Chroman-quinone

Itishould be noticed that the similarity between the osmophore theory and Witt s chromophore colour theory does not extand much beyond the initial conception and there seems to be no connection between the odour and the colour of a body, it is indeed quite the exception for a body to have both a strong odour and a strong colour. Two prolific sources of colour, viz. the diazo group and a large molecule have no counterpart as regards odour, and it is probably only by chance that quinone and chroman both have pronounced odours and are the sources of colour. 

Dorrestijn, E. Pugin, R. Ciriano Nogales, M. V. Mulder, P. Thermal decomposition of chroman. Reactivity of o-quinone methide. J. Org. Chem. 1997, 62, 4804-4810. 

Stokes, S. M. J. Ding, F. Smith, R L. Keane, J. M. Kopach, M. E. Jervis, R. Sabat, M. Harman, W. D. Formation of o-quinone methides from T 2-coordinated phenols and their controlled release from a transition metal to generate chromans. Organometallics 2003,22, 4170-4171. 

The oxidation behavior of 3-oxa-chromanols was mainly studied by means of the 2,4-dimethyl-substituted compound 2,4,5,7,8-pentamethylM /-benzo[ 1,3]dioxin-6-ol (59) applied as mixture of isomers 27a it showed an extreme dependence on the amount of coreacting water present. In aqueous media, 59 was oxidized by one oxidation equivalent to 2,5-dihydroxy-3,4,6-trimethyl-acetophenone (61) via 2-(l-hydroxyethyl)-3,5,6-trimethylbenzo-l,4-quinone (60) that could be isolated at low temperatures (Fig. 6.41). This detour explained why the seemingly quite inert benzyl ether position was oxidized while the labile hydroquinone structure remained intact. Two oxidation equivalents gave directly the corresponding para-quinone 62. Upon oxidation, C-2 of the 3-oxa-chroman system carrying the methyl substituent was always lost in the form of acetaldehyde. 

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>. 

A more direct way to attain the dehydrogenation is to allow a chromane to react with a high-potential quinone, such as chloranil or 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ138) [Eq. (12)]. The reaction, usually carried on in benzene or dioxan, with yields in the... 

Oxidation of chromans has been extensively studied, especially of those which resemble the tocopherols which act as antioxidants in nature and in food. The behaviour of a-tocopherol (vitamin E, 547) and many simpler model compounds under oxidizing conditions varies with the oxidizing agent. Among the many products formed are the o- and p-quinones (609) and (610), the spiran (611) and dimer (612). A detailed account is available (81HC(36)59). 

The double dehydrogenation of o-alkylphenols to chromenes has also been achieved with DDQ, the reaction presumably proceeding through the alkenylphenol rather than the chroman. The latter are not known for their propensity to undergo oxidation by DDQ unless a free hydroxyl group is present to allow quinone methide formation to occur. Once again, substitution at C-3 appears to be essential for success. 

Direct oxidation of chromans to chromenes can be achieved using a high potential quinone chloranil and dichlorodicyanobenzoquinone are suitable. Much attention has been devoted to the latter reagent. 

The dimerization of o-quinone methides in which one molecule acts as the heterodiene and another as dienophile leads to spiroannelated chromans (equation 12). The driving force for this considerable tendency to dimerize is associated with the ease with which the... 

Reaction of chlorotrimethylsilane with hydroxymethylspiroepoxycyclohexadienone (279) affords the spiroannelated chroman (280) (Scheme 73) (80TL4973). The proposed mechanism invokes a quinone methide intermediate which dimerizes to the chroman. 

In a similar manner, o-quinone methides and their benzologues react with alkenes to give chromans (63CR(256)3323). With styrene, flavans are formed from o-quinone methides (64CR(258)1526). Yields are better with 2,3-naphthoquinone 2-methide than with the ben-zoquinone analogue. 

The quinone methide (284) is stabilized by the trifluoromethyl groups but was not isolated. Trapping with styrene gave the fluorinated chroman (Scheme 76) (68JOC3297). 

It is pertinent at this point to refer briefly to the sources of quinone methides, though these have been reviewed (B-74M122400). The general approach used in chroman syntheses involves the thermal elimination of HX from an -substituted phenol. Commonly the eliminated molecules are water, methanol or dimethylamine (287 X = OH, OMe, NMe2, respectively). However, these methods are not entirely suitable because the eliminated molecules may promote side reactions. In the case of 1,2-naphthoquinone 1-methide, the thermal dissociation of the spirodimer (288) is a better source than the other methods. Its formation represents another example of dimerization by a [4+2]-cycloaddition, since it is prepared by heating l-dimethylaminomethyl-2-naphthol in dodecane or xylene with careful exclusion of moisture (73JCS(P1)120,81CJC2223). 

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... 

DFT theory at the B3LYP/6-31G(d,p) level was used to investigate the Diels-Alder reactions of o-quinone methides with various ethenes. Calculations show that solvent decreases the activation energy and increase the asynchronicity.116 The Diels-Alder reaction of ortho-quinone methides derived from 3//-1,2-benzoxathiole 2,3-dioxides with maleimides produces chroman 2,3-dicarboxylic acid derivatives.117... 

Pyrolysis of o-hydroxybenzyl alcohol at 550 °C resulted in the formation of simple o-quinone methide, which was directly observed using low-temperature IR spectroscopy.122 Pyrolysis of chroman (Scheme 33) at 400-600 °C gives the simple o-quinone methide and ethene along with o-cresol, benzofuran, and styrene.123,124 The o-quinone methide was trapped with alkenes to form Diels Adler adducts, with hydrogen gas or hydrogen atom to form o-cresol, or underwent a further pyrolysis to CO and fulvene. 

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... 

The one-pot reaction of 0-BOC protected salicylaldehydes and salicyl alcohols with electron-rich alkenes and a Grignard reagent involves a diastereoselective cycloaddition to an o-quinone methide and offers access to a wide range of 4-substituted chromans <02JOC6911>. 

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... 

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