Methanolysis pathways

For all methanolysis pathways considered in this study, increasing the bite angle of the diphosphine ligand increases the rate of methanolysis. This is attributed to the involvement of electron-rich intermediates and/or transition states in all three methanolysis pathways. 

Further examples of the effects of added cations on stereochemical pathways have been observed using 5-chloromethyl-5-methyl-2-oxo-l,3,2-dioxaphosphorinans. Under normal conditions, methanolysis of (107 R = SPh) leads to the methoxy-ester having the same configuration. In the presence of added cations, particularly Li+, both inversion and retention pathways are observed.79 Phenolysis of the phos-phorochloridate (107 R = Cl), normally proceeding with inversion, proceeds with complete retention of configuration in the presence of Li+.80... 

The rate and pathway of the methanolysis appear to depend strongly on the steric and electronic effects of the equatorial substituents. Because of the steric hindrance at the pentacoordinate silicon induced by N(Y/ substitution in N-silylated triazasilatranes, nucleophiles can attack their four-coordinate silicon atoms (equation 189)414. 

Not surprisingly, an attempt at direct Mitsunobu inversion of (3-hydroxyketone 14 led only to elimination, yielding the corresponding a,(3-unsaturated ketone. To circumvent this problem, 14 was converted to homoallylic alcohol 15 by Petasis methylenation via the corresponding TES ether. Attempts to methylenate (3-hydroxyketone 14 directly under Petasis conditions led to substantial decomposition via elimination and retro-aldol pathways. Alcohol 15 underwent smooth Mitsunobu inversion to give, following methanolysis and TES ether formation, the desired 1,4-anti compound 16 (Scheme 3). This was then converted in three straightforward steps to aldehyde 17, ready for the proposed aldol union with ketone 10. 

Combinations of product studies with kinetic data provide particularly powerful indications of reaction mechanisms. Either the presence or absence of a rate-product correlation may be of mechanistic significance. First, we have an explanation of rate-product correlations using the example of competing methanolysis (second-order rate constant, IcMeOH) and aminolysis (second-order rate constant, kam) of benzoyl chloride (59) in Scheme 2.21. The mechanism is initially assumed to involve independent competing pathways, as shown, so that the equations of correlation can be derived. 

Application of the extended Grunwald-Winstein equation to solvolyses of propyl chloroformate, PrOCOCl, in a variety of pure and binary solvents indicated an addition-elimination pathway in the majority of the solvents but an ionization pathway in the solvents of highest ionizing power and lowest nucleophilicity. For methanolysis, a solvent deuterium isotope effect of 2.17 was compatible with the incorporation of general-base catalysis into the substitution process.21... 

The hydrosilylation/methanolysis reaction sequence. One of the most convenient methods is to use a sequence of hydrosilylation/methanolysis reactions as shown in equation 4 for the formation of 39. This direct synthetic pathway was reported in cases of the alkyl family of precursors 1290. This sequence is also used for the preparation of dendrimers and arborols121,123. Alternatively, hydrosilylation with HSi(OEt)3 can be performed advantageously in the case of dendrimers125,126 but it is of more interest in the case of carbonate precursors 26111. Indeed, hydrosilylation of double bonds can be achieved selectively in the presence of a carbonyl group with hexachloroplatinic acid or a rhenium catalyst130. 

Within the first pathway, reduction of the nitrile was facilitated by preliminary methylation with dimethylbromonium hexafluoroantimonate in liquid sulfur dioxide and subsequent methanolysis to the iminoether, which was treated with sodium cyanoborohydride (Scheme 20). The secondary amine 191 was chlorinated with sodium hypochlorite to the corresponding iV-chloroamine to enable titanium... 

However, the stereochemical results on enzymatic reactions have not led to identifying one of the four possibilities as the general mechanism in enzyme catalysis. First, formation of a metaphosphate intermediate (mechanism A) may not necessarily result in racemization since in the enzyme active site it may not be free to rotate before it is trapped by the acceptor. Racemization did not even occur in the chemical methanolysis of some phosphomonoesters under dissociative conditions (143). Therefore an observed inversion does not rule out pathway A. Second, the two in-line associative pathways B and C may not be distinguishable in enzyme catalysis and may both proceed with inversion. Lastly, stereochemical results can not differentiate between mechanism D and a double displacement mechanism in which each displacement occurs with inversion. 

Knowles and co-workers have studied the stereochemical consequences of the presumed S>jl(P) reaction. They have shown that the methanolysis of chiral 0 0 0-substituted phenol- and 2,4-dinitrophenylphosphate and phosphocreatine (13, 14), under conditions where they were expected to react by the metaphosphate pathway, all undergo complete inversion of configuration at phosphorus. This result implies that the putative metaphosphate is not a free intermediate that it is not even long-lived enough to equilibrate with the solvent cage in which it is formed. It was concluded that the reaction must be preassociative at least in aqueous-alcoholic media. A recent report (24) has shown that the Conant-Swan fragmentation described earlier also occurs with inversion about the phosphorus atom. 

Figure 10 Reaction pathways of mono-functional hydrogenolytic demethylation ( methanolysis ). a = probability to remain adsorbed and be demethylated again...

In their early work Hughes and Ingold considered SnI and Sn2 pathways as competitive reactions of a single substrate, and borderline behavior resulted from a blend of the two processes. For example, they found that methanolysis of 1-phenylethyl chloride at 70°C is accelerated by sodium methdxide ... 

It is generally accepted that oleoyl-12-hydroxylase catalyzes the reaction from 2-oleoyl-PC to 2-ricinoleoyl-PC (5). We have recently characterized oleoyl-12-hydroxylase in micro-somes from the endosperm of immature castor bean using the putative substrate, 2-[i4C]-oleoyl-PC (2). Our results support the hypothesis that the actual substrate of oleoyl-12-hydroxylase is 2-oleoyl-PC. In our previous study, the enzyme activity was measured by the radioactivity of ricinoleate after methanolysis of the total lipids from the incubation products. In this report, for the purpose of establishing the biosynthetic pathway, radio-active intact lipid metabolites of 2-[i" C]oleoyl-PC were separated by HPLC and their radioactivity quantified. 

The aminolysis of 0,0-diethyl 4-nitrophenyl phosphate (Paraoxon) by piperidine in 10 ILs was compared to results in MeCN, dioxane, and DMSO. Generally, rates and selec-tivities in the ILs were similar to those in DMSO. P NMR analysis of the aminolysis products in the ILs showed that piperidine attacked P=0 (5n2(P)), the C( 1) aromatic carbon ( nAt) and the ethyl group (5 2(0)), the latter pathway not having been observed previously. A theoretical study of the effect of sulfur substitution on the methanolysis... 

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