Glycals polar additions

The polarized-TT frontier molecular orbital (PPFMO) method has been employed to study protonation and sulphenylation of sugar-related dihydrofurans and tetrahydropy-rans. The predictions are consonant with the experimental observations62. Contrary to expectations, the proton-catalysed addition of alcohols to glycals, such as 30, has been shown by isotope labelling (2H) not to be anii-diaxial addition. This observation has been rationalized by the initial attack by deuteron from the bottom, giving ion 31, and by the anomeric effect favouring axial substituent at C-l (32)63. 

The addition of chloro azide CIN3 on the double bond of glycals proceeds by either an ionic or a radical mechanism depending on experimental conditions. Under UV irradiation, in solvents of low polarity and in the absence of oxygen, radical addition is predominantly regio- and stereoselective [51, 52]. The double bond reactivity is affected by the substituent at C-3 position and its inductive effect. Therefore, the presence of acetates lowers the reactivity, but azidosides are formed following Scheme 25. 

The mechanism of glycal addition was further examined by Horton and coworkers,86 who have used this method to form (7S,9S)-4-demethoxy-7-0-(2,6-dideoxy-2-iodo-a-L-mannopyranosyl)-adriamycinone87 and -daunomycinone,88 which are iodinated analogs of natural antitumor compounds. The nature of the solvent was found to be critical. In particular, they were able to generalize that in non-coordinating polar solvents, where no possibility for interaction with iodine exists—that is, no lone-pair interactions—the formation of the iodonium intermediate was irreversible, and the resultant stereochemistry reflects the electronic... 

The cis addition of nitrosyl chloride to substituted cyclic enol ethers and O-protected glycals, rationalized as either molecular addition through a four-centered polar transition state or by radical mechanism, generally takes place with complete simple and induced diastereose-lectivity45-47. 

Unlike the carbohydrates with double bonds at positions other than between C-1 and C-2 ( isolated alkenes ), which exhibit normal alkene chemistry, glycals are vinyl ethers and therefore undergo a number of highly selective addition reactions due to the strongly polarized double bonds and the presence of bulky substituents at the C-3 allylic centers. Straightforward addition reaction includes initial electrophilic addition at the double bond, followed by the addition of a nucleophile at C-1 to give the 1,2-trans adduct (O Scheme 19). 

Addition of phenylselenyl azide to glycals under free radicai conditions [PhSeSeHi, NaNs, (AcO)2lPh] leads to phenyl 2-azido-2-deoxy-l-seleno-glycosides (Vol. 27, p.l32). Further examples have now been published, and the use of the products as glycosyl donors investigated. Notably, however, under polar reaction conditions, 2-phenylselenyl-2-deoxy-glycosyl azides can be formed, as exemplified in Scheme 12. ... 

A paper on the use of polarized n frontier orbital theory for correctly predicting the selectivities of protonation and sulfenylation of pyranoid and furanoid glycals has appeared. The cycloaddition adducts formed by the high pressure addition of tosyl isocyanate to glycal acetates (see Chmielewski et al.y Vol. 19, p. 131) have been shown to revert on heating to 60 -70 . The rate of retro-addition increases with rising temperatures and increasing solvent polarity. 

---