344 Organic Chemistry Laboratory Introduction to organometallic chemistry Portraits: http://scientistic.tumblr.com
Periodic Table Main group Alkali metals p electrons Electronegativity s electrons Transition metals d electrons
What is organometallic chemistry? Organic Organometallic Inorganic Chemistry Chemistry Chemistry C-M bonds “Carbon” “Metals” Organometallic chemistry = Study of compounds containing a Carbon-Metal bond Organometallic chemistry = Organic synthesis using metals
Organometallics – s-block compounds Organomagnesium halides (Grignard reagents) Organolithiums Lithium diorganocuprates (Gilman reagents) Loudon p. 429-432
Formation of Grignard reagents radical anion Why use diethyl ether as the solvent? Loudon p. 429-432
Charge distribution – Chlorobenzene A typical organic compound = positively charged = negatively charged -0.22 C -0.30 C d + d - C C Cl -0.25 +0.42 -0.34 X H = 2.20 C C -0.30 X C = 2.55 -0.21 X Cl = 3.16 NPA charges, B3LYP/6-31G(d) X = Pauling electronegativity
Charge distribution – Phenyl lithium An organometallic compound = positively charged = negatively charged -0.25 C C -0.27 d + d - -0.25 C C Li -0.81 +0.61 X H = 2.20 C C -0.27 X C = 2.55 -0.25 X Li = 0.98 X Mg = 1.31 NPA charges, B3LYP/6-31G(d) X = Pauling electronegativity
Carbon-Metal bond polarity drives reactivity % ionic Δ Electronegativity # C-M bond character* C-K 2.55 – 0.82 = 1.73 68 Ionic C-Na 2.55 – 0.93 = 1.62 63 R C-Li 2.55 – 0.98 = 1.57 61 E C-Mg 2.55 – 1.31 = 1.24 48 A Polar C covalent C-Ti 2.55 – 1.54 = 1.01 40 T C-Al 2.55 – 1.61 = 0.94 37 I C-Cu 2.55 – 1.90 = 0.65 25 V I C-O 2.55 – 3.44 = -0.89 35 Covalent T C-Cl 2.55 – 3.16 = -0.61 24 Y C-Br 2.55 – 2.96 = -0.41 16 C-H 2.55 – 2.20 = 0.35 14 * % ionic character = [( Χ C – Χ M ) ÷ Χ C ] # Pauling electronegativity, Χ
Reactivity of Grignard reagents d + d - carbanion ~50 % ionic character conjugate acid pKa = 43 d + d - protonolysis pKa 15.7 d + d - protonolysis Loudon p. 429-432
Reactivity of Grignard reagents C-atom bonded to metal in RMgX has carbanion character, reacts as a nucleophile The C-atom in a “typical” organic compound is electrophilic (C=O, C-O, C-N, C-Cl) d + d - d - d + 3 o alcohol new C-C bond Loudon p. 976-978
Reactivity of Grignard reagents +1.25 -0.60 -0.62 Mg C X O O C -0.51 +1.02 C-atom of PhMgBr is nucleophilic C-atom of CO 2 is electrophilic LUMO of CO 2 NPA/NBO calculation, B3LYP/6-31G(d) Loudon p. 1018
Metal exchange and coupling reactions Metal exchange (transmetallation) between RLi and CuX to form lithium diorganocuprate Lithium diorganocuprates are useful for C-C bond forming reactions Good : Not so good : Ideal:
Palladium: One metal, many reactions Suzuki-Miyaura Pd-catalyzed C-C bond Mizoroki-Heck formation Negishi 2010 Nobel Prize in Chemistry
Catalysis Many reactions are favorable thermodynamically but proceed slowly at room temp/pressure A + B C Energy A + B D G (rxn) C Reaction progress Loudon p. 170
Understanding the catalytic cycle A + B C Precatalyst Catalyst Product C Substrate A Intermediate 2 Intermediate 1 Substrate B Byproduct Z
Understanding the catalytic cycle A + B C Pd(PPh 3 ) 4 -2 PPh 3 Pd(PPh 3 ) 2 intermediate 2 intermediate 1 3 key steps a) Oxidative addition b) Transmetallation c) Reductive elimination byproduct Z
Kumada coupling – the catalytic cycle Pd(PPh 3 ) 4 Pd(PPh 3 ) 4 -2 PPh 3 Pd(PPh 3 ) 2 intermediate 2 intermediate 1 3 key steps a) Oxidative addition b) Transmetallation c) Reductive elimination byproduct Z
Ligands Ligands are molecules bonded to a transition metal via donor atoms such as P , N , C , etc. Ligands act as Lewis bases (i.e. electron donors) toward the transition metal Triphenyl phosphine (PPh 3 ) N -heterocyclic carbene (NHC) 2,2’ -Bipyridine (bpy) Loudon p. 888-893
Metal-ligand compounds are called coordination complexes - serve as precatalysts Pd(PPh 3 ) 4 T etrakis(triphenylphosphine)palladium Loudon p. 888-893 http://en.wikipedia.org/wiki/Tetrakis(triphenylphosphine)palladium(0)
Kumada coupling – the catalytic cycle Pd(PPh 3 ) 4 Pd(PPh 3 ) 4 -2 PPh 3 Pd(PPh 3 ) 2 oxidative reductive addition elimination intermediate 2 intermediate 1 3 key steps a) Oxidative addition b) Transmetallation transmetallation c) Reductive elimination byproduct Z
Key steps of the cycle – oxidative addition Pd(PPh 3 ) 4 First step of typical C-C coupling catalytic cycle Addition of organic substrate ( Ph-Br ) to Pd(PPh 3 ) 2 species Substrate can be aryl, alkenyl , or alkynyl halide oxidative addition Pd(0) Number of bonds to Pd increases by 2 Pd oxidation state increases by 2 (Pd 0 to Pd II ) Loudon p. 896-898, 904-907
Kumada coupling – the catalytic cycle Pd(PPh 3 ) 4 Pd(PPh 3 ) 4 -2 PPh 3 Pd(PPh 3 ) 2 oxidative reductive addition elimination intermediate 2 intermediate 1 3 key steps a) Oxidative addition b) Transmetallation transmetallation c) Reductive elimination byproduct Z
Key steps of the cycle – transmetallation Pd(PPh 3 ) 4 Middle step of typical C-C coupling catalytic cycle Exchange reaction between Ar-MgBr and oxidative addition product R = aryl, alkenyl, alkynyl group M = B (Suzuki), Sn (Stille), Zn (Negishi), etc. transmetallation Pd(II) Organic group Ar replaces Br on Pd atom Pd oxidation state and coordination number unchanged Drive toward less polar C-M bond in transmetallation product
Kumada coupling – the catalytic cycle Pd(PPh 3 ) 4 Pd(PPh 3 ) 4 -2 PPh 3 Pd(PPh 3 ) 2 oxidative reductive addition elimination intermediate 2 intermediate 1 3 key steps a) Oxidative addition b) Transmetallation transmetallation c) Reductive elimination byproduct Z
Key steps of the cycle – reductive elimination Pd(PPh 3 ) 4 Final step of typical C-C coupling catalytic cycle Elimination of product ( Ph-Ar ) from transmetallation product reductive elimination Pd(II) Coupling product Ph-Ar released, active catalyst Pd(PPh 3 ) 2 reformed Pd oxidation state and coordination number decrease by 2 Loudon p. 896-898, 904-907
Summary Organometallic chemistry - the chemistry of compounds containing a C-M bond Grignard and organolithium reagents - polar C-M bond, carbanion character, strong bases, carbon nucleophiles, C-C bond forming - used in stoichiometric (1:1 or greater) amounts Pd-catalyzed coupling reactions - a catalyst provides alternate, lower D G ‡ route to a product - a catalyst is not consumed but can participate in many turnovers - ligands coordinate to transition metal to form pre-catalyst complex - metal-ligand complexes serve as catalysts for organic reactions - bond forming/breaking takes place on metal atom - catalytic coupling cycle: oxidative addition, transmetallation, reductive elimination - Pd-catalyzed C-C bond forming reactions are hugely important in pharma and industry - Practice problem set!
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