organic compounds
(2R,4S,5S)-5-Methoxy-4-methyl-3-oxohept-6-en-2-yl benzoate
aFakultät für Chemie und Chemische Biologie, Technische Universität Dortmund, Organische Chemie, 44227 Dortmund, Germany
*Correspondence e-mail: lyuba.iovkova@tu-dortmund.de
The title compound, C16H20O4, was synthesized in the course of the total synthesis of fusaequisin A in order to verify and confirm the configurations of the stereogenic centers and to exclude the possibility of during the methylation process. The of the title compound at 100 K has orthorhombic (P212121) symmetry. The was determined by and agrees with the configuration of the allylic alcohol used in the synthesis.
Keywords: crystal structure; methylation; epimerization; structural elucidation.
CCDC reference: 2109383
Structure description
The title compound, C16H20O4 (Fig. 1), was obtained during the synthesis of the Western fragment of fusaequisin A. Background to fusaequisin A is given by Shiono et al. (2013). The of the Western fragment is based on Paterson's anti aldol chemistry (Paterson et al., 1994; Paterson, 1998). In the course of the total synthesis of curvicollide C (Che et al., 2004) the precursor of the title compound (I) was prepared (von Kiedrowski et al., 2017) and provided potential for further investigations regarding the total synthesis of fusaequisin A. The methylation process is shown in Fig. 2.
The title compound crystallizes in the orthorhombic P212121 with four molecules in the with H1A and H3A almost in plane (H1A—C1⋯C3—H3A pseudo torsion angle = −1°) and H2A and H3A in an antiperiplanar arrangement (H2A—C2—C3—H3A = 179°), which minimizes 1,3-allylic strain. Furthermore, the C8 methyl group and the O1 atom of the ether group are also in an antiperiplanar arrangement with a C8—C4—C3—O1 torsion angle of 177.32 (10)°. The ester moiety shows the most stable and expected s–cis-conformation. In the crystal, a weak C—H⋯O interaction arising from the aromatic C—H grouping para to the side chain links the molecules into C(10) chains propagating in the [010] direction (Table 1).
Synthesis and crystallization
The reaction (Fig. 3) was carried out under an argon atmosphere. To an ice-cooled solution of the allylic alcohol (C15H18O4, 262.31 g mol−1, 300 mg, 1.10 mmol, 1 equiv.) in CH2Cl2 were successively added dried (0.1 mbar, 250°C, 2 h) 3 Å molecular sieves (200 mg), 1,8-bis(dimethylamino)naphthalene (proton sponge®, C14H18N2, 214.31 g mol−1, 943 mg, 4.40 mmol, 4 equiv.) and trimethyloxonium tetrafluoroborate (Me3OBF4, C3H9BF4O, 147.91 g mol−1, 651 mg, 4.40 mmol, 4 equiv.). The opaque, orange solution was warmed to room temperature. The reaction mixture was stirred at room temperature for 4 h and was then diluted by the addition of aqueous phosphate pH 7 buffer. The phases were separated and the aqueous layer was extracted three times with CH2Cl2. The combined organic layers were dried (MgSO4) and all volatiles were removed under reduced pressure. The light yellow residue was purified by flash (cyclohexane-ethyl acetate, 20:1 to 10:1) to afford the title methyl ether (I) (C16H20O4, 276.33 g mol−1, 238 mg, 0.86 mmol, 78%) as a white solid. Colourless crystals of I suitable for X-ray crystallographic analysis were obtained under air by slow evaporation from the mixed solvents of diethyl ether and n-pentane. Rf = 0.56 (cyclohexane–ethyl acetate, 5:1); m.p. = 80–83°C; [a]D20 = −8.3° (c = 0.5 g ml−1 in CHCl3) ; 1H NMR (500 MHz, CDCl3) δ 1.06 (d, J = 7.1 Hz, 3H, 3-CH3), 1.55 (d, J = 7.0 Hz, 3H, 1-CH3), 2.93 (dq, J = 9.7, 7.1 Hz, 1H, 3-CH), 3.15 (s, 3H, 4-OCH3), 3.70 (dd, J = 10.1, 9.3 Hz, 1H, 4-CH), 5.24–5.35 (m, 2H, 6-CH2), 5.41 (q, J = 7.0 Hz, 1H, 1-CH), 5.56 (ddd, J = 17.1, 10.1, 8.5 Hz, 1H, 5-CH), 7.43–7.48 (m, 2H, aryl-CH), 7.55–7.60 (m, 1H, aryl-CH), 8.05–8.12 (m, 2H, aryl-CH); 13C NMR (126 MHz, CDCl3) δ 14.1 (3-CH3), 15.3 (1-CH3), 47.0 (3-CH), 56.6 (4-OCH3), 75.5 (1-CH), 85.4 (4-CH), 120.2 (6-CH2), 128.5 (aryl-CH), 129.8 (aryl-CH), 129.9 (aryl-CH), 133.3 (aryl-CH), 136.0 (5-CH), 166.0 (aryl-C), 210.1 (2-C); IR ν = 3075 (w), 2985 (w), 2935 (w), 2825 (w), 1720 (s), 1065 (w), 1450 (m), 1420 (w), 1375 (m), 1315 (m), 1265 (s), 1205 (w), 1175 (w), 1115 (s), 1090 (s), 1070 (m), 1025 (m), 1010 (m), 965 (m), 935 (m), 715 (s), 685 (w) cm−1; HRMS (ESI): m/z [M + H]+ calculated for C16H21O4: 277.1434; found: 277.1342.
Refinement
Crystal data, data collection and structure .
details are summarized in Table 2Structural data
CCDC reference: 2109383
https://doi.org/10.1107/S2414314621009512/hb4390sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314621009512/hb4390Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314621009512/hb4390Isup3.cdx
Supporting information file. DOI: https://doi.org/10.1107/S2414314621009512/hb4390Isup4.cml
Data collection: APEX3 (Bruker, 2016); cell
SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT2014/5 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: XP (Sheldrick, 2008); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).C16H20O4 | Dx = 1.215 Mg m−3 |
Mr = 276.32 | Melting point = 353–356 K |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54178 Å |
a = 8.1297 (4) Å | Cell parameters from 9807 reflections |
b = 11.8232 (6) Å | θ = 6.1–74.6° |
c = 15.7213 (9) Å | µ = 0.71 mm−1 |
V = 1511.12 (14) Å3 | T = 100 K |
Z = 4 | Block, colourless |
F(000) = 592 | 0.12 × 0.10 × 0.06 mm |
Bruker APEXII CCD diffractometer | 3054 reflections with I > 2σ(I) |
φ and ω scans | Rint = 0.027 |
Absorption correction: multi-scan (SADABS;Bruker, 2016) | θmax = 74.5°, θmin = 4.7° |
Tmin = 0.700, Tmax = 0.754 | h = −10→10 |
28627 measured reflections | k = −14→14 |
3078 independent reflections | l = −18→19 |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.023 | w = 1/[σ2(Fo2) + (0.0308P)2 + 0.2127P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.060 | (Δ/σ)max < 0.001 |
S = 1.07 | Δρmax = 0.18 e Å−3 |
3078 reflections | Δρmin = −0.12 e Å−3 |
184 parameters | Absolute structure: Flack x determined using 1293 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
0 restraints | Absolute structure parameter: 0.03 (2) |
Primary atom site location: dual |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.09507 (18) | 0.29265 (12) | 0.39623 (10) | 0.0306 (3) | |
H1A | 0.080921 | 0.309404 | 0.337584 | 0.037* | |
H1B | 0.010147 | 0.255322 | 0.426807 | 0.037* | |
O1 | 0.52090 (11) | 0.31350 (8) | 0.40027 (6) | 0.0257 (2) | |
C2 | 0.23199 (17) | 0.32109 (12) | 0.43502 (9) | 0.0260 (3) | |
H2A | 0.241816 | 0.302998 | 0.493680 | 0.031* | |
O2 | 0.57315 (12) | 0.55222 (8) | 0.31396 (6) | 0.0257 (2) | |
C3 | 0.37402 (15) | 0.38013 (10) | 0.39331 (8) | 0.0210 (3) | |
H3A | 0.348192 | 0.392678 | 0.331840 | 0.025* | |
O3 | 0.79670 (11) | 0.67523 (7) | 0.40634 (6) | 0.02254 (19) | |
C4 | 0.41493 (15) | 0.49330 (10) | 0.43492 (8) | 0.0200 (2) | |
H4A | 0.442788 | 0.480340 | 0.496105 | 0.024* | |
O4 | 0.58296 (11) | 0.79534 (7) | 0.39300 (6) | 0.0255 (2) | |
C5 | 0.56184 (15) | 0.54690 (10) | 0.39052 (8) | 0.0195 (2) | |
C6 | 0.69017 (16) | 0.59668 (11) | 0.45003 (8) | 0.0214 (3) | |
H6A | 0.633436 | 0.636762 | 0.497741 | 0.026* | |
C7 | 0.5209 (2) | 0.22018 (12) | 0.34321 (10) | 0.0346 (3) | |
H7A | 0.624899 | 0.178862 | 0.348492 | 0.052* | |
H7B | 0.508591 | 0.247754 | 0.284770 | 0.052* | |
H7C | 0.429206 | 0.169617 | 0.357046 | 0.052* | |
C8 | 0.27180 (16) | 0.57771 (12) | 0.42921 (10) | 0.0279 (3) | |
H8A | 0.180721 | 0.551481 | 0.464968 | 0.042* | |
H8B | 0.234674 | 0.583387 | 0.370058 | 0.042* | |
H8C | 0.308649 | 0.652131 | 0.448962 | 0.042* | |
C9 | 0.80093 (17) | 0.50522 (12) | 0.48637 (10) | 0.0298 (3) | |
H9A | 0.733683 | 0.448423 | 0.515567 | 0.045* | |
H9B | 0.878182 | 0.539103 | 0.526875 | 0.045* | |
H9C | 0.862385 | 0.469110 | 0.440132 | 0.045* | |
C10 | 0.72720 (16) | 0.77408 (10) | 0.38331 (7) | 0.0204 (3) | |
C11 | 0.85150 (16) | 0.85390 (10) | 0.34781 (8) | 0.0206 (3) | |
C12 | 0.79937 (18) | 0.96224 (11) | 0.32518 (8) | 0.0237 (3) | |
H12A | 0.686828 | 0.982661 | 0.330513 | 0.028* | |
C13 | 0.91308 (19) | 1.04000 (11) | 0.29482 (9) | 0.0286 (3) | |
H13A | 0.878073 | 1.114116 | 0.280093 | 0.034* | |
C14 | 1.07716 (19) | 1.01054 (12) | 0.28578 (9) | 0.0303 (3) | |
H14A | 1.153904 | 1.064064 | 0.264420 | 0.036* | |
C15 | 1.12937 (17) | 0.90223 (13) | 0.30810 (9) | 0.0294 (3) | |
H15A | 1.241701 | 0.881748 | 0.301761 | 0.035* | |
C16 | 1.01703 (17) | 0.82427 (11) | 0.33962 (8) | 0.0243 (3) | |
H16A | 1.052798 | 0.750788 | 0.355613 | 0.029* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0290 (7) | 0.0303 (7) | 0.0325 (7) | −0.0065 (6) | 0.0030 (6) | 0.0020 (6) |
O1 | 0.0265 (4) | 0.0206 (4) | 0.0298 (5) | 0.0050 (4) | −0.0010 (4) | −0.0022 (4) |
C2 | 0.0284 (7) | 0.0248 (6) | 0.0249 (6) | −0.0012 (5) | 0.0023 (5) | 0.0032 (5) |
O2 | 0.0317 (5) | 0.0244 (4) | 0.0211 (4) | −0.0027 (4) | 0.0034 (4) | −0.0001 (3) |
C3 | 0.0220 (6) | 0.0199 (6) | 0.0210 (6) | 0.0009 (5) | 0.0000 (5) | 0.0011 (5) |
O3 | 0.0210 (4) | 0.0178 (4) | 0.0289 (5) | −0.0008 (4) | 0.0021 (4) | 0.0021 (4) |
C4 | 0.0197 (5) | 0.0207 (6) | 0.0197 (5) | 0.0004 (5) | 0.0012 (5) | −0.0017 (5) |
O4 | 0.0226 (4) | 0.0211 (4) | 0.0326 (5) | 0.0007 (4) | 0.0033 (4) | −0.0017 (4) |
C5 | 0.0215 (6) | 0.0146 (5) | 0.0224 (6) | 0.0040 (5) | 0.0012 (5) | 0.0001 (5) |
C6 | 0.0210 (6) | 0.0199 (6) | 0.0234 (6) | −0.0018 (5) | 0.0013 (5) | 0.0028 (5) |
C7 | 0.0377 (8) | 0.0236 (6) | 0.0426 (8) | 0.0051 (6) | 0.0039 (7) | −0.0090 (6) |
C8 | 0.0234 (6) | 0.0264 (7) | 0.0339 (7) | 0.0053 (5) | 0.0006 (6) | −0.0059 (5) |
C9 | 0.0233 (6) | 0.0279 (7) | 0.0382 (7) | −0.0005 (6) | −0.0036 (6) | 0.0095 (6) |
C10 | 0.0244 (6) | 0.0174 (5) | 0.0196 (6) | −0.0006 (5) | −0.0008 (5) | −0.0030 (5) |
C11 | 0.0245 (6) | 0.0192 (6) | 0.0180 (6) | −0.0020 (5) | 0.0002 (5) | −0.0034 (5) |
C12 | 0.0277 (7) | 0.0209 (6) | 0.0226 (6) | 0.0005 (5) | 0.0004 (5) | −0.0015 (5) |
C13 | 0.0389 (7) | 0.0214 (6) | 0.0256 (6) | −0.0034 (6) | 0.0022 (6) | 0.0009 (5) |
C14 | 0.0354 (7) | 0.0296 (7) | 0.0260 (6) | −0.0119 (6) | 0.0064 (6) | −0.0015 (5) |
C15 | 0.0252 (7) | 0.0340 (7) | 0.0291 (7) | −0.0038 (6) | 0.0038 (5) | −0.0049 (6) |
C16 | 0.0257 (6) | 0.0236 (6) | 0.0235 (6) | −0.0003 (5) | 0.0003 (5) | −0.0026 (5) |
C1—C2 | 1.313 (2) | C7—H7B | 0.9800 |
C1—H1A | 0.9500 | C7—H7C | 0.9800 |
C1—H1B | 0.9500 | C8—H8A | 0.9800 |
O1—C7 | 1.4220 (17) | C8—H8B | 0.9800 |
O1—C3 | 1.4347 (15) | C8—H8C | 0.9800 |
C2—C3 | 1.5001 (18) | C9—H9A | 0.9800 |
C2—H2A | 0.9500 | C9—H9B | 0.9800 |
O2—C5 | 1.2087 (16) | C9—H9C | 0.9800 |
C3—C4 | 1.5261 (17) | C10—C11 | 1.4911 (18) |
C3—H3A | 1.0000 | C11—C12 | 1.3953 (18) |
O3—C10 | 1.3477 (15) | C11—C16 | 1.3965 (19) |
O3—C6 | 1.4438 (15) | C12—C13 | 1.3883 (19) |
C4—C5 | 1.5215 (17) | C12—H12A | 0.9500 |
C4—C8 | 1.5357 (17) | C13—C14 | 1.386 (2) |
C4—H4A | 1.0000 | C13—H13A | 0.9500 |
O4—C10 | 1.2089 (16) | C14—C15 | 1.394 (2) |
C5—C6 | 1.5199 (17) | C14—H14A | 0.9500 |
C6—C9 | 1.5188 (18) | C15—C16 | 1.389 (2) |
C6—H6A | 1.0000 | C15—H15A | 0.9500 |
C7—H7A | 0.9800 | C16—H16A | 0.9500 |
C2—C1—H1A | 120.0 | H7B—C7—H7C | 109.5 |
C2—C1—H1B | 120.0 | C4—C8—H8A | 109.5 |
H1A—C1—H1B | 120.0 | C4—C8—H8B | 109.5 |
C7—O1—C3 | 112.20 (11) | H8A—C8—H8B | 109.5 |
C1—C2—C3 | 124.65 (12) | C4—C8—H8C | 109.5 |
C1—C2—H2A | 117.7 | H8A—C8—H8C | 109.5 |
C3—C2—H2A | 117.7 | H8B—C8—H8C | 109.5 |
O1—C3—C2 | 110.60 (10) | C6—C9—H9A | 109.5 |
O1—C3—C4 | 105.50 (10) | C6—C9—H9B | 109.5 |
C2—C3—C4 | 112.85 (10) | H9A—C9—H9B | 109.5 |
O1—C3—H3A | 109.3 | C6—C9—H9C | 109.5 |
C2—C3—H3A | 109.3 | H9A—C9—H9C | 109.5 |
C4—C3—H3A | 109.3 | H9B—C9—H9C | 109.5 |
C10—O3—C6 | 115.73 (10) | O4—C10—O3 | 123.58 (12) |
C5—C4—C3 | 109.85 (10) | O4—C10—C11 | 124.96 (12) |
C5—C4—C8 | 107.29 (10) | O3—C10—C11 | 111.42 (11) |
C3—C4—C8 | 112.31 (10) | C12—C11—C16 | 119.97 (12) |
C5—C4—H4A | 109.1 | C12—C11—C10 | 118.07 (12) |
C3—C4—H4A | 109.1 | C16—C11—C10 | 121.92 (12) |
C8—C4—H4A | 109.1 | C13—C12—C11 | 119.56 (13) |
O2—C5—C6 | 122.72 (12) | C13—C12—H12A | 120.2 |
O2—C5—C4 | 122.56 (12) | C11—C12—H12A | 120.2 |
C6—C5—C4 | 114.69 (10) | C14—C13—C12 | 120.64 (13) |
O3—C6—C9 | 106.34 (10) | C14—C13—H13A | 119.7 |
O3—C6—C5 | 111.60 (10) | C12—C13—H13A | 119.7 |
C9—C6—C5 | 111.27 (11) | C13—C14—C15 | 119.88 (13) |
O3—C6—H6A | 109.2 | C13—C14—H14A | 120.1 |
C9—C6—H6A | 109.2 | C15—C14—H14A | 120.1 |
C5—C6—H6A | 109.2 | C16—C15—C14 | 119.95 (13) |
O1—C7—H7A | 109.5 | C16—C15—H15A | 120.0 |
O1—C7—H7B | 109.5 | C14—C15—H15A | 120.0 |
H7A—C7—H7B | 109.5 | C15—C16—C11 | 120.00 (13) |
O1—C7—H7C | 109.5 | C15—C16—H16A | 120.0 |
H7A—C7—H7C | 109.5 | C11—C16—H16A | 120.0 |
C7—O1—C3—C2 | 75.42 (14) | O2—C5—C6—C9 | −102.56 (14) |
C7—O1—C3—C4 | −162.25 (11) | C4—C5—C6—C9 | 79.43 (13) |
C1—C2—C3—O1 | −121.33 (15) | C6—O3—C10—O4 | −4.44 (17) |
C1—C2—C3—C4 | 120.75 (15) | C6—O3—C10—C11 | 173.50 (10) |
O1—C3—C4—C5 | 58.00 (12) | O4—C10—C11—C12 | 1.17 (19) |
C2—C3—C4—C5 | 178.86 (10) | O3—C10—C11—C12 | −176.74 (11) |
O1—C3—C4—C8 | 177.32 (10) | O4—C10—C11—C16 | 178.96 (13) |
C2—C3—C4—C8 | −61.81 (14) | O3—C10—C11—C16 | 1.06 (16) |
C3—C4—C5—O2 | 46.33 (16) | C16—C11—C12—C13 | −0.16 (19) |
C8—C4—C5—O2 | −76.02 (15) | C10—C11—C12—C13 | 177.67 (11) |
C3—C4—C5—C6 | −135.66 (10) | C11—C12—C13—C14 | 0.8 (2) |
C8—C4—C5—C6 | 101.99 (12) | C12—C13—C14—C15 | −0.6 (2) |
C10—O3—C6—C9 | −167.80 (11) | C13—C14—C15—C16 | −0.2 (2) |
C10—O3—C6—C5 | 70.68 (13) | C14—C15—C16—C11 | 0.9 (2) |
O2—C5—C6—O3 | 16.05 (17) | C12—C11—C16—C15 | −0.70 (19) |
C4—C5—C6—O3 | −161.96 (10) | C10—C11—C16—C15 | −178.45 (12) |
D—H···A | D—H | H···A | D···A | D—H···A |
C14—H14A···O2i | 0.95 | 2.54 | 3.2838 (18) | 135 |
Symmetry code: (i) −x+2, y+1/2, −z+1/2. |
Funding information
The TU Dortmund and the DFG are gratefully acknowledged for financial support.
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