Alkynes hydration, mercury catalyzed

Several preparative methods exist for the synthesis of 3(2//)-dihydrofuranones. 2,5-Disubstituted or 2,2,5,5-tetrasubstituted 3(2i/)-dihydrofuranones are usually prepared by reaction of sodium or lithium acetylide with a ketone to yield an alkynic alcohol which is then treated with a carbonyl compound in the presence of base to afford alkynic diols. Mercury catalyzed hydration of the resultant diols in the presence of acid affords the furanones in good yields (76JMC709). 

Except for very reactive alkynes, acid-catalyzed hydrations are usually sluggish. This slow hydration can be overcome by the addition of catalytic amounts of mercury(II) salts. Such hydrations are generally mild and will tolerate the presence of other functional groups. Specific examples of mercury-catalyzed hydrations are discussed in the next section. 

Alkynes undergo mercury-catalyzed hydration to afford ketones (equation 224).31 348-350... 

The initial product has a hydroxy group attached to a carbon-carbon double bond. Compounds such as this are called enols (ene + ol) and are very labile—they cannot usually be isolated. Enols such as this spontaneously rearrange to the more stable ketone isomer. The ketone and the enol are termed tautomers. This reaction, which simply involves the movement of a proton and a double bond, is called a keto—enol tautomerization and is usually very fast. In most cases the ketone is much more stable, and the amount of enol present at equilibrium is not detectable by most methods. The mechanism for this tautomerization in acid is shown in Figure 11.6. The mercury-catalyzed hydration of alkynes is a good method for the preparation of ketones, as shown in the following example ... 

Mercury. A short account of the discovery of metal-catalyzed hydration of alkynes by Kucherov (1881) appeared on the occasion of its 125th anniversary [116]. Mercury-catalyzed hydration of alkynes has been used as mechanistic principle for devising fluorogenic probes for mercuric ions by two research teams. In one system, a 3-butyn-l-yl group at the phenolic oxygen of a fluorescein dye was cleaved via catalytic oxymercuration and elimination to releases a fluorescent dye (Scheme 20) [117]. In another system the mercury-catalyzed hydration of an ethynyl to an acetyl group provoked the quenching of fluorescence in a coumarine-based dye [118]. 

There also exists an acidregioselective condensation of the aldol type, namely the Mannich reaction (B. Reichert, 1959 H. Hellmann, 1960 see also p. 291f.). The condensation of secondary amines with aldehydes yields Immonium salts, which react with ketones to give 3-amino ketones (=Mannich bases). Ketones with two enolizable CHj-groupings may form 1,5-diamino-3-pentanones, but monosubstitution products can always be obtained in high yield. Unsymmetrical ketones react preferentially at the most highly substituted carbon atom. Sterical hindrance can reverse this regioselectivity. Thermal elimination of amines leads to the a,)3-unsaturated ketone. Another efficient pathway to vinyl ketones starts with the addition of terminal alkynes to immonium salts. On mercury(ll) catalyzed hydration the product is converted to the Mannich base (H. Smith, 1964). 

In general ketones are more stable than their enol precursors and are the products actually isolated when alkynes undergo acid catalyzed hydration The standard method for alkyne hydration employs aqueous sulfuric acid as the reaction medium and mer cury(II) sulfate or mercury(II) oxide as a catalyst... 

Like alkenes (Sections 7.4 and 7.5), alkynes can be hydrated by either of two methods. Direct addition of water catalyzed by mercury(II) ion yields the Markovnikov product, and indirect addition of water by a hydroboration/ oxidation sequence yields the non-Markovnikov product. 

Figure 8.3 MECHANISM Mechanism of the mercury(II)-catalyzed hydration of an alkyne to yield a ketone. The reaction occurs through initial formation of an intermediate enol, which rapidly tautomerizes to the ketone.

The hydroboration/oxidation sequence is complementary to the direct, mercury(ll)-catalyzed hydration reaction of a terminal alkyne because different products result. Direct hydration with aqueous acid and mercury(IJ) sulfate leads to a methyl ketone, whereas hydroboration/oxidation of the same terminal alkyne leads to an aldehyde. 

The mercuric ion-catalyzed hydration of alkynes probably proceeds in a similar manner to the oxymercuration of alkenes (see Section 5.1). Electrophilic addition of Hg to the triple bond leads to a vinylic cation, which is trapped by water to give an vinylic organomercury intermediate. Unlike the alkene oxymercuration, which requires reductive removal of the mercury by NaBH4, the vinylic mercury intermediate is cleaved under the acidic reaction conditions to give the enol, which tautomerizes to the ketone. Hydration of terminal alkynes follows the Mai kovnikov rule to furnish methyl ketones. ° ... 

The mechanism of the mercurydD-catalyzed alkyne hydration reactioi is analogous to the oxymercuration reaction of alkenes (Section 7.4). Elec trophilic addition of mercury(II) ion to the alkyne gives a vinylic cation which reacts with water and loses a proton to yield a mercury-containii eiio) intermediate. In contrast to alkene oxymercuration, no treatment witll NaBH is necessary to remove the mercury the acidic reaction conditions alone are sufficient to effect replacement of mercury by hydrogen (Figure 8,3), A mixture of both possible ketones results when an unsymmetrically substituted internal alkyne (RCsCR ) is hydrated. The reaction is therefor ... 

The first step in the mercuric-ion-catalyzed hydration of an alkyne is formation of a cyclic mercurinium ion. (Two of the electrons in mercury s filled 5d atomic orbital are shown.) This should remind you of the cyclic bromonium and mercurinium ions formed as intermediates in electrophilic addition reactions of alkenes (Sections 4.7 and 4.8). In the second step of the reaction, water attacks the most substituted carbon of the cyclic intermediate (Section 4.8). Oxygen loses a proton to form a mercuric enol, which immediately rearranges to a mercuric ketone. Loss of the mercuric ion forms an enol, which rearranges to a ketone. Notice that the overall addition of water follows both the general rule for electrophilic addition reactions and Markovnikov s rule The electrophile (H in the case of Markovnikov s rule) adds to the sp carbon bonded to the greater number of hydrogens. 

Scheme 20 Applications of mercury catalyzed alkyne hydration...

The acid-catalyzed hydration of alkynes (Table 6.7, example 2) is commonly carried out using mercury (11) salts, such as mercuric sulfate (HgS04), as catalysts. The addition (Scheme 6.67) appears to involve a bridged mercurinium ion, which, for unsymmetrical cases such as 1-alkynes other than ethyne (acetylene [HC CH]), is subsequently attacked by water (FI2O) at the carbon that best supports a positive charge. The regiochemistry of Markownikoff addition, seen with alkenes, is followed. 

Like alkenes, alkynes can be hydrated. The reaction is generally catalyzed hy mercuric ions in an oxymercuration process (Fig. 10.71), although simple acid catalysis is also known. In contrast to the oxymercuration of alkenes, no second, reduction step is required in this alkyne hydration. By strict analogy to the oxymercuration of alkenes, the product should be a hydroxy mercury compound, hut the second double bond exerts its influence and further reaction takes place. The double hond is protonated and mercury is lost to generate a species called an enol. An enol is part alkene and part alcoho/, hence the name. 

Mechanism of the mercury(ll)-catalyzed hydration of an alkyne to yield a ketone. 

---