Dispoke Derivatives

The dispoke group is stable towards a variety of reaction conditions typically used in oligosaccharide synthesis and it can be used to tune the reactivity of typical monosaccharidic donors. It is removed by hydrolysis with 95% aqueous trifluoroacetic acid at room temperature. 

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The 2,2 -bis(phenylthiomethyl) dispiroketal (dispoke) derivative is cleaved by oxidation to the sulfone, followed by treatment with LiN(TMS)2. The related bromo and iodo derivatives are cleaved reductively with LDBB (lithium 4,4 -di- -butylbiphenylide) or by elimination with the P4- -butylphosphazene base and acid hydrolysis of the enol ether. The 2,2-diphenyl dispiroketal is cleaved with FeCl3 (CH2CI2, rt, overnight)." The dimethyl dispiroketal is cleaved with TFA, and the allyl derivative is cleaved by ozonolysis followed by elimination. ... 

In the gluco series, the problem is that there are three hydroxyl groups in a fru/tf-diequatorial relationship and hence there are two possible dispoke derivatives 104.2 and 1043 [Scheme 3 104] By using chiral bis(dihydropyrans) such as (J / )-104 4 and ( 5) 104, complete regioselectivity can be achieved owing to double diastereoselection.187188... 

In the same way, glycolic acid can be ste-reoselectively transformed into the Dispoke derivative 10 (61 %) with enantiomerically pure 3b. [8] Formation of the ester enolate, alkylation with methyl iodide, renewed enolate formation and treatment with benzyl bro-... 

Dispoke Derivatives 161 Cyck)hexane-1 -diacetals Butane-2,3-diacetals 165... 

Reaction of methyl a-D-galactopyranoside 102.1 with 6,6 -bis(3,4-dihydro-2//-pyran) (bis-DHP, 1023) in refluxing chloroform (thermodynamic conditions) gives the dispoke (dispiroketal) derivative 102.2 in 64% yield. - The preference for rram-diequatonal protection is a consequence of steric interactions and multiple stabilising anomeric effects of the two acetal functions in the dispoke derivative. The pure bis-DHP reagent 1023 is a low melting solid (mp 49-50 C) that is stable at -10 °C in the absence of acid and moisture. It is prepared in 55% yield by the oxidative dimerisation of 6-lithio-3,4-dihydro-2//-pyr-an. As can be seen from Scheme 3.103, the preference for frum-diequatorial protection is excellent in the fiico, manno, and fyxo series but it is poor in the case of the arabino and rhamno series. 

Regio- and enantioselective differentiation of symmetrical polyols has been accomplished with dispoke derivatives [Scheme 3.106]. Reaction of S,S)-6,6 -bis(2-methyl-3,4-dihydro-2//-pyran) (105.1) with 1,5-disilylated xylitol 106.2 in boiling chloroform containing a catalytic amount of camphorsulfonic acid gave the protected polyol 1063 as the only isolated product. The reaction was completely diastereoselective and the product formed was the most thermodynamically stable in which the two side chain methyl groups and the two hydro-xylated side chains on the dioxane ring were equatorially oriented, with the spirocentres benefiting from maximum anomeric stabilisation. 

Besides the 2,3-protected galactosides 5a and 6a (Scheme 1), other monosaccharides from the gluco, manno, rhamno, fuco, xylo, lyxo, and arabino series can be converted into the corresponding Dispoke- and CDA-blocked derivatives 5 and 6. [3,10,11] How-... 

This chemistry has gained rapid acceptance and variants based on cyclohex-anediacetals (CDA derivatives) and dispiroketals ( dispoke ) have been applied to efficient syntheses of oligosaccharides [86]. 

In a typical experiment, the carbohydrate derivative was reacted with TMC 2 in boiling methanol containing some trimethylorthoformate and a catalytic amount of camphorsulfonic acid. In all cases the corresponding CDA, often highly crystalline, were formed as the major product. Table 1 summarizes selected examples of CDA formation in comparison with the related dispoke protection. 

The efficiency of the CDA or dispoke strategies was, however, hampered by the lack of regioselection in D-gluco derivatives, owing to the presence of two 1,2-trans... 

Cyclitols and symmetrical acyclic polyols have been desymmetrized by fonnation of dispoke adducts such as myo-inositol derivative 7. ... 

Various cyclitols (and acyclic polyols) have been desynunetrized by formation of dispoke intermediates. (See for example, Vol. 28, p. 237, ref. 115). L-Chiro-inositol can be converted to the silyl derivative 67 in which the trans-diol units are protected on reaction with l,3-dichloro-l,l,3,3-tetraisopropylidisiloxane (TipsQ). Compound 67 was further converted into conduritol B epoxide and its thioepoxide analogue. The conversion of some tetra-O-substituted myo-inosi-tols into adipic dialdehyde derivatives is mentioned in Chapter IS. 

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