Heteroannular

In steroid systems, the homoannular diene in ring A and the heteroannular diene in AB rings are generated. The allylic 3a-carbonate 514 affords the homoannular conjugated diene 515 as a main product and a small amount of the heteroannular diene 516. On the other hand, the heteroannular conjugated diene 516 is obtained exclusively from 33-carbonates 517. The elimination reaction proceeds smoothly at room temperature. 

The reaction has been applied successfully to the synthesis of a precursor of provitamin D. 520, which has a homoannular conjugated diene in the B ring[340]. Treatment of the 7a-carbonate 518 with Pd cataJy.st at 40 C afforded the 5.7-diene 520 regioselcctively in good yield. No heteroannular diene 521... 

Only the heteroannular diene 523 is formed by treatment of both a- and, 3-allylic carbonates 522 and 524 in a hydrindan. system with a Pd catalyst. No homoannular diene is formed. 

Heteroannular and acyclic dienes usually display molar absorptivities in the 8000 to 20 000 range, whereas homoannular dienes are in the 5000 to 8000 range. 

Base value for heteroannular or open chain diene, nm 214... 

Addition of hydride ion from the catalyst gives the adsorbed dianion (15). The reaction is completed and product stereochemistry determined by protonation of these species from the solution prior to or concurrent with desorption. With the heteroannular enolate, (13a), both cis and trans adsorption can occur with nearly equal facility. When an angular methyl group is present trans adsorption (14b) predominates. Protonation of the latter species from the solution gives the cis product. Since the heteroannular enolate is formed by the reaction of A" -3-keto steroids with strong base " this mechanism satisfactorily accounts for the almost exclusive formation of the isomer on hydrogenation of these steroids in basic media. The optimum concentration of hydroxide ion in this reaction is about two to three times that of the substrate. 

An example of stereocontrol by high pressure is given by the regio- and diastereoselective synthesis of hydrophenanthrenones [18] which are useful intermediates for synthesizing diterpenes and steroids, by EtAlCli-catalyzed cycloadditions of heteroannular bicyclic dienone 50 with (E)-piperylene (24) and 2,3-dimethyl-1,3-butadiene (51) (Scheme 5.4). 

One of the major problems was the case of the cisoid heteroannular dienes30,31, which present a CD band at about 240 nm with a sign opposite to that predicted on the basis of the diene helicity by means of the DR. 

With this approach, it is possible to justify the behaviour of a series of compounds, with particular reference to heteroannular cisoid dienes, as shown in Figure 6, which exhibit an anti-DR Cotton effect. 

Hence, assuming that the axial allylic contribution outweighs that due to the internal twist, the anomalous behaviour of s-cis heteroannular dienes is explained. 

However, an important difficulty is still present in fact, while for heteroannular cisoid dienes the allylic axial contributions are opposite in sign to the intrinsic, as depicted in Figure 6, in the case of the homoannular cisoid compounds, the two contributions have the same sign, as pointed out already by Burgstahler. 

Another, very notable, case where the two definitions are in conflict is that of het-eroannular cisoid dienes. As we have mentioned, this was just the class of molecules that stimulated the introduction of the AAR. Here, in order to have the correct results one should refer the chirality of the axial substituent to the individual double bonds (olefin-picture), as depicted in Figure 6 and in the upper parts of Figure 7(b) and (c). The case of heteroannular dienes is anyway peculiar, because in these compounds the chromophore is unusually distorted. This case is treated in the following section. 

We can collect here two classes of molecules, characterized by very large skew angles, between 40° and 90°. Such a situation is found in the first instance in heteroannular dienes. 

The two representations lead to the same result in the majority of the cases studied so far, where agreement with experiment is rather good and there are only few exceptions. The cases in which the two pictures are in conflict can be divided into two classes strongly versus normally distorted dienes (0 + 30°). The former is typified by the heteroannular dienes, which seem to obey the olefin-picture . The latter, much less well characterized, seems to be better interpreted in terms of the diene-picture . 

Enolization of a,/J-unsaturated ketones, e.g. 19, under strong acid conditions leads to a mixture of homoannular and heteroannular A2,4- and A4,6-dienes (e.g. 20 and 21 see equation 6)42. 

The heteroannular diene is thermodynamically more stable and the UV spectra of the two dienes differ, as suggested by Woodward and Fieser s rules5. 

A synthetic method for the preparation of the diketone substrates has been presented HiU, C.L., McGrath, M., Hunt, T. and Grogan, G., A generic and reproducible route to homo- and heteroannular bicyclic /3-drketones via Knochel-type 1,4-conjugate additions to o ,/ -unsaturated cycloalkenones. Synlett, 2006, 309. 

Rhode and Hoffmann have investigated sequential radical-mediated cyclizations of enynes as a method for the stereocontrolled synthesis of heteroannular acetals. The sequence generally followed a S-exo-trigfi-endo-dig-patlmay and gave the products in a stereocontrolled manner <2000T6479>. 

Several generalizations are made on the basis of such data as in Table I. For instance, the two rings tend to absorb independently of one another10 that is, no conjugation of one ring to another. Nesmeyanov has also noted that while intensities of bands in the 220-600 m region increased from ferrocene to monosubstituted ferrocenes to heteroannularly disubstituted ferrocenes, the opposite is true in the 180-220 mjx region. 

The major product is the heteroannular disubstituted derivative, l,l -diacetyl-ferrocene (I), while a very small amount of a homoannular isomer, 1,2-diacetylfer-rocene (II), is also obtained. The first acetyl group therefore appears to deactivate the substituted ring toward further electrophilic substitution, and the second acetyl group preferentially enters the opposite ring. 

A portion of these data is summarized in Table I, in which the acidities of a number of heteroannular ferrocenecarboxylic acids are compared. Introduction of an electron-releasing alkyl group into the unsubstituted ring lowers the acidity of the corresponding acid, while the introduction of electron-withdrawing groups increases it. 

In some related studies, Little and Eisenthal have found that a plot of similarly obtained pKA values for substituted ferrocenecarboxylic acids vs. Hammett para-sigma constants yields a satisfactory straight line (52). They have also recently measured the second-order rate constants for the esterification of a series of heteroannular substituted ferrocenecarboxylic acids with diphenyldiazo-... 

The carbonyl stretching frequencies of a number of heteroannular ferro-cenecarboxylic acids have been measured (41). The spectral shifts vary in the direction expected from the electronic effects of the substituent groups, and parallel the effects of these substituents on the acid constants. Little and Clark have also demonstrated resonance interaction of the ferrocenyl group in ferro-cenylazobenzenes by measuring shifts in the absorption maxima in the visible and ultraviolet spectra (49). 

Although evidence for thermally induced migrations points to a sigmatropic shift of the substituent, as discussed above, the photochemical conversion of 2-cyanopyrrole into 3-cyanopyrrole proceeds by a [1,3] sigmatropic walk of the heteroannular atom by route (a), as shown in Scheme 2. 2-Cyano-3-methylpyrrole and 2-cyano-4-methylpyrrole undergo similar phototranspositions to produce 3-cyano-4-methylpyrrole (by route a) and 4-cyano-2-methylpyrrole (by route a), respectively (75CC786), whilst 2-cyano-5-methylpyrrole produces... 

Parent heteroannular diene Parent homoannular diene Add for each substituent ... 

A Transoid 1,3-Diene. In contrast to the considerable number of photochemical rearrangements of homoannular dienes only one photochemical rearrangement of a transoid heteroannular diene has been reported. Irradiation of 3,5-cholestadiene (Formula 400) in ethanol gives the pentacyclic ether (Formula 401) (176). 

In formulating the rules (Table 3.8) for cyclic dienes, these are classified as either heteroannular or homoannular, e.g. 

The base Amax value for the former is taken as 214 nm and for the latter as 253 nm. To these values are added increments according to the nature of the substituent present and other structural features as shown in the table. In those cases where homoannular and heteroannular chromophores coexist in conjugation, the base value for the homoannular contribution is used, to which is added the appropriate increment for extended conjugation. It should also be noted that homoannular dienes in ring systems other than the six-membered ring do not give a satisfactory correlation between calculated and experimentally determined Amax values. The rules however are adequate for acyclic or heteroannular... 

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