Acetoxymethyl ether

Me3SiCl, AC2O, 90%. Treatment of the resulting acetoxymethyl ether with acid or base readily affords the free alcohol. 

Coupling of the bis(trimethylsilyl) derivative of 5-benzyluracil 789 with 2-acetoxyethyl acetoxymethyl ether (791) in presence of SnCU was complex. In addition to the expected N-1 substituted product 790, the N-3 substituted derivative 792 and disubstituted product 793 were also isolated. However, treatment of 789 with 783 in CH3CN in the absence of SnCU gave 790 as the only isolated product. Deblocking of 790 with NHs-MeOH gave the free nucleoside (88SC931). 

The same experimental procedure was used for further N-alkylation reactions of 2,4-bis(trimethylsilyloxo)thieno[3,2-d]pyrimidine-2,4-diones 271. Thus, reaction of 271 with 2-acetoxyethyl acetoxymethyl ether, 2-(acetoxymethoxy)propane-l,3-dibenzoate, and benzyloxymethyl acetate gave the respective 1- and 3-alkylated derivatives 274 and 275, 276 and 277, and 278 and 279 (90MI1 94JHC305 94MI2, 94MI3). ... 

Notable progress in the structural analysis of methylene derivatives of the polyhydric alcohols resulted from the investigations of Hann, Hudson and their co-workers26 80,40-4 into the behavior of these compounds during acetolysis. It was found that a mixture of acetic anhydride, acetic acid and 1-2% sulfuric acid ruptures preferentially any methylene bridge which spans a primary and a secondary position, giving the acetate ester of the primary hydroxyl and the acetoxymethyl ether of the secondary hydroxyl subsequent treatment with sodium methoxide removes each of these substituents. Under similar conditions, the acetolysis of a benzylidene compound results in the replacement of the arylidene residue, wherever it is located in the molecule, by two acetyl groups.16 29 47 48... 

The reaction works equally well for the methylene acetals of 1,2-diols [Scheme 3.93J,172 and once again the less hindered methylene acetal is cleaved selectively to an acetoxymethyl ether and an acetate. 

The methylthiomethyl group is used as a protecting group of hydroxy functions. A deprotection can be carried out by electrolysis in an undivided cell with Pt electrodes in AcOH containing NaOAc. The resulting acetoxymethyl ether can be hydrolyzed in weakly alkaline medium [Eq. (43)] to the hydroxy function [132] ... 

MgE, ether, AC2O, rt, 90-100% yield. Cleavage occurs to give a mixture of acetate and an acetoxymethyl ether that is reported to be very acid- and base- sensitive. ... 

Much work was conducted by Hudson and his school on the acetolysis of methylene acetals of alditols. Their principal finding was that a methylene acetal that links primary and secondary positions is cleaved readily, and preferentially, at the primary position to give the primary acetate and the acetoxymethyl ether of the secondary hydroxyl group (Scheme 1). The reagent... 

Alcohol 45 was synthesized by treatment of 4-benzyloxy-l-butane oxide 44 with sodium benzyloxide, then converted to the acetoxymethyl ether 46, which condensed with diacetylguanine to give 47, whose deprotection gave 48 (86JMC1384). It is less active than DHPG against HSV-1. 

The synthesis of chiral acyclic nucleosides 276 utilizes the readily available protected acetoxymethyl ether of glycerol 275, which reacted with silylated nucleobases under phase transfer conditions using dibenzo-18-crown-6 to give N-9 purinyl and N-1 pyrimidinyl acyclonucleosides. Removal of the benzoyl groups by methanolic ammonia gave 277 (88JMC144 89TL6165). 

Acetoxymethyl ethers 539 and 540 could be prepared from the mixture of glycerol formals 537 and 538. Reaction of 539 with GuAca gave N-9 (541) (and N-7) guanine derivatives as racemic forms whose deacetylation gave 542 (84TL905 85JMC926). 

There have been further reports from the Leiden group on the synthesis of dinucleosides linked by a (3 - 5 ) methylene acetal (see Vol. 25, p. 270). A cytosine -(3 ->5>uridine unit with this type of link has been made, using activation of a 3 -0-methylthiomethyl ether with NIS and triflic acid to form the intemucleosidic acetal, and the product was converted to a 3 -phosphoramidite.298 An alternative way of establishing the link, using 3 -0-acetoxymethyl ethers, is illustrated in Scheme 19.299... 

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