Characterization of the low energy conformations and differential reactivities of d-glucose and d-mannose based oxepines

Abstract

Low energy conformations of two carbohydrate-based oxepines were characterized by computational methods and 3JH,H coupling constant analysis. Oxepine reactivity in Ferrier reactions was correlated with percentage vinylogous anomeric effect (VAE).

Characterization and Fate of a Septanosyl Ferrier Cation in the Gas and Solution Phases

“…Initial reactions of 8 with benzyl alcohol in the presence of Lewis acids (i.e., FeCl 3 and BF 3 •OEt 2 ) gave intractable product mixtures. On the other hand, HFIP septanoside 9 and septanose acetate 14 were prepared in modest yields (39 and 26%, respectively) 13 under less common conditions. 39,40 We then turned to a palladium- proved to be unstable in our hands; we were, however, able to conduct an explicit experiment to isolate it (12% BRSM) 41 and collect NMR spectra used in its structural assignment.…”

“…Irradiation of the chemical shift region shared by signals for H6 and H7 (δ 4.02 ppm) identified the spin system corresponding to H4 through H7 and enabled the assignment of H5 (Figure 7b). In light of that assignment, and with regard to the likely preference for the 5 H O conformation 13 of the compound, it was clear that it was H1 that overlapped with H5 in the NOE experiments (Figure 7c). Based on this NOE and the known configuration of C5, we assigned the product as the α-anomer, compound 18.…”

“…Furthermore, the selective formation of the αanomer was consistent with a similar kinetic trap experiment where D-glucal was used as the starting material and the αconfigured C-allyl glucoside was isolated as a product. Concomitant with the results of the kinetic trap experiment, 13 C{ 1 H} NMR spectra were collected in superacid media in conjunction with density functional theory calculations and used to characterize a protonated oxocarbenium ion exhibiting a β-face that was significantly hindered by the C6 acetoxymethyl group. 19 Looking at the calculated structures of oxocarbenium ion conformers, the C4_C3_NGP I and the oxocarbenium "sandwich" species XI should be quite similar; an attack on either of them should favor the α-face because it minimizes transannular interactions between the ring and the nucleophile (Figure S6).…”

“…Synthesized using Method A. R f 0.61 (40% EtOAc/ Hex). Spectroscopic data for compound 15: 1 H NMR (400 MHz, CDCl 3 ): δ ppm 7.41−7.24 (m, 5H), 5.88 (ddd, J = 12.1, 5.9, 1.5 Hz, 1H), 5.73 (dd, J = 12.1, 2.2 Hz, 1H), 5.38 (dd, J = 1.9, 1,9 Hz, 1H), 5.25 (dd, J = 5.9, 4.2 Hz, 1H), 5.21−5.04 (m, 1H), 4.87 (d, J = 12.0 Hz, 1H), 4.59 (d, J = 11.9 Hz, 1H), 4.35 (ddd, J = 9.4, 5.8, 2.9 Hz, 1H), 4.21 (dd, J = 11.9, 5.7 Hz, 1H), 4.15 (dd, J = 12.1, 2.9 Hz, 1H), 2.06 (s, 3H), 2.05 (s, 3H), 2.01 (s, 3H); 13 2-(2,3,5-tri-O-acetyl-D-arabino-pentofuranosyl)-acetaldehyde (17). Synthesized using Method A using 69.3 mg (0.201 mmol) of 8.…”

“…Minor isomer (R): 1 H NMR (400 MHz, CDCl 3 ): δ 9.77 (dd, J = 2.0, 1.5 Hz, 0H), 5.15 (dd, J = 2.7, 2.7 Hz, 1H), 5.05 (dd, J = 3.9, 2.4 Hz, 1H), 4.60−4.53 (m, 1H), 4.29−4.21 (m, 3H), 2.74 (dd, J = 5.8, 1.0 Hz, 1H), 2.70 (dd, J = 5.7, 1.0 Hz, 1H), 2.12 (s, 3H), 2.11 (s, 3H), 2.10 (s, 3H). ; 13 3-(4,5,7-tri-O-acetyl-2,3-dideoxy-α-D-arabino-2-enoseptanosyl)-1-propene (18). To a 10 mL round-bottom flask was added oxepine 8 (23.9 mg, 0.0694 mmol), and the sample was dried by azeotropic distillation from toluene (3 × 2 mL).…”