The intramolecular reductive coupling of a series of simple or polyoxygenated oxime ethers δ-or -functionalized with bromide, R, -unsaturated ester, aldehyde, or ketone groups is reported. The cyclization of a nitrile-tethered aldehyde is also studied. These reductive couplings are promoted by tributyltin hydride or samarium diiodide. The reactions proceed under mild conditions, in good chemical yield, and with high stereoselectivity. When applied to highly functionalized substrates derived from carbohydrates, this approach provides a selective entry to enantiomerically pure aminocyclitols of varying regio-and stereochemistry. In particular, the reductive coupling reaction of carbonyl-tethered oxime ethers promoted by samarium diiodide can be performed in a one-pot sequence, following a Swern oxidation step, allowing the direct transformation of hydroxyl-tethered oxime ethers into the corresponding aminocyclitols. Moreover, the resultant O-benzylhydroxylamine products of these cyclizations can be further reduced in situ with excess samarium diiodide, in the presence of water, to the corresponding amino alcohols in excellent yields. Some transformations of these compounds are discussed.

In our current work on the tributyltin hydride 1 -mediated cycloisomerizations of conveniently functionalized O-alkyl oxime ethers derived from carbohydrates, we were usually confronted with the necessary transformation of the resulting O-alkylhydroxylamines into the corresponding free amino derivatives. A detailed survey of the methods currently available for effecting this N-O bond cleavage 2 in our polyfunctionalized substrates proved in some cases inappropriate and, in practice, resulted in low yielding processes. 3,4 Obviously, a new and milder method was desired in order to overcome these unexpected difficulties.Although samarium diiodide is known to promote some N-O reductive cleavage reactions, 5 to our knowledge this reagent has never been exploited for the chemoselective reduction of O-alkylhydroxylamines to amines. We have recently shown 6 that samarium diiodide is a convenient and efficient reagent for effecting this particular transformation in densely functionalized aminocyclopentitols such as 3 6a and 5. 6b A recent report from Keck's laboratory describing a similar process using samarium diiodide 7 prompted us to report here in full our experimental conditions for the synthesis of amines from O-alkylhydroxylamines. Additional examples (compounds 1, 8 2, 6a and 4 8 ) have been included in order to test the scope and extent of the new methodology. For the sake of simplicity, only the corresponding free or N-acetylated Obenzylhydroxylamines have been studied, but in principle these conditions can be easily applied to other Oalkylhydroxylamines or O-alkylhydroxamic acids. 7 General and reliable conditions (see Experimental Section) were found for the successful implementation of the desired transformation. The results are shown in Table 1. These results deserve some comments. All reductions have been performed at room temperature either by adding the substrate to samarium diiodide in THF or by reverse addition, with no significant change in chemical yield. The reductive cleavage is strongly accelerated in the presence of a proton source. Water (20-25 equiv with respect to substrate) has proven to be most effective. 9,10 Compounds with free hydroxyl groups (e.g., 4 and 5) are reduced reasonably fast in the absence of added water, except if the hydroxyl group is tertiary (as in 1) or hindered (as in 4 11 ). The reduced products derived from 3-5 have been transformed in situ into the corresponding acetamides to ease isolation and characterization. Due to the highly functionalized nature of our precursors, we had the opportunity to test the stability of different functional groups to the reaction conditions: esters, acetals, silyl 12 or benzyl ethers, double bonds, and vinylstannylidene functions remain unaltered and the hydroxyl groups do not need to be protected. Finally, it is also important to emphasize the very simple workup manipulation required for the isolation of the final products. Tetrahedron Lett. 1995, 36, 7419. (8) The synthesis of these compounds will be reported elsewhere.(9) For pr...

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The synthesis of compounds 6-8, derived from 2,3:5,6-bis-O-isopropylidene-D-mannofuranose (3), and the preparation of products 16 and 17, obtained from 2,3-O-isopropylidene-D-ribose (13) is reported. The first free radical cyclization of enantiomerically pure alkyne-tethered oxime ethers derived from carbohydrates (6, 8, 16, and 17) is described. These radical precursors have been submitted to cyclization with tributyl or triphenyltin hydride plus triethylborane to yield, after ring closure, the aminocyclopentitols 9-12 and 18-20, respectively. These carbocycles have been obtained as mixtures of Z and E vinyltin isomers, but with excellent diastereoselection at the new stereocenter formed during the ring closure. After protodestannylation, only one diastereoisomer was detected and isolated. The absolute configuration at the new stereocenter formed during the carbocyclization has been established by detailed 1 H NMR analysis. The specific transformation of compound 19 (or 20) into aminocyclitol 24 is described. Compound 24 is an analogue of the aminocyclopentitol moiety of trehazolin (1a), a known and powerful glycosidase inhibitor of trehalase. From these results, we can conclude that a new method for the asymmetric synthesis of aminocyclitols of biological interest is now available.

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