Alkylation benzo -fused rings

C-Alkylations and -additions occur by prior formation of a carbanionic center bonded to the heterocycle. This carbanion will be formed only if the heterocycle contains a benzo-fused ring and/or electron-withdrawing substituents and/or a positive charge. 

Azete, trisdimethylamino-isolation, 7, 278 Azetes, 7, 237-284, 278-284 benzo fused, 7, 278 benzodiazepine fused applications, 7, 284 fused ring, 7, 341-362 structure, 7, 360 2,3-naphtho fusion, 7, 278 reactivity, 7, 279 structure, 7, 278 synthesis, 7, 282-283 Azetidine, acylring expansion, 7, 241 synthesis, 7, 246 Azetidine, 3-acyl-irradiation, 7, 239 synthesis, 7, 246 Azetidine, N-acyl-synthesis, 7, 245 Azetidine, alkyl-synthesis, 7, 246 Azetidine, 3-alkylthio-synthesis, 7, 246 Azetidine, 3-amino-synthesis, 7, 246 Azetidine, N-amino-oxidation, 7, 241 synthesis, 7, 246 Azetidine, aryl-synthesis, 7, 246... 

The pyrazine ring is stable toward permanganate oxidation, and this explains a variety of pyrazinecarboxylic acids that have been prepared from quinoxalines or benzo-fused quinoxalines. In contrast, alkyl side chains on pyrazines are effectively oxidized by permanganate, selenious acid, selenium dioxide, or dichromate to afford the corresponding carboxylic acids (Section 8.03.7.1). Oxidation of pyrazines with hydrogen peroxide or percarboxylic acids gives pyrazine A -oxides and/or A, A -dioxides (Section 8.03.5.2). 

The photolysis of nitrosopregnone steroid (117) afforded the 18,20-benzo-fused compound (118) as the major product (24%) along with the diol (119) (6%), whilst the expected C(18) rearranged product (120) is not isolated (Scheme 17).277 Reaction proceeds via the C(18) alkyl radical (121), formed in accordance with the accepted C(ll) O—NO bond homolysis and H-abstraction pathway, before either addition of C(11) radical (121) to the aromatic ring to afford (118) or H abstraction to give (119). 

The methods most frequently used to synthesize these compounds are [6 + 0(a)] cyclizations. Ring closures may take place via intramolecular alkylation, condensation, or nucleophilic substitution. The starting materials for the cyclizations in the case of pyrazino-oxazines are always pyrazine derivatives. Only a few representatives of these systems have been prepared. Pyrimido-oxazines are the most explored group of compounds. In the bicyclic series, cyclizations have been carried out in most cases from pyrimidine intermediates and only rarely from morpholino intermediates. For the preparation of benzo-fused derivatives, both benzoxazine and quinazoline intermediates have been used. Pyrazino-oxazines represent a small group of compounds. For cyclizations, both pyrazino and oxazino intermediates have been used. There are many lactone structures among these compounds. For their preparation, the usual methods of lactone formation have been applied. 

Alkylation and acylation at nitrogen in l-oxa-2,4-diazines, and the benzologs, has been discussed previously in summary, regioselective alkylation is possible at N-4 of 4/7-1-oxa-2,4-diazin-5(677)-ones, and acylation at N-2 of 2/7-benzo-l-oxa-2,4-diazines is slow <1996CHEC-II(6)651>. The N-2-alkylated l-oxa-2,4-diazines 68 and 69 have been produced as potential pesticides <2005W02005116032> the N-2-acylated fused-ring derivative 70 has been claimed as a reverse-turn peptidomimetic with potential anticancer activity <2002W02002096872>. 

Some benzo-fused, eight-membered ring, methyl-substituted sulfur ylides can show methyl resonance at unusually low values d 1.8-2.0 if the ylide methyl group can be shielded by the benzene ring in a predominant conformation <82CC1060,84CPB4360>. This would be expected to extend to other alkyl group substituted, benzo-fused ylides. 

In a similar manner to that described for bicyclic lactams (Section 1.1.1.3.3.4.1.5.I.). alkylation reactions of tricyclic lactams, which contain a fused benzene ring adjacent to the carbon undergoing alkylation, have been exploited14. The first alkylation of the benzo-annulated bicyclic lactam 1 gives a mixture of diastereomers, which is then further alkylated. In the second alkylation step, the counterion on the alkoxide, which is formed prior to enolate formation, proved to be crucial for the diastereoselectivity of the subsequent alkylation reaction. The best diastcrcoselectivity was obtained when either dichlorobis(ij5-cyclopentadienyl)zirconium or triisopropoxytitanium chloride was added to the preformed alkoxide, followed by enolization and alkylation. Using this method the second alkylation step gives a satisfactory diastereoselectivity. Hydride reduction of the purified major diastereomer 2, followed by acid treatment of the product, furnishes chiral naphthalenones 414. 

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