Literature review Angewandte Chemie Int. Ed. 2007, Issues , Issues 1-5 Synlett 2007, Issues , Issues 1-2 Nicolas Demoulin 24/01/08

2 Angew. Chem. Int. Ed. 2007, 46, Metal-Catalytic Hydrogenation P. A. Chase, G. C. Welch, T. Jurca, and D. W. Stephan* Hydrogenation is one of the most important catalytic method in synthetic organic chemistry (lab & industry) H 2 cleanest reducing agent Addition of hydrogen to unsaturated organic compounds usually mediated by homogeneous or heterogeneous transition-metal catalysts (Ni, Pd, Ru, Rh….)

3 Only few hydrogenations involve non-transition-metal catalysts Albrecht Berkessel, Thomas J. S. Schubert, and Thomas N. Müller J. Am. Chem. Soc. 2002, 124, P. I. Dalko, L. Moisan, Angew. Chem. Int. Ed. 2004, 116, ; Angew. Chem. Int. Ed. 2004, 43, D. Menche, J. Hassfeld, J. Li, G. Menche, A. Ritter, S. Rudolph, Org. Lett., 2006, 8, D. Menche, F. Arikan, Synlett, 2006, Angew. Chem. Int. Ed. 2007, 46,

4 “Frustrated Lewis pairs” Bulky Lewis acid and base  no Lewis adduct G. C. Welch, R. R. S. Juan, J. D. Masuda, D. W. Stephan Science 2006, 314, Gregory C. Welch and Douglas W. Stephan J. Am. Chem. Soc. 2007, 129,  Air & moisture stable  Metal-free hydrogenation catalysts of imines, nitriles and aziridines Angew. Chem. Int. Ed. 2007, 46,

5 Reduction of Imines EntrySubstrateCatT(°C) P(H 2 ) atm t(h) Yield( %) Product Bulky imines reduction (1-5) Electron poor imines less reactive Less bulky imines react with the catalyst forming a strong adduct and inhibit it Problem solved in presence of B(C 6 F 5 ) 3 Angew. Chem. Int. Ed. 2007, 46,  Basicity of N center at stake

6 Reaction with nitriles and aziridines EntrySubstratet(h) Yield (%) Product 1MeCN B(C 6 F 5 ) 3 - isonitrile -0- MeCNB(C 6 F 5 ) 3 Nitrile fonction clearly interacts with catalyst Problem solved in presence of activating B(C 6 F 5 ) 3 Ring opening of unactivated aziridines Activated isonitriles don’t react Angew. Chem. Int. Ed. 2007, 46,

7 Mechanism for Bulky Imines and Aziridines Angew. Chem. Int. Ed. 2007, 46, The bulkier the imine is, the quicker the reaction is 31 P, 11 B, 19 F NMR

8 Mechanism for activated Imines and Nitriles Nitriles or less bulky imines Protection with B(C 6 F 5 ) 3 Angew. Chem. Int. Ed. 2007, 46,

9 Angew. Chem. Int. Ed. 2007, 46, Asymmetric Sommelet-Hauser Rearrangement of N-Benzylic Ammonium Salts Eiji Tayama*, and Hiroshi Kimura C-N into new C-C Competion usually observed between Stevens & Sommelet-Hauser (SH) rearrangements So far, limited asymmetric SH rearrangement Eiji Tayama*, Shintaro Nanbara and Takeshi Nakai, Chem. Lett. 2006, 35,

10 Asymmetric SH rearrangement Para Ortho Meta R1T(°C)t(h)yielddr S/R COOtBu-40495>98:2 COOMe-60885>98:2 COPh-60882>98:2 CN :3 CF >98:2 H >98:2 OMe Good yields, good d.r EW groups accelerate the reaction Angew. Chem. Int. Ed. 2007, 46,

11 Mechanism Concerted stereoselective [2,3] S-H Rearrangement Ortho Meta Angew. Chem. Int. Ed. 2007, 46,

12 Wide variety of bioactive natural products with indoles framework Numerous methods to synthetize indoles Angew. Chem. Int. Ed. 2008, 47, One-Pot Multicomponent Synthesis of Indoles from 2-Iodobenzoic Acid Olivier Leogane and Hélène Lebel Curtius rearrangement / palladium-catalysed indolization

13 Study of the reaction Palladium-catalysed indolization (1) Without LiCl no reaction With excess of LiCl, low yield One-Pot Curtius rearrangement (2) / Palladium-catalysed indolization EntryLiClBase (eq.)Alkyne (eq.)Yield (%) 1yesK 2 CO 3 (5) noNa 2 CO 3 (1.5) noK 2 CO 3 (1.5) noCs 2 CO 3 (1.5) noNa 2 CO 3 (3) noK 2 CO 3 (3)3.073 NaCl formed during the Curtius rearrangement Synergic effect Angew. Chem. Int. Ed. 2008, 47, (1) Chris H. Senanayake Org. Lett. 2006, 8, (2) Hélène Lebel and Olivier Leogane, Org. Lett. 2006, 8,

14 Scope of the reaction Entry Coupling agent ProductYields (%) Unsymmetrical alkynes  Good yields and regiocontrol Moderate yields with aldehydes and ketones Angew. Chem. Int. Ed. 2008, 47,

15 Scope of the reaction Synthesis of indole N-carboxamide derivatives 64% 54% 59% 68% 62%39% Angew. Chem. Int. Ed. 2008, 47,

16 Diaryl ether widely present in bioactive compounds Synthesized using transition-metal-catalyzed cross-coupling reactions (Co, Pd…) Fe Chemistry: challenging, less expensive, less poluting, attractive industrial prospects Angew. Chem. Int. Ed. 2008, 47, Iron-Catalysed C-O Cross-Coupling of Phenols with Aryl Iodide Olivia Bistri, Arkaitz Correa and Carsten Bolm* Arkaitz Correa and Carsten Bolm*, Angew. Chem. Int. Ed. 2007, 46,

17 Study of the reaction [Fe]: FeCl 3, FeCl 3.6H 2 O, Fe(acac) 3 Base: K 3 PO 4, Cs 2 CO 3, NaOtBu, NaHCO 3, Na 2 CO 3, KOAc Solvent: toluene, MeCN, dioxane, DMF Ligand: Interplay between ligand, base, solvent strongly depend on the substrate Optimized conditions: FeCl 3 (10 mol%) L 3 (20 mol%) CsCO 3 (2 eq) DMF, 135°C Angew. Chem. Int. Ed. 2008, 47,

18 Scope of the reaction Excellent yields with electron-rich or electron-poor phenols Reaction fails to work when the phenol incorporates strongly electron-withdrawing groups Angew. Chem. Int. Ed. 2008, 47,

19 Scope of the reaction Angew. Chem. Int. Ed. 2008, 47,

20 Some good reading Protection-Group-Free Formal Synthesis of Platensimycin. J. Mulzer, Angew. Chem. Int. Ed. 2007, 46, Catalytic Enantioselective Passerini Three-Component reaction. MX. Wang and J. Zhu, Angew. Chem. Int. Ed. 2008, 47, Cyclic triolborates: Air and Water stable Ate complexes of Organoboronic Acids. Y. Yamamoto and N. Miyaura, Angew. Chem. Int. Ed. 2008, 47, Synthesis of  -Ketoamides by a Molecular-Sieves-Promoted Formal Oxidative Coupling of Aliphatic Aldehydes with Isocyanides. JM. Grassot, G. Masson and J. Zhu, Angew. Chem. Int. Ed. 2008, 47, A Stable, Convertible Isonitrile as a Formic Acid Carbanion Equivalent and Its Application in Multicomponent Reactions. L.A. Wessjohann, Synlett. 2007, 20, Novel Ir-SYNPHOS ® and Ir-DIFLUORPHOS ® Catalysts for Asymmetric Hydrogenation of Quinolines. JP. Genêt, K. Mashima, V. Ratovelomanana-Vidal, Synlett 2007, 17,