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Logo of actae2this articlesearchopen accesssubmitActa Crystallographica Section E: Crystallographic CommunicationsActa Crystallographica Section E: Crystallographic Communications
 
Acta Crystallogr E Crystallogr Commun. 2017 July 1; 73(Pt 7): 1070–1072.
Published online 2017 June 27. doi:  10.1107/S2056989017009318
PMCID: PMC5499293

Crystal structure of (−)-(S)-4-[(2S,3S,4S,Z)-3-hydroxy-4-methyl­hept-5-en-2-yl]-1,3-dioxolan-2-one

Abstract

The title compound, C11H18O4, consists of an anti,anti,anti-stereo­tetrad with a 1,2-carbonate and an alkene motif. The mol­ecule displays a common zigzag conformation. The five-membered ring has a twisted conformation on the C—C bond. In the crystal, a strong inter­molecular hydrogen bond between the hy­droxy group and the carboxyl­ate moiety from an adjacent mol­ecule forms chains propagating along the b-axis direction. The absolute structure of the mol­ecule in the crystal was determined by resonant scattering [Flack parameter = 0.05 (6)].

Keywords: crystal structure, polypropionate, 1,2-carbonate, stereo­tetra­ds, O—H(...)O hydrogen bonding

Chemical context  

The title compound was obtained as part of our studies toward the synthesis of (−)-dolabriferol and (−)-dolabriferol B (Ciavatta et al., 1996  ; Jiménez-Romero et al., 2012  ), using an epoxide-based approach for the stereo­tetrad construction. Polypropionate chains are structural motifs consisting of alternating methyl and hy­droxy groups within an aliphatic framework (Torres et al., 2004  , 2009  ; Tirado et al., 2005  , Rodríguez et al., 2006  ). Their structure is found in various natural products, many of them possessing a wide range of biological activity, typically anti­biotic, anti­tumor, anti­fungal, anti­parasitic, among others (Rohr, 2000  ). Different method­ologies for the synthesis of polypropionates have been developed, with aldol and aldol-related chemistry being the most used (Schetter & Mahrwald, 2006  ).

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In our laboratory, we have developed an epoxide-based methodology for the construction of polypropionates, consisting of a reiterative sequence of three steps. Our approach involves a regioselect­ive epoxide cleavage with an alkynyl aluminium reagent (Torres et al., 2005  ) or Grignard reagent (Rodríguez et al., 2006  ), cis or trans reduction of the alkyne (if needed), and the stereoselective epoxidation of the resulting alkenol for the elaboration of each propionate unit. In this approach, the configuration of the hydroxyl group is derived from the absolute configuration of the epoxide precursor, while the syn/anti relative configuration of the methyl and hydroxyl groups is derived from the epoxide geometry. One of the advantages of this methodology is that it is a substrate-controlled synthesis; the only enanti­omeric step in this sequence is the first epoxidation (Katsuki & Sharpless, 1980  ).

Structural commentary  

The mol­ecular structure of the title compound is illustrated in Fig. 1  . The alkyl back bone has a typical zigzag conformation with two of the three methyl groups, those located on C4 and C6, anti to one another. Likewise, the hy­droxy group located on C5 is in an anti relative conformation with respect to the methyl groups. The five-membered ring (O2/O3/C1–C3) has a twisted conformation on bond C2–C3 [puckering parameters Q(2) = 0.137 (2) Å and [var phi](2) = 307.4 (10)°].

Figure 1
The mol­ecular structure of the title compound, with the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Supra­molecular features  

The conformational distance between the hydroxyl group and the carbonyl moiety does not allow intra­molecular hydrogen-bond formation, therefore, hydrogen bonding is observed through inter­molecular inter­actions alone (Table 1  ). In the crystal, neighbouring mol­ecules are linked by the O4—H4(...)O1i hydrogen bond, forming chains along [010]; see Fig. 2  and Table 1  .

Figure 2
A view along the a axis of crystal packing of the title compound, with hydrogen bonds shown as dashed lines (see Table 1  ).
Table 1
Hydrogen-bond geometry (Å, °)

Database survey  

A search of the Cambridge Structural Database (Version 5.38, updated May 2017; Groom et al., 2016  ) revealed no related compounds with the 3-hy­droxy-2-methyl-1,2-carbonate substructure. However, a search for the 2,4-di­methyl­hex-5-en-3-ol fragment revealed more than 120 hits. Many of these involve reactants for the synthesis of natural products, such as superotolide A (Yakelis & Roush, 2003  ) and erythronolides A and B (Lynch et al., 1989a  ; 1989b  ).

Synthesis and crystallization  

The synthesis of the title compound, illustrated in Fig. 3  , was performed through the selective protection of the 1,2-diol of (+)-(2S,3S,4S,5S,Z)-3,5-di­methyl­oct-6-ene-1,2,4-triol with a carbonate using N,N′-carbonyl­diimidazole (CDI) in CH2Cl2 as solvent, favouring formation of the 1,2-carbonate over the 1,3-carbonate. This reaction afforded the optically active anti,anti,anti-polypropionate unit with the correct absolute configuration. To a dry round-bottom flask containing the 1,2-diol of (+)-(2S,3S,4S,5S,Z)-3,5-di­methyl­oct-6-ene-1,2,4-triol (0.04 g, 0.212 mmol) in dry CH2Cl2 (1.07 ml, 0.2 M) was added N,N′-carbonyl­diimidazole (0.048 g, 0.30 mmol). The reaction mixture was stirred at 298 K for 2.5 h, then saturated aqueous NaCl was added. The resulting mixture was then extracted with ethyl acetate (three times). The combined organic layer was dried over MgSO4 and concentrated at reduced pressure. The crude product was purified by flash chromatography (2:1, ethyl acetate:hexa­ne) to yield 0.027 g (62%) of the pure title carbonate product as a white solid (m.p. 360–363 K). Block-like clear crystals suitable for X-ray diffraction, were obtained by slow diffusion of a 1:1 (v:v) ethyl acetate:hexa­nes solution of the title compound at room temperature over a period of two days. NMR analyses were performed on a Bruker AV-500 spectrometer using Chloro­form-d as solvent (CDCl3). The solvent signal at 7.26 and 77.00 ppm were used as inter­nal standards for proton and carbon respectively. 1H NMR (500 MHz, CDCl3) δ 5.69 (dq, J = 10.9, 6.8 Hz, 1H), 5.23 (ddt, J = 11.2, 9.8, 1.8 Hz, 1H), 4.99 (td, J = 8.2, 5.0 Hz, 1H), 4.44 (t, J = 8.6 Hz, 1H), 4.37 (t, J = 8.6 Hz, 1H), 3.26 (dd, J = 7.5, 4.2 Hz, 1H), 2.72 (ddq, J = 6.9, 6.7, 3.1 Hz, 1H), 2.29 (ddq, J = 6.6, 4.5, 2.4 Hz, 1H), 2.00 (s, 1H, -OH), 1.65 (dd, J = 6.8, 1.9 Hz, 3H), 1.05 (d, J = 6.9 Hz, 3H), 1.00 (d, J = 6.6 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 155.3, 131.3, 127.4, 77.5, 77.3, 66.9, 36.8, 35.3, 17.1, 13.3, 11.7. [α]20 D = −2.0 (c = 1.0, CHCl3). Analysis calculated for C11H18O4: C, 61.66, H, 8.47%. Found: C, 61.74, H, 8.44%. IR data: C=O: 1761.32 cm−1, C—O: 1061.01 cm−1.

Figure 3
Reaction scheme

Refinement  

Crystal data, data collection and structure refinement details are summarized in Table 2  . H atoms were included in geometrically calculated positions and refined as riding: O—H = 0.82 Å, C—H = 0.93–0.98 Å with U iso(H) = 1.5U eq(O-hydroxyl and C-meth­yl) and 1.2U eq(C) for other H atoms.

Table 2
Experimental details

Supplementary Material

Crystal structure: contains datablock(s) Global, I. DOI: 10.1107/S2056989017009318/su5376sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989017009318/su5376Isup2.hkl

CCDC reference: 1548935

Additional supporting information: crystallographic information; 3D view; checkCIF report

Acknowledgments

The authors thank NIH RISE (5R25GM061151–15) and SCORE (2S06GM-08102–29) for the financial support. This material is based upon work supported by the National Science Foundation under Grant No. 1626103.

supplementary crystallographic information

Crystal data

C11H18O4Dx = 1.237 Mg m3
Mr = 214.25Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, P212121Cell parameters from 12810 reflections
a = 5.0968 (1) Åθ = 3.5–68.8°
b = 8.8153 (1) ŵ = 0.77 mm1
c = 25.6052 (3) ÅT = 100 K
V = 1150.44 (3) Å3Block, colourless
Z = 40.23 × 0.13 × 0.06 mm
F(000) = 464

Data collection

Rigaku OD SuperNova, Single source at offset/far, HyPix3000 diffractometer2131 independent reflections
Radiation source: micro-focus sealed X-ray tube, SuperNova (Cu) X-ray Source2081 reflections with I > 2σ(I)
Mirror monochromatorRint = 0.030
ω scansθmax = 69.0°, θmin = 3.5°
Absorption correction: gaussian (CrysAlis PRO; Rigaku OD, 2016)h = −6→6
Tmin = 0.739, Tmax = 1.000k = −10→10
17757 measured reflectionsl = −30→31

Refinement

Refinement on F2H-atom parameters constrained
Least-squares matrix: fullw = 1/[σ2(Fo2) + (0.0367P)2 + 0.4414P] where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.032(Δ/σ)max < 0.001
wR(F2) = 0.094Δρmax = 0.23 e Å3
S = 1.26Δρmin = −0.17 e Å3
2131 reflectionsExtinction correction: (SHELXL2016; Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
141 parametersExtinction coefficient: 0.0032 (6)
0 restraintsAbsolute structure: Flack x determined using 812 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Primary atom site location: dualAbsolute structure parameter: 0.05 (6)
Hydrogen site location: inferred from neighbouring sites

Special details

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)

xyzUiso*/Ueq
O10.9031 (4)−0.13807 (18)0.69895 (7)0.0267 (4)
O20.6220 (3)0.03761 (19)0.72821 (6)0.0234 (4)
O30.9752 (3)0.10820 (18)0.68416 (6)0.0214 (4)
O40.8749 (4)0.55481 (18)0.66999 (6)0.0241 (4)
H40.8382920.6445820.6741530.036*
C10.8397 (5)−0.0079 (3)0.70337 (9)0.0196 (5)
C20.6171 (5)0.2019 (3)0.73034 (9)0.0208 (5)
H2A0.6535810.2378550.7654070.025*
H2B0.4479870.2408570.7192850.025*
C30.8339 (5)0.2503 (2)0.69242 (9)0.0182 (5)
H30.9498590.3234860.7096910.022*
C40.7482 (5)0.3135 (2)0.63967 (8)0.0164 (5)
H4A0.9040160.3161100.6172750.020*
C50.6564 (5)0.4780 (2)0.64684 (9)0.0179 (5)
H50.5095160.4793380.6715470.021*
C60.5674 (5)0.5528 (3)0.59550 (8)0.0188 (5)
H60.4183220.4947730.5819170.023*
C70.7832 (5)0.5488 (3)0.55492 (9)0.0224 (5)
H70.9479440.5813760.5657940.027*
C80.7641 (5)0.5043 (3)0.50573 (9)0.0266 (5)
H80.9160880.5105630.4857560.032*
C90.5243 (6)0.4446 (4)0.47858 (10)0.0394 (7)
H9A0.4921380.5032090.4476250.059*
H9B0.3759770.4522280.5015300.059*
H9C0.5515400.3403780.4692130.059*
C100.5456 (5)0.2129 (3)0.61247 (9)0.0208 (5)
H10A0.3792570.2228930.6297350.031*
H10B0.6018340.1090620.6139320.031*
H10C0.5283490.2435980.5766610.031*
C110.4749 (6)0.7165 (3)0.60482 (10)0.0268 (6)
H11A0.3437480.7174390.6317190.040*
H11B0.4019160.7565730.5731280.040*
H11C0.6212980.7777090.6154200.040*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0337 (10)0.0144 (8)0.0319 (9)0.0021 (7)−0.0088 (8)−0.0007 (7)
O20.0230 (8)0.0183 (8)0.0289 (8)−0.0017 (7)0.0033 (7)0.0048 (7)
O30.0198 (8)0.0151 (7)0.0292 (8)0.0029 (7)0.0022 (7)0.0037 (6)
O40.0278 (9)0.0128 (7)0.0316 (9)0.0000 (7)−0.0107 (7)−0.0023 (7)
C10.0218 (11)0.0181 (11)0.0189 (10)−0.0010 (10)−0.0052 (9)0.0004 (9)
C20.0244 (12)0.0166 (11)0.0215 (11)0.0024 (11)0.0028 (10)0.0003 (9)
C30.0180 (11)0.0134 (10)0.0231 (11)0.0004 (9)−0.0006 (9)−0.0017 (8)
C40.0159 (10)0.0128 (10)0.0205 (10)0.0007 (9)0.0012 (9)−0.0006 (8)
C50.0175 (11)0.0146 (10)0.0214 (11)−0.0010 (9)−0.0012 (9)−0.0014 (9)
C60.0158 (11)0.0181 (11)0.0224 (11)−0.0002 (9)−0.0019 (9)0.0013 (9)
C70.0164 (11)0.0230 (11)0.0277 (11)0.0002 (10)−0.0008 (9)0.0054 (10)
C80.0217 (12)0.0331 (13)0.0251 (11)0.0042 (11)0.0026 (10)0.0053 (10)
C90.0310 (15)0.0616 (19)0.0258 (13)−0.0003 (15)−0.0020 (11)−0.0064 (13)
C100.0218 (12)0.0182 (11)0.0224 (11)−0.0015 (10)−0.0008 (9)−0.0013 (9)
C110.0314 (14)0.0192 (12)0.0299 (12)0.0065 (11)−0.0050 (11)0.0029 (10)

Geometric parameters (Å, º)

O1—C11.198 (3)C6—H60.9800
O2—C11.340 (3)C6—C71.513 (3)
O2—C21.450 (3)C6—C111.536 (3)
O3—C11.329 (3)C7—H70.9300
O3—C31.461 (3)C7—C81.323 (3)
O4—H40.8200C8—H80.9300
O4—C51.432 (3)C8—C91.501 (4)
C2—H2A0.9700C9—H9A0.9600
C2—H2B0.9700C9—H9B0.9600
C2—C31.532 (3)C9—H9C0.9600
C3—H30.9800C10—H10A0.9600
C3—C41.525 (3)C10—H10B0.9600
C4—H4A0.9800C10—H10C0.9600
C4—C51.535 (3)C11—H11A0.9600
C4—C101.529 (3)C11—H11B0.9600
C5—H50.9800C11—H11C0.9600
C5—C61.539 (3)
C1—O2—C2109.32 (19)C5—C6—H6107.9
C1—O3—C3110.52 (17)C7—C6—C5111.25 (19)
C5—O4—H4109.5C7—C6—H6107.9
O1—C1—O2123.7 (2)C7—C6—C11110.58 (19)
O1—C1—O3124.2 (2)C11—C6—C5111.11 (18)
O3—C1—O2112.07 (19)C11—C6—H6107.9
O2—C2—H2A111.0C6—C7—H7116.3
O2—C2—H2B111.0C8—C7—C6127.4 (2)
O2—C2—C3104.01 (18)C8—C7—H7116.3
H2A—C2—H2B109.0C7—C8—H8116.4
C3—C2—H2A111.0C7—C8—C9127.2 (2)
C3—C2—H2B111.0C9—C8—H8116.4
O3—C3—C2102.04 (17)C8—C9—H9A109.5
O3—C3—H3109.4C8—C9—H9B109.5
O3—C3—C4109.03 (18)C8—C9—H9C109.5
C2—C3—H3109.4H9A—C9—H9B109.5
C4—C3—C2117.2 (2)H9A—C9—H9C109.5
C4—C3—H3109.4H9B—C9—H9C109.5
C3—C4—H4A107.1C4—C10—H10A109.5
C3—C4—C5109.04 (18)C4—C10—H10B109.5
C3—C4—C10112.68 (18)C4—C10—H10C109.5
C5—C4—H4A107.1H10A—C10—H10B109.5
C10—C4—H4A107.1H10A—C10—H10C109.5
C10—C4—C5113.36 (19)H10B—C10—H10C109.5
O4—C5—C4105.02 (18)C6—C11—H11A109.5
O4—C5—H5108.7C6—C11—H11B109.5
O4—C5—C6112.33 (18)C6—C11—H11C109.5
C4—C5—H5108.7H11A—C11—H11B109.5
C4—C5—C6113.11 (18)H11A—C11—H11C109.5
C6—C5—H5108.7H11B—C11—H11C109.5
O2—C2—C3—O3−13.8 (2)C2—C3—C4—C10−49.2 (3)
O2—C2—C3—C4105.2 (2)C3—O3—C1—O1175.2 (2)
O3—C3—C4—C5−167.31 (18)C3—O3—C1—O2−4.5 (2)
O3—C3—C4—C1065.9 (2)C3—C4—C5—O456.7 (2)
O4—C5—C6—C761.8 (2)C3—C4—C5—C6179.52 (19)
O4—C5—C6—C11−61.9 (3)C4—C5—C6—C7−56.9 (3)
C1—O2—C2—C312.2 (2)C4—C5—C6—C11179.4 (2)
C1—O3—C3—C211.6 (2)C5—C6—C7—C8131.2 (3)
C1—O3—C3—C4−113.0 (2)C6—C7—C8—C9−1.0 (4)
C2—O2—C1—O1174.9 (2)C10—C4—C5—O4−176.93 (18)
C2—O2—C1—O3−5.3 (2)C10—C4—C5—C6−54.1 (3)
C2—C3—C4—C577.5 (2)C11—C6—C7—C8−104.8 (3)

Hydrogen-bond geometry (Å, º)

D—H···AD—HH···AD···AD—H···A
O4—H4···O1i0.822.052.811 (2)155

Symmetry code: (i) x, y+1, z.

Funding Statement

This work was funded by National Institutes of Health grant 5R25GM061151-15. National Institutes of General Medical Sciences grant 2S06GM-08102-29. National Science Foundation grant 1626103.

This paper was supported by the following grant(s):

National Institutes of Health 5R25GM061151-15.
National Institutes of General Medical Sciences 2S06GM-08102-29.
National Science Foundation 1626103.

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