Scandium triflate acylation

These reactions are presumed to occur through aroyl triflate intermediates which dissociate to aiyl acylium ions. Lithium perchlorate and scandium triflate also promote acylation. ... 

Ishihara, K. Kubota, M. Kurihara, H. Yamamoto, H. Scandium triflate as an extremely active Lewis acid catalyst in acylation of alcohols with acid anhydrides and mixed anhydrides./. Org. Chem. 1996, 61, 4560-4567. Zhao, H. Pendri, A. Greenwald, R. B. General procedure for acylation of tertiary alcohols Sc(OTf)3/DMAP reagent. /. Org. Chem. 1998, 63, 7559-7562. 

Other RE(OTf)3 were also examined as catalysts in the reaction of 1 with acetic anhydride (Table 2). Catalytic amounts of all the RE(OTf)3 listed effectively mediated the acylation of 1. Among these, scandium trifluoromethanesulfonate (scandium triflate, Sc(OTf)3)[6] or Yb(OTf)3 was superior to other RE(OTf)3 and afforded the acylation product 2 quantitatively. When, on the other hand, lanthanum trifluoromethanesulfonate (lanthanum triflate, La(OTf)3) was used, the yield of 2 was relatively low. The yields shown in Table 2 may reflect the catalytic activity of respective RE(OTf)3. 

Scandium triflate (Sc(OTf)3), which is commercially available, is a practical and useful Lewis acid catalyst for acylation of alcohols with acid anhydrides or the esterification of alcohols by carboxylic acids in the presence of... 

Commercially available scandium triflate is a remarkably active acid catalyst for acylation of alcohols with acid anhydrides.603 Its catalytic activity is even higher than DMAP However, in the case of allylic and some tertiary alcohols, migration or elimination products are observed. Moreover, scandium is expensive. 

Similarly, scandium triflate (Sc(OTf)3), zirconium triflate (Zr(OTf)4) and titanium chloro(tris)triflate (TiCl(OTf)3) were also used for the orf/zo-acylation of phenols and 1-naphthols using acid chlorides . ... 

Anisole can be acylated with acetic anhydride in 99% yield (6.12). Yttterbium triflate can also be used. The yields are low when there is no activating group in the ring. The rate is accelerated by the addition of lithium perchlorate.56 Acylation of alcohols works well with 1 mole% of scandium triflate as a catalyst (6.13).57 The less toxic toluene has also been used as the solvent in such acylations. The... 

Very interesting results can be achieved when scandium triflate is utilized instead of ytterbium triflate. Indeed, acylation of methoxy- and... 

Scandium triflate has been patented as an efficient homogeneous catalyst in the electrophilic acylation of aromafic compounds wifh carboxylic acids. 1-Naphfhol reacf s wifh AAC af 100°C in fhe presence of little scandium triflate for 6 h, giving 2-acefyl-l-naphfhol in 54% yield. ... 

When mcte-xylene is acylated in the presence of scandium triflate (20% mol) combined with lithium perchlorate in nitromethane, 2,4-dimethyl-acetophenone is obtained in 89% yield. In the absence of scandium triflate, lithium perchlorate is not soluble in the reaction mixture, and no acylation... 

Intramolecular Friedel-Crafts acylation of enolizable benzyl Meldrum acids 22 wifh scandium triflate (7%-12% mol) in refluxing nitromethane or acetonitrile is a powerful tool for the preparation of a variety of indan-l-ones 23 (Table Meldrum acid derivatives, mono- and dis-... 

Matsushita, Y.-L, Sugamoto, K., and Matsui, T. 2004. The Eriedel-Crafts acylation of aromatic compounds with carboxylic acids by the combined use of perfluoroalkanoic anhydride and bismuth or scandium triflate. Tetrahedron Lett. 45 4723-4727. 

Table 5.3 Scandium-triflate-catalyzed acylation of aromatics with acyl chlorides...

Metal triflates are efficiently utilized as reusable catalysts in the direct acylation of phenols as well as in the Fries rearrangement. Scandium triflate is employed as catalyst (5% mol) in the direct acylation of phenols and naphfhols wifh acyl chlorides in toluene-nitromefhane mix-fures af 100°C for 6 h. Resulfs from Table 5.3 show fhaf fhe reacfion is very efficienf complefe regioselecfivify is observed wifh mefa-cresol and 1-naphfhol derivafives. 

Metal triflates can also be efficiently utilized as reusable catalysts in the acylation of phenols [104, 113, 114]. For example, with scandium triflate (5% mol), a complete regioselectivity is... 

In addition to the works previously reported [50] Bi(0Tf)3 x H20 proved to be as active as scandium triflate in the EC acylation of aromatic compounds with carboxylic acids in the presence of perfluoroalkanoic anhydrides using solvent-free conditions (Equation 31) [60]. Under these conditions no reactions were reported with aromatics less activated than benzene. As previously reported [21], Bi(0Tf)3 xH20 was shown to be recoverable in good yields with no loss of activity. In addition, Bi(NTf2)3 [61] is proved to be an excellent catalyst for the intramolecular EC cyclization of 4-arylbutyric acids [62]. 

Highly enantiosele ctive annulation reactions of (tert-butyldiphenylsilyl)allenes with ethyl glyoxylate using bis(oxazolinyl)pyridine-scandium triflate complex was described [120]. This [3 + 2] cycloaddition gave the corresponding dihydrofurans in moderate to high yields with high enantioselectivities (Scheme 12.54). The vinyl-silane functionality was acylated in Friedel-Crafts reaction with acetyl chloride to produce a-alkoxyenone. 

Enantioselective Friedel-Crafts alkylation of indoles with a,P-unsaturated acyl phosphonates was investigated in the presence of bis(oxazolinyl)pyridine-scandium triflate complexes [151]. The intermediate -indolyl acyl phosphonates were converted to the corresponding methyl esters by direct addition of methanol and DBU (1,8-diazobicyclo [5.4.0] undec-7-ene) to the reaction mixture. Various acyl phosphonates and indole derivatives gave the alkylated products in moderate to good yields with high to excellent enantioselectivities (Scheme 12.57). It was also shown that the reaction was quenched by morpholine to give the corresponding amide, and that electron-rich 3-dimethylaminoanisole was also an effective nucleophile in this reaction. 

Fukuzawa et al. [99] found analogous scandium(III)triflate/ Pr-PyBOx complex as efficient catalyst for the asymmetric Diels-Alder reaction between cyclopentadiene or acyclic dienes and acyl-l,3-oxazohdin-2-ones with up to 90% ee. They latter described the same reaction in super critical CO2 in the presence of MSdA [ 100] that proceeded more rapidly than in CH2CI2 leading to the expected product with analogous selectivity. 

Enantioselective additions of a,f)-unsaturated 2-acyl imidazoles, catalyzed by bis(oxazolinyl)pyridine-scandium(III)triflate complex, were used for the asymmetric synthesis of 3-substituted indoles. The complex 114 was one of the most promising catalysts. The choice of acetonitrile as the solvent and the use of 4 A molecular sieves were also found to be advantageous. The 2-acyl imidazole residue in the alkylation products of u,(i-unsaturated 2-acyl imidazoles could be transformed into synthetically useful amides, esters, carboxylic acid, ketones, and aldehydes (Scheme 32) [105]. Moreover, the catalyst 114 produced both the intramolecular indole alkylation and the 2-substituted indoles in good yield and enantioselectivity (Scheme 33) [106]. The complex... 

Against this background it is important that—quite fitting in this still new millennium— the first catalytic Friedel-Crafts acylations of (still relatively electron-rich) aromatic compounds were reported (Figure 5.35). Trifluoromethane sulfonates ( triflates ) of rare-earth metals, e. g., scandium(III)triflate, accomplish Friedel-Crafts acylations with amounts of as little as 1 mole percent. Something similar is true of the tris(trifluoromethanesulfonyl)-methides ( triflides ) of rare-earth metals. Unlike conventional Lewis acids, the cited rare-earth metal salts can form 1 1 complexes with the ketone produced, but these are so unstable that the Lewis acid can re-enter the reaction. Whether this works analogously for the third catalytic system of Figure 5.35 is unclear. 

Chiral 2-(3-oxoalkyl)pyrroles and 3-(3-oxoalkyl)indoles can also be accessed by reaction in the presence of 10 mol% of chiral bis(oxazoline)/metal complexes in CH2C12 in very high yields and with ee values over 90% <2005JA4154>. Alkylation of pyrrole and of substituted indoles with, -unsaturated acyl phosphonates <2003JA10780> or 2-acyl N-methylimidazoles catalyzed by a chiral bis(oxazolinyl)pyridine (pybox)/scandium(III) triflate complex also exhibits good enantioselectivity over a broad range of substrates <2005JA8942>. 

Enantioselective Michael-type indole Friedel-Crafts reaction with a,P-unsaturated acyl thiazole has been disclosed <07JA10029>. Reaction of indole 127 and 128 in the presence of 10% mol of bis(oxazolinyl)pyridine-scandium(III) triflate complex 129 in acetonitrile at -40 °C affords 130 with high level of enantioselectivity. 

The Friedel-Crafts alkylation of the parent pyrrole and of substituted indoles with a,P-unsaturated acyl phospho-nates 468 <2003JA10780> and 2-acyl iV-methylimidazoles 469 catalyzed by the chiral bis(oxazolinyl)pyridine (pybox)/scandium(lIl) triflate complex 467 exhibits good enantioselectivities over a broad range of substrates (Scheme 97, Equation 113) <2005JA8942>. The desired alkylation products 470-472 were formed in good yields and enantioselectivities. 

Evans and coworkers [44] expanded the scope of enanti-oselective Friedel-Crafts alkylation of indoles 122 through the utilization of a series of p-snbstituted a,p-unsaturated phosphonates 123 and a,p-nnsaturated 2-acyl imidazoles 124 (Scheme 10.25). The active catalyst was proposed to be the respective complex of these enones in a bidentate fashion with bis(oxazolinyl)pyridine-scandium(III) triflate 125. Generally, this asymmetric addition reaction was found to be... 

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