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

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

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 ▸).

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 φ(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 ▸.

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4⋯O1i	0.82	2.05	2.811 (2)	155

Symmetry code: (i) .

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 ▸).

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

Crystal data
Chemical formula	C11H18O4
M r	214.25
Crystal system, space group	Orthorhombic, P212121
Temperature (K)	100
a, b, c (Å)	5.0968 (1), 8.8153 (1), 25.6052 (3)
V (Å3)	1150.44 (3)
Z	4
Radiation type	Cu Kα
μ (mm−1)	0.77
Crystal size (mm)	0.23 × 0.13 × 0.06
Data collection
Diffractometer	Rigaku OD SuperNova, single source at offset/far, HyPix3000
Absorption correction	Gaussian (CrysAlis PRO; Rigaku OD, 2016 ▸)
T min, T max	0.739, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	17757, 2131, 2081
R int	0.030
(sin θ/λ)max (Å−1)	0.606
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.032, 0.094, 1.26
No. of reflections	2131
No. of parameters	141
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.23, −0.17
Absolute structure	Flack x determined using 812 quotients [(I +)−(I −)]/[(I +)+(I −)] (Parsons et al., 2013 ▸)
Absolute structure parameter	0.05 (6)

Computer programs: CrysAlis PRO (Rigaku OD, 2016 ▸), SHELXT (Sheldrick, 2015a ▸), SHELXL2016 (Sheldrick, 2015b ▸), Mercury (Macrae et al., 2008 ▸) and OLEX2 (Dolomanov et al., 2009 ▸).

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

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989017009318/su5376Isup3.cml

CCDC reference: 1548935

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

C11H18O4	Dx = 1.237 Mg m−3
Mr = 214.25	Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, P212121	Cell parameters from 12810 reflections
a = 5.0968 (1) Å	θ = 3.5–68.8°
b = 8.8153 (1) Å	µ = 0.77 mm−1
c = 25.6052 (3) Å	T = 100 K
V = 1150.44 (3) Å3	Block, colourless
Z = 4	0.23 × 0.13 × 0.06 mm
F(000) = 464

Rigaku OD SuperNova, Single source at offset/far, HyPix3000 diffractometer	2131 independent reflections
Radiation source: micro-focus sealed X-ray tube, SuperNova (Cu) X-ray Source	2081 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.030
ω scans	θmax = 69.0°, θmin = 3.5°
Absorption correction: gaussian (CrysAlis PRO; Rigaku OD, 2016)	h = −6→6
Tmin = 0.739, Tmax = 1.000	k = −10→10
17757 measured reflections	l = −30→31

Refinement on F2	H-atom parameters constrained
Least-squares matrix: full	w = 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) = 0.094	Δρmax = 0.23 e Å−3
S = 1.26	Δρmin = −0.17 e Å−3
2131 reflections	Extinction correction: (SHELXL2016; Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
141 parameters	Extinction coefficient: 0.0032 (6)
0 restraints	Absolute structure: Flack x determined using 812 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Primary atom site location: dual	Absolute structure parameter: 0.05 (6)
Hydrogen site location: inferred from neighbouring sites

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
O1	0.9031 (4)	−0.13807 (18)	0.69895 (7)	0.0267 (4)
O2	0.6220 (3)	0.03761 (19)	0.72821 (6)	0.0234 (4)
O3	0.9752 (3)	0.10820 (18)	0.68416 (6)	0.0214 (4)
O4	0.8749 (4)	0.55481 (18)	0.66999 (6)	0.0241 (4)
H4	0.838292	0.644582	0.674153	0.036*
C1	0.8397 (5)	−0.0079 (3)	0.70337 (9)	0.0196 (5)
C2	0.6171 (5)	0.2019 (3)	0.73034 (9)	0.0208 (5)
H2A	0.653581	0.237855	0.765407	0.025*
H2B	0.447987	0.240857	0.719285	0.025*
C3	0.8339 (5)	0.2503 (2)	0.69242 (9)	0.0182 (5)
H3	0.949859	0.323486	0.709691	0.022*
C4	0.7482 (5)	0.3135 (2)	0.63967 (8)	0.0164 (5)
H4A	0.904016	0.316110	0.617275	0.020*
C5	0.6564 (5)	0.4780 (2)	0.64684 (9)	0.0179 (5)
H5	0.509516	0.479338	0.671547	0.021*
C6	0.5674 (5)	0.5528 (3)	0.59550 (8)	0.0188 (5)
H6	0.418322	0.494773	0.581917	0.023*
C7	0.7832 (5)	0.5488 (3)	0.55492 (9)	0.0224 (5)
H7	0.947944	0.581376	0.565794	0.027*
C8	0.7641 (5)	0.5043 (3)	0.50573 (9)	0.0266 (5)
H8	0.916088	0.510563	0.485756	0.032*
C9	0.5243 (6)	0.4446 (4)	0.47858 (10)	0.0394 (7)
H9A	0.492138	0.503209	0.447625	0.059*
H9B	0.375977	0.452228	0.501530	0.059*
H9C	0.551540	0.340378	0.469213	0.059*
C10	0.5456 (5)	0.2129 (3)	0.61247 (9)	0.0208 (5)
H10A	0.379257	0.222893	0.629735	0.031*
H10B	0.601834	0.109062	0.613932	0.031*
H10C	0.528349	0.243598	0.576661	0.031*
C11	0.4749 (6)	0.7165 (3)	0.60482 (10)	0.0268 (6)
H11A	0.343748	0.717439	0.631719	0.040*
H11B	0.401916	0.756573	0.573128	0.040*
H11C	0.621298	0.777709	0.615420	0.040*

	U11	U22	U33	U12	U13	U23
O1	0.0337 (10)	0.0144 (8)	0.0319 (9)	0.0021 (7)	−0.0088 (8)	−0.0007 (7)
O2	0.0230 (8)	0.0183 (8)	0.0289 (8)	−0.0017 (7)	0.0033 (7)	0.0048 (7)
O3	0.0198 (8)	0.0151 (7)	0.0292 (8)	0.0029 (7)	0.0022 (7)	0.0037 (6)
O4	0.0278 (9)	0.0128 (7)	0.0316 (9)	0.0000 (7)	−0.0107 (7)	−0.0023 (7)
C1	0.0218 (11)	0.0181 (11)	0.0189 (10)	−0.0010 (10)	−0.0052 (9)	0.0004 (9)
C2	0.0244 (12)	0.0166 (11)	0.0215 (11)	0.0024 (11)	0.0028 (10)	0.0003 (9)
C3	0.0180 (11)	0.0134 (10)	0.0231 (11)	0.0004 (9)	−0.0006 (9)	−0.0017 (8)
C4	0.0159 (10)	0.0128 (10)	0.0205 (10)	0.0007 (9)	0.0012 (9)	−0.0006 (8)
C5	0.0175 (11)	0.0146 (10)	0.0214 (11)	−0.0010 (9)	−0.0012 (9)	−0.0014 (9)
C6	0.0158 (11)	0.0181 (11)	0.0224 (11)	−0.0002 (9)	−0.0019 (9)	0.0013 (9)
C7	0.0164 (11)	0.0230 (11)	0.0277 (11)	0.0002 (10)	−0.0008 (9)	0.0054 (10)
C8	0.0217 (12)	0.0331 (13)	0.0251 (11)	0.0042 (11)	0.0026 (10)	0.0053 (10)
C9	0.0310 (15)	0.0616 (19)	0.0258 (13)	−0.0003 (15)	−0.0020 (11)	−0.0064 (13)
C10	0.0218 (12)	0.0182 (11)	0.0224 (11)	−0.0015 (10)	−0.0008 (9)	−0.0013 (9)
C11	0.0314 (14)	0.0192 (12)	0.0299 (12)	0.0065 (11)	−0.0050 (11)	0.0029 (10)

O1—C1	1.198 (3)	C6—H6	0.9800
O2—C1	1.340 (3)	C6—C7	1.513 (3)
O2—C2	1.450 (3)	C6—C11	1.536 (3)
O3—C1	1.329 (3)	C7—H7	0.9300
O3—C3	1.461 (3)	C7—C8	1.323 (3)
O4—H4	0.8200	C8—H8	0.9300
O4—C5	1.432 (3)	C8—C9	1.501 (4)
C2—H2A	0.9700	C9—H9A	0.9600
C2—H2B	0.9700	C9—H9B	0.9600
C2—C3	1.532 (3)	C9—H9C	0.9600
C3—H3	0.9800	C10—H10A	0.9600
C3—C4	1.525 (3)	C10—H10B	0.9600
C4—H4A	0.9800	C10—H10C	0.9600
C4—C5	1.535 (3)	C11—H11A	0.9600
C4—C10	1.529 (3)	C11—H11B	0.9600
C5—H5	0.9800	C11—H11C	0.9600
C5—C6	1.539 (3)
C1—O2—C2	109.32 (19)	C5—C6—H6	107.9
C1—O3—C3	110.52 (17)	C7—C6—C5	111.25 (19)
C5—O4—H4	109.5	C7—C6—H6	107.9
O1—C1—O2	123.7 (2)	C7—C6—C11	110.58 (19)
O1—C1—O3	124.2 (2)	C11—C6—C5	111.11 (18)
O3—C1—O2	112.07 (19)	C11—C6—H6	107.9
O2—C2—H2A	111.0	C6—C7—H7	116.3
O2—C2—H2B	111.0	C8—C7—C6	127.4 (2)
O2—C2—C3	104.01 (18)	C8—C7—H7	116.3
H2A—C2—H2B	109.0	C7—C8—H8	116.4
C3—C2—H2A	111.0	C7—C8—C9	127.2 (2)
C3—C2—H2B	111.0	C9—C8—H8	116.4
O3—C3—C2	102.04 (17)	C8—C9—H9A	109.5
O3—C3—H3	109.4	C8—C9—H9B	109.5
O3—C3—C4	109.03 (18)	C8—C9—H9C	109.5
C2—C3—H3	109.4	H9A—C9—H9B	109.5
C4—C3—C2	117.2 (2)	H9A—C9—H9C	109.5
C4—C3—H3	109.4	H9B—C9—H9C	109.5
C3—C4—H4A	107.1	C4—C10—H10A	109.5
C3—C4—C5	109.04 (18)	C4—C10—H10B	109.5
C3—C4—C10	112.68 (18)	C4—C10—H10C	109.5
C5—C4—H4A	107.1	H10A—C10—H10B	109.5
C10—C4—H4A	107.1	H10A—C10—H10C	109.5
C10—C4—C5	113.36 (19)	H10B—C10—H10C	109.5
O4—C5—C4	105.02 (18)	C6—C11—H11A	109.5
O4—C5—H5	108.7	C6—C11—H11B	109.5
O4—C5—C6	112.33 (18)	C6—C11—H11C	109.5
C4—C5—H5	108.7	H11A—C11—H11B	109.5
C4—C5—C6	113.11 (18)	H11A—C11—H11C	109.5
C6—C5—H5	108.7	H11B—C11—H11C	109.5
O2—C2—C3—O3	−13.8 (2)	C2—C3—C4—C10	−49.2 (3)
O2—C2—C3—C4	105.2 (2)	C3—O3—C1—O1	175.2 (2)
O3—C3—C4—C5	−167.31 (18)	C3—O3—C1—O2	−4.5 (2)
O3—C3—C4—C10	65.9 (2)	C3—C4—C5—O4	56.7 (2)
O4—C5—C6—C7	61.8 (2)	C3—C4—C5—C6	179.52 (19)
O4—C5—C6—C11	−61.9 (3)	C4—C5—C6—C7	−56.9 (3)
C1—O2—C2—C3	12.2 (2)	C4—C5—C6—C11	179.4 (2)
C1—O3—C3—C2	11.6 (2)	C5—C6—C7—C8	131.2 (3)
C1—O3—C3—C4	−113.0 (2)	C6—C7—C8—C9	−1.0 (4)
C2—O2—C1—O1	174.9 (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—C5	77.5 (2)	C11—C6—C7—C8	−104.8 (3)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···O1i	0.82	2.05	2.811 (2)	155