Ketene acetals mechanism

Even though poly(ortho esters) contain hydrolytically labile Linkages, they are highly hydrophobic materiads and for this reason are very stable and can be stored without careful exclusion of moisture. However, the ortho ester linkage in the polymer is inherently thermally unstable and at elevated temperatures is believed to dissociate into an alcohol and a ketene acetal (33). A possible mechanism for the thermal degradation is shown below. This thermal degradation is similar to that observed with polyurethanes (34). 

Interestingly, fundamentally different stereoinduction mechanisms have been proposed for the activation of a number of related imine substrates, studies that resulted in the development of simple and highly effective new catalytic systems (27) for the addition of silyl ketene acetals to Al-Boc-protected aldimines (Mannich reaction) (Scheme 11.12c). ... 

The undefined mechanism of the aldol-type Mukaiyama and Sakurai allylation reactions arose the discussion and interest in mechanistic studies [143-145]. The proposed mechanism was proved to proceed through the catalytic activation of the aldehyde and its interaction with the silyl ketene acetal or allylsilane producing the intermediate. From that point the investigation is complicated with two possible pathways that lead either to the release of TMS triflate salt and its electrophihc attack on the trityl group in the intermediate or to the intramolecular transfer of the TMS group to the aldolate position resulting in the evolution of the trityl catalyst and the formation of the product (Scheme 51). On this divergence, series of experimental and spectroscopic studies were conducted. 

The formation of orthoester may be explained tiy the preferential addition of tlie ketene acetal to the most reactive alcohol function (primary hydroxyl g,roup) giving thc f non - i so 1 a t ed) acyclic orthoester whicti is attacked by the neighbouring OH-4 with subsequent elimination of methanol. The partial hydrolysis of the diacetate is assumed to proceed through protonation of the methoxyl group (7), via the dioxocarbenium ion 8 and the orthoacid 9. collapse of 9 by either [lath b or path a accor-ding to the mechanism generally proposed (see, for instance, ref. 29 and refs. cited therein) affords the compounds 5 or respectively. 

Aliphatic polyesters occupy a key position in the field of polymer science because they exhibit the remarkable properties of biodegradability and biocompatibihty, which opens up a wide range of applications as environmentally friendly thermoplastics and biomaterials. Three different mechanisms of polymerization can be implemented to synthesize aliphatic polyesters (1) the ring-opening polymerization (ROP) of cyclic ketene acetals, (2) the step-growth polymerization of lactones, and (3) the ROP of lactones (Fig. 1). 

The first route relies on the ROP of cyclic ketene acetals [1-3]. The electron-rich double bond is prone to react with radicals and electrophiles. Therefore, this class of monomers undergoes cationic and radical polymerization. For example, radical initiators react with the double bond to provide a new tertiary radical (Fig. 2). Two distinct mechanisms of polymerization can then take place direct vinyl polymerization or indirect ring opening of the cycle accompanied by the formation of a new radical, which is the propagating species (Fig. 2). The ester function is formed... 

The mechanisms for nucleophilic GTP and electrophilic GTP are not the same. Electrophilic GTP proceeds by an associative or concerted mechanism that does not involve anionic propagating centers. Initiation involves a concerted addition of methyl trimethylsilyl dimethyl ketene acetal to monomer to form species XXV. The overall effect is to transfer... 

Pyrolysis of the ethylene acetal of bicyclo[4.2.0]octa-4,7-diene-2,3-dione yields a-(2-hydroxyphenyl)-y-butyrolactonc 11 a mechanism involving a phenyl ketene acetal is proposed. Tartrate reacts with methanediol (formaldehyde hydrate) in alkaline solution to give an acetal-type species (9) 12 the formation constant was measured as ca 0.15 by H-NMR. Hydroxyacetal (10a) exists mainly in a boat-chair conformation (boat cycloheptanol ling), whereas the methyl derivative (10b) is chair-boat,13 as shown by 1 H-NMR, supported by molecular mechanics calculations. 

In other studies, analysis of the products of reaction between formaldehyde and guanosine at moderate pH shows a new adduct—formed by condensing two molecules of each reactant—which has implications for the mechanism of DNA cross-linking by formaldehyde,17 while the kinetics of the mutarotation of N-(/ -chlorophcnyl)-//-D-glucopyranosylamine have been measured in methanolic benzoate buffers.18 For a stereoselective aldol reaction of a ketene acetal, see the next section. 

The molecular mechanisms for the nucleophilic addition of lithium enolates and silyl ketene acetals to nitrones in the absence and in the presence of a Lewis acid catalyst to give isoxazolidin-5-ones or hydroxylamines have been investigated by DFT methods at the B3LYP/6-31G level.13 An analysis of the global electrophilicity of the reagents accounts for the strong electrophile activation of the Lewis acid-coordinated nitrone, (g) and the analysis of the local indices leads to an explanation for the experimentally observed regioselectivity. 

Early work on the GTP mechanism showed that the silyl groups on chain ends rapidly exchange in the presence of anionic catalysts [33, 34]. Without catalyst no exchange occurs [35]. No exchange occurred in the bifluoride catalyzed polymerization of MMA with dimethylphenylsilyl ketene acetal (Scheme 19a) in the presence of dimethyltolylsilyl fluoride [1]. However, in a similar experiment with trimethylsilyl acetate, TBA Ac, and dimethylphenylsilyl ketene acetal, complete exchange occurred within 5 min [36] (Scheme 19b). 

In the dissociative mechanism the exchange is readily explained by the formation and dissociation of the enolate ends with neutral silyl ketene acetal ends (Scheme 13). The lack of exchange of fluorosilane with enolate ends could be caused by the complex with fluorosilane breaking only at the SiO bond to revert to fluorosilane (no exchange). 

The main evidence for the associative mechanism consists in double-labeling experiments conducted by Farnham and Sogah [33, 34]. At -90 °C in THF a mixture of PMMA with a dimethyltolylsilyl ketene acetal end group and PBMA with a dimethylphenylsilyl ketene acetal end group was treated with a small amount of BMA and TASF catalyst (Scheme 20). After 5 min the polymerization was quenched and the polymers separated by solubility. NMR showed a small PBMA block on the PMMA polymer but the end group was only tolyldimethylsilyl. 

Evidence favoring an associative mechanism was obtained in dual initiator studies. Under an associative mechanism with two different initiators in the same reactor each set of chains would grow at slightly different rates. Thus the MWD of the resulting polymer should be higher than the one with one initiator. This is the case when dimethylphenylsilyl ketene acetal and TMS were used to polymerize MMA with TBA biacetate as catalyst [38] (Scheme 22). 

The fact that known anionic initiators for MMA can act as catalysts for GTP and the need for low amounts of catalysts in itself nearly puts to rest the associative mechanism. Seven of the other factors support the dissociative process. Except for the low temperature exchange studies, none supports the associative mechanism. Based on the lack of exchange of added silyl fluoride with silyl ketene acetal ends it looks like fluoride and bifluoride catalysts operate by irreversible generation of ester enolate chain ends [1] (Scheme 19b). On the other hand carboxylate catalysts appear to operate by reversible generation of ester enolate ends as evidenced by rapid exchange of silyl acetate with silyl ketene acetal ends [36] (Scheme 19c). 

Methyl trichlorosilyl ketene acetal reacts with aromatic and aliphatic ketones (the former enantioselectively), using chiral pyridine bis-N-oxide catalysts.134 Computations and an X-ray crystal structure of a catalyst-SiCU complex have helped to elucidate the mechanism. 

That the substitution mechanism depends on the nature of the nucleophile is shown by the formation of the ketene acetals (151) from the reaction of vinylidene chloride with alkoxide ions. It was suggested that two consecutive eliminations-additions take place, and that in both cases the alkoxide attacks the acetylene at the substituted carbon (Kuryla and Leis, 1964). Since chloroacetylene (132) is also an inter-... 

First, chemoselective (Chapter 24) conjugate addition of the silyl ketene acetal on the enone is preferred to direct aldol reaction with the aldehyde. Then an aldol reaction of the intermediate silyl enol ether on the benzaldehyde follows. The stereoselectivity results, firstly, from attack of benzalde-hyde on the less hindered face of the intermediate silyl enol ether, which sets the two side chains trans on the cyclohexanone, and, secondly, from the intrinsic diastereoselectivity of the aldol reaction (this is treated in some detail in Chapter 34). This is a summary mechanism. 

Coupling with Silyl Enol Ethers and Silyl Ketene Acetals. Silyl enol ethers can couple to the bromooxazinone to give both the syn and anti diastereomers. - The reaction can proceed via the Sn 1 mechanism discussed above or by a Lewis acid assisted Sn2 displacement of the bromide. The reaction conditions can be manipulated to favor the SnI (stronger Lewis acids, more polar solvents) or Sn2 path (weaker Lewis acids, less polar solvents) (eq 12 and eq 13). ... 

Pacsu has proposed a mechanism for the hydrolysis of the ketene acetals which are formed by enolization.i From studies of the C—C bond-distances and from thermodynamic calculations, it has been determined that 27.8% of glyoxal exists in its enolic form, hydroxyketene (XXIII). Where there are strong electrophilic groups on the carbon atom... 

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