthesized utilizing a sequence of [2 + 2] cycloaddition and cycloreversion. (369), one of the dimers obtained from cyclooctatetraene upon heating to 100 °C, was transformed by carbethoxycarbene addition to two tetracyclic carboxylates, which subsequently lead to the isomeric azides (368) and (370). Upon direct photolysis of these, (371) was obtained in 25 and 28% yield, respectively 127). Aza[14]annulene could be synthesized in a similar fashion I28). 

On the contrary, a-lithiated epoxides have found wide application in syntheses . The existence of this type of intermediate as well as its carbenoid character became obvious from a transannular reaction of cyclooctene oxide 89 observed by Cope and coworkers. Thus, deuterium-labeling studies revealed that the lithiated epoxide 90 is formed upon treatment of the oxirane 89 with bases like lithium diethylamide. Then, a transannular C—H insertion occurs and the bicyclic carbinol 92 forms after protonation (equation 51). This result can be interpreted as a C—H insertion reaction of the lithium carbenoid 90 itself. On the other hand, this transformation could proceed via the a-alkoxy carbene 91. In both cases, the release of strain due to the opening of the oxirane ring is a significant driving force of the reaction. 

It should be noted, however, that the 1,3-dipolar cycloaddition chemistry of diazo compounds has been used much less frequently for the synthesis of natural products than that of other 1,3-dipoles. On the other hand, several recent syntheses of complex molecules using diazo substrates have utilized asymmetric induction in the cycloaddition step coupled with some known diazo transformation, such as the photochemical ring contraction of A -pyrazolines into cyclopropanes. This latter process often occurs with high retention of stereochemistry. Another useful transformation involves the conversion of A -pyrazolines into 1,3-diamines by reductive ring-opening. These and other results show that the 1,3-dipolar cycloaddition chemistry of diazo compounds can be extremely useful for stereoselective target-oriented syntheses and presumably we will see more applications of this type in the near future. 

According to the reaction types these syntheses may be classified as cyclocondensations, cycloadditions, or oxidative cyclizations (80PAC1611). To some extent TPs are prepared by other transformations of the five- and/or six-membered ring. 

We consider successively the synthesis of fully-conjugated derivatives by ring closures of type 215 (Section 4.3.3.2.2), 216 (Section 4.3.3.2.3), and 217 (Section 4.3.3.2.4). This is followed by a consideration of methods involving C-C bond formation and/or 1,3-dipolar cycloadditions (Section 4.3.3.2.5), and syntheses of oxo-containing and reduced rings from acyclic precursors (Section 4.3.3.2.6). Finally, transformations from other heterocycles are described (Section 4.3.3.2.7). 

Very many syntheses of isoxazoles from other heterocyclic compounds have been reported. The subject of ring transformations of heterocycles has been well reviewed35-37 and since many of the reactions are covered by the categories already discussed (the starting heterocycle serving merely as precursor of the appropriate intermediate), only a brief summary, with... 

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