Chapter 18: The Chemistry of Aryl Halides, Vinylic Halides, and Phenols. Transition-Metal Catalysis

aryl halides

halogen bound to carbon of benzene ring

vinylic halides

halogen bound to carbon of double bond

Do aryl and vinyl halides participate in S_N2 reactions?

no

If the LG is attached to sp³ carbon, S_N1 and S_N2 are (possible/impossible).

possible

If the LG is attached to sp² carbon, S_N1 and S_N2 are (possible/impossible).

impossible

Why don’t vinylic halides undergo S_N2 reactions?

• nucleophile must backside attack through the plane of the alkene (geometrically impossible)

• carbon undergoing substitution rehybridizes from sp² to sp (high energy cost → slow rate)

• van der Waals repulsions

Why don’t aryl halides undergo S_N2 reactions?

• nucleophile must backside attack through the plane of the benzene (geometrically impossible)

• carbon undergoing substitution rehybridizes from sp² to sp (high energy cost → slow rate)

• van der Waals repulsions

Do vinyl halides participate in elimination reactions?

yes, but very difficult; requires harsh conditions (heat/very strong bases);

they can do base-promoted β-elimination reactions

What is the rate determining step in S_N1 and E1 mechanisms for aryl and vinylic halides?

formation of carbocation (intermediate)

Vinylic and aryl cations are considerably (more/less) stable than alkyl carbocations.

less

Why are vinylic and aryl cations considerably less stable than alkyl carbocations?

• the e- deficient carbon is sp hybridized

• the vacant 2p orbital is not conjugated w the π e- system of the double bond

Nucleophilic aromatic substitution of aryl halides typically follow ____-order kinetics.

second;

rate = k[aryl halide][nucleophile]

What are the requirements for nucleophilic aromatic substitution of aryl halides?

strongly e- withdrawing substituents, most commonly NO₂ groups at ortho and para positions, to stabilize the anionic intermediate

More nitro groups at ortho and para positions → (more/less) reactivity

more

draw the mechanism for nucleophilic aromatic substitution of aryl halides

What is the reactivity trend for nucleophilic aromatic substitution of aryl halides?

fluorine is highly EN and exerts a very strong inductive e- withdrawing effect;

more susceptible for nucleophilic attack;

strongly stabilizes the negatively charged Meisenheimer intermediate

What is the substrate for S_NAr?

aromatic

What is the substrate for S_N1?

alkyl, benzyl, or allyl

What is the substrate for S_N2?

alkyl, benzyl, or allyl

What is the mechanism for S_NAr called?

addition-elimination

What is the substrate for S_N1 called?

carbocation

What is the substrate for S_N2 called?

backside attack

Does S_NAr need an e- withdrawing group?

yes (usually)

Does S_N1 need an e- withdrawing group?

no

Does S_N2 need an e- withdrawing group?

no

What is the S_NAr intermediate?

Meisenheimer complex

What is the S_N1 intermediate?

carbocation

What is the S_N2 intermediate?

none

Which orbitals do transition metals fill?

n s orbital and (n - 1) d orbital;

since they have similar energies, you can think of these two together as valence e-

ex: Ni → [Ar]4s²3d⁸ = a 10-electron valence atom

What are groups surrounding transition metals called?

ligands

All ligands are Lewis ____.

bases

Metal-ligand compounds are called…

coordination compounds or transition-metal complexes

What are the four steps to evaluate transition metal complexes?

1. classify ligands

2. specify formal charge

3. calculate the oxidation state

4. count electrons around the metal

Neutral 2-electron donor → L- or X-type ligand?

L

Donates a lone pair to the metal → L- or X-type ligand?

L

Remains neutral before and after coordination → L- or X-type ligand?

L

Bonding electrons belong completely to the ligand → L- or X-type ligand?

L

When dissociated from the metal with their electrons, this ligand is neutral → L- or X-type ligand?

L

Anionic 1-electron donor → L- or X-type ligand?

X

Carries a negative charge in the ionic description → L- or X-type ligand?

X

Contributes one electron to the covalent bond from the ligand and one from the metal → L- or X-type ligand?

X

One electron belongs to the metal and one to the ligand → L- or X-type ligand?

X

When dissociated from the metal, it takes the electrons on the bond and gets a negative charge → L- or X-type ligand?

X

Can ligands operate as both L- and X-type ligands?

yes, π electrons can coordinate to metals;

ex: cyclopentadienyl anion has one X-type bond and two L-type bonds

NH₃ → L- or X-type ligand?

L

H₂O → L- or X-type ligand?

L

R₃P → L- or X-type ligand?
R = alkyl, allyl

L

C=O → L- or X-type ligand?

L

CH₂=CH₂ → L- or X-type ligand?

L

N≡CCH₃ → L- or X-type ligand?

L

benzene → L- or X-type ligand?

L₃

halogens (F, Cl, Br, I) → L- or X-type ligand?

X

H^- → L- or X-type ligand?

X

acetate → L- or X-type ligand?

X

alkyl → L- or X-type ligand?
ex: CH₃

X

C≡N → L- or X-type ligand?

X

CH₂=CH—CH₂ (allyl) → L- or X-type ligand?

LX

cyclopentadienyl → L- or X-type ligand?

L₂X

oxidation state of M =

(number of X-type ligands) + overall charge

draw the mechanism for ligand dissociation-association

draw the mechanism for ligand substitution (analogous to S_N1 or S_N2)

draw the mechanism for oxidative addition

draw the mechanism for reductive elimination

draw the mechanism for ligand insertion (syn-addition across the double bond)

draw the mechanism for β-elimination

What is required for β-elimination?

an empty orbital on the metal

β-elimination is a __-elimination.

syn

Does β-elimination change oxidation states?

no

Heck reaction

palladium-catalyzed [ Pd(0) ], C—C bond-forming reaction between an aryl or vinyl halide and an alkene, producing a substituted alkene

In the Heck reaction, what can occur after syn insertion across a noncyclic alkene?

internal rotation

Can cyclic alkenes internally rotate?

no, prevented by the ring

What is the Suzuki coupling?

coupling of an aryl or vinyl boronic acid with an aryl or vinyl group

What is the Suzuki coupling catalyzed by?

Pd(0)

What is necessary for the Suzuki coupling?

base (typically NaOH or Na₂CO₃)

Does the orientation change with the Suzuki coupling?

no, orientation is unchanged

syn

What are two ways to produce boronic acids?

1. Grignard/organolithium reagent

2. hydroboration

draw the mechanism for making boronic acid using a Grignard reagent

draw the mechanism for making boronic acid using hydroboration

draw a reaction to illustrate the use of a vinylic catechol borane coupling with a vinyl halide to form a conjugated diene

What are the 6 methods used to form C—C bonds?

1. addition of carbenes and carbenoids to alkenes

2. reaction of Grignard reagents with ethylene oxide and lithium organocuprate reagents

3. reaction of acetylenic anions with alkyl halides or sulfonates

4. Diels-Alder reaction

5. Friedel-Crafts alkylation and acylation reactions

6. Heck and Suzuki coupling reactions

phenol

a hydroxy group is bound to an aromatic ring

Like alcohols, phenols can…

ionize

Phenols are (more/less) acidic than regular alcohols.

more

Why are phenols more acidic than regular alcohols?

the conjugate base is stabilized by resonance