Penta-substituted aromatics

Beller and coworkers recently reported a new strategy for the synthesis of poly-substituted anilines based on a three-component-coupling reaction and a domino deprotec-tion/aromatization reaction (equation l)44. A mixture of O-benzyl carbamate, p-toluene-sulfonic acid, aldehyde, AC2O and dienophile in /V-rnclhy I pyrrol idone was allowed to react for 24 h at 120 °C, followed by Pd/C catalyzed dehydrogenation in triglyme at 140 °C. A variety of tri-, tetra- and penta-substituted anilines were efficiently created by this domino process. 

Ellman and co-workers developed a rhodium-catalyzed C-H alkenylation followed by 67t-electrocyclization to give di-, tri-, tetra-, and penta-substituted pyridines. The dihyropyridine intermediates 285 can be directly aromatized via hydrogenolysis to pyridine derivatives 286 in moderate to good yields. ... 

The chiral penta-substituted corannulene, 1,3,5,7,9-penta-terfbutylcorannulene (37), which shows anomalous dynamic behavior [116], was reduced with Li and four reduction stages were observed [117]. The behavior of the anti-aromatic dianion and the aromatic tetraanion resemble that of the parent corannulene. In the final stage of the reduction, three distinct tetraanionic species could be detected. Two of the species are sandwich-type dimers, as in the case of corannulene, and are diastereomers, due to the chirality of 37 (RR/SS and meso - RS/SR). The third species was assigned as a tetraanionic monomer, which slowly disappears. 

Zirconium tetrachloride promotes a tandem nucleophilic addition and aldol-type condensation reaction of methyl propynoate, or /V,/V-dimethylpropynamidc, with aldehydes, or ketones, in the presence of tetra-n-butylammonium iodide (Scheme 6.13) [8] with a high selectivity towards the formation of Z-isomers. A similar reaction occurs between aliphatic and aromatic aldehydes and penta-3,4-dien-2-one to yield 1-substituted 2-acetyl-3-iodobut-3-enols (50-75%) [9]. 

The chemistry involved in nucleophilic aromatic substitution is well reflected in the reactions of a variety of nucleophiles with methyl penta-fluorophenyl ether (Ingemann et al 1982a). For most of the nucleophiles such as alkoxide, thiolate, enolate and (un)substituted allyl anions, the dominant reaction channel is the attack upon the fluoro-substituted carbon atoms, as is the case for OH-. The latter ion reacts approximately 75% by attack upon the fluoro-substituted carbon atoms and the remaining 25% by Sn2 (20%) and ipso (5%) substitution as summarized in (41). In the attack upon the fluorinated carbon atoms, the interesting observation is made that a F- ion is displaced via an anionic o-complex to form a F- ion/molecule complex, which is not observed to dissociate into F- as a free ionic product. 

The H NMR spectra of anionic and neutral phenyl-substituted penta-coordinate silicon complexes exhibited two distinct sets of aromatic multiplets arising from ortho-protons at low field and meta and para protons at high field. Thus, in the series RSi[ o-CgH )C(CF3)20]J the multiplet separation is 0.73 (R = CH3) and 0.66 ppm (H) relative to 0.35 ppm in Si[(o-CgH4)C(CF3)20]2 For 1-phenylsilatrane... 

In the monocyclic series, the 2,4-cyclohexadienones rearrange to photoproducts of potential synthetic value. However, for efficient 1,2-acyl migration, only a relatively small number of substrates are suitable. These must be highly substituted, for example (48). Whereas on direct excitation in methanol, cleavage to the isomeric ketenes (49) (4> 2 0.42) predominates, the remarkably stereoselective 1,2-acyl shift to the bicyclohexenone (50) is found either in trifluoroethanol or when the dienone is adsorbed on silica gel. The conversion to (50) is followed by a reversible phototransformation to the cross-conjugated dienone (51) and accompanied by aromatization to (52) to a minor extent. Such reactivity has also been verified for tetra- and penta-methylated 2,4-cyclohexadienones. The only photoreaction of the hexamethylated homolog, on the other hand, is ketene formation. ° ... 

There are several lines of evidence pointing to formation of a complexes as intermediates in EAS. One approach involves measurement of isotope effects on the rate of substimtion. If removal of the proton at the site of substitution is concerted with the introduction of the electrophile, a primary isotope effect is expected when electrophilic attack on the ring is rate determining. This is not the case for nitration. Nitration of aromatic substrates partially labeled by tritium shows no selectivity between protium-and tritium-substituted sites. Similarly, the rate of nitration of nitrobenzene is identical to that of penta-deuterio-nitrobenzene. ... 

There are several reports this year of photocycloaddition reactions between polycyclic aromatic hydrocarbons and 1,3-dienes. Anthracene (58 R = H) or 9-cyanoanthracene (58 R = CN) give [4 -I- 4] and [4 -I- 2]adducts on irradiation with buta-1,3-diene, but the different product ratios and temperature effects are used to support the previously proposed biradical mechanism for the reaction. Another report from the same group deals with anthracene-hexa-2,4-diene and 9-phenylanthracene-penta-1,3-diene or cyclohexa-1,3-diene systems in the case of 9-phenylanthracene (59) and cyclohexa-1,3-diene, two [2 -I- 2]cycloadducts involving a terminal aromatic ring are isolated, as well as the more usual [4 + 2] and [4 -f- 4]adducts involving the central ring. Irradiation of substituted anthracenes... 

Dialkyl acetone-1 -dicarboxylates 1 were transformed with DMFDMA by heating in ethanol into dialkyl l,5- is(dimethylamino)-3-oxo-penta-l,4-diene-2,4-dicarboxylates 52 in good yields. They were treated with ammonia, hydrazine, primary aliphatic, aromatic or heterocyclic amines to form dialkyl 1-substituted 4-oxo-l,4-dihydrop5u--idine-3,5-dicarboxylates 53 and 54.1,4-Diaminobenzene reacts with 52 in a 1 2 molar ratio to produce l,4-bis[3,5-fcis(alcoxycarbonyl)-4-oxo-l, 4-dihydropyridin-l-yl]benzene 55 in 57% yield. Hydrazine and mono-substituted hydrazines afforded 1-amino-1,4-dihydro-4-oxop5uidines 54 (00H2033) (Scheme 20). 

The principle of exciton coupling between vicinal benzoate chromophores has been extended to other aromatic carboxylic acid derivatives , including those of ring-substituted benzoic acids, 9-anthranoic acid (141) and p-methoxycinnamic acid (142). These derivatives have been widely used for the determination of the absolute stereochemistry in polyol natural products. The circular dichroism of the A -p-bromobenzoyl group combined with various 0-, 0,0 -di- and 0,0, 0"-tii-(p-bromobenzoyl) derivatives of 2-amino-2-deoxygalactopyranoside and an iV-anthranoyl group combined with tri-, tetra- and penta-p-methoxycinnamoyl derivatives of acyclic 1-amino polyols were studied to improve and develop microscale CD methods for the structural study of amino sugars. 

Krygowski, T. M., Ciesielski, A., and Cyrahski, M. 1995. Aromatic character and energy of the five- and seven-membered rings in derivatives of penta- and heptafulvene substituted in exocyclic position. Chem. Pap. 49 128-132. 

---