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 o f tri-O-benzyl-D-glucal under various conditions has been compared to that of substituted dihydropyrans 2-5. IN3 addition in acetonitrile affords tran s-alpha -iodoazides (80-87%), besides small amounts of trans-beta -adducts, in the presence or the absence of benzyloxy substituents at C-3 or C-4, an d in agreement with bridged iodonium ion intermediates. In contrast, the di astereofacial selectivity of bromine addition in dichloroethane going throu gh open bromo oxacarbenium ions depends strongly on the substituents. Where as the trans-alpha -dibromides are the main (85-95%) adducts in the absence of C-4 and C-5 substituents, in their presence a moderate to exclusive sel ectivity for cis-alpha -addition (60-99%) is observed. The predominance of trans-alpha -addition is again observed whatever the substituents when the bromination is carried out in the same solvent but with a tribromide ion sa lt, supporting a concerted addition of the two bromine atoms under these co nditions. Finally, bromine addition in methanol exhibits a completely diffe rent behavior with the nonselective formation of trans-alpha- and trans-bet a -methoxybromides and a small dependence on the substituents. In agreement with the absence of azide trapping of any cationic intermediate, it is con cluded that these brominations which do not go through an ionic intermediat e are concerted additions of bromine and methanol with very loose rate- and product-determining transition states. Finally, the substituent conformati on at C-4 influences drastically the stereoselectivity in all these bromina tions. Evidence for alpha -anomeric control of the nucleophile approach at C-4 is given by the highly predominant formation of alpha -adducts, except in the methanolic bromination. The factors determining the versatile select ivity of the electrophile approach are discussed in terms of PPFMO theory a nd of the special mechanisms of glycal reactions.