Presentation on theme: "Carbon Nucleophiles : Organometallics of Li, Mg etc. 1. Cyanide :Well known 1 carbon unit 2. Acetylides :pKa = 25 Requires polar solvent to solubilize."— Presentation transcript:
Carbon Nucleophiles : Organometallics of Li, Mg etc. 1. Cyanide :Well known 1 carbon unit 2. Acetylides :pKa = 25 Requires polar solvent to solubilize CN - LiCN – THF NaCN – DMSO KCN – need 18-C-6
3. Grignard Reagent : R-MgX a. preparation Additives : mechanical force, I 2, MeI, BrCH 2 CH 2 Br to activate the surface of heterogeneous reaction. Reactive Mg ( Rieke Mg) : prepared from MgX 2 + K --- black Mg powder Reactivity of Halides : RI > RBr > RCl radical intermediates through electron transfer Loses stereochemistry !! b. structure Solvent dependent, sometimes temp. dependent
3. Grignard Reagent : R-MgX c. reaction Usually not so good reaction except for MeI or BnI With CuI or LiCuCl 4 cat. Reaction works Self condensation is called Wurtz coupling – problem during Grignard formation
3. Grignard Reagent : R-MgX c. reaction Reduction of ketones Very low e.e.
4. Alkyl lithium a. generation Usually contains Na(0.02%) Accelerates reaction Cl : ppt. Br : soluble I : cannot form Except MeI, ArI ii) Metal-Halogen exchange rxn.Sometimes faster than acid-base reaction
4. Alkyl lithium a. generation iii) Transmetallation – gives clean generation Too reactive to form by other ways Too slow to form by other ways iv) Metal-Hydrogen Exchange
a. generation iv) Metal-Hydrogen Exchange – directed metallation O- inductive effect through chelation
b. structure Tetramer in Solid state In solution : monomer to hexamer depending on solvents, salts, additives Reactivity : less aggregate, more reactive c. reactions Similar reactivity to Grignard for RX, carbonyls, nitriles Often times act as base rather than nucleophile Unusual reaction JACS 1989, 111, 765 Cf.
c. reactions Quenching excess R’Li is important ! via Weinreb amide
Asymmetric synthesis Felkin-Anh Model : Chem. Rev (’99) Chelation control