Chapter 5 Reactions of Alkynes.  Introduction to Multistep Synthesis

Alkynes play a very important role in designing a multistep synthesis.  First we learn about alkynes and their reactions, then we learn how to design a synthesis.

I.  Alkynes.
    A.  Nomenclature:  terminal and internal
        1.  Common Names
            a.  acetylene:  2 carbons and a triple bond
            b.  substituted acetylenes
            c.  propargyl group
        2.  IUPAC
            a.  "yne"
            b.  substituents lowest number, listed alphabetically
    B.  Physical properties of unsaturated hydrocarbons
        1.  Similar to alkanes, alkenes, and alkynes
        2.  Alkynes more linear and more polarizable, thus higher Van der Waals forces
            a.  internal alkynes have higher BP than terminal
        3.  sp hybridized, linear
        4.  total bond energy = 200 kcal/mol, sigma bond = 91 kcal/mol, pi bonds about 55 kcal/mol each

II.  Reaction Consideration
    A.  Compared to Alkene
        1.  alkynes and alkenes are both nucleophiles
        2.  electrophilic addition to terminal alkynes, like alkenes, are regioselective.
        3.  alkynes are less reactive than alkenes
            a.  alkynes are less stable than alkenes
            b.  transition state for the first step in the reaction with an alkyne is less stable.
            c.  (Energy of activation) change of G alkyne > change of G alkene
        4.  Relative stability of carbocations:  tertiary > secondary > secondary vinylic ~ primary > primary vinylic > methyl
    B.  Addition of Hydrogen Halides
        1.  to a terminal alkyne occurs via Markovnikov's rule, because a secondary vinylic cation is more reactive than a primary vinylic cation.
        2.  two equivalents of HX results in a geminal dihalide
        3.  second addition also occurs via Markovnikov's rule, because the halogen can share the positive charge.
        4.  alkyne is less reactive than an alkene, but an alkyne is more reactive than a halo-substituted alkene, because of the electron-withdrawing effects of the halogen.
        5.  HBr in the presence of peroxide results in anti-Markovnikov addition.
    C.  Addition of Cl2 and Br2
        1.  one equivalent results in disubstituted alkene
        2.  two equivalents results in tetrasubstituted alkane
    D.  Addition of Water.
        1.  Acid catalyzed addition to an internal alkyne results in an enol that rearranges to a ketone. (tautomer)
        2.  Terminal alkynes
            a.  Acid catalyzed with Hg+2 results in a methyl ketone
            b.  Hydroboration-oxidation results in an aldehyde
    E.  Addition of H2 (hydrogen gas)
        1.  H2 and metal catalyst results in alkane
        2.  Lindlar's catalyst results in cis-alkene
        3.  Na or Li in liquid ammonia results in trans
    F.  Acidity of a terminal alkyne
        1.  The elctronegativity of carbon atoms follows the order sp > sp2 > sp3, therefore the acidity of a terminal alkyne > alkene > alkane.
        2.  relative acidities:  alkane, pKa = 50 < alkenes, pKa = 44 < ammonia, pKa = 36 < alkynes, pKa = 25 < water, pKa = 15.7 < HF, pKa = 3.2
        3.  relative basicity:  acetylide anion < amide anion
    G.  Synthesis using acetylide ions.
        1.  Alkylation reaction:  carbon-carbon bond formation.
            a.  begin with a terminal alkyne
            b.  acid/base reaction with an amide ion
            c.  add acetylide ion to a primary or methyl halide

III.  Designing a Synthesis:  Retrosynthetic Reaction.