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The title compound, C12H16O6, prepared by a standard synthetic method, was determined by single-crystal X-ray crystallography to exist with a cyclo­propane ring fused to a cyclo­pentene ring. Comparison of the unit-cell dimensions and space group of this material with those of a crystal of the same material prepared using a route involving pig liver esterase hydro­lysis shows them to be identical.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270100007757/qa0312sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270100007757/qa0312Isup2.hkl
Contains datablock I

Comment top

Enzymatic reactions have been a powerful tool for the development of elegant methodologies for the syntheses of natural products (Wong & Whitesides, 1994; Drauz & Waldmann, 1995; Ohno & Otuska 1989; Schoffers et al., 1996). In particular, enzymatic dissymmetrization of symmetric meso compounds is a versatile enantio-differentiating reaction as it potentially produces only the desired enantiomer in quantitative yield without the need for separation from the mirror-image molecule.

Most enzymatic reactions, when used in organic synthesis, induce simple chemicoselective conversion of a limited range of functional groups. However, we discovered earlier the first chemicoenzymatic rearrangement which accomplishes skeletal change during enzymatic asymmetric hydrolysis of a meso diester (I) to produce the rearranged product (IV) (Niwayama et al., 1994, 1994, 1998). It is initiated by enzymatic reaction, but completed by a subsequent chemical skeletal conversion in one pot in a stereo- and regiospecific manner in a slightly basic aqueous medium. We have observed that diesters (Ia), (Ib) and (Ic) all undergo this rearrangement in quantitative to high yields, although the optical purities of the products are somewhat low under the limited conditions developed up to the present. The structures of rearranged products (IVa), (IVb) and (IVc) were established as 1-alkoxycarbonyl-6-formylbicyclo[3.1.0]hex-2-ene-2-carboxylic acids based on the 1H and 13C NMR, MS and IR spectroscopic data of these materials and their derivatives.

We have treated (IVa), isolated as an oil, with methanol and a catalytic amount of p-toluenesulfonic acid and obtained a white crystal. This crystal was identical in 1H and 13C NMR, MS and IR spectroscopic data, and in unit-cell dimensions and space group with the material 6-dimethoxymethyl-1-methoxycarbonylbicyclo[3.1.0]hex-2-ene-2-carboxylic acid, (Va), prepared by an alternative chemical route and whose crystal structure is reported here. While the material crystallizes in a centrosymmetric space group, indicating the equal presence of both enantiomers, the acetal prepared from (IVa) via the enzymatic reaction displayed optical activity. Thus, the enzymatic reaction has produced an enantiomeric excess of one form of the racemic mixture present in the crystal.

The acetal derivative has a strained bicyclic structure composed of fused cyclopropane and cyclopentene rings with three consecutive stereocentres including a quaternary carbon. The planes of the cyclopropane and cyclopentene rings subtend an angle of 67.0 (1)°.

Carboxylic-acid groups of adjacent molecules are hydrogen bonded in pairs H4c···O3(2 − x, 1 − y, −z) 1.74 Å, O4—H4c···O3 162° and O4···O3 2.668 (3) Å. There is no hydrogen-bonding between the carboxyl group and the carbomethoxy or acetal groups. The hydroxy group of the carboxyl group, which is almost coplanar with the cyclopentene ring (standard deviation from planarity of the five-membered ring is 0.02), is oriented syn to the double bond [C3—C2—C9—O4 5.0 (4)°] and the carbonyl group in the carbomethoxy group is at an angle to the cyclopentene ring [C2—C1—C7—O1 34.3 (4)°]. The two methoxy groups in the acetal group are directed away from the bicyclic ring, with the proton at C10 directed over the cyclopentene ring. This orientation in the solid may explain the somewhat shielded chemical shift (σ 3.93 p.p.m.) for this acetal proton.

Experimental top

6-Formyl-1-methoxycarbonylbicyclo[3.1.0]hex-2-ene-2-carboxylic acid was prepared as described previously (Niwayama et al., 1998). It was treated with a catalytic amount of p-toluenesulfonic acid in approximately 1 ml of methanol at room temperature, to afford the title compound, (Va), in crystalline form. The solid material was recrystallized from a hexane/diethyl ether mixture at room temperature to produce a crystal suitable for X-ray diffraction studies. The product showed no optical activity.

Computing details top

Data collection: XSCANS (Siemens, 1991); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).

6-Dimethoxymethyl-1-methoxycarbonylbicyclo[3.1.0]hex-2-ene-2-carboxylic acid top
Crystal data top
C12H16O6F(000) = 544
Mr = 256.25Dx = 1.303 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 7.537 (4) ÅCell parameters from 28 reflections
b = 13.602 (8) Åθ = 5.6–12.8°
c = 12.779 (5) ŵ = 0.11 mm1
β = 94.57 (2)°T = 293 K
V = 1305.9 (12) Å3Cube, colourless
Z = 40.2 × 0.2 × 0.2 mm
Data collection top
Syntex P4 four-circle
diffractometer
Rint = 0.126
Radiation source: fine-focus sealed tubeθmax = 27.1°, θmin = 4.3°
Graphite monochromatorh = 19
θ/2θ scansk = 117
3773 measured reflectionsl = 1616
2845 independent reflections3 standard reflections every 97 reflections
1975 reflections with I > 2σ(I) intensity decay: none
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.067Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.233H-atom parameters constrained
S = 0.99Calculated w = 1/[σ2(Fo2) + (0.1511P)2 + 0.1243P]
where P = (Fo2 + 2Fc2)/3
2845 reflections(Δ/σ)max < 0.001
164 parametersΔρmax = 0.11 e Å3
0 restraintsΔρmin = 0.08 e Å3
Crystal data top
C12H16O6V = 1305.9 (12) Å3
Mr = 256.25Z = 4
Monoclinic, P21/cMo Kα radiation
a = 7.537 (4) ŵ = 0.11 mm1
b = 13.602 (8) ÅT = 293 K
c = 12.779 (5) Å0.2 × 0.2 × 0.2 mm
β = 94.57 (2)°
Data collection top
Syntex P4 four-circle
diffractometer
Rint = 0.126
3773 measured reflections3 standard reflections every 97 reflections
2845 independent reflections intensity decay: none
1975 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0670 restraints
wR(F2) = 0.233H-atom parameters constrained
S = 0.99Δρmax = 0.11 e Å3
2845 reflectionsΔρmin = 0.08 e Å3
164 parameters
Special details top

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 (Å2) top
xyzUiso*/Ueq
C10.7023 (3)0.72696 (17)0.15677 (19)0.0400 (6)
C20.6771 (3)0.66163 (18)0.06139 (18)0.0394 (6)
C30.5121 (3)0.6704 (2)0.0124 (2)0.0485 (6)
H3A0.44600.63470.05350.050*
C40.4010 (3)0.7463 (2)0.0634 (2)0.0543 (7)
H4A0.29210.71810.08370.080*
H4B0.37330.80050.01690.080*
C50.5208 (3)0.77995 (18)0.1608 (2)0.0483 (7)
H5A0.52210.84840.17900.080*
C60.5815 (3)0.70636 (17)0.24505 (19)0.0421 (6)
H6A0.62220.73530.31120.080*
C70.8776 (3)0.78091 (17)0.1753 (2)0.0472 (6)
C81.0960 (4)0.8403 (3)0.3052 (3)0.0757 (10)
H8A1.11780.84390.38020.080*
H8B1.19060.80450.27650.080*
H8C1.09050.90560.27650.080*
C90.8167 (3)0.59090 (18)0.03472 (18)0.0406 (6)
C100.4876 (3)0.60834 (18)0.25657 (18)0.0413 (6)
H10A0.42650.59170.19010.080*
C110.7129 (5)0.5464 (3)0.3835 (3)0.0862 (12)
H11A0.78660.49000.39980.080*
H11B0.78680.60290.37500.080*
H11C0.63810.55800.43960.080*
C120.2272 (4)0.5514 (3)0.3339 (3)0.0688 (9)
H12A0.14640.56830.38540.080*
H12B0.16290.54620.26620.080*
H12C0.28310.48970.35210.080*
O10.9631 (3)0.81238 (18)0.10620 (19)0.0708 (7)
O20.9284 (3)0.79096 (16)0.27818 (17)0.0628 (6)
O30.9586 (2)0.58392 (15)0.08861 (15)0.0550 (6)
O40.7758 (2)0.53716 (16)0.05012 (15)0.0590 (6)
H4C0.86450.48660.05180.050*
O50.6047 (3)0.52982 (14)0.28781 (16)0.0576 (6)
O60.3600 (2)0.62621 (14)0.32987 (15)0.0529 (5)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0363 (12)0.0356 (11)0.0497 (13)0.0031 (9)0.0133 (10)0.0003 (9)
C20.0377 (12)0.0417 (12)0.0402 (12)0.0013 (10)0.0123 (9)0.0031 (9)
C30.0431 (13)0.0599 (15)0.0435 (13)0.0041 (12)0.0087 (10)0.0068 (11)
C40.0413 (13)0.0602 (16)0.0626 (16)0.0137 (12)0.0127 (11)0.0164 (13)
C50.0400 (13)0.0375 (12)0.0700 (17)0.0049 (10)0.0206 (11)0.0011 (11)
C60.0432 (13)0.0387 (12)0.0460 (13)0.0001 (10)0.0138 (10)0.0081 (10)
C70.0409 (13)0.0350 (12)0.0673 (17)0.0024 (10)0.0147 (11)0.0059 (11)
C80.0465 (16)0.079 (2)0.101 (3)0.0055 (16)0.0009 (16)0.031 (2)
C90.0398 (12)0.0439 (12)0.0392 (11)0.0002 (10)0.0104 (9)0.0045 (9)
C100.0435 (12)0.0428 (13)0.0389 (12)0.0020 (10)0.0113 (9)0.0023 (9)
C110.062 (2)0.096 (3)0.098 (3)0.014 (2)0.0106 (19)0.025 (2)
C120.0543 (16)0.082 (2)0.071 (2)0.0231 (16)0.0148 (14)0.0068 (17)
O10.0568 (13)0.0771 (15)0.0816 (15)0.0193 (11)0.0250 (11)0.0044 (12)
O20.0467 (11)0.0706 (14)0.0714 (13)0.0107 (10)0.0059 (9)0.0171 (11)
O30.0470 (10)0.0614 (12)0.0559 (11)0.0141 (9)0.0000 (8)0.0175 (9)
O40.0450 (10)0.0710 (13)0.0606 (12)0.0110 (9)0.0023 (8)0.0241 (10)
O50.0607 (12)0.0435 (10)0.0706 (13)0.0059 (9)0.0170 (9)0.0057 (9)
O60.0454 (10)0.0592 (11)0.0564 (11)0.0067 (8)0.0194 (8)0.0044 (9)
Geometric parameters (Å, º) top
C1—C21.508 (3)C8—H8A0.9601
C1—C71.513 (4)C8—H8B0.9600
C1—C61.531 (3)C8—H8C0.9601
C1—C51.551 (3)C9—O31.228 (3)
C2—C31.353 (4)C9—O41.323 (3)
C2—C91.485 (3)C10—O61.416 (3)
C3—C41.509 (4)C10—O51.422 (3)
C3—H3A1.0613C10—H10A0.9600
C4—C51.548 (4)C11—O51.433 (4)
C4—H4A0.9600C11—H11A0.9600
C4—H4B0.9599C11—H11B0.9600
C5—C61.514 (4)C11—H11C0.9600
C5—H5A0.9601C12—O61.431 (3)
C6—C101.522 (3)C12—H12A0.9600
C6—H6A0.9600C12—H12B0.9600
C7—O11.212 (3)C12—H12C0.9600
C7—O21.347 (3)O4—H4C0.9600
C8—O21.448 (4)
C2—C1—C7117.63 (19)O2—C7—C1112.2 (2)
C2—C1—C6116.36 (19)O2—C8—H8A109.8
C7—C1—C6122.5 (2)O2—C8—H8B109.5
C2—C1—C5104.3 (2)H8A—C8—H8B109.5
C7—C1—C5122.1 (2)O2—C8—H8C109.1
C6—C1—C558.83 (16)H8A—C8—H8C109.5
C3—C2—C9126.4 (2)H8B—C8—H8C109.5
C3—C2—C1112.0 (2)O3—C9—O4123.5 (2)
C9—C2—C1121.4 (2)O3—C9—C2121.5 (2)
C2—C3—C4112.4 (2)O4—C9—C2115.0 (2)
C2—C3—H3A133.1O6—C10—O5112.48 (19)
C4—C3—H3A114.5O6—C10—C6105.02 (19)
C3—C4—C5104.0 (2)O5—C10—C6113.7 (2)
C3—C4—H4A111.1O6—C10—H10A108.8
C5—C4—H4A110.9O5—C10—H10A108.3
C3—C4—H4B111.1C6—C10—H10A108.3
C5—C4—H4B110.8O5—C11—H11A109.8
H4A—C4—H4B108.9O5—C11—H11B109.0
C6—C5—C159.93 (15)H11A—C11—H11B109.5
C6—C5—C4120.0 (2)O5—C11—H11C109.6
C1—C5—C4107.1 (2)H11A—C11—H11C109.5
C6—C5—H5A118.2H11B—C11—H11C109.5
C1—C5—H5A117.8O6—C12—H12A109.8
C4—C5—H5A118.4O6—C12—H12B109.0
C5—C6—C10122.1 (2)H12A—C12—H12B109.5
C5—C6—C161.24 (15)O6—C12—H12C109.7
C10—C6—C1122.68 (19)H12A—C12—H12C109.5
C5—C6—H6A114.3H12B—C12—H12C109.5
C10—C6—H6A113.1C7—O2—C8117.1 (3)
C1—C6—H6A114.0C9—O4—H4C107.2
O1—C7—O2123.3 (2)C10—O5—C11114.8 (2)
O1—C7—C1124.5 (3)C10—O6—C12114.5 (2)
C3—C2—C9—O45.0 (4)C2—C1—C7—O134.3 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O4—H4c···O3i0.961.742.668 (3)162
Symmetry code: (i) x+2, y+1, z.

Experimental details

Crystal data
Chemical formulaC12H16O6
Mr256.25
Crystal system, space groupMonoclinic, P21/c
Temperature (K)293
a, b, c (Å)7.537 (4), 13.602 (8), 12.779 (5)
β (°) 94.57 (2)
V3)1305.9 (12)
Z4
Radiation typeMo Kα
µ (mm1)0.11
Crystal size (mm)0.2 × 0.2 × 0.2
Data collection
DiffractometerSyntex P4 four-circle
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
3773, 2845, 1975
Rint0.126
(sin θ/λ)max1)0.641
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.067, 0.233, 0.99
No. of reflections2845
No. of parameters164
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.11, 0.08

Computer programs: XSCANS (Siemens, 1991), XSCANS, SHELXS97 (Sheldrick, 1990), SHELXL97 (Sheldrick, 1997).

Selected bond lengths (Å) top
C1—C21.508 (3)C7—O11.212 (3)
C1—C71.513 (4)C7—O21.347 (3)
C1—C61.531 (3)C8—O21.448 (4)
C1—C51.551 (3)C9—O31.228 (3)
C2—C31.353 (4)C9—O41.323 (3)
C2—C91.485 (3)C10—O61.416 (3)
C3—C41.509 (4)C10—O51.422 (3)
C4—C51.548 (4)C11—O51.433 (4)
C5—C61.514 (4)C12—O61.431 (3)
C6—C101.522 (3)O4—H4C0.9600
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O4—H4c···O3i0.961.742.668 (3)162
Symmetry code: (i) x+2, y+1, z.
 

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