Quinones dihydro-, synthesis

The cis-2,3-diaryl-2,3-dihydro-l,4-benzoxathiin is a very unique structural motif. Other than scattered reports in the literature on the formation of this scaffold, there was no effective asymmetric synthesis for it [6]. We explored two major synthetic approaches to realize the key chiral as-diaryl dihydrobenzoxathiin scaffold, as shown in Scheme 5.3. One was the quinone ketal route in which the quinone ketal 13 and the chiral mercaptol alcohol 14 were the key intermediates. The other approach was the stereo- and enantioselective reduction of the diaryl benzoxathiin 16. The key mercaptol alcohol 14 and the diaryl benzoxathiin 16 were both envisioned to be prepared from the key, common iodoketone intermediate 15. 

Electrophilic aromatic substitution of the arylamine 780a using the iron-complex salt 602 afforded the iron-complex 785. Oxidative cyclization of complex 785 in toluene at room temperature with very active manganese dioxide afforded carbazomycin A (260) in 25% yield, along with the tricarbonyliron-complexed 4b,8a-dihydro-3H-carbazol-3-one (786) (17% yield). The quinone imine 786 was also converted to carbazomycin A (260) by a sequence of demetalation and O-methylation (Scheme 5.86). The synthesis via the iron-mediated arylamine cyclization provides carbazomycin A (260) in two steps and 21% overall yield based on 602 (607-609) (Scheme 5.86). 

In the synthesis of the monocyclic bisabolene-type sesquiterpenoids (-f)-curcuquinone and (—)-curcuhydro-quinone, 1,3-diol 107 was obtained by ozonolysis of 4,5-dihydro-l,3-dioxepin 106 (obtained by Heck reaction, see Section 13.11.10) and reductive workup (Scheme 25) <2003ARK232>. 

The BF3-catalyzed reaction of a-aminoaldehydes with 10 is valuable for highly stereoselective synthesis of 2,3,5-trisubstituted pyrrolidines with all -cis configurations (Equation (50)).197 The stereochemical outcome like chelation-controlled stereochemistry might result from the inherent conformational arrangement of the aldehyde-BF3 complex. />-Quinoneimines, o-quinones, and a-alkoxyhydroperoxides undergo similar types of [3 + 2]-cycloadditions with allylsilanes to afford dihydro indoles, dihydrobenzofurans, and 1,2-dioxolanes, respectively.164,175,198... 

Coupling carbonyl compounds with aromatic amines bearing amino, hydroxy, or thiol groups in o -positions is known to be a general method for the synthesis of 1,3-benzazoles, with the intermediate formation of the respective 2,3-dihydro derivatives. No heterocyclization occurs, however, in the reaction of o-phenylene-diamines or o-aminophenols with /i-quinones. In these cases, the reaction stops at the stage of formation of the deeply colored quinoneimine 105 which is similar to that obtained by the previously studied reaction of a variety of / -substituted anilines with derivatives of p -bcn/oquinonc.6 Compounds 10 do not undergo cyclization under heating or irradiation of its solution (Scheme 4). 

A series of dibenzofuran-l,4-diones illustrated in the following scheme were constructed via a DDQ-mediated intramolecular oxidative cyclization of quinone-arenols <070L2807>. Dibenzo[b] furans were also found to be made from 2//-pyran-2-ones and 6,7-dihydro-577-benzo[Z>]furan-4-one <07T1610>. The asymmetric synthesis of chiral furo-fused BINOL derivatives was achieved via copper(II)-mediated oxidative coupling from naphthofuranol in the presence of chiral phenylethylamine <07TL317>. 

An enantioselective aryloxylation of aldehydes is based on their prior conversion to an enamine through reaction with a chiral secondary amine catalyst. A subsequent inverse HDA reaction with o-quinones leads to 3-alkyl-2-hydroxy-l,4-benzodioxins with ee ca. 80% (Scheme 47). Manipulation allows the synthesis of (S)-2-alkyl-2,3-dihydro-l,4-benzodioxins <07TL1605>. In like manner, racemic nitidanin, which possesses antimalarial properties, has been synthesised through a regioselective cycloaddition of an o-quinone with a protected 3-arylpropen-l-ol <07TL771>. 

Perumal has described a four-component sequential protocol that allows the synthesis in good yields of antitubercular 2-aryl-5-methyl-2,3-dihydro-l/f-3-pyrazolones 18 from atylhydrazines, methyl acetoacetate, aromatic aldehydes and 5-naphthol in the presence of / -TSA in water under reflux conditions [13], The reaction proceeds by an initial acid-catalyzed cyclocondensation of the hydrazine and dicarbonyl components to give pyrazolinone 19. A parallel acid-catalyzed condensation between p-naphthol and the aromatic aldehyde affords the intermediate quinone methide 20, and Michael addition of the enol form of 19 onto the exocyclic double bond of 20 furnishes the final product (Scheme 1.9). 

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