Synthesis of chiral 2-furyl and 3-nitro-7-oxabicyclo[2.2.1]heptane derivatives from sugars

“On water” reactivity between carbohydrate-derived nitroalkenes and furans

“…10a: 1 H-NMR (CDCl 3 , 500 MHz) δ: 8.11 (s, 1H, OCHO), 6.12 (d, 1H, J 3′,4′ = 3.0 Hz, H-3′), 5.94 (m, 1H, J 4′,CH 3 < 1.0 Hz, H-4′), 5.42 (dd, 1H, J 2,3 = 3.0 Hz, J 3,4 = 8.5 Hz, H-3), 5.12 (ddd, 1H, H-4), 4.71 (dd, 1H, J 1a,2 = 7.0 Hz, J 1a,1b = 13.5 Hz, H-1a), 4.67 (dd, 1H, J 1b,2 = 8.5 Hz, H-1b), 4.24 (dd, 1H, J 4,5a = 2.5 Hz, J 5a,5b = 12.5 Hz, H-5a), 4.16 (dd, 1H, J 4,5b = 4.5 Hz, H-5b), 4.08 (ddd, 1H, H-2), 2.26 (s, 3H, CH 3 -5′), 2.13 (s, 3H, OCOCH 3 ), 2.07 (s, 3H, OCOCH 3 ). 13 16 To a solution of (E)-3,4,5,6,7-penta-O-acetyl-D-manno-1-nitrohept-1-enitol 20 8 (0.50 g, 1.15 mmol) in 2-methylfuran 9 (1.0 mL, 11.16 mmol) distilled water was added (3.0 mL) and the mixture was subjected to vigorous magnetic stirring. After 6.5 days, 1 H-NMR showed completion of the reaction and the crude mixture was treated with brine (5 mL) and extracted with dichloromethane (3 × 5 mL).…”

“…With respect to the stereochemistry of the reaction, the R configuration at C-2 in 3 was assigned by an analogy between the 1 H-NMR signals of its diastereotopic nitromethylene protons with those of the same group in compounds of similar structures. 16 When the above reaction was carried out under "on water" conditions, but using a wrist-action shaker, the starting material disappeared after 2 days and, by acetylation of the resulting crude product, cyclic nitroalkene 5 (Scheme 2) was obtained. It was noteworthy that the 1 H-NMR spectrum showed that 5 was the major compound in the mixture before acetylation (with 3 and 4 also present); thus, this latter process showed that 5 was the only product.…”

“…A fraction of this mixture (0.1 g) was acetylated with acetic anhydride and pyridine, thus resulting in 0.08 g of compound 12 as the only detected product. 16 To a solution of (E)-3,4,5,6,7-penta-O-acetyl-D-manno-1-nitrohept-1-enitol 20 8 (0.50 g, 1.15 mmol) in 2-methylfuran 9 (1.0 mL, 11.16 mmol) distilled water was added (3.0 mL) and the mixture was subjected to vigorous magnetic stirring. After 6.5 days, 1 H-NMR showed completion of the reaction and the crude mixture was treated with brine (5 mL) and extracted with dichloromethane (3 × 5 mL).…”

“…In addition, to test the "on water" methodology using a solid nitroalkene, the mixture of crystalline 8 20 and 9 was subjected to vigorous magnetic stirring; thus, the reaction was completed after 6.5 days, leading to a 1.7 : 1.0 mixture of 10b and 11b. We had synthesized 16 this same Michael adducts through a ringopening reaction from 7-oxabicyclic compounds prepared by ultra-high pressure Diels-Alder cycloaddition between 2-methylfuran 9 and nitroalkene 8. It is noteworthy that the formation of such compounds, which had not been detected in our "on water" reactions, required conditions of 13 000 kbar for 3 days.…”

“…It is worth noting that, as far as we are aware, there were no previous reports on reactions describing the formation of new carbon bonds on C-3 of 2-nitroglycals. Until now, it should be considered that there are only two general routes for the synthesis of furyl derivatives from carbohydrates: the first is based on treating simple derivatives of furan activated with the corresponding acceptors (such as 2-and 3-furyllitium with aldehydes 14 or 2-nitroglycals 12c ), and the second is based on the use of acid catalysis 15 or high pressure to prepare heterocyclic rings from cyclic 16 or acyclic precursors. 17…”