The enantioselective addition of aromatic thiols to a,b-unsaturated g-oxoesters bearing an imidazole substituent in the d position and catalyzed by an inert octahedral bis-cyclometalated iridium(III) complex is reported. High enantioselectivity down to catalyst loadings of 0.05 mol % is achieved mediated by the formation of wellarranged hydrogen bonds within the ligand sphere of the catalyst after the initial proton transfer. This work highlights the manifold opportunities provided by this metaltemplated design strategy in which the metal exerts a purely structural role whereas catalysis occurs through the organic ligand sphere (metal-templated organocatalysis).The Michael addition is a highly versatile reaction due to the diversity of nucleophiles (Michael donor) and electrophiles (Michael acceptor) that are suitable for this transformation. In this respect, the sulfa-Michael addition, namely the reaction of sulfurbased nucleophiles with electron-acceptor-substituted alkenes, constitutes a convenient method for the formation of CÀS bonds. Furthermore, the acidity of thiols in combination with a significant increase in the nucleophilicity upon conversion to thiolates provides an excellent handle for the asymmetric construction of stereogenic centers through chiral Brønsted base catalysis under mild conditions. [1,2] We recently introduced a class of chiral Brønsted base catalysts in which an iridium atom serves as a structural center in an inert octahedral metal complex and provides the source of chirality (metal-centered chirality) [3] and we demonstrated the excellent performance of this class of catalysts for asymmetric aza-Henry reactions and sulfa-Michael additions of thiols to a,b-unsaturated N-acyl pyrazoles. [4][5][6] To further explore the merit of such metal-templated chiral Brønsted base catalysts in asymmetric catalysis, we herein expand the scope of this sulfa-Michael addition to a,b-unsaturated g-oxoesters, leading to products with CÀS bonds in the a and b position to a carbonyl group and constituting a valuable structural motifs towards sulfur-containing pharmaceuticals (Figure 1).When we attempted to expand the L-IrBB-catalyzed sulfaMichael addition by using a,b-unsaturated N-acyl pyrazoles, bearing b-carboxylic esters instead of b-alkyl groups (Figure 1), we were surprised to find that the enantioselectivity of the CÀS bond formation in the reaction 1 a + 2 a!3 a was just modest and could not be optimized significantly, although running the reactions at lower concentrations improved the ee values slightly ( 79 % ee, Table 1, entries 1-4). [7] Since the pyrazole group of 1 a is supposed to serve as an important hydrogen bond acceptor in the activation mode, we decided to investigate other hydrogen bond acceptor functionalities (entries 5-9). And indeed, the results in Table 1 reveal that, compared with different N-acyl pyrazoles (1 a-c), 2-acyl imidazoles (1 d and 1 e) were identified to be superior for the sulfa-Michael addition with 4-methylbenzenethiol in terms of the ee of Figure 1. ...

A highly diastereo- and enantioselective synthesis of 3,3-disubstituted oxindoles bearing vicinal quaternary-tertiary carbon centers is enabled by a chiral-at-rhodium Lewis acid catalyst starting from isatin N-protected ketimines and 2-acyl imidazoles. The excellent results with 93-99% yields, diastereoselectivities of 43:1 to >200:1, and high enantioselectivities of 98.4 to >99% confirm the potential of bis-cyclometalated rhodium catalysts for the development of effective asymmetric transformations.

Enantioselective Sulfa-Michael Addition to ,-Unsaturated -Oxoesters Catalyzed by a Metal-Templated Chiral Broensted Base. -Substrate (II) is selected as the best educt for the title reaction. Aromatic thiols add to the double bond to form sulfurated products which contain carbonyl groups at the  and  positions in relation to the stereogenic center. The  configuration at the iridium center of the catalyst (I) leads to an (S) configuration of the target thioethers which are of interest as synthons for chiral sulfur-containing pharmaceuticals. -(DING, X.; LIN, H.; GONG*, L.; MEGGERS, E.; Asian J. Org. Chem. 4 (2015) 5, 434-437, http://dx.