Crystal structure of (2S,4R)-ethyl 4-nitromethyl-1-[(S)-1-phenylethyl]-6-sulfanylidenepiperidine-2-carboxylate

In the title compound, C17H22N2O4S, a thiopiperidine derivative, the piperidine ring has an envelope conformation with the methylene C atom opposite to the C=S bond as the flap. The nitromethyl substituent is equatorial while the ethoxycarbonyl group is axial. The mean planes of the nitromethyl group, the carboxy group and phenyl ring are inclined to the mean plane through the five planar atoms of the piperidine ring [maximum deviation = 0.070 (4) Å] by 56.8 (2), 83.8 (5) and 87.1 (2)°, respectively. There is an intramolecular C—H⋯O hydrogen bond involving an H atom of the ethoxycarbonyl group and a nitro O atom. In the crystal, molecules are linked by C—H⋯O hydrogen bonds, forming chains along [100]. The chains are linked by further C—H⋯O hydrogen bonds, forming corrugated layers lying parallel to (001).


S1. Comment
The Michael addition is one of the most important synthetic strategies performed in organic synthesis. Among the many applications, conjugate addition to α,β-unsaturated δ-lactams has been used in the synthesis of functionalized piperidines, due to a wide range of biological activities (Leung et al., 2000). Similar to α,β-unsaturated δ-lactams, α,β-unsaturated δthiolactams are promising Michael acceptors affording 4-substituted piperidine-2-thiones (Sośnicki, 2009). They also form C-C bonds in the reaction with organometallics such as alkyllithium, alkylmagnesium (Tamaru et al., 1978) and lithium enolates (Tamaru et al., 1979). Among a broad range of nucleophiles applied to the C-C bond formation, the addition of aliphatic nitrocompounds play a significant role (Ballini et al., 2007). In the presence of a base catalyst, the introduction of a nitroalkyl group into a α,β-unsaturated compound represent a key step in the preparation of chiral molecules due to versatile reactivity of the nitro functionality. The corresponding nitro compounds can be transformed into a wide range of synthetically valuable products such as amines (Poupart et al., 1999), ketones (Pinnick et al., 1990), carboxylic acids, nitrile oxides and other functionalities (Mukaiyama et al., 1960).
In the crystal, molecules are linked by C-H···O hydrogen bonds forming chains along [100], which are linked by further C-H···O hydrogen bonds forming corrugated layers lying parallel to (001); see Table 1 and Fig. 2.

S2. Experimental
α,β-Unsaturated piperidine-2-thione derived from (S)-(-)-phenylethylamine (1.0 mmol) was dissolved in a solution of nitroalkane, and a catalytic amount of DBU was added. The mixture was stirred at room temperature for 2 h. When the reaction was complete, 5 ml of concentrated NH 4 Cl was added and the solution was extracted twice with ethyl acetate.

S3. Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The C-bound H atoms were placed in idealized positions and refined as riding on their parent atoms, with C-H = 0.93-0.98 Å and with U iso (H) = 1.5U eq (C) for methyl H atoms and = 1.2U eq (C) for other H atoms. In the final cycles of refinement 18 reflections were omitted owing to poor agreement.

Figure 1
A view of the molecular structure of the title compound, with atom labelling. Displacement ellipsoids are drawn at the 30% probability level.

Figure 2
A view along the a axis of the crystal packing of the title compound. Hydrogen bonds are shown as dashed lines (see Table 1 for details; H atoms not involved in the intermolecular hydrogen bonding have been omitted for clarity).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq S1 0.