Alkynes regioselective hydration

Table 2.7 Regioselective hydration of functionalized terminal alkynes with 13e as a catalyst.

Indeed, p-unsaturated bicyclic spiroketones were obtained from triynes via a regioselective cyclization (Scheme 73). Model reactions suggest that the platinum catalyzed reactions include two regioselective hydrations, an alkyne insertion, and an aldol condensation (Scheme 74). 

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). 

Because of the regioselectivity of alkyne hydration acetylene is the only alkyne structurally capable of yielding an aldehyde under these conditions... 

The most synthetically valuable method for converting alkynes to ketones is by mercuric ion-catalyzed hydration. Terminal alkynes give methyl ketones, in accordance with the Markovnikov rule. Internal alkynes give mixtures of ketones unless some structural feature promotes regioselectivity. Reactions with Hg(OAc)2 in other nucleophilic solvents such as acetic acid or methanol proceed to (3-acetoxy- or (3-methoxyalkenylmercury intermediates,152 which can be reduced or solvolyzed to ketones. The regiochemistry is indicative of a mercurinium ion intermediate that is opened by nucleophilic attack at the more positive carbon, that is, the additions follow the Markovnikov rule. Scheme 4.8 gives some examples of alkyne hydration reactions. 

The stereochemistry around the double bond was exclusively trans in the case of disubstituted olefins and it was also noteworthy that the hydration of methyl propargyl ether alkynes was regioselective, which was not the case with other alkynes. 

Both acid and metal catalysis are usually required to accomplish hydration of alkynes to yield carbonyl compounds.34 The addition is usually regioselective, allowing for conversion of terminal alkynes to ketones. Hydration of acetylene to produce acetaldehyde used to be an industrially significant process but was replaced by the Wacker synthesis. 

A highly regioselective, efficient, and clean anti-Markovnikov hydration of terminal acetylenes has been realized through the use of catalytic amounts of Ru complexes.561 Typically, [CpRu(dppm)Cl] catalyzes the reaction at 100°C to give aldehydes in high yields (81-94%). Triflic acid or trifluoromethanesulfonimide effectively catalyzes the hydration of alkynes without a metal catalyst to afford Markovnikov products (ketones).562... 

The hydration of terminal alkynes produces methyl ketones. Simple unsymmetrical internal alkynes generally afford mixtures of regioisomeric ketones, but alkynes bearing certain functional groups exhibit high regioselectivity (equations 226 and 227).333-333... 

The direct hydration of a terminal alkyne, with dilute sulphuric acid in the presence of a mercury salt, yields initially an enol which rearranges to the more stable ketone. The regioselectivity of the reaction is consistent with that predicted on the basis of mechanistic theory. 

On the other hand, lithium enolates derived from substituted endocyclic ketones have largely been exploited in the synthesis of steroids since the regioselectivity of their deprotonation can be controlled and high levels of 1,2- and 1,3-stereoselection occur9,418. The control is steric rather than electronic, with the attack directed to the less substituted ji-face of the enolate for conformationally rigid cyclopentanones, whereas stereoelectronic control becomes significant for the more flexible cyclohexanones. Finally, an asymmetric variant of the formation of a-branched ketones by hydration of camphor-derived alkynes followed by sequential alkylation with reactive alkyl halides of the resulting ketones was recently reported (Scheme 87)419. 

The ability of water to attack the ruthenium-carbon double bond suggested that the ruthenacyclopentadiene might add water as depicted in Scheme 1.4. Remarkably, heating a tethered diyne in aqueous acetone to 60 °C in the presence of the trisacetonitrile complex 16 gave a nearly quantitative yield of the hydrated cyclization product as depicted in Equation 1.29 [26], Unsymmetrical diynes showed exquisite regioselectivity wherein the water attacked the least sterically hindered alkyne carbon (Equation 1.30). 

In substrates bearing suitable functionality that could lead to internal nucleophilic attack by an oxygen, even a carbonyl oxygen, excellent regioselectivity may occur. Equation 1.31 illustrates an example of a ketone playing such a role [27]. Such an effect can even lead to hydration at the more hindered alkyne as shown in... 

Catalytic conversions of allenes are sometimes considered models for catalytic reactions of alkenes, even though allene reactivity is more closely comparable to that of alkynes rather than alkenes. The catalytic hydration of allenes was achieved by means of a cationic gold(I) complex with a carbene steering ligand, (IPr)AuCl/ AgOTf (5 mol%), in dioxane (rt, 4—9 h) in fair yield [180]. Attack of water is selective for the terminal carbons, whereas regioselectivity in nonsymmetric substrates is controlled by steric, electronic, and solvation factors. 

Oxidation of organoboranes to alcohols is usually effected with alkaline hydrogen peroxide. The reaction is of wide applicability and many functional groups are unaffected by the reaction conditions, so that a variety of substituted alkenes can be converted into alcohols by this procedure. Several examples have been given above. A valuable feature of the reaction is that it results in the overall addition of water to the double (or triple) bond, with a regioselectivity opposite to that from acid-catalysed hydration. This follows from the fact that, in the hydroboration step, the boron atom adds to the less-substituted carbon atom of the multiple bond. Terminal alkynes, for example, give aldehydes in contrast to the methyl ketones obtained by mercury-assisted hydration. 

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