Boron trifluoride epoxide ring opening

Boron trifluoride is a highly moisture-sensitive gas (31). It is utilized in esterification, ether formation, Friedel-Crafts alkylation and acylation, and Lewis acid-catalyzed Diels-Alder reactions. A more widely used, easy-to-handle and convenient liquid source of BF3 is boron trifluoride etherate [BF3-0(C2H5)2] (32). Its main usage as catalyst is in the direct esterification of all types of acids, rearrangements, aldol condensation, and Lewis acid-catalyzed Diels-Alder reactions. It is the most frequently used acid in epoxide ring opening and rearrangement (33). 

Reagents of choice for reduction of epoxides to alcohols are hydrides and complex hydrides. A general rule of regioselectivity is that the nucleophilic complex hydrides such as lithium aluminum hydride approach the oxide from the less hindered side [511, 653], thus giving more substituted alcohols. In contrast, hydrides of electrophilic nature such as alanes (prepared in situ from lithium aluminum hydride and aluminum halides) [653, 654, 655] or boranes, especially in the presence of boron trifluoride, open the ring in the opposite direction and give predominantly less substituted alcohols [656, 657,658]. As far as stereoselectivity is concerned, lithium aluminum hydride yields trans products [511] whereas electrophilic hydrides predominantly cis products... 

In the event, iodolactonization of the carboxylate salt derived from the ester 458 afforded 459, and subsequent warming of the iodo lactone 459 with aqueous alkali generated an intermediate epoxy acid salt, which suffered sequential nucleophilic opening of the epoxide moiety followed by relactonization on treatment with methanol and boron trifluoride to deliver the methoxy lactone 460. Saponification of the lactone function in 460 followed by esterification of the resulting carboxylate salt with p-bromophenacylbromide in DMF and subsequent mesylation with methanesulfonyl chloride in pyridine provided 461. The diazoketone 462 was prepared from 461 by careful saponification of the ester moiety using powdered potassium hydroxide in THF followed by reaction with thionyl chloride and then excess diazomethane. Completion of the D ring by cyclization of 462 to the keto lactam 463 occurred spontaneously on treatment of 462 with dry hydrogen chloride. 

However, these conditions have not been applied to other epoxides. Catalysis by the boron trifluoride -diethyl ether complex is very useful for the ring opening of cyano-substituted epoxides " and glycidic esters see the formation of and Table 14. This is demonstrated by the regioselective opening of the epoxide ring in 2,3-dimethyloxirane-2-carbonitrile to provide 3-fluoro-2-hydroxy-2.3-dimcthylbutanonitrile... 

Some noteworthy intramolecular nucleophilic ring openings have been reported in the recent literature, which can be used to prepare functionalized heterocycles of synthetic interest. For example, the highly oxygenated epoxide 100 undergoes rearrangement induced by boron trifluoride etherate, whereby anchimeric assistance from the pendant phenylthio substituent leads to an intermediate episulfonium ion 101 which subsequently suffers 5-e o-tet cyclization to form the tetrahydrofiiran derivative 102 <03TL5547>. 

Further examples of fluorinating ring-opening reactions of epoxides with the boron trifluoride-diethyl ether complex are given by the formation of 6.43 7,52 8,35 9.54 and 10.56... 

Alkyl stannyl selenides are also useful nucleophilic selenium reagents. Tri-methylstannyl or tributylstannyl methyl selenides 58 react with halides 59 to produce unsymmetrical selenides 60 in good yields in the presence of a fluoride ion or by treatment with n-butyllithium (Scheme 44) [84]. Tributylstannyl phenyl selenide (61) reacts smoothly with acetals to give monoselenoacetals 62 in the presence of boron trifluoride etherate (Scheme 45 a) [85]. Similar reaction conditions were applied to the regioselective ring opening of epoxides (Scheme 45b) [86]. 

If migration of the hydride and ring opening of the epoxide are concerted, stereospecificity of the reaction is assured. Nucleophilic displacement by ethyl ether (derived from boron trifluoride etherate) removes boron trifluoride to generate the product ketone. 

Indoles react with epoxides and aziridines in the presence of Lewis acids (see 20.4.1 for reaction of indolyl anions with such reactants) with opening of the three-membered ring and consequent 3-(2-hydroxyethylation) and 3-(2-aminoethylation) of the heterocycle. Both ytterbium triflate and phenylboronic acid are good catalysts for reaction with epoxides under high pressure silica gel is also an effective catalyst, but reactions are slow at normal pressure and temperature. Reaction with aziridines can be catalysed by zinc triflate or boron trifluoride. °... 

Particularly good results are obtained when anhydrous hydrogen fluoride is used in combination with a Lewis acid, such as antimony(V) fluoride or boron trifluoride-diethyl ether complex, for the ring opening of epoxides bearing electron-withdrawing substituents. Pcr-fluoro(2,2-dimethyloxirane) is opened to pcrfluoro(2-methylpropan)-2-ol (1) in 56% yield with hydrogen fluoride and catalytic amounts of antimony(V) fluoride at 100 C.31... 

When triptolide 1 was reacted with nucleophillic reagents HBr, CH3CH2CH2SH, HOAc, MeOH, ammonium thiocyanide or 4-methoxybenzenesulfonyl chloride, the same C12-C13 epoxide reacted to form compounds 69-73 [70-72], Refluxing 1 for 96 hrs in phosphate buffer solution at pH 4 generated triptriolide 10 in 43% yield [72], In contrast, when 1 was stirred with sodium cyanoborohydride followed by dropwise addition of neat boron trifluoride diethyl etherate at room temperature for 16 hrs, the epoxide ring at C-7-C-8 opened and the compound 74 was obtained. Subsequently, reaction of compound 74 with HC1 at room... 

The rate of nucleophilic ring opening of epoxides with unreactive organocuprates has been demonstrated to be vastly enhanced by the addition of boron trifluoride etherate to the reaction mixture. 

Oxabicyclo[5,l,0]octa-2,4-diene has been prepared by epoxidation of cyclo-heptatriene its reactions include lithium aluminium hydride reduction to cyclohepta-3,5-dienol, hydrogenation to cycloheptanol, boron trifluoride-catalysed rearrangement to cyclohepta-3,5-dienone, and acid hydrolysis to a mixture of all six cyclo-heptadienols. Pyrolysis of the epoxide gave ring-opened products (see Section 12).2- °... 

Traditionally, nucleophilic ring opening of aziridines, in a way similar to that of an epoxide, has been regarded as a difficult reaction to achieve. However boron trifluoride diethyl etherate has been shown to promote addition of dialkyl cuprates to suitably... 

The only case in which this type of migration occurs is the acidolytic ring opening of epoxides . Phenyl a-methyl-/ra 5-j3-phenylthiolglycidate (187) gave, upon treatment with boron trifluoride etherate, 45% yield of the enol tautomer of phenyl a-phenylacetothiolacetate (188). 

Regioselective ring opening of epoxides to the less-substituted alcohol, by hydride capture at the better potential carbenium ion centre, is achieved with a sodium cyanoborohydride-boron trifluoride combination anti ring opening is favoured. 

Epoxy fatty acids (as the methyl esters) give El mass spectra which are not easily interpreted in terms of the position of the oxygen atom (especially when double bonds are also present), although it is possible with some effort if suitable model compounds are available [116,473,481]. It is generally recommended that the epoxide be isomerised to a mixture of keto compounds [473], or that the ring should be opened with boron trifluoride-methanol reagent to a mixture of methoxy-hydroxy derivatives [481,833] or with lithium aluminium hydride to hydroxy derivatives followed by trimethylsilylation [940], for identification by GC-MS. MS was used to study the incorporation of into the oxirane ring of 9,10-epoxyoctadecanoic acid in wheat tissues [488]. If derivatization is undesirable, more useful spectra are obtained with chemical ionisation [474,717]. 

Starting materials, like 141, which are accessible from alkenes by azido-selenenylation, afforded only in a few cases vinyl azides exclusively as shown by the example 141 142 (Scheme 5.19). In most cases, after oxidation of the vicinal phenylseleno azides and elimination reaction on the intermediate selenoxide, mixtures of allyl and vinyl azides were obtained. Ring opening of trialkylsilyl-substituted epoxides was utilized several times for stereoselective synthesis of vinyl azides. Thus, treatment of the frani -contigured oxiranes 143 with azidotrimethylsilane and boron trifluoride etherate yielded cis-conflgured products 145. This result was explained by the intermediate 144 which should undergo anti-elimination. On the other hand, when subjected to sodium azide in dimethylformamide, epoxides 146 were transformed into vinyl azides 148 via... 

The ring-opening polymerizations of oxetanes (1,3-epoxides) with Lewis acids such as boron trifluoride etherate and aluminum alkyls are well documented. Hall and coworkers reported the ring-opening polymerization of 7-oxabicyclo[2.2.Ijheptane (50) with Lewis acids such as boron trifluoride etherate to give poly(cyclohexene oxide) (51). Ogata reported that the polymerization of... 

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