organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2414-3146

(2R,4S,5S)-5-Meth­­oxy-4-methyl-3-oxohept-6-en-2-yl benzoate

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aFakultät für Chemie und Chemische Biologie, Technische Universität Dortmund, Organische Chemie, 44227 Dortmund, Germany
*Correspondence e-mail: lyuba.iovkova@tu-dortmund.de

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 1 September 2021; accepted 13 September 2021; online 17 September 2021)

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 epimerization during the methyl­ation process. The crystal structure of the title compound at 100 K has ortho­rhom­bic (P212121) symmetry. The absolute configuration was determined by anomalous dispersion and agrees with the configuration of the allylic alcohol used in the synthesis.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

The title compound, C16H20O4 (Fig. 1[link]), was obtained during the synthesis of the Western fragment of fusaequisin A. Background to fusaequisin A is given by Shiono et al. (2013[Shiono, Y., Shibuya, F., Murayama, T., Koseki, T., Poumale, H. M. P. & Ngadjui, B. T. (2013). Z. Naturfosch. Teil B, 68, 289-292.]). The asymmetric synthesis of the Western fragment is based on Paterson's anti aldol chemistry (Paterson et al., 1994[Paterson, I., Wallace, D. J. & Velázquez, S. M. (1994). Tetrahedron Lett. 35, 9083-9086.]; Paterson, 1998[Paterson, I. (1998). Synthesis, pp. 639-652.]). In the course of the total synthesis of curvicollide C (Che et al., 2004[Che, Y., Gloer, J. B. & Wicklow, D. T. (2004). Org. Lett. 6, 1249-1252.]) the precursor of the title compound (I) was prepared (von Kiedrowski et al., 2017[Kiedrowski, V. von, Quentin, F. & Hiersemann, M. (2017). Org. Lett. 19, 4391-4394.]) and provided potential for further investigations regarding the total synthesis of fusaequisin A. The methyl­ation process is shown in Fig. 2[link].

[Figure 1]
Figure 1
The mol­ecular structure of I showing displacement ellipsoids at the 50% probability level
[Figure 2]
Figure 2
Methyl­ation of O-desmethyl­fusaequisin A.

The title compound crystallizes in the ortho­rhom­bic space group P212121 with four mol­ecules in the unit cell 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[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
C14—H14A⋯O2i 0.95 2.54 3.2838 (18) 135
Symmetry code: (i) [-x+2, y+{\script{1\over 2}}, -z+{\script{1\over 2}}].

Synthesis and crystallization

The reaction (Fig. 3[link]) 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 chromatography (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.

[Figure 3]
Figure 3
Reaction conditions for the methyl­ation of the allylic alcohol.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link].

Table 2
Experimental details

Crystal data
Chemical formula C16H20O4
Mr 276.32
Crystal system, space group Orthorhombic, P212121
Temperature (K) 100
a, b, c (Å) 8.1297 (4), 11.8232 (6), 15.7213 (9)
V3) 1511.12 (14)
Z 4
Radiation type Cu Kα
μ (mm−1) 0.71
Crystal size (mm) 0.12 × 0.10 × 0.06
 
Data collection
Diffractometer Bruker APEXII CCD
Absorption correction Multi-scan (SADABS;Bruker, 2016[Bruker (2016). APEX3, SAINT and SADABS (version 2016/2). Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.700, 0.754
No. of measured, independent and observed [I > 2σ(I)] reflections 28627, 3078, 3054
Rint 0.027
(sin θ/λ)max−1) 0.625
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.023, 0.060, 1.07
No. of reflections 3078
No. of parameters 184
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.18, −0.12
Absolute structure Flack x determined using 1293 quotients [(I+)−(I)]/[(I+)+(I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])
Absolute structure parameter 0.03 (2)
Computer programs: APEX3 and SAINT (Bruker, 2016[Bruker (2016). APEX3, SAINT and SADABS (version 2016/2). Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT2014/5 (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2018/3 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), XP (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]) and OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]).

Structural data


Computing details top

Data collection: APEX3 (Bruker, 2016); cell refinement: 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).

(2R,4S,5S)-5-Methoxy-4-methyl-3-oxohept-6-en-2-yl benzoate top
Crystal data top
C16H20O4Dx = 1.215 Mg m3
Mr = 276.32Melting point = 353–356 K
Orthorhombic, P212121Cu Kα radiation, λ = 1.54178 Å
a = 8.1297 (4) ÅCell parameters from 9807 reflections
b = 11.8232 (6) Åθ = 6.1–74.6°
c = 15.7213 (9) ŵ = 0.71 mm1
V = 1511.12 (14) Å3T = 100 K
Z = 4Block, colourless
F(000) = 5920.12 × 0.10 × 0.06 mm
Data collection top
Bruker APEXII CCD
diffractometer
3054 reflections with I > 2σ(I)
φ and ω scansRint = 0.027
Absorption correction: multi-scan
(SADABS;Bruker, 2016)
θmax = 74.5°, θmin = 4.7°
Tmin = 0.700, Tmax = 0.754h = 1010
28627 measured reflectionsk = 1414
3078 independent reflectionsl = 1819
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-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 = 1.07Δρmax = 0.18 e Å3
3078 reflectionsΔρmin = 0.12 e Å3
184 parametersAbsolute structure: Flack x determined using 1293 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
0 restraintsAbsolute structure parameter: 0.03 (2)
Primary atom site location: dual
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.09507 (18)0.29265 (12)0.39623 (10)0.0306 (3)
H1A0.0809210.3094040.3375840.037*
H1B0.0101470.2553220.4268070.037*
O10.52090 (11)0.31350 (8)0.40027 (6)0.0257 (2)
C20.23199 (17)0.32109 (12)0.43502 (9)0.0260 (3)
H2A0.2418160.3029980.4936800.031*
O20.57315 (12)0.55222 (8)0.31396 (6)0.0257 (2)
C30.37402 (15)0.38013 (10)0.39331 (8)0.0210 (3)
H3A0.3481920.3926780.3318400.025*
O30.79670 (11)0.67523 (7)0.40634 (6)0.02254 (19)
C40.41493 (15)0.49330 (10)0.43492 (8)0.0200 (2)
H4A0.4427880.4803400.4961050.024*
O40.58296 (11)0.79534 (7)0.39300 (6)0.0255 (2)
C50.56184 (15)0.54690 (10)0.39052 (8)0.0195 (2)
C60.69017 (16)0.59668 (11)0.45003 (8)0.0214 (3)
H6A0.6334360.6367620.4977410.026*
C70.5209 (2)0.22018 (12)0.34321 (10)0.0346 (3)
H7A0.6248990.1788620.3484920.052*
H7B0.5085910.2477540.2847700.052*
H7C0.4292060.1696170.3570460.052*
C80.27180 (16)0.57771 (12)0.42921 (10)0.0279 (3)
H8A0.1807210.5514810.4649680.042*
H8B0.2346740.5833870.3700580.042*
H8C0.3086490.6521310.4489620.042*
C90.80093 (17)0.50522 (12)0.48637 (10)0.0298 (3)
H9A0.7336830.4484230.5155670.045*
H9B0.8781820.5391030.5268750.045*
H9C0.8623850.4691100.4401320.045*
C100.72720 (16)0.77408 (10)0.38331 (7)0.0204 (3)
C110.85150 (16)0.85390 (10)0.34781 (8)0.0206 (3)
C120.79937 (18)0.96224 (11)0.32518 (8)0.0237 (3)
H12A0.6868280.9826610.3305130.028*
C130.91308 (19)1.04000 (11)0.29482 (9)0.0286 (3)
H13A0.8780731.1141160.2800930.034*
C141.07716 (19)1.01054 (12)0.28578 (9)0.0303 (3)
H14A1.1539041.0640640.2644200.036*
C151.12937 (17)0.90223 (13)0.30810 (9)0.0294 (3)
H15A1.2417010.8817480.3017610.035*
C161.01703 (17)0.82427 (11)0.33962 (8)0.0243 (3)
H16A1.0527980.7507880.3556130.029*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0290 (7)0.0303 (7)0.0325 (7)0.0065 (6)0.0030 (6)0.0020 (6)
O10.0265 (4)0.0206 (4)0.0298 (5)0.0050 (4)0.0010 (4)0.0022 (4)
C20.0284 (7)0.0248 (6)0.0249 (6)0.0012 (5)0.0023 (5)0.0032 (5)
O20.0317 (5)0.0244 (4)0.0211 (4)0.0027 (4)0.0034 (4)0.0001 (3)
C30.0220 (6)0.0199 (6)0.0210 (6)0.0009 (5)0.0000 (5)0.0011 (5)
O30.0210 (4)0.0178 (4)0.0289 (5)0.0008 (4)0.0021 (4)0.0021 (4)
C40.0197 (5)0.0207 (6)0.0197 (5)0.0004 (5)0.0012 (5)0.0017 (5)
O40.0226 (4)0.0211 (4)0.0326 (5)0.0007 (4)0.0033 (4)0.0017 (4)
C50.0215 (6)0.0146 (5)0.0224 (6)0.0040 (5)0.0012 (5)0.0001 (5)
C60.0210 (6)0.0199 (6)0.0234 (6)0.0018 (5)0.0013 (5)0.0028 (5)
C70.0377 (8)0.0236 (6)0.0426 (8)0.0051 (6)0.0039 (7)0.0090 (6)
C80.0234 (6)0.0264 (7)0.0339 (7)0.0053 (5)0.0006 (6)0.0059 (5)
C90.0233 (6)0.0279 (7)0.0382 (7)0.0005 (6)0.0036 (6)0.0095 (6)
C100.0244 (6)0.0174 (5)0.0196 (6)0.0006 (5)0.0008 (5)0.0030 (5)
C110.0245 (6)0.0192 (6)0.0180 (6)0.0020 (5)0.0002 (5)0.0034 (5)
C120.0277 (7)0.0209 (6)0.0226 (6)0.0005 (5)0.0004 (5)0.0015 (5)
C130.0389 (7)0.0214 (6)0.0256 (6)0.0034 (6)0.0022 (6)0.0009 (5)
C140.0354 (7)0.0296 (7)0.0260 (6)0.0119 (6)0.0064 (6)0.0015 (5)
C150.0252 (7)0.0340 (7)0.0291 (7)0.0038 (6)0.0038 (5)0.0049 (6)
C160.0257 (6)0.0236 (6)0.0235 (6)0.0003 (5)0.0003 (5)0.0026 (5)
Geometric parameters (Å, º) top
C1—C21.313 (2)C7—H7B0.9800
C1—H1A0.9500C7—H7C0.9800
C1—H1B0.9500C8—H8A0.9800
O1—C71.4220 (17)C8—H8B0.9800
O1—C31.4347 (15)C8—H8C0.9800
C2—C31.5001 (18)C9—H9A0.9800
C2—H2A0.9500C9—H9B0.9800
O2—C51.2087 (16)C9—H9C0.9800
C3—C41.5261 (17)C10—C111.4911 (18)
C3—H3A1.0000C11—C121.3953 (18)
O3—C101.3477 (15)C11—C161.3965 (19)
O3—C61.4438 (15)C12—C131.3883 (19)
C4—C51.5215 (17)C12—H12A0.9500
C4—C81.5357 (17)C13—C141.386 (2)
C4—H4A1.0000C13—H13A0.9500
O4—C101.2089 (16)C14—C151.394 (2)
C5—C61.5199 (17)C14—H14A0.9500
C6—C91.5188 (18)C15—C161.389 (2)
C6—H6A1.0000C15—H15A0.9500
C7—H7A0.9800C16—H16A0.9500
C2—C1—H1A120.0H7B—C7—H7C109.5
C2—C1—H1B120.0C4—C8—H8A109.5
H1A—C1—H1B120.0C4—C8—H8B109.5
C7—O1—C3112.20 (11)H8A—C8—H8B109.5
C1—C2—C3124.65 (12)C4—C8—H8C109.5
C1—C2—H2A117.7H8A—C8—H8C109.5
C3—C2—H2A117.7H8B—C8—H8C109.5
O1—C3—C2110.60 (10)C6—C9—H9A109.5
O1—C3—C4105.50 (10)C6—C9—H9B109.5
C2—C3—C4112.85 (10)H9A—C9—H9B109.5
O1—C3—H3A109.3C6—C9—H9C109.5
C2—C3—H3A109.3H9A—C9—H9C109.5
C4—C3—H3A109.3H9B—C9—H9C109.5
C10—O3—C6115.73 (10)O4—C10—O3123.58 (12)
C5—C4—C3109.85 (10)O4—C10—C11124.96 (12)
C5—C4—C8107.29 (10)O3—C10—C11111.42 (11)
C3—C4—C8112.31 (10)C12—C11—C16119.97 (12)
C5—C4—H4A109.1C12—C11—C10118.07 (12)
C3—C4—H4A109.1C16—C11—C10121.92 (12)
C8—C4—H4A109.1C13—C12—C11119.56 (13)
O2—C5—C6122.72 (12)C13—C12—H12A120.2
O2—C5—C4122.56 (12)C11—C12—H12A120.2
C6—C5—C4114.69 (10)C14—C13—C12120.64 (13)
O3—C6—C9106.34 (10)C14—C13—H13A119.7
O3—C6—C5111.60 (10)C12—C13—H13A119.7
C9—C6—C5111.27 (11)C13—C14—C15119.88 (13)
O3—C6—H6A109.2C13—C14—H14A120.1
C9—C6—H6A109.2C15—C14—H14A120.1
C5—C6—H6A109.2C16—C15—C14119.95 (13)
O1—C7—H7A109.5C16—C15—H15A120.0
O1—C7—H7B109.5C14—C15—H15A120.0
H7A—C7—H7B109.5C15—C16—C11120.00 (13)
O1—C7—H7C109.5C15—C16—H16A120.0
H7A—C7—H7C109.5C11—C16—H16A120.0
C7—O1—C3—C275.42 (14)O2—C5—C6—C9102.56 (14)
C7—O1—C3—C4162.25 (11)C4—C5—C6—C979.43 (13)
C1—C2—C3—O1121.33 (15)C6—O3—C10—O44.44 (17)
C1—C2—C3—C4120.75 (15)C6—O3—C10—C11173.50 (10)
O1—C3—C4—C558.00 (12)O4—C10—C11—C121.17 (19)
C2—C3—C4—C5178.86 (10)O3—C10—C11—C12176.74 (11)
O1—C3—C4—C8177.32 (10)O4—C10—C11—C16178.96 (13)
C2—C3—C4—C861.81 (14)O3—C10—C11—C161.06 (16)
C3—C4—C5—O246.33 (16)C16—C11—C12—C130.16 (19)
C8—C4—C5—O276.02 (15)C10—C11—C12—C13177.67 (11)
C3—C4—C5—C6135.66 (10)C11—C12—C13—C140.8 (2)
C8—C4—C5—C6101.99 (12)C12—C13—C14—C150.6 (2)
C10—O3—C6—C9167.80 (11)C13—C14—C15—C160.2 (2)
C10—O3—C6—C570.68 (13)C14—C15—C16—C110.9 (2)
O2—C5—C6—O316.05 (17)C12—C11—C16—C150.70 (19)
C4—C5—C6—O3161.96 (10)C10—C11—C16—C15178.45 (12)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C14—H14A···O2i0.952.543.2838 (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.

References

First citationBruker (2016). APEX3, SAINT and SADABS (version 2016/2). Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationChe, Y., Gloer, J. B. & Wicklow, D. T. (2004). Org. Lett. 6, 1249–1252.  Web of Science CrossRef PubMed CAS Google Scholar
First citationDolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationKiedrowski, V. von, Quentin, F. & Hiersemann, M. (2017). Org. Lett. 19, 4391–4394.  PubMed Google Scholar
First citationParsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
First citationPaterson, I. (1998). Synthesis, pp. 639–652.  Web of Science CrossRef Google Scholar
First citationPaterson, I., Wallace, D. J. & Velázquez, S. M. (1994). Tetrahedron Lett. 35, 9083–9086.  CrossRef CAS Web of Science Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationShiono, Y., Shibuya, F., Murayama, T., Koseki, T., Poumale, H. M. P. & Ngadjui, B. T. (2013). Z. Naturfosch. Teil B, 68, 289–292.  CrossRef CAS Google Scholar

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