Substituent Dependence of the Diastereofacial Selectivity in Iodination and Bromination of Glycals and Related Cyclic Enol Ethers

The stereochemical course of the electrophilic iodination and bromination of tri-O-benzyl-d-glucal under various conditions has been compared to that of substituted dihydropyrans 2−5. IN3 addition in acetonitrile affords trans-α-iodoazides (80−87%), besides small amounts of trans-β-adducts, in the presence or the absence of benzyloxy substituents at C-3 or C-4, and in agreement with bridged iodonium ion intermediates. In contrast, the diastereofacial selectivity of bromine addition in dichloroethane going through open bromo oxocarbenium ions depends strongly on the substituents. Whereas the trans-α-dibromides are the main (85−95%) adducts in the absence of C-4 and C-5 substituents, in their presence a moderate to exclusive selectivity for cis-α-addition (60−99%) is observed. The predominance of trans-α-addition is again observed whatever the substituents when the bromination is carried out in the same solvent but with a tribromide ion salt, supporting a concerted addition of the two bromine atoms under these conditions. Finally, bromine addition in methanol exhibits a completely different behavior with the nonselective formation of trans-α- and trans-β-methoxybromides and a small dependence on the substituents. In agreement with the absence of azide trapping of any cationic intermediate, it is concluded that these brominations which do not go through an ionic intermediate are concerted additions of bromine and methanol with very loose rate- and product-determining transition states. Finally, the substituent conformation at C-4 influences drastically the stereoselectivity in all these brominations. Evidence for α-anomeric control of the nucleophile approach at C-1 is given by the highly predominant formation of α-adducts, except in the methanolic bromination. The factors determining the versatile selectivity of the electrophile approach are discussed in terms of PPFMO theory and of the special mechanisms of glycal reactions.