Keto-alkynes

Propargylic alcohol, after lithiation, reacts with CO2 to generate the lithium carbonate 243, which undergoes oxypalladation. The reaction of allyl chloride yields the cyclic carbonate 244 and PdC. By this reaction hydroxy and allyl groups are introduced into the triple bond to give the o-allyl ketone 245[129]. Also the formation of 248 from the keto alkyne 246 with CO2 via in situ formation of the carbonate 247 is catalyzed by Pd(0)[130]. 

The 4-kcto group in the alkyne 262 as an enol form adds to the triple bond to give the furan 263[133], Even the conjugated keto alkyne 264 was converted into the furan 266 via isomerization to the allenyl ketone 265[134],... 

This cyclization was used in a synthesis of the tricyclic bisallylic diol (3) from the keto-alkyne (l).3... 

The Eschenmoser fragmentation does not have to be a ring expansion, and it is a useful synthetic method for making keto-alkynes. The following reaction, which we will use to discuss the fragmentation s mechanism, was used to make an intermediate in the synthesis of an insect pheromone, exo-brevicoinin. 

Equation (32) shows another example of this type of rearrangement, in which a phenylselenoallenic ester is converted to an a keto alkynic ester in quantitative yield... 

In Section III.E we noted that alkynes may be attacked by hydroxylamines at oxygen or nitrogen and illustrated nitrone formation in equation (111). The possibility of rearrangement of the nitrogen and oxygen products was also indicated. Hiere we give an example of the former (equation 176) . By comparison, isoxazole formation from keto alkynes is routine (equation 177) . 

Phosphorus yhds are quite common (see 16-44) and keto-phosphorus ylids [RCOCH=PPh3] are also known. When these compounds are heating (flash vacuum pyrolysis, FVP) to > 500°C, alkynes are formed. Simple alkynes can be formed as well as keto-alkynes and en-ynes. Rearrangement from ylids derived from tertiary amines an a-diazo ketones is also known. ... 

Hortmann and Harris have reported further information on the reaction of dimethyloxysulphonium-methylide with a-keto-alkynes. Under certain conditions the initial adduct (69) could be isolated, but at higher temperatures the 1-methylthiabenzene 1-oxide (70) was obtained. The adduct (69) could be converted into (70) by heating in chloroform or by treating with ethanolic sodium ethoxide. Tamura et al. have reported an X-iay crystallographic analysis of one such structure which had C—S (ring) bond lengths of 1.706 and 1.696 A, lengths very similar to those of other sulphonium ylides. Treatment of (70 = R = Ph) with n-butyl-... 

As an alternative to keto-alkyne isomerization, aDenylketones themselves can undergo cycloisomerization, providing access to furans and dimeric products, depending upon the palladium catalyst and allene employed (Scheme 6.24) [33]. 

An alternative approach to multicomponent heterocycle synthesis involves the use of palladium catalysis to construct keto-alkynes for cycloaddition reactions. Muller has demonstrated the power of this approach in the construction of a range of aromatic heterocycles. For example, the palladium-catalyzed coupling of acid chlorides with terminal alkynes provides a method to assemble 36. The trapping of this substrate can provide routes to aromatic heterocycles. As an example, the addition of amidines provides a multicomponent synthesis of pyrimidines (Scheme 6.69) [97]. This same substrate 36 is available via the carhonylative coupling of aryl halides with terminal alkynes, providing a four-component synthesis of pyrimidines (98j. 36 can also be employed in 1,3-dipolar cydoaddition reactions. For example, cydoaddition... 

A lactone-based synthesis converted keto-alkyne 6.245 to carboxylic acid 6.246 in four steps. Formation of lactone 6.247 was followed by conversion to azide 6.248. Reaction with butylamine and hydrogenation gave N-butyl 5-amino-6-cycIohexyI-2-isopropylhexanamide, 6.249. This amino acid product is considered to an hydroxy-ethylene dipeptide isostere. 115,143 jn the case of 6.249, the term isostere essentially refers to replacing one group in a molecule with another that will give similar chemical or physiological properties. 

Under similar conditions of phase-transfer carbonylation, a-keto alkynes gave either unsaturated hydroxybutyrolactones 4S (Equation 10.22) or 2-alkylidene 3-keto carboxylic add 46 (Scheme 10.11), depending on whether hydrogen atoms were attached... 

However, when secondary propargyUc alcohols were used as substrates to perform reactions with 1,3-dicarbonyl compounds, tetrasubstituted furans 22 instead of diene-diones were obtained (Scheme 5.11) [17]. In this case, the process combines trifluoroacetic acid-promoted propargylation of 1,3-dicarbonyl compounds and a Ru-catalyzed cycloisomerization of the resulting y-keto alkynes 23. 

SCHEME 25.80. Mn(III)-based oxidative cyclization of a keto alkyne. 

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