The conformational behaviour of 2-aryloxytetrahydropyrans and 2-acetoxytetrahydropyran, and barrier to ring inversion

Ouedraogo, Adama; Lessard, Jean

doi:10.1139/v91-071

Cited by 14 publications

(2 citation statements)

References 25 publications

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“…Purification by flash chromatography (pentane/ether 95:5) gave 6 as a white solid (21.99 g, 98%). Spectroscopic data were in accordance with the literature (19).…”

Section: -(Tetrahydropyran-2′-yloxy)-1-bromobenzene (6)mentioning

confidence: 62%

Identification of Centrolobol as the Platyphylloside Metabolite Responsible for the Observed Effect on in Vitro Digestibility of Hay

Sunnerheim

Bratt

2004

J. Agric. Food Chem.

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Syntheses of the metabolites from platyphylloside, a phenol causing digestibility inhibition in rumen fluid, have been performed to identify the active metabolite. 1,7-Bis(4'-hydroxyphenyl)-3-heptanone (3-platyphyllone), racemic, and the two enantiomers of 1,7-bis(4'-hydroxyphenyl)-3-heptanol (centrolobol) and 1,7-bis(4-hydroxyphenyl)heptane (platyphyllane) were synthesized and tested regarding digestibility inhibition in vitro in cow rumen fluid. All compounds tested induced a decreased digestion. Centrolobol was found to be the metabolite causing the observed effect, and (R)-centrolobol was found to be the enantiomer formed in the rumen liquor in vitro.

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“…Purification by flash chromatography (pentane/ether 95:5) gave 6 as a white solid (21.99 g, 98%). Spectroscopic data were in accordance with the literature (19).…”

Section: -(Tetrahydropyran-2′-yloxy)-1-bromobenzene (6)mentioning

confidence: 62%

Identification of Centrolobol as the Platyphylloside Metabolite Responsible for the Observed Effect on in Vitro Digestibility of Hay

Sunnerheim

Bratt

2004

J. Agric. Food Chem.

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“…12 For the preparation of the THP ether 1b we used a modified procedure. 13 By addition of 4-(trifluoromethyl)phenol (1a) to a solution of 3,4-dihyro-2H-pyran (DHP) and a catalytic amount of HCl/dioxane in dichloromethane the ether 1b was obtained in 90% yield (Scheme). Due to its distinct sensitivity to acid, the inverse sequence of addition of DHP to phenol 1a produced a considerable amount of insoluble solid.…”

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confidence: 99%

2-Substituted 4-(Trifluoromethyl)phenols by Directed ortho-Lithiation

Geneste¹,

Schäfer²

2001

Synthesis

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A broad variety of 2-substituted 4-(trifluoromethyl)phenols can be prepared in a large scale by o-lithiation and reaction with electrophiles in good to excellent yields. The key for the selectivity is the superior ortho-directing effect of the THP-protected hydroxy group (OTHP) as compared to the CF 3 -group.In the course of the development of new methods for the synthesis of intermediates for pharmaceuticals we became interested in 2-substituted 4-(trifluoromethyl)phenols. Although usually rather low, the reactivity of the trifluoromethyl group is greatly enhanced in p-trifluoromethylsubstituted phenols. 1 Traces of hydrogen fluoride or basic conditions induce polymerization. 2 Reaction with aqueous ammonia furnishes the corresponding nitrile. 3 When 4-(trifluoromethyl)phenol is heated, decomposition is observed at 130°C. 4 Due to conjugation, 1,6-elimination of hydrogen fluoride and formation of 4-(difluoromethylene)-2,5-cyclohexadiene-1-one seems to be the most prominent reaction. 5 In most cases this elimination is the reason why yields of substitution of 4-(trifluoromethyl)phenols are poor (< 50%). 6,7a,b,8a,b In other cases very toxic reagents (e.g. anhydrous hydrogen fluoride, 7c,d chloromethyl methyl ether 8g ) are used or the syntheses are tedious. [8][9][10] We became interested in the directed ortho-lithiation, a general method which offers the possibility of synthesising all of these derivatives of 4-(trifluoromethyl)phenol selectively, in good yields, short reaction times and convenience of handling. O-Tetrahydropyranyl (OTHP) is a very efficient ortho-directing group. 11 Due to the stabilising effect, the lithium complexes are stable enough to avoid very low reaction temperatures. 12For the preparation of the THP ether 1b we used a modified procedure. 13 By addition of 4-(trifluoromethyl)phenol (1a) to a solution of 3,4-dihyro-2H-pyran (DHP) and a catalytic amount of HCl/dioxane in dichloromethane the ether 1b was obtained in 90% yield (Scheme). Due to its distinct sensitivity to acid, the inverse sequence of addition of DHP to phenol 1a produced a considerable amount of insoluble solid. SchemeCompound 1b was lithiated with butyllithium at -70°C or with butyllithium/TMEDA at -10°C or -20°C and subsequently quenched with an electrophile ElX (Table). Although CF 3 is a strongly electron-withdrawing group, it has the least ortho-directing aptitude because of its bulkiness. Therefore, the deprotonation occurs at the ortho-position relative to the O-containing function. 8h,14 The protective group can be removed during workup by addition of HCl/dioxane (entry 1 and 5), an advantage as compared to the methoxymethyl group, which requires a supplementary deprotection step. 8h,15 Moreover, the methoxymethyl group has to be introduced using a highly toxic chloro compound. A very efficient and convenient method for the chlorination of 1b was the addition of hexachloroethane (entry 6). 16 For the synthesis of the boronic ester 2g an excess of triisopropyl borate and an inverse sequence of addition was important...

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