Ring dearomatization

Halogenation of diazines containing one or more activating groups proceeds easily (Br2 or Cl2 in H20, AcOH, or CHC13, 20-100°C). Sometimes 5,5-dihalo products are formed by ring dearomatization, e.g. barbituric acid (107) gives successively (108) and (109). 

Scheme 13 Previously unobserved aryl transfer from palladium to a coordinated biaryl monophosphine ancillary ligand resulting in lower ring dearomatization...

Dipolar addition of mesitylene nitrile oxide with 4,7-phenanthroline 159 gave a 2 1 adduct 160 with a very low yield (Equation 19), the dearomatization of the pyridine ring giving rise to a more reactive double bond which, in turn, underwent cyclization <1998T9187>. 

Recently, some examples of the dearomatizing cyclization of unstabilized a-amino-organolithium compounds have been reported. For example, Clayden and Kenworthy showed that cyclization onto an oxazoline-activated naphthalene ring gives a lithium azaenolate. Note the high diastereoselectivity of the subsequent electrophilic quench, which places the electrophile cis to the carbon-carbon bond formed in the cyclization step (Scheme 25). "... 

Reaction of nucleophiles with the polarized N=C bond of azines proceeds via dearomatization and formation of the corresponding 1,2-adduct. With alkyllithiums, for example, it is possible to isolate the dihydro products by careful neutralization of the reaction mixtures these are, in general, rather unstable, however, and can easily be reoxidized to the fully aromatic compounds (Scheme 4). The dihydro adducts formed in these direct nucleophilic addition reactions can also be utilized for the introduction of substituent groups /3 to the heteroatom. Thus, reaction of (35) with one of a number of electrophiles, followed by oxidation of the intermediate dihydro product, constitutes a simple and, in many cases, effective method for the introduction of substituent groups at both the 2- and 5-positions of the pyridine ring (Scheme 4). Use of LAH in this sequence, of course, results in the formation of 3-substituted pyridines. 

Oxidation of a phenol to an acetoxy enone The key step in a recent synthesis of anthracyclinones is the oxidative dearomatization of the A ring of 1 to the enone 2 in 50-55% yield. The product was converted in several steps into the aglycone SM-173B (3). 

Complex 267 with methyl or phenyl lithium results in the opening of one of the chelate rings in bis-chelate 267 and the formation of anionic dearomatized 268 (R = Me, Ph) (08OM2627). The products are readily... 

The chemistry of seleninium salts is dominated by the electrophilicity of the cationic nucleus. The strongly electron-deficient heterocyclic ring and the annulled benzene ring are deactivated toward electrophilic attack. The nucleophiles are added to a- or y-carbons and the heterocyclic ring is dearomatized [7],... 

Regioselectivity of the Birch reductive alkylation of polysubstituted biaryls is affected by the electronic nature of substituents on both aromatic rings. The electron-rich 3,5-dimethoxyphenyl moiety is selectively reduced and then alkylated, whereas phenols and aniline are not dearomatized under these conditions. Biaryls possessing a phenol moiety are alkylated on the second ring, provided that the acidic proton has been removed prior to the Li-NH3 reduction.300... 

Fig. 5. The C(10) alkylation of -estradiol using osmium(ll) to dearomatize the A ring.

Nucleophilic attack at ring carbon occurs in benzenes only when strongly electron-withdrawing substituents are present. Even with pyridine, only the strongest nucleophiles react. This is because the formation of the initial adduct 9 from pyridine 8 involves dearomatization and consequently, once formed, many such adducts tend to rearomatize by dissociation (8 9). Benzo fusion decreases the loss in aromaticity for the formation of an adduct and thus quinoline 10 and especially acridine 11 react more readily with nucleophiles. 

The complex Re(Tp)(CO)(Melm)() -C6H6) is indeed able to effect dearomatization of the benzene ring aUowing its uncoordinated diene system to participate in Diels-Alder and other cycloadditions and, therefore, prodnce a synthetically useful protocol for benzene functionalization. ... 

Cyclizations of organolithiums onto pyrrole or aromatic rings leading to a fused heterocycle activation of the cyclizations by oxazolinyl substitutents use of dearomatization cyclization in the synthesis of cainoids, pyrrolidine-2,3-dicarboxylic acid derivatives capable of interaction with receptors of neurotransmitters 04S1721. 

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