Issue in Honor of Prof. Lutz F. Tietze ARKIVOC 2007 (v) 20-37
commercially available corresponding diamine.13a,b In this paper we describe full details of our work towards a general approach to this kind of chiral ligand, based on the aminolysis of aziridines.13c
NH2 NHTs
NHTs NHSO2R
NH2 NH2
NHTs NHTs
(S,S)-1
(S,S)-3
Figure 1. Cyclohexane-based symmetrical and unsymmetrical chiral ligands.
Results and Discussion
It was envisaged that if N-tosylcyclohexyl aziridine were opened with a benzylamine in a diastereoselective manner, the product could be converted into an amino-sulfonamide after debenzylation. With this idea, several N-tosyl aziridines were synthesized using known procedures.14 Although ring-opening of such N-activated aziridines with aromatic amines has been studied extensively using Lewis acids,15 little has been published on the opening with aliphatic amines.16 At the outset, 10 mol.% of several Lewis acids such as Cu(OTf)2 (70%), Zn(OTf)2 (81%), Sn(OTf)2 (78%), YbCl3 (70%), ErCl3 (68%), and LiClO4 (88%), were screened for opening of N-tosylcyclohexyl aziridine (1 mmol) with benzylamine (1.25 mmol) in MeCN at room temperature over more than 24 h. From this study, it appeared that LiClO4 is more effective, as indicated by isolated yields. Long reaction times at room temperature prompted us to try the same reaction at reflux temperature using LiClO4 as a catalyst. To our delight, the reaction was complete in 4 h and the ring-opened product was obtained in 94% yield (Table 1, entry 1). The trans- stereochemistry in the product was deduced from the coupling constants (J =
10.5 Hz and 3.9 Hz) of the signal at 2.29 ppm (-CH-NH-) in the 1H- NMR spectrum. The ring opening reaction was also tried with other amines such as phenylethylamine, piperidine, morpholine, and N-ethoxycarbonyl piperazine. In all cases, high yields of product were obtained (Table 1, entries 2-5). The reaction was extended to a few other N-tosyl aziridines and the results are summarized in Table 1. Aziridines derived from cyclopentene and cyclohexa-1,4-diene gave the ring-opened products in good to excellent yields (Table 1, entries 6-9). An acyclic terminal aziridine gave products resulting from terminal attack only (Table 1, entries 10 and 11). Once the methodology for cleavage of N-tosylaziridines with aliphatic amines,18 especially benzylamine, was established it was extended to chiral amines. Initially, (R)-amethylbenzylamine (1.25 mmol) was used for desymmetrization of N-tosylcyclohexyl aziridine (1 mmol) in the presence of LiClO4 (0.1 mmol) in MeCN. The reaction was complete in 6 h at reflux temperature and the product was obtained in 94% yield as a separable mixture of diastereomers in a 1:1 ratio (Table 2, entry 1). The reaction was scaled up to 25 g scale without any problem. The (S,S,R)-9 diastereomer is more polar (Rf 0.28) than (R,R,R)-9 (Rf 0.42). The
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