Furans 2- -, selective acylation

The ruthenium-catalyzed addition of C-H bonds in aromatic ketones to olefins can be applied to a variety of ketones, for example acetophenones, naphthyl ketones, and heteroaromatic ketones. Representative examples are shown in the Table 1. Terminal olefins such as vinylsilanes, allylsilanes, styrenes, tert-butylethy-lene, and 1-hexene are applicable to this C-H/olefin coupling reaction. Some internal olefins, for example cyclopentene and norbornene are effective in this alkylation. The reaction of 2-acetonaphthone 1 provides the 1-alkylation product 2 selectively. Alkylations of heteroaromatic ketones such as acyl thiophenes 3, acyl furans, and acyl pyrroles proceed with high yields. In the reaction of di- and tri-substitued aromatic ketones such as 4, which have two different ortho positions, C-C bond formation occurs at the less congested ortho position. Interestingly, in the reaction of m-methoxy- and m-fluoroacetophenones C-C bond formation occurs at the congested ortho position (2 -position). 

However, considerable amounts of 2,3-dihydrofuran 50 and tetrahydro-furan-2-carbaldehyde 53 were present because of an isomerization process. The isomerization takes place simultaneously with the hydroformylation reaction. When the 2,5-dihydrofuran 46 reacts with the rhodium hydride complex, the 3-alkyl intermediate 48 is formed. This can evolve to the 2,3-dihydrofuran 50 via /3-hydride elimination reaction. This new substrate can also give both 2- and 3-alkyl intermediates 52 and 48, respectively. Although the formation of the 3-alkyl intermediate 48 is thermodynamically favored, the acylation occurs faster in the 2-alkyl intermediates 52. Regio-selectivity is therefore dominated by the rate of formation of the acyl complexes. The modification of the phosphorus ligand and the conditions of the reaction make it possible to control the regioselectivity and prepare the 2- or 3-substituted aldehyde as the major product [78]. As far as we know, only two... 

A -Butylpyridinium tetrafluoroborate, containing dissolved phosphorus pentachloride, allows catalytic Beckmann rearrangement of cyclohexanone oxime giving e-caprolactam with good conversion and selectivity <2001TL403>. The same ionic liquid containing dissolved ytterbium(m) trifluoromethanesulfonate was used to perform Friedel-Crafts acylation of furan and thiophene <2005JIG398>. 

Three reactions, which were known from the literature to be catalyzed by Lewis acids were selected as test reactions. A, was the Reetz alkylation of silyl enol ethers with -butyl chloride for which titanium tetrachloride is known to be useful [52]. B, was the Diels-Alder reaction between furan and acetylenedicarboxylic ester for which aluminium trichloride is a good catalyst [53]. C, was a Friedel-Crafts acylation for which aluminium trichloride is the preferred catalyst [54]. The reactions are summarized in Scheme 6. 

These substitutions are facilitated by electron release from the heteroatom pyrroles are more reactive than furans, which are in turn more reactive than thiophenes. Quantitative comparisons of the relative reactivities of the three heterocycles vary from electrophile to electrophile, but for trifluoroacetylation, for example, the pyrrole furan thiophene ratio is 5 x 10 1.5 x 10 I " in formylation, furan is 12 times more reactive than thiophene, and for acetylation, the value is 9.3. In hydrogen exchange (deuteriodeproton-ation), the partial rate factors for the a and p positions of A-methylpyrrole are 3.9 x 10 ° and 2.0 x 10 ° respectively for this same process, the values for furan are 1.6 x 10 and 3.2 x l(f and for thiophene, 3.9 X 10 and 1.0 x 10 respectively, and in a study of thiophene, a P ratios ranging from 100 1 to 1000 1 were found for different electrophiles. Relative substrate reactivity parallels positional selectivity i.e. the a P ratio decreases in the order furan > thiophene > pyrrole. ° Nice illustrations of these relative reactivities are found in acylations of compounds containing two different systems linked together. ... 

Kinetic studies of acylation reactions are somewhat limited by the insolubility of the acyl halide-Lewis acid complexes in many of the solvent systems that are used. However, useful results have been obtained and, as far as we are concerned, relative rates of reactions are of greater importance than absolute values. In any case it is not possible to distinguish between the two mechanistic extremes on the basis of the observed kinetics." Friedel-Crafts acylations are generally characterized by high substrate selectivity and frequently by high positional selectivity. Relative rate data show, as expected, that toluene is more reactive than benzene and that /n-xylene is the most reactive of the dimethylbenzenes. Values, relative to benzene, for benzoylation catalyzed by aluminum chloride were r-butylbenzene (72), toluene (1.1 X 10 ), p-xylene (1.4 x 10 ), o-xylene (1.12 x 10 ), and m-xylene (3.94 x 10- ). Competition data for the trifluoroacetylation of a number of heterocycles using trifluoroacetic anhydride at 75 "C gave the relative rates thiophene (1.0), furan (1.4 x lO ), 2-methylfuran (1.2 x 10 ) and pyrrole (5.3 x 10 ). ... 

Acylation of an oxygen would also be expected to lower its ability to coordinate to a metal ion, and thus to form chelates. Results from the reduction of (5)-4,5-dihydro-5-(l -oxopropyl)furan-2(3//)-one, available in optically active form from glutamic acid, support this notion24. Thus, zinc borohydride gives the chelation-controlled other hand, excellent syn selectivity in the Felkin-Anh sense can be achieved with L-Selectride. The latter method was extended to several other substrates and was uniformly successful24. 

Heterocyclic compounds, namely, pyrrole, thiophene, and furan, can be efficiently acylated with AAN in the presence of differenf mefal-exchanged KIO clays, in particular, wifh clayfen (Scheme A.2A)P 2-Acefylheferoaromatics 35 are produced wifh high heterocyclic conversions (97%-98%) accompanied by excellent selectivities (92%-99%). The rate of fhe acefylation reaction is increased as fhe total acidity is increased, which is in the order Fe + Zn + > H+ > KIO > AF+ the activity is thus correlated to the acidity of fhe clay cafalysf. 

Tin Derivatives. 3-(Tri-n-butylstannyl)furan can be converted into a 3-furyl ketone 37 either by a StiUe-type coupling under CO pressure or by acylation with an acid chloride (Scheme 18). When 3-(phenylethyl) -(tii- -butylstannyl)thiophene was allowed to react with benzyl bromide under an atmosphere of CO, formation of the carbonylated product 38 was accompanied by 13% yield of the symmetrical ketone, bis[4-(phenylethyl)thiophen-3-yl] ketone.f In 3,4-bis(tri-n-butylstannyl)furan 39 selective monoacylation can be achieved with acid chlorides. The ketones can subsequently be further carbonylated. ... 

Inokuchi, T., and Kawafuchi, H. (2006). E- orZ-selective Knoevenagel condensation of acetoacetic derivatives Effect of acylated substituent, that is, TEMPO and amines, as an auxiliary, and new accesses to trisubstituted E- and Z-2-aDcraials and furans. 7. Org. Chem., 71, 947-953. 

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