(1S*,3S*,8S*,10S*)-10-Fluoro-15-oxa­tetra­cyclo­[6.6.1.01,10.03,8]penta­deca-5,12-dien-3-ol

Goverdhan Mehta; Saikat Sen

doi:10.1107/S1600536811026857

. 2011 Jul 9;67(Pt 8):o1985. doi: 10.1107/S1600536811026857

(1S,3S,8S,10S)-10-Fluoro-15-oxatetracyclo[6.6.1.0^1,10.0^3,8]pentadeca-5,12-dien-3-ol

Goverdhan Mehta ^a,^*, Saikat Sen ^a

PMCID: PMC3213441 PMID: 22091020

Abstract

The title compound, C₁₄H₁₇FO₂, was obtained from anti-4a,9a:8a,10a-diepoxy-1,4,4a,5,8,8a,9,9a,10,10a-decahydroanthracene via tandem hydrogen-fluoride-mediated epoxide ring-opening and transannular oxacyclization. With the two cyclohexene rings folded towards the oxygen bridge, the title tetracyclic fluoroalcohol molecule displays a conformation reminiscent of a pagoda. The crystal packing is effected via intermolecular O—H⋯O hydrogen bonds, which link the molecules into a zigzag chain along the b axis.

Related literature

For applications of organofluorine compounds as pharmaceuticals, see: Kirsch (2004 ▶); Bégué & Bonnet-Delpon (2006 ▶); Müller et al. (2007 ▶). For the use of diethylaminosulfur trifluoride, 1-chloromethyl-4-fluorodiazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) and pyridinium poly(hydrogen fluoride) as reagents for selective introduction of C—F bonds, see: Middleton (1975 ▶); Olah et al. (1979 ▶); Banks et al. (1992 ▶). For the preparation of the title compound, see: Mehta et al. (2007 ▶); Mehta & Sen (2010 ▶).

Experimental

Crystal data

C₁₄H₁₇FO₂
M _r = 236.28
Monoclinic,
a = 8.1603 (6) Å
b = 10.9148 (8) Å
c = 13.5558 (10) Å
β = 96.285 (3)°
V = 1200.13 (15) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 291 K
0.26 × 0.22 × 0.12 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2003 ▶) T _min = 0.976, T _max = 0.989
10752 measured reflections
2454 independent reflections
2038 reflections with I > 2σ(I)
R _int = 0.020

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.113
S = 1.03
2454 reflections
155 parameters
H-atom parameters constrained
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: SMART (Bruker, 1998 ▶); cell refinement: SAINT (Bruker, 1998 ▶); data reduction: SAINT; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶) and CAMERON (Watkin et al., 1993 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811026857/is2740sup1.cif

e-67-o1985-sup1.cif^{(23.9KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811026857/is2740Isup2.hkl

e-67-o1985-Isup2.hkl^{(118.1KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811026857/is2740Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O2ⁱ	0.82	2.14	2.9554 (14)	177

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Symmetry code: (i) Inline graphic .

Acknowledgments

We thank the Department of Science and Technology (DST), India, for the CCD facility at the Indian Institute of Science (IISc), Bangalore. GM thanks the Council for Scientific and Industrial Research (CSIR), India, for research support and the award of a Bhatnagar Fellowship.

supplementary crystallographic information

Comment

Organofluorine compounds, while rarely occurring naturally, constitute around 20% of all known pharmaceuticals (Bégué & Bonnet-Delpon, 2006; Müller et al., 2007). The wide- spread applications of fluorinated organic compounds in the therapeutic arena has been attributed to the fact that incorporating fluorine in a drug can significantly enhance its lipophilicity and in vitro stability towards cytochrome P450 enzymatic oxidation (Kirsch, 2004; Müller et al., 2007).

Not surprisingly, various reagents, such as diethylaminosulfur trifluoride (DAST) (Middleton, 1975) and 1-chloromethyl-4-fluorodiazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) (Banks et al., 1992) have been developed over the years for achieving controlled and selective introduction of C—F bonds. The Olah's reagent [pyridinium poly(hydrogen fluoride)] was, in this context, among the first such fluorinating agents to be reported (Olah et al., 1979; Müller et al., 2007).

In a recent endeavor, we employed this reagent as means of accessing the difluorodiol 1via one-pot HF-mediated ring-opening in the syn-diepoxide 2 (Fig. 1; Mehta & Sen, 2010). The complete regio- and stereoselectivity, observed in this bis-fluorination step, was intriguing and goaded us to investigate the outcome of reacting pyridine poly(hydrogen fluoride) with the anti-diepoxide 3 (Fig. 2; Mehta et al., 2007).

The title compound 4, bearing a 7-oxanorbornane core inscribed in a 1,4,4a,5,8,8a,9,9a,10,10a-decahydroanthracene framework, was obtained as the major product. Formation of the tetracyclic fluoroalcohol 4 can be explained by an initial HF-mediated epoxide ring opening in 3 to yield the fluorohydrin 5, followed by a novel variant of a hydroxy-mediated bishomo-Payne rearrangement in 5 to afford 4 (Fig. 3).

The crystal structure of 4 was solved and refined in the centrosymmetric monoclinic space group P2₁/c (Z = 4). The two flanking cyclohexene rings, folded towards the oxa bridge of the bicyclic core, and the pendant syn-4-fluoro-butan-1-ol moiety afforded the molecule an interesting pagoda-like architecture (Fig. 4). Crystal packing in 4 was effected via the agency of intermolecular O—H···O hydrogen bonds which linked the tetraacetate molecules into zigzag chains along the b axis (Fig. 5).

Experimental

A solution of the anti-diepoxide 3 (35 mg, 0.162 mmol) in 1 ml of dry THF was treated with pyridine- poly(hydrogen fluoride) (0.5 ml, 27.5 mmol) at 273 K. The reaction was allowed to proceed for 7 h at ambient temperature. The mixture was then quenched with saturated sodium bicarbonate solution. The product was extracted with ethyl acetate; the combined extracts were washed with brine and then dried over anhydrous sodium sulfate. Removal of solvent, column chromatography over silica gel and subsequent recrystallization using 20% EtOAc-petroleum ether afforded 4 (25 mg, 65%) as a colorless crystalline solid.