Acylation with diketenes

The reaction of methane tricarboxylate with indoline 342 gave the tricyclic derivative 361 which can be transformed to the amide derivatives 362 (97JHC969). Alkylation of the iV-benzyl indoline 360 with pentafluor-oacetone gave 363 which upon debenzylation and subsequent acylation with diketene followed by cyclization gave 364. Other haloacetones were used to prepare different halogenated derivatives (79BEP872311) (Scheme 63). 

Ketenes. Derivatives of the compound ketene, CH2=C=0, are named by substitutive nomenclature. For example, C4Hc,CH=C=0 is butyl ketene. An acyl derivative, such as CH3CH2—CO—CH2CH=C=0, may be named as a polyketone, l-hexene-l,4-dione. Bisketene is used for two to avoid ambiguity with diketene (dimeric ketene). 

The acylation of dienamines has not been extensively investigated. The dienamine (127) prepared by Birch reduction of N,N-dimethyl-p-toluidine has been shown to react with diketene (90) to give the chromone (128), showing that attack occurs at the /9-carbon of the dienamine system. 

Aliquat is an efficient catalyst for the acetoacetylation of amines by diketene. The initially formed amides react with an excess of the diketene to form, after cyclization of the secondary product, 1-substituted 3-acetyl-4-hydroxy-6-methylpyrid-2-ones [39]. Amides react under similar conditions with diketene to form A-acyl aceto-acetamides, which react further with a second molecule of diketene to yield, after cleavage of the A-acyl group, 3-acetyl-4-hydroxy-6-methylpyrid-2-one [39]. 

With diketene, intermediates of type (III) were isolated and subsequently cyclized under basic conditions following step (b). In the case of 3-oxo-carboxylic acid esters or 3-acyl Meldrum s acids, cyclization step (b) immediately follows reaction step (a), if a slight excess of amine is employed (85TH1 87TH1). Note that conversion of (III) to (V) involves the (IH)-enol (Table I cf. 75BSF2731). The relatively low yield in the case of malonic acid ester, as well as the failure of the reaction with the non-enolizable diphenyl phosphinylacetic ester and cyanoacetate, points to the participation of an enol structure of (III). 

The enolate ions of acetoacetic ester and other active methylene compounds react with 0-propiolactone to give the ethoxycarbonyl derivative, but the yields are generally not high. Application of this reaction to 2-ethoxycarbonyldodecanone (equation 53) has been recently patented, with the product reported to be a useful perfume intermediate (77JAP(K)77133952). The reaction is used quite widely with diketene, which gives C-acylation rather than alkylation of the enolate ion, followed by cyclization (72CPB1574). 

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... 

Quite efficient nucleophilic catalysts with planar (21a-c) and axial (22a-d) chirality were recently developed by Fu et al. [17-22] and Spivey et al. [23-25], The ferrocene-derived catalysts developed by Fu (21a-c) were first tested in the kinetic resolution of aryl alkyl carbinols with diketene as the acyl donor. 

Papers in which the reactions of isatins with various reagents leading mainly to derivatives of 2-quinolone-4-carboxylic acid were studied are discussed below. The condensation of isatins 180 with diketene gave quinolonecarboxylic acids 181 acylated at position 3 [152],... 

Diethylaluminium dimethylamide and ethanethiolate, Et2AlX (X = NMe2 or SEt), react with diketen, via acyl-oxygen bond cleavage and a 1,3-hydrogen shift, to give the chelates (67 X = NMe2 or SEt).372... 

The acylation of the enamine of a cyclic ketone with diketene leads directly to bicycUc 4-pyrones, as indicated below. ° ... 

Martin et developed a biogenetic entry into Ala-methylvellosimine (168) which employed an iminium ion-mediated cyclization similar to van Tamelen s original proposal. As shown in Scheme 4, dihydrocar-boline 169, which was readily obtained from commercially available D-tryptophan, was allowed to react with the vinyl ketene acetal 170 to afford a single product which was directly converted into the i-butyl ester 171. The Nb acylation of amine 171 with diketene furnished an intermediate P-keto amide that underwent facile cyclization via an intramolecular... 

Keten S,N-acetals, e.g. CH2= (SR )NRL " and N-acyl analogues have been described, and their use in synthesis of 2-dialkylaminopyran-4-ones by reaction with diketen. ... 

Recently, 1-ethoxyvinyl acetate has been proposed as a novel and reliable acyl donor for the enzymatic resolution of alcohols (Scheme 24) in a lipase-catalyzed irreversible transesterification procedure [135]. A similar protocol has been utilized for the irreversible acetoacetylation of alcohols with diketene in the presence of lipases in organic solvents [136,137] and the reaction has been reported to proceed with high enantioselectivity [136], as shown in Scheme 25. 

Acyl carbonates (234), alkoxyquinones (235) as vinylogous esters, imino ethers (236), and diketene (237) react with ethyleneimine to give the corresponding acylated ethyleneimines. 

The reaction of phenols with the spiro /3-lactone (397), obtained from the reaction of diketene with ethyl diazoacetate, leads to coumarins (79JCS(Pl)525). Initial ring opening of the spiro compound to the diketo ester followed by regioselective intramolecular acylation would seem to be a possible mechanism (Scheme 129). 

Fig. 6.25. Acylation of alcohols with a diketene (A preparation Section 15.4). The reaction product is the acetoacetic ester F.

Surprisingly little work appears to have been published on the acylation of dienamines. Annulations which may be effected with a,/ -unsaturated acid chlorides and diketene are discussed in Sections VII.C and VIII.C, respectively. 

Diketones have been prepared by the Friedel-Crafts method. Both acyl chloride groups in adipyl chloride react with benzene in the presence of aluminum chloride to form the diketo compound, 1,4-dibenzoylbutane (81%). When diketene is treated with benzene under the conditions of the Friedel-Crafts reaction, benzoylacetone, COCHjCOCH, is formed... 

An Al-acyl-(3-keto derivative has been prepared by reaction with a diketene equivalent and the tranj-N-cinnamoyl derivative by a Heck type coupling reaction. The A-fluoro derivative (3) is prepared by direct fluorination (eq 2). ... 

---