The Methoxymethyl System

4-dinitrophenolate showed a very weak quantitative dependence on Swain-Scott nucleophilicity/ with points badly scattered about a trend line of gradient 0.2-0.3, indicating that bond formation was only about one-quarter as developed as in nucleophilic displacements of methyl bromide. Likewise, the value of )Snu/ for attack of a series of primary amines on the VV-(methoxy-methyl)-A, A -dimethyl-m-nitroanilinium ion was only 0.14. The neutral leaving group system permitted values of of —0.89 for the attack of water and —0.7 for the attack of propylamine to be obtained. Values of p, 

Such exploded transition states, in which the reaction centre carries a pronounced positive charge, are the commonest type of nucleophilic displacements at acetal centres. The reactions are unambiguously bimolecular, but in quantitative measures of transition state structure they differ only slightly from those of true 5 nI reactions. Thus, the value of for the hydrolysis of aryloxytetrahydropyrans, in which the solvent-equilibrated tetrahydropyranyl cation is a true intermediate, is —1.18, modestly but significantly more negative than the value of —0.82 obtained for hydrolysis of methoxymethyl esters of the type CH30CH20C0R.  

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Pi (governing the phenol) was 0.89 for the methoxymethyl system and 0.93 for substituted analogues of compound LV (R = Et) pj (governing the carboxylic acid) was 0.02 for the methoxymethyl system and 0.2 for the benzaldehyde derivatives (LV). The similarity of these effects is some reassurance that the requirement for a nucleophile to participate in the reactions of methoxymethyl derivatives does not have very significant effects on the consequences of the application of acidic catalysis. 

Detailed structural calculations have been carried out for this system. This is because the neutral isomer, C2HsO, which is implicated in the thermochemistry of ethanol, is of interest in pollution control, atmospheric chemistry, and combustion. Also, there is new information available from photoionization experiments with which to compare theoretical calculations. For details of these comparisons, see Curtiss et al.73 In the earlier theoretical studies of Nobes et al.,74 calculations were performed at the MP2 and MP3 levels with basis sets of double plus polarization (6-13G ) with electron correlation. These studies revealed four stable minima for the system protonated acetaldehyde, CHj-C H-OH <-> CH3-CH=0+H the methoxymethyl cation, CH3OCH2 protonated oxirane, (CH2)2OH+ and vinylox-... 

Enamides, in addition to the acrylates shown above, are also asymmetrically hydrogenated with many of the same systems that prove useful for the acetamidoacrylate reductions. The Rh(I)/BICP (2(/J)-2/(i)-bis(dipenylphosphino)-1(R),] (R)-dicyclopenlane) 132 and Rh(I)/DuPHOS systems work well (>90% ee) for the asymmetric hydrogenation of /3-acctamidovinyl methoxymethyl ethers... 

The asymmetric alkylation of the P-carboline ring system affords access to indole alkaloids. The simplest is tetrahydroharman, whose synthesis is mediated by asymmetric alkylation of a formamidine, as shown in Scheme 30. In the racemic series (c/. Scheme 16), the indole nitrogen may be protected simply by deprotonation with potassium hydride. However, in the chiral series the presence of a potassium ion lowers the selectivity. Thus, the methoxymethyl protecting group was used. 

Second, the oxonlum lon-carbenlum Ion equilibrium In the orthoester systems was Investigated. A model compound for the active center was synthesized. 4-Methoxymethyl-l,3-dloxolan-2-yllum cation Is the model compound for the carbenlum Ion In the polymerization of 2,6,7-trloxablcyclo[2.2.1]heptane, and was obtained by hydride transfer from 4-methoxymethyl-l,3-dloxolane to trlphenyl-methyllum cation. 

Both ADM [31] and Avantium [29,30] have reported on the oxidation of MMF, the more stable methyl ether of HMF. Avantium is currently scaling up its process based on an optimized process in its pilot plant, yielding greater than 96 mol% FDCA -I- FDCAMe from MMF. Though this compound could not be oxidized over heterogeneous catalyst systems (discussed earlier), facile oxidation using the Co/Mn/Br catalyst system has been reported (see Table 19.3). Since ethers are hydrolytically very stable, it clearly indicates that the activation of MMF must proceed via a direct oxidation of the methylene carbon of the methoxymethyl moiety. 

A soln. of ethyl 3-[octahydro-3a-(methoxymethyl)-2-methyl-l-(phenylthio)-3,6-dioxo-[li/]isoindol-4-yl]-2-propenoate in benzene treated with 2 eqs. BujSnH and a little AIBN in the same solvent over 10 h ethyl octahydro-3a-(methoxymethyl)-2-methyl-3,6-dioxo-l,4-methano[l //]isoindole-8-acetate. Y 83%. The ring system is the basic component of the gelsemine skeleton. F.e.s. J.-K. Choi et al., J. Org. Chem. J4, 279-90 (1989) 8-methyleneperhydro-3-indolizidinones s. J.M. Dener et al., ibid. 53, 6022-30 (1988). 

Different alcohols and protected alcohols (as hemiacetals, silyl, methoxymethyl or phenyl ethers) were lithiated at the d-position to give the corresponding organolithium compounds. In the case of alcohols, a previous deprotonation of the hydroxyl functionality is required. The chiral intermediate 197 was prepared from the phenylsulfanyl derivative 196 first by deprotonation followed by carbon-sulfur bond cleavage with LiDTBB at low temperature. The reaction of the dianionic system 197 with y- and d-lactones in the presence of cerium(III) salts gave, after hydrolysis, spiroketal pheromones 198 (Scheme 2.27) [163]. 

Lindo-rv.ff oselecli ve oxacydization of polyepoxides is less common the first ster-eospedfic tandem endo-regioselective biomimetic oxacydization of polyepoxides to fused THP rings has only recently been reported [38a], The cyclization of the hydroxy-methoxymethyl-substituted triepoxide 75 (a 1,4,7-triepoxide), promoted and directed by La(OTf)3 through an intramolecular chelation and based on a procedure originally described for a monoepoxide system [38b], afforded the tri-... 

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