Acylation with ketenes

Route (b), based on an aliphatic Friedel-Crafts reaction, gives a good yield of (31) which is duly acylated with ketene dimer. 

Simple 1,1-enediamines have been shown to undergo a vigorous acylation with ketenes with the formation of acyl-substituted 1,1-enediamines (equation 65)139. 

The reactions of vinylogous amides and vinylogous urethanes with excess ketene were found to give a-pyrones (421), which could also be obtained from further reactions of acylated enamines with ketene (383,421). 

Analogously, the reactions of ketene aminals with ketene or dimethyl ketene gave y-amino-a-pyrones and the linear acylation products, respectively 422). 

The reaction of enamines with ketenes can be conveniently carried out by generating the ketene in situ from an acyl halide and a tertiary amine. 

The reactions of nitroalkenes (42) with various enols (43b) (vinyl ethers, silyl, and acyl enolates, ketene acetals) have been studied in most detail (110, 111, 125—154). As a mle, these reactions proceed smoothly to give the corresponding nitronates (35f) in yields from high to moderate. As in the reactions with enamines, the formation of compounds (44b) is attributed to the ambident character of the anionic centers in zwitterionic intermediates analogous to those shown in Scheme 3.43. 

The (aziridin-l-ylimino)phosphoranes (57) react with ketens to give nitrile derivatives, presumably from an intermediate ketenimine by breaking the N—N bond and migration of the aziridinyl group.60 They also react with acyl halides and... 

We have studied this reaction in considerable detail (88) and have found that when one uses quinine (eq. [25]) or any one of the chiral bases, a variety of aldehydes react with ketene to form the corresponding p-lactones in excellent chemical and nearly quantitative enantiomeric yields. Equation [25] exemplifies the reaction. Note that mild basic hydrolysis of the lactone furnishes a trichlo-rohydroxy acid that was prepared earlier by McKenzie (89). If one uses quinidine as catalyst, the process furnishes the natural (S)-malic acid. Note that ketene first acylates the free hydroxyl group of quinine, so that the actual catalyst is the alkaloid ester. 

Intramolecular acylation reactions with ketene complexes, generated, for instance, by thermolysis or photolysis of carbene complexes, can also be used for the preparation of six-membered rings. Illustrative examples are shown in Table 2.23. 

Further methods for preparing seven-membered rings with the aid of heteroatom-substituted carbene complexes include the intramolecular acylation reactions with ketene complexes discussed in Section I.2.6.2. 

Malonyl chloride reacted with boiling acetone to give the bicyclic 2 1 adduct 210 comprising a pyranone and a l,3-dioxan-4-one moiety (Scheme 99). The modest yield was compensated for by the ease of its preparation. Compound 210 bears a chloride which is almost as reactive as an acyl chloride and which can be substituted by various nucleophiles in a Stille coupling in modest yields <1997SL895>. Treatment of malonyl chloride with ketene and acetone at low temperature afforded symmetric bis(l,3-dioxin-4-ones) in 60% yield although a different reaction pathway may be assumed (Scheme 99) <2000TL4959>. 

Solid Catalysts. Nafion-H is an active catalyst for acylation with aroyl halides and anhydrides.60,61 The reaction is carried out at the boiling point of the aromatic hydrocarbons. Yields with benzoyl chloride using 10-30% Nafion-H for benzene, toluene, and p-xylene are 14%, 85% and 82%, respectively. Attempted acylation with acetyl chloride, however, led to HC1 evolution and ketene formation. Nation resin-silica nanocomposite materials containing a dispersed form of the resin within silica exhibits significantly enhanced activity in Friedel-Crafts acylations.62,63... 

TV-Acylation of (73) can be achieved with acyl chlorides and pyridine or triethylamine, or with ketene (75S547 p. 560). 7V-Trimethylsilylazetidin-2-ones have been reported to undergo acyldesilylation on treatment with acetyl chloride. Acylation of (73) with imidates (78) at 150-160 °C was followed by ring expansion to give the pyrimidin-4-ones (79). Pyrimid-4-ones were obtained from a similar reaction of imidates with 4-alkoxyazetidin-2-ones (74CB270). Acylation with subsequent ring expansion also occurs with dithioimidates (73CPB1305). 

Ketene itself reacts with enamines and if in excess produces pyran-2-ones which are substituted in the 4-, 5- and 6-positions (65JOC2642). It seems likely that the acylated enamine undergoes a 1,4-addition with ketene to give an intermediate 4-amino-3,4-dihydropyranone, which eliminates the secondary amine on further reaction with ketene. 

Acyl isocyanates can also react with ketene to give derivatives of 4/f-l,3-oxazine (63)172 [Eq. (50)]. 

The reported gas-phase acylations with Nafion-H catalyst were generally carried out at the boiling point of the hydrocarbon to be acylated. The yield of aroylation reaction depends on the relative amount of the catalyst used. Optimum yields were obtained when 10-30% of Nafion-H was employed relative to the aroyl halide. Although this procedure allows very clean reactions with no complex formation and easy work-up procedures, it is presently limited to only aroylation. Attempted acetylation of aromatics with acetyl chloride under similar conditions led to thermal HC1 elimination from the latter to form ketene and products thereof. In the reaction of acetyl chloride by itself with Nafion-H, diketene was detected by IR and NMR... 

Simple amines can rapidly add to ketenes in the absence of a catalyst, but less reactive nitrogen nucleophiles such as the pyrroles do not react at room temperature with ketenes such as phenyl ethyl ketene <2002JA10006>. In contrast, additions can proceed swiftly when planar chiral 4-(pyrrolidino)pyridine (PPY) derivative 235 is employed as a catalyst (Equation 58). In the presence of enantiopure PPY derivative 235 and an appropriate pyrrole, the A -acylpyrroles 236 and 237 can be generated in high enantiomeric excess (Equations 58 and 59) <2002JA10006>. With pyrrole itself as the nucleophile, the new stereocenter is produced in moderate ee (42%). It was discovered that l-acyl-l/7-pyrrole-2-carbonitriles 236 can be converted into a wide array of useful compounds with essentially no erosion in enantiomeric excess. 

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