2,5-Anhydro-N-benzyl-2-C-methyl-d-arabinona­mide [(2S,3R,4R)-N-benzyl-3,4-dihydr­oxy-2-methyl­tetra­hydro­furan-2-carboxamide]

Cox, D.J.; Håkansson, A.E.; Fleet, G.W.J.; Watkin, D.J.

doi:10.1107/S1600536806055322

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 63| Part 2| February 2007| Pages o574-o576

https://doi.org/10.1107/S1600536806055322

2,5-Anhydro-N-benzyl-2-C-methyl-D-arabinonamide [(2S,3R,4R)-N-benzyl-3,4-dihydroxy-2-methyltetrahydrofuran-2-carboxamide]

Daniel J. Cox,^a Anders E. Håkansson,^a ^* George W. J. Fleet ^a and David J. Watkin ^b

^aDepartment of Organic Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, England, and ^bDepartment of Chemical Crystallography, Chemical Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, England
^*Correspondence e-mail: anderseh@hotmail.com

(Received 15 December 2006; accepted 19 December 2006; online 10 January 2007)

The size of the ring and relative configuration of the chiral centres in the title compound, C₁₃H₁₇NO₄, formed by the preferential formation of the hindered five-membered ring tetrahydrofuran rather than the expected three-membered ring epoxide, was established by X-ray crystallographic analysis; the absolute configuration was determined by the use of 2-C-methyl-D-arabinono-lactone as the starting material. The crystal structure consists of hydrogen-bonded layers lying with their hydrophobic surfaces in contact.

Comment

Carbohydrate lactones are among the most powerful chirons (Lundt & Madsen, 2001 ), being ideal scaffolds for the synthesis of optically pure complex natural products (Lichtenthaler & Peters, 2004 ; Bols, 1996 ). Epimerization at C4 of the lactone is usually a very efficient reaction, which effectively doubles the number of lactones that are readily available (Kold et al., 1994 ; Frank & Lundt, 1995 ); the transformation can be conducted on a multikilogram scale (Batra et al., 2006 ). Among other recent examples (Håkansson et al., 2006 ; Van Ameijde et al., 2004 ; Simone et al., 2005 ), the treatment of the 2-C-methyl-D-ribonolactone tosylate (1) with base allows access to the L-lyxono-epimer (2) in very high yield (Hotchkiss et al., 2007 ).

It was thus expected that treatment of the tosylate (3) of 2-C-methyl-D-arabinonolactone (Hotchkiss et al., 2006 ) would give the L-xylono epimer (6); however, a complex mixture of products was obtained. Accordingly the reaction sequence treatment of (3) with benzylamine was expected to give ring opening of the lactone unit to (4) which would be followed by formation of the epoxide (5) from attack of the C4 hydroxyl group; (5) could be subsequently closed to the target (6). A product was isolated from the reaction of benzylamine with (3) in 61% yield. X-ray crystallographic analysis showed that the much hindered tertiary alcohol at C2 of (4) had closed to form the tetrahydrofuran (7). The connectivity of the C and H atoms is the same in both (5) and (7), and the X-ray experiment unequivocally established that the five-membered ring THF (7) was formed in preference to the three-membered ring epoxide (5); the absolute configuration of (7) is determined by the use of 2-C-methyl-D-arabinonolactone as the starting material.

The molecular structure (Fig. 1) shows no abnormal features, even a short internal N—H⋯O contact (Table 1) having no visible influence [largest distance deviation from the MOGUL norms (Bruno et al., 2004 ) is C1—O5 (1.46 vs 1.43 Å), largest angle deviation is C11—C16—C10 (122.8 vs 120.8°)]. The crystal structure consists of hydrogen-bonded sheets (Fig. 2). Both faces of the sheets are composed largely of phenyl groups which lie in contact in the crystal structure (Fig. 3).

Figure 1
The molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitary radius.

Figure 2
Partial packing diagram of the title compound showing a single hydrogen-bonded (dotted lines) layer lying perpendicular to the c axis. Each molecule is involved in only two hydrogen bonds.

Figure 3
Partial packing diagram viewed perpendicular to the plane of the molecular sheets showing hydrophobic (largely aromatic) plane-to-plane contacts at (x, y, $[1\over2]$ ). Hydrogen bonds are shown as dotted lines.

Experimental

The synthesis of (3) is described in the Comment and shown in the scheme; full details will be reported elsewhere. The sample for analysis was crystallized from a 2:1 mixture of ethanol and methanol to yield colourless needles with m.p. 402–404 K and [α]_D¹⁹ = −18.5 (c =1.00, CH₃OH).

Crystal data

C₁₃H₁₇NO₄
M_r = 251.28
Orthorhombic, P 2₁ 2₁ 2₁
a = 5.6899 (2) Å
b = 11.3507 (4) Å
c = 18.5291 (9) Å
V = 1196.69 (8) Å³
Z = 4
D_x = 1.395 Mg m⁻³
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 190 K
Needle, colourless
0.40 × 0.06 × 0.06 mm

Data collection

Nonius KappaCCD diffractometer
ω scans
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997 ) T_min = 0.96, T_max = 0.99
5880 measured reflections
1575 independent reflections
1249 reflections with I > 2σ(I)
R_int = 0.049
θ_max = 27.5°

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.038
wR(F²) = 0.087
S = 0.93
1575 reflections
163 parameters
H-atom parameters constrained
w = 1/[σ²(F²) + (0.03P)² + 0.15P], where P = [max(F_o²,0) + 2F_c²]/3
(Δ/σ)_max < 0.001
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.29 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N9—H1⋯O5	0.88	2.15	2.606 (2)	112
O7—H15⋯O5ⁱ	0.86	2.15	2.878 (2)	142
O6—H19⋯O17ⁱⁱ	0.85	1.96	2.816 (2)	179
Symmetry codes: (i) x-1, y, z; (ii) $[-x, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

In the absence of significant anomalous scattering, Friedel pairs were merged and the absolute configuration assigned on the basis of the starting material.

The H atoms were all located in a difference map, but those attached to C atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C—H in the range 0.93–0.98, N—H to 0.86, O—H = 0.82 Å) and U_iso(H) (in the range 1.2–1.5 times U_eq of the parent atom), after which the positions were refined with riding constraints.

Data collection: COLLECT (Nonius, 2001 ); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 ); molecular graphics: CAMERON (Watkin et al., 1996 ); software used to prepare material for publication: CRYSTALS.

Supporting information

Crystal structure: contains datablocks 3, global. DOI: https://doi.org/10.1107/S1600536806055322/lh2277sup1.cif

Structure factors: contains datablock 3. DOI: https://doi.org/10.1107/S1600536806055322/lh22773sup2.hkl

Computing details top

Data collection: COLLECT (Nonius, 2001); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: CAMERON (Watkin et al., 1996); software used to prepare material for publication: CRYSTALS.

(2S,3R,4R)-N-benzyl-3,4-dihydroxy-2-methyltetrahydrofuran-2-carboxamide top

Crystal data top

C₁₃H₁₇NO₄	F(000) = 536
M_r = 251.28	D_x = 1.395 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 1482 reflections
a = 5.6899 (2) Å	θ = 5–27°
b = 11.3507 (4) Å	µ = 0.10 mm⁻¹
c = 18.5291 (9) Å	T = 190 K
V = 1196.69 (8) Å³	Needle, colourless
Z = 4	0.40 × 0.06 × 0.06 mm

Data collection top

Nonius KappaCCD diffractometer	1249 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.049
ω scans	θ_max = 27.5°, θ_min = 5.2°
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997)	h = −7→7
T_min = 0.96, T_max = 0.99	k = −14→14
5880 measured reflections	l = −23→24
1575 independent reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.038	H-atom parameters constrained
wR(F²) = 0.087	w = 1/[σ²(F²) + (0.03P)² + 0.15P], where P = [max(F_o²,0) + 2F_c²]/3
S = 0.93	(Δ/σ)_max = 0.000314
1575 reflections	Δρ_max = 0.26 e Å⁻³
163 parameters	Δρ_min = −0.29 e Å⁻³
0 restraints

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.3695 (4)	0.87162 (16)	0.68888 (11)	0.0238
C2	0.1269 (4)	0.92388 (17)	0.70375 (12)	0.0232
C3	0.1815 (4)	1.05659 (17)	0.70497 (12)	0.0263
C4	0.3572 (4)	1.06701 (17)	0.64355 (12)	0.0276
O5	0.4874 (3)	0.95765 (11)	0.64303 (8)	0.0252
O6	−0.0177 (3)	1.12786 (12)	0.69160 (8)	0.0350
O7	−0.0220 (3)	0.89610 (12)	0.64455 (8)	0.0285
C8	0.3483 (4)	0.75530 (17)	0.64905 (11)	0.0234
N9	0.4204 (4)	0.75485 (14)	0.58042 (9)	0.0251
C10	0.4019 (4)	0.65227 (17)	0.53332 (11)	0.0270
C11	0.5649 (4)	0.55154 (18)	0.55273 (11)	0.0237
C12	0.5025 (5)	0.43760 (18)	0.53198 (11)	0.0298
C13	0.6467 (5)	0.34319 (19)	0.54704 (13)	0.0336
C14	0.8585 (5)	0.36011 (19)	0.58300 (12)	0.0325
C15	0.9219 (5)	0.47346 (18)	0.60362 (12)	0.0294
C16	0.7760 (4)	0.56814 (18)	0.58866 (11)	0.0265
O17	0.2690 (3)	0.66711 (11)	0.67971 (8)	0.0310
C18	0.5116 (5)	0.85472 (17)	0.75818 (12)	0.0291
H21	0.0645	0.8960	0.7502	0.0298*
H31	0.2547	1.0760	0.7522	0.0332*
H41	0.4648	1.1341	0.6513	0.0358*
H42	0.2711	1.0756	0.5971	0.0353*
H101	0.2363	0.6224	0.5355	0.0336*
H102	0.4378	0.6791	0.4831	0.0332*
H121	0.3554	0.4257	0.5067	0.0376*
H131	0.6045	0.2649	0.5329	0.0439*
H141	0.9573	0.2931	0.5930	0.0413*
H151	1.0701	0.4855	0.6277	0.0365*
H161	0.8204	0.6463	0.6032	0.0324*
H181	0.6674	0.8204	0.7470	0.0452*
H182	0.5332	0.9322	0.7826	0.0449*
H183	0.4234	0.8015	0.7916	0.0450*
H1	0.4836	0.8202	0.5635	0.0321*
H15	−0.1367	0.9437	0.6516	0.0451*
H19	−0.0960	1.1394	0.7302	0.0551*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0249 (12)	0.0234 (9)	0.0231 (11)	−0.0022 (10)	0.0022 (10)	0.0027 (9)
C2	0.0201 (12)	0.0275 (10)	0.0220 (10)	0.0004 (10)	0.0014 (10)	−0.0018 (9)
C3	0.0299 (14)	0.0234 (9)	0.0255 (11)	0.0064 (11)	−0.0004 (10)	−0.0002 (9)
C4	0.0276 (13)	0.0217 (9)	0.0334 (12)	0.0015 (11)	0.0030 (11)	0.0003 (9)
O5	0.0226 (8)	0.0209 (6)	0.0319 (8)	−0.0002 (8)	0.0055 (8)	0.0037 (6)
O6	0.0369 (10)	0.0352 (7)	0.0328 (8)	0.0166 (9)	0.0048 (9)	0.0012 (7)
O7	0.0221 (9)	0.0337 (7)	0.0297 (8)	0.0038 (8)	−0.0020 (8)	−0.0065 (7)
C8	0.0197 (11)	0.0243 (9)	0.0262 (10)	0.0032 (10)	−0.0011 (10)	0.0026 (9)
N9	0.0283 (10)	0.0223 (7)	0.0248 (9)	−0.0013 (9)	0.0066 (9)	−0.0005 (7)
C10	0.0279 (13)	0.0282 (10)	0.0248 (11)	0.0020 (11)	0.0003 (10)	−0.0030 (9)
C11	0.0235 (13)	0.0264 (9)	0.0210 (10)	0.0008 (10)	0.0039 (10)	−0.0012 (9)
C12	0.0315 (14)	0.0310 (10)	0.0268 (11)	−0.0017 (13)	0.0014 (12)	−0.0046 (9)
C13	0.0436 (16)	0.0259 (10)	0.0313 (12)	−0.0021 (12)	0.0050 (12)	−0.0026 (10)
C14	0.0400 (16)	0.0290 (10)	0.0285 (12)	0.0078 (12)	0.0057 (12)	0.0023 (10)
C15	0.0278 (14)	0.0347 (11)	0.0257 (12)	0.0019 (11)	−0.0007 (11)	0.0025 (9)
C16	0.0268 (13)	0.0266 (10)	0.0260 (11)	−0.0028 (11)	0.0049 (11)	−0.0017 (10)
O17	0.0375 (10)	0.0241 (6)	0.0314 (8)	−0.0043 (8)	0.0063 (8)	0.0010 (6)
C18	0.0283 (12)	0.0299 (10)	0.0292 (11)	0.0018 (12)	−0.0026 (11)	0.0002 (9)

Geometric parameters (Å, º) top

C1—C2	1.528 (3)	N9—H1	0.882
C1—O5	1.458 (2)	C10—C11	1.515 (3)
C1—C8	1.517 (3)	C10—H101	1.002
C1—C18	1.529 (3)	C10—H102	1.001
C2—C3	1.538 (3)	C11—C12	1.395 (3)
C2—O7	1.422 (2)	C11—C16	1.386 (3)
C2—H21	0.983	C12—C13	1.378 (3)
C3—C4	1.520 (3)	C12—H121	0.968
C3—O6	1.414 (3)	C13—C14	1.391 (4)
C3—H31	0.995	C13—H131	0.957
C4—O5	1.445 (2)	C14—C15	1.390 (3)
C4—H41	0.987	C14—H141	0.964
C4—H42	0.995	C15—C16	1.386 (3)
O6—H19	0.852	C15—H151	0.963
O7—H15	0.857	C16—H161	0.961
C8—N9	1.336 (3)	C18—H181	0.990
C8—O17	1.236 (2)	C18—H182	0.997
N9—C10	1.459 (2)	C18—H183	1.001

C2—C1—O5	105.11 (15)	C10—N9—H1	119.3
C2—C1—C8	110.72 (18)	N9—C10—C11	114.59 (17)
O5—C1—C8	109.64 (16)	N9—C10—H101	108.3
C2—C1—C18	112.01 (18)	C11—C10—H101	108.1
O5—C1—C18	109.28 (18)	N9—C10—H102	107.4
C8—C1—C18	109.96 (16)	C11—C10—H102	109.0
C1—C2—C3	101.57 (17)	H101—C10—H102	109.4
C1—C2—O7	108.26 (16)	C10—C11—C12	118.6 (2)
C3—C2—O7	110.41 (17)	C10—C11—C16	122.80 (19)
C1—C2—H21	111.1	C12—C11—C16	118.6 (2)
C3—C2—H21	112.0	C11—C12—C13	120.9 (2)
O7—C2—H21	112.9	C11—C12—H121	118.8
C2—C3—C4	101.42 (17)	C13—C12—H121	120.3
C2—C3—O6	113.31 (19)	C12—C13—C14	120.4 (2)
C4—C3—O6	110.59 (17)	C12—C13—H131	121.1
C2—C3—H31	108.4	C14—C13—H131	118.5
C4—C3—H31	111.5	C13—C14—C15	119.0 (2)
O6—C3—H31	111.3	C13—C14—H141	119.2
C3—C4—O5	105.97 (16)	C15—C14—H141	121.8
C3—C4—H41	111.0	C14—C15—C16	120.5 (2)
O5—C4—H41	110.2	C14—C15—H151	119.0
C3—C4—H42	109.3	C16—C15—H151	120.5
O5—C4—H42	109.3	C11—C16—C15	120.6 (2)
H41—C4—H42	110.9	C11—C16—H161	119.2
C1—O5—C4	109.63 (15)	C15—C16—H161	120.1
C3—O6—H19	111.1	C1—C18—H181	110.3
C2—O7—H15	101.4	C1—C18—H182	109.6
C1—C8—N9	116.22 (17)	H181—C18—H182	109.4
C1—C8—O17	120.67 (18)	C1—C18—H183	109.3
N9—C8—O17	123.11 (18)	H181—C18—H183	109.9
C8—N9—C10	123.38 (17)	H182—C18—H183	108.3
C8—N9—H1	117.3

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N9—H1···O5	0.88	2.15	2.606 (2)	112
O7—H15···O5ⁱ	0.86	2.15	2.878 (2)	142
O6—H19···O17ⁱⁱ	0.85	1.96	2.816 (2)	179

Symmetry codes: (i) x−1, y, z; (ii) −x, y+1/2, −z+3/2.

Acknowledgements

Financial support to AEH provided through the European Community's Human Potential Programme under contract HPRN-CT-2002-00173 is gratefully acknowledged.

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