Light and Palladium Induced Carbonylation Reactions of Alkyl Iodides Mechanism and Development Pusheng Wang Gong Group Meeting April 12 th 2014

 Traditional Concept for Transition Metal Catalyzed Carbonylation of Alkyl Halides PART 1. Background 2

 Progress has been made in efficient transition metal catalyzed cross-coupling reactions of alkyl halides PART 1. Background 3 Fu’s Pd catalysts with electron-rich and bulky trialkylphosphine ligands Ni catalysts with bidentate nitrogen ligands Organ’s Pd catalysts with bulky NHC ligands Kambe’s Grignard type coupling catalyzed by transition metals, such as Ni, Pd, Cu, and Co with π-carbon ligands Oshima’s Co catalysts with bidentate phosphine ligands Top. Organomet. Chem. 2005, 14, 85. J. Am. Chem. Soc. 2012, 134, J. Am. Chem. Soc. 2013, 135, 624. J. Am. Chem. Soc. 2013, 135, Chem. Eur. J. 2010, 16, Acc. Chem. Res. 2008, 41, Pure Appl. Chem. 2006, 78,  Key Point: Suitable ligand and Metal for a stable RMX intermediate.

 The most successful example of industrial carbonylation processes with alkyl halides  Isomerization of alkyl-M intermediates via β-hydride elimination limite the extension of this methord to the synthesis of C4 and higher acid. PART 1. Background 4 M = Rh, The Monsanto process M = Ir, The Cativa process

 Conceptually Different Way - Alkyl Radicals Approach with Palladium (Atom Transfer Carbonylation, ATC)  Key Point: Alkyl radicals are more stable than the corresponding alkyl metal species.  For primary alkyl iodides, it is important to be able to accelerate the reaction. PART 1. Background 5 Ryu, I. Chem. Rev. 1996, 96, 177. Ryu, I. Chem. Rev. 1999, 99, Ryu, I. Chem. Soc. Rev. 2001, 30, 16 Ryu, I. Acc. Chem. Res. ASAP

 First founding: Acceleration of Photoinduced ATC Reaction of 1-Iodooctane by Pd Catalysts PART 2. Background 6 Watanabe, Y. Tetrahedron Lett. 1988, 29, Watanabe, Y. J. Organomet. Chem. 1994, 473, 163. Suzuki, A. Tetrahedron Lett. 1991, 32, Suzuki, A. J. Chem. Soc., Chem. Commun. 1995, 295.

 Mechanism? Comparison of Diastereomeric Isomer Ratios for Atom Transfer PART 2. Development 7

 Mechanism? Comparison of Diastereomeric Isomer Ratios for Atom Transfer PART 2. Development 8

 Mechanism? Pd(I) species PART 2. Development 9 Kubiak, C. P. J. Am. Chem. Soc. 1985, 107, 3517.

 General Principle for R ∙ PART 2. Development 10

PART 2. Development 11 RICONuH RCONu  Three-Component Coupling Reaction

 Pd/light Accelerated Carbonylation of Alkyl Iodides Leading to Esters PART 2. Development 12 Ryu, I. Org. Lett. 2006, 8, Ryu, I. Chem. Eur. J. 2012, 18, 9415.

 Pd/light Accelerated Carbonylation of Alkyl Iodides Leading to Amides Double Carbonylation PART 2. Development 13 Ryu, I. Chem. Commun. 1998, Yamamoto, A. Bull. Chem. Soc. Jpn. 1995, 68, 433. Yamamoto, A. Organometallics 1998, 17, Yamamoto, A. J. Chem. Soc., Dalton Trans. 1999, 1027.

 Synthesis of Alkyl Alkynyl Ketones by Three-Component Coupling Reaction PART 2. Development 14 Ryu, I. Org. Lett. 2010, 12, 2410.

 Synthesis of Alkyl Aryl Ketones by Three-Component Coupling Reaction PART 2. Development 15 Ryu, I. Org. Lett. 2013, 15, 3142.

 Synthesis of Carbamoyl Acetates by Three-Component Coupling Reactions PART 2. Development 16 Ryu, I. Synlett 2012, 23, 1331.

PART 2. Development 17 RICONuH  Three-Component Coupling Reaction

 Synthesis of Functionalized Esters by Four-Component Coupling Reaction PART 2. Development 18 Ryu, I. Chem. Eur. J. 2012, 18, Ryu, I. Org. Lett. 2011, 13, 2114.

 Synthesis of Lactones by Three-Component Coupling Reactions PART 2. Development 19 Ryu, I. Chem. Eur. J. 2012, 18, Ryu, I. Org. Lett. 2011, 13, 2114.

 Two Reaction Courses in Three-Component Reaction of α-Iodo Acetate, 4- Pentenylamine, and CO PART 2. Development 20

 Cyclizative Double and Triple Carbonylation Reactions PART 2. Development 21 Ryu, I. J. Am. Chem. Soc. 2002, 124, 3812.

 Proposed Reaction Mechanism of Cyclizative Double Carbonylation PART 2. Development 22

 Cyclizative Double Carbonylation Reactions PART 2. Development 23

 Heck Type Carbonylation Reaction by Pd/photoirradiation System PART 2. Development 24

 Light induced radical chemistry and Palladium Chemistry Combination PART 2. Conclusion 25

 Light induced radical chemistry and Palladium Chemistry Combination PART 2. Conclusion 26