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

Annika Gille; Dieter Bläser; Roland Boese; Hans Preut; Martin Hiersemann

doi:10.1107/S1600536808042414

. 2008 Dec 17;65(Pt 1):o154. doi: 10.1107/S1600536808042414

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

Annika Gille ^a, Dieter Bläser ^b, Roland Boese ^b, Hans Preut ^a,^*, Martin Hiersemann ^a

PMCID: PMC2968068 PMID: 21581612

Abstract

The relative configuration of the title compound, C₁₁H₁₈O₃, was corroborated by single-crystal X-ray diffraction analysis. In the crystal, molecules are linked via a O—H⋯O hydrogen bond and a chain of molecules is formed along [010].

Related literature

For further synthetic details, see: Abraham, Körner & Hiersemann (2004 ▶); Abraham, Körner et al. (2004 ▶); Evans et al. (1981 ▶, 1999 ▶); Körner & Hiersemann (2006 ▶, 2007 ▶); Mitsunobu (1981 ▶); Mitsunobu & Yamada (1967 ▶); Mitsunobu et al. (1967 ▶); Otera et al. (1992 ▶); Pollex & Hiersemann (2005 ▶).

Experimental

Crystal data

C₁₁H₁₈O₃
M _r = 198.25
Monoclinic,
a = 7.604 (2) Å
b = 6.574 (2) Å
c = 11.323 (4) Å
β = 91.211 (7)°
V = 565.9 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 173 (2) K
0.35 × 0.10 × 0.07 mm

Data collection

Siemens SMART three-axis goniometer with APEXII area-detector diffractometer
Absorption correction: none
7868 measured reflections
1507 independent reflections
1076 reflections with I > 2σ(I)
R _int = 0.131

Refinement

R[F ² > 2σ(F ²)] = 0.054
wR(F ²) = 0.098
S = 0.98
1507 reflections
132 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; 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 and PLATON (Spek, 2003 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808042414/hb2861sup1.cif

e-65-0o154-sup1.cif^{(17.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808042414/hb2861Isup2.hkl

e-65-0o154-Isup2.hkl^{(74.3KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O3ⁱ	0.84	2.02	2.830 (3)	163

Open in a new tab

Symmetry code: (i) Inline graphic .

supplementary crystallographic information

Comment

The title compound, (I), was synthesized using a catalytic asymmetric Claisen rearrangement (Abraham, Körner et al., 2004; Abraham, Körner & Hiersemann, 2004; Pollex & Hiersemann, 2005; Körner & Hiersemann, 2006, 2007), a diastereoselective reduction with K-Selectride (Körner & Hiersemann, 2006, 2007), a Mitsunobu reaction (Mitsunobu & Yamada, 1967; Mitsunobu et al., 1967; Mitsunobu, 1981) 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 (Otera et al., 1992) and subsequent in situ lactonization. Fig. 1 depicts the structure of the isolated 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) followed by Mitsunobu reaction (C5 R), 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).

In the crystal, an O—H···O hydrogen bond (Table 1) links the molecules into chains propagating in [010].

Experimental

The title compound, (I), was synthesized from the corresponding syn-aldol adduct, (II), using tetrabutylammonium fluoride (TBAF) in the presence of acetic acid (Otera et al., 1992) for the removal of the silyl protecting group. The subsequent lactonization proceeded in situ.

To a solution of diastereomerically pure (II) (66 mg, 0.15 mmol, 1.0 eq) in tetrahydrofuran (0.8 ml) was added acetic acid (0.9 µl, 0.015 mmol, 0.1 eq) in tetrahydrofuran (0.1 ml) and TBAF (1 M in tetrahydrofuran, 0.225 ml, 1.5 eq) at 273 K. After stirring for 20 min at 273 K, the mixture was allowed to warm to room temperature. After stirring the reaction mixture for 4.5 h at room temperature, the reaction was quenched by the addition of sat. aqueous NH₄Cl solution. The phases were separated, and the aqueous phase was extracted with CH₂Cl₂ (3 × 5 ml). The combined organic layers were dried (MgSO₄) and concentrated under reduced pressure. Flash chromatography (isohexane/ethyl acetate 20/1 to 10/1 to 5/1) afforded (I) as a single diastereomer in quantitative yield (29.6 mg, 0.15 mmol) as colourless crystals. Colourless needles of (I) were obtained by vapor diffusion recrystallization technique from isohexane and ethyl acetate: mp 361 K; R_f 0.35 (cyclohexane/ethyl acetate 2/1); ¹H NMR (CDCl₃, 400 MHz, δ): 0.92 (d, J = 6.8 Hz, 3H), 1.05 (d, J = 6.8 Hz, 3H), 1.31 (d, J = 7.1 Hz, 3H), 1.73 (dqd, J = 6.8, 6.8, 3.6 Hz, 1H), 2.14 (br. s, 1 H), 2.33 (apparent sex, J = 7.7 Hz, 1H), 2.59 (dq, J = 8.6, 7.1 Hz, 1H), 3.91 (dd, J = 8.6 Hz, 1H), 4.20 (dd, J = 8.6, 3.6 Hz, 1H), 5.04 (d, ³J(Z) = 10.0 Hz, 1H), 5.05 (d, ³J(E) = 17.8 Hz, 1H), 5.73 (ddd, ³J(E) = 17.8 Hz, ³J(Z) = 10.0 Hz, ³J = 7.7 Hz, 1H); ¹³C NMR (CDCl₃, 100 MHz, δ): 10.7 (CH₃), 12.8 (CH₃), 17.2 (CH₃), 39.4 (CH), 41.0 (CH), 44.2 (CH), 77.2 (CH), 85.2 (CH), 115.1 (CH₂), 143.0 (CH), 176.7 (C); IR (cm^-1): 3405(br,s) (ν O—H, OH in H-bridges), 3090(w) 3005(w) (ν C—H, olefin), 2965(s) 2935(m) 2900(m) 2855(w) (ν_as,s C—H, CH₂, CH₃, CH), 1740(s) (ν C=O, lactone), 1640(w) (ν C=C), 1460(s) (δ_as C—H, CH₃, CH₂), 1380(s) (δ_s C—H, CH₃); Anal. Calcd. for C₁₁H₁₈O₃: C, 66.6; H, 9.2; Found: C, 66.7; H, 9.3; [α]_D²⁰ +61.4 (c 0.487, CHCl₃).