3-Elimination reaction, ester-bound

Hydroxylaminolysis, treatment with stronger alkali (0.5 m NaOH, 2 h, 100°C) and alkaline methanolysis (0.25 m NaOMe, 1 h, 50°C) lead to complete O-deacylation of LPS and lipid A (176). Particularly in the case of alkaline methanolysis, ester-linked 3-acyloxyacyl residues undergo, in addition to transmethylation, a -elimination reaction, whereby the (R)-3-hy-droxy fatty acid ester is first transformed into the a,/ -unsaturated and then into the (S.-R -methoxy fatty acid methyl ester. The acyl substituent, on the other hand, is eliminated in the form of the free fatty acid (176). In fact, the presence of a 3-methoxyacyl derivative in the fatty acid spectrum of a given LPS is a strong indication for the presence of an ester-bound 3-acyloxyacyl... 

Tertiary aliphatic alcohol linkers have only occasionally been used in solid-phase organic synthesis [73], This might be because of the vigorous conditions required for their acylation. Esterification of resin-bound linker 4 with /V-Fmoc-prolinc [72,74] could not be achieved with the symmetric anhydride in the presence of DMAP (20 h), but required the use of /V-Fmoc-prolyl chloride (10-40% pyridine in DCM, 25 °C, 10-20 h [72]). A further problem with these linkers is that they can undergo elimination, a side reaction that cannot occur with benzyl or trityl linkers. Hence, for most applications in which a nucleophile-resistant linker for carboxylic acids is needed, 2-chlorotri-tyl- or 4-acyltrityl esters will probably be a better choice than ferf-alkyl esters. 

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). 

Substituted 2-aminonaphthalenes have been prepared on Wang resin by cyclocondensation of resin-bound 2-trifluoromethylphenyl acetate with arylacetonitriles (Figure 10.7). This reaction probably proceeds via an electrophilic o-quinone methide intermediate, formed by base-induced elimination of HF from the resin-bound ester [229]. 

To avoid the formation of ketenes by alkoxide elimination, ester enolates are often prepared at low temperatures. If unreactive alkyl halides are used, the addition of BU4NI to the reaction mixture can be beneficial [134]. Examples of the radical-mediated a-alkylation of support-bound a-haloesters are given in Table 5.4. Further methods for C-alkylating esters on insoluble supports include the Ireland-Claisen rearrangement of O-allyl ketene acetals (Entry 6, Table 13.16). Malonic esters and similar strongly C,H-acidic compounds have been C-alkylated with Merrifield resin [237,238]. 

Computational studies concerning theoretical approaches to the intrinsic basicity of neutral nitrogen bases have been reported, including those of phos-phoranimines. The non-ionic phosphazene bases BEMP (112), BTPP (113) and (114, R = Ph) appear to be excellent catalysts for the Michael addition reactions. Thus the yield of the coupling reaction of ethyl isocyanoacetate with l,2-bis(4-bromomethylphenyl)ethane is increased by the addition of the phosphazene base BEMP. Polymer-supported BEMP (P-BEMP) has been applied for the allylation of 2H-benzo[d]l,3-dioxolan-5-ol by allyl bromide. " Cyclodehydration of 1,2 diacylhydrazines by tosyl chloride in the presence of P-BEMP leads to excellent yields of 1,3,4,-oxadiazoles. Addition of P-BEMP also improves the yield of the Hofmann elimination step in the synthesis of tertiary mines using REM resin (polymer-bound acrylate ester). ... 

An interesting side reaction has also been observed in alcohol transesterification of polymer-bound trichlorophenyl esters. Thus, transesterification with secondary alcohols at 50-100 °C is accompanied by the formation of free carboxyl groups on the polymer. Free carboxyl groups may form via elimination of the resulting alkyl esters, or more probably from the corresponding transition states. In the case of tertiary alcohols no transesterification takes place, and only free carboxyl groups are formed. 

Resin-bound diazoimides 190 were subsequently reacted with different electron deficient acetylenes 191 in benzene at 80°C for 2 hours in the presence of Rh2(OAc)4 as a catalyst. Analysis of the crude products showed exclusively the presence of the desired furans 192 and excess unreacted acetylene, which, when sufficiently volatile (e.g propiolate esters), were eliminated in vacuo to provide furans of high purity. To avoid contamination of the desired furan product with residual, non-volatile acetylene, a two step sequence was implemented for the cycloaddition reaction. Thus, C-labelled diazoimide 193 was allowed to react with a large excess (10 eq) of dimethyl acetylenedicarboxylate (DMAD) 194 in the presence of Rhj(OAc)4 at room temperature in anticipation of trapping the bicyclic intermediate 196 on the polymeric support. After washing the... 

The use of chiral esters as 2tx-substrates permit the production of diastereomer-ically enriched cycloadducts. For example, the menthyl ester 48 was obtained as a 4 ldiastereomeric mixture. The most intriguing feature of polystyrene-bound catalyst 46 is the fact that it can be removed from the reaction mixture by simple filtration and repeatedly reused. This means that the two basic problems of homogeneous catalysis, separation and recycling of the catalyst, can be solved by using the solid-supported complex 46. Additionally, the environmental problems associated with chromium can also be effectively eliminated. 

There are two pieces of evidence in the literature that support the prediction that the cholesterol content of tissue membranes of children with SCD is increased relative to children without this hematological disease, and both are related to the phenomenon of reverse cholesterol transport, which allows the liver to eliminate excess cholesterol in peripheral tissues. Central to the reverse cholesterol transport is the efflux of cholesterol from the membranes followed by the lecithin-cholesterol acyltransferase-catalyzed acylation of that cholesterol with a fatty acid from phosphatidylcholine. This reaction is activated by high density lipoprotein (HDL) and is favored by n-3 PUFA in the HDL particles. The cholesterol esters are finally delivered to the liver bound to low density lipoprotein or by very low density Hpoproteins. 

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