Download Reaction of Alkenes

Review from 1st Year Organic Chemistry:
g
y
Synthesis & Reactions of Alkenes
Di
Discussed briefly in class: Chapter 8 (except 8.9‐
d b i fl i l
Ch t 8 (
t 8 9 8.11)
8 11)
Material that should be reviewed independently: Chapter 7
1
Chemistry Connections
Terpenes in Natural Product Synthesis
• Terpenes represent the largest class of secondary metabolites that are made up of linked isoprene units, t b lit th t
d
f li k d i
it
leading to an extensive array of complex molecular structures with a broad range of biological properties. Terpenes as Anti‐HIV Drugs
• HIV is a global epidemic with over 35 million people carrying the virus world‐wide! • New anti‐retrovirals with y
y
better efficacy and safety are needed
Thunder Duke Vine
(tripterygium wilfordii)
2
Reaction of Alkenes: HX Addition
Markovnikov’s Rule: In electrophilic addition reactions of M
k ik ’ R l I l t hili dditi
ti
f
alkenes, the electrophile adds to the least substituted carbon giving rise to the more stable intermediate. Example: Addition of HX Markovnikov
Addition
(only product)
Non‐Markovnikov
Addition
(NOT observed)
Regioselectivity: When two or more regioisomers (constitutional R
i l i i Wh
i i
(
i i
l
isomers) are possible but one is preferentially formed 3
Reaction of Alkenes: Halogenation with X2
Chlorine (Cl2) and bromine (Br2) react with alkenes to give dihalide products through an anti‐addition mechanism:
Br
Br
Br
CH2Cl2
Br
+
H
H
H
Br
H
Br
bromonium ion
Stereoselectivity: The preferential formation of one stereoisomer over another. Example: anti‐addition vs syn‐addition th E
l
ti dditi
dditi
4
Reaction of Alkenes: Halohydrin formation (X2 and H2O) The bromonium ion can be ring‐opened by a variety of nucleophiles, including water:
bromonium ion
The concentration of water (solvent) is very high so it beats the bromide anion as a nucleophile
the bromide anion as a nucleophile
5
Reaction of Alkenes: Halohydrin Regioselectivity
The bromonium ion is opened by the nucleophilic water at the higher‐substituted carbon because the partial positive charge is more stabilized (hyperconjugation):
more stabilized (hyperconjugation):
6
Hydration of Alkenes: Oxymercuration
Oxymercuration is a two‐step reaction for the hydration of alkenes f h h d
f lk
that gives Markovnikov alcohol products:
Partial Mechanism:
Partial Mechanism:
7
Hydration of Alkenes: Hydroboration
Hydroboration is also a two‐step reaction for the hydration of H
d b ti i l
t
t
ti f th h d ti
f
alkenes that produces syn non‐Markovnikov alcohol products:
3
3
3
2
3
Non-Markovnikov
(syn-addition)
2,
Partial Mechanism:
CH3 BH3
H
H B
H
H
CH3 H2O2,
H
BH2
CH3
NaOH
C
H3
H
OH
r
e
m
o
i
t
n
a
n
+e
H
H
The reaction is regioselective
The
reaction is regioselective (alcohol on the least‐substituted carbon) (alcohol on the least substituted carbon)
and stereoselective (syn‐addition)
8
Hydrogenation of Alkenes to Alkanes
Hydrogenation involves the syn‐addition of H2 to an alkene using a catalyst (ex. Pd/C, PtO2):
Partial Mechanism:
Partial Mechanism:
9
Dihydroxylation of Alkenes
OsO4 allows for the syn‐selective addition of two hydroxyl groups:
Partial Mechanism:
Partial Mechanism:
Due to the toxicity of OsO4, it is sometimes used in a catalytic amount with a stoichiometric amount of t l ti
t ith t i hi
ti
t f
N‐methylmorpholine N‐oxide (NMO) as a co‐oxidant 10
Oxidative Cleavage to Carbonyl Products
Periodate cleaves diols to give carbonyl groups:
Ozonolysis accomplishes the same transformation (alkene to carbonyls) in one step!
11
Summary of Alkene Reactivity
Reagent
Stereoselective?
HBr
No
X2
Yes (Anti)
X2/H2O
Yes (Anti)
1. Hg(OAc)2, H2O Depends on 2. NaBH4
reaction condns.
1. BH3
Yes (Syn)
( )
2. H2O2, OH‐
H2, Pd/C
Pd/C
Yes (Syn)
Yes (Syn)
1. OsO4
Yes (Syn)
2 NaHSO3, H
2. NaHSO
H2O O
12
Regioselective?
Yes (Markovnikov)
(
)
N/A
Yes (Markovnikov)
Yes (Markovnikov)
Yes (Non‐Markovnikov)
(
k
k )
N/A
N/A
Take‐Home Activity
In-Class Problems
Draw structures of the following three alkenes:
Tip: You may want to review the naming principles in Chapter 7, Tip:
You may want to review the naming principles in Chapter 7
sections 7.3‐7.5
(R,E)-3-ethyl-4-methylhept-2-ene
(Z) 3
(Z)-3-methyloct-3-ene
th l t 3
13
(E)-penta-1,3-diene
Take‐Home Activity
In-Class Problems
H
Ph
Ph
Ph
OH
+ enantiomer
,
3
O
4 S
H
a O
2
N H
2
︶
O
s
O
1
︶
HBr
H2, Pd/C
1) O3
2) Zn/ HOAc
Ph
Br2, H2O
Br2,
CH2Cl2
HO
Ph
Ph
14
Review from 1st Year Organic Chemistry:
g
y
The Chemistry of Alkyl Halides
Chapter 10 (
(excluding 10.2‐10.4, 10.7 (only Gilman Reactions)
g
,
( y
)
15
Structure of Alkyl Halides
Alkyl halide (R‐X): A compound containing a halogen atom
covalently bonded to an sp3‐carbon atom
The electronegative halogen polarizes the C‐X bond, resulting in an electron deficient (electrophilic) carbon atom
16
Preparation of Alkyl Halides: Two Main Methods
1) Reaction of alkenes with HX or X2 (discussed previously)
2) Reaction of alcohols
)
a) with mineral acid (HCl or HBr)
3°
b) with thionyl chloride (SOCl2) or phosphorus tribromide (PBr3): 1° or 2°
17
Reaction of Alkyl Halides: Grignard Reagents
Alkyl (and alkenyl/aryl halides) (X = Cl, Br, I) react with magnesium to form organomagnesium halides (Grignard reagents):
18
The Grignard Reaction
Reaction with Carbonyls
R
ti
ith C b
l
Grignard reagents act as strong nucleophiles: The Grignard reaction is one of the most important The
Grignard reaction is one of the most important
carbon‐carbon bond forming reactions in organic chemistry
19
Gilman Reagents
Gilman reagents (lithium diorganocopper) are similar in reactivity to Grignard reagents but use lithium and copper instead of magnesium and requires a 2 step process to make:
magnesium and requires a 2‐step process to make: 1) alkyl halide  alkyllithium
2) alkyllithium  lithium diorganocopper (Gilman reagent)
20
Gilman Reagents
Gilman reagents are also strong nucleophiles
Gil
l
l
hil that can form C‐C h
f
CC
bonds with alkyl, alkenyl or aryl halides (X = Cl, Br, I):
21
In‐Class Problem
Take‐Home Activity
Draw structures for the following three alkyl halides:
Tip: You may want to review the naming principles in Chapter 10, Tip:
You may want to review the naming principles in Chapter 10
Section 10.1
3-ethyl-4,4-difluorooctane
(E S)-6-bromohept-2-ene
(E,S)-6-bromohept-2-ene
(2S 4R)-1-chloro-4-iodo-2-methylhexane
(2S,4R)-1-chloro-4-iodo-2-methylhexane
22
In‐Class Problem
Take‐Home Activity
Grignard reagents are generated and used in polar aprotic solvents including THF or diethyl ether. Explain why polar protic solvents like water or alcohols cannot be used
solvents like water or alcohols cannot be used. 23
In‐Class Problem
Take‐Home Activity
Which of the following compounds cannot be used to generate Grignard reagents? Why?
24
In‐Class Problem
Take‐Home Activity
Design a synthesis of the secondary alcohol below using the two given starting materials as your only source of carbon:
O
OH
+
OH
H
25