(S)-(Z)-Methyl 2-[2,3-bis(benzyloxycarbonyl)guanidino]-4-methylpentanoate

The title molecule, C24H29N3O6, has a nearly planar ten-atom C3N3O4 core, on account of both N—H groups forming six-membered-ring intramolecular hydrogen bonds to carbamate carbonyl O atoms. The absolute configuration was determined from resonant scattering of light atoms in Mo Kα radiation, agreeing with the configuration of starting materials.

The title molecule, C 24 H 29 N 3 O 6 , has a nearly planar ten-atom C 3 N 3 O 4 core, on account of both N-H groups forming sixmembered-ring intramolecular hydrogen bonds to carbamate carbonyl O atoms. The absolute configuration was determined from resonant scattering of light atoms in Mo K radiation, agreeing with the configuration of starting materials.  Table 1 Hydrogen-bond geometry (Å , ).

Comment
Molecules used as drugs frequently contain heterocyclic subunits, and substituted guanidine or amidine compounds are very important intermediates in the synthesis of many heterocyclic compounds. However, substituted guanidines and amidine compounds themselves can be difficult to synthesize. Thus, synthesis of substituted guanidines is important and interesting.
One possible route to these compounds is to use 1,3-bis(benzyloxycarbonyl)-2-methyl-2-thiopseudourea, which has a good leaving group and L-leucine methyl ester hydrochloride, which is a good nucleophile. Reaction of these starting materials led to successful synthesis of the chiral title compound, which was confirmed by crystal structure determination.
The structure, shown in Figure 1, has a guanidine at its core. The three C-N distances of the guanidine vary from 1.3225 (12) to 1.3864 (12) Å, with the shortest being the formal double bond to the unprotonated N atom N2 and the longest being to the other carbamate N atom N3. These values are in good agreement with those seen in 1,2-bis(methoxycarbonyl)-3-phenylguanidine, (Travlos & White, 1994), in which the length pattern is the same and the range of lengths is 1.309 (3) to 1.388 (4) Å. In N,N',N''-tris(t-butoxycarbonyl)guanidine (Feichtinger et al., 1998;space group corrected by Marsh, 2002), the C═N and C-NH groups are disordered, and the C-N distance is 1.343 Å. In the title compound, the two N-H groups form intramolecular hydrogen bonds with graph set (Etter, 1990) S(6). The hydrogen bonding leads to a fairly planar central C 3 N 3 O 4 portion of the molecule, which has a mean deviation 0.019 Å from coplanarity and a maximum deviation 0.0533 (10) Å for N3.
The lone stereocenter is carbon C3, with (S) configuration, as known from starting material L-leucine. Absolute configuration determination based on resonant scattering of the light atoms in Mo Kα radiation was possible for this structure, on account of the excellent quality of the crystal, the fact that it is relatively rich in O and N, the high resolution of the data, and the completeness of the set of 4545 Bijvoet pairs, which were kept separate in the refinement. While the Flack (1983) parameter is unconvincing, with a value of 0.2 (5), the Hooft et al. (2008) parameter y = 0.0 (2) has a much smaller uncertainty, and the Hooft P2(true) value is 1.000. A number of oxygen-rich compounds producing Mo data sets of similar high quality have been shown to yield similarly reliable absolute-structure results, agreeing with the known configurations (Fronczek, 2010;Lutz & van Krieken, 2010;Thompson et al., 2008).

Experimental
A mixture of 1,3-bis(benzyloxycarbonyl)-2-methyl-2-thiopseudourea (2.79 mmol, 1 g), L-leucine methyl ester hydrochloride (2.79 mmol, 0.51 g), and triethylamine (2.79 mmole, 0.4 ml) in THF (absolute, 10 mL) was stirred at 338 K. The mixture was brought to room temperature, and the precipitate was filtered by vacuum. After evaporation of all solvents from the filtrate, the product was purified by chromatography (EtOAc/hexane, 1:4). The product was isolated as colorless crystals in 46% yield. 1  All H atoms were visible in difference maps, and those on C were placed in idealized positions with C-H distances 0.95 -1.00 Å and thereafter treated as riding. Coordinates for the H atoms on N were refined. U iso for H was assigned as 1.2 times U eq of the attached atoms (1.5 for methyl). A torsional parameter was refined for each methyl group. Friedel pairs were kept separate in the refinement. Fig. 1. Ellipsoids at the 50% level, with H atoms having arbitrary radius.