[Show abstract][Hide abstract] ABSTRACT: A facile and efficient approach for the synthesis of a variety of acridines via the tandem coupling/cyclization of substituted 2-bromobenzaldehydes and anilines is described. The reaction can be accomplished with ease in the presence of a catalytic amount of Pd2(dba)3 and diphosphine ligand dppf, providing a broad range of substituted acridines in good to excellent yields (up to 99%). Lewis acid AlCl3 is required to promote the cyclization when less electron-rich anilines are employed.
[Show abstract][Hide abstract] ABSTRACT: A highly enantioselective rhodium-catalyzed intramolecular addition of arylboronic acids to unactivated ketones has been developed. By employing a simple, chiral sulfur-based branched olefin as the ligand, the reaction occurs efficiently under mild conditions. A wide range of chiral 3-hydroxy-2,3-dihydrobenzofurans bearing a tetrasubstituted stereocenter at C-3 position can be obtained in high yields (up to 98%) with excellent enantiomeric excesses (up to 98% ee).
[Show abstract][Hide abstract] ABSTRACT: A unique Rh(I)-catalyzed asymmetric B-H insertion of α-diazo carbonyl compounds with easily available amine-borane adducts using a newly developed C1-symmetric chiral diene as ligand was achieved. This first rhodium(I) carbene-directed B-H insertion example represents an attractive and promising approach for synthesis of highly enantioenriched organoboron compounds, allowing for the efficient construction of α-boryl esters and ketones with excellent enantioselectivities (up to 99% ee) under exceptionally mild conditions.
Journal of the American Chemical Society 03/2015; 137(16). DOI:10.1021/jacs.5b00892 · 12.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A Lewis acid promoted highly diastereoselective asymmetric Friedel-Crafts alkylation of indoles with isatin-derived N-tert-butanesulfinyl ketimines is described. The reaction can be accomplished with ease in the presence of a catalytic amount of Bi(OTf)3, providing a series of 3-indolyl-3-aminooxindoles in excellent diastereoselectivities (up to 98% de) and yields (up to 99%).
[Show abstract][Hide abstract] ABSTRACT: A simple catalyst system of Rh(I)/sulfur-olefin with exceptional catalytic performance has been developed for the highly enantioselective arylation of cyclic N-sulfonyl aryl alkyl ketimines with arylboroxines/arylboronic acids. Optically active α-arylalkyl-substituted benzosultams and benzosulfamidates which are generally difficult to obtain were easily prepared with excellent stereocontrol (up to 99.9% ee). The synthetic utility of the approach was demonstrated by the facile construction of NMDA antagonist FR115427 and benzoxazinone derivatives. This protocol offers new opportunities for the efficient synthesis of diverse chiral α-tertiary amines.
[Show abstract][Hide abstract] ABSTRACT: An efficient method for the preparation of highly optically active 3-allenyl- and 3-vinyl-4-aminochromanes by In-mediated intramolecular cyclization has been developed. The synthetic utilities of the approach were demonstrated by the construction of various chiral polycyclic heterocycles, especially the interesting spiroheterocyclic compound 9 and steroid analogue 10.
[Show abstract][Hide abstract] ABSTRACT: A practical and efficient method for preparation of highly enantiomerically enriched 3-cyano-3-aminooxindoles and 3-trifluoromethyl-3-aminooxindoles with up to 99% optical purity by a Lewis acid promoted diastereoselective Strecker reaction and trifluoromethylation of isatin-derived N-tert-butanesulfinyl ketimines has been developed. This protocol allows direct use of N-free isatin substrates under mild conditions.
The Journal of Organic Chemistry 07/2014; 46(7). DOI:10.1021/jo501360g · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A highly enantioselective rhodium-catalyzed arylation of cyclic diketimines with arylboronic acids was achieved under mild conditions by employing a simple, sulfinamide-based branched olefin ligand. This protocol provides an efficient access to valuable chiral tetrasubstituted 1,2,5-thiadiazoline 1,1-dioxides in high yields with excellent enantioselectivities of up to 99% ee.
[Show abstract][Hide abstract] ABSTRACT: A novel type of open-chain chiral chelating olefin bearing a simple monophosphite unit with a binaphthyl backbone was designed and synthesized, which could serve as an elegant chiral bidentate ligand in the rhodium-catalyzed asymmetric 1,2-additions of organoboron reagents to α-diketones and N-sulfonyl aldimines.
[Show abstract][Hide abstract] ABSTRACT: SIRT1 is a NAD(+)-dependent deacetylase. It deacetylates a broad range of substrates and is involved in multiple diseases such as type 2 diabetes and cancer. Here we discovered a new class of SIRT1 inhibitors with the scaffold of 3-(furan-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole. The inhibitors up-regulate acetyl p53 level in human breast cells MCF-7. The docking simulations indicated that the scaffold and the R-substituents of the inhibitors bind in the C and D pocket of SIRT1, respectively, which was supported by the structure-activity relationship and SIRT1 mutagenesis studies. We propose that binding of the inhibitors repels the entering of the nicotinamide moiety of NAD(+) to the C pocket, prevents its transformation to the productive conformation and therefore inhibits the deacetylation catalyzed by SIRT1.
[Show abstract][Hide abstract] ABSTRACT: The first Rh-catalyzed asymmetric tandem cyclization of nitrogen- or oxygen-bridged 5-alkynones with arylboronic acids was achieved. The simple catalytic system involving a rhodium(I) complex with readily available chiral BINAP ligand promotes the reaction to proceed in a highly stereocontrolled manner. This protocol provides a very reliable and practical access to a variety of chiral heterocyclic tertiary allylic alcohols possessing a tetrasubstituted carbon stereocenter and an all-carbon tetrasubstituted olefin functionality in good yields with great enantioselectivities up to 99% ee.
[Show abstract][Hide abstract] ABSTRACT: Since 2003, the discovery of chiral dienes as steering ligands in asymmetric processes has opened the field of chiral chelating olefin catalysis. However, despite the impressive advances, the development of readily accessible and catalytically promising chiral olefins has been much less successful. In very recent years, chiral sulfur-containing olefins have emerged as a new exciting class of hybrid ligands for asymmetric catalysis. This article summarizes our efforts in developing extremely simple chiral sulfur-olefins as ligands for a variety of transition-metal-catalyzed asymmetric transformations, and the recent progress by other groups in the design and use of sulfinamide- or sulfoxide-based olefins in asymmetric catalysis.
Chemical Communications 02/2014; 50(29). DOI:10.1039/c3cc49431d · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A novel arylation-cyclization strategy for the highly enantioselective synthesis of titled heterocycles with a quaternary stereogenic center has been developed.
Chemical Communications 11/2013; 49(99). DOI:10.1039/c3cc47927g · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Simple and readily available chiral N-(sulfinyl)allylamines have been developed as efficient novel ligands for the rhodium-catalyzed enantioselective 1,2-addition of arylboronic acids to challenging aliphatic α-ketoesters. By employing the linear or branched sulfinamide-olefin ligands, interesting enantioselectivity as well as regioselectiv-ity reversal in the related asymmetric additions were observed.
Chinese Journal of Chemistry 10/2013; 2013(31):321. DOI:10.1002/cjoc.201300063 · 1.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The domino effect: An efficient and general catalytic one-pot synthesis of quaternary-substituted isochroman derivatives has been developed. The cascade transformation relies on rhodium-catalyzed highly regio- and enantioselective 1,2-addition of arylboronic acids to unsymmetrical α-diketones and intramolecular etherification or esterification, and provides a variety of enantioenriched isochromanones under exceptionally mild conditions.
Chemistry - A European Journal 06/2013; 19(3). DOI:10.1002/chem.201203701 · 5.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Enantioselective synthesis of potentially useful chiral 3-aryl-1-indanones was achieved through a rhodium-catalyzed asymmetric intramolecular 1,4-addition of pinacolborane chalcone derivatives using extraordinary simple MonoPhos as chiral ligand under relatively mild conditions. This novel protocol offers an easy access to a wide variety of enantioenriched 3-aryl-1-indanone derivatives in high yields (up to 95%) with excellent enantioselectivities (up to 95% ee).
The Journal of Organic Chemistry 02/2013; 78(6). DOI:10.1021/jo302656s · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The kinetic characteristics of hydroxamate-based inhibitors of matrix metalloproteinase (MMP)-12 were explored using an SPR biosensor-based assay and enzyme inhibition analysis. These high-affinity inhibitors were shown to dissociate very slowly from the enzyme–inhibitor complex while a carboxylate analogue had a much faster dissociation rate, verifying the importance of the hydroxamate group for the slow dissociation. Progress curve enzyme inhibition analysis confirmed that the hydroxamate compounds but not the carboxylate compound acted as time-dependent inhibitors. The slow dissociation excluded steady-state estimation of IC50-values and Ki values but also made Ki values from progress curve analysis unreliable. Although a full characterization of the inhibitors using biosensor analysis was limited by slow dissociation, it provided kinetic and mechanistic information of relevance for MMP drug discovery and avoided some pitfalls of conventional enzyme inhibition assays.
Medicinal Chemistry Communication 01/2013; 4(2):432-442. DOI:10.1039/C2MD20268A · 2.50 Impact Factor