Furanoid glycals, cycloaddition

Dihydrooxadiazines can be made in related fashion and they too offer novel access to important products. For example, the (9-silylated D-glucal 70, irradiated at 350 nm in cyclohexane with dibenzyl azodicarboxylate, affords adduct 74 in 71% yield,74 and this with an acid catalyst can be used as a glycosylating agent to make /J-linked 2-amino-2-deoxy-D-glucosides.75 This chemistry also is applicable to furanoid glycals.74 Scheme 6 outlines the regio- and stereoselectivities of these cycloaddition reactions and their applications in synthetically useful processes. 

By the cycloaddition of dibenzyl diazenedicarboxylate and furanoid and pyranoid glycals it is possible to diastereoselectively introduce an amino function at the C-2 position of a carbohydrate29-34. A single diastereomer is produced from furanoid glycals, where the cycloaddition takes place trans to the C-3 hydroxy substituent protected as the silyl ether, e.g., formation of 14-1630. The more reactive bis(2,2,2-trichloroethyl) diazenedicarboxylate can be employed even with less reactive 3-acetyl glycals31. 

This is illustrated in Scheme 12 by the example of the synthesis of p-lactam 28.Until now 14 structures derived from dihydro-2H-pyrans and glycals were obtained, and are shown in Scheme 13. The same procedure could be applied to the cycloaddition of trichloroacetyl isocyanate to the furanoid glycal 29.The reaction proceeded with the same high stereoselectivity to produce [2+2] and [4+2]cycloadducts having the a-D-gluco configuration (Scheme 14). J Deprotection led to the formation of stable compound 30. 

For this study, the commercially available triacetyl D-glucal (17) (Table II) was the first substrate subjected to the cycloaddition conditions. Unfortunately, under the conditions used for furanoid glycals, the cycloaddition did not take place. However, when the reaction was carried out at 90 C a 3/2 diastereomeric mixture of adducts 27 was obtained in low yield. Since dihydropyran was found to be a good substrate in the cycloaddition reaction under irradiation, this suggested that the low reactivity of triacetyl D-glucal was due to the acetoxy groups on the ring. 

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. 

Amino glycosides.1 Furanoid or pyranoid glycals (2) when irradiated with this azodicarboxylate undergo a [4 + 2]cycloaddition to form a dihydrooxadiazine (3) in 70-80% yield. The adducts on treatment with methanol (TsOH) open with inversion at C, to give hydrazines (4), which furnish 2-amino glycosides (5) on hydrogenolysis and deprotection. 

The [4+2] cycloaddition reaction of furanoid and pyranoid glycals with azodicarboxylates allows the introduction of a nitrogen atom at C-2 of a carbohydrate, and the adducts thus obtained can be converted to structurally complex 2-amino saccharides under mild conditions. Towards this end, dibenzyl and bis(2,2,2-trichloroethyl) azodicarboxylates were used as dienes since they allow the free amines to be generated in a single operation under mild conditions later in the synthetic sequence. 

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