Furans mercuration

Pd(II) salts promote the carbonylation of organomercury compounds. Reaction of phenylmercury chloride and PdCh under CO pressure affords benzophenone (429)[387]. Both esters and ketones are obtained by the carbonylation of furylmercury(Il) chloride in alcohol[388]. Although the yields are not satisfactory, esters are obtained by the carbonylation of aryl- and alkylmercuryfll) chlorides[389,390]. One-pot catalytic carbonylation of thiophene, furan, and pyrrole (430) takes place at the 2-position via mercuration and transmetallation by the use of PdCb, Hg(N03), and CuCl2[391]. 

Mercury(II) acetate tends to mercurate all the free nuclear positions in pyrrole, furan and thiophene to give derivatives of type (74). The acetoxymercuration of thiophene has been estimated to proceed ca. 10 times faster than that of benzene. Mercuration of rings with deactivating substituents such as ethoxycarbonyl and nitro is still possible with this reagent, as shown by the formation of compounds (75) and (76). Mercury(II) chloride is a milder mercurating agent, as illustrated by the chloromercuration of thiophene to give either the 2- or 2,5-disubstituted product (Scheme 25). 

Using these assumptions and conventions, Imoto and co-workers have correlated a number of series of reactions of thiophenes and furans. The reactions studied are the acid-base equilibria pK values) and the acid catalyzed methylations (thiophenes only) of thiophene-and furan-carboxylic acids and the alkaline hydrolyses of their ethyl esters the side-chain bromination of the a-acetylthiophenes, and the a-mercuration of thiophenes and the polarographic half-wave potentials of the methyl esters of thiophene- and furan-carboxylic acids and of nitrothiophenes. The pK values were determined and the ester hydrolyses studied for all three substitution orientations in the thiophene series. For the 4-R-2-Y and 5-R-2-Y series, the p-values do not appear significantly different and the data could probably be combined into a single series unfortunately, however, no limits of accuracy are reported for the p-values, and some of the raw data are not readily available so recalculation is not easily possible. For the 5-R-3-Y series the p-values deviate considerably from the other values however, whereas they are higher for the pK values, they are lower for the ester hydrolyses, and it is possible that the differences are neither systematic nor significant. 

Iodination of 4 with molecular iodine in the presence of mercuric oxide formed the 3-iodo derivative (52JA4951 66CJC2283). Iodine in tetrahydro-furan oxidatively cyclized /3-(3-benzo[b]thienyl)-a-mercaptoacrylic acids rather than iodinating the thiophene ring [70JCS(C)2431]. 

Studies are restricted to syntheses of Group 2B - organometallics and mainly to mercurials. Early studies of reactions of mercuric salts with furan- and thiophencarboxylic acids or their salts have been thoroughly reviewed (7-4). More recently several tetrafluoropyridyl derivatives have been prepared by decarboxylation [Eqs. (78) (87), (79) (88), or (80),... 

Ring-closing reactions promoted by mercuric salts are valuable transformations which find an increasing use in the total synthesis of various natural products.130-140 Several examples of solvomercurations demonstrating the applicability of these transformations to the synthesis of natural product precursors are presented in Table 2. Piperidines (entry a), 141 pyrans (entries b-d), 142-144 and furans (entries e, f)14S>146 have been obtained in good yields and diastereoselectivity. These derivatives serve as starting materials for various natural products and can be demercu-rated under reducing conditions.147... 

Ferrocene, like thiophene, furan, and other so-called superaromatic systems, reacts readily with mercuric acetate to form mercurated derivatives. Nes-meyanov and coworkers first reported that ferrocene could be mercurated under relatively mild conditions in either ethyl ether-alcohol or benzene-alcohol solution (63). The acetoxymercuriferrocenes formed in this manner are usually treated with an alcoholic solution of an alkali metal halide. The resulting products, chloro-mercuriferrocene (XXVII) and l,l -di(chloromercuri)ferrocene (XXVIII), can be conveniently separated by extraction with n-butyl alcohol. 

Iodomethyl-2,3-dihydrobenzofurans (196) and the corresponding 2-iodomercurimethyl derivatives can be obtained from o-allylphenols and mercuric acetate, via the 2-acetoxymercuri-2,3-dihydrobenzo-furans.420... 

A mercurated furan has been studied the relevant dimensions of the sheep liver toxin derivative are shown in (35). It is obvious that the metal causes some deformation, though not much, which is distributed around the ring. The methyl group is pushed away from the metal and the C(2)—C(3)—Me angle widens the furan ring is not exactly planar though it is nearly so (74JOC3392). 

The corresponding methyl-derivative (342, R = Me) leads to a furan under these conditions but deprotection by mercuric oxide and boron trifluoride produces an E/Z mixture of diketones corresponding to (343). Replacing one of the phenyl substituents in (342, R = H) with methyl leads instead to the (E)-ketone (344). Various mechanisms are possible for these reactions, but an attractive one involves methylation on sulphur and ring expansion to (345), followed by trapping by water and ring opening272 ... 

Verkade and co-workers179 described a somewhat different method of mercuration of the furan ring. They converted furan into 15 by direct reaction with HgCl2 in water, in the presence of sodium acetate and ethanol. 

The reaction of 1,2-dibromocycloalkenes (13) with magnesium in the presence of l,3-diphenylbenzo[c]furan (16) affords a cycloalkyne adduct (17). Also, the mercuric oxide oxidation of bishydrazone, which has been used extensively in the preparation of open-chain and medium or large cyclic acetylenes " , is adapted for small ring bishydrazones (18) . Treatment of 18 with mercuric oxide in the presence of 16 or of phenyl azide results in the adducts, 17 and 19, respectively. It seems... 

Tetra-acetoxymercuri-furane is formed when mercuric acetate reacts with furane. It decomjjoses at 226" to 228 C. and is converted by potassium hydroxide into the Mrahydroxy mmfmndy dea>mposing... 

Polymercuration frequently occurs. The Hg atom is not large [the non-bonded radius is 1.50-1.73 A (150-173 pm), compared, e.g., with 1.95 A (195 pm) for Br], and its electronic effect is weak. Permercuration of aromatics is possible, and not all compounds require drastic conditions, such as fusion with reactive Hg salts . Furan , pyrrole , thiophene and cyclobutadiene iron tricarbonyl are mercurated under mild circumstances. For the monomercuration of the more reactive aromatics, the extent of reaction must be limited, e.g., by using the mild HgCl2 in the presence of Na02CCH3 to buffer the solution. 

As a preparative route mercuration of arenes suffers from a lack of selectivity often all possible ring substitution products are formed. The directing influences of substituents operate, but selectivity is poor. The initial products can isomerize. Isomer distributions in mercuration of toluene under different conditions are given in Table 3. These effects coupled with the ease of polymercuration can be disadvantagous. Mild conditions must be used to limit the extent of mercuration of five-membered heterocyclic aromatics such as pyrrole, thiophene, selenophen and furan. These are among the most reactive aromatics toward Hg salts use of HgCl2 in the presence of Na02CCH3 at RT is... 

Intramolecnlar alkenylation at a furan a- or P-position by an alkyne occurs, with the formation of bicycUc derivatives, when promoted by mercury(II) acetate (or Hg(OAc)(OTf), generated in situ from mercuric acetate and scandinm triflate). In the case of closure onto a p-position, a spirocyclic intermediate from preferred attack at the a-position, may be involved, as shown. 

The reaction is applicable to benzene, benzene derivatives,174-176,183,184 polycyclic aromatic hydrocarbons,185 and also heterocyclic compounds of aromatic character such as thiophen, furan, and pyridine Volhard, for instance, in 1892 mercurated thiophen directly with mercuric chloride.186... 

Thiophen and furan are both very readily mercurated the mercury enters at the 2-position or, if that is occupied, at the 3-position if an excess of mercuric acetate is used, further hydrogen atoms can be replaced by acetoxymercuri groups, in fact all four in the case of furan. 

Chlorination of fiiran at -40°C yields 2-chlorofuran and 2,5-dichlorofuran. Bromination with the di-oxane-Br2 complex at -5°C gives 2-bromofuran. Nitration is best carried out with fuming nitric acid in acetic anhydride at -10° to -20°C, and yields 2-nitrofuran. Pyridine-S03 or dioxane-S03 complex converts furan into furan-2-sulfonic acid and then further into furan-2,5-disulfonic acid. Alkylation and acylation are also possible. The action of mercury(II) chloride and sodium acetate in aqueous ethanol brings about mercuration of furan ... 

Thiophene is chlorinated by CI2 or SO2CI2. Bromination occurs by Br2 in acetic acid or with N-bromosuccinimide. Nitration is effected by concentrated nitric acid in acetic acid at 10°C. Further substitution predominantly yields 2,4-dinitrothiophene. Sulfonation with 96% H2SO4 occurs at 30°C within minutes. Benzene reacts extremely slowly under these conditions. This provides the basis for a method to remove thiophene from coal tar benzene (see p 77). Alkylation of thiophenes often gives only poor yields. However, more efficient procedures are the Vilsmeier-Haack formylation, which yields thiophene-2-carbaldehyde, and acylation with acyl chlorides in the presence of tin tetrachloride, to give 2-acylthiophenes. Like furan, thiophene is mercurated with mercury(II) chloride. 

Chen and Lu used a mercuric acetate-mediated annulation of homopropargylic alcohols to generate iodinated furans for use in crosscoupling reactions. Treatment of 2-(3-methylbut-1 -yn-1 -yl)-2-pheny 1-1,3-dithiolane with nBuLi, followed by reaction with -butylaldehyde, produced a mercuric acetate intermediate that was subsequently trapped with iodine to give the corresponding 3-iodofiian. Further cross-coupling with a series of compounds (in this example naphthalene) led to the desired tetrasubstituted fiiran in 87% yield over three steps. 

Mercuric sulfate/sulfuric acid Furans from acetyleneoxido compounds... 

The furan reaction was shown to be an equilibrium, and to be catalyzed by mercuric chloride 116). Tris(2-furyl)arsine has also been prepared by Wurtz-Fittig and Grignard procedures 119). The most recent use of mercury compounds has been in the preparation of dichloroperfluorovinyl-arsine 120,121). 

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