Rearranged quinone-methide 3,3 -Rearrangement

Pirkle, W. H. Smith, S. G. Koser, G. F. Stereospecificity and wavelength dependence in the photochemical rearrangement of spiro[2.5]octa-4,7-dien-6-ones to quinone methides. j. Am. Chem. Soc. 1969, 91, 1580-1582. 

We also wanted to evaluate the disassembly of our dendritic system under physiological conditions. Thus, we synthesized a self-immolative AB6 dendron 32 with water-soluble tryptophan tail units and a phenylacetamide head as a trigger (Fig. 5.26) to evaluate disassembly in aqueous conditions. The phenylacetamide is selectively cleaved by the bacterial enzyme penicillin G amidase (PGA). The trigger was designed to disassemble through azaquinone methide rearrangement and cyclic dimethylurea elimination to release a phenol intermediate that will undergo six quinone methide elimination reactions to release the tryptophan tail units. 

Hulbert, P. B. Grover, P. L. Chemical rearrangement of phenol-epoxide metabolites of polycyclic aromatic hydrocarbons to quinone-methides. Biochem. Biophys. Res. Commun. 1983, 117, 129-134. 

Bolton, J. L. Acay, N. M. Vukomanovic, V. Evidence that 4-ally 1-o-quinones spontaneously rearrange to their more electrophilic quinone methides potential bioactivation mechanism for the hepatocarcinogen safrole. Chem. Res. Toxicol. 1994, 7, 443 450. 

Photolyses of spiroanthronetriazolines (Scheme 35) are anomalous they fail to yield aziridines.193 Complex reaction mixtures are obtained when the starting quinone methide has R = Ph, the aryliminoanthrone and the 10-arylamino (or imino) dibenzotropolones are obtained, but not when R = H (Scheme 155). The quinone methide may arise from a photochemical deamination of the diradical, whereas photofragmentation and rearrangement may account for the other products.193... 

Nucleophilic addition of a-halo-4-tolylsulfonyl methyl anions to quinone methides has been reported to afford three kinds of products as a result of domino reactions. Two of them were identified as rearrangement products and one as the vicarious nucleophilic substitution (VNS) product. An unexpected 1,2-migration of the tosyl group was observed.180... 

In another case, 4-alkylphenols can be transformed with the help of the flavoenzyme vanillyl alcohol oxidase (VAO) to either (R)-l-(4 -hydroxyphenyl) alcohols or to 1 -(4 -hydroxyphenyl)alkenes. Both products pass through a common intermediate, the p-quinone methide, which then either is attacked by water or rearranges. The product spectrum can be controlled by medium engineering in organic solvents such as acetonitrile and toluene, more ris-alkene but not trans-alkene, and less alcohol, are produced (van den Heuvel, 2001). A similar shift in cis/trans-alkene was achieved by the addition of monovalent anions that bind specifically close to the active site. 

In view of the reported lability of the chromene skeleton under environmental-like conditions, i.e. acid promotes dimerization and light causes rearrangement of chromene to quinone methide (4) one of our first concerns was the chemical stabilization of the precocene structures for its potential application in field trials. 

Lewis acidic activation, 529 mechanism, 532 Ph3SiCL-AgCI04 promoter, 538 polarity inversion, 529 quinone methide, 533 reaction profile, 531 rearrangement, 531 regioselectivity, 533 ot/p selectivity, 533 SnCl promoter, 537 stereoelectronic factor, 528 stereoselectivity promoter, 532 thermodynamic stability, 528 thiopyridyl donor, 531 trichloroacetimidate donor, 531 l,3,5-ttimethoxybenzene, 531 Glycosyltransferases, 469, 487, 488... 

A second class of mechanism-based inhibitors are those that in the course of their cleavage by the enzyme release an aglycone that rearranges to give a reactive species. Two examples may be cited. Salicortin [164], a natural product, is hydrolyzed by )6-glucosidases to produce, by rearrangement, a reactive quinone methide as shown inO Fig. 75 [165]. 

Quinones - Quinone methides are produced on irradiation of /7-benzoqui-nones in the presence of the eneyne (267) in methylene chloride as solvent. 1,4-Naphthoquinones also afford quinone methides but unstable spirooxetenes were also detected. The photochemical addition of phenanthraquinone and ace-naphthenequinone to eneynes has also been studied. 1,4-Benzoquinones undergo addition to electron donating alkenes to yield spirooxetanes. The resultant cyclohexadienones are themselves photochemically reactive and irradiation converts these into dihydrobenzofurans via a dienone-phenol rearrangement. " ... 

The hydroformylation of the orf/zo-prop-2-enylphenol 81 which contains no benzylic hydroxy group gives a mixture of the open-chain aldehyde 82 and the seven-membered cyclic hemiacetal 83 in a 82 83 ratio of approximately 40 60 (equation 34) °. The ben-zofuran epoxide 85 and its valence-isomeric quinone methide 86, both readily obtainable from benzofuran 84, rearrange thermally above —20°C to form the allylic alcohol 87 and the tautomeric phenol 88 (equation 35) . ... 

The mushroom tyrosinase-catalyzed oxidative decarboxylation of 3,4-dihydroxyphenyl mandelic acid (111, R = H) and a-(3,4-dihydroxyphenyl) lactic acid (111, R = Me) proceeds via the quinone methide intermediate 112. The coupled dienone-phenol rearrangement and keto-enol tautomerism transforms the quinone methide 112 into 1-acyl-3,4-dihydroxyphenyl compounds 113 (equation 48) . ... 

The quinone methides 343 undergo a rapid and practically quantitative rearrangement on neutral alumina at 70-80 °C to afford the alkenylphenols 344 (equation 164). 

The carbenes (23 R = H, Me) have been generated in Ar matrices at 10 K, by visible light irradiation of the diazoanthrone precursors. The carbenes were identified by trapping with O2, comparison of IR and UV-visible spectra with those of the parent anthronylidene, and by comparison of the IR spectra with spectra calculated by DFT methods. Further irradiation of the carbenes with visible or UV light induces hydrogen migration and rearrangement to the quinone methides (24 R = H, Me). 

The likely pathway of photochemical cleavage is a Norrish type II cleavage reaction (Scheme 17.1). During the photoisomerization, the activated oxygen of the nitro group abstracts a y-hydrogen from the benzylic position to produce a quinone methide-like intermediate, which subsequently rearranges to afford an o-nitrosobenzaldehyde and thereby releases the carboxylic acid product. 

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