Epoxides, reaction with acid dianions

The isomeric epoxy triflates 153 and 157 undergo triflate displacement-epoxide opening with the dianion of methyl propanoyl acetate. Reaction of 153 generates the epimeric bicyclic tetrahydrofurans 154 and 155, subsequent treatment with triflic acid leading to isomerization about the alkene bond to a mixture of 154-156. Isomeric 157 under similar conditions gives 158 and 159, with triflic acid catalysis leading to some of the alkene isomers 160 along with 158 (Scheme 32). ... 

Epoxides - The first indication of the synthetic utility of metalated carboxylic acids resulted from efforts to prepare steroidal aldosterone inhibitors from spiroepoxides.39 Model studies indicated that the reaction fails as a result of severe steric hindrance in either the epoxide or carboxylic acid and that monosubstitution occurs for the same reason.39 The reaction has been used in a key step of an elegant synthesis of vernolepin, 5. 40 Forcing conditions are required, and, in contrast to acid dianions, anions of unactivated esters fail to react with epoxides.39 41... 

Dianions of this type react with ketones, epoxides,and esters " as well as a wide variety of other electrophiles. As an example, the dilithio anion of 2-methylpropionic acid was condensed with the epoxide moiety in 229 to form an hydroxy acid, which cyclized to form the lactone ring in 230. Since most of the enolates of acid derivatives contain a leaving group, the alkoxide resulting from reaction with an epoxide often displaces that leaving group to give the lactone. 

A full report has been published on the generation of the dianionic species (14) by halogen/metal exchange with 2-bromo-3-phenylcinnamic acid (Bu"Li, -100 C). Subsequent trapping with electrophiles leads to 2-substituted-3-phenylcinnamic acids in 47—74% yield (six examples) reactions with epoxides. 

Keto-acids.—Optimum conditions have been reported for the generation of the dianion (20). Some very efficient alkylations are reported along with methods for the condensations of (20) with an epoxide and N-tosylaziridine unmasking of these products to the corresponding keto-acids can be accomplished using N-bromosuccinimide, while treatment with l2-MeOH leads to the dimethylketals of the keto-acids. a-Keto-acids can also be obtained from keto-alcohols (RCOCH2OH) by reaction with tetrazolium salts yields seem to be rather variable. ... 

The dianions derived from furan- and thiophene-carboxylic acids by deprotonation with LDA have been reacted with various electrophiles (Scheme 64). The oxygen dianions reacted efficiently with aldehydes and ketones but not so efficiently with alkyl halides or epoxides. The sulfur dianions reacted with allyl bromide, a reaction which failed in the case of the dianions derived from furancarboxylic acids, and are therefore judged to be the softer nucleophiles (81JCS(Pl)1125,80TL505l). 

Other examples of oxidant-iron(III) adducts as intermediates in iron porphyrin-catalyzed reactions have been published as listed in references 54a-k. Competitive alkene epoxidation experiments catalyzed by iron porphyrins with peroxy acids, RC(0)00F1, or idosylarenes as oxidants have been proposed to have various intermediates such as [(porphyrin)Fe (0-0-C(0)R] or [(porphyrin)Fe (0-I-Ar)]. Alkane hydroxylation experiments catalyzed by iron porphyrins with oxidant 3-chloroperoxybenzoic acid, m-CPBA, have been proposed to operate through the [(porphyrin)Fe (0-0-C(0)R] intermediate. J. P. CoUman and co-workers postulated multiple oxidizing species, [(TPFPP )Fe =0] and/or [(TPFPP)Fe (0-I-Ar)] in alkane hydroxylations carried out with various iodosylarenes in the presence of Fe(TPFPP)Cl, where TPFPP is the dianion of me50-tetrakis(pentafluorophenyl)porphyrin. ... 

Treatment of aminophenols with alkylating agents can yield either O- or N-alky-lated products, depending on the type of electrophile used and on the reaction conditions. If weak bases and hard electrophiles are used, either clean O-alkylation or mixtures of products can result (Scheme 6.20). Acid-catalyzed alkylation of aminophenols with epoxides usually yields N-alkylated products [47] (Scheme 6.12). Selective N-alkylation of aminophenols can also be achieved by using softer electrophiles or by conversion of the aminophenol into a dianion, followed by treatment with one... 

There are currently two proposed mechanisms for the acyloin ester condensation reaction. In mechanism A the sodium reacts with the ester in a single electron transfer (SET) process to give a radical anion species, which can dimerize to a dialkoxy dianion. Elimination of two alkoxide anions gives a diketone. Further reduction (electron transfer from the sodium metal to the diketone) leads to a new dianion, which upon acidic work-up yields an enediol that tautomerizes to an acyloin. In mechanism B an epoxide intermediate is proposed. ... 

A similar transformation can be carried out under milder conditions by taking advantage of silyl ketene acetals, a masked form of the earboxylate dianion. When epichlorohydrin 53 was treated with the ketene acetal 79 in the presence of titanium(IV) chloride, a regioseleetive epoxide ring opening occurs at the less substituted carbon. Treatment of the crude reaction mixture with catalytic p-toluenesulfonic acid promoted a lactonization to the y-butanolide 80 in high overall yield <04T8957>. 

Deprotonation of allyl tetramethylphosphorodiamidate, readily prepared from allyl alcohol, induces the migration of phosphorus from oxygen to carbon. A second deprotonation then occurs to give the dianion (33 Scheme 16). Alkylation with 1-iodopropane takes place at the 7-position to give hexanoic acid after hydrolysis. Reaction of (33) with aldehydes and ketones followed by hydrolysis gives 7-lac-tones, and a similar sequence with epoxides produces 6-lactones. 

Keto-acids.—The generation and reactions of dianions (7) have been reported. These react very efficiently with alkylating agents (even cyclohexyl tosylate affords a 64% yield of the expected adduct) to give a-keto-acid derivatives. Treatment of (7) with epoxides leads to butyrolactones and with aziridines to y-amino-a-keto-acid derivatives (see also ref. 77a). A simple looking route to /8-keto-acids (9) is by condensation between an acid chloride and the enolate of... 

Despite its own valuable synthetic potential, the use of [ C2]acetylene as a starting material for various building blocks is of much higher relevance. Mercury(II)-catalyzed hydration, for example, gives [ C2]acetaldehyde (Figure 8.5, Route 1) The same reaction carried out in the presence of ammonium persulfate furnishes [ 2] acetic acid (Route 2). Trapping of its mono- or dianion with formaldehyde or carbon dioxide affords [2,3- C2]propynol, [2,3- C2]butyne-l,4-diol, [2,3- C2]propiolic acid " and [2,3- C2]acetylenedicarboxylic acid, respectively (Routes 3-6). UV irradiation of a mixture of HBr and [ C2]acetylene produces l,2-dibromo[ C2]ethane (Route 8) . Reduction with chromium(II) chloride followed by a two-step epoxidation of the initially formed [ C2]ethylene converts [ 2]acetylene into [ C2]ethylene oxide (Route 7) . Finally, catalytic homotrimerization or co-trimerization with other alkynes provides [ " C ]benzene or substituted [ " C ]benzenes, respectively, the central starting materials for the vast majority of substituted benzenoid aromatic compounds (Route 9). 

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