Timothy W. Wallace

Cycloadditions of substituted benzopyran-4-ones to electron-rich dienes: a new route to xanthone derivatives

Abstract The benzopyranones 1 and 3 reacted with 2,3-dimethyl-1,3-butadiene in the presence of titanium (IV) chloride to give the corresponding (4 + 2) cycloadducts 8 and 11 , the former undergoing facile deformylation to give 9 and 10 . Compounds 1 , 3 , and 4 underwent efficient uncatalysed cycloaddition to 1- methoxy-3-(trimethylsilyloxy)-l,3-butadiene 12 to give the respective adducts 13,14 , and 18 as mixtures of C-l stereoisomers. Heating the 3-arylsulphinylchromone 5 with the diene 12 afforded 3-hydroxyxanthone 23 in 50% yield, the presumed cycloaddition - elimination sequence constituting a new route to xanthone systems. Desilylation of 13,14 , and 18 in acidic media provided 25,26 , and 27 respectively.

Thermal electrocyclic ring-opening of cyclobutenes: stereoselective routes to functionalised conjugated (Z,E)- and (E,E)-2,4-dienals

Abstract The cyclobutenecarbaldehyde 12 undergoes thermal electrocyclic ring-opening at low temperature, producing the (2Z,4E)-hexadienal 13 exclusively. By contrast, unsymmetrical derivatives of cis-3-cyclobutene-1,2-dicarboxylic acid undergo ring-opening at 80–110°C with low levels of stereoselectivity, which vary according to the balance of the electronic and, to a lesser extent, the steric nature of the substituents located on the rehybridising carbon atoms.

Conjugate addition to 3-(ptolylsulphinyl)chromone: a route to 2-substituted chromones and chiral substituted chroman-4-ones

Abstract 3-(p-Tolylsulphinyl)chromone 3a undergoes diastereoselective conjugate addition of lithium dimethylcuprate, producing a mixture of 2-methyl-3-(p-tolylsulphinyl)chroman-4-ones. Heating the mixture to 140°C gives 2-methylchromone in quantitative yield. Desulphurisation of the mixed products from (S)-3a gives (S)-2-methylchroman-4-one with 90% e.e. Chelation of the carbonyl and sulphoxide oxygens during methyl addition accounts for the diastereoselection.

A simple route to methyl 5S-(benzoyloxy)-6-oxohexanoate, a key intermediate in leukotriene synthesis

Abstract Methyl 5S -(benzoyloxy)-6-oxohexanoate 2 , an intermediate in synthetic routes to the lipoxygenase-derived arachidonic acid metabolite leukotriene B 4 , is available in three steps from 2-cyclohexen-1-one, using Schreibers unsymmetrical ozonolysis protocol.

Conjugate addition of cuprate reagents to chromones : a route to 2-substituted chroman-4-ones

Abstract Chromones (4-oxo-4H-1-benzopyrans) activated by electron-withdrawing groups attached to C-3 undergo efficient 1,4-additon of cuprate reagents, producing 2,3-disubstituted chroman-4-ones. The addition products from methyl chromone-3-carboxylates can be converted into 2-substituted chroman-4-ones by treatment with sodium chloride in wet dimethylsulphoxide.

Synthesis of 2-substituted chromones, chromanones, and their thio analogues using organocopper reagents

Improved use of organocopper reagents provides a general route to unsymmetrical 2,2-dialkylchomanones and thiochromanones from chromones and thiochromones via a simple addition - oxidation - addition sequence

Conjugate addition to 3-arylsulfinylchromones as a synthetic route to homochiral 2-substituted chromanones: Scope and limitations

A route to homochiral 2-substituted chromanones via the diastereoselective conjugate addn. of organocopper reagents to 3-(p-tolylsulfinyl)chromones has been improved and used to prep. 2,6-dimethylchromanone and LL-D253a Me ether [i.e., (2R)-2,3-dihydro-8-(2-hydroxyethyl)-5,7-dimethoxy-2-methyl-4H-1-Benzopyran-4-one]. The attempted prepn. of a 2-phenylchromanone (flavanone) using this strategy was unsuccessful due to the lability of the intermediate 2-phenyl-3-(p-tolylsulfinyl)chromanone, which underwent sulfoxide elimination at room temp. to give the corresponding 2-phenylchromone (flavone).

36-Dimethoxybenzocyclobutenone: a reagent for quinone synthesis

Abstract 3,6-Dimethoxybenzocyclobutenone 4 is prepared in four efficient steps from 2,5-dimethoxybenzoic acid 8. The derived benzocyclobutenol 13 undergoes electrocyclic ring opening at 110–115°C to give the hydroxy- o -quinone dimethide 21, which reacts with dienophiles to give 5,8-dimethoxy-1,2,3,4-tetrahydro-1-naphthol derivadves stereoselecdvely. Since the ketone 4 can be functionalised at C-5 using electrophiles and at C-2 via hoimolytic bromination, the ring opening and cycloaddition sequence offers a flexible route to linear fused hydroquinone and quinone derivatives. In model studies, the benzocyclobutenol derivative 48 underwent thermal electrocyclic ring opening and intramolecular cycloaddition to give 49, while the analogous reaction with 52 failed due to adverse steric effects during the cycloaddition step. In photochemical experiments, attempts to generate the silyi ether 57 by in situ silylation of the dienol 55 and to prepare the benzocyclobutenol 62 via irradiation of the o -phthalaldehyde monoacetal 60 were unsuccessful.

Conjugate addition to chromones: Synthesis of substituted 4-chromanones

Abstract Chromones activated by carbonyl substituents at C-3 are transformed into the corresponding 2-methyl 4-chromanones by treating with lithium dimethylcuprate

Heterodiene cycloadditions: Preparation and transformations of some substituted pyrano[4,3-b][1]benzopyrans

Abstract Heterodiene cycloadditions of 4-oxo-4H-1-benzopyrans with formyl, acetyl, or carboxyl substituents at C-3 to 1-alkoxy- or 1,1-dialkoxyalkenes produce 3-alkoxy- or 3,3-dialkoxy-4,4a- dihydropyrano[4,3-b][1]benzopyran-10-ones which are capable of a variety of selective transformations, including acid-induced epimerisation and/or retro-cycloaddition, reduction, hydrolysis and alcoholysis, in some cases under very mild conditions.