Protection of 1,2- and 1,3-Diols

Study the following sequence, and answer the questions posed  

17(a) 1,3- and 1,2-diols form rings of a favorable size on reaction with ketones. Thus, the product is 

17(b) Although the conditions are not quite the usual ones, what is happening here should be obvious. The OH is benzylated. The silver facilitates the reaction by precipitation of AgBr. 

18(a) This very hindered silylating reagent only reacts with primary alcohols, and not with secondary alcohols. 

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Isopropylidene acetals are convenient protecting groups in carbohydrate chemistry, particularly for the protection of 1,2- and 1,3-diols, and are readily formed by reaction of the diol with acetone or 2,2-dimethoxypropane under acidic conditions. Several protic and Lewis acids have been reported as catalysts for this purpose.98... 

Isopropylidene acetals (also known as acetonides) are used more frequently than any other protecting group for the protection of 1,2- and 1,3-diols. They are easily prepared and they are stable to most reaction conditions except pro-tic and Lewis acids. They typically survive strong metal hydride reactions, but the Lewis acidic nature of diisobutylalane and borane can cause complications as shown by the solvent-dependent reductive cleavage of a dioxolane in Scheme 3.L2... 

Isopropylidene (acetonides) and benzylidene derivatives are the most commonly used acetals for the simultaneous protection of 1,2- and 1,3-diols in carbohydrate and nucleoside chemistry [123]. Cyclohexylidene acetals are occasionally used, most often as an alternative to benzylidene acetals. Protection using cyclohexane- 1,2-diacetals or the related butane-2,3-diacetals represents a new approach which has proved its value in complex oligosaccharide synthesis [124]. 

Reviews Concerning the Protection of 1,2- and 1.3-Diols Reviews Concerning Acetal Derivatives of Carbohydrates Reviews Concerning 1,2-Diacetals 180 Reviews Concerning A/,0-Acetals... 

Uses Sterically hindered reducing agent to install highly hindered di-t-butylsilylene group for protection of 1,2 and 1,3-diols upon thermolysis, as source of silicon for the CVD of silicon carbide... 

A review on the use of protecting groups derived from organosilicon reagents includes a discussion of the protection of 1,2- and 1,3-diols many examples from carbohydrate and nucleoside chemistry are included, ... 

Acetonide formation is the most commonly used protection for 1,2- and 1,3-diols. The acetonide has been used extensively in carbohydrate chemistiy to mask selectively the hydroxyls of the many different sugars. In preparing acetonides of triols, the 1,2-derivative is generally favored over the 1,3-derivative, but the extent to which the 1,2-acetonide is favored is dependent on stmcture. Note that the 1,2-selectivity for the ketal from 3-pentanone is better than that from acetone. ... 

Protective Groups for Diols. Diols represent a special case in terms of applicable protecting groups. 1,2- and 1,3-diols easily form cyclic acetals with aldehydes and ketones, unless cyclization is precluded by molecular geometry. The isopropylidene derivatives (also called acetonides) formed by reaction with acetone are a common example. 

The Arylmethylene Acetal Family of 1,2- and 1,3-Diol Protecting Groups... 

Oxidative cleavage of arylmethylene acetals offers another method for the transformation of an arylmethylene acetal to a mono-protected diol. For example, benzylidene acetals of 1,2- and 1,3-diols undergo ozonolytic cleavage rapidly at -78 °C at rates that compete with cleavage of alkenes to give a benzoate ester [Scheme 3.71]. The reaction is not restricted to benzylidene acetals since ethyli-dene and /erf-butylmethylidene acetals also cleave rapidly. The reaction was creatively exploited by Stork and Rychnovsky in the closing stages of their synthesis of dihydroerythronolide A when it was used to unmask a 1,2-diol protected as a 2-methyl-l,3-dioxolane in the presence of a 2-methyl-l,3-dioxane. It is noteworthy that a 1,3-dioxane function cleaved very much slower [Scheme 3.72). 

TBDMSCl has been used to selectively protect the primary hydroxyl group of 1,2- and 1,3-diols under mild conditions, via dibutylstannylene acetal intermediates. For example, treatment of the dibutylstannylene acetal of l-phenylethane-l,2-diol with TBDMSCl in chloroform affords the primary ether in excellent yield (eq 27). This selectivity for the primary hydroxyl group is different from acylation or alkylation of dibutylstannylene acetal... 

Perhaps classical for the protection of 1,2- and 1,3-cis-diols is the isopropyl-idene (acetonide) function. This acid labile ketal may be formed by reaction of a ribonucleoside with acetone in the presence of an acid (HCl, p-toluene-sulfonic, H2SO4) and water scavenger (2,2-dimethoxypropane, ethyl orthoformate). Other similar protecting groups include the benzylidene and cyclohexylidene functions. 

PROTECTION FOR THE HYDROXYL GROUP, INCLUDING 1.2- AND 1,3-DIOLS Half-lives for cleavage of 5 -protected thymidine in 80% AcOH at 15 ... 

A benzylidene acetal is a commonly used protective group for 1,2- and 1,3-diols. In the case of a 1,2,3-triol the 1,3-acetal is the preferred product. It has the advantage that it can be removed under neutral conditions by hydrogenolysis or by acid hydrolysis. Benzyl groups and isolated olefins have been hydrogenated in the presence of 1,3-benzylidene acetals. Benzylidene acetals of 1,2-diols are more susceptible to hydrogenolysis than are those of 1,3-diols. In fact, the former can be removed in the presence of the latter. A polymer-bound benzylidene acetal has also been prepared." ... 

One widely used method of formation of protected compounds involves polymer-supported reagents,21-27 with the advantage of simple workup by filtration and automated syntheses, especially of polypeptides. Polymer-supported reagents are used to protect a terminal —COOH group as a polymer-bound ester (RCOOR — ) during peptide syntheses,21 to protect primary alcohols as — trityl ethers,28 and to protect 1,2- and 1,3-diols as —phenyl boronates.29 Monoprotection of symmetrical dialdehydes and diacid chlorides has been reported 23 some diprotection occurs with diols and diamines.23... 

Bimolecular heteronine syntheses remain the most important way of ring assembly. Utility of 1,2- and 1,3-dielectrophilic reagents predominates in [7+2] and [6+3] syntheses, while cyclization of 1,2-diamines (or their protected counterparts), 1,2-diols, or 1,2-thiols with dielectrophiles remains the primary means of entry to the 1,4-diheteronine ring system. 

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