Acyl ketenes

Pyran-4-ones are formed when acyl ketenes derived from dioxofurans and dioxinones react with vinyl ethers. Intermediate products are 1,3,5-triketones and reduced pyranones <96CPB956,96H(43)2457,96TL6499>. 

In Entry 13, the dioxinone ring undergoes thermal decomposition to an acyl ketene that is trapped by the solvent methanol. The resulting (3-keto-y,8-enoate ester then undergoes stereoselective cyclization. The stereoselectivity is controlled by the preference for pseudoequatorial conformations of the C(6) and C(9) substituents. 

The title phosphonate and related substances undergo thermal decomposition to B-acyl ketenes at temperatures in excess of 50°C. Thus thermolysis in the presence of alcohols, amines, a-hydroxy esters, and a-amino esters affords the corresponding g-keto esters and amides the latter two classes can be cyclized upon subsequent base treatment to unsaturated tetronic and tetramic acids and the related phosphonate reagents. ... 

The procedure described here offers a general route to a variety of unsymmetrically substituted y-pyrones from Meldrum s acid.2 Substitution at the 2-position depends on the acid chloride chosen, while substitution at the 5-position is derived from the vinyl ether. A variety of substituted y-pyrones have been synthesized by utilization of this method as illustrated in the Table. The intermediate pyrandione is believed to arise through the addition of the vinyl ether to an acyl ketene that results... 

Acyl ketenes also react with a variety of dienophiles such as enol ethers to give the corresponding 2-alkoxy-2,3-dihydro-4-pyranones [147]. 

A convenient synthesis of thiazolo-fused 2-pyridones 41 has been developed <07JOC4917>. Thus, A2-thiazolines 39 undergo acyl ketene imine cyclocondensation with Meldrum s acid derivatives 38 to give the dihydro thiazolo-fused 2-pyridones 40, which transform to 41 via bromination-elimination process. Pyridones 41 are converted to the 2-substituted analogs 43 and the saturated products 42 by Heck coupling and conjugate addition, respectively. 

Some new methods for the synthesis of the oxadiazole ring have been recently published. 1,2,4-Oxadiazoles can be easily obtained in a one-pot solvent-free process starting from P-keto esters 169 and amidoximes 170. The process is likely to go through an acyl ketene intermediate <07TL2231>. 

The reaction starts from [4+1] cycloaddition of the isocyanide to the electron-deficient heterodiene moiety of acid 396 to form intermediate iminolactone 397 that loses acetone to give acyl ketene 398 which then reacts with pyrrole at the ketene carbonyl to form the second acyl ketene 399 (Scheme 86). Ring closure of this ketene leads to the final product 400. Similar reaction conditions as described above, were employed for indole and 2-methylindole (Equation 94). 

Recently, Boeckman and Pruitt [58] demonstrated the use of dioxolenones as precursors of P-acyl ketenes, which can be thermally generated under mild neutral conditions in the absence of other nucleophiles and trapped intramolecularly by the hydroxy group to afford good yields of macrocyclic lactones. The 16-membered macrolide (—)-kromycin 102) has been synthesized in this way by thermolysis of the P-acyl ketene precursor 101 in toluene at high dilution (0.0001 M) in 70% yield (Scheme 34). 

Cycloaddition of a,3-unsaturated ketones, acyl ketenes, acyl, thioacyl, imidoyl and vinyl isocyanates, as well as the corresponding isothiocyanates, to the C=C bond of vinylidenephosphoranes leads to the formation of six-membered heterocycles carrying an exocyclic ylide function e.g. equation 117). In some instances the mentioned thioisocyanates, however, may undergo [2 + 2] cycloaddition at the C=S bond. Interestingly N-aryliminovinylidenetriphenylphosphoranes dimerize in a [4 2] cycloaddition on heating alone. 

Ethoxyacetylene adds, catalyzed by mercury acetate and ZnCh, alii atic or aromatic alcohols to produce mixed substituted orthoesters, e.g. (391)-(393) (Scheme 72). ° Acyl ketenes are formed on thermolysis of l,3-dioxin-4-ones, which can be trapped with ketene acetals to give orthoesters (394 equation 181) 861-863 2,2-Dialkoxydihydrofurans (395 equation 182) are accessible by addition of ketones to cy-clopropenone acetals. Treatment of 2-chloro-2,3-dimethoxy-l,4-dioxane with sodium methoxide affords the 2,2,3-trimethoxy-l,4-dioxane (396 equation 183). ... 

Tosyl azide reacts with the CH of an acyl ketene NS-cyclic ketal in refluxing dioxane to form a fused triazole ring. 

Bei Acyl-keten-N,S-acetalen kommt es immer zur Abspaltung des Alkylthio-Restes und zur Bildung der entsprechenden 3(5)-Amino-lH-pyrazole469 ... 

Zur Eliminierung einer Benzoyl-Gruppe446 und zum Einsatz von Acyl-keten-aryliminen943 (3-Anilino-lH-pyrazole) s. Lit. 

The methods for generating acyl ketenes (Scheme 7-V) and their subsequent in situ participation in [4 + 2] cycloadditions with a wide range of hetero- or olefinic and acetylenic dienophiles (Scheme 7-VI), including acyl ketenes,185 186,197 carbonyl compounds, 86-188 nitriles,1874,189,191 isocyanates and isothiocyanates,1864,190,191 ketenes,191 imines,1864,1874,191,192 carbo-diimides,l87c 190,191,193 ynamines,194 ketene acetals,1864,195 enol ethers,1864,191,196 and V-sulfinylamines197 have been extensively reviewed.5,9,12 Two reports have detailed the 4-n- participation of allenic ketones in [4 + 2] cycloaddition reactions [Eq. (51)].198,199... 

Alkyl P-oxoalkanedithioates. The combination of H2S-Bp3.0Et2 dealkylate one of the S-substituents of acyl ketene dithioacetals in refluxing dioxane. 

Synthesis of Triazoles from Cyclic Acyl Ketene Aminals. 50... 

A procedure (Equation (12)), starting with dioxolenones (71) to give eight-membered ring j8-ketolactones (72), has been described <90CC836>. The key step is a thermolysis reaction which results in extrusion of acetone and formation of an acyl ketene which reacts intramolecularly with the hydroxy functionality in >90% yield. 

Phenyl(chlorocarbonyl)ketene 170 reacts with N-phenylacetyknorpho-line forming 4-hydroxy-6-morpholino-3,5-diphenylpyran-2-one in a process interpreted as involving initial esterification of the acylketene with the enol of the amide followed by generation of a second acyl ketene 171 and further cyclization to 172 (Eqn (4.109)). Ketene 170 also reacts similarly with 1,3-diketones and heterocyclic 3-hydroxy-2-ene-l-ones forming polycyclic lactones. 

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