Ortho esters cyclic

The formation of the six-membered ether ring via epoxy ester-ortho ester cyclic ether rearrangement supports the hypothesis that epoxy ester-ortho ester cyclic ether rearrangement may be involved in the biosynthesis of ladder-type marine polyether toxins. This reaction represents a biomimetic preparation of medium ring cyclic ethers. 

A variety of cyclic ortho esters,including cyclic orthoformates, have been developed to protect czs-1,2-diols. Cyclic ortho esters are more readily cleaved by acidic hydrolysis (e.g., by a phosphate buffer, pH 4.5-7.5, or by 0.005-0.05 M HCl) than are acetonides. Careful hydrolysis or reduction can be used to prepare selectively monoprotected diol derivatives. 

When enantiomerically pure fni/is-2-acetoxycyclohexyl tosylate is solvolyzed, tiie product is racemic /mn -diacetate. This is consistent with the proposed mechanism, since the acetoxonium intennediate is achiral and can only give rise to racemic material. Additional evidence for diis interpretation comes from the isolation of a cyclic ortho ester when the solvolysis is carried out in ethanol. In this solvent the acetoxonium ion is captured by the solvent. 

The addition of nucleophiles to cyclic fluoroolefins has been reviewed by Park et al. [2 ]. The reaction with alcohols proceeds by addition-elimination to yield the cyclic vinylic ether, as illustrated by tlie reaction of l,2-dichloro-3,3-di-fluorocyclopropene Further reaction results in cyclopropane ring opening at the bond opposite the difluoromethylene carbon to give preferentially the methyl and ortho esters of (Z)-3-chloro-2-fluoroacrylic acid and a small amount of dimethyl malonate [29] (equation 8). 

Note 1. The last two examples contain cyclic ortho ester structures. These compounds are conveniently named as cyclic acetals. 

The hydrolysis of acetals and ortho esters is governed hy the stereoelectronic control factor previously discussed (see A and B on p. 427) though the effect can generally be seen only in systems where conformational mobility is limited, especially in cyclic systems. There is evidence for synplanar stereoselection in the... 

Cyclization of 776 with ortho-esters gave (83JOC1628) [l,2,4]triazolo-[4,3-fc]pyrimido[5,4-< ][ 1,2,4]triazines 777, whereas reaction with sodium nitrite afforded the corresponding tetrazolopyrimidotriazine 778.3-Azido-pyrimido[4,5-e][l, 2,4]triazine 779 exists in a cyclic form as tetrazolo derivative 780, as shown by X-ray analysis (86KGS114). In solution the position of the 779 780 equilibrium depended on temperature and solvent. Higher temperatures favored 779. Azido compound 779 predominated in water, and tetrazolo compound 780 predominated in pyridine. Addition of sodium azide to the aqueous solution shifted the equilibrium toward 780. The... 

Steroids [59-69] and a number of carbohydrates [70-73] also react with acyclic ortho esters to give cyclic ortho esters by transesterification. 

Without trapping agents, cyclic ortho esters were formed. 

A tertiary radical can be formed by elimination during AF of ter/-butyl methyl and ethyl ethers thus, isolation of the respective perfluoro-/erf-butyl ethers, e.g. 1, occurs in only 36 and 42% yield.28 Significant quantities of perfluoro(2-methylpropane) (2) are also isolated. The longer alkyl chains (ethyl and larger) appear to be slightly less prone to scission than the methyl group. Apparently, carbonyl fluoride is more readily eliminated than trifluoroacetyl fluoride, a phenomenon observed during AF of esters.29 Elimination becomes most serious in the special class of polyethers called ortho esters, e.g. 3-5.30 Cyclic ortho esters, acetals and ketals are much less affected than acyclics. 

Co2(CO)8-catalyzed reactions of benzylic acetates with trimethylsilane and CO proceed under mild reaction conditions to give trimethylsilylethers of /3-phenethylalcohol in 43-76% yield. The highest yields are observed for benzyl acetates with electron-donating substituents.111 Secondary alkyl acetates are also good substrates in the reaction system, yielding enol silyl ethers.112 In addition, the cobalt complex is an effective catalyst for siloxymethylation of five-membered cyclic ortho esters, as shown in Eq. (41).113... 

The reaction is highly regioselective for substituted cyclic ortho esters, with ring opening mainly at the primary carbon center. However, reversed reactivity is observed for the phenyl-substituted derivative. Corresponding 1,4- and 1,5-diol derivatives are obtained in reaction of six- and seven-membered cyclic ortho esters. 

Dihydrazones of cyclic 1,2-diketones react with ortho esters and similar reagents to form aza macrocycles, which coordinate as for (31). 

Acylated Corticoids. The corticoid side-chain of (30) was converted into the cyclic ortho ester (96) by reaction with a lower alkyl ortho ester RC(OR/)3 in benzene solution in the presence of yw/T7-toluene sulfonic acid (88). Acid hydrolysis of the product at room temperature led to the formation of the 17-monoesters (97) in nearly quantitative yield. The 17-monoesters (97) underwent acyl migration to the 21-monoesters (98) on careful heating with H+. In this way, prednisolone 17a,21-methylorthovalerate was converted quantitatively into prednisolone 17-valerate, which is a very active antiinflammatory agent (89). The intermediate ortho esters also are active. Thus, 17a,21-(l,-methoxy)-pentylidenedioxy-l,4-pregnadiene-llp-ol-3,20-dione [(96), R/ = CH3, R = C4H9] is at least 70 times more potent than prednisolone (89). The above conversions... 

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