Bicyclic orthoester

Carboxylic acids can also be protected as ortho esters. Ortho esters derived from simple alcohols are very easily hydrolyzed, and a more useful ortho ester protecting group is the 4-methyl-2,6,7-trioxabicyclo[2.2.2]octane structure. These bicyclic orthoesters can be prepared by exchange with other ortho esters, by reaction with iminoethers, or by rearrangement of the ester derived from 3-hydroxymethyl-3-methyloxetane. 

An interesting experimental result was observed in the study of the mild acid hydrolysis of the cis and the trans bicyclic orthoesters 87 and 88 (60). The cis orthoester 87 gave under kinetically controlled conditions the dihydroxy methyl ester 89 whereas the trans orthoester 88 produced directly the hydroxy-lactone 90 under the same experimental conditions. These results can be explained on the basis of the principle of stereoelectronic control. 

The cis bicyclic orthoester 87 can exist in the two different conformations 91 and 92. The conformation 92 corresponds to that of the unreactive tricyclic orthoester 62, i. e. conformer it can therefore be eliminated. Con-former 91 can undergo the cleavage of the axial C —0 bond with stereoelectronic control to produce the lactonium ion 93 which after hydration will give the hemi-orthoester 94. Since the chair inversion in 94 is not favored because the hydroxyalkyl side chain would have to take the axial orientation, it is expected that 94 would give the dihydroxy methyl ester 89 preferentially. 

The study of the cleavage of the axial and the equatorial vinyl bicyclic orthoesters HO and H (Fig. 10) with potassium permanganate was reported recently (1, 3). Permanganate reacts with the vinyl orthoester double-bond yielding first 142 and then the tetrahedral intermediate 143. On that basis,... 

More precise information concerning the course of events in the acid hydrolysis of orthoesters was obtained from the study of the four bicyclic orthoesters 77-80 which have two different alkoxy groups. Each orthoester yielded exclusively the hydroxy-ester resulting from the ejection of the axial alkoxy group. Thus, 77, T, and 79 afforded the same hydroxy methyl ester 81 whereas orthoester 80 furnished the hydroxyl ethyl ester 82. The reverse process which occurs under basic conditions, i,e. the addition of alkoxide ion to the corresponding bicyclic lactonium salt, has already been described (cf. p. 71) and it was shown to take place with the same specificity. 

In marked contrast, bicyclic orthoesters are less reactive than another acyclic reference compound, trimethyl orthoformate. [79] For instance, the rate of hydrolysis of 2,6,7-trioxabicyclo[2.2.1]heptane (80) was slower by about 50% than that of trimethyl orthoformate. In addition, there are relatively small differences among the rate constants for the bicyclic orthoesters of [2.2.1]heptane, [3.3.1]no-nane, [3.2.1]octane and [4.2. l]nonane systems. This unexpected behavior was... 

Standard synthetic methods are used to couple partially protected penta-erythritol to the core cell and subsequent dendrimer surfaces [82, 133]. Synthesis of the first generation involves displacement of bromide from C(CH2Br)4 with a masked pentaerythritol (bicyclic orthoester). One obtains three hydroxyl groups per terminal group after deprotection (Scheme 24). Therefore, a series that triples both its surface hydroxyl groups and its molar mass is obtained (see Table 5). 

Conversion of the mono-p-methoxybenzyl ethers of 1,2 and 1,3-diols to the corresponding l, 3-dioxolanes or 1.3-dioxanes using DDQ in the absence of water is now a common ploy in synthesis (see section 3.2.3). Evans and co-workers333 recently showed that the transformation could be taken one stage further. Thus, treatment of the p-methoxybenzyl ether 180.1 [Scheme 4.180] with 2 equivalents of DDQ resulted in two sequential cyclisations to give the bicyclic orthoester 180.2 in 70% yield. 

Monomers listed above polymerize by the cationic mechanism. For some groups of monomers (lactones, carbonates) anionic or coordinate mechanism also operates and, from a synthetic point of view, this is the preferred method of converting cyclic esters into linear polyesters. The cationic polymerization of lactones, glycolide and it substituted analog, lactide, as well as spiroorthoesters and bicyclic orthoesters has been studied in some detail. 

This is similar to polymerization of bicyclic orthoesters reported earlier where, depending on reaction conditions, polymers resulting from the opening of one or both rings could be prepared [210]. 

Thermodynamical studies of the polymerization of bicyclic orthoesters has not yet been done. 

Bicyclic orthoesters of phosphorus acids, monograph 89MI3. 

By means of silver salts, alcohols and 2,6-dimethylpyridine sugar orthoesters (405 equation 189) have been prepared from (7-acetylated glycosyl halides. Bicyclic orthoesters (407 equation 190) are accessible by rearrangement of the esters (406). Excess oxalyl chloride reacts with tetrahydrocarb-azole to give the acid chloride (408 equation 191) which is converted by alcohols to orthoesters... 

Bicyclic orthoesters. Together with a catalytic amount of AgClO zirconocene dichloride converts 3-methyl-3,4-epoxy esters to the 2,7,8-trioxabicyclo[3.2.1]octane derivatives. These orthoesters are less susceptible to acid hydrolysis than Corey s 2,6,7-trioxabicyclo[2.2.2]octanes. 

This review summarizes all the data we obtained on the synthesis and cationic ring-opening polymerization of bicyclic acetals and orthoesters, and discusses the relationship between ring-strain and poly-merlzablllty. This ties In with earlier work on the polymerlzabll-Ity of monocyclic and bicyclic lactams ( - ). A new mechanism for the propagation step In the polymerization of bicyclic orthoesters Is supported. 

Reactivity. The reactivities of the bicyclic orthoesters can be compared examining the conditions necessary to form polymer. Although the hydrolytic reactivities were not accelerated, these monomers were Indeed very reactive In polymerization. In contrast to the behavior of the bicyclic acetals, no correlation Is found between the hydrolytic reactivity and the reactivity towards cationic Initiators for the bicyclic orthoesters. The following order can be proposed [2.2.1] > [2.2.2] > [3.2.1] > [3.3.1] which Is the expected order from the ring strains (18-19). 

Taking all these data Into account, the following A( 2 mechanism (blmolecular addition on a carbenlum Ion) Is supported for the polymerization of the [2.2.1]blcycllc orthoester. It presumably Is valid for all bicyclic orthoesters, at least at room temperature or higher temperatures. ... 

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