Benzannelation

Allylic protection groups and their removal through catalytic palladium rr-allyl methodology in transformations of heterocycles 98T2967. [3- -3]Benzannelation of heteroaromatics consisting of successive nucleophilic... 

In 1986 Yamashida et al. found that the reaction of the (morpholino)phenyl-carbene complex 46 with symmetric alkynes 47 gave the morpholinylindene derivatives 48 and 49, as well as the indanones 50 derived from the latter by hydrolysis, in excellent yields (Scheme 9) [54]. This contrasts with the behavior of the corresponding (methoxy)phenylcarbene complex, which solely undergoes the Dotz reaction [55]. This transformation of the amino-substituted complex 46 apparently does not involve a CO insertion, which is an important feature of the Dotz benzannelation. 

This crisscross or von Halban-White-type cyclization product is formed from the (E)-configured intermediate 87, which cannot undergo the 67r-electrocy-clization like the (Z)-configured isomer 88, to yield the benzannelation product 86 [78,79]. While the diastereoselectivity of the alkyne insertion must have been controlled by the electronic and not the steric factors of the substituents on the alkyne, the anti-configuration of the tricyclic system 85 was confirmed by an X-ray structure analysis [77]. 

Fig. 11 Comparison of the energy gap between highest occupied in-plane MO and lowest unoccupied in-plane MO in acyclic (left) and cyclic (right) benzannelated enediynes. Incorporation of the enediyne moiety into a cyclic structure simultaneously increases the energy of the occupied MO and lowers the energy of the unoccupied MO.

Fig. 12 Correlation between the calculated activation energy of the Bergman cyclization and the product of natural charges at the terminal acetylenic atoms of benzannelated enediynes. Only para substituents obey the correlation. Adapted from reference49.

Fig. 14 The correlation between C1-C6 distance and relative energies of ortho and para isomers of substituted benzannelated enediynes.

Since four-electron repulsion is the dominant factor in the reactant destabilization, any structural perturbation that either increases electron repulsion in the reactant or decreases the electron repulsion in the TS will decrease the activation energy for the cyclization. One way for placing an accelerating substituent in direct spatial proximity to the in-plane re-orbitals is to use appropriate ortho substituents in benzannelated enediynes. 

In this analysis, the activation barrier for both C1-C6 and C1-C5 cyclizations of enediyne radical-anions can be described as the avoided crossing between the out-of-plane and in-plane MOs (configurations). One-electron reduction populates the out-of-plane LUMO of the enediyne moiety. At the TS (the crossing), the electron is transferred between the orthogonal re-systems to the new (in-plane) LUMO. This effect leads to the accelerated cyclization of radical-anions of benzannelated enediynes, a large sensitivity of this reaction to re-conjugative effects of remote substituents and the fact that this selectivity is inverse compared to that of the Bergman cyclization. Similar electronic effects should apply to the other reductive cyclization reactions that were mentioned in the introduction. 

Fig. 20 The reaction energy profiles for thermal (on the left) and radical-anionic (on the right) C1-C6 and C1-C5 cyclizations of the parent benzannelated enediyne computed at the B3LYP/6-31G level.62...

Fig. 24 Relative energies for the transition states and radical products for the different cyclization pathways (benzannelated systems in parentheses).

These results, of course, contrast the significant effect of benzannelation in radical-anionic cycloaromatization reactions discussed above12 where not just the formation of a new aromatic cycle but also restoration of aromaticity in the previously existing cycle occurs at the same time in the cyclorearomatization process. 

Anthracyclinone synthesis. Wulf and Xu1 have reported a high-yield formal synthesis of 11-deoxydaunomycinone (5) in which the first step is a benzannelation of the chromium carbene 1 with the acetylene 2 to provide the naphthol 3, which is not isolated but treated with TFA to induce cleavage of the /-butyl ester and to... 

Numerous derivatives of the various systems discussed above are known (Story and Clark, 1972 Paquette, 1978 Childs, 1984). In most cases addition of a simple group, or even benzannelation, does not result in drastic changes to the parent homoaromatic nucleus. Systems falling within this category will not be further considered here. In this section radically different cationic homoaromatics that do not fall naturally under any of the other subheadings will be briefly examined. 

PET-5, PET-6 and PET-7 are examples of macrobicydic structures (cryptands) (Figure 10.12). The cavity of PET-6 and PET-7 fits well the size of K+. PET-6 has been successfully used for monitoring levels of potassium in blood and across biological membranes, but pH must be controlled because of pH sensitivity of this compound via protonation of the nitrogen atoms. This difficulty has been elegantly overcome in benzannelated cryptand PET-7, in which the aromatic nitrogens have lower pKa than those of aliphatic amines. 

Direct irradiation of orf/io-divinylbenzene (164) leads to the formation of the benzobi-cyclo[3.1.0]hex-2-ene isomer 167 as the major product. Deuterium labelling and methanol trapping experiments suggested the intermediacy of both 165 and 166, the expected products of irradiation of a benzannelated 1,3,5-hexatriene (equation 62)144. 

Other researchers have reported that the cyclization step is believed to be rate determining in the cycloaromatization (Bergman) reaction of aliphatic enediynes." It has been found that the rate-limiting step is hydrogen abstraction by benzannelation. This effect should be attributable to the faster rate of retro-Bergman cyclization from the aromatic ring-condensed 1,4-didehydrobenzene diradicals and/or the slower rate of hydrogen abstraction by them. 

Ullmann and Buncel attempted to deprotonate A -carene-2,5-dione (4) and the benzannelated derivative 5 in the hope of generating the possibly aromatic dianions 6 and 7. However, the dianions (and the monoanions) could not be isolated. On the grounds of deuterium exchange experiments, the strain energy of benzocyclopropene (1) was estimated to at least 45.5 kcal/mol higher than that of cyclopropane. 

Aromatization of dihalocarbene adducts to 1,4-cyclohexadiene or synthetic equivalents is the method of choice for the synthesis of the parent benzocyclo-propene (1). ° The mechanism of the aromatization step of the intermediate 7,7-dihalogenobicyclo[4.1.0]hept-2-ene (51) has been shown by labeling experiments with 51 depleted of C at Cl, to proceed via a series of elimination and double bond migration steps via cyclopropene- and alkylidenecyclopropane intermediates 52 to 54 with preservation of the original carbon skeleton. The synthesis of the benzannelated homologue, l//-cyclopropa[b]naphthalene (42), by the same route confirms these findings. Some skeletal rearrangement has, however, been observed in an isolated case. ... 

Arenium ion energies (AAH ion - neutral) and changes in carbon charges [Aq = (ion) - q (neutral)] for protonation of 90 and 91 were probed by the AMI method. The singlet oxidation dication of 90 was also calculated. The charge delocalization modes in the PAH arenium ions were discussed and compared. The AMI studies indicated that benzo[<3]coronene cations were less delocalized than benzo[g/z/]perylene ions. Benzannelation (91 92) severely limited the conjugation path in the carboca-tions despite the fact that coronene 92 was still planar. Further benzannelation (92 90) had a minimal effect on the charge delocalization mode. 

The benzannelated 1,2,5-oxadithiole 2,5-dioxide (38) shows strong S=0 stretching absorptions at 1120 cm and 1140 cm <8UOC269i>. The related 2,2,5,5-tetroxide (23) displays bands at 1390 cm (SO2 asymmetric stretch), 1180 cm and 1170 cm (both SO2 symmetric stretch) <82MI415-01 >. The IR spectrum of the latter compound also shows bands at 800 cm and 730 cm , attributed to ring SOS asymmetric and symmetric stretching vibrations, respectively. 

The benzannelated 1,2,5-oxadithiole 2,5-dioxide (38) was obtained upon acidification of diammonium benzene-1,2-disulfinate (Equation (28)) <8lJOC269l>. The corresponding tetroxide was similarly prepared by treatment of dipotassium benzene-1,2-disulfonate with chlorosulfonic acid <66HC(21-1)1>. 

This section also includes syntheses of annelated rings in which the annelating ring remains intact throughout the process, for example, formation of benzannelated rings from the appropriate benzene... 

Intramolecular Friedel-Crafts reactions have also been used to synthesize benzannelated dibenzofurans. 126... 

Scheme 16.5). Thus, the mechanism of the thermal decomposition of 7 has not been fully clarified, yet although the aryne contraction pathway has been established for some benzannellated derivatives of 4. A number of theoretical studies has been devoted to rearrangements on the CeKU potential energy surface. At... 

In further matrix isolation studies, cyclophanedione (38), was envisioned as a precursor, which upon long wavelength irradiation fragments quantitatively to p-xylylene and bisketene (39) (Scheme 16.14). In contrast to benzannellated derivative 32, however, the latter turned out to be photochemically stable under matrix isolation conditions. 

The use of butadienes with oxygen-bonded substituents with the same type of dieno-phile allows access to benzannelated pyranosides for example the phenol 77 can be... 

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