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F.C. Moraes et al. / Journal of Molecular Structure 1164 (2018) 109e115
0
2. Experimental section
(1H, d, J8 ,8 ¼ 11.1 Hz, H8); 2.44 (1H, dd, J7a,3a ¼ 8.1 Hz, H3a); 2.56
(1H, m, H4); 2.71 (2H, d, J7a,7 ¼ 8.1 Hz, H7a and OH); 2.88 (1H, m,
H7); 3.16 (1H, m, H5); 3.23 (1H, m, H6); 3.63 (1H, dd, J9,9’ ¼ 12.3 and
2.1. General
J9 ,3 ¼ 3.3 Hz, H90); 3.85 (1H, dd, J9 ,9 ¼ 12.3, and J9,3 ¼ 3.0 Hz, H9);
4.21 (1H, q, J3,7a ¼ 2.2 and J9,3 ¼ 3.0 Hz, H3).
0
0
Reagents and solvents were obtained from commercial sources
and were purified according to standard procedures when neces-
sary. (S)-5-Hydroxymethylfuran-2(5H)-one (6) [24], endo (7) and
exo (8) [25] were prepared as previously described in the literature.
The progress of the reactions was monitored by silica gel thin layer
chromatography (TLC). The TLC plates were visualized in a UV
chamber [26] prior to staining the spots by chemical means. Col-
umn chromatography was carried out on silica gel (60e230 mesh).
Melting points were determined on a MQAPF- 301 melting point
apparatus and are uncorrected. IR spectra were acquired in a Varian
660-IR spectrometer (equipped with GladiATR) using thin film
solid method. NMR experiments were performed on a Varian
Mercury 300 spectrometer with CDCl3 as solvent. The chemical
shifts were referenced to CDCl3 (d 77.0 for 13C NMR) and residual
CHCl3 (7.26 for 1H NMR). Optical rotations were measured using
Bellingham Stanley digital polarimeter ADP 220 at 22 ꢀC and
angular range from ꢁ255ꢀ to 255ꢀ. High Resolution Mass Spectra
(HRMS) were obtained on a MicrOTOF II (Bruker Daltonics) in-
strument wtih Electron Spray Ionization (ESI) in the positive ion
mode.
13C NMR (75 MHz, CDCl3) d 21.8 (C8); 41.5 (C3a); 41.6 (C7); 42.5
(C4); 47.0 (C7a); 50.5 (C5); 50.9 (C6); 64.2 (C9); 84.0 (C3); 177.5
(C8).
IR (thin film solid, cmꢁ1): 3412, 3038, 2956, 2885, 2161, 1730,
1458, 1366, 1295, 1196, 1002, 909, 844, 789, 552, 478.
EM m/z (%): 165 (32); 105 (11); 91 (24); 83 (26); 82 (61); 81
(100); 80 (10); 79 (64); 77 (36); 67(10); 66 (12); 65 (12); 55 (23); 54
(19); 53 (31); 51 (18); 41 (31); 40 (10).
[
a
]
¼ ꢁ1.94.
D
m.p.: 98.8e100.2 ꢀC
HRMS m/z C10H13O4 (M þ H)þ calcd 197.0808, found 197.0806.
2.2. Computational
Step 1: The conformational search was performed for all
candidate structures en1-en4 and ex1-ex4 in the gas phase using
MMFF force field and Monte-Carlo procedure which was set by
specifying the maximum number of conformers examined equal to
1000. For the candidate structures en1, en2, en3, and en4, the
number of conformers found was 6, 6, 6, and 5, respectively. For the
candidate structures ex1, ex2, ex3, and ex4, the number of con-
formers found was 6, 7, 6, and 6 conformers, respectively. All con-
formers were subjected to the DP4 and MAE analyses
[17e19,27,28].
Synthesis of (1aR,2R,2aR,5S,5aS,6S,6aS)-5-(hydroxymethyl)
hexahydro-2,6-methanooxireno [2,3-f]isobenzofuran-3(1aH)-one
(9)
To a sealed tube were added the endo adduct 7 of the Diels-
Alder (0.200 g, 1.1 mmol) reaction and m-chloroperbenzoic acid
(1.5 eq) dissolved in dichloromethane (10 mL). The reaction
mixture was kept under stirring at 50 ꢀC for 4 h until all the starting
material was consumed. Subsequently, 10 mL of 20% Na2SO3 solu-
tion was added to the reaction mixture, and extracted with
dichloromethane (3 ꢂ 10 mL). The organic extracts were combined
and the organic phase was washed with 10% Na2CO3 solution
(2 ꢂ 10 mL) and dried with anhydrous MgSO4. After evaporation of
the solvent under reduced pressure the residue was purified by
silica gel column chromatography using hexane/ethyl acetate 2:1
(v/v) to afford the title compound in 65% yield (0.142 g).
2.3. DP4 analysis
Step 2: Each of these conformers of en1, en2, en3, en4, ex1, ex2,
ex3, and ex4 (Step 1) were subjected to NMR shielding tensor cal-
culations at B3LYP/6-31G(d,p) level of theory using Gaussian 09
[29].
Step 3: The resulting set of Boltzmann-weighted tensor values
were converted to chemical shifts by subtracting the shielding
tensor value of tetramethylsilane (TMS) at this level of theory.
Step 4: DP4 analysis was accomplished by inputting computed
and experimental chemical shifts into the DP4 analysis tool (located
1H NMR (300 MHz, CDCl3) 0.91 (1H, m, J 8 ,4 ¼ 0.6, J 8 ,7 ¼ 0.9 and
J8,8’ ¼ 10.2 Hz, H80); 1.51 (1H, dt, J8,7 ¼ 1.8 and J8,8’ ¼ 10.2 Hz, H8);
2.70 (1H, m, H4); 2.79 (1H, ddd, J4,3a ¼ 3.0, J3,3a ¼ 4.5 and
J3a,7a ¼ 10.2 Hz, H3a); 2.89 (1H, m, H7); 3.11 (1H, dd, J7a,7 ¼ 5.4 and
J3a,7a ¼ 10.2 Hz, H7a); 3.26 (1H, m, H5); 3.29 (1H, m, H6); 3.56 (1H,
0
0
2.4. MAE analysis
dd, J9,9’ ¼ 12.3 and J9 ,3 ¼ 3.6 Hz, H90); 3.81 (1H, dd, J9,9’ ¼ 12.3 and
0
0
J9,3 ¼ 2.8 Hz, H 9); 4.50 (1H, ddd, J3,9 ¼ 2.8, J9 ,3 ¼ 3.6, J3,3a ¼ 4.5 Hz,
Step 5: Each of these conformers of en1, en2, en3, en4, ex1, ex2,
ex3, and ex4 (Step 1) were subjected to geometry optimization and
frequency calculation at M06-2x/6-31 þ G(d,p) level of theory in
Gaussian 09.
Step 6: NMR shielding tensor values were computed for each
optimized conformer with B3LYP functional and 6-311 þ G(2d,p)
basis set in Gaussian 09.
H3).
13C NMR (75 MHz, CDCl3) 28.9 (C8); 39.0 (C7); 39.5 (C4); 43.9
(C3a); 46.7 (C7a); 47.6 (C5); 48.5 (C6); 64.7 (C9); 79.7 (C3); 177.1
(C1).
IR (thin film solid, cmꢁ1): 3466, 3319, 2981, 2163, 1737, 1455,
1353, 1180, 1012, 968, 842, 642, 510.
EM m/z (%): 165 (32); 105 (11); 91 (24); 83 (26); 82 (61); 81
(100); 80 (10); 79 (64); 77 (36); 66 (12); 55 (23); 54 (19); 53 (31); 51
(18); 41 (31); 40 (10).
Step 7: The computed shielding tensors for each nucleus were
Boltzmann-weighted and then converted to empirically scaled
chemical shift values for each nucleus for en1, en2, en3, en4, ex1,
ex2, ex3, and ex4. Regression analysis parameters were used to
scale and reference 1H and 13C NMR chemical shifts [30]. The
experimental data sets of epoxide 9 and 10 were compared with
their respective calculated data sets: (en1, en2, en3, and en4) and
(ex1, ex2, ex3, and ex4). Then the mean absolute error values were
calculated.
[a
]
¼ ꢁ18.87.
D
m.p.: 87.2e87.7 ꢀC
HRMS m/z C10H13O4 (M þ H)þ calcd 197.0808, found 197.0812.
Synthesis of (1aS,2S,2aR,5S,5aS,6R,6aR)-5-(hydroxymethyl)
hexahydro-2,6-methanooxireno [2,3-f]isobenzofuran-3(1aH)-one
(10)
The epoxide 10 was obtained in 88% yield (0.070 g) from the exo
adduct 8 (0.100 g, 0.55 mmol) using the same procedures employed
to prepare epoxide 9.
3. Results and discussions
1H NMR (300 MHz, CDCl3) 0.87 (1H, d, J8,8’ ¼ 11.4 Hz, H80); 1.40
D-mannitol was acetalated following a methodology described