Organic Reactions Summary Alkenes, alkynes and variations For Use as a Study Guide Beauchamp

45 Pages·2015·0.44 MB·English

Alkenes, Alkynes & Variations Beauchamp 1

Organic Reactions Summary
Alkenes, alkynes and variations

For Use as a Study Guide

Beauchamp

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Alkenes, Alkynes & Variations Beauchamp 2

Making alkenes and alkynes

a. mechanism using potassium t-butoxide, KOC(CH ) , S 2 at and E2 at 1o, 2o and 3o RBr,
3 3 N

H3C O H SN2 H3C H
C C Br O C
Br
H3C H H
CH3 H H
D H H
E2
C Br C D C D
H C
3 O H R Z
H3C C Ha C CH3 Hb C CH3 H3C C HaE Br
CH H
3 b
H
H C
3 O C Br
C H C E2 (-CH -H)
H3C H2 E2 2 Br
CH
CH 3
3 H C
a E2 (-CH -H)
b
Hb E2 (-CHa-H)

Example reactions

E2 > S 2
N
KOC(CH ) anti
Br 33 elimination
Br
KOC(CH ) E2
33
R
KOC(CH ) E2
3 3
Br

R Br
KOC(CH ) E2
3 3
S S

H C
3 CH
3
Br C
KOC(CH3)3 O CH3 SN2
no other
option

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b. Double elimination from dibromoalkanes to form alkynes and terminal acetylides used in many additional
reactions (S 2 with RBr, C=O addition to aldehyses and ketones, and reaction with epoxides)
N

Br Br Br
2 eqs. Br H
2
Na
h H Na
N N
H R R H N R R
R R 3rd equivalent
H
most stable
a
anion in mixture
O
H a
H H Na
2. workup
H b
2. 2
H C
C2 b X R Na
R
H
O c SN2
CH H2O H O 2. H c
b R CH C Na
R O R
b d d
HO 2.
H2O H O O Na

The zipper reaction moves a triple bond in an unbranched linear chain to the end and allows all of the above
reactions.
H
2
C CH CH2
C H N Na C 2 C
C R R C C
R R
R
H
N
R R
R R
N H
H H
Na H C C
C
C C C
R R C H
C C C R
R C
C H
H H Na
H H N H
N
R R R R
R R
N
H
C
2. workup
R C H H
C
O C
H H H H R C
C
H
2

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Alkenes, Alkynes & Variations Beauchamp 4

c. mechanism using NaCC-R to make a bigger alkyne, S 2 at methyl, 1o and 2o RBr and only E2 at 3o RBr,
N

H H
S 2
N
C C Br R C C C Br
C H
H
R H H
D D
S 2
N
C C Br R C C C Br
C H R
H
R CH2 H2C
H3C CH3
H
H C H
C C Br 3
C H C O C Br
R H2 E2 > SN2
CH H
Ha C 3 E2 (-CH2-H) E2 (-CHa-H) E2 (-CH -H) H2C
b SN2 CH3
H
b

Example reactions

S 2
N
NaCC-R inversion of
Br configuration
R
Br
NaCC-R
R E2 > S 2
N
NaCC-R E2
Br

R Br
NaCC-R E2 > S 2
N
S S

C achiral
Br
NaCC-R
C
R
S 2
N

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Alkenes, Alkynes & Variations Beauchamp 5

d. mechanism using triphenylphosphine to make triphenylphosphonium salt, S 2 at methyl, 1o and 2o RBr and
N
only E2 at 3o RBr, used to make a triphenylphosphonium ylid to make Z and E alkenes with aldehydes and ketones.

Br
Ph H Br S 2 Ph H Ph O
Ph P C N Ph P C CH2 12.. Hn-BCu=LOi Ph P CH3 C
2
Ph H CH3 Ph H CH3 Li Ph C HH CH3
betaine
ylid salt
Ph = phenyl
H Ph O Ph O
Ph H C CH Ph P C H Ph P C H
Ph P O C 3 Ph C CH3 Ph C CH3
Ph Z alkenes
CH3 H CH3 H CH3
oxaphosphatane

Ph H Br S 2 Ph Br H Ph H3C O
Ph P C N Ph P C CH2 12.. nH-BCu=LOi Ph P CH2 C
2 H CH
Ph H3C CH2 Ph CH3CH2 Li Ph C CH3 3
Ph = phenyl H3C ylid salt CH3 betaine
H Ph O Ph O
Ph H C C CH Ph P C H Ph P C H
Ph P O 3 C 3 Ph C CH3 Ph C CH3
Ph Z alkenes
CH2 H3C CH2 H3C CH2
H3C H3C oxaphosphatane H3C

Schlosser Modification of the Wittig reaction to make E alkenes
H OH
2
H
H H H
O C
Ph3P CO HC R Ph3P C H R aacti -d7/b8aoCse Ph3P CO C R neutralize Ph3P CO RC R
R
The stereochemistry
R R H
betaine H C of the alkene is
2 flat sp2 carbon determined in this step.
Li
can react from
extra equivalent of n-BuLi
either side
H
H
O O C
Ph3P C R Ph3P
R C R
phosphine C R
oxide
H
H
E alkene

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Example reactions

1. Br
P
2. n-BuLi
Ph Ph
3. CH CH=O Normal Wittig
Ph 3 Z alkene preferred
1. Br
R
P
Ph Ph
2. n-BuLi
Ph 3. CH CH=O Normal Wittig
3 Z alkene preferred
1.
P Br
Ph Ph 2. n-BuLi
Ph 3. CH3CH=O E2

1. R Br
P
S
Ph Ph 2. n-BuLi
Ph 3. CH CH=O Normal Wittig
3 S Z alkene preferred

1.
Br
P
Ph Ph
Ph 2. n-BuLi Normal Wittig
3. CH3CH=O Z alkene preferred

1. Br
2. n-BuLi
3. CH CH=O
P 3
Ph Ph 4. -78oC, n-BuLi Schlosser modification
of the Wittig
Ph 5. HCl, warm 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

O O
O O H O O
P R K
OMe K N R P
R H OMe R N O O OMe
N OMe
terminal
given
alkynes
N

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Possible mechanism – with mechanism details

O O O O O
O
O P P
R P
R OMe O OMe R
OMe
OMe OMe O
OMe
N N
N
N given N O
N
R H
R H R H
H C C
O O
C O O
C C C
R P
R O R P
N resonance N O P H OMeOMe H OMeOMe
N N OMe N N
N
N rearrangement = N2 leaves, OMe N
and H migrates across N

Example reactions

1. RO Na
O O O
P 2.
OMe H difficult to make
alkyne at branch
OMe
N point
2
1. RO Na
O O
2. O
P
OMe difficult to make
alkyne at branch
OMe H
N point
2
1. RO Na
O O O
2.
P
OMe H difficult to make
alkyne at branch
OMe
N point
2

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Alkenes, Alkynes & Variations Beauchamp 8

f. ROH with sulfuric acid / heat. Synthesis of alkenes (our only useful E1 reaction. Rearrangement is
possible).
H H
H O SO H
3 O SO H
3
H O H O H
H

(heat) H
O O E1
H H O SO3H H
slow step
H
O SO H
secondary alcohol pKa = -10 wleaatevri nigs ag rgoouopd H 3 bp = +83oC
bp = +161oC alcohol alkene distills out
T = 78oC
bp

H
H O (heat) H H CH H H O H CH3
O 3 H H
H O SO3H H3C C H3C C
C C C C
H rearrangement H
pKa = -5 slow step CH3 H CH3 H
alcohol 2o carbocation 3o carbocation
H C
3
H
H C C
3
HO3S O H O H C CH3
alkene
(E1 mechanism) CH
3

Example reactions
H SO /  probably E2
OH 2 4
OH
H SO / 
2 4 E1
H SO / 
2 4 E1
OH
OH
H SO / 
2 4 E1
OH
E1
H SO / 
2 4
rearrangement

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Alkenes, Alkynes & Variations Beauchamp 9

g. Making Allylic Alcohols from Epoxides using LDA (E2 reaction using LDA + epoxides)

a
H
O H
Li
Li O
O O
C C H
H  H N H H H
C C
H CH2 E2-like H  H C C
reaction H CH2 2. workup H C H
H  2
proton
LDA, lithium diisopropyl amide
transfer
(always a base in our course)

b
H
O H
Li
Li O
O O
C C CH
H  CH3 N C C 3 H H CH3
H CH2 E2-like H  H C C
reaction H CH2 2. workup H C H
H  2
proton
LDA, lithium diisopropyl amide transfer
(always a base in our course)

Example reactions
OH
1. LDA, -78oC
O 2. workup
allylic alcohols,
can oxidize to C=O

O
1. LDA, -78oC OH
2. workup
allylic alcohols,
can oxidize to C=O

allylic alcohols,
can oxidize to C=O
O 1. LDA, -78oC
OH
2. workup

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Alkenes, Alkynes & Variations Beauchamp 10

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)
HBr H2
overall reaction H C Br
C R2O2 (cat.)
H C C
H3C CH2 h 3 H2
1. initiation (two steps)
R O
h R O H = 40 kcal/mole
O R
O R
(cat.)
BE = +88 kcal/mole
R
BE = -111 kcal/mole
O H Br R H Br
O
reagent H = -23 kcal/mole
2a propagation
H H
C BE = +63 kcal/mole
H3C CH2 Br C Br BE = -68 kcal/mole
H C C
3 H = -5 kcal/mole
H
2
2b propagation
H
H2 BE = +88 kcal/mole H = -15
C Br H Br C Br Br BE = -98 kcal/mole
H C C both steps
H C C 3
3 H H2 H = -10 kcal/mole (2a + 2b)
2
3. termination = combination of two free radicals - relatively rare because free radicals are at low concentrations
H H Br
Br
C Br C Br H = -68 kcal/mole
H C C H C C
3 3
H H
2 2
CH
3
H H
H
2
Br C C Br C CH Br H = -80 kcal/mole
Br CH C
CH2 CH3 H3C CH2 H2
CH very minor products
3

Example reactions
H-Br / h
Br
ROOR (cat.) achiral

Br / h
2
ROOR (cat.)
Br achiral

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