N-(Fluoren-9-ylmethoxycarbonyl)-l-isoleucine

In the crystal structure of the title compound [systematic name fluoren-9-ylmethyl N-(1-carboxy-2-methylbutyl)carbamate], C21H23NO4, the molecular plane of the O=C—NH—Cα unit is slightly pyramidalized. The N atom deviates from the basal plane by 0.2086 (12) Å. The O=C—N—Cα torsion angle is −17.2 (2)°, and the C—N and O=C bond lengths are 1.3675 (17) and 1.2122 (17) Å, respectively. Apparently the character of the sp 2 hybrids of the molecular plane is, to some extent, reduced. The crystal structure exhibits two intermolecular hydrogen bonds (O—H⋯O and N—H⋯O), in which the hydroxy O atom acts as a donor to the carbonyl group and an acceptor of the amide group, respectively.


S1. Comment
The fluoren-9-ylmethoxycarbonyl (Fmoc) group is commonly used for protecting the terminal amine of the peptide for the current solid-phase peptide synthesis protocol. This is because cleavage of the Fmoc protecting group is easily achieved by mild basis conditions, e.g., piperidine, but it is very stable under acidic conditions. The crystal structures of It is interesting to compare the present structure with that of the analog of the title compound, i.e., N-α-Fmoc-protected-L-leucine, (II). A large fraction of the bond distances and angles, and torsion angles of (I) are consistent with those of (II) except for the following points. First, the orientation of the carboxyl group around the C1-C6 bond is found to be opposite. The torsion angle of O2-C6-C1-N1 for (I) is -6.3 (2)°, while the corresponding angle of (II) is 159.29 (17)°. Second, the angle between the fluorine ring and the NC(=O)O plane is quite different. For example, the torsion angle of C7-O4-C8-C9 and O4-C8-C9-C10 are 121.17 (13) and -73.17 (14)°, respectively, for (I). The corresponding torsion angles of (II), on the other hand, are 93.78 (16) and 60.54 (17)°, respectively. Third, it can be seen that the O3-C7-N1-C1 plane of (I) is slightly pyramided. The N1 atom deviates from the basal plane (C1, C7, H1N) by 0.2086 (12) Å. Moreover, the distances of the N1-C7 and O3-C7 bonds are 1.3675 (17) and 1.2122 (17) Å, respectively, which are approximately 0.026 longer and 0.010 Å shorter than the corresponding bond lengths of (II), respectively. Apparently, the sp 2 character of the N1 atom is, to some extent, reduced.
In addition, hydrogen-bond environments are slightly different between the two Fmoc-protected L-amino acids. The crystal of (I) contains two intermolecular hydrogen bonds (Table 1), while that of (II) has three hydrogen bonds. For (I), atom O1 forms two hydrogen bonds with O2 and N1, as shown in Figure 2. The molecules, which related by translation along the a axis are assembled via the N1-H1N···O1 hydrogen bonds to form a one dimensional tape structure. The tapes around the 2 1 axis, which is parallel to the a axis, are joined together, then the column structure is formed.

S2. Experimental
A powdered sample of the title compound (I) was purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan) and was used for the sample preparation without further purifications. Colorless needle like crystals of (I) were obtained from a saturated dichloromethane solution.

S3. Refinement
All H atoms were found on a difference map and were refined applying isotropic temperature factors. In the absence of significant anomalous scattering effects, Friedel pairs have been merged.

Figure 1
A view of the molecular structure of (I), showing the atom labeling scheme. Displacement ellipsoids are drawn at the 50% probability level.  A packing diagram of (I). The hydrogen atoms were omitted for clarity, except for those forming the hydrogen bonds.

Special details
Experimental. All Friedel pairs were merged, and all f′'s of containing atoms were set to zero. Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. 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 > 2σ(F 2 ) is used only for calculating R-factors(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.