Alkenes, Alkynes & Variations Beauchamp 1 y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Organic Reactions Summary Alkenes, alkynes and variations For Use as a Study Guide Beauchamp
Alkenes, Alkynes & Variations Beauchamp 1
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc
Organic Reactions Summary Alkenes, alkynes and variations
For Use as a Study Guide
Beauchamp
Alkenes, Alkynes & Variations Beauchamp 2
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Making alkenes and alkynes a. mechanism using potassium t-butoxide, KOC(CH3)3, SN2 at and E2 at 1o, 2o and 3o RBr,
C
H
HH
Br CO
H
HH
H3C
Br
SN2
C
D
HC
Br
Br
E2
CO C
H
CH2
Br
BrE2H
CHa
CH3
Hb
E2 (-CH2-H)
E2 (-CHa-H)
E2 (-CHb-H)
R Z
H3C
H3C
CH3
CO
H3C
H3C
CH3
CO
H3C
H3C
CH3
HaCH3
Hb
C
C
CH3
D
H
HbE
C
C
Ha
D
H
H3C
Example reactions
BrKOC(CH3)3
E2 > SN2anti
elimination
Br
R
E2KOC(CH3)3
Br
E2KOC(CH3)3
BrR
S S
KOC(CH3)3 E2
BrO SN2
no other option
C
H3CCH3
CH3KOC(CH3)3
Alkenes, Alkynes & Variations Beauchamp 3
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b. Double elimination from dibromoalkanes to form alkynes and terminal acetylides used in many additional reactions (SN2 with RBr, C=O addition to aldehyses and ketones, and reaction with epoxides)
BrBr
HN
R R
Na
Br
H
H
NR R
H
NR R
Na
Na
2. workup
H
H2C
RX
H2C
R
HO
H
H
2.
a
a
b
SN2
2 eqs. Br2h
3rd equivalent
most stable anion in mixture
b
Na
CHR O
CR
2.b
c
Na
2.b d
NaO
OH2O HCH
R
OH
H
OH2O HHO
d
c
The zipper reaction moves a triple bond in an unbranched linear chain to the end and allows all of the above reactions.
CC
R
H2C
H
RN
R
Na
CC
R
CH2
CC
R
CH2
CC
C
R
H
H
H
RN
R
CC
C
R
H
H
RN
R
HC
CC
R
H
HR
NR
H
CC
C
R
2. workup
HO
H
H
Na
RN
R
Na
H H
H
CC
C
R
H H
RN
R
H
CH2
CC
R
H
Alkenes, Alkynes & Variations Beauchamp 4
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c. mechanism using NaCC-R to make a bigger alkyne, SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr,
CC C
H
HH
Br CC
H
HH
Br
SN2
C
D
HCH2
Br Br
SN2
H3C
R
C
CC
D
HH2C
C
CH3
R
CC
R
CC
R
R
R
C
H
CH2
Br
CO
H
HH2C
H3C
BrE2 > SN2
CH3
H
CHa
CH3
Hb
SN2E2 (-CH2-H) E2 (-CHa-H) E2 (-CHb-H)
Example reactions
Br
SN2inversion of
configurationNaCC-R
R
Br
R
NaCC-R
E2 > SN2
Br
E2NaCC-R
BrR
S S
E2 > SN2NaCC-R
Br C achiral
SN2
CNaCC-R
R
Alkenes, Alkynes & Variations Beauchamp 5
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d. mechanism using triphenylphosphine to make triphenylphosphonium salt, SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr, used to make a triphenylphosphonium ylid to make Z and E alkenes with aldehydes and ketones.
Br
CBr
H CH3
H
CH2
Li PhP
C
Ph
CH CH3
O
PhP
C
Ph
C
Ph = phenyl
1. n-BuLi2. H2C=O
ylid salt
SN2
CP
H
CH3H
P
Ph
Ph
PhPh
Ph
PhCH3
H
Ph
O
Ph
CH3
CH3
H
H
PhP
C
Ph
C
O
Ph
CH3
CH3
H
HP
Ph
Ph
Ph O CC
H
CH3
H
CH3
Z alkenes
oxaphosphatane
betaine
Br
CBr
H3C CH2
H
CH2
Li PhP
C
Ph
CH CH3
O
PhP
C
Ph
C
Ph = phenyl
1. n-BuLi2. H2C=O
ylid salt
SN2
CP
H
CH2CH3
P
Ph
Ph
PhPh
Ph
PhCH2
CH3
Ph
O
Ph
CH2
CH3
H3C
H
PhP
C
Ph
C
O
Ph
CH2
CH3
H3C
HP
Ph
Ph
Ph O CC
H3C
CH2
H
CH3
Z alkenes
oxaphosphatane
betaineH3C CH3
H3C
H3CH3CH3C
Schlosser Modification of the Wittig reaction to make E alkenes
C
R
H
Ph3PCO
H
R C
R
H
Ph3PCO
H
R
C
H
R
Ph3PCO
H
R
E alkene
Ph3PO
phosphine oxide
The stereochemistry of the alkene is
determined in this step.H2C
C
Ph3PCO
H
R
R
OH2H
C
H
R
Ph3PCO
H
R
Li
acid/baseat -78oC neutralize
flat sp2 carbon can react from either side
betaine
extra equivalent of n-BuLi
C
C R
H
H
R
Alkenes, Alkynes & Variations Beauchamp 6
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Example reactions
PhP
Ph
1. Br2. n-BuLi3. CH3CH=O
PhNormal Wittig
Z alkene preferred
BrR
1.
PhP
PhPh
2. n-BuLi3. CH3CH=O Normal Wittig
Z alkene preferred
Br
1.
PhP
PhPh
2. n-BuLi3. CH3CH=O E2
BrR
S
S
1.
PhP
PhPh
2. n-BuLi3. CH3CH=O Normal Wittig
Z alkene preferred Br
1.
PhP
PhPh 2. n-BuLi
3. CH3CH=ONormal Wittig
Z alkene preferred
PhP
Ph
1. Br2. n-BuLi3. CH3CH=O4. -78oC, n-BuLi5. HCl, warmPh
Schlosser modification of the Wittig
E alkenes preferred
e. Ohira-Bestmann modification of the Seyferth-Gilbert reaction (makes terminal alkynes from aldehydes and a special ‘Wittig’ reagent). Overall reaction from aldehyde to the terminal alkyne – simplified Ohira-Bestmann reaction
P
O
OMeOMe
O
N
N
R H
O
R
H
NN
O
OR P
O
OOMe
OMe
K
terminalalkynes
RO
K
given
Alkenes, Alkynes & Variations Beauchamp 7
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Possible mechanism – with mechanism details
RO P
O
OMeOMe
O
N
N
P
O
OMeOMeO
N
N
O
R
O
OR
P
O
OMeOMe
N
N
R H
O
P
O
OMeOMe
N
N
O
R
H
P
O
OMeOMe
N
N
O
R
HP
O
C
OMeOMe
N
NO
CR H
C
N
N
CR H
RC
C
NN
H
resonance
given
rearrangement = N2 leaves, and H migrates across
Example reactions
O
N2
P
O
OMeOMe
O
H2.
1. RO Na
difficult to make alkyne at branch point
O
N2
P
O
OMeOMe
O
H
2.
1. RO Na
difficult to make alkyne at branch point
O
N2
P
O
OMeOMe
O
H
2.
1. RO Na
difficult to make alkyne at branch point
Alkenes, Alkynes & Variations Beauchamp 8
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f. ROH with sulfuric acid / heat. Synthesis of alkenes (our only useful E1 reaction. Rearrangement is possible).
secondary alcohol
O
H
H O
H
H H
OH OH SO3H
(heat) O
H
H
O SO3H
E1
bp = +83oCdistills outbp = +161oC
OH SO3HO SO3H
H
H
H
alcohol alkene Tbp = 78oC
pKa = -10 water is a good leaving group
slow step
CC
C
H
H
HHslow step
H3C
CH3
CH3
CC
C
H
HH
H3C
CH3
CH3H
rearrangement
alcohol 2o carbocation 3o carbocation
OH
OH H
OH SO3H
(heat)
pKa = -5
OHO3S CC
CH3
H3C
CH3
H3C
alkene (E1 mechanism)
O
H
H
O
H
H H
Example reactions
probably E2OH H2SO4 /
OH
E1H2SO4 /
OH
E1H2SO4 /
OHE1H2SO4 /
E1H2SO4 /
OH
rearrangement
Alkenes, Alkynes & Variations Beauchamp 9
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g. Making Allylic Alcohols from Epoxides using LDA (E2 reaction using LDA + epoxides)
a
C C
O
HH CH2
H N
Li
LDA, lithium diisopropyl amide(always a base in our course)
H
C CHH CH2
OH
Li
HO
H
H
2. workupC CH
H CH2
OH
H
E2-likereaction
protontransfer
b
C C
O
HH CH2
CH3 N
Li
LDA, lithium diisopropyl amide(always a base in our course)
H
C CHH CH2
OCH3
Li
HO
H
H
2. workupC CH
H CH2
OCH3
H
protontransfer
E2-likereaction
Example reactions
O1. LDA, -78oC2. workup
OH
allylic alcohols, can oxidize to C=O
1. LDA, -78oC2. workup
OH
allylic alcohols, can oxidize to C=O
O
1. LDA, -78oC2. workup
OH
allylic alcohols, can oxidize to C=O
O
Alkenes, Alkynes & Variations Beauchamp 10
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Reactions of alkenes, alkynes and conjugated variations
a. RBr from alkenes (anti-Markovnikov addition of HBr using free radical chemistry):
mechanism using HBr / ROOR / h for free radical addition to alkane pi bonds (anti-Markovnikov addition = Br adds to less substituted position to form most stable free radical intermediate, and then H adds to more substituted position)
H3C
H2C
CH2
Br
H3C
HC
CH2
HBrR2O2 (cat.)
h
overall reaction
1. initiation (two steps)
RO
OR h R
OO
R
BrHR
O RO
H Br
H = 40 kcal/mole
H = -23 kcal/mole
BE = +88 kcal/moleBE = -111 kcal/mole
(cat.)
reagent
2a propagation
H3C
HC
CH2Br
H3CC
CH2
Br
H
H = -5 kcal/mole
BE = +63 kcal/mole BE = -68 kcal/mole
H = -15
both steps(2a + 2b)
2b propagation
H3CC
CH2
Br
H
BrH H3C
H2C
CH2
BrBr
H = -10 kcal/mole
BE = +88 kcal/mole BE = -98 kcal/mole
3. termination = combination of two free radicals - relatively rare because free radicals are at low concentrations
Br
H3CC
CH2
H Br
CH2
CCH3
H
CH2
CH3C
H
CH
CH3
H2C CH
CH2
CH3
H = -68 kcal/mole
H = -80 kcal/mole
very minor products
H3CC
CH2
Br
H
Br
Br BrBr
Br
Example reactions H-Br / h
ROOR (cat.) Br achiral
Br2 / h
ROOR (cat.)Br achiral
Alkenes, Alkynes & Variations Beauchamp 11
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Br2 / hROOR (cat.)
Br
R/Senantiomers
BrBr2 / h
ROOR (cat.) cis and trans
b. RBr from alkenes (anti-Markovnikov addition of HBr using borane chemistry):
mechanism using 1. BH3 2. Br2 / CH3O-- for anti-Markovnikov addition of H-Br to alkane pi bonds (concerted, syn
addition of H-BH2 to alkene pi bond, followed by complex with Br2 and migration of R group to Br)
H3C
H2C
CH2
Br
H3C
HC
CH2
overall reaction
step 1
BH
R
R
1. (BH3)22. Br2, CH3O
H2CC
CH
H2CCH2
CH2
CH3
H2CC
C
H2CCH2
CH2
H3C
H
H
B
R
R
syn addition, with H at more substituted position and B at less substituted position.
step 2
H2CC
C
H2CCH2
CH2
H3C
H
H
B
R
R
Br Br H2CC
C
H2CCH2
CH2
H3C H
B
R
R
Br Br
HH2C
CC
H2CCH2
CH2
H3C HB
R
R
Br
H
Br
OH3C
H2CC
C
H2CCH2
CH2
H3C HB
R
R
Br
H
OCH3
H2CC
C
H2CCH2
CH2
H3C HB
R
R
Br
H
OCH3
Example reactions Br achiral
1. (BH3)22. Br2, CH3O
Alkenes, Alkynes & Variations Beauchamp 12
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Br achiral1. (BH3)22. Br2, CH3O
Br
R/Senantiomers
1. (BH3)22. Br2, CH3O
Br
() or (dl) enantiomers
1. (BH3)22. Br2, CH3O
c. Alkenes with aqueous sulfuric acid. Alcohol synthesis (Markovnikov addition, rearrangements are possible).
OH
H
H
OH H
H3CC
C
H
H
HH
CH3C
H
CH3
OH H
OH HCH3C
H
CH3
OH
Protonate alkene pi bond.
Attack carbocation with water nucleophile.
Acid/base proton transfer.
slow step
alkene
alcohol
alkene + water alcohol
alkene + alcohol ether
acid catalysis
acid catalysis
OH
H
H
OH H
CC
C
H
H
HH
CH3C
CH3
CH2
OH3C H
OH
CH3C
CH3
CH2
OH
slow stepH3C
CH3
H
CC
C
H
HH
H3C
CH3
HH
CH3
H
CH3
rearrangement
alcohol
alkene2o carbocation 3o carbocation
Example Reactions
OHH2SO4 / H2O (H3O+)
hydration
achiral
OH
H2SO4 / H2O (H3O+)
hydration
enantiomers (R and S)
Alkenes, Alkynes & Variations Beauchamp 13
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OH
H2SO4 / H2O (H3O+)
hydration
enantiomers (R and S)
OH
H2SO4 / H2O (H3O+)
hydration
achiral
OHH2SO4 / H2O (H3O+)
hydration
achiral
rearrangement
OH
H2SO4 / H2O (H3O+)
hydration
diastereomers (SR and SS)S S
d. Alkenes with alcohol + sulfuric acid. Markovnikov addition, ether synthesis (rearrangements are possible).
OH
H
CH3
OH CH3
H3CC
C
H
H
HH
CH3C
H
CH3
OH3C H
OH CH3
CH3C
H
CH3
OH3C
alkene + water alcohol
alkene + alcohol ether
acid catalysis
acid catalysis
slow step
OH
H
CH3
OH CH3
CC
C
H
H
HH
CH3C
CH3
CH2
OH3C H
OH3C
CH3C
CH3
CH2
OH3C
slow stepH3C
CH3
H
CC
C
H
HH
H3C
CH3
HH
CH3
H
CH3
rearrangement
alkene
ether
ether
alkene2o carbocation
3o carbocation
Example Reactions OR
H2SO4 / ROH (ROH2
+)
hydration
achiral
OR hydration
enantiomers (R and S)
H2SO4 / ROH (ROH2
+)
Alkenes, Alkynes & Variations Beauchamp 14
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OR hydration
enantiomers (R and S)
H2SO4 / ROH (ROH2
+)
ORhydration
achiral
H2SO4 / ROH (ROH2
+)
Ohydration
achiral
H2SO4 / ROH (ROH2
+)
R
rearrangement
diastereomers (SR and SS)
OR
hydration
SS
H2SO4 / ROH (ROH2
+)
e. Alkenes with 1. HgX2 / H2O 2. NaBH4. Alcohol synthesis with minimal rearrangements (Markovnikov).
HgO O
OO
mercuric acetateHg(OAc)2
ethanoate has a common name of acetate = OAc
+Hg(OAc)electrophile
HgO O
OO
These d orbital electrons on mercury are available. They are not usually drawn, but are helpful for understanding the Hg+ bridge in the cationic intermediate.
Hg O
O
Hg O
O resonance
Hg O
O
The large mercury atom with extra d electron densitiy bridges across the two carbons (like Br+ in the next section) or the protonated epoxide bridge and prevents rearrangement. Nucleophilic attack in the next step occurs from the opposite side to the mercury bridge and occurs at the more + carbon (the more substituted carbon).
OH
H
Hg O
O
OH
HO
HH
Hg O
O
O
HO
HH
Hprotontransfer
The initial adduct is a stable, organomercury compound, but is not usually isolated. It is relatively toxic and need not be isolated. The next step can be run in the same reaction pot (reduction of mercury with NaBH4).
OR
H R = H = water nucleophile forms alcohol product
R = C = alcohol nucleophile forms ether product
Alkenes, Alkynes & Variations Beauchamp 15
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Hg O
O
O
H
BHH
HH
Hg
O
H
H
BHO
HH
O
Hg
O
H
HHH
O
H
H
H
Hg metal
SN2 nucleophilic attack by hydride at the mercury atom displaces acetate as the leaving group. Acetate can complex at boron taking the place of the transferred hydride. This keeps boron with an octet, which also is negatively charged.
Free radical dissociation of the weak Hg-C bond occurs. Other free radical reactions are possible here, but not emphasized in our course.
A hydrogen atom is abstracted from the mercury by the highly reactive carbon free radical. This forms mercury metal as one of the products. No stereoselectivity is observed here because of the sp2 free radical carbon.
The Hg bridge helps to prevent rearrangement.
Example Reactions
1. HgX2 / H2O2. NaBH4 achiral
OH
OH
enantiomers R and S
1. HgX2 / H2O2. NaBH4
OH
enantiomers R and S
1. HgX2 / H2O2. NaBH4
OH
achiral1. HgX2 / H2O2. NaBH4
achiral1. HgX2 / H2O2. NaBH4
no rearrangement
OH
OH
CH3
diastereomers SR and SS
S
1. HgX2 / H2O2. NaBH4
S
Alkenes, Alkynes & Variations Beauchamp 16
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f. Alkenes with 1. HgX2 / ROH 2. NaBH4. Ether synthesis with minimal rearrangements (Markovnikov).
HgO O
OO
mercuric acetateHg(OAc)2
ethanoate has a common name of acetate = OAc
+Hg(OAc)electrophile
HgO O
OO
These d orbital electrons on mercury are available. They are not usually drawn, but are helpful for understanding the Hg+ bridge in the cationic intermediate.
Hg O
O
Hg O
O resonance
Hg O
O
The large mercury atom with extra d electron densitiy bridges across the two carbons (like Br+ in the next section) or the protonated epoxide bridge and prevents rearrangement. Nucleophilic attack in the next step occurs from the opposite side to the mercury bridge and occurs at the more + carbon (the more substituted carbon).
OH3C
H
Hg O
O
OH
H3CO
H3CH
Hg O
O
O
H3CO
H3CH
Hprotontransfer
The initial adduct is a stable, organomercury compound, but is not usually isolated. It is relatively toxic and need not be isolated. The next step can be run in the same reaction pot (reduction of mercury with NaBH4).
OR
H R = H = water nucleophile forms alcohol product
R = C = alcohol nucleophile forms ether product
Hg O
O
O
H3C
BHH
HH
Hg
O
H3C
H
BHO
HH
O
Hg
O
H3C
HHH
O
H3C
H
H
Hg metal
SN2 nucleophilic attack by hydride at the mercury atom displaces acetate as the leaving group. Acetate can complex at boron taking the place of the transferred hydride. This keeps boron with an octet, which also is negatively charged.
Free radical dissociation of the weak Hg-C bond occurs. Other free radical reactions are possible here, but not emphasized in our course.
A hydrogen atom is abstracted from the mercury by the highly reactive carbon free radical. This forms mercury metal as one of the products. No stereoselectivity is observed here because of the sp2 free radical carbon.
The Hg bridge helps to prevent rearrangement.
Alkenes, Alkynes & Variations Beauchamp 17
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Example Reactions
1. HgX2 / CH3OH2. NaBH4
achiral
O
Oenantiomers R and S
1. HgX2 / CH3OH2. NaBH4
O
enantiomers R and S
1. HgX2 / CH3OH2. NaBH4
O
achiral1. HgX2 / CH3OH2. NaBH4
1. HgX2 / CH3OH2. NaBH4
achiral
no rearrangement
O
O
CH3
diastereomers SR and SS
S
1. HgX2 / CH3OH2. NaBH4
S
Alkenes, Alkynes & Variations Beauchamp 18
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g. Electrophilic addition of HCl, HBr, HI to alkenes = Markovnikov addition, synthesis of RX compounds with possibile rearrangements
Cl
Which carbon atom reacts first, ...second?
There are two carbon choices for an electrophile to react with. Which carbon gives up the electrons and becomes a carbocation is based on the most stable carbocation that can form (leading to a regioselective reaction). Such a reaction is generally not stereoselective because the flat carbocation allows attack of the nucleophile to both faces. We expect three possible reactions from the carbocation, add a nucleophile, lose a beta proton or rearrange.
a
b
b
a
C
H
H
primary carbocation (less stable)
CH2
tertiary carbocation (more stable)
Cl
Cl
Cl
Cl
only product
not observed
add a nucleophile
lose beta proton
rearrange
H
H
not this way
H
Forms pi bonds.
Starts over.
ClH
Cl
Cl
Cl
a
a
b
Clrearrangement
40%
40%
20%
O
OH
O
OH
resonance
O
OH
O
O
c.b
(dl mixture)
achiral
achiral
O
OH(solvent)
Example Reactions
only shows regioselectivity
H-Br
Br
Markovnikov additioni
only shows stereoselectivity
I
D-ID
I
D(dl) enantiomers (dl) enantiomers
Alkenes, Alkynes & Variations Beauchamp 19
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only shows stereoselectivity
I
D-ID
I
D(dl) enantiomers (dl) enantiomers
shows regioselectivity but not stereoselectivity
H-BrBr
CH3CH3
Br
diastereomers (if no rearrangement)
shows possible rearrangements
H-Br
Br
h. Electrophilic addition of HCl, HBr, HI to alkynes = Markovnikov addition, synthesis of RX compounds, can use 1 equivalent or 2 equivalents
ClHH3C
CC
H
H3CC
CH2
ClH3C
CC
H
H
Cl
H3CC
CH2
Cl
1 eq. HCl
ClH
H3CC
CH3
Cl
2 eqs. HClH3C
C
CH3
Cl
Cl
Cl
shows regioselectivity
H-Br
Br
Markovnikov additioni
E/Z diastereomers
H-Br
Br Br
E/Z diastereomers
H-Br Ph
Br
Ph
Br
shows regioselectivity
ClH
Cl
O
O
O
OH(solvent)
50% / 50%shows regioselectivity
Alkenes, Alkynes & Variations Beauchamp 20
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i. Electrophilic addition of HCl, HBr, HI to conjugated diene or triene = Markovnikov addition, synthesis of RX compounds, can use 1 equivalent or 2 equivalents
+
Br H H2C
HC
CH
CH2
BrBr
H3CC
CH
CH2
H
H3CC
CH
CH2
H
Br
resonance
Temp = -80oC 80% 20%(a kinetic choice)
Temp = +40oC 20% 80%(a thermodynamic choice when more energy is available)
1,2-addition 1,4-additionA
B
BrH
12
34
resonance
Br
a b
Br
ab
Br
kinetic product larger + in intermediate
thermodynamic product more stable alkene
3o carbocationis best
resonance
Br
a b
Br
ab
Br
1
23 5
64
BrH
resonance
Brc
c
H H H
1,2 addition - This looks secondbecause the alkenes are conjugated.
1,4 additionleast favorable because it breaks conjugation
1,6 addition - This looks best because the alkenes are more substituted and conjugated.
Alkenes, Alkynes & Variations Beauchamp 21
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j. Alkenes with Br2 or Cl2. Synthesis of vicinal dihalide (anti addition).
HC CH2
BrBr
CHHC
CH2
CH2
Br
Brb
a
CHHC
Br
CH2
Bra b
HC
CH2
a
1,4-addition is the thermodynamic product because the double bond is more substituted (E or Z is possible)
H2C
88% 12%
HC
HC
CH2
H2CBr
Br
1,2-addition is the kinetic product because bromine attack is faster at the more positive seconday carbon atom.
HC CH2
BrBr
CHHC
CH2
CH2
Br
Brb
a
CHHC
Br
CH2
Bra b
HC
CH2
a
1,4-addition is the thermodynamic product because the double bond is more substituted (E or Z is possible)
H2C
88% 12%
HC
HC
CH2
H2CBr
Br
1,2-addition is the kinetic product because bromine attack is faster at the more positive seconday carbon atom.
chlorine is a green gas,dissolved in the solvent
CHCl3 81%
Br
Br
bromine is a red orange liquid dissolved in the solvent, the color disappears as it is added
CCl4 85%
(dl) mixture
Br
BrBr
Br
Cl
Cl Cl
Cl
meso (achiral)
Cl
Cl
BrBrBr
(or Cl2)
bromination
Br enantiomers R and S
Br
meso, RS
bromination
Br
BrBr(or Cl2)
Br
Brenantiomers RR and SS
brominationBrBr(or Cl2)
Alkenes, Alkynes & Variations Beauchamp 22
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Br
bromination
Br
enantiomers RR and SS
BrBr(or Cl2)
Brbromination
achiral
BrBr(or Cl2) Br
Br diastereomersSRR and SSS
brominationBr
S
BrBr(or Cl2)
1
2 3
4Br2 / CHCl3 / 0oC
Br
Br
BrBr
BrBr Br
Br
3% 21%
5% 71%
k. Alkenes with Br2/H2O or Cl2/H2O. Synthesis of bromohydrin or chlorohydrin (anti + Markovnikov addition).
Br
O
(dl) mixture
Br
Br Br
Br
Cl
Cl Cl
Cl
HO
HH
O
H
HO
H
H
H
HO
H Br
O
H
HO
H
Cl
O H
H
HO
H Cl
O
H(dl) mixture
OH
Br enantiomers R and S
anti + Markovnikov addition Br2 / H2O
(or Cl2 / H2O)
Alkenes, Alkynes & Variations Beauchamp 23
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OH
Br
Br2 / H2O(or Cl2 / H2O)
enantiomers RS and SR
anti + Markovnikov addition
OH
Brenantiomers RR and SS
Br2 / H2O(or Cl2 / H2O)
anti + Markovnikov addition
OH
Br
enantiomers RR and SS
Br2 / H2O(or Cl2 / H2O)
anti + Markovnikov addition
anti + Markovnikov addition
achiral
Br2 / H2O(or Cl2 / H2O)
Br
OH
no rearrangement
OHdiastereomersSRR and SSS
Br
S
Br2 / H2O(or Cl2 / H2O)
S
anti + Markovnikov addition
l. Alkenes with Br2/ROH or Cl2/ROH. Synthesis of bromo or chloro “ethers”.
Br
O
(dl) mixture
Br
Br Br
Br
Cl
Cl Cl
Cl
HO
CH3H
O
CH3
HO
CH3
H
H3C
HO
H Br
O
H3C
HO
CH3
Cl
O H
H3C
HO
H Cl
O
H3C(dl) mixture
OR
Br enantiomers R and S
Br2 / ROH(or Cl2 / ROH)
anti + Markovnikov addition
Alkenes, Alkynes & Variations Beauchamp 24
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OR
Br
enantiomers RS and SR
Br2 / ROH(or Cl2 / ROH)
anti + Markovnikov addition
OR
Br
enantiomers RR and SS
Br2 / ROH(or Cl2 / ROH)
anti + Markovnikov addition
OR
Brenantiomers RR and SS
Br2 / ROH(or Cl2 / ROH)
anti + Markovnikov addition
OR
achiralBr
Br2 / ROH(or Cl2 / ROH)
anti + Markovnikov addition
OR diastereomersSRR and SSS
Br
S
Br2 / ROH(or Cl2 / ROH)
anti + Markovnikov addition
S
m. Alkenes with 1. BH3 2. H2O2/HO--. Hydroboration/oxidation = anti-Markovnikov alcohols.
The mechanism for this reaction is given at the beginning of this document.
1. BH32. H2O2 / HO OH
achiral
1. syn addition2. oxidation
OH
enantiomers R and S
1. BH32. H2O2 / HO
1. syn addition2. oxidation
OH
1. BH32. H2O2 / HO
enantiomers R and S
1. syn addition2. oxidation
OH
1. BH32. H2O2 / HO
achiral
1. syn addition2. oxidation
Alkenes, Alkynes & Variations Beauchamp 25
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achiral
1. BH32. H2O2 / HO
1. syn addition2. oxidation
OH
H
CH3 diastereomersSRR and SSS
OH
S
1. BH32. H2O2 / HO
S
1. syn addition2. oxidation
n. Alkenes with 1. BH3 2. Br2/CH3O--. Hydroboration/bromination = anti-Markovnikov R-Br.
BRH2CH2C
CH2CH2R
CH2CH2R
strong Lewis base Lewis acid (trigonal planar)
B
CH2CH2RRH2CH2CCH2CH2R
Br
Br
BR
R
Br
OH3C
B
RR
O
H3Csimilar reactions,(two more times)
trivalent borontetravalent
borontrivalent boron
tetravalent boron
A weaker -Br-Br bond is broken and a stronger C-Br bond is formed. Bromide is a good leaving group in the strongly basic solution.
alkyl migration, with bromide leaving group, reacts 2x more but not shown.
Lewis acid/base reaction
Br Br3 CH2CH2R
Br
CH2CH2R
BR
R
OCH3
H2C
Br
CH2
R
anti-Markovnikov product3x total
B(OCH3)4H2C
Br
CH2
R
1. BH32. Br2 / CH3O Br
achiral
1. syn addition2. bromination
Br
enantiomers R and S
1. BH32. Br2 / CH3O
1. syn addition2. bromination
Br achiral
1. BH32. Br2 / CH3O
1. syn addition2. bromination
achiral
Br1. BH32. Br2 / CH3O
1. syn addition2. bromination
H
CH3 diastereomersSRR and SSS
Br
S
1. BH32. Br2 / CH3O
S
1. syn addition2. bromination
Alkenes, Alkynes & Variations Beauchamp 26
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o. Alkynes with 1. HBR2 2. H2O2/HO--. Hydroboration/oxidation = anti-Markovnikov aldehydes.
B O
H
HH
B O
H
H H
borane/THF complexreactive form of borane (a good Lewis acid)
THF = tetrahydrofurane
BHHH
C C
H
H
R
H
The transfer of two electron pairs is concerted. The boron and hydrogen atom add from the same face (syn), so this reaction is stereoselective. The boron adds at the less substituted carbon so this reaction is also regioselective. In subsequent reactions the boron can be converted to another group in exactly the same position, so whereever the boron ends up will indicate the position of the actual group introduced (OH or Br for us).
CH
H
C
H B
HR
HH
CH
R CH2
similar reaction a second time
CH
R CH2
similar reaction a third time
monoaklylboranealkene + borane diaklylborane triaklylborane There are no more hydrides to transfer.
concerted reaction
CH
H
C
H B
HR
CH2
CH2
H2C
R
CH
H
C
H B
HR
HCH2
H2C
RH2C
R
O
H
O
HHO O
H
O HOH
There is a strong electron pair donor on each side of the equilibrium equation that can complex with trivalenet boron, but only the peroxide anion reacts further. All of these are present.
weak strong weakstrong
O
H
O BRH2CH2C
CH2CH2R
CH2CH2R
strong Lewis base Lewis acid (trigonal planar)
B
CH2CH2RRH2CH2CCH2CH2R
O
OH
BRH2CH2C
CH2CH2R
OCH2CH2R
OH
B
CH2CH2RRH2CH2COCH2CH2R
O
Hsimilar reactions,(two more times)
B
OCH2CH2RRH2CH2COOCH2CH2R
O
H
B
O
H
RH2CH2C O
O O
CH2CH2R
CH2CH2R
O
H
H
OH
H2C
R CH2
OH
Anti-Markovnikov alcohol is formed in a regioselective and stereoselective manner.
trivalent boron
tetravalent boron
trivalent boron
tetravalent boron
tetravalent boron
trivalent boron
A weaker -O-O- bond is broken and a stronger C-O bond is formed. Hydroxide, HO is an acceptable leaving group in the strongly basic solution (compatible with the reaction conditions).
alkyl migration, with hydroxide leaving group
Lewis acid/base reaction
similar reactions,(two more times)
ligand dissociation
proton transfer
Step 1
Step 2
Alkenes, Alkynes & Variations Beauchamp 27
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1. HBR22. H2O2 / HO
O
H
anti-Markovnikovaddition
aldehyde
1. HBR22. H2O2 / HO
O
H
anti-Markovnikovaddition
aldehyde
O
1. HBR22. H2O2 / HO ketone
O
1. HBR22. H2O2 / HO
2 ketones
O
p. Alkenes with CHCl3 / RO-- or CHBr3 / RO--. Carbene synthesis of dihalocyclopropanes.
C H
Cl
Cl
Cl
chloroform(trichloromethane) pKa 25
RO
alkoxidestrong base
C
Cl
Cl
Cl
CCl
Cl
singlet carbene
= CCl
Cl
Cl
A different type of elimination reaction.
C C
R
H
R
H
C
Cl Cl
C C
C
R R
H H
electron acceptance
electron donation
"cis" alkenes form "cis" cyclopropane rings
"trans" alkenes form "trans" cyclopropane rings
concerted reaction(occurs in one step)
ClClstereoselective reaction
Alkenes, Alkynes & Variations Beauchamp 28
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q. Alkenes with CH2I2 / Zn (Simmons-Smith Rxn). Carbenoid synthesis of cyclopropanes. Example Reactions
enantiomers R and S
syn addition
CHBr3 / NaOH CBr2
enantiomers RR and SS
syn additionCBr2CHBr3 / NaOH
mesoRS and SR
syn additionCBr2CHBr3 / KOC(CH3)3
mesoRS and SR
syn additionCCl2CHCl3 / NaOH
achiral
syn additionCCl2
CHCl3 / NaOH
diastereomersSSR and SRS
S
syn addition
S
CCl2
CH3
CHCl3 / KOC(CH3)3
C
I
H I
H
Zn C
I
H
H
Zn+2 I
C
I
H
H
Zn+2
I
The first pair of dots represents easily lost 4s electrons on zinc, that reduce a C-I bond.
The second pair of dots represents 3d electrons on zinc that are invoked in the metal complex.
carbenoid complex
The stabilization by the metal makes the complex more stable, and less reactive. This makes the carbenoid complex more selective for the desired reaction.
C C
R
H
R
H
C
H H
C C
H2C
R R
H H
electron acceptance
electron donation
"cis" alkenes form "cis" cyclopropane rings
"trans" alkenes form "trans" cyclopropane rings
concerted reaction(occurs in one step)
Simmons-Smith reaction
Alkenes, Alkynes & Variations Beauchamp 29
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Example Reactions (Simmons-Smith reaction)
enantiomers R and S
syn addition
CH2I2 / Zn(Cu) CH2
enantiomers RR and SS
syn additionCH2
CH2I2 / Zn(Cu)
mesoRS and SR
syn additionCH2
CH2I2 / Zn(Cu)
mesoRS and SR
syn additionCH2
CH2I2 / Zn(Cu)
achiral
syn additionCH2
CH2I2 / Zn(Cu)
diastereomersSSR and SRS
S
syn addition
S
CH2
CH3
CH2I2 / Zn(Cu)
r. Alkenes with meta chloroperbenzoic acid (mCPBA). Synthesis of epoxides.
C C
R
H
R
H
O
O
OH
Cl
OCl
O
H
C C
O
H H
R R
mCPBA (peroxyacid) has two electron poor oxygen atoms in the peroxide bond, and the meta-Cl makes them even more electron poor by its inductive effect.
View this complicated group of arrows as two different groupings in the transition state, one of five atoms and one of three atoms. It might be easier to think about this way.
one step concerted reaction
The alkene is electron rich.
The reaction can occur from either the top face or the bottom face.
costs (bond energy in kcal/mole)
C=O (even trade) = +176O-H (even trade) = + 110O-O (very weak) = +45C=C (weak pi bond) = +64ring strain of an epoxide is also a cost = + 27 Total = + 422
gains (bond energy in kcal/mole)
C=O (even trade) = -176O-H (even trade) = - 110C-O (very weak) = -90C-O (very weak) = -90 Total = - 466
changes in energy
H = -44 kcal/mole exothermic, even with ring strain
buffered solution prevents acid from reacting with epoxide
5 atoms
3 atoms
Example Reactions (mCPBA)
Alkenes, Alkynes & Variations Beauchamp 30
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Ar
O
O O
H
(mCPBA)
O
enantiomers R and S
syn addition
Ar
O
O O
H
(mCPBA)
O
enantiomers RR and SS
syn addition
Ar
O
O O
H
(mCPBA)
O
mesoRS and SR
syn addition
Ar
O
O O
H
(mCPBA)
O mesoRS and SR
syn addition
Ar
O
O O
H
(mCPBA)
O
achiral
syn addition
Ar
O
O O
H
(mCPBA)O
diastereomersSSR and SRSS
syn addition
S
Alkenes, Alkynes & Variations Beauchamp 31
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s. Alkenes with OsO4 or KMnO4. “Syn” synthesis of vicinal diols.
Mn
O
O
O
O K
C C
R
H
R
H
C C
OO
R RH H
HH
H2OHO
C C
O
Mn
O
H HR R
O O
KMnO4
C C
O
Mn
O
H HR R
O O
HO
H
C C
O
Mn
O
H HR R
O O
H
HO
C C
O
Mn
O
H HR R
O
H
O
OH
C C
O
Mn
O
H HR R
O
H
O
OH
HO
H
The alkene is electron rich
KMnO4 and OsO4are electron poor
The stereochemistry isset at this point as "syn" addition
Use analogies with hydroxide hydrolysis of esters and imides presented earlier.
change in oxidation state...?each carbon goes from -1 to 0 (2 electrons lost)manganese goes from +7 to +5 (2 electrons gained)
OsO4 has a similar mechanism.
Very expensive OsO4 can be continually reoxidized with an inexpensive amine oxide (like morpholine N-oxide)
Os
O
OOOs
O
O
O
O+NOO
NO
amine oxide (N = -1)
reduced OsO3 (Os = +6)
morpholine (N = -3)
osmium tetroxide (Os = +8)
Os
O
O
O
Oresonance
Example Reactions
Alkenes, Alkynes & Variations Beauchamp 32
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achiral
OHOsO4
KMnO4
or
OH
syn addition
OH
CH3diastereomersSSR and SRS
S
OsO4
KMnO4
or
OH
syn addition
S
t. Alkenes with 1. O3 / -78oC 2. CH3SCH3 or Zn. Synthesis of aldehydes or ketones.
Ozone is an electron poor oxidzing reagent.
OO O
C1 C2
R
R
R
H
Simple alkenes are electron rich.
-78oC
Molozonide is highly unstable, even at -78oC and rearranges to a more stable ozonide with only one peroxide bond.
resonancerotate 180o
C1R R
OO
C1 C2
O
O
O
R
R H
R-78oC
C2H R
O
C1
R R
OO
C2
H R
O
Rejoins with only one peroxide bond(use polarities).
Peroxide bond ruptures(shown).
O O
C2
O
C1R
R
R
H
The C=C is completely cleaved at -78oC. The second step decides what will happen to the ozonide. In this example, it is reduced by DMS to two carbonyl compounds, (an aldehyde and a ketone).
SH3C CH3
C2H R
O
C1
R R
O
aldehydeketone
SH3C CH3
O
dimethylsulfoxide (DMSO)
SH3C CH3
O
ozonide
Cyclic five atom transition state with six electron movement.
resonance
Example Reactions
H3CCH
H2C
1. O3 / -78oC2. CH3SCH3
O
O
H3CCH HC
OCH3
O
1. O3 / -78oC2. CH3SCH3
1. O3 / -78oC2. CH3SCH3
H3CCH HC
OCH3
O
Alkenes, Alkynes & Variations Beauchamp 33
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CHHC
O
O
1. O3 / -78oC2. CH3SCH3
1. O3 / -78oC2. CH3SCH3
H2COO
CH
O
CH3S
O
1. O3 / -78oC2. CH3SCH3
S
u. Alkenes with 1. O3 / -78oC 2. NaBH4. Synthesis of alcohols.
-78oC
C2
H R
O
C1
R R
OaldehydeketoneBH3H
BH3
BH3H BH3H
C
O
R R
H
C
O
H R
H
OH H
HC
O
R R
H
C
O
H R
H
HH
The ketone becomes a secondary alcohol.
several steps
The aldehyde becomes a primary alcohol.
b. NaBH4 workup
final workup (neutralization)
BH4-- is electron
rich, the ozonide is electron poor
OO O
C1 C2
R
R
R
H
O O
C2
O
C1R
R
R
H
ozonide
Example Reactions
H3C
1. O3 / -78oC
2. NaBH4
OH
OH
OH
OH
1. O3 / -78oC2. NaBH4
Alkenes, Alkynes & Variations Beauchamp 34
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OH
OH
1. O3 / -78oC2. NaBH4
H3COHOH
1. O3 / -78oC2. NaBH4
OH
CH3S
OH
1. O3 / -78oC2. NaBH4
S
diastereomers (SR and SS)
v. Alkenes with 1. O3 / -78oC 2. H2O2 / HO--. Synthesis of carboxylic acids or ketones.
-78oC
C1
R R
O
ketone
several steps
b. NaBH4 workup
BH4-- is electron
rich, the ozonide is electron poor
O
O O
C1 C2
R
R
R
H
O O
C2
O
C1R
R
R
H
ozonide
O H
C2R H
OH H
H
O OOH
C2
R O
O
H
rearrangement of peroxide(hydride shift)
C2
R O
O basic conditions
O H
H
final workup(neutralization)
C2
R O
O
H
peroxide intermediate
O H
carboxylic acid
Example Reactions
1. O3 / -78oC2. H2O2 / HO
H3CC
C
O O
OH
HO
OH
H3CC
O
OH
1. O3 / -78oC2. H2O2 / HO
H3CC
O
OH
1. O3 / -78oC2. H2O2 / HO
Alkenes, Alkynes & Variations Beauchamp 35
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CO2H
CO2H
1. O3 / -78oC2. H2O2 / HO
O COHO
OH
1. O3 / -78oC2. H2O2 / HO
CO2H
O
CH3SS
1. O3 / -78oC2. H2O2 / HO
w. Alkenes with Pd / H2. Synthesis of “alkane” from “alkene” (hydrogenation). Simplistic mechanism:
M
Neutral metal atom can begin the process over = catalytic.
MH
HM
H
HC
C
metal HOMO H2 LUMO
metal HOMO bond LUMO
M
H
HC
C
metal hydridepi bond complex
M
H CC
H
CC
H
H
Syn (cis) addition of two hydrogensto the pi bond. Generally H2 adds from the less sterically hindered face (i.e. the H2 adds to the more open face).
metal hydridesigma bond complex
Hydride transferreleases an alkaneand regeneratesthe metal catalyst.
adds H2.
Hydride transfer also bonds carbon to the metal atom.
Example reactions
achiral
Pd / H2syn addition
achiral
Pd / H2
syn addition
Alkenes, Alkynes & Variations Beauchamp 36
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achiral
Pd / H2
syn addition
achiral
Pd / H2
syn addition
achiral
Pd / H2
syn addition
diastereomers SR and SSS
Pd / H2
syn addition
S
x. Alkenes with Pd / D2. Same hydrogenation reactions with deuterium from “alkene” (hydrogenation w/”D” = deuterium).
R / SPd / D2
syn additionD
D*
* = chiral center
S
RR and SS(enantiomers)
syn addition
Pd / D2
D
D
* *R
R
D
syn addition
Pd / D2
D
RS and SR(meso,achiral)
** S
R
syn additionPd / D2
D
D
RS and SR(meso,achiral)
*
*S
R
achiral
syn additionPd / D2
D D
Alkenes, Alkynes & Variations Beauchamp 37
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diastereomersSSR and SRS
Rsyn addition
S
Pd / D2
D
D*
*
*S
S
y. Alkynes with aqueous sulfuric acid (plus some Hg+2 catalyst). Synthesis via enols (Markovnikov addition).
H2SO4 / H2O = H3O+ (Hg+2)
H2SO4 / H2O = H3O+ (Hg+2)
H2SO4 / H2O = H3O+ (Hg+2)
O
O
O
O
Markovnikov addition (enol tautomerization to keto)
Markovnikov addition (enol tautomerization to keto)
H2SO4 / H2O = H3O+ (Hg+2)
O
Markovnikov addition (enol tautomerization to keto)
y. HX addition to alkynes. Markovnikov addition.
BrH(or HCl or HI) Markovnikov
addition
BrH(or HCl or HI)
BrH(or HCl or HI)
BrH(or HCl or HI)
Br
Br
Br
Br
Markovnikov addition
Br
Markovnikov addition
Alkenes, Alkynes & Variations Beauchamp 38
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z. Bromination (or chlorination) of alkynes. Bridging bromonium ion.
or
Br2
Cl2anti addition
Br
Br
Br
Br
or
Br2
Cl2
or
Br2
Cl2
or
Br2
Cl2
Br
Br
Br
Br
anti addition
anti addition
anti addition
aa. 1. Hydroboration 2. oxidation of alkynes (anti-Markovnikov addition makes aldehydes or ketones via enolate).
1. HBR22. H2O2 / HO anti Markovnikov
addition
1. HBR22. H2O2 / HO
1. HBR22. H2O2 / HO
1. HBR22. H2O2 / HO
O
H
O
O
O
O
anti Markovnikov addition
anti Markovnikov addition
Alkenes, Alkynes & Variations Beauchamp 39
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bb. Catalytic hydrogenation reduces triple bond to “alkane”.
Pd / H2
Pd / H2
Pd / H2
Pd / H2
cc. Catalytic hydrogenation with quinoline “poison” of Pd catalyst reduces triple bond to Z alkene (syn addition).
Pd / H2 quinoline(Lindlar's Cat.)
Pd / H2 quinoline(Lindlar's Cat.)
Pd / H2 quinoline(Lindlar's Cat.)
Pd / H2 quinoline(Lindlar's Cat.)
Alkenes, Alkynes & Variations Beauchamp 40
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dd. Sodium metal + liquid ammonia reduction of triple bond to E alkenes.
Na / NH3 (liq - =33oC)
Na / NH3 (liq - =33oC)
Na / NH3 (liq - =33oC)
Na / NH3 (liq - =33oC)
ee. Zipper reaction moves triple bond to terminal position where it can be removed to form sp carbanion nucleophile.
1. NaNR22. WK
Zipper reaction
1. NaNR22. WK
Zipper reaction
1. NaNR22. WK
Zipper reaction
1. NaNR22. WK
Zipper reaction
Alkenes, Alkynes & Variations Beauchamp 41
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ff. Formation of conjugate base + addition of aldehyde electrophile forms propargyl alcohol.
1. NaNR22. O
H
1. NaNR22. O
H
1. NaNR22. O
H
1. NaNR22. O
H
OH
OH
OH
OH
gg. Formation of conjugate base + addition of ketone electrophile forms propargyl alcohol.
OH
1. NaNR22.
O
1. NaNR22.
O
1. NaNR22.
O
1. NaNR22.
O
OH
OH
OH
Alkenes, Alkynes & Variations Beauchamp 42
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hh. Formation of conjugate base + addition of methyl or primary RX electrophile forms a longer alkyne.
1. NaNR22.
Br
1. NaNR22.
Br
1. NaNR22.
Br
1. NaNR22.
Br
ii. Formation of conjugate base + addition of secondary electrophile reacts in a nonproductive E2 reaction.
1. NaNR22. Br
1. NaNR22. Br
1. NaNR22. Br
1. NaNR22. Br
E2 reaction
E2 reaction
E2 reaction
E2 reaction
Alkenes, Alkynes & Variations Beauchamp 43
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jj. Use zipper reaction to move alkyne through a linear chain to the end position. Work up 4 ways: a. with mild acid to generate the terminal alkyne, b. with an MeX or primary RCH2X to make a longer alkyne, c. with an aldehyde or ketone compound (C=O) or d. with an epoxide.
1. excess NaNR22. workup
Br
1. excess NaNR22.
Ph Ph = phenylPh
1. excess NaNR22. OHH2C O
3. workup
1. excess NaNR22.
Ph Ph = phenylPh
3. workup
OHO
kk. Formation of conjugate base + addition of epoxide electrophile forms an alkynyl alcohol via SN2 reaction.
O
O
1. NaNR22.
1. NaNR22.
O
1. NaNR22.
O
1. NaNR22.
OHR
RR
OH
OH
OH
R
Alkenes, Alkynes & Variations Beauchamp 44
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ll. Epoxides with terminal acetylides (followed by workup = neutralization).
Na
R
2. WK
HO
O
R
O
O
O
HO
OH
OHS
S
R
S
and SRR
S
S
diastereomers
achiral
chiral
achiral
RNa
R
2. WK
Na
R
2. WK
Na
R
2. WK
R
R
R
R
mm. Epoxides with lithium diisopropyl amide (LDA, followed by workup = neutralization).
NR R
Li
lithium diisopropylamide (LDA)
1.
2. WK
O
R
O
O
OHS
S
R
S
not stereoismers
achiral
OH
achiral
S
R
S
NR R
Li
lithium diisopropylamide (LDA)
1.
2. WK
NR R
Li
lithium diisopropylamide (LDA)
1.
2. WK
NR R
Li
lithium diisopropylamide (LDA)
1.
2. WK
O
S
ROHR
Senantiomers
OH
OH
Alkenes, Alkynes & Variations Beauchamp 45
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nn. Aldehydes and ketones with terminal acetylides.
Na
R
O
H
O
O
achiral diastereomers
enantiomers (R and S)
OH
enantiomers (R and S)
HO
OH
2. WK
1.
Na
R
2. WK
1.
Na
R
2. WK
1.
R
R
R
O Na
R
2. WK
1.
OH
R
enantiomers (R and S)
oo. Aldehydes and ketones with secondary amines (enamine synthesis, alkylation, hydrolysis).
N
H
TsOH (-H2O)O
H
O
N
H
2o amines
N
H
TsOH (-H2O)
2o amines
E & Z possible
E & Z possibleN
O
O
N
H
TsOH (-H2O)
2o amines
N
H
TsOH (-H2O)
2o amines
N
N
achiral S R also possible