(RS,RS)-5-[Hydr­oxy(4-methyl­phen­yl)meth­yl]furan-2(5H)-one

The crystal structure of the racemic title compound, C₁₂H₁₂O₃, allowed the determination of the relative configuration at the two stereogenic centers. For the R,R isomer, the O—C—C—O and C—C—C—C torsion angles around the bond between the two methine C atoms are 62.38 (15) and −175.49 (13)°, respectively. The furan and tolyl groups are almost perpendicular, with a dihedral angle of 79.39 (5)°. Strong and linear inter­molecular O—H...O hydrogen bonding (H...O = 2.04 Å and O—H...O = 177°) is observed between the hydroxyl group and the C=O oxygen.

Key indicators

• Single-crystal X-ray study
• T = 100 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.026
• wR factor = 0.072
• Data-to-parameter ratio = 8.4

checkCIF/PLATON results

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Alert level C
PLAT230_ALERT_2_C Hirshfeld Test Diff for    O1     -   C1      ..       6.57 su

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           27.50
           From the CIF: _reflns_number_total               1158
           Count of symmetry unique reflns         1159
           Completeness (_total/calc)             99.91%
           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
PLAT792_ALERT_1_G Check the Absolute Configuration of C4     = ...          R
PLAT792_ALERT_1_G Check the Absolute Configuration of C5     = ...          R
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          1

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

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

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S1. Comment

In the context of our research on the bismuth(III)-catalyzed condensation reactions (Ollevier et al., 2007; Ollevier et al., 2005), we focused on the vinylogous Mukaiyama aldol of silyl dienol ethers with various aldehydes (Ollevier et al., 2006). We carried out the reaction of 2-(trimethylsilyloxy)furan with p-tolualdehyde. The vinylogous Mukaiyama aldol reaction afforded 5-(hydroxy(4-tolyl)methyl)furan-2(5H)-one as the syn major diastereoisomer (syn/anti = 94:6) (Fig. 2). From the present crystallographic analysis of a racemic compound, the relative configuration at the two stereogenic centers (C4 and C5) was established (4R,5R) (Fig. 1) or (4S,5S).

Related literature

For information on bismuth(III)-catalyzed condensation reactions, see: Ollevier et al. (2005, 2006, 2007).

S2. Experimental

To a solution of p-tolualdehyde (85 mg, 0.71 mmol) in diethyl ether (0.5 ml), was added Bi(OTf)₃.4H₂O (5.0 mg, 0.007 mmol). The mixture was brought to -78 °C, stirred at this temperature for 0.25 h, and a solution of 2-(trimethylsilyloxy)furan (133 mg, 0.85 mmol) in 0.5 ml of diethyl ether was added dropwise. The mixture was stirred at -78 °C until the reaction was completed as indicated by TLC. The reaction was diluted in tetrahydrofuran (1.0 ml) and quenched with 10% aqueous HCl (1.0 ml). The mixture was stirred for 0.25 h at room temperature, neutralized by addition of a saturated aqueous NaHCO₃ solution, and extracted with ethyl acetate. The organic phases were combined, dried over Na₂SO₄, and concentrated under reduced pressure (rotary evaporator). The syn/anti ratio (94:6) was determined by ¹H NMR analysis of the crude product (δ major: 4.66 p.p.m., δ minor: 5.03 p.p.m.). The residue was purified by silica gel chromatography (25% ethyl acetate/hexane) to afford 130 mg (90%) of the pure syn diastereoisomer (white solid). The product was recrystallized (hexane/ethyl acetate) to afford the title compound as white crystals.

S3. Refinement

The H atoms were generated geometrically with C—H and O—H distances of 0.95 - 1.00Å and 0.84Å respectively, and were included in the refinement in the riding model approximation; their temperature factors were set to 1.5 times those of the equivalent isotropic temperature factors of the parent site (methyl) and 1.2 times for others. Due to weak anomalous scattering effects of the light atoms with Mo radiation, Friedel pairs were merged.

Computing details

Data collection: APEX2 (Bruker, 2005); cell refinement: APEX2 (Bruker, 2005); data reduction: SAINT (Bruker, 2003); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 2001); software used to prepare material for publication: SHELXTL (Bruker, 2001).

Figures

	Fig. 1. Ellipsoid plot.
	Fig. 2. The preparation.

(RS,RS)-5-[Hydroxy(4-methylphenyl)methyl]furan-2(5H)-one

Crystal data

C12H12O3	Dx = 1.386 Mg m^−3
Mr = 204.22	Melting point: 413 K
Orthorhombic, Pna21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2n	Cell parameters from 5985 reflections
a = 8.9068 (6) Å	θ = 2.2–28.1°
b = 5.9555 (4) Å	µ = 0.10 mm^−1
c = 18.4541 (11) Å	T = 100 K
V = 978.89 (11) Å^3	Rectangular, colorless
Z = 4	0.44 × 0.24 × 0.14 mm
F(000) = 432

Data collection

Bruker SMART APEXII CCD diffractometer	1158 independent reflections
Radiation source: fine-focus sealed tube	1139 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.014
ω scans	θmax = 27.5°, θmin = 2.2°
Absorption correction: multi-scan (SADABS; Sheldrick, 2004)	h = −11→11
Tmin = 0.948, Tmax = 0.986	k = −7→7
7650 measured reflections	l = −23→23

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)] = 0.026	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.072	H-atom parameters constrained
S = 1.08	w = 1/[σ^2(Fo^2) + (0.0489P)^2 + 0.1853P] where P = (Fo^2 + 2Fc^2)/3
1158 reflections	(Δ/σ)max = 0.001
138 parameters	Δρmax = 0.25 e Å^−3
1 restraint	Δρmin = −0.14 e Å^−3

Special details

Experimental. Mp 140 °C; R_f = 0.20 (30% ethyl acetate/hexane); ¹H NMR (400 MHz, CDCl₃): δ = 7.25 (d, J = 7.6 Hz, 2H), 7.21 (d, J = 7.6 Hz, 2H), 7.13 (dd, J = 5.9, 1.6 Hz, 1H), 6.12 (dd, J = 5.9, 2.0 Hz, 1H), 5.13–5.16 (m, 2H), 4.66 (d, J = 7.2 Hz, 1H), 2.80 (br s, 1H), 2.36 (s, 3H); RMN ¹³C (100 MHz, CDCl₃): δ = 172.6, 153.4, 139.1, 134.9, 129.7, 126.9, 123.2, 87.2, 75.8, 21.5; IR (KBr): 3411, 1742 cm^-1; HRMS: Calcd for C₁₂H₁₂O₃ (M⁺) 204.0786, found 204.0782.

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 F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ > σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ 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	0.50432 (13)	0.5539 (2)	0.67957 (7)	0.0191 (3)
C1	0.38910 (18)	0.5085 (2)	0.64822 (10)	0.0153 (3)
O2	0.39225 (12)	0.43751 (19)	0.57840 (6)	0.0146 (2)
C2	0.23233 (18)	0.5146 (3)	0.67242 (10)	0.0164 (3)
H2	0.1986	0.5591	0.7191	0.020*
C3	0.14558 (18)	0.4476 (3)	0.61813 (10)	0.0159 (3)
H3	0.0392	0.4373	0.6197	0.019*
C4	0.24068 (17)	0.3909 (3)	0.55420 (9)	0.0144 (3)
H4	0.2147	0.4927	0.5130	0.017*
C5	0.23120 (17)	0.1448 (3)	0.52891 (8)	0.0141 (3)
H5	0.1268	0.1152	0.5115	0.017*
O3	0.26211 (13)	−0.00292 (19)	0.58730 (7)	0.0175 (3)
H3A	0.1863	−0.0119	0.6142	0.026*
C6	0.33994 (16)	0.0935 (3)	0.46734 (8)	0.0142 (3)
C7	0.41772 (18)	−0.1102 (3)	0.46543 (9)	0.0171 (3)
H7	0.4074	−0.2135	0.5043	0.021*
C8	0.51017 (18)	−0.1631 (3)	0.40711 (9)	0.0187 (3)
H8	0.5611	−0.3033	0.4067	0.022*
C9	0.4542 (2)	0.1892 (3)	0.35204 (9)	0.0196 (3)
H9	0.4669	0.2940	0.3137	0.023*
C10	0.36031 (18)	0.2425 (3)	0.40992 (9)	0.0178 (3)
H10	0.3094	0.3827	0.4103	0.021*
C11	0.52985 (19)	−0.0159 (3)	0.34946 (9)	0.0177 (3)
C12	0.6291 (2)	−0.0768 (3)	0.28616 (10)	0.0250 (4)
H12A	0.5777	−0.1873	0.2556	0.038*
H12B	0.7234	−0.1409	0.3041	0.038*
H12C	0.6507	0.0582	0.2576	0.038*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0148 (5)	0.0221 (6)	0.0205 (6)	−0.0026 (5)	−0.0003 (4)	−0.0030 (5)
C1	0.0189 (8)	0.0103 (6)	0.0168 (7)	0.0008 (5)	0.0027 (6)	0.0001 (5)
O2	0.0113 (5)	0.0165 (5)	0.0159 (5)	−0.0011 (4)	0.0019 (4)	−0.0003 (4)
C2	0.0166 (7)	0.0144 (7)	0.0182 (7)	0.0011 (5)	0.0044 (6)	0.0001 (6)
C3	0.0151 (7)	0.0126 (7)	0.0198 (7)	0.0011 (6)	0.0029 (6)	0.0028 (6)
C4	0.0108 (7)	0.0157 (7)	0.0167 (7)	0.0005 (5)	−0.0001 (5)	0.0017 (6)
C5	0.0122 (7)	0.0157 (7)	0.0145 (7)	−0.0001 (5)	0.0011 (6)	0.0012 (6)
O3	0.0168 (5)	0.0184 (6)	0.0174 (6)	0.0020 (4)	0.0041 (5)	0.0054 (5)
C6	0.0115 (6)	0.0164 (7)	0.0148 (7)	−0.0016 (5)	−0.0011 (6)	−0.0016 (6)
C7	0.0173 (7)	0.0142 (7)	0.0199 (7)	−0.0016 (6)	0.0006 (6)	0.0006 (6)
C8	0.0186 (7)	0.0153 (7)	0.0223 (8)	0.0003 (6)	−0.0009 (6)	−0.0034 (6)
C9	0.0221 (8)	0.0214 (8)	0.0152 (7)	−0.0010 (7)	0.0001 (6)	0.0005 (6)
C10	0.0181 (7)	0.0172 (7)	0.0181 (7)	0.0026 (6)	−0.0013 (6)	0.0016 (7)
C11	0.0169 (8)	0.0209 (8)	0.0152 (7)	−0.0031 (6)	0.0004 (6)	−0.0059 (6)
C12	0.0278 (9)	0.0277 (9)	0.0196 (8)	0.0001 (7)	0.0060 (7)	−0.0066 (7)

Geometric parameters (Å, º)

O1—C1	1.209 (2)	C6—C10	1.394 (2)
C1—O2	1.356 (2)	C6—C7	1.397 (2)
C1—C2	1.466 (2)	C7—C8	1.391 (2)
O2—C4	1.4489 (18)	C7—H7	0.9500
C2—C3	1.327 (3)	C8—C11	1.390 (2)
C2—H2	0.9500	C8—H8	0.9500
C3—C4	1.491 (2)	C9—C10	1.393 (2)
C3—H3	0.9500	C9—C11	1.396 (2)
C4—C5	1.541 (2)	C9—H9	0.9500
C4—H4	1.0000	C10—H10	0.9500
C5—O3	1.4179 (19)	C11—C12	1.509 (2)
C5—C6	1.524 (2)	C12—H12A	0.9800
C5—H5	1.0000	C12—H12B	0.9800
O3—H3A	0.8400	C12—H12C	0.9800
O1—C1—O2	120.45 (15)	C10—C6—C5	121.47 (14)
O1—C1—C2	131.09 (16)	C7—C6—C5	120.51 (14)
O2—C1—C2	108.46 (14)	C8—C7—C6	120.64 (15)
C1—O2—C4	109.47 (12)	C8—C7—H7	119.7
C3—C2—C1	108.50 (15)	C6—C7—H7	119.7
C3—C2—H2	125.8	C11—C8—C7	121.59 (15)
C1—C2—H2	125.8	C11—C8—H8	119.2
C2—C3—C4	109.56 (14)	C7—C8—H8	119.2
C2—C3—H3	125.2	C10—C9—C11	121.03 (15)
C4—C3—H3	125.2	C10—C9—H9	119.5
O2—C4—C3	104.00 (13)	C11—C9—H9	119.5
O2—C4—C5	109.07 (12)	C9—C10—C6	121.05 (14)
C3—C4—C5	115.09 (13)	C9—C10—H10	119.5
O2—C4—H4	109.5	C6—C10—H10	119.5
C3—C4—H4	109.5	C8—C11—C9	117.71 (15)
C5—C4—H4	109.5	C8—C11—C12	120.98 (15)
O3—C5—C6	108.60 (12)	C9—C11—C12	121.31 (15)
O3—C5—C4	110.45 (12)	C11—C12—H12A	109.5
C6—C5—C4	112.43 (12)	C11—C12—H12B	109.5
O3—C5—H5	108.4	H12A—C12—H12B	109.5
C6—C5—H5	108.4	C11—C12—H12C	109.5
C4—C5—H5	108.4	H12A—C12—H12C	109.5
C5—O3—H3A	109.5	H12B—C12—H12C	109.5
C10—C6—C7	117.96 (14)
O1—C1—O2—C4	178.96 (14)	O3—C5—C6—C10	−164.99 (14)
C2—C1—O2—C4	−0.91 (16)	C4—C5—C6—C10	−42.46 (19)
O1—C1—C2—C3	−179.55 (17)	O3—C5—C6—C7	17.78 (19)
O2—C1—C2—C3	0.31 (17)	C4—C5—C6—C7	140.31 (15)
C1—C2—C3—C4	0.41 (18)	C10—C6—C7—C8	−1.2 (2)
C1—O2—C4—C3	1.11 (16)	C5—C6—C7—C8	176.12 (14)
C1—O2—C4—C5	−122.16 (13)	C6—C7—C8—C11	0.7 (2)
C2—C3—C4—O2	−0.92 (17)	C11—C9—C10—C6	0.5 (3)
C2—C3—C4—C5	118.32 (15)	C7—C6—C10—C9	0.6 (2)
O2—C4—C5—O3	62.38 (15)	C5—C6—C10—C9	−176.71 (15)
C3—C4—C5—O3	−54.01 (18)	C7—C8—C11—C9	0.4 (2)
O2—C4—C5—C6	−59.10 (16)	C7—C8—C11—C12	−179.29 (15)
C3—C4—C5—C6	−175.49 (13)	C10—C9—C11—C8	−1.0 (2)
H4—C4—C5—H5	−59	C10—C9—C11—C12	178.67 (16)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3A···O1^i	0.84	2.04	2.8747 (17)	177

Symmetry code: (i) x−1/2, −y+1/2, z.