(3S,4S,5S)-4-Hydr­oxy-3-methyl-5-[(2S,3R)-3-methyl­pent-4-en-2-yl]-4,5-dihydro­furan-2(3H)-one

The title compound, C₁₁H₁₈O₃, was synthesized to prove the relative configuration of the corresponding acyclic C1—C8 stereopentade. Mol­ecules are linked via O—H...O hydrogen bonds, forming a chain along the b axis.

Key indicators

• Single-crystal X-ray study
• T = 291 K
• Mean [sigma](C-C) = 0.009 Å
• R factor = 0.037
• wR factor = 0.088
• Data-to-parameter ratio = 9.3

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT026_ALERT_3_A Ratio Observed / Unique Reflections too Low ....         28 Perc.

Author Response: Despite using a long exposure time (180 s per frame) the ratio could not be significantly improved. A data collection with 100 s per frame resulted in a ratio of 26 Perc. It was a very weak reflecting crystal. Better crystals could not be achieved.

Alert level C
PLAT220_ALERT_2_C Large Non-Solvent    C     Ueq(max)/Ueq(min) ...       2.93 Ratio
PLAT230_ALERT_2_C Hirshfeld Test Diff for    C7     --  C8      ..       6.05 su
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for         C6
PLAT340_ALERT_3_C Low Bond Precision on C-C Bonds (x 1000) Ang ...          9
PLAT368_ALERT_2_C Short  C(sp2)-C(sp2) Bond  C7     -   C8     ...       1.21 Ang.
PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd.  #          1
              C11 H18 O3

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           25.01
           From the CIF: _reflns_number_total               1223
           Count of symmetry unique reflns         1224
           Completeness (_total/calc)             99.92%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no
PLAT791_ALERT_4_G Confirm the Absolute Configuration of C2     ...          S
PLAT791_ALERT_4_G Confirm the Absolute Configuration of C3     ...          S
PLAT791_ALERT_4_G Confirm the Absolute Configuration of C4     ...          S
PLAT791_ALERT_4_G Confirm the Absolute Configuration of C5     ...          S
PLAT791_ALERT_4_G Confirm the Absolute Configuration of C6     ...          R

   1 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   6 ALERT level C = Check and explain
   6 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   4 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   7 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

---

S1. Comment

The title compound, (I), was synthesized using a catalytic asymmetric Claisen rearrangement (Abraham et al., 2004a; Abraham et al., 2004b; Pollex & Hiersemann, 2005; Körner & Hiersemann, 2006; Körner & Hiersemann, 2007), a diastereoselective reduction with K-Selectride (Körner & Hiersemann, 2006; Körner & Hiersemann, 2007), and an Evans aldol addition (Evans et al., 1981). In order to verify the relative configuration of the obtained aldol adduct, 4-(tert-butyldimethylsilyloxy)-3-hydroxy-2,5,6-trimethyloct-7-enoyl)-4-isopropyloxazolidin-2-one, (II), a γ-lactone, (I), was prepared by removal of the silyl protecting group (Corey & Snider, 1972) and subsequent in situ lactonization. Fig. 1 depicts the structure of the isolated major diastereomer (I). The configuration of the chiral C atoms in (I) can be attributed to the stereochemical course of the Evans aldol addition (C3 S and C4 S), the diastereoselective reduction with K-Selectride (C5 S), and the catalytic asymmetric Claisen rearrangement (C(2) S and C(3) R) using the chiral Lewis acid [Cu{(S,S)-tert-Butyl-box}](H₂O)₂(SbF₆)₂ (Evans et al., 1999).

Related literature

For related literature, see: Abraham et al. (2004a,b); Corey & Snider (1972); Evans et al. (1981, 1999); Körner & Hiersemann (2006, 2007); Pollex & Hiersemann (2005).

S2. Experimental

The title compound, (I), was synthesized from the corresponding syn-aldol adduct, (II), using tetrabutylammonium fluoride (Corey & Snider, 1972) for the removal of the silyl protecting group. The subsequent lactonization proceeded in situ.

To a solution of diastereomerically pure (II) (50 mg, 0.113 mmol, 1.0 eq) in dry tetrahydrofuran (1 ml) was added TBAF (1 M in tetrahydrofuran, 0.34 ml, 3.0 eq) at 273 K. The mixture was stirred at 273 K for 25 min. The reaction was then quenched by the addition of sat. aqueous NaHCO₃ solution. The phases were separated, and the aqueous phase was extracted with CH₂Cl₂. The combined organic layers were dried over MgSO₄ and concentrated under reduced pressure. Flash chromatography (isohexane/ethyl acetate 20/1 to 10/1) afforded (I) as a single diastereomer and additionally a mixture of (I) and the minor diastereomer with an overall yield of 96% (21.4 mg, 0.108 mmol) as colourless crystals. Single crystals of (I) were obtained by vapor diffusion recrystallization technique from isohexane and ethyl acetate to yield colourless needles: mp 374 K; R_f 0.28 (cyclohexane/ethyl acetate 2/1); ¹H NMR (CDCl₃, 400 MHz, δ): 0.83 (d, J = 7.0 Hz, 3H), 0.98 (d, J = 6.8 Hz, 3H), 1.30 (d, J = 7.8 Hz, 3H), 2.21 (dqd, J = 10.7, 7.0, 3.3 Hz, 1H), 2.64 (q, J = 7.8 Hz, 1H) overlapped by 2.61 - 2.76 (m, 1H), 4.14 (d, J = 3.4 Hz, 1H), 4.23 (dd, J = 10.7, 3.4 Hz, 1H), 5.04 (dd, ³J(Z) = 11.0 Hz, ²J = 1.5 Hz, 1H), 5.05 (dd, ³J(E) = 17.0 Hz, ²J = 1.5 Hz, 1H), 5.84 (ddd, ³J(E) = 17.0 Hz, ³J(Z) = 11.0 Hz, ³J = 6.3 Hz, 1H); ¹³C NMR (CDCl₃, 100 MHz, δ): 9.8 (CH₃), 12.5 (CH₃), 13.7 (CH₃), 35.6 (CH), 37.2 (CH), 46.5 (CH), 75.0 (CH), 83.9 (CH), 114.4 (CH₂), 142.7 (CH), 179.1 (C); IR (cm^-1): 3520(br,s) (ν O—H, OH in H-bridges), 3085(w) (ν C—H, olefin), 2975(m) 2940(m) 2885(s) 2855(w) (ν_as,s C—H, CH₂, CH₃, CH), 1755(s) (ν C=O, lactone), 1640(w) (ν C=C), 1455(m) (δ_as C—H, CH₃, CH₂), 1385(m) (δ_s C—H, CH₃); Anal. Calcd. for C₁₁H₁₈O₃: C, 66.6; H, 9.2; Found: C, 66.5; H, 9.3; [α]_D²⁰ -14.5 (c 0.775, CHCl₃).

S3. Refinement

The H atoms were geometrically placed (C-H = 0.93-0.98, O-H = 0.82 Å) and refined as riding with U_iso(H) = 1.2_eq(C, O) or 1.5U_eq(methyl C).

Computing details

Data collection: COLLECT (Nonius, 1998); cell refinement: DENZO and SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL-Plus (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2003).

Figures

Fig. 1. : The molecular structure of the title compound, showing the labelling of all non-H atoms. Displacement ellipsoids are shown at the 30% probability level.

(3S,4S,5S)-4-Hydroxy-3-methyl-5-[(2S,3R)-3- methylpent-4-en-2-yl]-4,5-dihydrofuran-2(3H)-one

Crystal data

C11H18O3	F(000) = 432
Mr = 198.25	Dx = 1.139 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 7554 reflections
a = 5.4414 (14) Å	θ = 2.8–25.0°
b = 10.132 (2) Å	µ = 0.08 mm^−1
c = 20.975 (8) Å	T = 291 K
V = 1156.4 (6) Å^3	Needle, colourless
Z = 4	0.36 × 0.06 × 0.02 mm

Data collection

Nonius KappaCCD diffractometer	346 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.048
Graphite monochromator	θmax = 25.0°, θmin = 2.8°
Detector resolution: 19 vertical, 18 horizontal pixels mm^-1	h = −6→6
111 frames via ω–rotation (Δω=2%) and two times 180 s per frame (three sets at different κ–angles) scans	k = −12→12
7554 measured reflections	l = −24→24
1223 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.036	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.087	H-atom parameters constrained
S = 0.97	[1.0 exp(5.65(sinθ/λ)^2)]/[σ^2(Fo^2)]
1223 reflections	(Δ/σ)max = 0.007
131 parameters	Δρmax = 0.09 e Å^−3
0 restraints	Δρmin = −0.13 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.1778 (7)	0.0092 (4)	−0.3153 (2)	0.0647 (11)
O2	0.4408 (8)	0.0462 (4)	−0.2370 (2)	0.0971 (19)
O3	0.3095 (10)	−0.2710 (5)	−0.3391 (2)	0.0890 (15)
H3	0.4090	−0.3080	−0.3158	0.133*
C1	0.2948 (12)	−0.0261 (7)	−0.2615 (3)	0.075 (2)
C2	0.2076 (11)	−0.1595 (6)	−0.2396 (3)	0.0641 (19)
H2A	0.3449	−0.2114	−0.2227	0.077*
C3	0.1142 (11)	−0.2191 (6)	−0.3017 (3)	0.0635 (19)
H3B	−0.0147	−0.2849	−0.2942	0.076*
C4	0.0156 (11)	−0.0982 (5)	−0.3372 (3)	0.0596 (18)
H4A	−0.1522	−0.0803	−0.3227	0.072*
C5	0.0176 (10)	−0.1020 (6)	−0.4090 (3)	0.0578 (17)
H5A	0.1854	−0.1235	−0.4225	0.069*
C6	−0.0502 (11)	0.0338 (6)	−0.4390 (3)	0.069 (2)
H6A	0.0627	0.0986	−0.4205	0.082*
C7	0.0064 (15)	0.0286 (7)	−0.5094 (4)	0.107 (3)
H7A	0.1591	−0.0070	−0.5193	0.129*
C8	−0.1131 (18)	0.0629 (9)	−0.5549 (4)	0.170 (4)
H8A	−0.2681	0.0996	−0.5491	0.205*
H8B	−0.0501	0.0527	−0.5958	0.205*
C9	0.0066 (12)	−0.1412 (5)	−0.1883 (3)	0.093 (2)
H9A	−0.0491	−0.2261	−0.1740	0.140*
H9B	−0.1291	−0.0932	−0.2062	0.140*
H9C	0.0731	−0.0929	−0.1529	0.140*
C10	−0.1534 (11)	−0.2165 (5)	−0.4322 (3)	0.085 (2)
H10A	−0.0821	−0.2998	−0.4207	0.128*
H10B	−0.1712	−0.2119	−0.4777	0.128*
H10C	−0.3118	−0.2079	−0.4125	0.128*
C11	−0.3096 (12)	0.0798 (6)	−0.4222 (3)	0.102 (3)
H11A	−0.3376	0.1657	−0.4401	0.152*
H11B	−0.3269	0.0840	−0.3767	0.152*
H11C	−0.4273	0.0187	−0.4393	0.152*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.064 (3)	0.056 (3)	0.074 (3)	−0.002 (3)	−0.011 (3)	−0.006 (2)
O2	0.091 (4)	0.110 (4)	0.091 (4)	−0.027 (3)	−0.026 (3)	−0.012 (3)
O3	0.105 (4)	0.080 (3)	0.083 (3)	0.034 (3)	0.005 (3)	0.002 (3)
C1	0.062 (6)	0.083 (6)	0.081 (6)	0.010 (5)	−0.004 (5)	−0.010 (5)
C2	0.073 (5)	0.065 (5)	0.054 (5)	0.008 (4)	−0.013 (4)	0.009 (3)
C3	0.072 (5)	0.048 (4)	0.071 (5)	0.000 (4)	0.009 (4)	0.005 (4)
C4	0.053 (5)	0.056 (4)	0.070 (5)	0.000 (4)	0.002 (4)	−0.006 (4)
C5	0.039 (4)	0.068 (4)	0.066 (5)	0.001 (4)	−0.002 (4)	−0.008 (4)
C6	0.072 (6)	0.073 (4)	0.061 (5)	0.005 (4)	−0.013 (4)	0.009 (4)
C7	0.133 (7)	0.106 (6)	0.082 (7)	0.050 (6)	−0.028 (6)	0.007 (5)
C8	0.233 (13)	0.159 (9)	0.119 (10)	−0.006 (8)	−0.019 (9)	0.019 (7)
C9	0.119 (7)	0.089 (5)	0.071 (6)	0.002 (5)	0.021 (6)	0.004 (4)
C10	0.094 (6)	0.078 (5)	0.084 (5)	−0.016 (4)	−0.015 (5)	−0.013 (4)
C11	0.085 (6)	0.111 (6)	0.109 (6)	0.048 (5)	0.007 (5)	0.021 (4)

Geometric parameters (Å, º)

O1—C1	1.344 (6)	C6—C7	1.508 (8)
O1—C4	1.475 (6)	C6—C11	1.527 (6)
O2—C1	1.196 (6)	C6—H6A	0.9800
O3—C3	1.422 (6)	C7—C8	1.207 (8)
O3—H3	0.8200	C7—H7A	0.9300
C1—C2	1.504 (7)	C8—H8A	0.9300
C2—C3	1.523 (7)	C8—H8B	0.9300
C2—C9	1.546 (7)	C9—H9A	0.9600
C2—H2A	0.9800	C9—H9B	0.9600
C3—C4	1.531 (6)	C9—H9C	0.9600
C3—H3B	0.9800	C10—H10A	0.9600
C4—C5	1.506 (6)	C10—H10B	0.9600
C4—H4A	0.9800	C10—H10C	0.9600
C5—C6	1.557 (6)	C11—H11A	0.9600
C5—C10	1.564 (7)	C11—H11B	0.9600
C5—H5A	0.9800	C11—H11C	0.9600
C1—O1—C4	110.5 (5)	C7—C6—C5	108.4 (5)
C3—O3—H3	109.5	C11—C6—C5	113.3 (5)
O2—C1—O1	120.8 (7)	C7—C6—H6A	106.5
O2—C1—C2	129.0 (7)	C11—C6—H6A	106.5
O1—C1—C2	110.2 (6)	C5—C6—H6A	106.5
C1—C2—C3	101.6 (5)	C8—C7—C6	130.9 (9)
C1—C2—C9	109.1 (5)	C8—C7—H7A	114.6
C3—C2—C9	114.0 (6)	C6—C7—H7A	114.6
C1—C2—H2A	110.6	C7—C8—H8A	120.0
C3—C2—H2A	110.6	C7—C8—H8B	120.0
C9—C2—H2A	110.6	H8A—C8—H8B	120.0
O3—C3—C2	111.7 (5)	C2—C9—H9A	109.5
O3—C3—C4	106.8 (5)	C2—C9—H9B	109.5
C2—C3—C4	102.5 (5)	H9A—C9—H9B	109.5
O3—C3—H3B	111.8	C2—C9—H9C	109.5
C2—C3—H3B	111.8	H9A—C9—H9C	109.5
C4—C3—H3B	111.8	H9B—C9—H9C	109.5
O1—C4—C5	109.1 (5)	C5—C10—H10A	109.5
O1—C4—C3	103.2 (4)	C5—C10—H10B	109.5
C5—C4—C3	117.6 (5)	H10A—C10—H10B	109.5
O1—C4—H4A	108.8	C5—C10—H10C	109.5
C5—C4—H4A	108.8	H10A—C10—H10C	109.5
C3—C4—H4A	108.8	H10B—C10—H10C	109.5
C4—C5—C6	112.3 (5)	C6—C11—H11A	109.5
C4—C5—C10	109.0 (5)	C6—C11—H11B	109.5
C6—C5—C10	112.8 (5)	H11A—C11—H11B	109.5
C4—C5—H5A	107.5	C6—C11—H11C	109.5
C6—C5—H5A	107.5	H11A—C11—H11C	109.5
C10—C5—H5A	107.5	H11B—C11—H11C	109.5
C7—C6—C11	115.1 (5)
C4—O1—C1—O2	177.8 (6)	C2—C3—C4—O1	31.7 (6)
C4—O1—C1—C2	−3.8 (7)	O3—C3—C4—C5	34.3 (8)
O2—C1—C2—C3	−157.8 (7)	C2—C3—C4—C5	151.8 (5)
O1—C1—C2—C3	24.0 (7)	O1—C4—C5—C6	−54.5 (6)
O2—C1—C2—C9	81.5 (9)	C3—C4—C5—C6	−171.5 (5)
O1—C1—C2—C9	−96.7 (6)	O1—C4—C5—C10	179.7 (5)
C1—C2—C3—O3	80.8 (6)	C3—C4—C5—C10	62.7 (7)
C9—C2—C3—O3	−162.0 (5)	C4—C5—C6—C7	168.6 (6)
C1—C2—C3—C4	−33.2 (6)	C10—C5—C6—C7	−67.7 (7)
C9—C2—C3—C4	84.0 (6)	C4—C5—C6—C11	−62.3 (7)
C1—O1—C4—C5	−143.8 (5)	C10—C5—C6—C11	61.4 (7)
C1—O1—C4—C3	−18.0 (6)	C11—C6—C7—C8	5.6 (14)
O3—C3—C4—O1	−85.8 (5)	C5—C6—C7—C8	133.7 (11)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O2^i	0.82	2.02	2.798 (6)	158

Symmetry code: (i) −x+1, y−1/2, −z−1/2.