(1′S,6′S,8′S,9′R)-9′-Bromo-12′-oxaspiro[1,3-dioxolane-2,4′-tricyclo[6.3.1.01,6]dodecane]

In an endeavor directed towards the construction of the oxabicyclic[3.2.1]octane segment present in the bioactive natural products of cortistatins and icetexanes genre, the title compound, C13H19BrO3, was synthesized from (4aR,9aS)-1,3,4,4a,5,6,9,9a-octahydrospiro[benzo[7]annulene-2,2′-[1,3]dioxolane]-4a-ol via a transannular bromo-etherification protocol. The six-membered ring adopts a twist-boat conformation, while the fused cycloheptane ring adopts a chair conformation. The crystal packing is effected through two distinct intermolecular C—H⋯O hydrogen-bond patterns and molecules are arranged to define an interesting motif along the b axis.

TBK thanks the University Grants Commission, India for the award of Dr Kothari post-doctoral fellowship. We thank Mr Saikat Sen for his help in determining the X-ray crystal structure at the CCD facility of the Indian Institute of Science (IISc), Bangalore. GM acknowledges the research support from Eli Lilly and Jubilant-Bhartia Foundations.
Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: DS2204). Mehta, G. & Yaragorla, S. (2011). Tetrahedron Lett. 52, 4485-4489. Sheldrick, G. M. (2008. Acta Cryst. A64, 112-122. Uchiyama, N., Kabututu, Z., Kubata, B. K., Kiuchi, F., Ito, M., Nakajima-Shimada, J., Aoki Esquivel et al., 1995& Uchiyama et al., 2005 and cortistatin family ( Fig. 1; Aoki et al., 2006, 2007& Watanabe et al., 2007. In particular, cortistatin A and its structural siblings isolated in trace amounts by Kobayashi & coworkers from an Indonesian marine sponge corticium simplex were shown to possess novel architecture and exhibited potent and promising anti-angiogenic activity (Zhao, 2010) and were effective in treating blindness (Czako et al., 2009), thereby triggering interest to devise tactics for their total synthesis and diversity creation. These attributes of cortistatins encouraged us to devise a strategy to gain rapid access to the oxatricyclic ABC core present in cortistatins. A two step transannular bromoetherification protocol on 7 furnished the title compound 3 (Fig. 2) as the major product corresponding to the oxatricyclic core present in icetexanes along with a minor regioisomeric compound 4 representing the oxatricyclic segment present in cortistatins.
The title compound 3 was crystallized from ethylacetate-hexane(1:1) and the structure was solved and refined in monoclinic P2 1 /c space group with one molecule of 3 in the asymmetric unit. An ORTEP diagram of 3 drawn at 30% ellipsoidal probability is depicted in Fig 3. From the packing diagram it can be seen that the centrosymmetric molecules are connected by weak C11-H11···O2 (2.53 Å, 156°) hydrogen bonds forming a dimeric motif and these dimeric units are further connected by C1-H1···O1 (2.57 Å, 153°)) hydrogen bonds, three dimensionally (Fig. 4).These two hydrogen bond patterns link the molecules to define an interesting motif along the b axis.

Refinement
All the non-hydrogen atoms were refined anisotropically. Hydrogen atoms on the C atoms were introduced on calculated positions and were included in the refinement riding on their respective parent atoms

Figure 2
The synthesis of the title compound.  The molecular structure of the title compound 3, with the atom numbering scheme. Dispalcement ellipsoids for non-H atoms are drawn at 30% probability. 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 R-factors(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