(9H-Fluoren-9-yl)methyl N-{(2R,3R,4S)-4-hydroxy-2-[(2S,5R)-2-isopropyl-5-methylcyclohexyloxy]-5-oxooxolan-3-yl}carbamate propan-2-ol 0.334-solvate

The title compound, C29H35NO6.0.334C3H8O, a novel chiral N-(fluoren-9-ylmethyloxyxcarbonyl) precursor, crystallizes with two independent carbamate (M) molecules and propan-2-ol solvent molecules in the unit cell. Its crystal structure has been determined from barely adequate data obtained from a multi-fragment needle crystal. In the crystal, N—H⋯O hydrogen bonds link M molecules related by translation along the a axis into two independent chains. The ordered solvent molecule, having a partial occupancy of 0.334, is attached to one independent M molecule through O—H⋯O hydrogen bonds. The crystal packing exhibits weak intermolecular C—H⋯O interactions and voids of 270 Å3 filled with randomly disordered solvent molecules which were handled using the SQUEEZE methodology.

The title compound, C 29 H 35 NO 6 .0.334C 3 H 8 O, a novel chiral N-(fluoren-9-ylmethyloxyxcarbonyl) precursor, crystallizes with two independent carbamate (M) molecules and propan-2-ol solvent molecules in the unit cell. Its crystal structure has been determined from barely adequate data obtained from a multi-fragment needle crystal. In the crystal, N-HÁ Á ÁO hydrogen bonds link M molecules related by translation along the a axis into two independent chains. The ordered solvent molecule, having a partial occupancy of 0.334, is attached to one independent M molecule through O-HÁ Á ÁO hydrogen bonds. The crystal packing exhibits weak intermolecular C-HÁ Á ÁO interactions and voids of 270 Å 3 filled with randomly disordered solvent molecules which were handled using the SQUEEZE methodology.

Comment
The title compound was prepared as part of our current research into the applicability of 4-chlorobenzoyloxycarbamates as highly efficient nitrogen reagents for the intermolecular aminohydroxylation under base-free reaction conditions. When the target compound, (R)-5-[(1R)-menthyloxy]-2(5H)-furanone 1 was treated with the Fmoc-reagent 3 (Fig. 1) using the standard aminohydroxylation conditions that we reported previously (Harris et al., 2011) the title compound 2 was isolated in 74% yield. Formation of the corresponding regioisomer was not observed in our experiments.
The title compound crystallizes with two independent molecules in the asymmetric unit and one resolved partial (occupancy = 0.667) 2-propanol molecule (Fig. 2) as well as disordered 2-propanol solvent; the latter was handled using the SQUEEZE methodology (Spek, 2009), see Experimental. It seems highly likely that all the included solvent of crystallization was not stable to X-rays during the experiment, a further complicating factor which makes it impossible to define the total 2-propanol concentration in the crystal. Nevertheless, only confirmation of structure was required of this study, with the absolute configurations of C2,C102(S), C3,C103(R), C4,C104(R), C1',C11'(R), C2',C12'(S), C5',C15'(R) & C7,C107(S) expected from the synthesis. With only 61% Friedel coverage it is surprising that the chirality indications based on the oxygen anomalous dispersion is correct, although of very low statistical significance. Confidence in the structural solution and final dataset is gained from the self-consistency of the two independent molecules which are almost identical: they have an r.m.s. atom fit of 0.171 Å, r.m.s. bond fit of 0.034 Å and r.m.s. angle fit of 2.04 ° (Spek, 2009). The 5-oxotetrahydrofuran rings have envelope conformations with C3, C103 as the flap atoms respectively and the cyclohexyloxy rings are in chair conformations (Spek, 2009).

Refinement
All crystals mounted gave multiple crystal diffraction profiles; the largest of these was chosen. Data was then extracted by using a 30 by 30 pixel spotsize from data collected with a 5 degree scan width and redundancy 3. During processing, frames 101-127 & 408-423 were observed to be incorrectly measured with noticeable icing and so the dataset was reprocessed omitting these frames. As the compound was known to be one chiral form, space group P1 was chosen. One structural solution was achieved using SHELXS with the rather extreme parameter TREF 10000! Analysis of the F o /F c data table then showed, consistent with the observed frames, that data beyond 0.87 Å was both weak and incorrectly positioned; this data was excluded using the SHEL command. The initial solution gave a best R1 of ~18% after attempts to include partial C atoms as disordered solvent had been attempted. One 2-propanol could be identified (at about 0.7 occupancy), but the remaining solvent was fully disordered. The PLATON SQUEEZE processing method (Spek, 2009) was then applied with the 5756 2σ(I) data converging to an R1 of ~13%. At this point extreme The occupancy of partial resolved 2-propanol solvent was based on electron densities at the non-hydrogen atom sites determined by a refinement with fixed average isotropic U values of 0.08 e.Å -3 . This lead to the fixed value of 0.667; the non-hydrogen atoms were then refined with one common isotropic thermal parameter.The hydrogen on the partial resolved 2-propanol oxygen was placed at its calculated position based on hydrogen bonding criteria (Nardelli, 1999). it was considered that this systematic change was not justifiable.
In the absence of any significant anomalous scatterers in the molecule and the low fraction of Friedel pairs measured (0.46), the refinement of Flack parameter led to a formally inconclusive value of 0.1 (3). Therefore, in the final refinement, the Flack parameter was not refined, and the absolute configuration was assigned to correspond with that of the known chiral centres in a precursor molecule, which remained unchanged during the synthesis of the title compound.