Lewis acid catalysis compounds

On the basis of the studies described in the preceding chapters, we anticipated that chelation is a requirement for efficient Lewis-acid catalysis. This notion was confirmed by an investigation of the coordination behaviour of dienophiles 4.11 and 4.12 (Scheme 4.4). In contrast to 4.10, these compounds failed to reveal a significant shift in the UV absorption band maxima in the presence of concentrations up to one molar of copper(ir)nitrate in water. Also the rate of the reaction of these dienophiles with cyclopentadiene was not significantly increased upon addition of copper(II)nitrate or y tterbium(III)triflate. 

I owe a lot to Federica Bertondn and Giovanni Boccaletti. During their stay as Erasmus students in Groningen they brought a little bit of Italy with them (I remember some very good meals). Also from a chemical point of view their stays were successful. The compounds prepared and purified by Federica are at the basis of the work described in this thesis. The work of Giovanni has paved the way to enantioselective Lewis-acid catalysis in water, which is perhaps the most significant result of this thesis. 

The mechanism of chemical modification reactions of PS were determined using toluene as a model compound with EC in the presence of BF3-0(C2H5)2 catalyst and the kinetics and mechanism of the alkylation reaction were also determined under similar conditions [53-55]. The alkylation reaction of toluene, with epichlorohydrin, underwent polymerization of EC in the presence of Lewis acid catalysis at a low temperature (273 K) as depicted in Scheme (9). 

The cycloaddition of chiral, racemic and non-racemic alkoxybutadienes 109 with phenyltriazolinedione led to aza compounds [110] in high yield, with good facial selectivity (diastereomeric excess 87-92%) (Equation 2.31). The cycloadditions of the same dienes with N-phenylmaleimide require Lewis acid catalysis. 

Lewis-acid catalysis is effective in intermolecular as well as intramolecular /zomo-Diels-Alder reactions. Thus, complex polycyclic compounds 93 have been obtained in good yield by the cycloaddition of norbornadiene-derived dienynes 92 by using cobalt catalyst, whereas no reaction occurred under thermal conditions [91] (Scheme 3.18). 

Different kinds of nucleosides (778) were prepared by condensation of compound 400 (see Section 11,3) with trimethylsilylated uracils under Lewis acid catalysis, and removal of one fluorine atom at C-2 of the sugars. Uridine 5 -(2-acetamido-2,4-dideoxy-4-fluoro-a-D-galactopyranosyl di-... 

For the Cu(OTf)2-promoted reaction between ethyl diazoacetate and cinnam-aldehyde dimethyl acetal, products 143-145 account for only 35% the total yield. C/C and C/H insertion products 151 and 152 are obtained additionally in 49 and 14% yield, respectively154). It was assumed that the copper compound acts through Lewis-acid catalysis here, just as it is believed to do when orthoesters are used as substrates 160). According to this, catalyst-induced formation of a methoxy-... 

Judging from these findings, the mechanism of Lewis acid catalysis in water (for example, aldol reactions of aldehydes with silyl enol ethers) can be assumed to be as follows. When metal compounds are added to water, the metals dissodate and hydration occurs immediatdy. At this stage, the intramolecular and intermolecular exchange reactions of water molecules frequently occur. If an aldehyde exists in the system, there is a chance that it will coordinate to the metal cations instead of the water molecules and the aldehyde is then activated. A silyl enol ether attacks this adivated aldehyde to produce the aldol adduct. According to this mechanism, it is expected that many Lewis acid-catalyzed reactions should be successful in aqueous solutions. Although the precise activity as Lewis acids in aqueous media cannot be predicted quantitatively... 

The reaction of alkynyllithium compounds with alkoxycarbene tungsten complexes leads to anionic propargyl tungsten complexes (Figure 2.33 see also Figure 3.9). These intermediates are stable at low temperatures and react upon Lewis acid catalysis with aldehydes or A -sulfonyl imines to yield five-membered heterocycles [280]. Oxidative methoxycarbonylation [375] of the intermediate vinyl tungsten complex, followed by elimination of methanol leads to pyrroles or furanes (Figure 2.33 Entry 6, Table 2.22). 

Also acetylenic dienophiles have been used, this time both in the Ugi [127,128] and in the Passerini MCRs [128]. The bicyclic compounds 148 (Z = NR ), stemming from an Ugi reaction on furaldehyde, are somewhat unstable and can be converted, under Lewis acid catalysis, into isoindolinones 149 [127,128]. On the contrary, compounds 148 (Z = O), coming from a Passerini reaction, are stable under the same conditions and therefore are not converted into isobenzofuranones. 

Due to increasing demands for optically active compounds, many catalytic asymmetric reactions have been investigated in this decade. However, asymmetric catalysis in water or water/organic solvent systems is difficult because many chiral catalysts are not stable in the presence of water [19]. In particular, chiral Lewis acid catalysis in aqueous media is extremely difficult because most chiral Lewis acids decompose rapidly in the presence of water [20, 21]. To address this issue, catalytic asymmetric reactions using water-compatible Lewis acids with chiral ligands have been developed [22-29]. 

Beside the Friedel-Crafts-type alkylation of arenes, the direct functionalization of 2,4-pentanediones is of great interest in Lewis acid catalysis. Although Pd-catalyzed Tsuji-Trost type allylations of 1,3-diketones are known, direct benzylation procedures catalyzed by Lewis acids are less explored [40-43]. Based on the previously described Friedel-Crafts alkylation of arenes and heteroarenes, the Rueping group developed a Bi(OTf)3-catalyzed benzylation of 2,4-pentanediones. Alcohols such as benzyl, allyl or cinnamyl alcohols were used as the electrophilic component to yield important 2-alkylated 1,3-dicarbonyl compounds. Initially, different Bi(III) salts were screened. In contrast... 

Alcohols can also be prepared from support-bound carbon nucleophiles and carbonyl compounds (Table 7.4). Few examples have been reported of the a-alkylation of resin-bound esters with aldehydes or ketones. This reaction is complicated by the thermal instability of some ester enolates, which can undergo elimination of alkoxide to yield ketenes. Traces of water or alcohols can, furthermore, lead to saponification or transesterification and release of the substrate into solution. Less prone to base-induced cleavage are support-bound imides (Entry 2, Table 7.4 see also Entry 3, Table 13.8 [42]). Alternatively, support-bound thiol esters can be converted into stable silyl ketene acetals, which react with aldehydes under Lewis-acid catalysis (Entries 3 and 4, Table 7.4). 

This compound 11 was actually used3 to make the trifluorocompound 13. The chlorination of toluene with Lewis acid catalysis gives mostly 12 and chlorine and PCI5 does the, probably radical, chlorination of the methyl group. 

Oxime derivative (32) can be cyclized to quinoline compound (33) under Lewis-acid catalysis (Scheme22) <95CL5>. 

Indole (2) undergoes electrophilic substitution preferentially at the b(C3)-position whereas pyrrole (1) reacts predominantly at the a(C2)-position [15]. The positional selectivity in these five-membered ring systems is well explained by the stability of the Wheland intermediates for electrophilic substitution. The intermediate cations from 3 (for indole, 2) and a (for pyrrole, 1) are the more stabilized. Pyrrole compounds can also participate in cycloaddition (Diels-Alder) reactions under certain conditions, such as Lewis acid catalysis, heating, or high pressure [15]. However, calculations of the frontier electron population for indole and pyrrole show that the HOMO of indole exhibits high electron density at the C3 while the HOMO of pyrrole is high at the C2 position [25-28] (Scheme 3). 

Reactions of compound 8a with butadiene, 2,3-dimethylbutadiene, and isoprene required more drastic conditions (150°C, autoclave) [24]. In the case of isoprene, a 60 40 regioisomeric mixture was obtained (the major product being the para-adduct). The influence of Lewis acid catalysis on the reaction of cyclopentadiene with different ethynyl aryl sulfoxides [Ar =p-Tolyl, o-nitrophenyl, and l(2-methoxynaphthyl)] has been recently reported [25].Dienophilicities of acetylenic sulfoxides were greatly enhanced by the presence of various Lewis acids (the effect being greater with stronger Lewis acid), but the stereoselectivity was scarcely affected by the catalysis. 

A major problem in the reaction of a,/3-unsaturated carbonyl compounds and alkenes proves to be the competition between hetero Diels-Alder and ene reactions. Intramolecular cycloadditions of 1,6- and 1,7-dienes with ester and cyano groups at the double bond yield the ene product nearly exclusively, but with alkylidene- and benzylidene-ketoesters and 1,3-diketones the Diels-Alder reaction is preferred under thermal conditions, however under Lewis acid catalysis also ene reactions occur [12]. 

Due to the high reactivity and high sensitivity of thioaldehydes, Lewis acid catalysis has not been applied to thia Diels-Alder reactions. However, Heim-garten et al. clearly demonstrated the suitability of Lewis acids to make less reactive thiocarbonyl compounds, e. g. thiazole thiones, react as heterodieno-philes in hetero Diels-Alder reactions [412]. 

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