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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
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.
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
C12H16O6 | F(000) = 544 |
Mr = 256.25 | Dx = 1.303 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 7.537 (4) Å | Cell parameters from 28 reflections |
b = 13.602 (8) Å | θ = 5.6–12.8° |
c = 12.779 (5) Å | µ = 0.11 mm−1 |
β = 94.57 (2)° | T = 293 K |
V = 1305.9 (12) Å3 | Cube, colourless |
Z = 4 | 0.2 × 0.2 × 0.2 mm |
Data collection top
Syntex P4 four-circle diffractometer | Rint = 0.126 |
Radiation source: fine-focus sealed tube | θmax = 27.1°, θmin = 4.3° |
Graphite monochromator | h = −1→9 |
θ/2θ scans | k = −1→17 |
3773 measured reflections | l = −16→16 |
2845 independent reflections | 3 standard reflections every 97 reflections |
1975 reflections with I > 2σ(I) | intensity decay: none |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.067 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.233 | H-atom parameters constrained |
S = 0.99 | Calculated w = 1/[σ2(Fo2) + (0.1511P)2 + 0.1243P] where P = (Fo2 + 2Fc2)/3 |
2845 reflections | (Δ/σ)max < 0.001 |
164 parameters | Δρmax = 0.11 e Å−3 |
0 restraints | Δρmin = −0.08 e Å−3 |
Crystal data top
C12H16O6 | V = 1305.9 (12) Å3 |
Mr = 256.25 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 7.537 (4) Å | µ = 0.11 mm−1 |
b = 13.602 (8) Å | T = 293 K |
c = 12.779 (5) Å | 0.2 × 0.2 × 0.2 mm |
β = 94.57 (2)° | |
Data collection top
Syntex P4 four-circle diffractometer | Rint = 0.126 |
3773 measured reflections | 3 standard reflections every 97 reflections |
2845 independent reflections | intensity decay: none |
1975 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.067 | 0 restraints |
wR(F2) = 0.233 | H-atom parameters constrained |
S = 0.99 | Δρmax = 0.11 e Å−3 |
2845 reflections | Δρmin = −0.08 e Å−3 |
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 | x | y | z | Uiso*/Ueq | |
C1 | 0.7023 (3) | 0.72696 (17) | 0.15677 (19) | 0.0400 (6) | |
C2 | 0.6771 (3) | 0.66163 (18) | 0.06139 (18) | 0.0394 (6) | |
C3 | 0.5121 (3) | 0.6704 (2) | 0.0124 (2) | 0.0485 (6) | |
H3A | 0.4460 | 0.6347 | −0.0535 | 0.050* | |
C4 | 0.4010 (3) | 0.7463 (2) | 0.0634 (2) | 0.0543 (7) | |
H4A | 0.2921 | 0.7181 | 0.0837 | 0.080* | |
H4B | 0.3733 | 0.8005 | 0.0169 | 0.080* | |
C5 | 0.5208 (3) | 0.77995 (18) | 0.1608 (2) | 0.0483 (7) | |
H5A | 0.5221 | 0.8484 | 0.1790 | 0.080* | |
C6 | 0.5815 (3) | 0.70636 (17) | 0.24505 (19) | 0.0421 (6) | |
H6A | 0.6222 | 0.7353 | 0.3112 | 0.080* | |
C7 | 0.8776 (3) | 0.78091 (17) | 0.1753 (2) | 0.0472 (6) | |
C8 | 1.0960 (4) | 0.8403 (3) | 0.3052 (3) | 0.0757 (10) | |
H8A | 1.1178 | 0.8439 | 0.3802 | 0.080* | |
H8B | 1.1906 | 0.8045 | 0.2765 | 0.080* | |
H8C | 1.0905 | 0.9056 | 0.2765 | 0.080* | |
C9 | 0.8167 (3) | 0.59090 (18) | 0.03472 (18) | 0.0406 (6) | |
C10 | 0.4876 (3) | 0.60834 (18) | 0.25657 (18) | 0.0413 (6) | |
H10A | 0.4265 | 0.5917 | 0.1901 | 0.080* | |
C11 | 0.7129 (5) | 0.5464 (3) | 0.3835 (3) | 0.0862 (12) | |
H11A | 0.7866 | 0.4900 | 0.3998 | 0.080* | |
H11B | 0.7868 | 0.6029 | 0.3750 | 0.080* | |
H11C | 0.6381 | 0.5580 | 0.4396 | 0.080* | |
C12 | 0.2272 (4) | 0.5514 (3) | 0.3339 (3) | 0.0688 (9) | |
H12A | 0.1464 | 0.5683 | 0.3854 | 0.080* | |
H12B | 0.1629 | 0.5462 | 0.2662 | 0.080* | |
H12C | 0.2831 | 0.4897 | 0.3521 | 0.080* | |
O1 | 0.9631 (3) | 0.81238 (18) | 0.10620 (19) | 0.0708 (7) | |
O2 | 0.9284 (3) | 0.79096 (16) | 0.27818 (17) | 0.0628 (6) | |
O3 | 0.9586 (2) | 0.58392 (15) | 0.08861 (15) | 0.0550 (6) | |
O4 | 0.7758 (2) | 0.53716 (16) | −0.05012 (15) | 0.0590 (6) | |
H4C | 0.8645 | 0.4866 | −0.0518 | 0.050* | |
O5 | 0.6047 (3) | 0.52982 (14) | 0.28781 (16) | 0.0576 (6) | |
O6 | 0.3600 (2) | 0.62621 (14) | 0.32987 (15) | 0.0529 (5) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0363 (12) | 0.0356 (11) | 0.0497 (13) | 0.0031 (9) | 0.0133 (10) | −0.0003 (9) |
C2 | 0.0377 (12) | 0.0417 (12) | 0.0402 (12) | 0.0013 (10) | 0.0123 (9) | 0.0031 (9) |
C3 | 0.0431 (13) | 0.0599 (15) | 0.0435 (13) | 0.0041 (12) | 0.0087 (10) | 0.0068 (11) |
C4 | 0.0413 (13) | 0.0602 (16) | 0.0626 (16) | 0.0137 (12) | 0.0127 (11) | 0.0164 (13) |
C5 | 0.0400 (13) | 0.0375 (12) | 0.0700 (17) | 0.0049 (10) | 0.0206 (11) | −0.0011 (11) |
C6 | 0.0432 (13) | 0.0387 (12) | 0.0460 (13) | −0.0001 (10) | 0.0138 (10) | −0.0081 (10) |
C7 | 0.0409 (13) | 0.0350 (12) | 0.0673 (17) | 0.0024 (10) | 0.0147 (11) | −0.0059 (11) |
C8 | 0.0465 (16) | 0.079 (2) | 0.101 (3) | −0.0055 (16) | −0.0009 (16) | −0.031 (2) |
C9 | 0.0398 (12) | 0.0439 (12) | 0.0392 (11) | 0.0002 (10) | 0.0104 (9) | −0.0045 (9) |
C10 | 0.0435 (12) | 0.0428 (13) | 0.0389 (12) | −0.0020 (10) | 0.0113 (9) | −0.0023 (9) |
C11 | 0.062 (2) | 0.096 (3) | 0.098 (3) | 0.014 (2) | −0.0106 (19) | 0.025 (2) |
C12 | 0.0543 (16) | 0.082 (2) | 0.071 (2) | −0.0231 (16) | 0.0148 (14) | 0.0068 (17) |
O1 | 0.0568 (13) | 0.0771 (15) | 0.0816 (15) | −0.0193 (11) | 0.0250 (11) | 0.0044 (12) |
O2 | 0.0467 (11) | 0.0706 (14) | 0.0714 (13) | −0.0107 (10) | 0.0059 (9) | −0.0171 (11) |
O3 | 0.0470 (10) | 0.0614 (12) | 0.0559 (11) | 0.0141 (9) | 0.0000 (8) | −0.0175 (9) |
O4 | 0.0450 (10) | 0.0710 (13) | 0.0606 (12) | 0.0110 (9) | 0.0023 (8) | −0.0241 (10) |
O5 | 0.0607 (12) | 0.0435 (10) | 0.0706 (13) | 0.0059 (9) | 0.0170 (9) | 0.0057 (9) |
O6 | 0.0454 (10) | 0.0592 (11) | 0.0564 (11) | −0.0067 (8) | 0.0194 (8) | −0.0044 (9) |
Geometric parameters (Å, º) top
C1—C2 | 1.508 (3) | C8—H8A | 0.9601 |
C1—C7 | 1.513 (4) | C8—H8B | 0.9600 |
C1—C6 | 1.531 (3) | C8—H8C | 0.9601 |
C1—C5 | 1.551 (3) | C9—O3 | 1.228 (3) |
C2—C3 | 1.353 (4) | C9—O4 | 1.323 (3) |
C2—C9 | 1.485 (3) | C10—O6 | 1.416 (3) |
C3—C4 | 1.509 (4) | C10—O5 | 1.422 (3) |
C3—H3A | 1.0613 | C10—H10A | 0.9600 |
C4—C5 | 1.548 (4) | C11—O5 | 1.433 (4) |
C4—H4A | 0.9600 | C11—H11A | 0.9600 |
C4—H4B | 0.9599 | C11—H11B | 0.9600 |
C5—C6 | 1.514 (4) | C11—H11C | 0.9600 |
C5—H5A | 0.9601 | C12—O6 | 1.431 (3) |
C6—C10 | 1.522 (3) | C12—H12A | 0.9600 |
C6—H6A | 0.9600 | C12—H12B | 0.9600 |
C7—O1 | 1.212 (3) | C12—H12C | 0.9600 |
C7—O2 | 1.347 (3) | O4—H4C | 0.9600 |
C8—O2 | 1.448 (4) | | |
| | | |
C2—C1—C7 | 117.63 (19) | O2—C7—C1 | 112.2 (2) |
C2—C1—C6 | 116.36 (19) | O2—C8—H8A | 109.8 |
C7—C1—C6 | 122.5 (2) | O2—C8—H8B | 109.5 |
C2—C1—C5 | 104.3 (2) | H8A—C8—H8B | 109.5 |
C7—C1—C5 | 122.1 (2) | O2—C8—H8C | 109.1 |
C6—C1—C5 | 58.83 (16) | H8A—C8—H8C | 109.5 |
C3—C2—C9 | 126.4 (2) | H8B—C8—H8C | 109.5 |
C3—C2—C1 | 112.0 (2) | O3—C9—O4 | 123.5 (2) |
C9—C2—C1 | 121.4 (2) | O3—C9—C2 | 121.5 (2) |
C2—C3—C4 | 112.4 (2) | O4—C9—C2 | 115.0 (2) |
C2—C3—H3A | 133.1 | O6—C10—O5 | 112.48 (19) |
C4—C3—H3A | 114.5 | O6—C10—C6 | 105.02 (19) |
C3—C4—C5 | 104.0 (2) | O5—C10—C6 | 113.7 (2) |
C3—C4—H4A | 111.1 | O6—C10—H10A | 108.8 |
C5—C4—H4A | 110.9 | O5—C10—H10A | 108.3 |
C3—C4—H4B | 111.1 | C6—C10—H10A | 108.3 |
C5—C4—H4B | 110.8 | O5—C11—H11A | 109.8 |
H4A—C4—H4B | 108.9 | O5—C11—H11B | 109.0 |
C6—C5—C1 | 59.93 (15) | H11A—C11—H11B | 109.5 |
C6—C5—C4 | 120.0 (2) | O5—C11—H11C | 109.6 |
C1—C5—C4 | 107.1 (2) | H11A—C11—H11C | 109.5 |
C6—C5—H5A | 118.2 | H11B—C11—H11C | 109.5 |
C1—C5—H5A | 117.8 | O6—C12—H12A | 109.8 |
C4—C5—H5A | 118.4 | O6—C12—H12B | 109.0 |
C5—C6—C10 | 122.1 (2) | H12A—C12—H12B | 109.5 |
C5—C6—C1 | 61.24 (15) | O6—C12—H12C | 109.7 |
C10—C6—C1 | 122.68 (19) | H12A—C12—H12C | 109.5 |
C5—C6—H6A | 114.3 | H12B—C12—H12C | 109.5 |
C10—C6—H6A | 113.1 | C7—O2—C8 | 117.1 (3) |
C1—C6—H6A | 114.0 | C9—O4—H4C | 107.2 |
O1—C7—O2 | 123.3 (2) | C10—O5—C11 | 114.8 (2) |
O1—C7—C1 | 124.5 (3) | C10—O6—C12 | 114.5 (2) |
| | | |
C3—C2—C9—O4 | 5.0 (4) | C2—C1—C7—O1 | 34.3 (4) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O4—H4c···O3i | 0.96 | 1.74 | 2.668 (3) | 162 |
Symmetry code: (i) −x+2, −y+1, −z. |
Experimental details
Crystal data |
Chemical formula | C12H16O6 |
Mr | 256.25 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 293 |
a, b, c (Å) | 7.537 (4), 13.602 (8), 12.779 (5) |
β (°) | 94.57 (2) |
V (Å3) | 1305.9 (12) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.11 |
Crystal size (mm) | 0.2 × 0.2 × 0.2 |
|
Data collection |
Diffractometer | Syntex P4 four-circle diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3773, 2845, 1975 |
Rint | 0.126 |
(sin θ/λ)max (Å−1) | 0.641 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.067, 0.233, 0.99 |
No. of reflections | 2845 |
No. of parameters | 164 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.11, −0.08 |
Selected bond lengths (Å) topC1—C2 | 1.508 (3) | C7—O1 | 1.212 (3) |
C1—C7 | 1.513 (4) | C7—O2 | 1.347 (3) |
C1—C6 | 1.531 (3) | C8—O2 | 1.448 (4) |
C1—C5 | 1.551 (3) | C9—O3 | 1.228 (3) |
C2—C3 | 1.353 (4) | C9—O4 | 1.323 (3) |
C2—C9 | 1.485 (3) | C10—O6 | 1.416 (3) |
C3—C4 | 1.509 (4) | C10—O5 | 1.422 (3) |
C4—C5 | 1.548 (4) | C11—O5 | 1.433 (4) |
C5—C6 | 1.514 (4) | C12—O6 | 1.431 (3) |
C6—C10 | 1.522 (3) | O4—H4C | 0.9600 |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O4—H4c···O3i | 0.96 | 1.74 | 2.668 (3) | 162 |
Symmetry code: (i) −x+2, −y+1, −z. |
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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.