Exchange acetal

Preferential formation of a 5-membered cyclic acetal is not a general rule in the steroid series e.g., the 1,3-dioxolane (23) is obtained directly from the parent triol (22) and acetone. 17,21-Acetals are obtained only by acetal exchange. ... 

Methoxymethylation of alcohols is generally achieved through alkylation with chloromethyl methyl ether. The procedure described here for the preparation of Bu3SnCH20CH20CH3 avoids the use of the highly toxic chloromethyl ether by employing an acid-catalyzed acetal exchange reaction with dimethoxymethane for the... 

Acetal exchange has previously been achieved using molecular sieves in combination with p-toluenesulfonic acid Roelofsen, 0. P. Wils, E. R. J. Van Bekkum, H. Red. Trav. Chim. Pays-Bas1971, SO, 1141. 

TVansacetalation. Hus strategy, based on an acetal exchange in acid conditions, has been introduced mote recently in carbohydrate chemistry [32-34]. It offers several advantages over the direct condensation of the corresponding free carbonyl group (1) anhydrous conditions can be strictly followed, as the only by-product is 2 mol of the alcohol (e.g MeOH) used to prepare the reagent (Scheme 2) this alcohol can even be removed by... 

Initiator. During polymerization in ethyl acetate exchanging ethyl azodiisobutyrate for tert-butyl perpivalate the visual homogeneity limit rises from Pv = 600 to ca. 4000. In accordance with the visual result... 

Discussion In principle, acetals are cleaved by acid-catalyzed hydrolysis. In most cases aqueous acetic acid, aqueous trifluoracetic acid, dilute HC1 in THF or DOWEX 50W (H+) resin are used. Thus, treatment of 6 with DOWEX ion exchange resin in methanol rapidly furnishes the corresponding 1,2-diol without any further chromatographic purification steps. Generally, polymer supported reagents benefit from the ease of removal from the reaction mixture just by filtration of the insoluble resin. The resulting diol is acetylated by addition of acetic anhydride and pyridine. Final acetal exchange is achieved by acetic anhydride and catalytic amounts of concentrated sulfuric acid. A mixture (2 1) of anomers is obtained. 

An intermediate in the synthesis of laulimalide by Davidson8 illustrates the differential protection of alcohols. The starting materials 56 and 57 already have an alcohol protected as a TBDMS silyl ether and a diol protected as an acetal. The alcohol in 58 is protected as a p-methoxybenzyl ether and the acetal hydrolysed by acetal exchange to give the free diol 60. Selective protection of the primary alcohol by a bulky acyl group (pivaloyl, i-BuCO ) 61 allows silylation of the secondary alcohol with a TIPS group 62. Finally the pivaloyl group is selectively removed by DIBAL reduction to release just one free alcohol 63. 

The aliphatic Claisen rearrangement is simpler in that there is no rearomatisation at the end but there is an ionic step first as the vinyl ether 67 has to be made and the easiest way to do that is from the allylic alcohol 65 by acetal exchange with another vinyl ether to give 66 and elimination to give 67. All these steps, including the rearrangement occur under the same conditions16 and the product is a y,S-unsaturated carbonyl compound 68. 

A key reaction in the synthesis of the TIA alcohol 18 was the Suarez fragmentation (33) of the 2,3-O-isopropylidene-D-lyxose derivative 23 (34). Treatment of 23 with diiodobenzene diacetate (DIB) provided the 1,2-0-isopropylidene acetate 24 in 88% yield. Acetal exchange was effected by treatment of 24 with thiophenol and BF3.Et20 at -78 °C. Mild base hydrolysis of the product provided 18 in 90% yield from 24, and in 65% overall yield over the four one-pot operations for commercially available D-lyxose 22 (Scheme 3). 

The details on the preparation of the glycone synthon 16 have been described in the earlier report on 3 (24). The key reactions in this synthesis is the Suarez radical fragmentation of the 1,2-O-isopropylidene furanose 17 to give the 1-O-acetyl-1,2-isopropylidene 18 (35), and acetal exchange of 18 to the phenylthio monothioacetal 16 (Scheme 2). Overall, 16 is easily obtained on multi-gram scale (ca. 20 g), in 60% yield, over five steps from commercially available D-lyxose. 

Ketones or aldehydes can undergo acetal exchange with orthoesters. The mechanism starts off as if the orthoester is going to hydrolyse but the alcohol released adds to the ketone and acetal formation begins. The water produced is taken out of the equilibrium by hydrolysis of the orthoester. 

B. Suggest a detailed mechanism for the acetal exchange used in this chapter to make an acetal of a ketone from an orthoester. 

It is not necessary to isolate the allyl vinyl ether as long as some of it is formed and rearranges into the final product. The acid catalyst usually used, propanoic acid, has a conveniently high boiling point so that the whole mixture can be equilibrated at high temperature. The first step is an acetal exchange in which the allylic alcohol displaces methanol. 

Rates of Acetate-exchange and Anomerization of Some D-Glucopyranosyl Acetates and Derivatives ... 

Acetal exchange reactions using 1,1-dimethoxycyclohexane [Scheme 3.44 67 or 1,1 -dimethoxycyclopentane [Scheme 3.45J68 results in the formation of the corresponding cycloalkylidene acetals. 1-Methoxy-1-cyclohexene can also be used as shown for the protection of Lyxose [Scheme 3.46] 69... 

Owing to the higher acid and hydrolytic lability of p-methoxybenzylidene acetals, they are usually made by acetal exchange processes using anisaldehyde di-methylacetal and pyridinium p-toluenesulfonate or camphorsuifonic add [Scheme 3.80].149 Alternatively, the Noyori protocol can be implemented under very mild conditions [Scheme 3.81].150... 

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