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

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.


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).
In a recent endeavor, we employed this reagent as means of accessing the difluorodiol 1 via one-pot HF-mediated ringopening 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 crystal structure of 4 was solved and refined in the centrosymmetric monoclinic space group P2 1 /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.

Refinement
The methine (CH) and methylene (CH 2 ) H atoms were placed in geometrically idealized positions with C-H distances 0.93 and 0.97 Å respectively, and allowed to ride on their parent atoms with U iso (H) = 1.2U eq (C). The hydroxyl hydrogen atom was constrained to an ideal geometry with the O-H distance fixed at 0.82 Å and U iso (H) = 1.5U eq (O). During refinement, the hydroxyl group was however allowed to rotate freely about its C-O bond. Fig. 1. Chemical structural diagrams of 1 and 2.     Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 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 (Å 2 )
x y z U iso */U eq