Ketone To alkyne

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

Addition of a hydroxy group to alkynes to form enol ethers is possible with Pd(II). Enol ether formation and its hydrolysis mean the hydration of alkynes to ketones. The 5-hydroxyalkyne 249 was converted into the cyclic enol ether 250[124], Stereoselective enol ether formation was applied to the synthesis of prostacyclin[131]. Treatment of the 4-alkynol 251 with a stoichiometric amount of PdCl2, followed by hydrogenolysis with formic acid, gives the cyclic enol ether 253. Alkoxypalladation to give 252 is trans addition, because the Z E ratio of the alkene 253 was 33 1. 

The most common synthetic application of mercury-catalyzed addition to alkynes is the conversion of alkynes to ketones. This reaction is carried out under aqueous acidic conditions, where the addition intermediate undergoes protonation to regenerate Hg. ... 

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. 

Table 3.6 Oxidative cleavage of alkenes to acids and alkynes to ketones or acids...

Hydration and Hydroalkoxylation of Alkynes Gold compounds were first applied to catalyze these types of reactions by Utimoto et al. in 1991, when they studied the use of Au(III) catalysts for the effective activation of alkynes. Previously, these reactions were only catalyzed by palladium or platinum(II) salts or mercury(II) salts under strongly acidic conditions. Utimoto et al. reported the use of Na[AuCI41 in aqueous methanol for the hydration of alkynes to ketones [13]. 

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. 

The anthracyciinone class of anticancer compounds (which includes daunomycin and adriamycin) can be made using a mercury (I I )-promoted alkyne hydration. You saw the synthesis of alkynes in this class on Chapter 9 where we discussed additions of metallated alkynes to ketones. Here is the final step in a synthesis of the anticancer compound deoxydaunomycinone the alkyne is hydrated using Hg2+ in dilute sulfuric acid the sulfuric acid also catalyses the hydrolysis of the phenolic acetate to give the final product. 

HydrosilyUUion. This silane is useful for hydrosilylation of alkencs and alkynes because the C—Si bond of the adducts is oxidized by 30% H,0, in the presence of KF, KHF, or NaHCO, with formation of the corresponding alcohol. The oxidation occurs with retention of configuration at carbon. At least one alkoxy group on silicon is necessary for this oxidation. Hydrosilylation followed by oxidation permits conversion of 1-alkenes to anti-Markownikoff alcohols (equation 1) and of internal alkynes to ketones (equation II). 

Whereas transition metal-catalyzed 1,2-additions of alkynes to ketones proceed with only poor conversions, the 1,4-addition to a,/0-unsaturated ketones (eq. (4)) in the presence of Rh -phosphine complexes produces high yields [12]. 

Another prototypical example of the application of intermolecular oxypalladation to the synthesis of natural products and related compounds is shown in Scheme 3. Unlike the Wacker oxidation of alkenes to give ketones, the conversion of alkynes to ketones is a net nonredox process involving hydration of the triple bond. It should also be clearly noted that the observed high regioselectivity can most readily be explained in terms of intramolecular oxypalladation involving anchimeric participation by the cyclopentanone moiety followed by hydrolysis. 

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 Markownikoff rule. Internal alkynes will give mixtures of ketones unless some structural feature directs regioselectivity. Scheme 4.8 gives some examples of alkyne hydrations. 

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