Sodium borohydride epoxy acids

The synthesis of key intermediate 12, in optically active form, commences with the resolution of racemic trans-2,3-epoxybutyric acid (27), a substance readily obtained by epoxidation of crotonic acid (26) (see Scheme 5). Treatment of racemic 27 with enantio-merically pure (S)-(-)-1 -a-napthylethylamine affords a 1 1 mixture of diastereomeric ammonium salts which can be resolved by recrystallization from absolute ethanol. Acidification of the resolved diastereomeric ammonium salts with methanesulfonic acid and extraction furnishes both epoxy acid enantiomers in eantiomerically pure form. Because the optical rotation and absolute configuration of one of the antipodes was known, the identity of enantiomerically pure epoxy acid, (+)-27, with the absolute configuration required for a synthesis of erythronolide B, could be confirmed. Sequential treatment of (+)-27 with ethyl chloroformate, excess sodium boro-hydride, and 2-methoxypropene with a trace of phosphorous oxychloride affords protected intermediate 28 in an overall yield of 76%. The action of ethyl chloroformate on carboxylic acid (+)-27 affords a mixed carbonic anhydride which is subsequently reduced by sodium borohydride to a primary alcohol. Protection of the primary hydroxyl group in the form of a mixed ketal is achieved easily with 2-methoxypropene and a catalytic amount of phosphorous oxychloride. 

The full paper on the synthesis of onikulactone and mitsugashiwalactone (Vol. 7, p. 24) has been published.Whitesell reports two further useful sequences (cf. Vol. 7, p. 26) from accessible bicyclo[3,3,0]octanes which may lead to iridoids (123 X=H2, Y = H) may be converted into (124) via (123 X = H2, Y = C02Me), the product of ester enolate Claisen rearrangement of the derived allylic alcohol and oxidative decarboxylation/ whereas (123 X = 0, Y = H) readily leads to (125), a known derivative of antirride (126) via an alkylation-dehydration-epoxi-dation-rearrangement sequence. Aucubigenin (121 X = OH, R = H), which is stable at —20°C and readily obtained by enzymic hydrolysis of aucubin (121 X = OH, R = j8-Glu), is converted by mild acid into (127) ° with no dialdehyde detected sodium borohydride reduction of aucubigenin yields the non-naturally occurring isoeucommiol (128 X=H,OH) probably via the aldehyde (128 X = O). ... 

A mixture of 39.2 g (71.2 mmol) of (2S,3R,4R,5S)-2,5-bis-(N-(((benzyl)oxy)carbonyl)amino)-3,4-epoxy-l,6-diphenylhexane in 600 ml of THF was treated under N2 with 13 g (0.36 mol) of sodium borohydride. The resulting mixture was treated dropwise with 27.7 ml (0.36 mol) of trifluoroacetic acid. After being stirred for 3.5 h at ambient temperature, the resulting mixture was quenched with 1 N aqueous HCI, diluted with water, and stirred for 16 h. The resulting mixture was filtered, washed with water, and dried to provide 22.85 g (58%) of the hydroxide octahydrate in 400 ml of 1,4-dioxane and 400 ml desired compound as a white solid. 

Next step of this synthesis consisted in the conversion of alcohol (17) to pisiferic acid (1) and this has been described in Fig. (3). The alcohol (17) in hexane was treated with Pb(OAc)4 in presence of iodine at room temperature to obtain the epoxy triene (19) (51%) whose structure was confirmed by spectroscopy. Treatment of (19) with acetyl p-toluene-sulfonic in dichloromethane yielded an olefinic acetate (20) and this was hydrogenated to obtain (21). The compound (22) could be isolated from (21) on subjection to reduction, oxidation and esterification respectively. The conversion of (22) to (23) was accomplished in three steps (reduction with sodium borohydride, immediate dehydration in dichloromethane and catalytic hydrogenation). Demethylation of (23) with anhydrous aluminium bromide and ethanethiol at room temperature produced pisiferic acid (1). Similar treatment of (23) with aluminium chloride and ethanethiol in dichloromethane yielded methylpisiferate (3). 

Epoxy-a-pinene, produced by epoxidation of (+)-a-pinene, rearranges in the presence of Lewis acids to (-)-campholenealdehyde which is not only one of the constituents of various juniper species, but also the starting reagent for the synthesis of fragrances with the odor of sandalwood. Sandalore, for example, is produced by Knoevenagel aUcenylation of campholenealdehyde with propanal followed by reduction of the aldehyde function with sodium borohydride... 

The g.l.c. separation of cis- and /m/w-epoxy-esters forms the basis of a new procedure for determining the proportion of cis- and tra/w-isomers in a mixture. The report that w-chloroperbenzoic acid can be used at 90 without decomposition in the presence of suitable radical inhibitors may be of value when epoxidizing alkenes of reduced reactivity. Several fluorostearic acids have been prepared by interaction of mesyloxy-acids with tetrabutyl-ammonium fluoride in acetonitrile. A procedure for methylation (by diazomethane in the presence of boron trifluoride) and demethylation (by reaction with sodium borohydride and iodine, followed by methanol), with retention of optical activity, could prove useful in the synthesis of compounds of known configuration. ... 

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