O-Quinone methides, synthesis

Amouri, H. Vaissermann, J. Rager, M. N. Grotjahn, D. B. Rhodium-stabilized o-quinone methides synthesis, structure, and comparative study with their iridium congeners. Organometallics 2000, 19, 5143-5148. 

Amouri, H. Besace, Y. Bras, J. L. Vaissermann, J. General synthesis, first crystal structure, and reactivity of stable o-quinone methide complexes of Cp Ir. J. Am. Chem. Soc. 1998, 120, 6171-6172. 

The pyrano[3,2-c][l]benzopyran system is available from the reaction between salicylaldehyde and 5-phenylthio-4-penten-l-ols which proceeds by an intramolecular cycloaddition of an o-quinone methide desulfurisation is facile (Scheme 29) <00TL2643>. Mild conditions have been established for the synthesis of (-)-hexahydrocannabinol 50 from the olivetol derivative 49 which also involves a quinone methide (Scheme 30) <00SC1431>. 

The groups of Liebeskind and Moore independently explored the ring expansion of allenyl-substituted cyclobutenol derivatives. This allows either the preparation of 5-alkylidene-2-cyclopentenones, which are substructures of naturally occurring bioactive compounds [59], or the generation of o-quinone methides, which are very attractive intermediates in the synthesis of hexahydrocannabinols [109]. As shown in Scheme 8.42, the ring expansion of the tetrasubstituted methoxyallene derivative 170 furnished the vinylhydroquinone 172 in high yield [109]. 

Cycloaddition Anodically generated phe-noxy cations, o-quinones, and o-quinone methides react with olefins to bicyclic and tricyclic annelated compounds in stereoselective cycloadditions [250-252]. In the synthesis of a Euglobal skeleton, a quinone methide has been generated in situ by anodic oxidation mediated by DDQ. The cycloaddition was promoted by the use of lithium perchlorate... 

There are a number of examples of the synthesis of chromans using o-quinone methides as the heterodiene in a hDA reaction. Both pyrano[3 -c]-benzopyrans and cyclopenta[c][l]benzopyrans result from an intramolecular cycloaddition of a substituted o-quinonemethide generated under mild conditions. In the former case, salicylaldehyde and an unsaturated alcohol yield the rra/is-fused tetrahydropyranobenzopyran (Scheme 10) <99JOC9507>. However, the latter synthesis (Scheme 11) is less selective <99BCJ73>. 

The JACS paper describes the total synthesis of the more highly oxygenated (-)-tetracycline 16. To this end, the alcohol S was carried on to the enone 10. Opening of the cyclobutane 11 to the o-quinone methide followed by Diels-Alder cycloaddition to 10 delivered the endo adduct 12. 

All attempts to trap a with dienophiles failed. However, a synthesis of the benzoquinolizidine 4 involves an intramolecular Diels-Alder reaction with an o-quinone methide imine b, generated from 3 by CsF.1... 

A novel synthesis of chroman-2,3-dicarboxylic acid derivatives has been performed by thermal extrusion of sulfur dioxide from benzosultones via o-quinone methides.27... 

Triflates of transition metals catalyse the reaction between alkenes, salicylaldehydes and trimethyl orthoformate (TMOF) that is particularly useful for the synthesis of fused chromans. Generation of an o-quinone methide and its capture by the alkene is the key feature. The examples in Scheme 4 are illustrative. Tran.v-fused pyrano[3,2-c]benzopyrans... 

A facile generation of o-quinone methides by the fluoride-induced desilylation of o-silyloxybenzyl derivatives is the key step in a synthesis of a range of chromans, including those which contain part of the puupehedione structure <06T6012>. A formal synthesis of puupehedione is based on a Ti-catalysed cyclisation of epoxypolyenes <06EJO4115>. A quinone methide is also involved in a synthesis of robustadials A and B from 2,4,6-trihydroxybenzene-l,3-dicarboxaldehyde, 3-methylbutanal and (-)-P-pinene. The... 

Shaterian and co-workers [180] have described an efficient and expeditious route towards the synthesis of l-amidoalkyl-2-naphthols 127 via a three-component reaction of an aryl aldehyde, 2-naphthol and acetamide in the presence of Fe(HS04)3 using a domestic microwave oven. The reaction of 2-naphthol with an aromatic aldehyde in the presence of an acid catalyst gives an o-quinone methide that is subsequently reacted with acetamide to give the desired product 127. This solvent-free microwave-assisted green procedure offers the advantages of short... 

Synthesis o/eslra-l,3,5(10)-(rieiie-17-oii . Nicolaou and Barnette report that sultone 1 is metalated with KH in DME to afford a clear yellow solution of the anion 2. Alkylation of 2 with tosylate 3 followed by acid hydrolysis affords 4 as a mixture of diastereomers in 77% yield. Thermolysis of 4 affords estra-1,3,5(10)-triene-17-one (5) directly in 85% yield, probably by way of an intermediate o-quinone methide a. This sequence constitutes an exceedingly short and efficient synthesis of the steroid nucleus. 

Saegusa s group (81JA5250) found that [o-[(trimethylsilyl)alkylamino]-benzyljtrimethylammonium halide underwent the fluoride-anion induced 1,4-elimination under mild conditions to generate an o-quinone methide N-alkylamine intermediate. They performed the formal synthesis of gephyro-toxin 434 on the basis of an intramolecular cycloaddition of the o-quinone methide A-alkylamine 426 (83TL2881). Treatment of azadiene precursor 425... 

Fluoride-induced fragmentation reactions were used in two stages of a synthesis of hexahydrocannabi-nol methyl ether (144 Scheme 52). One of the phenolic hydroxy functions in the resorcinol derivative (140) was selectively liberated from the SEM ether to give the diol (141), which was converted to the bis (trimethylsilyl) ether (142). Subsequent treatment with CsF resulted in a 1,4-elimination to the o-quinone methide (143) intermediate, which underwent an intramolecular [4 -i- 2] cycloaddition to give the product in good yield. 

Since the remarkable demonstration of the facility of an intramolecular Diels-Alder reaction (dimerization) of an o-quinone methide, generated by the oxidation of a substituted o-alkylphenol in the development of a biomimetic synthesis of carpanone [Eq. (44)],170... 

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)]. 

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