Lewis acid testing

The most general conclusion is that in almost all of the Lewis acids tested the normal Evans jyn-aldol 101 is formed in only trace amount, if at all. The unique behaviour of the different Lewis acids may be summarised as follows TiCl4 shows syn selectivity regardless of stoichiometry, Et2AlCl is anti selective regardless of stoichiometry and SnCl4 shows syn or anti, depending on whether an excess of aldehyde (entry 5) or Lewis acid (entry 7) is used. 

Bis(trimethylsilyl) enol ethers react with a variety of 1,4-dicarbonyl substrates in the presence of a Lewis acid promoter to afford [3 -t- 4] annulation products [45]. The use of TiCU, employed in the initial studies, poses difficulties and complete regiocon-trol in the cyclization is often lacking. Among many Lewis acids tested, surprisingly, la promotes the [3 -(- 4] annulation with high regio- and diastereoselectivity (Sch. 14). 

Alkylation Using Alkanes. Direct alkylation of pyridines and quinolines using simple alkanes and terf-butyl peroxide as oxidant was developed. This C-C bond forming reaction was carried out by using Sc(OTf)3 as a Lewis acid to increase the reactivity of pyridine and quinoline derivatives (eq 37). Scandium triflate demonstrated the best catalytic activity among the Lewis acids tested. While bis-alkylation product was obtained using quinoline, only mono-alkylation products were afforded when isoquinoline was used. Cycloheptane, cyclohexane, and norbornane were determined to be suitable reaction partners. 

The nucleophilic substitution of a-acetoxyhydrazones by silyl enol ethers takes place with high chemical yields and moderate diastereomeric excesses. Among the several Lewis acids tested (AsCL, AICI3, TiCLj, ZnCL,...), only BF3-OEt2 provides a slightly higher diastereoselectivity than TMSOTf. 7... 

The chiral a-cyano-a,p-unsaturated sulfoxide (269) has been shown to be an efficient enophile in a Lewis acid-catalysed intramolecular ene reaction [200,201]. Of the Lewis acids tested, the use of diethylaluminium chloride in dichloromethane gave particularly high diastereoselectivities (97% de) (Scheme 5.89). The results obtained using various Lewis acids are summarized in Table 5.9, in each case the major product being diastereoisomer (270a). 

Of the numerous classical Lewis acids tested as initiators for the polymerization of 3-pinene, EtAlCl2 has proved by far the most efficient, particularly in terms of the possibility of preparing polymers with high molecular weights. Three studies have tackled this system over the last 15 years [20-22] using different strategies, particularly in the... 

MacMillan has reported examples of synergistic catalysis in which copper salts are used. Although these results were driven by ad hoc hypotheses, most of these transformations are related to a Cu(i)/Cu(m) catalytic cycle. In any case, the superior performances offered by copper(i) salts, compared to strong Lewis acids tested in the processes, is an indication that the Lewis acidity of the metal salt is not playing a decisive role in these transformations. The complexation of the enamine 7i-system with Cu(iii)-R is expected to lead to rjl-iminium organocopper species that, upon reductive elimination, will form a carbon-carbon bond and liberate the active Cu(i) catalyst. Hydrolysis of the resulting iminium will also release the imidazolidinone catalyst to complete the organocatalytic cycle as shown in Scheme 18.7. 

TABLE 3.1 Qualitative Pearson Classification of Lewis Acids Tested (Pearson, 1963, 1997)... 

TABLE 3.4 Hardness Values for the Molecular Lewis Acids Tested in this Work Computed Upon Atomic Values of Table 3.3 in Molecular Chemical Hardness Recursive Approach... 

TABLE 3.6 Values of the Maximum Hardness Index for the Lewis Acids Tested in this Work Computed Upon Molecular Chemical Hardness of Table 3.4 in Maximum Hardness Definition... 

Intramolecular reactions work well, both for allylstannanes and allylsilanes. An epoxide can be the electrophile. Opening of the epoxide with allylic attack gives the cyclic product (eq 21). TiCU is superior to Ti(0-i-Pr)4, SnCU, and Aluminum Chloride, the other Lewis acids tested in the cyclization reaction. The reaction is stereospecific. 

Boron trioxide is not particularly soluble in water but it slowly dissolves to form both dioxo(HB02)(meta) and trioxo(H3B03) (ortho) boric acids. It is a dimorphous oxide and exists as either a glassy or a crystalline solid. Boron trioxide is an acidic oxide and combines with metal oxides and hydroxides to form borates, some of which have characteristic colours—a fact utilised in analysis as the "borax bead test , cf alumina p. 150. Boric acid. H3BO3. properly called trioxoboric acid, may be prepared by adding excess hydrochloric or sulphuric acid to a hot saturated solution of borax, sodium heptaoxotetraborate, Na2B407, when the only moderately soluble boric acid separates as white flaky crystals on cooling. Boric acid is a very weak monobasic acid it is, in fact, a Lewis acid since its acidity is due to an initial acceptance of a lone pair of electrons from water rather than direct proton donation as in the case of Lowry-Bronsted acids, i.e. 

Spectroscopic methods such as uv and fluorescence have rehed on the polyene chromophore of vitamin A as a basis for analysis. Indirectly, the classical Carr-Price colorimetric test also exploits this feature and measures the amount of a transient blue complex at 620 nm which is formed when vitamin A is dehydrated in the presence of Lewis acids. For uv measurements of retinol, retinyl acetate, and retinyl palmitate, analysis is done at 325 nm. More sensitive measurements can be obtained by fluorescence. Excitation is done at 325 nm and emission at 470 nm. Although useful, all of these methods suffer from the fact that the method is not specific and any compound which has spectral characteristics similar to vitamin A will assay like the vitamin... 

The irradiation of calciferol in the presence of iodine leads to the formation of 5,6-/n7 j -vitaniin D2 [14449-19-5] (31) or [22350 1-0] (32) (67,68). 5,6-/ra j -Vitainin D as well as vitamin D (2) or (4) can be converted to isovitamin D by treatment with mineral or Lewis acids. Isocalciferol (35) [469-05-6] or (36) [42607-12-5] also forms upon heating of 5,6-/ -vitamin D. Isotachysterol (33) [469-06-7] or (34) [22350-43-2] forms from isocalciferol or vitamin D upon treatment with acid, and its production appears to be the result of sequential formation of trans- and isocalciferol from calciferol. These reactions are the basis of the antimony trichloride test for vitamin D (69—72). 

An isopropyl ether was developed as a phenol protective group that would be more stable to Lewis acids than would be an aryl benzyl ether. The isopropyl group has been tested for use in the protection of the phenolic oxygen of tyrosine during peptide synthesis."... 

For 10 years, attention has been focused on the intramolecular additions ofallylic and alkynyl-silanes to enones. In early studies, a variety of Lewis acids were tested and reaction conditions were optimized to make this reaction a powerful tool in the synthesis of spiro-annulated, and 1,2-fused ring systems, which can be utilized in the total synthesis of natural products34,35. 

Identify Bronsted and Lewis acids and bases in a chemical reaction (Self-Test 10.2). 

Self-Test 14.7B Is the reaction between CaO and SiO, a redox reaction or a Lewis acid-base reaction If redox, identify the oxidizing and reducing agents. If Lewis acid-base, identify the acid and the base. 

The cyclopentadienyl triflate complexes of zirconium and titanium 51 and 52 (Figure 3.7) are also active catalysts [51]. Their activity has been tested in a wide variety of dienes and dienophiles. It is noteworthy that even at low catalyst loadings, rate accelerations between 10 and > 10 times have been observed. No special precautions were taken to dry the solvents or the substrates, in contrast with the traditional Lewis acids which require either predried solvents or high catalyst loadings. 

Silica gel [11] or alumina [11a, 12] alone, or silica and alumina together modified by Lewis-acid treatment [13] and zeolites [14], have been widely used as catalysts in Diels-Alder reactions, and these solids have also been tested as catalysts in asymmetric Diels-Alder reactions [12,13b,14]. Activated silica gel and alumina at 140 °C were used [15] to catalyze the asymmetric cycloaddition of (-)-menthyl-N-acetyl-a, S-dehydroalaninate (3) (R = NHCOMe) with cyclopentadiene in the key step for synthesizing optically active cycloaliphatic a-amino acids. When the reactions were carried out in the absence of solvent, a higher conversion was obtained. Some results are reported in Table 4.5 and compared with those obtained by using silica and alumina modified by treatment with Lewis acids. Silica gel gives a reasonable percentage of conversion after 24 h with complete diastereofacial selectivity in exo addition. 

The use of Lewis acids (ZnU, BF3 Et20) in ionic liquids, tested in the cycloaddition of but-3-en-2-one with isoprene, increases both the rate and selectivity of the reaction. The ionic liquid remains catalytically active after the work-up and can be reused. 

The role of Lewis acids in the formation of oxazoles from diazocarbonyl compounds and nitriles has primarily been studied independently by two groups. Doyle et al. first reported the use of aluminium(III) chloride as a catalyst for the decomposition of diazoketones.<78TL2247> In a more detailed study, a range of Lewis acids was screened for catalytic activity, using diazoacetophenone la and acetonitrile as the test reaction.<80JOC3657> Of the catalysts employed, boron trifluoride etherate was found to be the catalyst of choice, due to the low yield of the 1-halogenated side-product 17 (X = Cl or F) compared to 2-methyI-5-phenyloxazole 18. Unfortunately, it was found that in the case of boron trifluoride etherate, the nitrile had to be used in a ten-fold excess, however the use of antimony(V) fluoride allowed the use of the nitrile in only a three fold excess (Table 1). 

Of the various Lewis acid catalysts tested, SnCl4 gave the highest diastereoselective product formation with predominance for the antz-diastereoisomer. This azztz-selectivity can be rationalized by invoking the Cram chelation model. 

Ghosh et al. [70] reviewed a few years ago the utihty of C2-symmetric chiral bis(oxazoline)-metal complexes for catalytic asymmetric synthesis, and they reserved an important place for Diels-Alder and related transformations. Bis(oxazoline) copper(II)triflate derivatives have been indeed described by Evans et al. as effective catalysts for the asymmetric Diels-Alder reaction [71]. The bis(oxazoline) Ugand 54 allowed the Diels-Alder transformation of two-point binding N-acylimide dienophiles with good yields, good diastereos-electivities (in favor of the endo diastereoisomer) and excellent ee values (up to 99%) [72]. These substrates represent the standard test for new catalysts development. To widen the use of Lewis acidic chiral Cu(ll) complexes, Evans et al. prepared and tested bis(oxazoHnyl)pyridine (PyBOx, structure 55, Scheme 26) as ligand [73]. 

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