Pyramidalization of a carbonyl C atom in (2S)-N-(selenoacetyl)proline methyl ester

The title compound, C8H13NO2Se, crystallizes as a non-merohedral twin with an approximate 9:1 component ratio with two symmetry-independent molecules in the asymmetric unit. Our density-functional theory (DFT) computations indicate that the carboxy C atom is expected to be slightly pyramidal due to an n→ π* interaction, wherein the lone pair (n) of the Se atom overlap with the antibonding orbital (π*) of the carbonyl group. Such pyramidalization is observed in one molecule of the title compound but not the other.

The title compound, C 8 H 13 NO 2 Se, crystallizes as a nonmerohedral twin with an approximate 9:1 component ratio with two symmetry-independent molecules in the asymmetric unit. Our density-functional theory (DFT) computations indicate that the carboxy C atom is expected to be slightly pyramidal due to an n! * interaction, wherein the lone pair (n) of the Se atom overlap with the antibonding orbital (*) of the carbonyl group. Such pyramidalization is observed in one molecule of the title compound but not the other.
Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: KJ2221).

Pyramidalization of a carbonyl C atom in (2S)-N-(selenoacetyl)proline methyl ester Ilia A. Guzei, Amit Choudhary and Ronald T. Raines Comment
We have previously reported on extensive studies of geometrical and conformational attributes of several amide bond isosteres (Choudhary & Raines, 2011a). In contrast, selenoamides have not received much attention. Herein we report the crystal structure of the title compound N-selenoacetyl-(2S)-proline methyl ester (Scheme 1, (I)) and the results of a hybrid density functional theory (DFT) and Natural Bond Orbital (NBO) analysis (Glendening et al., 2001, Weinhold, 1998, Weinhold & Landis, 2005 of its geometrical features. Compound (I), Figure 1, crystallizes as a non-merohedral twin with the minor component contribution of 10 (2)%. The two components are related by 179° degree rotation about the [110] vector. The asymmetric unit in the relatively rare space group P1 contains two symmetry-independent molecules with the same handedness. The absolute structures of both components have been unequivocally established by anomalous dispersion effects: the Flack x parameters for the two components have been refined independently to 0.04 (2) and 0.02 (2). The two molecules have essentially identical geometries and their non-H atoms can be superimposed with a RMS of 0.042 Å. All geometrical parameters in the molecules are typical within experimental error (Bruno et al., 2002). The conformations of the five-membered rings in (I) are characterized by the puckering coordinates (Cremer & Pople, 1975) q 2 and φ 2 which measured 0.376 (14) Å and 89.8 (19)° for the Se1 molecule and 0.370 (15) Å and 85 (2)° for the Se1a molecule. Whereas the extent of puckering of the rings is the same, the ring in the Se1 molecule is in twisted conformation 3 T 4 whereas the ring in the other molecule is in the 3 T 4 conformation with a small 3 E envelope character. The envelope character is probably statistically significant.
The key feature of (I) is pyramidalization of atom C7 described with parameters Δ and Θ defined in Figure 2. These parameters are 0.016 (12) Å and 0.06 (5)° for the Se1 molecule and 0.040 (13) Å and 1.5 (5)° for the Se1a molecule. In the Se1 molecule the pyramidalization is not observed whereas in the second molecule the slight pyramidalization is statistically significant. For comparison, in the sulfur analog of (I) the relevant pyramidalization parameters Δ and Θ are 0.0293 (13) Å and 1.10 (5)°, also small and statistically significant.
We conducted DFT and NBO analyses of four low energy conformations of (I) (DeRider et al., 2002, Choudhary et al., 2009, Choudhary et al., 2010b, Choudhary et al., 2010a, Jakobsche et al., 2010 at the B3LYP/6-311+G(2 d,p) level of theory using Gaussian 03 (Frisch et al., 2004) and comment here on the most stable conformer. We have previously reported an interaction in proteins, termed the n→π* interaction, wherein the lone pairs (n) of an oxygen (O i-1 ) of a carbonyl group overlap with the antibonding orbital (π*) of C i =O i of an adjacent carbonyl group. The similar overlap in (I) between the lone pairs (n) of the selenium and the antibonding orbital (π*) of the carbonyl group is shown in Figure 3. (Bartlett et al., 2010, Choudhary & Raines, 2011b. This interaction resembles the Bürgi-Dunitz trajectory for nucleophilic additions to the carbonyl group and induces pyramidalization of the acceptor carbonyl group (Choudhary et al., 2009). The second-order perturbation theory as implemented in NBO 5.0 suggests n→π* interaction mediated supplementary materials stabilization of the trans conformation by 0.84 kcal/mol. The findings of our crystallographic studies partially support our theoretical findings: molecule Se1A shows pyramidalization whereas molecule Se1 does not. We attribute these results to the twinned nature of the crystals that lead to relatively high e.s.d.'s on geometrical parameters, but it was not possible to isolate a better crystal.

Experimental
Compound (I) was synthesized following from its oxygen congener by using (PhPSe 2 ) 2 (Woolins′ reagent) following a procedure reported previously (Bhattacharyya & Woollins, 2001). A small amount of (I) was dissolved in hexanes with a minimal amount of ethyl acetate. Slow evaporation of the solution afforded X-ray quality crystals of (I) after ~4 days.

Refinement
All H-atoms were placed in idealized locations and refined as riding with appropriate thermal displacement coefficients U iso (H) = 1.2 or 1.5 times U eq (bearing atom).

Figure 1
Molecular structure of (I). The thermal ellipsoids are shown at 50% probability level.  Pyramidalization parameters Δ and Θ of an n→π* interaction in (I).