Mercuration cyclopropanation

The stereochemistry of the reaction of mercuric trifluoroacetate with cyclopro panes has been determined formation in the rate-determining step of corner-mercurated cyclopropanes, e.g. (34) from cM.-l,2,3-trimethylcyclopropane, is proposed. For other uses of mercuric trifluoroacetate and related compounds see discussion on formation of perfluoroalkyl derivatives of mercury and carbenes (see p. 193), and on preparation of polyfluoroarylmercuric trifluoroacetates (see p. 437). An X-ray determination of the crystal structure of mercuric trifluoroacetate has been carried out and a further report has appeared on the formation of the cyclohexyl-mercurinium ion [from addition of cyclohexene-SOs to (CF3 C02)2Hg-FS03H-SbFs-S02 at -60°C via mercuric ion attack on the w-system of the alkene] (see Vol. 2, p. 128). 

Malonic acid, amino-, diethyl ester, HYDROCHLORIDE, 40, 24 Malonic acid, bts(hydroxymethyl)-, DIETHYL ETHER, 40, 27 Malonitrile, condensation with tetra-cyanoethylene, 41, 99 2-Mercaptopyrimidine, 43, 6S hydrochloride of, 43, 68 Mercuric oxide in preparation of bromo-cyclopropane, 43, 9 Mesityl isocyanide, 41,103 5-Methallyl-l,2,3,4,5-pentachlorocyclo-pentadiene, 43, 92 Methane, dimesityl-, 43, 57 Methanesiileinyl chloride, 40, 62 Methanesulfonic acid, solvent for making peroxybenzoic acid from benzoic acid, 43, 93... 

Even more scrambling was found in trifluoroacetolysis of 1-propyl l- " C-mercuric perchlorate. " However, protonated cyclopropane intermedi... 

The threo stereoisomer was the major product obtained by the synthesis in Scheme 13.14. This stereochemistry was established by the conjugate addition in Step A, where a significant (4-6 1) diastereoselectivity was observed. The C(4)-C(7) stereochemical relationship was retained through the remainder of the synthesis. The other special features of this synthesis are in Steps B and C. The mercuric acetate-mediated cyclopropane ring opening was facilitated by the alkoxy substituent.19 The reduction by NaBH4 accomplished both demercuration and reduction of the aldehyde group. 

Some variations of the method have been used to prepare cyclopropyl and cyclobutyl halides. Simultaneous addition of bromine and 3-bromocyclobutanecarboxylic acid to the suspension of mercuric oxide gives 1,3-dibromocyclobutane in good yield.7 Similarly, cyclopropanecarboxylic acid gives bromo-cyclopropane,9 and 3-(bromomethyl)cyclobutanecarboxylic acid gives 3-(bromomethyl)cyclobutyl bromide.10 In the latter reaction, it was found desirable to remove the water from the reaction as it is formed in order to obtain high yields. Another variation is the addition of a mixture of the acid and mercuric oxide to excess bromine in bromotrichloromethane.6... 

The calculated energies again confirm that cyclopropane is much more easily attacked by electrophiles than is cyclobutane, and this accounts for the common observation that cyclobutanes are much less reactive toward electrophiles than are cyclopropanes, despite the similar strain energy relief for these compounds.55 The reactions of cyclopropane with other electrophiles, such as mercuric ion,65 and metal radical cations,67 have also been studied. 

The oxymercuration procedure (with mercuric trifluoroacetate) has been used to open cyclopropane rings, e.g.,158... 

Coupling of ketones with electron-deficient alkenes via a methylene group (cf. 11, 315-316). This modified Giese reaction involves cyclopropanation of the silyl enol ether of a ketone, mercuration, and finally demercuration and coupling with an alkene via a radical chain reaction.7 Example ... 

Lavina and coworkers i>42) have extensively studied the reaction of cyclopropanes with mercuric acetate. In water or methanol solution the product is an organomercury alcohol or methyl ether (Eq. (29)). Studies... 

The first stereochemical study of the cleavage of a cyclopropane derivative by a mercuric salt was reported by DeBoer and DePuy 22). By the series of reactions given (Eq. (30)), they showed that 1-phenyl-cts, fyaws-2,3-dimethylcyclopropanol 33) and l-phenyl- ra s, methyl ethers, react with mercuric acetate in acetic acid exclusively with inversion of configuration at the carbon to which the mercury becomes attached. More recently... 

In agreement with the stereochemical studies just reported, it has been shown that the absolute rate of attack by mercuric acetate on a cyclopropane is sensitive to the degree of substitution on the bond attacked. For example the relative rates of reaction of the three cyclopropanols 22) shown, 4G, 41 and 42, toward mercuric acetate, are in the ratio 1 10 10 . In unsymmetrical cyclopropanes the direction of ring opening... 

Cyclopropanol is significantly (a factor of 10 ) more reactive toward mercuric acetate than is phenyl cyclopropane. A cyclopropyl methyl ether is less reactive than the corresponding cyclopropanol by a factor of 10—20, and the cyclopropyl acetate is decreased in reactivity by a factor of nearly 10. These results are fully consistent with the large q value for the mercuration reaction reported by Oullette (vide supra). 

Even more scrambling was found in trifluoroacetolysis of 1-propyl-l- C-mercuric perchlorate. " However, protonated cyclopropane intermediates accounted for < 1 % of the products from diazotization of labeled isobutyla-mine and from formolysis of labeled 1-propyl tosylate. ... 

Siloxycyclopropanes are quantitatively converted into )5-acetoxymercuriketones by reaction with mercuric acetate. Successive treatment with PdCl2 or PdCl2 + CO gives a-methyleneketones or y-ketoesters, respectively. The ring cleavage takes place highly selectively at the least substituted cyclopropane carbon atom (equation 60) . 

Hunsdiecker degradation of l-(trimethylsilyl)cyclopropanecarboxylic acid (4) using bromine and red mercuric oxide in dichloromethane affords l-bromo-l-(trimethylsilyl)cyclopropane (5) in 55% yield. ... 

Dibromocyclopropane is obtained in 36% yield from the reaction of cyclopropane-1,1-dicarboxylic acid with bromine and mercuric oxide in refluxing dichloromethane. ... 

The mercuration of cyclopropane was also studied from a stereochemical point of view. The reaction of all-c/s-l,2,3-trideuteriocyclopropane (10) was shown to proceed with inversion of configuration in both steps whereas in methyl-substituted cyclopropanes, e.g. 11, the attack of the electrophile was not stereospecific, but the addition of the nucleophile occurred with 100% inversion of configuration. ... 

The acid-catalysed cleavage of cyclopropanes has been extended by use of mercuric acetate as an alternative electrophilic reagent. 3(x,5a-Cyclocholestane... 

Mercuric acetate opens the cyclopropane ring of 3a,5a-cyclocholestane to produce the non-mercurated A-nor steroid (318) in moderate yield. Base attacks the 4,4-dimethyldiosphenol (319) only at the C-3 carbonyl to give the ring-contracted hydroxyacid (320). Such 3,3-dimethyl-A-norcholest-5-enes are... 

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