Intramolecular transacetalization

Only a few reports have dealt with this type of synthesis of the 1,3-dioxepin and 1,3-dithiepin moiety. Dithiepane 148 could be obtained by an intramolecular transacetalization of mercaptane 147 (Scheme 40) <2000T10101>. 

As illustrated in Scheme 2, [12] four possible reactions produce the cis unit (P-form). They are (1) the oxonium exchange reaction at a penultimate unit (upper left), (2) the propagation by an oxacarbenium ion (upper right), (3) the propagation by a covalent species (lower left), [16] and (4) the inter- or intramolecular transacetalization via macrocyclic or linear trialkyloxonium ions (lower right). The common features of the polymerization of the monomers 3 and 6-8 described above cannot be accounted for either by the propagation involving oxacarbenium ions or covalent species or by the transacetalization. 

The occurrence and a limited importance of chain transfer by transacetalization cannot be doubted. We proposed this type of reaction for trioxane polymerization as early as 1959 (6) and assumed that intramolecular transacetalization produces some thermally stable macrocyclic polyoxymethylene (10). We have utilized bimolecular chain transfer by polymers to produce thermally stable block copolymers at temperatures over 100°C. [—e.g., with polyesters, polypropylene oxide, or with polyvinyl butyral)] (12). 

Dioxanes are prepared from 1,3-diols and either an aldehyde. - a ketone, " an acetal, or mcthoxyniethyl chloride. 4-Tolucnesulfonic acid is the catalyst ofchoice, - - e g. diol 9 reacts with isobutyraldchyde to give the cyclic acetal 10. For the intramolecular transacetalization of bis(methoxymethyl)-protccted diol 11 to dioxane 12, Amberlyst-15 (beaded polyslyrcnesulfonic acid) is needed. ... 

The chiral phosphoric acid TRIP (3) was found to be an efficient and highly enantioselective catalyst of the intramolecular transacetalization reaction of hydroxyacetals enabling the asymmetric synthesis of acetals with the acetal carbon... 

Although initially developed as a rather exotic reaction, the intramolecular transace-talization reaction can also be a very useful tool in asymmetric synthesis of important chiral compounds and natural products. Both, starting materials and products of the intramolecular transacetalization reaction are protected y-hydroxycarbonyl compounds, orhomoaldols (Scheme 13). Homoaldols are versatile motifs in organic synthesis that can be easily transformed into a vast array of important chiral compounds. However, due to the problematic homoaldol disconnection, these compounds are not readily available in a catalytic asymmetric fashion. 

Such kinetic resolutions via intramolecular transacetalization reaction represent an atom economic method that does not require any stoichiometric reagents and forms ethanol as the only by-product. This reaction also is the first example of a kinetic resolution of alcohols via acetal formation and the first example of a chiral Brpnsted acid-catalyzed kinetic resolution of alcohols. The utility of the reaction... 

Although 0,0-acetals are among the most common stereocenters in organic molecules, their catalytic asymmetric syntheses have only been achieved recently. Due to problems associated with asymmetric additions to oxocarbenium ions using chiral Brpnsted acid catalysts, intermediates in the synthesis of acetals, design of a suitable reaction was necessary. We have presented the invention of a catalytic asymmetric intramolecular transacetalization reaction for the synthesis of acetals... 

The transacetalization also proceeds intramolecularly. It then leads to the formation of cyclic acetals which participate as monomers in the propagation reaction. 

Inspired by these results, Nicolaou et al. used a temporary boronate tether to overcome the undesired regiochemical bias in the intermolecular Diels-Alder reaction of diene 56 and dienophile 57, required for their approach to the C-ring of taxol 58 [21a, b, 24], Thermolysis of a benzene solution of 56 and 57 in the presence of PhB(OH)2 under dehydrating conditions provided the cycloadduct 59 in 79% yield (77% conversion) after transacetalization of the boron tether with 2,2-dimethylpropane-l,3-diol and intramolecular acyl transfer to the less strained [4.3.0]bicyclic system. This was further elaborated to an advanced intermediate in the ultimately successful synthesis of taxol (Scheme 10-21) [21c]. 

These findings are inconsistent with the essentially random nature of the final copolymer. Weissermel et al[5] proposed a rearrangement mechanism which accounts for the redistribution of the comonomer units. Transacetalization is the term given to this rearrangement. In 1972, Cherdron[8) described this redistribution as the result of "the reaction of the polymeric carbonium ions with oxygen atoms of the same or of another polymer molecule (intramolecular and intermolecular transacetalization)". He depicted the mechanism as follows ... 

NMR and stability studies, that the comonomers are randomly distributed along the chains [237, 238]. This is attributed to the fact that intermolecular chain transfer (transacetalization), contrary to THF polymerization, proceeds on a time scale similar to propagation, and the same holds for the intramolecular chain transfer leading to cycUc polymer [239, 240]. Cationic polymerization of trioxane is usually a precipitation polymerization leading to crystalline polymers, and the size of the macrocydes is determined by the size of the crystalline lamdlae [240]. 

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