Acylation 5-dicarbonyl compounds

The initially formed ]5-dicarbonyl compounds are subject to further photo-transformations. One example is provided in the case of epoxy ketone (88), where the resulting /5-diketone (89) undergoes partly a-cleavage and acyl-alkyl... 

The reaction of tnfluoromethyl-substituted A -acyl umnes toward nucleophiles in many aspects parallels that of the parent polyfluoro ketones Heteronucleophiles and carbon nucleophiles, such as enarmnes [37, 38], enol ethers [38, 39, 40], hydrogen cyanide [34], tnmethylsilylcarbomlnle [2,47], alkynes [42], electron-nch heterocycles [43], 1,3-dicarbonyl compounds [44], organolithium compounds [45, 46, 47, 48], and Gngnard compounds [49,50], readily undergo hydroxyalkylation with hexafluoroace-tone and amidoalkylation with acyl imines denved from hexafluoroacetone... 

Another important application is the acylation of enamines 1 with an acyl chloride 9 to give a 1,3-dicarbonyl compound as final product ... 

This sequence is equally applicable to keto esters. Thus, condensation of guanidine with ethyl acetoacetate gives the pyrimidone, 134. Elaboration as above gives the pyrimidine, IJ5 acylation with the sulfonyl chloride (88) followed by hydrolysis yields sulfamerazine (107). Reaction of guanidine with beta dicarbonyl compounds gives the pyrimidine directly. Condensation of the base with acetonyl acetone affords the starting amine for sulfadimidine (108). ... 

Although the antithyroid activity of compounds incorporating an enolizable thioamide function was discussed earlier, this activity was in fact first found in the pyrimidine series. The simplest compound to show this activity, methylthiouracil (80) (shown in both enol and keto forms), is prepared quite simply by condensation of ethyl acetoacetate with thiourea.Further work in this series shows that better activity was obtained by incorporation of a lipophilic side chain. Preparation of the required dicarbonyl compound starts with acylation of the magnesium enolate of the unsyrametrically esterified malonate, 81, with butyryl chlo-... 

Two other examples of microwave-assisted Paal-Knorr reactions were reported in 2004, describing the synthesis of a larger set of pyrroles with different substituents around the ring. The methods differ mainly in the syntheses employed to produce the 1,4 dicarbonyl compounds required for the cyclization. A variation of the Stetter reaction between an acyl silane and dif-... 

Friedel-Crafts disconnection (38a) Is unambiguous because of the synunetry of (39). Further disconnection requires FGA. A carbonyl group next to the aromatic ring gives a 1,4-dicarbonyl compound (40) and allows disconnection of an acyl anion equivalent to give an enone (41). This can be made by Mannich reaction from (42). 

In 1976, Stetter extended the synthetic utility of the Breslow intermediate (1) as an acyl anion equivalent by showing that aldehydes could be coupled with Michael acceptors to generate 1,4-dicarbonyl compounds [55]. 

The reaction pattern can be used for the synthesis of 1,3-dicarbonyl compounds and other systems in which an acyl group is (3 to an anion-stabilizing group. 

The Michael addition of nitroalkanes to a,P-unsaturated ketones followed by the Nef reaction has been extensively used as a method for the conjugated addition of acyl anions to enones (see Section 6.1, Nef Reaction). This strategy is one of the best methods for the preparation of 1,4-dicarbonyl compounds.156a h Various natural products have been prepared via this route.157 For example, r/.v-jasmone is prepared from readily available materials, as shown in Scheme 4.19.156f... 

The reaction between dialkyl phosphorocyanatidite and acyl cyanides in dichloro-methane at 0 °C parallels that between the same phosphite and 1,2-dicarbonyl compounds, and is probably initiated by attack of tervalent phosphorus on the carbonyl group the formation of O- and V-alkyl products, (30) and (29), is an indication of the probable nature (28) of an intermediate.25 The extension of the reaction (see Organophosphorus Chemistry , Vol. 7, pp. 108, 126) to include ethyl phosphorodicyanatidite and 1-keto-esters provides a route to the 5-phosphabicyclo-[3,2,0]heptanes (31) in high yields.26... 

Acyloxy-l-cyanoalkanes [45, 46], which can be used as precursors for ketones [47], a-hydroxy ketones [48] and 1,4-dicarbonyl compounds [47], are prepared in one pot from the appropriate aldehyde, sodium or potassium cyanide, and the acylating agent under phase-transfer catalytic conditions [47-49]. Attempts to synthesize chiral cyanhydrins using chiral phase-transfer catalysts have been unsuccessful (see Section 12.3). 

The rate of reaction of phosphorus oxychloride with phenols to produce triaryl phosphates is increased by the addition of quaternary ammonium salts and the reaction temperature can be reduced without loss of overall yield [1,2]. The analogous reaction between phenoxide anions and thiophosphoryl chloride produces aryl phosphoro-dichloridothoates [3]. As with the acylation of enolizable (3-dicarbonyl compounds (3.3.12), phosphorylation leads to the predominant formation of the E-O-phos-phoryiated derivatives [4,5]. 

Alkylation of P-dicarbonyl compounds and p-keto esters occurs preferentially on the carbon atom, whereas acylation produces the 0-acyl derivatives (see Chapter 3). There are indications that C- and 0-alkylated products are produced with simple haloalkanes and benzyl halides, but only C-alkylated derivatives are formed with propargyl and allyl halides [e.g. 90]. Di-C-alkylation frequently occurs and it has been reported that the use of tetra-alkylammonium 2-oxopyrrolidinyl salts are more effective catalysts (in place of aqueous sodium hydroxide and quaternary ammonium salt) for selective (-90%) mono-C-alkylation of p-dicarbonyl compounds [91]. 

The regiospecificity of the exclusive O-acylation [8] and O-phosphorylation [9] of P-dicarbonyl compounds (Chapter 3) also illustrates the effect of phase-transfer catalysts on the stereochemical course of reactions. Similarly, directed reduction of P-hydroxy ketones using tetramethylammonium trisacetoxyborohydride leads to the preferential formation of the anti dihydroxy system in high yield with a stereoselectivity >95% [10] (Section 11.4). 

A mechanistic study of acetophenone keto-enol tautomerism has been reported, and intramolecular and external factors determining the enol-enol equilibria in the cw-enol forms of 1,3-dicarbonyl compounds have been analysed. The effects of substituents, solvents, concentration, and temperature on the tautomerization of ethyl 3-oxobutyrate and its 2-alkyl derivatives have been studied, and the keto-enol tautomerism of mono-substituted phenylpyruvic acids has been investigated. Equilibrium constants have been measured for the keto-enol tautomers of 2-, 3- and 4-phenylacetylpyridines in aqueous solution. A procedure has been developed for the acylation of phosphoryl- and thiophosphoryl-acetonitriles under phase-transfer catalysis conditions, and the keto-enol tautomerism of the resulting phosphoryl(thiophosphoryl)-substituted acylacetonitriles has been studied. The equilibrium (388) (389) has been catalysed by acid, base and by iron(III). Whereas... 

The enolates of ketones can be acylated by esters and other acylating agents. The products of these reactions are all /5-dicarbonyl compounds. They are all rather acidic and can be alkylated by the procedures described in Section 1.4. Reaction of ketone enolates... 

This procedure is an excellent method to prepare 1,4-dicarbonyl compounds 163 (Scheme 7.48) and, using triethylamine, has been extended to include other activated double bonds.Thus, the starting a-amino acids can be considered as nucleophilic acyl equivalents. Representative examples of 5(47/)-oxazolones prepared via Michael additions are shown in Table 7.18 (Fig. 7.20). 

Acid treatment of (6) furnishes products (13) including minor quantities of tricyclic condensation products, which result from the reaction of (13) with excess (6). This side reaction may be extended to become a synthesis of double anellated pyridines when (6) is fused with cyclic 1,3-dicarbonyl compounds. As expected, the spatial requirement of the acyl substituent R affects the yield of (15) (87TH1). (See Fig. 7.) Dipyrrolo[3,4-b 3, 4 -e]-pyridinediones of type (15a) were synthesized by Snyder et al. starting... 

Enol Ethers and Esters 0-15 O-Alkylation of carbonyl compounds with diazo alkanes 0-17 Transetherification 0-20 Reaction between acyl halides and active hydrogen compounds 0-23 Transesterification 0-24 Acylation of vinylic halides 0-94 Alkylation with ortho esters 0-107 O-Acylation of 1,3-dicarbonyl compounds... 

Knoevenagel condensation of aldehydes with 1,3-dicarbonyl compounds and subsequent NBS bromination yields allylic bromides, which are converted thermally to 3-acyl- or 3-alkoxycarbonyl furans (Scheme 51) (78JOC4596). 

Acylation of ethoxymagnesio derivatives of 1,3-dicarbonyl compounds with a-chloroacid chlorides produces 4-carbonyl substituted 3(2//)-furanones (72JCS(P1)1225). Potassium phenylacetate reacts with a-bromoaldehydes in the presence of 18-crown-6 ether to give 2(5//)-furanones (311) (Scheme 81) (75JOC3139). Dihydrofuranones such as (312) have... 

Numerous examples of the preparation of tetramic acids from N-acylated amino acid esters by a Dieckmann-type cyclocondensation have been reported (Entries 7-9, Table 15.4). Deprotonated 1,3-dicarbonyl compounds and unactivated amide enolates can be used as carbon nucleophiles. In most of these examples, the ester that acts as electrophile also links the substrate to the support, so that cyclization and cleavage from the support occur simultaneously. The preparation of five-membered cyclic imi-des is discussed in Section 13.8. 

Several types of cyclocondensation have been used to prepare imidazoles on insoluble supports (Figure 15.7). These include the condensation of 1,2-dicarbonyl compounds with aldehydes and amines, the 1,3-dipolar cycloaddition of iV-sulfonylimines to miinchnones, and the condensation of /V-acylated a-amino ketones with ammonia (Table 15.11). 

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