The first crystal structure of the pyrrolo[1,2-c]oxazole ring system

The title compound is the first crystal structure of the pyrrolo[1,2-c]oxazole ring system. In the crystal, weak C—H⋯O and C—H⋯F hydrogen bonds link the molecules into [001] chains and π–π stacking interactions consolidate the structure.


Chemical context
In the context of an approach to the synthesis of prolinederived ketones 3 by the proposed palladium-catalyzed Negishi coupling of organozinc reagent 1 with protected 4-hydroxyproline-derived acid chloride 2, we needed access to a suitably N,O-diprotected 4-hydroxyproline derivative (Fig. 1). Our initial choice was to use TFA protection, since related cross-coupling reactions with the TFA-protected proline acid chloride had been successful (Deboves et al. 2001), and so the preparation of N,O-bis-trifluoroacetyl-4hydroxy-l-proline 4 was attempted. The preparation of this compound had been reported, but without a detailed procedure (Mori et al., 1986).
Treatment of (2S,4R)-4-hydroxyproline with trifluoroacetic anhydride TFAA (3 eq.) in dichloromethane at 273 K, followed by heating at reflux, gave a mixture of two compounds, which could be separated by column chromatography (Fig. 2). The more polar compound was the desired bis-TFA protected (2S,4R)-4-hydroxyproline 4 (47%), and the less polar material was an unknown by-product 5 (52%). This Proposed reaction scheme to access proline-derived ketones 3 from the Negishi coupling of organozinc reagents 1 with 4-hydroxyproline-derived acid chlorides 2, specifically towards the formation of compound 3

Figure 2
Reaction scheme for the synthesis of 5 along with the desired product 4. latter unknown compound exhibited signals in the aromatic region of the 1 H NMR spectrum, suggesting that the hydroxy group had been eliminated and a pyrrole derivative had been formed. The mass spectrum obtained for 5 showed a base peak at m/z 190 (100%), and the IR spectrum exhibited a stretching frequency in the carbonyl region at 1781 cm À1 . A crystal structure was obtained (see below), which confirmed that the compound was a new bicycle, a rare representative of the pyrrolo[1,2-c]oxazole ring system as first described by Katritzky et al. (2004).
When the reaction was repeated under milder conditions, omitting the period of heating under reflux, the desired bis-TFA protected 4-hydroxy-l-proline 4 was obtained in near quantitative yield, suggesting that it was partially converted into the novel pyrrolo[1,2-c]oxazole 5 under reflux conditions, presumably by elimination from an intermediate of structure 6.

Supramolecular features
In the crystal, two weak hydrogen bonds (Table 1) are observed between 5 and the adjacent molecule related by the symmetry operation (x, Ày + 1 2 , z À 1 2 ). These form between the sp 3 hydrogen atom H1 and the carbonyl oxygen atom O2 and the aromatic proton H6 and F1 of the triflomethyl group: together, they generate an [001] chain. The molecules pack in sheets parallel to the (010) plane with alternating layers of interdigitated CF 3 groups andstacked ring systems (Fig. 4). The shorteststacking interaction between centrosymmetrically related N1/C3-C6 rings has a centroidcentroid separation of 3.5785 (7) Å with a vertical distance of 3.4196 (5) Å and a shift of 1.017 Å with an inter-planar angle of 0 .

3-Trifluoromethyl-1H-pyrrolo[1,2-c]oxazol-1-one
Crystal data Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.