(1α,6α,7α,7aβ)-2,3,5,6,7,7a-Hexa­hydro-1,6-epoxy-1H-pyrrolizin-7-ol

The title compound, C₇H₁₁NO₂, is an intermediate in a synthetic approach to the pyrrolizidine alkaloid loline. It has a brendane skeleton with a 91.8(2)° bond angle for the bridging carbon bearing the OH group.

Key indicators

• Single-crystal X-ray study
• T = 200 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.032
• wR factor = 0.081
• Data-to-parameter ratio = 9.4

checkCIF/PLATON results

No syntax errors found



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           28.33
           From the CIF: _reflns_number_total                880
           Count of symmetry unique reflns          880
           Completeness (_total/calc)            100.00%
           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

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

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

---

S1. Comment

Loline alkaloids (Powell & Petroski, 1992) are a group of pyrrolizidine alkaloids that feature a novel bridging ether as illustrated in loline, (1). These alkaloids occur in Lolium cuneatum (Dannhardt & Steindl, 1985), Festuca arundinacea (Yates & Tookey, 1965), Adenocarpus decorticans (Ribas-Barceló & Ribas-Marqués, 1968), and Argyreia mollis (Tofern et al. 1999) and have interesting biological properties. A number of synthetic approaches to these alkaloids have been reported (Wilson & Sawicki, 1978, Glass et al., 1978; Wilson et al., 1981), as well as a successful synthesis of (±)-loline (Tufariello et al., 1986) and (+)-loline (Blakemore et al., 2001). In our synthetic approach, the title compound, (2), was synthesized and characterized structurally. This paper reports its complete X-ray structural elucidation. This X-ray study shows that the molecule is an analogue of brendane and, in particular, the small bond angle of the one carbon bridge bearing the OH group of 91.8° renders alcohol derivatives unreactive in nucleophilic displacement reactions. In addition, neighboring group participation by ß-nitrogen is precluded by the geometry of the tricyclic ring system. Molecules of (2) form infinite linear chains through hydrogen bonding of the alcohol moiety of one molecule with the amine moiety of the next molecule.

S2. Experimental

The synthesis of (2) was carried out as reported (Glass et al., 1978). Crystals of (2) were grown by evaporation from benzene.

S3. Refinement

Due to the very weak anomalous scattering in this experiment [Flack (1983) parameter x = 0.0(1.8)], all Friedel pairs were merged in the final cycles of refinement. The absolute structure of the crystal of this racemic mixture is unknown. All H atoms were positioned geometrically at idealized positions, constrained to ride on the atom to which they are attached and given thermal parameters equal to 1.2 or 1.5 times U_iso of that bonded atom. In the final cycles of refinement, the hydroxyl H atom was freed from the riding constraint.

Computing details

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

Figures

Fig. 1. View of (2). Ellipsoids are drawn at the 50% probability level.

(1α,6α,7α,7aβ)-2,3,5,6,7,7a-Hexahydro-1,6-epoxy-1H-pyrrolizin-7-ol

Crystal data

C7H11NO2	F(000) = 304
Mr = 141.17	Dx = 1.413 Mg m^−3
Orthorhombic, Pna21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2n	Cell parameters from 2854 reflections
a = 9.9294 (16) Å	θ = 3.5–28.2°
b = 7.2910 (12) Å	µ = 0.10 mm^−1
c = 9.1653 (15) Å	T = 200 K
V = 663.52 (19) Å^3	Irregular block, colorless
Z = 4	0.09 × 0.09 × 0.08 mm

Data collection

Bruker SMART CCD area-detector diffractometer	880 independent reflections
Radiation source: fine-focus sealed tube	795 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.029
ϕ and ω scans	θmax = 28.3°, θmin = 3.5°
Absorption correction: multi-scan (SADABS; Sheldrick, 2000)	h = −12→13
Tmin = 0.893, Tmax = 0.992	k = −9→9
6311 measured reflections	l = −12→12

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)] = 0.032	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.081	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0382P)^2 + 0.1884P] where P = (Fo^2 + 2Fc^2)/3
880 reflections	(Δ/σ)max = 0.006
94 parameters	Δρmax = 0.29 e Å^−3
1 restraint	Δρmin = −0.17 e Å^−3

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
O1	0.01469 (17)	0.1313 (2)	0.26377 (19)	0.0351 (4)
H1A	−0.049 (3)	0.128 (4)	0.309 (4)	0.053*
C1	0.12400 (19)	0.1983 (3)	0.3451 (2)	0.0266 (4)
H1B	0.2028	0.1133	0.3384	0.032*
O2	0.00274 (14)	0.40236 (19)	0.48968 (17)	0.0278 (3)
C2	0.09750 (19)	0.2541 (3)	0.5037 (2)	0.0267 (4)
H2A	0.0667	0.1516	0.5680	0.032*
C3	0.2343 (2)	0.3352 (3)	0.5451 (2)	0.0289 (4)
H3A	0.2260	0.4200	0.6289	0.035*
H3B	0.2997	0.2375	0.5697	0.035*
N4	0.27594 (16)	0.4365 (2)	0.40824 (19)	0.0249 (3)
C5	0.2674 (2)	0.6374 (3)	0.4267 (3)	0.0307 (5)
H5A	0.3190	0.7005	0.3492	0.037*
H5B	0.3045	0.6741	0.5226	0.037*
C6	0.1160 (2)	0.6882 (3)	0.4167 (3)	0.0332 (5)
H6A	0.0805	0.7261	0.5131	0.040*
H6B	0.1012	0.7887	0.3459	0.040*
C7	0.0495 (2)	0.5109 (3)	0.3650 (2)	0.0267 (4)
H7A	−0.0232	0.5332	0.2916	0.032*
C8	0.16481 (19)	0.3943 (3)	0.3040 (2)	0.0239 (4)
H8A	0.1863	0.4144	0.1986	0.029*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0353 (8)	0.0405 (8)	0.0295 (8)	−0.0126 (7)	0.0049 (6)	−0.0091 (8)
C1	0.0276 (9)	0.0246 (9)	0.0275 (10)	−0.0004 (7)	0.0039 (8)	−0.0022 (8)
O2	0.0236 (6)	0.0310 (6)	0.0287 (7)	0.0001 (6)	0.0054 (6)	−0.0015 (6)
C2	0.0278 (9)	0.0273 (9)	0.0250 (9)	0.0010 (8)	0.0048 (8)	0.0021 (8)
C3	0.0270 (10)	0.0357 (11)	0.0239 (10)	0.0001 (8)	0.0001 (8)	0.0038 (9)
N4	0.0217 (7)	0.0285 (8)	0.0244 (8)	−0.0003 (7)	0.0005 (7)	0.0015 (7)
C5	0.0312 (10)	0.0286 (10)	0.0323 (11)	−0.0071 (8)	0.0004 (9)	−0.0025 (9)
C6	0.0354 (11)	0.0237 (9)	0.0405 (12)	0.0015 (8)	0.0044 (10)	−0.0014 (9)
C7	0.0238 (9)	0.0268 (9)	0.0295 (10)	0.0032 (8)	−0.0009 (8)	0.0012 (8)
C8	0.0249 (8)	0.0249 (9)	0.0219 (9)	−0.0002 (7)	0.0005 (8)	−0.0007 (7)

Geometric parameters (Å, º)

O1—C1	1.404 (2)	N4—C5	1.477 (3)
O1—H1A	0.76 (3)	N4—C8	1.492 (2)
C1—C8	1.532 (3)	C5—C6	1.551 (3)
C1—C2	1.532 (3)	C5—H5A	0.9900
C1—H1B	1.0000	C5—H5B	0.9900
O2—C2	1.439 (2)	C6—C7	1.527 (3)
O2—C7	1.465 (3)	C6—H6A	0.9900
C2—C3	1.529 (3)	C6—H6B	0.9900
C2—H2A	1.0000	C7—C8	1.532 (3)
C3—N4	1.513 (3)	C7—H7A	1.0000
C3—H3A	0.9900	C8—H8A	1.0000
C3—H3B	0.9900
C1—O1—H1A	112 (3)	N4—C5—H5A	110.4
O1—C1—C8	113.47 (18)	C6—C5—H5A	110.4
O1—C1—C2	117.58 (17)	N4—C5—H5B	110.4
C8—C1—C2	91.80 (15)	C6—C5—H5B	110.4
O1—C1—H1B	110.9	H5A—C5—H5B	108.6
C8—C1—H1B	110.9	C7—C6—C5	103.61 (16)
C2—C1—H1B	110.9	C7—C6—H6A	111.0
C2—O2—C7	105.57 (15)	C5—C6—H6A	111.0
O2—C2—C3	108.19 (16)	C7—C6—H6B	111.0
O2—C2—C1	103.13 (16)	C5—C6—H6B	111.0
C3—C2—C1	100.69 (16)	H6A—C6—H6B	109.0
O2—C2—H2A	114.5	O2—C7—C6	110.63 (18)
C3—C2—H2A	114.5	O2—C7—C8	102.79 (16)
C1—C2—H2A	114.5	C6—C7—C8	105.06 (16)
N4—C3—C2	103.06 (16)	O2—C7—H7A	112.6
N4—C3—H3A	111.2	C6—C7—H7A	112.6
C2—C3—H3A	111.2	C8—C7—H7A	112.6
N4—C3—H3B	111.2	N4—C8—C1	103.34 (15)
C2—C3—H3B	111.2	N4—C8—C7	101.79 (15)
H3A—C3—H3B	109.1	C1—C8—C7	103.31 (16)
C5—N4—C8	103.63 (15)	N4—C8—H8A	115.5
C5—N4—C3	111.93 (17)	C1—C8—H8A	115.5
C8—N4—C3	103.17 (14)	C7—C8—H8A	115.5
N4—C5—C6	106.62 (16)
C7—O2—C2—C3	65.4 (2)	C5—C6—C7—O2	93.1 (2)
C7—O2—C2—C1	−40.65 (19)	C5—C6—C7—C8	−17.2 (2)
O1—C1—C2—O2	−62.7 (2)	C5—N4—C8—C1	−151.00 (16)
C8—C1—C2—O2	55.11 (17)	C3—N4—C8—C1	−34.16 (19)
O1—C1—C2—C3	−174.39 (18)	C5—N4—C8—C7	−44.06 (19)
C8—C1—C2—C3	−56.62 (16)	C3—N4—C8—C7	72.77 (17)
O2—C2—C3—N4	−68.9 (2)	O1—C1—C8—N4	177.33 (16)
C1—C2—C3—N4	38.83 (18)	C2—C1—C8—N4	56.09 (16)
C2—C3—N4—C5	107.82 (18)	O1—C1—C8—C7	71.5 (2)
C2—C3—N4—C8	−2.98 (19)	C2—C1—C8—C7	−49.69 (17)
C8—N4—C5—C6	33.9 (2)	O2—C7—C8—N4	−77.98 (16)
C3—N4—C5—C6	−76.6 (2)	C6—C7—C8—N4	37.8 (2)
N4—C5—C6—C7	−9.9 (2)	O2—C7—C8—C1	28.98 (19)
C2—O2—C7—C6	−104.85 (18)	C6—C7—C8—C1	144.78 (18)
C2—O2—C7—C8	6.88 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1A···N4^i	0.76 (3)	2.01 (3)	2.760 (2)	167 (3)

Symmetry code: (i) x−1/2, −y+1/2, z.