The development of CÀC bond-forming reactions that create two new stereogenic centers with high diastereo-and enantioselectivity in a single step can open new routes to highly valuable optically active compounds. The catalytic enantioselective addition to imines [1] belongs to this class of important reactions, and recently new catalytic asymmetric processes, for example, for Mannich-type, [2] ene, [3] allylation and alkylation, [4] aza-Diels ± Alder, [5] Strecker, [6] and aromatic electrophilic substitution reactions [7] have appeared. Another important reaction of imines is the nitro-Mannich (aza-Henry) reaction, which is a powerful CÀC bond-forming method that leads to 2-nitroamines. [8] To the best of our knowledge there is only one other paper that describes the catalytic enantioselective version of the nitro-Mannich reaction. [9] Although this reaction was catalyzed by a heterobimetallic complex, it has been described for nitromethane only and requires 60 mol % of the chiral ligand. In a very recent paper, we described the first catalytic asymmetric reaction of silyl nitronates with imines. [10] The reaction proceeds at À 100 8C in the presence of bisoxazoline ± copper catalysts to give 2-nitroamines with high enantioselectivities.
Herein we present a new and significantly simplified approach to the catalytic diastereo-and enantioselective nitro-Mannich reaction of an N-protected a-imino ester 1 with nitro compounds 2. The reactions can be performed under ambient conditions to give b-nitro-a-amino esters 3 in good yields, and with high diastereo-and enantioselectivies [Eq. (1); Pg protecting group].
In the screening process, the reaction of N-(p-methoxyphenyl)-a-imino ester 1 [11] with nitropropane 2 a in the presence of NEt 3 as the base has been studied at room temperature by using different combinations of chiral ligands and Lewis acids (Scheme 1). The use of chiral bisoxazoline
The structure was determined by mass spectrometry, 1 H and 19 F NMR spectroscopy as well as by X-ray diffraction. [14]