Ketones by hydration of alkynes

Borane, BH3, is an avid electron pair acceptor because only a sextet of valence electrons is present at boron in the monomeric molecule. The pure material exists as a dimer. In aprotic solvents which act as electron pair donors such as ethers, tertiary amines, and sulfides, diborane forms stable Lewis acid-Lewis base 

Diborane can be generated in situ from sodium borohydride and boron trifluoride. Solutions in tetrahydrofuran are commercially available. An alternative commercially available reagent is the borane-dimethyl sulfide complex  

It is more amenable to storage over extended periods than diborane and exhibits comparable reactivity toward alkenes. 

Organic Synthesis via Boranes, John Wiley and Sons, New York (1975). 

CHAPTER 4 ELECTROPHILIC ADDITIONS TO CARBON-CARBON MULTIPLE BONDS 

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B-ll. Which one of the following is the intermediate in the preparation of a ketone by hydration of an alkyne in the presence of sulfuric acid and mercury(II) sulfate ... 

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. 

Aldehydes and ketones can be prepared by oxidation of alcohols or alkenes by the partial reduction of carboxyhc acid derivatives (aldehydes only) or by hydration of alkynes. 

By analogy to the hydration of alkenes, hydration of an alkyne would be expected to yield an alcohol. This alcohol, however, would be a special kind, called an enol, one in which the —OH group is attached to a carbon-carbon double bond. Except for the enol of acetylene itself, the enols formed by hydration of alkynes rapidly isomerize to ketones under conditions of their formation. 

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. 

Acid catalyzed hydration (Section 9 12) Water adds to the triple bond of alkynes to yield ketones by way of an unstable enol intermediate The enol arises by Markovnikov hydration of the alkyne Enol formation is followed by rapid isomerization of the enol to a ketone... 

You have had earlier experience with enols m their role as intermediates m the hydration of alkynes (Section 9 12) The mechanism of enolization of aldehydes and ketones is precisely the reverse of the mechanism by which an enol is converted to a carbonyl compound... 

Aldehydes and ketones are obtained by ozonolysis of alkenes (see Section 5.7.6) and hydration of alkynes (see Section 5.3.1). 

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. 

Hydration of alkynes yields carbonyl compounds and the ketone used in pyrylium syntheses has been successfully replaced by an alkyne (65CB334). Phenylacetylene, for example, reacts with 3-chloro-l-phenylprop-2-en-l-one to yield the 2,6-diphenylpyrylium salt. 

Isotope effect studies of the mechanism of hydration of alkynes with formic acid as water donor485b,485c leading to ketones (equation 234a) have been undertaken recently4854 by observing the kinetic isotope fractionation of 13C in the course of carbon monoxide... 

Ketones such as 2-heptanone may be readily prepared by hydration of terminal alkynes. Thus, if we had 1-heptyne, it could be converted to 2-heptanone. 

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 ... 

Methyl ketones arc prepared by hydration of terminal alkynes in presence of Hg " catalyst Section 8.5) ... 

Problem 8.4 What product would you obtain by hydration of 4-octyne Of 2 methyl-4-octyn Problem 8.5 What alkynes would you start with to prepare the following ketones ... 

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. ° ... 

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