(4aR,6aS,10aR,10bS)-7,7,10a-Trimethyl-1,4,4a,5,6,6a,7,8,9,10,10a,10b-dodecahydro-2H-naphtho[2,1-c]pyran (Pyamber)

The crystal structure of the title compound, C16H28O, features C—H⋯O hydrogen bonds making C(6) zigzag chains along one 21 screw axis. Within the limits of the data collection affected by crystal quality, the Hooft parameter gave correct indications of the known molecular chirality based on the single O atom anomalous dispersion in contrast to the indeterminate Flack value. Synthetic steps starting from manool are reported.

The crystal structure of the title compound, C 16 H 28 O, features C-HÁ Á ÁO hydrogen bonds making C(6) zigzag chains along one 2 1 screw axis. Within the limits of the data collection affected by crystal quality, the Hooft parameter gave correct indications of the known molecular chirality based on the single O atom anomalous dispersion in contrast to the indeterminate Flack value. Synthetic steps starting from manool are reported.

Comment
The title compound ("pyamber") was synthesized from methyl ketone 1, which is readily synthesized from manool in multigram quantites (Grant et al., 1988), in 4 synthetic steps (Fig. 1). A Baeyer-Villager insertion reaction of neat 1 was achieved using mCPBA to afford the previously described acetate 2 in good yield (Evans & Grant, 1997). Treatment of 2 with aluminium bromide in anhydrous diethyl ether gave one major product, aldehyde 3, which was not characterized but then immediately reduced with lithium aluminium hydride to afford diol 4 in moderate yield for the two steps (Vlad et al., 1978).
Cyclization through dehydration was readily achieved under Dean and Stark conditions to afford crystalline pyamber in good yield, following chromatography; the analytical data was identical to that previously reported by Vlad et al. (1983).
There are very few structures reported with these same three fused six-membered rings (Allen, 2002. CSD version 5.32, with May 2011 update); each ring is in a standard chair conformation. The closest related compound is the epoxide structure methyl 8,9-epoxy-12-oxo-13-oxototarane-14β-carboxylate (Cambie et al., 1988) reported in the inverted configuration. The molecules pack in zigzag chains along the b 2 1 screw axis bound by one C-H···O hydrogen bond (Fig. 3, Table 1) described by the motif C(6) (Bernstein et al., 1995). These chains are efficiently interlocked in the other two cell directiions via van der Waals interactions. (2): mCPBA (26.4 g, 50% b.w., 76.4 mmol) was added portionwise to a stirred solution of methyl ketone 1 (5 g, 19.1 mmol) in chloroform (150 ml). The round bottom flask was transferred to a rotavapor and the chloroform removed in vacuo at 40° C and the resulting paste left to rotate at 40° C overnight. The paste was redissolved in chloroform (200 ml) and stirred with calcium hydroxide (20 g) for 2 h, filtered through Celite&reg; and then concentrated in vacuo. The resulting oil was purified by flash chromatography on silica gel (1:4 ethyl acetate:petrol) to afford compound 2 (3.7 g, 66%). 1 H and 13 C NMR were identical to that described in the literature (Evans & Grant, 1997).

Refinement
After structural refinement it was noted that high angle data (d < 0.90 Å) had systematically F o **2 << F c **2; this reflected the poor profiles noticed for higher angle data, but may have also been affected by minor movement (some icing was noted).
As a consequence data was limited to that within the d resolution of 0.90 Å. A further 8 reflections (one at low angle) within this shell were clearly outliers and so were excluded.

Special details
Geometry. All e.s. 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.