Syn addition reactions – typically go through 3-, 4-, or 5-membered cyclic intermediates.
Small rings cannot form simultaneously on both top and bottom so either only top or only
bottom. SYN.
1. Cyclopropanation Reactions
+
Carbenes
a. CH2N2
:CR2
Neutral, Only 6 e- (e- poor, no octet)
Sp2 hybridized, empty p orbital
Both a Lewis Acid and a Lewis Base
Diazomethane “:CH2”
CH2N2
b. CHCl3, KOH – Forms a dichlorocarbene “:CCl2”
Cl
CHCl3, KOH
Cl
CHCl3
KOH
c. Carbenoid Reaction: Simmons-Smith Reaction (“:CR2”)
CH2I2, Zn(Cu)
H
H
CH(CH2CH3)I2
Zn(Cu)
2. Epoxide Formation
mCPBA
O
+
O
mCPBA = meta-chloroperbenzoic acid
O
Cl
O
OH
mCPBA is an electrophilic oxidizing agent and reacts with the most electron-rich alkene
present first.
mCPBA
1 equiv.
mCPBA
3. Hydrogenations – Addition of H, H – SYN Addition
H2
H
H
+
Pd/C or PtO2
H
H
H2, Pd/C
This reaction, like the other alkene reactions, does not affect aromatic rings. Which
are aromatic rings?
4. Dihydroxylation – SYN Addition of OH, OH (1,2 diol)
OH
OH
+
OH
OH
Reagents: (interchangeable)
KMnO4, NaOH, H2O
OR
1. OsO4
2. NaHSO3, H2O
2
KMnO4, NaOH,
H2O
1. OsO4
2. NaHSO3, H2O
5. Hydroboration-Oxidation – SYN Addition of H, OH “Non-Markovnikov”
1. BH3
H
2. NaOH, H2O2
OH
1. BH3
2. NaOH, H2O2
BH3 – Borane – 6 electrons on B (Group III element)
• Hybridization? Sp2
• Empty perpendicular p orbital – Lewis Acid and Electrophile
Step 1 determines Regiochemistry and Stereochemistry – Concerted, 4-membered cyclic
transition state (no intermediate formation – no chance for the molecule to rotate!)
H BH2
H
BH2
H BH2
Why “Syn”?
four-membered, cyclic transition state
Why “Non-Markovnikov”?
H-B bond can line up in 2 possible ways with the alkene pi bond:
3
H
H
CH3
H
CH3
H
CH3
H2B H
CH3
H BH2
The favored transition state occurs for two reasons:
1. Sterics: More unstable steric interactions occur when B is located under alkyl group
on more substituted side.
2. Electronics: as the e- density shifts from alkene towards B of BH3, a δ+ charge
develops. The more highly substituted partial charge is more stable, forms faster.
6. Acid-Catalyzed Hydration – Addition of H, OH
Markovnikov
OH
H2O, H2SO4
H
H2O, H2SO4
or
H2O, H+
or
H3O+
Mechanism:
H
H
H2O
H
H
O
H
H2O
H
O
H
7. Oxymercuration-Demercuration – Addn of H, OH Markovnikov
4
OH
1. Hg(OAc)2, H2O
H
2. NaBH4
1. Hg(OAc)2, H2O
2. NaBH4
The second step is the conversion of mercury to a hydrogen atom (referred to as a
reduction reaction or “demercuration”, and whose mechanism will not be discussed).
The regiochemistry of this reaction is determined in the first step. Why “Markovnikov”?
Like in the halonium ion, one C-Hg bond is weaker and easier to break. Whichever end is
more substituted will result in a δ+ charge that is more stable and faster to form and
react.
AcO
Hg
H
CH3
8. Oxidative Cleavage of Alkenes – requires the breaking of both the pi AND sigma
bonds of alkenes, thus fracturing the carbon skeleton into pieces.
R1
R3
R1
R2
R4
R2
+
O
O
R3
R4
a. Ozonolysis – forms aldehydes and/or ketones
Reagent:
1. O3
2. Zn, H3O+
1. O3
2.Zn, H3O+
H
H
1. O3
2.Zn, H3O+
O
O
5
1. O3
2.Zn, H3O+
b. KMnO4, H2O or H3O+
• Conversion of alkenes to ketones/carboxylic acids/H2CO3
R1
R3
R1
R2
H
R2
O
+
O
O
R3
H
R3
OH
KMnO4, H2O or H3O+
Synthesis: The combination of a series of steps to build a bigger molecule or to
construct new functional groups
Br
OH
Br
Br
OH
Mechanisms:
Halogenation
Halohydrin formation
Addition of HX
Acid-Catalyzed Hydration
Dehydration
6