Quinone methides thermal generation

The combination of neutral non-aromatic and zwitterionic aromatic contributing valence bond structures confers a distinctive chemical reactivity to quinone methides, which has attracted the interest of a tremendous number of chemist and biochemists. This chapter reviews reactions that generate quinone methides, and the results of mechanistic studies of the breakdown of quinone methides in nucleophilic substitution reactions. The following pathways for the formation of quinone methides are discussed (a) photochemical reactions (b) thermal heterolytic bond... 

Irradiation of 2,2-dimethyl chromene through Pyrex using a 550-W Hanovia lamp initiates a retro 4 + 2 reaction to form the extended quinone methide 4, which reacts with methanol to form a pair of methyl ethers (Scheme 6A).18 Flash photolysis of coniferyl alcohol 5 generates the quinone methide 6 (Scheme 6B) by elimination of hydroxide ion from the excited-state reaction intermediate.19 The kinetics for the thermal reactions of 6 in water were characterized,20 but not the reaction products. These were assumed to be the starting alcohol 5 from 1,8-addition of water to 6 and the benzylic alcohol from 1,6-addition of water (Scheme 6). A second quinone methide has been proposed to form as a central intermediate in the biosynthesis of several neolignans,21a and chemical synthesis of neolignans has been achieved... 

The various methods of generating o-quinone methides,4-5 including the thermal or (Lewis) acid-catalyzed elimination of a phenol Mannich base,149 150-160-161163 the thermal or (Lewis) acid-catalyzed dehydration of an o-hydroxybenzyl alcohol (ether),147-149-151-153-156-157-162-163-165-168 171-175-178-183 the thermal 1,5-hydride shift of an o-hydroxy styrene,171-173 175 178-183 the thermal dissociation of the corresponding spirochromane dimer,158 163-164,166 oxidation of substituted o-alkylphenols,152-170 and the thermal or photochemical-promoted cheletropic extrusion154-155 159 of carbon monoxide, carbon dioxide, or sulfur dioxide (Scheme 7-III), as well as their subsequent in situ participation in regiospecific, intermolecular [4 + 2] cycloadditions with simple olefins and acetylenes,147 149-151 152 153159 162-164... 

Full details of a careful study of the regio- and stereospecific intramolecular [4 + 2] cycloadditions of o-quinone methides generated by the thermal or acid-catalyzed (CF3CO2H) dehydration of o-hydroxybenzyl alcohols have been described 75 and have found application in the total synthesis of enantiomerically pure (3/ )-26 and (3/ )-27 possessing the ring system and correct absolute configuration of the cannabinol family [Eq. (47)]. 

The various methods of generating o-quinone methides, including the thermal or (Lewis) acid-catalyzed elimination of a phenol Mannich base, the thermal or (Lewis) acid-catalyzed dehydration of an o-hydroxybenzyl alcohol (ether),... 

Dimerization of o-fuchsones, generated from o-hydroxybenzyl halides by treatment with either triethylamine or a diethylamino-derivatized polymer, affords dibenzo[i>/][l,5]dioxocin (115) and dinaphtho analogues (116 Ar = Ph, 4-FQH4, 4-MeOC6H4) in unspecified yield (Scheme 34). These reactions are reported to follow a stepwise, ionic pathway rather than radical or concerted [ttSs + r8a] thermal cycloaddition paths <82CCC838>. Curiously, no [4 + 2] dimers are formed in these reactions, although such products are favored for simpler o-quinone methides. 

Scheme 7.57 Photochemical and thermal generation of o-quinone methide (o-QM).

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