Methyl ketones, terminal acetylenes

Methyl ketones are important intermediates for the synthesis of methyl alkyl carbinols, annulation reagents, and cyclic compounds. A common synthetic method for the preparation of methyl ketones is the alkylation of acetone derivatives, but the method suffers limitations such as low yields and lack of regioselectivity. Preparation of methyl ketones from olefins and acetylenes using mercury compounds is a better method. For example, hydration of terminal acetylenes using HgSO gives methyl ketones cleanly. Oxymercuration of 1-olefins and subsequent oxidation with chromic oxide is... 

The hydration of triple bonds is generally carried out with mercuric ion salts (often the sulfate or acetate) as catalysts. Mercuric oxide in the presence of an acid is also a common reagent. Since the addition follows Markovnikov s rule, only acetylene gives an aldehyde. All other triple-bond compounds give ketones (for a method of reversing the orientation for terminal alkynes, see 15-16). With allqmes of the form RC=CH methyl ketones are formed almost exclusively, but with RC=CR both possible products are usually obtained. The reaction can be conveniently carried out with a catalyst prepared by impregnating mercuric oxide onto Nafion-H (a superacidic perfluorinated resinsulfonic acid). ... 

The above-postulated overall mechanism considers two alternative pathways depending on the nature of the acetylene derivative. Region A outlines a proposal in which the formation of the a-complex intermediate is supported by the fact that the treatment of aliphatic terminal acetylenes with FeCl3 led to 2-chloro-l-alkenes or methyl ketones (Scheme 12). The catalytic cycle outlined in region B invoked the formation of the oxetene. Any attempt to control the final balance of the obtained... 

CONVERSION OF METHYL KETONES INTO TERMINAL ACETYLENES VIA ENOL PHOSPHATES... 

A rather different reaction of acetylenes is the addition of water, usually catalysed by Hg(II), to give ketones. Terminal acetylenes 41 reliably give methyl ketones 44 as the intermediate vinyl cation 42 is secondary. Water adds to the cation 42 to give the enol 43 which equilibrates to the ketone 44 with the loss of Hg(OAc)2. 

Methoxybenzenetellurinic anhydride served as catalyst for the preparation of methyl ketones from terminal acetylenic compounds4. 

Oxidations by oxygen and catalysts are used for the conversion of alkanes into alcohols, ketones, or acids [54]-, for the epoxidation of alkenes [43, for the formation of alkenyl hydroperoxides [22] for the conversion of terminal alkenes into methyl ketones [60, 65] for the coupling of terminal acetylenes [2, 59, 66] for the oxidation of aromatic compounds to quinones [3] or carboxylic acids [65] for the dehydrogenation of alcohols to aldehydes [4, 55, 56] or ketones [56, 57, 62, 70] for the conversion of alcohols [56, 69], aldehydes [5, 6, 63], and ketones [52, 67] into carboxylic acids and for the oxidation of primary amines to nitriles [64], of thiols to disulfides [9] or sulfonic acids [53], of sulfoxides to sulfones [70], and of alkyl dichloroboranes to alkyl hydroperoxides [57]. 

A mild and efficient synthesis of terminal alkynes starts with readily accessible methyl ketones and converts them to the corresponding enolates with LDA. The eno-lates produced are trapped with diethyl chlorophosphate to give enol phosphates, which possess a good leaving group for elimination. Subsequent treatment of the enol phosphates with LDA furnishes the corresponding lithium alkynylides and on protonation of these, the corresponding terminal acetylenes. 

Negishi, E., King, A.O., and Klima, W.L., Conversion of methyl ketones into terminal acetylenes and ( )-trisubstituted olefins of terpenoid origin, J. Org. Chem., 45, 2526, 1980. 

Hydration of a triple bond with Hg(II) catalysis depends on forming the more stable vinyl cation (23). Hence terminal acetylenes always give methyl ketones. The carnation perfume (24) can be made this way. 

The mercuric-ion-catalyzed hydration of terminal acetylenes has been a significant method for synthesis of methyl ketones. The reaction can also be used with internal acetylenes if they are symmetrical. Unsymmetrical alkynes would be... 

Because the sense of the addition reaction is in the Markownikoff direction terminal alkynes, with the exception of ethyne (acetylene, HC CH), will always generate methyl ketones. 

Following conversion into its kinetic enol phosphate (terminal olefinic bond), treatment of a methyl ketone with LDA or lithium 2,2,6,6-tetramethylpiperidide effects highly regioselective /3-elimination to give a terminal acetylene e.g. Scheme 107).This is the first method for this transformation that works consistently, even for methyl ketones with a-methylene or a-methine hydrogen atoms, without significant quantities of allenes being formed concurrently. 

The most synthetically valuable method for converting acetylenes to ketones is by mercuric-ion-catalyzed hydration. Terminal alkynes give methyl ketones in good yields. Unsymmetrical internal alkynes give a mixture of two possible ketones in the absence of some special stabilizing feature. Scheme 4.6 gives some examples of acetylene hydrations. 

Polin, J. Schottenberger, H. Conversion of Methyl Ketones into Terminal Acetylenes Ethyny Iferrocene OS, (1995), 73,262. 

In the first route, methylbutenol is made from acetone and acetylene followed by hydrogenation. Reaction with methyl isopro-penyl ether yields methylheptenone (6). The second route involves the reaction of isobutylene, formaldehyde and acetone (7 ). Methyl vinyl ketone is an intermediate. Finally, methylheptenone is made by alkylation of acetone with prenyl chloride which is derived from isoprene (8). The initial product is the terminal olefin which is isomerized to the desired isopropylidene compound. 

Palladium complexes provide a catalytic means for introducing a carbonyl functionality to many organic substrates [185]. The unique value of PdCl2(dppf) as a carbonylation catalyst was realized over a decade ago in the synthesis of acetylenic ketones from terminal acetylenes and organic halides (Scheme 1-25) [186]. Catalytic carbonylation of arylacetylenes in the presence of HI in methanol gives methyl... 

Copper sulfate, CuS04 5H20, is used for the oxidative coupling of terminal acetylenes [5S] for the conversion of a-hydroxy ketones (acyloins) into a-diketones [351, 352] and, in cooperation with potassium peroxy-disulfate, for the selective oxidation of methyl groups on benzene rings to aldehyde groups [355],... 

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