Helicene-like chiral auxiliaries in asymmetric catalysis

International audienceThis literature overview demonstrates that helically chiral ligands and organocatalysts have been largely neglected so far. However, a few recent studies on helical pyridine, the corresponding ammonium salts and N-oxides have highlighted the significant potential of these compounds as organocatalysts for Michael type additions, aldehyde propargylations, epoxide openings, and others. In addition, helicenes displaying a fused phosphole ring at the end of their polyaromatic structures, have been used as ligands in enantioselective gold promoted cycloisomerization reactions, giving both excellent catalytic activity and high enantiomeric excesses. These recent results are expected to stimulate further research on the catalytic applications of helically chiral auxiliaries in the next few years

Functionalization of phospha-thiahelicenes and application of their gold(I) complexes in enantioselective catalysis

Helically chiral structures are known to display peculiar properties and applications in many fields, including asymmetric catalysis. However, both the synthesis of helical phosphorus ligands and their uses in enantioselective organometallic catalysis have been underdeveloped so far [1]. In the course of our studies on helical phosphane derivatives as potential chiral ligands in asymmetric organometallic catalysis [2], we have recently reported the synthesis of a new chiral phospha-thiahelicene based gold (I) complex, which is an excellent and selective pre-catalyst for the enantioselective cycloisomerization of N-tethered enynes [3]. On the basis of these very promising results we have effectively functionalized the phospha-thiahelicene scaffold to obtain new gold (I) complexes, which are then tested as pre-catalysts in other challenging enantioselective cycloisomerization reactions. 1. a) Y. Shen, C.-F. Chen, Chem. Rev. 2012, 112, 1463; b) P. Aillard , A. Voituriez, A. Marinetti, Dalton Trans. 2014, 43, 15263. 2. a) S. Cauteruccio, A. Loos, A. Bossi, M. C. Blanco Jaimes, D. Dova, F. Rominger, S. Prager, A. Dreuw, E. Licandro, A. S. K. Hashmi, Inorg. Chem. 2013, 52, 7995; b) K. Yavari, P. Aillard, Y. Zhang, F. Nuter, P. Retailleau, A. Voituriez, A. Marinetti, Angew. Chem. Int. Ed. 2014, 53, 861. 3. P. Aillard, A. Voituriez, D. Dova, S. Cauteruccio, E. Licandro, and A. Marinetti, Chem. Eur. J. 2014, 20, 12373

PHOSPHA-THIAHELICENE BASED GOLD(I) COMPLEXES IN ENANTIOSELECTIVE CATALYSIS

Helically chiral structures are known to display peculiar properties and applications in many fields, including asymmetric catalysis. However, both the synthesis of helical phosphorus ligands and their uses in enantioselective organometallic catalysis have been underdeveloped so far.1 In the course of our studies on helical phosphane derivatives as potential chiral ligands in asymmetric organometallic catalysis,2 we have recently synthesized a new chiral phospha-thiahelicene based gold (I) complex 1, through a highly diastereoselective procedure. Preliminary studies on its catalytic activity have shown that 1 is an excellent and selective precatalyst for the enantioselective cycloisomerization of N-tethered enynes (up to 96% ee).3 These promising results are especially rewarding as far as enantioselectivity in gold catalysed processes remain to date a highly challenging target

Phosphathiahelicenes : synthesis and uses in enantioselective gold catalysis

Enantiomerically pure thiahelicenes displaying a terminal phosphole unit and a stereogenic phosphorus center have been prepared by oxidative photocyclization of a diaryl-olefin precursor. Starting from one of these phosphathiahelicene oxides, the corresponding trivalent phosphine-Au(I) complex is obtained with complete diastereoselectivity. It affords a new, excellent precatalyst for the enantioselective cycloisomerization of N-tethered enynes (up to 96\u2009% ee)

The synthesis of substituted phosphathiahelicenes : Via regioselective bromination of a preformed helical scaffold : A new approach to modular ligands for enantioselective gold-catalysis

Substituted phosphathiahelicenes have been prepared via a straightforward two-step procedure involving the regioselective bromination of a preformed helical scaffold, followed by palladium catalyzed coupling reactions. The new helicenes have been used as ligands in gold(i)-catalyzed [4+2] cyclizations of 1,6-enynes. The resulting dihydro-cyclopenta[b]naphthalene derivative was obtained in excellent yields and with up to 91% ee

Synthesis and evaluation of a (3R, 6S, 9S)-2-oxo-1-azabicyclo[4.3.0]nonane scaffold as a mimic of Xaa-transPro in poly-L-proline type II helix conformation

We describe the development of a small-molecule mimic of Xaa-trans-Pro dipeptide in poly-L-proline type II helix conformation, based upon a (3R,6S,9S)-2-oxo-1-azabicyclo[4.3.0]nonane core structure. Stereoselective synthesis of the mimic from L-pyroglutamic acid is achieved in twelve linear steps and 9.9% yield. Configurational and conformational analyses are conducted using a combination of 1H NMR spectroscopy, X-ray crystallography and circular dichroism spectroscopy; and evaluation of the mimic as a promising surrogate dipeptide, in a protein–protein interaction between the SH3 domain of human Fyn kinase (Fyn SH3) and peptidomimetics of its biological ligand, are conducted by 1H-15N HSQC NMR titration experiments

Gas phase synthesis of [4]-helicene

Helicenes represent key building blocks leading eventually to carbonaceous nanostructures. Here, exploiting [4]-helicene as a benchmark, the authors present a synthetic route to racemic helicenes via a vinylacetylene mediated gas phase chemistry with aryl radicals involving ring annulation