I. Organometallic Reagents = carbon-metal bonds Nucleophilic Carbon OH- contains a nucleophilic oxygen that can give a new C—O bond Formation of new C—C bonds is the key requirement in organic synthesis Alkylmetal Reagents Haloalkanes can be transformed into organometallic compounds Alkyllithium Synthesis (I > Br > Cl reactivity) Alkylmagnesium Synthesis (Grignard Reagent)

Alkylmetals are very basic, very strong Nucleophiles pKa of CH3—H bond is about 50 Alkylmetal reagent is the conjugate base of a very weak acid H3C:- Use them as soon as you make them (…made in situ…) Air and water sensitive, must do reaction under N2 or Ar True structure involves coordinated solvent—require ether or THF Very polar bond, metal is electropositive Opposite of usual situation for carbon, as in Haloalkanes Treat the molecule like R- = Carbanion Resonance forms Hydrolysis :

C. Alkylmetal reagents in Alcohol Synthesis Goal: Formation of new C—C bonds by using C Nucleophile Nucleophilic attack of Haloalkane by alkylmetal reagent is unsuccessul Elimination Reactions give side products because of extreme basicity We will need a more successful carbon electrophile

5) Carbonyl electrophiles (Cd+==Od-) react more cleanly with alkylmetals Ketones give tertiary alcohol products Aldehydes give secondary alcohol products Formaldehyde (CH2O) gives primary alcohol product -

II. Oxidation of Alcohols to Carbonyls Reduction reactions can be reversed to give the aldehydes or ketones Oxidizing Reagent is Cr(VI) (Na2Cr2O7 or K2Cr2O7 or CrO3) and H2SO4 and H2O Primary alcohols can be overoxidized to carboxylic acids

Do Primary alcohol oxidation without water PCC = pyridinium chlorochromate = Anhydrous conditions and PCC don’t overoxidize primary alcohol 4) Mechanism involves Chromic Ester

III. Synthesis of Complex Alcohols Using Alkylmetal Reagents A. Useful Reaction Sequence B. Retrosynthetic Analysis = Work Backwards from Target Complex molecules are made from simple parts Look for C—C bonds to break (form)