Organic Chemistry Notes: Addition Reactions & Alkynes

Dissolving Metal Reductions: Hydrogenation of Alkynes

• In dissolving metal reduction involving $NH_3(l)/Na(s)$, the active radical species is an electron that doesn't formally belong to any atom.

Anti-Hydrogenation: Synthesis of Trans Alkenes

• Dissolving metal reduction of an alkyne is highly regioselective.
• It almost exclusively produces the E alkene.

Anti-Hydrogenation Mechanism

• Mechanism for the dissolving metal reduction of an alkyne:
  1. Radical addition: Solvated electron adds to the alkyne.
  2. Proton transfer: Formation of a radical.
  3. Radical coupling.
  4. Proton transfer.
• The trans radical is more stable than the cis radical.

Stereoselectivity of Anti-Hydrogenation

• Steric strain makes the cis configuration less stable.

Selectivity of the Dissolving Metal Reduction

• A dissolving metal reduction will selectively reduce an alkyne over an alkene.

Radical Reactions and Stereochemistry

• Using $Na(s)/NH_3(l)$, -78 °C, a trans alkene is formed.
• Using Lindlar's catalyst and $H_2$, a cis alkene is formed.

Radical Addition of HBr: Anti-Markovnikov Addition

• Markovnikov addition of HBr:
  • Reactants: Propene, HBr, no peroxides.
  • Product: 2-Bromopropane.
• Anti-Markovnikov addition of HBr:
  • Reactants: Propene, HBr, Peroxide.
  • Product: 1-Bromopropane.

Mechanism for Anti-Markovnikov Addition of HBr to an Alkene

• Steps:
  1. Homolysis: $RO-OR → 2RO•$
  2. SH2: $RO• + H-Br → RO-H + Br•$
  3. Radical addition: $Br•$ adds to the alkene.
  4. SH2: Radical abstracts a hydrogen from H-Br.
• Propagation steps continue until termination.

Schematic Representation of the Mechanism for the Radical Addition of HBr

• Initiation: $RO-OR → RO•$
• Propagation: A cycle involving $Br•$ and alkene, leading to product formation.
• Termination: Radicals combine to stop the chain reaction.

Regiochemistry in the Radical Addition of HBr

• Radical addition to an alkene generally takes place to produce the more stable alkyl radical intermediate.

Relative Stability of Alkyl Radicals

• Stability increases as follows: Methyl radical < 1° radical < 2° radical < 3° radical.
• Radicals are electron-poor.
• Alkyl groups donate electron density to the carbon radical, stabilizing it.

Resonance Stability in Allyl & Benzyl Cations

• Allyl cation and benzyl cation stability is explained through resonance structures.
• The positive charge is delocalized over multiple carbon atoms.

Resonance Stability in Allyl & Benzyl Radicals

• The unpaired electron is shared over multiple carbon atoms, leading to increased stability.

Structure of Alkyl Radicals

• $H<em>3C•$ and $H</em>3C^+$ are both planar, so each one's C atom is $sp^2$-hybridized, possessing a single unhybridized p orbital.
• The unhybridized p orbital in $H_3C•$ contains the unpaired electron.
• The unhybridized p orbital in $H_2C^+$ is empty.

Summary of Alkene Addition Chemistry

• Summary Table:
  • Bromine addition ($X_2$): anti-addition
  • Bromohydrins and epoxides: formed with $X<em>2, H</em>2O$
  • Hydration: requires $i) Hg(OAc)<em>2, H</em>2O; ii) NaBH_4$
  • Hydrogenation: requires $H_2, Pd/C (10$
  • Radical addition: requires $HBr, ROOR$

Carbanions

• A carbon atom is nucleophilic when it bears a formal negative charge, and it is a carbanion.
• Carbanions possess a lone pair of electrons that can be used to form a bond.

Forming Carbanions through Deprotonation

• The simplest way to generate carbon nucleophiles is to deprotonate the uncharged carbon.
• Alkanes have $pK_a$ values around 50, so they are such weak acids that deprotonation is unfeasible.
• But the $pK<em>a$ values of alkynes are much lower than those of corresponding alkanes ($pK</em>a ≈ 25$).

Alkynide Anion

• $pK_a$ values: Alkane (50) > Alkene (44) > Terminal Alkyne (25).
• Hybridization: $sp^3$ (25% s character) for alkanes, $sp^2$ (33% s character) for alkenes, $sp$ (50% s character) for alkynes.
• Terminal alkynes are easier to deprotonate (have a lower $pK_a$) than alkenes or alkanes.
• Acidity is related to the stability of the anion (conjugate base) formed upon deprotonation. Increasing anion stability facilitates deprotonation.

Alkylation of a Terminal Alkyne

• Mechanism for the alkylation of a terminal alkyne:
  1. Proton transfer: Formation of alkynide anion.
  2. $S<em>N2$: Alkylation of the alkynide anion with an alkyl halide ($CH</em>3I$).
• Example: Formation of 2-Methyloct-2-en-6-yne from 6-Methylhept-5-en-1-yne using $NaH$ and $H_3C-I$.