l a -Fig. . Crystal structure of 2a [3, Prim cyclization. Subsequent pinacol rearrangement provides 5.[51 Desilylation and cyclization affords the tetrahydrofuran 6, whose labile glycosidic bond is cleaved by trimethylsilyl iodide to give the cyclic oxonium ion 8. Unreacted glycoside 6 adds to 8 to form dimer 9, which eliminates benzyl iodide giving 2 a. The overall yield is roughly 50 YO, which indicates an average yield of 91 % for each step. 3 5 6 4 -Me3SiOBn I-7 8 9 Scheme 2. Mechanism for the formation of 2a
In this sequence the stereogenic center at C, controls the configurations at C,, C,, and C,. Conformations 3 and 10 are the possible transition states for the Prins cyclization (Scheme 3). Conformation 3 is clearly preferred, since the side chain at C, is equatorial. This explains the formation of 4. The pinacol rearrangement proceeds suprafacially, and 3 4 5 10 11 12 Scheme 3. Intermediates in the formation of the glycoside. thus only 5 is formed from 4. Starting from 10, an analogous sequence would generate 12, which cannot form a second ring due to the trans arrangement of the necessary appendages.[61 Finally, the stereogenic center at C, is formed by attack of 6 at the less hindered, convex face['] of the bicyclo[3.3.0]octane structure 8. According to our proposed mechanism, the geometry of the double bond in 1 reappears in the A ring in 2. The rearrangements of 1 a-2a ( E olefin) and lc-2c (2 olefin) do confirm this.
Within the limits of HPLC detection ( + S o / , ) the rearrangements are stereoselective. Their preparative value lies in the synthesis of complex bis(furan0sides) from simple precursors. At present we are investigating the formation of cross-coupled bis(furanosides) from mixtures of unlike enetriols 1.
Experimental Procedure l a (l.OOg, 3.6mmol) in CH,CI, (2 mL) was stirred at 0Β°C with Me,SiI (0.57 mL, 4.0 mmol, 1.1 mol equiv). After 5 min the reaction was quenched with MeOH, and stirred for approximately 15 hover solid Na,S,O,. The mixture was concentrated under vacuum and diluted with ether. The organic phase was washed several times with water and dried over Na,SO,, and the solvent was removed under vaccum. Preparative column chromatography (silica gel, hexane/ethyl acetate 5:l) gave 2a (310mg, 24%) as colorless crystals, m.p. 134Β°C.