No abstract

No abstract

The first direct asymmetric Mannich reaction of malononitrile to N-Boc-protected imines has been developed with cinchona alkaloid as catalyst. The procedure could tolerate a relatively wide range of substrates, and results in excellent yields and good enantioselectivities even in the presence of only 1 mol% of catalyst loading. The present work provides an easy access to β-amino malononitrile derivatives.

An efficient direct aldol reaction has been developed for the synthesis of chiral b-hydroxy ketone using a combination of C 1 -symmetric chiral prolinamides based on o-phenylenediamine and zinc triflate as catalyst. The reaction was convenient to carry out in aqueous media with up to 98% chemical yields and up to 94% ee values. The current strategy can be regarded as the analogue of aldolase type II, which suggests a new pathway for the designing of new organocatalysts. The development of stereoselective and enantioselective aldol reaction has become an interesting and challenging topic in modern organic and medicinal chemistry (1-3), because the resulting chiral b-hydroxy ketones belong to an extremely important class of biological compounds. In fact, b-hydroxy ketones can serve as versatile building block for the asymmetric synthesis of carbohydrates, amino acids and many other biomolecules (4-6). They also provide privileged structural functionalities that exist in many important natural products (7-12). For example, the b-hydroxy ketones functionalities exist in macrolide classes of antibiotics such as telithromycin and cethromycin which are targeted primarily against Gram-positive bacterial strains including Streptococcus pneumoniae and S. pyogenes, fastidious Gram-negative strains including Haemophilus influenzae and Moraxella catarrhalis, atypicals Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophilia (13). They were also found in conagenin that can improve the antitumor efficacy of adriamycin and mitomycin C against murine leukemias, which suggest its potential utility for cancer chemotherapy (14).In virtue of the importance of chiral b-hydroxy ketones, several approaches aiming to prepare them have been reported in the last decade (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Among all the catalytic direct aldol, the most attractive one is the mimic of the actions of the enzymes. Although the direct catalytic aldol systems which were assumed to proceed through an enamine mechanism by mimic of aldolase type I have been well explored (28-32), the direct aldol systems by using the methods analogue to the actions of aldolase type II containing a zinc cofactor have still remained challenging. In fact, there were only a few reports for direct aldol reactions promoted by the zinc complexes with N-donor ligands in the presence of water until now (33-38). Herein, we reported a chiral ligands and zinc triflate catalyzed asymmetric direct aldol reaction with water as solvent. To our knowledge, this is the first example that mimics type II aldolase utilizing C 1 -symmetric organic molecular based on o-phenylenediamine as chiral ligand. Results and DiscussionsAccording to the mechanism of type II aldolase (33-38), we designed and prepared a series of chiral ligands (Figure 1). These chiral ligands 1-6 were easily prepared from proline and aniline or o-phenylenediamine in high yields. Most of these ligands have C 1 symmetry, expect compound 4, which is a C 2 -symmetric ligand. Then, all thes...

No abstract