A highly enantioselective catalytic asymmetric access to 3-aminooxindoles with a tetrasubstituted carbon stereocenter is described. 1-2 mol % of homobimetallic (R)-Ni(2)-Schiff base 1 catalyzed the asymmetric amination of 3-substituted oxindoles with azodicarboxylates to give (R)-products in 99-89% yield and 99-87% ee. Reversal of enantiofacial selectivity was observed between bimetallic and monometallic Schiff base complexes, and monometallic (R)-Ni-Schiff base 2c gave (S)-products in 98-80% ee. Transformation of the products into an optically active oxindole with a spiro-beta-lactam unit and a known key intermediate for AG-041R synthesis is also described.

A homodinuclear Ni(2)-Schiff base 1 complex (0.1-1 mol%) promoted the direct catalytic asymmetric aldol reaction of beta-keto esters with formaldehyde, giving hydroxymethylated adducts in 94-66% ee.

Thioesters are synthetically versatile building blocks that can be transformed to aldehydes, ketones, amides, and other functional groups under mild reaction conditions. [1] The use of malonic acid half-thioesters (MAHTs) as thioester enolate equivalents is an attractive method to mimic the biosynthesis of fatty acids and polyketides. [2][3][4][5] A highly enantioselective catalytic asymmetric decarboxylative aldol reaction of MAHT using a Cu/box catalyst was realized by Shair and co-workers. [3] Recently, the first organocatalytic enantioselective decarboxylative 1,4-addition of MAHTs to nitroalkenes was also developed by Wennemers and co-workers. [4a] The method provides straightforward access to the g-amino acids found in many pharmaceuticals, [6,7] such as rolipram [8] and pregabalin. The enantioselectivity of the reaction, however, remains unsatisfactory, because only one substrate had greater than 90 % ee. [4a] Thus, the development of new catalysts to achieve high enantioselectivity in decarboxylative 1,4-addition of MAHTs is highly desirable for the efficient short synthesis of pharmaceuticals. Herein, we report our efforts to address this issue. A new heterobimetallic Ni/Lasalan complex (Figure 1) was developed for catalytic asymmetric decarboxylative 1,4-addition of MAHT to nitroalkenes. The Ni/La-salan complex (10 mol %) gave products in up to 99 % yield and 94 % ee. A short synthesis of rolipram was also achieved.The stability of chiral metal complexes is important for realizing a highly enantioselective metal-catalyzed reaction using MAHTs. Chiral metal complexes should be tolerant to stoichiometric amounts of carboxylic acids (= MAHTs). We hypothesized that bimetallic Schiff base 1 complexes (Figure 1), [9][10][11][12] which we recently developed, could be applied for the reaction of MAHTs because dinucleating Schiff bases work as tetradentate ligands to form stable bimetallic complexes. [10] We first screened previously reported bimetallic Schiff base complexes, such as Cu/Sm-1 a, [10a] Pd/ La-1 a, [10b] Ni 2 -1 c, [12a, b] and Co 2 -1 c, [12c] and a heterobimetallic system containing a rare earth metal gave promising results. The optimization studies using MAHT 3 and nitroalkene 4 a are summarized in Table 1. Screening of metal combinations using ligand 1 a (entries 1-5) revealed that Ni/La gave the best reactivity and selectivity (entry 5). Thus, further optimization was performed using the Ni/La combination. Modification of the diamine moiety in Schiff bases 1 was effective (entries 5-8), and Schiff base 1 d gave product 5 a in 75 % ee, [a] M.

An efficient protocol for direct catalytic alkynylation of ketoimines is described. The simultaneous activation of a soft Lewis basic terminal alkyne and a ketoimine bearing a thiophosphinoyl group by soft Lewis acid Cu(I) is crucial for high conversion. The reaction can be rendered asymmetric with a chiral bisphosphine ligand (S,S)-Ph-BPE.

The reaction of 1-alkoxy-1-siloxyethene with [60]fullerene in 20% DMSO/chlorobenzene at ambient temperature under an oxygen atmosphere gave a penta-addition product, while the reaction of 1-alkoxy-1-siloxyalkenes or 1,2-siloxyalkenes under argon gave monoaddition products. The new method has merits over the previously reported syntheses of these compounds in that the synthesis does not require the use of heavy metals or photolysis conditions, and it can be carried out under simple and mild conditions.