Synthetic possibilities Chem 315 Beauchamp 1

Reactions Study List Through Chem 315

For Use as a Study Guide

Beauchamp

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 Synthetic possibilities Chem 315 Beauchamp 2

Important acid/base reactions used in the examples below.

Acid Base New Base Comments
sodium hydroxide

O Na O H O
Na Carboxylates are good
Ka(RCO2H) C
C H Keq = nucleophiles,
Ka(H2O) R O
R O SN2 > E2 at Me, 1o and 2o RX
-5
Keq = 10-16 = 10+11
carboxylic acids 10 carboxylates
sodium hydride
Na H
alkoxides are OK nucleophiles,
H2 H2 Na
Ka(ROH) C SN2 > E2 at Me and 1o RX, and
C H Keq =
Ka(H2) R O strong bases, E2 > SN2 at 2o
R O
10-17 = 10+18 and 3oRX.
alcohols Keq = alkoxides
10-35
sodium hydroxide
Na OH
thiolates are good nucleophiles,
H2 H2 Na
Ka(RSH) C SN2 > E2 at Me, 1o and 2o RX,
C H Keq =
Ka(H2O) R S and strong bases, E2 > SN2 at
R S
-8 3oRX.
Keq = 10-16 = 10+8 thiolates
thiols 10
sodium amide
Na NR2
terminal acetylides are OK
R C C H Ka(RCCH) nucleophiles, SN2 > E2 at Me and
Keq = R C C Na
Ka(HNR2) 1o RX, and strong bases, E2 > SN2
10-25 = 10+12 at 2o and 3oRX.
terminal alkynes Keq = terminal acetylides
10-37

H n-butyl lithium
Li n-Bu Li
N N LDA is a very strong base that
Ka(HNR2) is also very sterically hindered,
Keq = it always acts as a base in our
Ka(H-C4H9)
course.
-37
diisopropylamine Keq = 10-50 = 10+13
10 LDA = lithium diisopropylamide
LDA = lithium diisopropylamide
O Na NR2 O
enolates are good nucleophiles,
C H Ka(RCOCH3) C SN2 > E2 at Me, 1o and 2o RX,
Keq =
R C Ka(HNR2) R CH2 Na and strong bases, E2 > SN2
H2
10-20 = 10+17 at 3oRX.
ketones / aldehydes Keq = ketone enolates
10-37

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LDA = lithium diisopropylamide

O Na NR2 O
enolates are good nucleophiles,
R C H Ka(ROCOCH3) R C SN2 > E2 at Me, 1o and 2o RX,
Keq =
O C Ka(HNR2) O CR2 Na and strong bases, E2 > SN2
R2
10-25 = 10+12 at 3oRX.
ketones / aldehydes Keq = ester enolates
10-37
n-butyl lithium

H Li n-Bu
R R n-butyl lithium removes proton
C X Ka(HCR2PPh3) from Wittig salt and makes a
Keq = C
R PPh3
Ka(H-C4H9) good nucleophile at ketones and
R PPh3
-33 aldehydes, forming alkenes.
Wittig salt = ylid Keq = 10-50 = 10+17
10 betaine
n-butyl lithium
n-butyl lithium removes proton
Li n-Bu from dithiane and makes a
good nucleophile at RX compounds.
S S Ka(dithiane) S S Can react once or twice in SN2
Keq =
C
Ka(H-C4H9) C reactions. Sulfur acetal forms
-33 Li carbonyl group after hydrolysis.
H
dithiane
H Keq = 10-50 = 10+17 H
10 dithiane carbanion Makes aldehydes and ketones.

SN2 versus E2 choices at 2oRX.

At secondary RX (X= OTs, I, Br, Cl) SN2 and E2 products are in close competition with each other. Anions whose
conjugate acids have higher pKa’s (stronger bases have weaker acids) generally produce more E2 relative to SN2. The
two examples that we will emphasize at 2oRX centers are carboxlyates (SN2 > E2) vs hydroxide and alkoxides (E2 >
SN2), and cyanide (SN2 > E2) vs terminal acetylides (E2 > SN2). Steric hindrance in RX or the electron pair donor
also favors E2 > SN2.

Similar looking base/nucleophiles (used in our course) that react differently with 2oRX structures. (They all react by
SN2 at methyl and 1oRX and they all react by E2 at 3oRX.)

2o RX structures

Less basic, so SN2 > E2. More basic, so E2 > SN2. Less basic, so SN2 > E2. More basic, so E2 > SN2.
O

N C R C C C H O R O
R O
cyanide terminal acetylides carboxylates hydroxide and alkoxides
pKa of conjugate acid = 9 pKa of conjugate acid = 25 pKa of conjugate acid = 5 pKa of conjugate acid = 16-19

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Alkanes with Br2 / hν. (Synthesis of RX compounds, X = Br, Cl.)

Br2 / hν free radical
CH4 H 3C Br halogenation
achiral
free radical
Br2 / hν halogenation
Br
achiral
Br free radical
halogenation
Br2 / hν
enantiomers
(R and S)

free radical
Br halogenation
Br2 / hν
achiral

1. a. RX compounds with NaOH / H2O. (Alcohol synthesis.)

NaOH
H3C Br H2O SN 2
H3C OH

E2 SN2
NaOH OH
Br
H2O
major enantiomers
minor achiral
(R and S)

Br NaOH
H2O E2

NaOH
H2O OH SN2
Br
allylic and benzylic, very fast SN2 reactions

NaOH no reaction (vinyl and phenyl RX)

Br H2O
Forcing conditions can induce E2 reactions.
b. RX compounds with NaOR / ROH. (Ether synthesis, need to make RO--,Na+.)
SN 2
H3C Br O Na
O

E2 SN 2
O
Br
O Na

major enantiomers minor achiral

(R and S)

Br
O Na
E2

SN 2
O Na O
Br
allylic and benzylic, very fast SN2 reactions

no reaction (vinyl and phenyl RX)

O Na
Br
Forcing conditions can induce E2 reactions.

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c. RX compounds with potassium t-butoxide (favors E2 > SN2).

K
SN2
O
H 3C Br
O

K E2
Br O
enantiomers
(R and S)

Br K E2
O

SN2
K
O
Br O

allylic and benzylic, very fast SN2 reactions

K no reaction (vinyl and phenyl RX)

O
Br
Forcing conditions can induce E2 reactions.

d. RX compounds with sodium carboxylates. Ester synthesis (can hydrolyze with base to ROH and
RCO2H).
O O

H3C Br Na S N2
R O O

O
O
Br Na
O SN2 > E2
R O
achiral

O
Br Na
E2
R O

O
O S N2
Na
Br O
R O
allylic and benzylic, very fast SN2 reactions

Na
Br no reaction
R O

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e. RX compounds with NaCN / DMSO. Nitrile synthesis.

NaCN
H3C Br DMSO H 3C C N S N2

SN2 > E2
Br
NaCN C N
DMSO
achiral

Br NaCN
DMSO E2

NaCN S N2
Br
DMSO C
N

NaCN
Br
DMSO no reaction
f.
RX compounds with terminal acetylides (need to make). Alkyne synthesis at methyl and primary RX.
Na
H3C Br H 3C R S N2
R

Na mainly E2
Br
R
enantiomers
(R and S)

Br Na
R E2

Na S N2
Br R
R

Na
Br no reaction
R

g.
o
RX compounds with conjugate base of phthalimide (need to make). 1 RNH2 synthesis, after hydrolysis.
O
1.
Na
N
1. SN2
H3C Br H3C NH2
O 2. acyl hydrolysis
2. NaOH
3. WK (neutralize)

O
1.
Na 1. SN2
N 2. acyl hydrolysis
Br NH2
O
2. NaOH
3. WK (neutralize) achiral

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O
1.
Na
Br N
E2
O
2. NaOH
3. WK (neutralize)

O
1.
Na
N

Br NH2
O
2. NaOH 1. SN2
3. WK (neutralize) 2. acyl hydrolysis

O
1.
Na
N
no reaction
Br O
2. NaOH
3. WK (neutralize)

h. RX compounds with LiAlH4 (LAH). Nucleophilic hydride displaces “X” on carbon.

1. LiAlH4
H3C Br 2. WK CH4 SN2

1. LiAlH4
Br 2. WK SN2

Br 1. LiAlH4 not our

2. WK usual
mechanism

1. LiAlH4
2. WK S N2
Br

1. LiAlH4 no reaction
Br 2. WK
i.
RX compounds with NaBH4. Nucleophilic hydride displaces “X” on carbon.
1. NaBH4
H3C Br CH4
2. WK SN2

1. NaBH4
Br 2. WK SN2

Br 1. NaBH4 not our

2. WK usual
mechanism

1. NaBH4
2. WK SN2
Br

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1. NaBH4
no reaction
Br 2. WK

j. RX compounds with enolates (need to make with LDA/-78oC). Alkylation of carbonyl compounds.
O
Li
H3C Br CH4 SN2
H2C

S N2
O
Li achiral
Br
H2C

O
O
Br Li

H2C E2

O O
Li
SN 2
Br
H2C

O
Li
no reaction
Br
H2C

k. RX compounds with water. Alcohol synthesis (rearrangements are possible).

H 3C Br
H2O
no reaction

SN1 > E1
H2O OH
Br diastereomers
top & bottom
achiral

Br H2O OH SN1 > E1

top = bottom

H2O
Br
SN1
Br

H2 O
no reaction
Br

l. RX compounds with alcohols. Ether synthesis (rearrangements are possible).

H3C Br OH
no reaction

SN1 > E1 diastereomers

top & bottom
Br OH achiral
O

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Br O SN1 > E1
OH
top = bottom

OH O
S N1
Br

OH no reaction
Br

m. RX compounds with liquid carboxylic acids. Ester synthesis (rearrangements are possible).
O

H3C Br OH
no reaction

O SN1 > E1
O

Br OH diastereomers
O
top & bottom
achiral
O

Br O O SN1 > E1
OH top = bottom

O
O

Br OH SN1
O

Br no reaction
OH

2. a. ROH with: SOCl2 or PCl3 or HCl or 1. TsCl/pyridine 2. NaCl. Synthesis of R-Cl.

SN 2
given reagent SN 2
OH
in the list SN 2
Cl
SN 2
OH Cl SN 1
given reagent SN 1
in the list SN 1
SN 2

SN1
given reagent SN1
in the list SN1
SN1
OH Cl

SN 1
OH given reagent Cl SN 1
in the list SN 1
SN 2

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OH given reagent Cl
in the list
SN2 or SN1

b. ROH with: PBr3 or HBr or 1. TsCl/pyridine 2. NaBr. Synthesis of R-Br.

given reagent SN 2
in the list SN 2
OH Br SN 2

OH Br
SN1
given reagent SN1
in the list
SN2

SN 1
given reagent SN 1
in the list
SN 1
OH Br

OH given reagent Br SN1

in the list SN1
SN2

OH given reagent Br
in the list
SN2 or SN1

c. ROH with: PI3 or HI or 1. TsCl/pyridine 2. NaI. Synthesis of R-I.

given reagent SN 2
in the list SN 2
OH I SN 2

OH I
SN1
given reagent SN1
in the list SN2

SN 1
given reagent SN 1
in the list SN 1
OH I

OH given reagent I SN1

in the list SN1
SN2

OH given reagent I
in the list
SN2 or SN1

d. ROH with: CrO3 / pyridine (PCC). Synthesis of aldehydes or ketones.

H
CrO3 / pyridine
OH (PCC) oxidation
O

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OH O
CrO3 / pyridine
(PCC) oxidation

CrO3 / pyridine
(PCC) no reaction

OH

OH CrO3 / pyridine O
(PCC) oxidation

OH CrO3 / pyridine
(PCC) H

oxidation

e. ROH with: CrO3 / acid / water (Jones). Synthesis of carboxylic acids or ketones.
OH
CrO3 / acid / H2O
OH (Jones) oxidation
O

OH O
CrO3 / acid / H2O
(Jones) oxidation

CrO3 / acid / H2O

(Jones) no reaction

OH

OH CrO3 / acid / H2O O

(Jones)
oxidation

OH CrO3 / acid / H2O

(Jones) OH

oxidation

f. ROH with acid chlorides. Synthesis of esters. (Need to make RCOCl with SOCl2 + acid.)
O
O acyl
substitution
OH R Cl
R O

O acyl
OH O substitution

R Cl
R O

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O acyl
O substitution

R Cl
OH R O
O O acyl
OH substitution

R Cl R O

O O
acyl
OH substitution

R Cl R O

g. ROH with sodium hydride, NaH. Synthesis of sodium alkoxides.

OH Na H acid/base
O Na

OH O Na
Na H acid/base

K H acid/base

OH O K

OH
Na H O Na
acid/base

OH O Na
Na H acid/base

h. ROH with sulfuric acid / heat. Synthesis of alkenes (useful E1 reactions, rearrangement possible).
OH H2SO4 / ∆ probably E2

OH

H2SO4 / ∆
E1

H2SO4 / ∆
E1
OH

OH
H2SO4 / ∆ E1

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3. a. Alkenes with aqueous sulfuric acid. Alcohol synthesis (rearrangements are possible).
OH
H2SO4 / H2O hydration
(H3O+)
achiral

OH hydration
H2SO4 / H2O
(H3O+) enantiomers
(R and S)

OH hydration
H2SO4 / H2O
(H3O+) enantiomers
(R and S)

OH
hydration
H2SO4 / H2O
(H3O+)
achiral

OH hydration
H2SO4 / H2O
(H3O+)
achiral

hydration

H2SO4 / H2O
OH
(H3O+)
S S diastereomers
(SR and SS)

b. Alkenes with alcohol + sulfuric acid. Ether synthesis (rearrangements are possible).
OR
H2SO4 / ROH hydration
(ROH2+)
achiral

OR hydration
H2SO4 / ROH
(ROH2+) enantiomers
(R and S)

OR hydration
H2SO4 / ROH
(ROH2+) enantiomers
(R and S)

OR

H2SO4 / ROH hydration

(ROH2+)
achiral

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H2SO4 / ROH OR hydration

(ROH2+)
achiral

hydration
H2SO4 / ROH
(ROH2+) OR
S S diastereomers
(SR and SS)

c. Alkenes with HX acid (HCl, HBr, HI). Synthesis of RX compounds.

Br
H Br addition
(or HCl or HI)
achiral

Br addition
H Br
(or HCl or HI) enantiomers
(R and S)

Br
addition
H Br
(or HCl or HI)
enantiomers
(R and S)

Br

H Br addition
(or HCl or HI)
achiral

H Br Br addition
(or HCl or HI)
achiral

H Br addition
(or HCl or HI)
Br
S diastereomers
S (SR and SS)

d. Alkenes with Br2 or Cl2. Synthesis of vicinal dihalide (anti addition).

Br bromination
Br Br
(or Cl2) Br enantiomers
R and S

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Br
bromination
Br Br
(or Cl2)
meso, RS

Br
Br

Br Br bromination
Br
(or Cl2)
enantiomers
RR and SS

Br

Br Br bromination
(or Cl2)
enantiomers
Br RR and SS

bromination
Br Br Br
(or Cl2) Br
achiral

Br
bromination
Br Br
(or Cl2)
Br diastereomers
S SRR and SSS

e. Alkenes with Br2/H2O or Cl2/H2O. Synthesis of bromohydrin or chlorohydrin (anti + Markovnikov

addition).
OH anti + Markovnikov
Br2 / H2O addition
(or Cl2 / H2O) Br enantiomers
R and S
OH
anti + Markovnikov
addition
Br2 / H2O
(or Cl2 / H2O)
enantiomers
RS and SR
Br

OH anti + Markovnikov
addition
Br2 / H2O Br
(or Cl2 / H2O) enantiomers
RR and SS

OH anti + Markovnikov
addition
Br2 / H2O
(or Cl2 / H2O) enantiomers
RR and SS
Br

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Br2 / H2O OH
anti + Markovnikov
(or Cl2 / H2O) addition
Br
achiral

Br
Br2 / H2O anti + Markovnikov
(or Cl2 / H2O) addition
OH
S S diastereomers
SRR and SSS

f. Alkenes with Br2/ROH or Cl2/ROH. Synthesis of bromo or chloro “ethers”.

OR anti + Markovnikov
Br2 / ROH addition
(or Cl2 / ROH) Br enantiomers
R and S
OR
anti + Markovnikov
addition
Br2 / ROH
(or Cl2 / ROH)
enantiomers
RS and SR
Br
OR anti + Markovnikov
addition
Br2 / ROH Br
(or Cl2 / ROH)
enantiomers
RR and SS

OR
anti + Markovnikov
Br2 / ROH addition
(or Cl2 / ROH)
enantiomers
Br RR and SS

anti + Markovnikov
Br2 / ROH OR addition
(or Cl2 / ROH)
Br
achiral

Br
Br2 / ROH anti + Markovnikov
(or Cl2 / ROH) addition
OR
diastereomers
S S SRR and SSS

g. Alkenes with 1. BH3 2. H2O2/HO--. Hydroboration/oxidation = anti-Markovnikov alcohols.

1. BH3 1. syn addition
2. H2O2 / HO OH 2. oxidation
achiral

OH 1. syn addition
1. BH3 2. oxidation
2. H2O2 / HO
enantiomers
R and S

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OH
1. syn addition
1. BH3 2. oxidation
2. H2O2 / HO
enantiomers
R and S

1. syn addition
1. BH3 2. oxidation
2. H2O2 / HO

OH achiral

OH 1. syn addition
1. BH3 2. oxidation
2. H2O2 / HO

achiral

OH
1. syn addition
1. BH3 2. oxidation
2. H2O2 / HO
CH3
diastereomers
S S
SRR and SSS
H

h. Alkenes with 1. BH3 2. Br2/CH3O--. Hydroboration/bromination = anti-Markovnikov R-Br.

1. BH3 1. syn addition
2. Br2 / CH3O Br 2. bromination
achiral

Br
1. syn addition
1. BH3 2. bromination
2. Br2 / CH3O
enantiomers
R and S

Br
1. syn addition
1. BH3 2. bromination
2. Br2 / CH3O
enantiomers
R and S

1. BH3 1. syn addition

2. Br2 / CH3O 2. bromination

Br achiral

Br 1. syn addition
1. BH3 2. bromination
2. Br2 / CH3O

achiral

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Br
1. syn addition
1. BH3 2. bromination
2. Br2 / CH3O
CH3
S diastereomers
S SRR and SSS
H

i. Alkenes with 1. HgX2 / H2O 2. NaBH4. Alcohol synthesis with minimal rearrangements (Markovnikov).
OH
1. HgX2 / H2O
2. NaBH4 achiral

OH

1. HgX2 / H2O enantiomers

2. NaBH4 R and S

OH

1. HgX2 / H2O
2. NaBH4 enantiomers
R and S

1. HgX2 / H2O
2. NaBH4 achiral

OH

1. HgX2 / H2O OH achiral

2. NaBH4

1. HgX2 / H2O diastereomers

2. NaBH4 SR and SS
CH3
S S
OH

j. Alkenes with 1. HgX2 / ROH 2. NaBH4. Ether synthesis with minimal rearrangements (Markovnikov).
O
1. HgX2 / CH3OH
2. NaBH4 achiral

O
1. HgX2 / CH3OH
enantiomers
2. NaBH4 R and S

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1. HgX2 / CH3OH enantiomers

2. NaBH4 R and S

1. HgX2 / CH3OH
achiral
2. NaBH4
O

1. HgX2 / CH3OH O achiral

2. NaBH4

diastereomers
1. HgX2 / CH3OH SR and SS
2. NaBH4
CH3
S S
O

k. Alkenes with OsO4 or KMnO4. “Syn” synthesis of vicinal diols.

OsO4
OH syn addition
or
KMnO4 OH
enantiomers
R and S

OH
OsO4
or syn addition
KMnO4
enantiomers
RR and SS
OH

OH
OsO4
or syn addition
OH
KMnO4
meso
RS and SR

OH
OsO4
syn addition
or
KMnO4 meso
OH RS and SR

OsO4
or OH syn addition
KMnO4 OH
achiral

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OH
OsO4
or syn addition
KMnO4 CH3
S S diastereomers
OH SSR and SRS

l. Alkenes with 1. O3 / -78oC 2. CH3SCH3 or Zn. Synthesis of aldehydes or ketones.

O
1. O3 / -78oC
2. CH3SCH3 CH O
H3C H2C

O
1. O3 / -78oC CH3
2. CH3SCH3 CH HC
H3C
O

O
o CH3
1. O3 / -78 C
CH HC
2. CH3SCH3
H3C
O

O
o
1. O3 / -78 C C
H
2. CH3SCH3 H
C
O

1. O3 / -78oC
2. CH3SCH3 O
O
H2C

1. O3 / -78oC C
H
2. CH3SCH3
CH3
S S
O

m. Alkenes with 1. O3 / -78oC 2. NaBH4. Synthesis of alcohols.

OH
1. O3 / -78oC
2. NaBH4 OH
H3C

OH
1. O3 / -78oC
2. NaBH4

OH

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OH
o
1. O3 / -78 C
2. NaBH4

OH

OH
o
1. O3 / -78 C
2. NaBH4

OH

1. O3 / -78oC
2. NaBH4 OH
OH
H3C

OH
o diastereomers
1. O3 / -78 C (SR and SS)
2. NaBH4
CH3
S S
OH

n. Alkenes with 1. O3 / -78oC 2. H2O2 / HO--. Synthesis of carboxylic acids or ketones.

O HO O
1. O3 / -78oC C
2. H2O2 / HO C
H3C OH OH

O
1. O3 / -78oC
2. H2O2 / HO C
H3C OH

1. O3 / -78oC
C
2. H2O2 / HO
H3C OH

CO2H
1. O3 / -78oC
2. H2O2 / HO CO2H

HO O
1. O3 / -78oC O C
2. H2O2 / HO
OH

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CO2H
1. O3 / -78oC
2. H2O2 / HO CH3
S S
O

o. Alkenes with meta chloroperbenzoic acid (mCPBA). Synthesis of epoxides.

O

Ar H O syn addition

(mCPBA) O O
enantiomers
R and S

O
O
Ar H
syn addition

(mCPBA) O O enantiomers
RR and SS

O
O
syn addition
Ar H
meso
(mCPBA) O O RS and SR

O
syn addition
Ar H
O
meso
(mCPBA) O O RS and SR

O
O syn addition
Ar H

(mCPBA) O O achiral

O
syn addition
Ar H
O
(mCPBA) O O diastereomers
S S SSR and SRS

p. Alkenes with CH2I2 / Zn (Simmons-Smith Rxn). Carbenoid synthesis of cyclopropanes.

syn addition
CHI2 / Zn(Cu)
Simmons-Smith enantiomers
R and S

syn addition
CHI2 / Zn(Cu)
Simmons-Smith enantiomers
RR and SS

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syn addition
CHI2 / Zn(Cu)
Simmons-Smith
meso
RS and SR

syn addition
CHI2 / Zn(Cu)
Simmons-Smith meso
RS and SR

syn addition
CHI2 / Zn(Cu)
Simmons-Smith
achiral

syn addition
CHI2 / Zn(Cu)
Simmons-Smith
diastereomers
S S SSR and SRS

q. Alkenes with CHCl3 / RO-- or CHBr3 / RO--. Carbene synthesis of dihalocyclopropanes.

CHCl3 / NaOH CCl2 syn addition
or
enantiomers
CHBr3 / NaOH R and S

CHCl3 / NaOH CCl2 syn addition

or
enantiomers
CHBr3 / NaOH RR and SS

CCl2
CHCl3 / NaOH syn addition
or
CHBr3 / NaOH meso
RS and SR

CHCl3 / NaOH syn addition

or CCl2
meso
CHBr3 / NaOH RS and SR

CHCl3 / NaOH syn addition

CCl2
or
CHBr3 / NaOH
achiral

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CHCl3 / NaOH syn addition

or CCl2
CHBr3 / NaOH
diastereomers
S (haloform rxn) S SSR and SRS
r.
Alkenes with Pd / H2. Synthesis of “alkane” from “alkene” (hydrogenation).
syn addition
Pd / H2
achiral

syn addition
Pd / H2

achiral

syn addition
Pd / H2

achiral

syn addition
Pd / H2
achiral

syn addition
Pd / H2

achiral

syn addition
Pd / H2
diastereomers
S SR and SS
S

4. a. Alkynes with aqueous sulfuric acid (plus some Hg+2 catalyst). Synthesis via enols (Markovnikov addition).
O
H2SO4 / H2O
Markovnikov addition
= H3O+ (Hg+2) (enol tautomerization
to keto)

O
H2SO4 / H2O Markovnikov addition
= H3O+ (Hg+2) (enol tautomerization
to keto)

H2SO4 / H2O O
= H3O+ (Hg+2)
O

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H2SO4 / H2O
= H3O+ (Hg+2)
Markovnikov addition
(enol tautomerization
to keto)

b. HX addition to alkynes. Markovnikov addition.

Br
H Br
(or HCl or HI) Markovnikov
addition

Br
H Br
Markovnikov
(or HCl or HI) addition

H Br Br

(or HCl or HI)

Br

Br

H Br
(or HCl or HI)
Markovnikov
addition

c. Bromination (or chlorination) of alkynes. Bridging bromonium ion.

Br2 Br

or
Cl2 anti addition

Br
Br
Br2
or anti addition
Cl2
Br
Br
Br2
or anti addition
Cl2
Br
Br

Br2
or
Cl2 anti addition
Br

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d. 1. Hydroboration 2. oxidation of alkynes (anti-Markovnikov addition makes aldehydes or ketones via enolate).
O
1. HBR2
2. H2O2 / HO anti Markovnikov
addition
H

O
1. HBR2 anti Markovnikov
2. H2O2 / HO addition

O
1. HBR2
2. H2O2 / HO
O

1. HBR2
2. H2O2 / HO anti Markovnikov
O addition

e. Catalytic hydrogenation reduces triple bond to “alkane”.

Pd / H2

Pd / H2

Pd / H2

Pd / H2

f. 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.)

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Pd / H2
quinoline
(Lindlar's Cat.)

Pd / H2
quinoline
(Lindlar's Cat.)

g. 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)

h. Zipper reaction moves triple bond to terminal position where it can be removed to form sp carbanion nucleophile.
1. NaNR2
2. WK

Zipper reaction

1. NaNR2
2. WK

Zipper reaction

1. NaNR2
2. WK

Zipper reaction

1. NaNR2
2. WK

Zipper reaction

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i. Formation of conjugate base + addition of aldehyde electrophile forms propargyl alcohol.

1. NaNR2 OH
2. O

1. NaNR2 OH
2. O

1. NaNR2 OH
2. O

1. NaNR2
2. O

H
OH

j. Formation of conjugate base + addition of ketone electrophile forms propargyl alcohol.

1. NaNR2
2.

O
OH

1. NaNR2
2.

O
OH

1. NaNR2
2.

O
OH

1. NaNR2
2. OH

k. Formation of conjugate base + addition of methyl or primary RX electrophile forms a longer alkyne.
1. NaNR2
2.
Br

1. NaNR2
2.
Br

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1. NaNR2
2.
Br

1. NaNR2
2.
Br

l. Formation of conjugate base + addition of secondary electrophile reacts in a nonproductive E2 reaction.

1. NaNR2
2. Br

E2 reaction

1. NaNR2
2. Br

E2 reaction

1. NaNR2
2. Br

E2 reaction

1. NaNR2
2. Br

E2 reaction

j. Formation of conjugate base + addition of epoxide electrophile forms an alkynyl alcohol via SN2

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reaction.
1. NaNR2
2. O R

R OH

1. NaNR2 OH
2. O

1. NaNR2
OH
2. O

1. NaNR2
2. O

R OH
R

5. a. Epoxides with aqueous hydroxide (followed by workup = neutralization).

O NaOH
HO
H 2O achiral
OH
2. WK

O NaOH HO R
H2O OH
chiral
R 2. WK

O NaOH OH
H 2O OH
achiral
2. WK

S OH
R
NaOH R OH
O H 2O

2. WK S S OH
S S
S R OH
diastereomers

b. Epoxides with alcoholic alkoxide (followed by workup = neutralization).

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O HO
RO / ROH
OR
achiral
2. WK

O HO R
RO / ROH OR
chiral
R 2. WK

O OH
RO / ROH
OR
achiral
2. WK

S OR
R
R OH
O
RO / ROH

2. WK S S OH
S S
S R OR
diastereomers

c. Epoxides with aqueous acid.

O H2SO4 / H2O
HO
(H3O+) achiral
OH
2. WK

O H2SO4 / H2O S
(H3O+) OH chiral
R (inversion)
2. WK OH

O H2SO4 / H2O OH
(H3O+) OH achiral
2. WK

S OH
R
H2SO4 / H2O R OH
O (H3O+)
S S OH
S S 2. WK
S R OH
diastereomers

d. Epoxides with alcoholic sulfuric acid.

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O
H2SO4 / ROH
HO
(ROH2+) achiral
OR
2. WK

O S
H2SO4 / ROH
OH
(ROH2+) chiral
R (inversion)
2. WK OR

O H2SO4 / ROH
OH
(ROH2+) achiral
OR
2. WK

S OR
R
H2SO4 / ROH R OH
O (ROH2+)
S S OH
S S 2. WK
S R OR
diastereomers

e. Epoxides with cyanide (followed by workup = neutralization)..

O NaCN HO
DMSO achiral
C
2. WK N

O HO
NaCN R
C
DMSO chiral
N
R
2. WK

O NaCN OH N
DMSO C
achiral
2. WK

N
R
C
S
NaCN
O
DMSO and SRR
S S 2. WK
S S OH
diastereomers

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f. Epoxides with terminal acetylides (followed by workup = neutralization).

Na HO
O
R
achiral
2. WK R

O Na HO R
R chiral
R
2. WK R

Na R
O
OH
R
achiral
2. WK
R
R
Na
S
O
R and SRR
S S
2. WK
S S OH diastereomers

g. Epoxides with LiAlH4 (LAH) (followed by workup = neutralization).

1. LiAlH4
O
2. WK HO achiral

HO
O chiral
1. LiAlH4
No inversion,
R 2. WK but priorities
S
have changed.

O 1. LiAlH4 OH
2. WK achiral

No inversion, OH
R but priorities
1. LiAlH4 have changed.
O achiral
2. WK
S S
S R OH not stereoismers

h. Epoxides with NaBH4 (followed by workup = neutralization).

1. NaBH4
O
2. WK HO achiral

HO
O chiral
1. NaBH4
No inversion,
2. WK but priorities
R S
have changed.

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O
1. NaBH4 OH

2. WK achiral

No inversion, OH
R but priorities
have changed.
1. NaBH4 achiral
O
2. WK
S S
S R OH not stereoismers

i. Epoxides with cuprates (followed by workup = neutralization).

O 1. (CH3)2Cu Li
cuprate reagent HO achiral
2. WK CH3

HO
O
1. (CH3)2Cu Li
cuprate reagent achiral
R 2. WK
CH3

O 1. (CH3)2Cu Li OH
cuprate reagent achiral
CH3
2. WK

not stereoismers R OH
R
1. (CH3)2Cu Li S CH3
O
cuprate reagent
2. WK S R CH3
S S
S S OH

j. Epoxides with lithium diisopropyl amide (LDA, followed by workup = neutralization).

1. Li R OH
R N
R R
O lithium diisopropylamide (LDA)
2. WK S
S enantiomers

1. Li
O N
R R achiral
lithium diisopropylamide (LDA) OH
R 2. WK

1. Li
O N OH
R R
lithium diisopropylamide (LDA) achiral
2. WK

not stereoismers R OH
R 1. Li
N
O R R
lithium diisopropylamide (LDA)
S S 2. WK S
S S OH

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k. Epoxides with Grignard reagents (followed by workup = neutralization).

1. H2
C
O H3C H2C (MgBr)
Grignard reagent HO achiral
2. WK
1. H2 HO
O C
H3C H2C (MgBr) chiral
Grignard reagent R
R
2. WK
1. H2
O
C
H3C H2C (MgBr) OH

Grignard reagent achiral

2. WK
S
R 1. H2
C
O H3C H2C (MgBr) S S OH R OH
Grignard reagent
S S 2. WK R
not stereoismers S

l. Epoxides with organolithium reagents (followed by workup = neutralization).

1. H3C organolithium reagent
HO
O
HC Li achiral
H3C 2. WK
organolithium reagent HO
O
1. H3C
HC Li R chiral
R
H3C 2. WK

1. H3C organolithium reagent

O
OH
HC Li
achiral
H3C 2. WK

R organolithium reagent R
1. H3C R OH
O HC Li
S S H3C S S OH S S
2. WK
not stereoismers

m. Epoxides with conjugate base of phthalimide (followed by hydrolysis and workup = neutralization).
O
1.
NaOH
N H
HO
O
2. epoxide NH2
O achiral
3. NaOH
4. WK

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O
1.
NaOH
N H HO
O

2. epoxide R chiral
O
R 3. NaOH NH2
4. WK

O
1.
NaOH
N H
O
OH
2. epoxide O achiral
3. NaOH NH2
4. WK

O
R 1. R
NaOH NH2
R OH
O N H

S S 2. epoxide O S S OH S S NH2
3. NaOH
4. WK not stereoismers

6. a. Aldehydes and ketones in aqueous acid form carbonyl hydrates.

O
H2SO4 / H2O HO OH
(H3O+)
H
carbonyl hydrate H

O
H2SO4 / H2O
HO OH
(H3O+)

carbonyl hydrate

O OH
H2SO4 / H2O
OH
(H3O+)

carbonyl hydrate

O OH
H2SO4 / H2O
(H3O+) OH

carbonyl hydrate

b. Aldehydes and ketones in aqueous base form carbonyl hydrates.

O
NaOH HO OH
H 2O
H carbonyl hydrate H

O
NaOH
HO OH
H 2O

carbonyl hydrate

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O OH
NaOH
H 2O OH

carbonyl hydrate

O OH
NaOH
H 2O OH

carbonyl hydrate

c. Aldehydes and ketones with Jones reagent. Converts aldehydes to carboxylic acids.
O CrO3 O
acid / water
Jones
H OH

O CrO3
acid / water
Jones No reaction with ketones.

d. Aldehydes and ketones with Zn/HCl (Clemmenson reduction).

O
Zn / HCl

H Clemmenson reduction

O
Zn / HCl

Clemmenson reduction

O
Zn / HCl

Clemmenson reduction

O
Zn / HCl

Clemmenson reduction

e. Aldehydes and ketones with hydrazine and base (Wolff-Kishner reduction).

O
H2NNH2 / RO / ∆

H Wolff-Kishner reduction

O
H2NNH2 / RO / ∆

Wolff-Kishner reduction

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O
H2NNH2 / RO / ∆

Wolff-Kishner reduction

O
H2NNH2 / RO / ∆

Wolff-Kishner reduction

f. Aldehydes and ketones with LiAlH4 (LAH).

1. LiAlH4
O
2. WK

OH
achiral
H

OH
O
1. LiAlH4
2. WK
enantiomers (R and S)

O OH OH

1. LiAlH4
2. WK

achiral diastereomers
OH OH
O
1. LiAlH4 R S
2. WK
chiral enantiomers

g. Aldehydes and ketones with NaBH4.

O
1. NaBH4
2. WK
OH
achiral
H

OH
O
1. NaBH4
2. WK
enantiomers (R and S)

O OH OH

1. NaBH4
2. WK

achiral diastereomers
OH OH
O

1. NaBH4 R S
2. WK
chiral enantiomers

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h. Aldehydes and ketones with cyanide, cyanohydrin synthesis or conjugate addition to alpha-beta
unsaturated C=O.
cyanohydrins OH
O
1. NaCN
2. acid addition
C
H
enantiomers (R and S) N

O
cyanohydrins
HO N
C
1. NaCN
2. acid addition
enantiomers (R and S)

cyanohydrins OH
O N
C

1. NaCN
2. acid addition
achiral diastereomers

O
O conjugate addition,
R and S enantiomers
1. NaCN
2. acid addition

C
N

i. Aldehydes and ketones with terminal acetylides.

OH
O Na
1. R
2. WK
H enantiomers (R and S)
R

O Na enantiomers (R and S) R
1. R HO
2. WK

OH R
O Na
1. R
2. WK
achiral diastereomers

O OH
Na
1. R R
2. WK

enantiomers (R and S)

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j. Aldehydes and ketones with LDA makes enolates (carbanion nucleophiles).

O
O enolate
N Li
R R
lithium diisopropylamide (LDA) H
H

O enolate O
N Li
R R
lithium diisopropylamide (LDA)

O enolate
O
N Li
R R
lithium diisopropylamide (LDA)

O
N Li O
R R enolate
lithium diisopropylamide (LDA)

k. Aldehydes and ketones with Grignard (Mg) reagents.

H2 OH
O 1.
C
H3C H2C (MgBr)
Grignard reagent
H
2. WK enantiomers (R & S)

O OH
1. H2
C
H3C H2C (MgBr)
Grignard reagent
2. WK enantiomers (R & S)

O OH
1. H2
C
H3C H2C (MgBr)
Grignard reagent
2. WK diastereomers (cis & trans)

O
H2 OH
1.
C
H3C H2C (MgBr)
Grignard reagent
2. WK enantiomers (R & S)

l. Aldehydes and ketones with organolithium reagents.

OH
1. H3C
O
HC Li organolithium
reagent
H3C
H
2. WK enantiomers (R & S)

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OH
O 1. H3C
HC Li organolithium
reagent
H3C
2. WK enantiomers (R & S)

O 1. H3C OH

HC Li organolithium
reagent
H3C
2. WK diastereomers (cis & trans)

O 1. H3C OH
HC Li organolithium
reagent
H3C
2. WK enantiomers (R & S)

m. Aldehydes and ketones with cuprates.

O
1. (CH3)2Cu Li
cuprate Cuprates react slowly with
reagent ketones, esters and aldehydes.
2. WK
H

O
1. (CH3)2Cu Li
cuprate Cuprates react slowly with
reagent ketones, esters and aldehydes.
2. WK

O
1. (CH3)2Cu Li
cuprate Cuprates react slowly with
reagent ketones, esters and aldehydes.
2. WK

O O
1. (CH3)2Cu Li
cuprate
reagent
2. WK conjugate addition
to α,β-unsaturated
CH3 carbonyl compounds

n. Aldehydes and ketones with secondary amines (enamine synthesis, alkylation, hydrolysis).
H
TsOH (-H2O)
O N N
E & Z possible
2o amines
H H

H
O
TsOH (-H2O)
N
N
E & Z possible
o
2 amines

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H
O
TsOH (-H2O)
N N

2o amines
achiral S R also possible

H
O
TsOH (-H2O)
N
N

2o amines

o. Aldehydes and ketones with primary amines (imine synthesis).

O N
NH2
TsOH (-H2O)
H H E & Z possible

O
N
NH2
TsOH (-H2O)
E & Z possible

O N
NH2
TsOH (-H2O)

E & Z possible

O N

NH2
TsOH (-H2O)

E & Z possible

p. Aldehydes and ketones with ammonia + NaBH3CN = primary amine synthesis.

O
1. NH3 NH2
2. NaH3BCN
3. WK
H

O
1. NH3 NH2
2. NaH3BCN
3. WK

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q. Aldehydes and ketones primary amine + NaBH3CN = secondary amine synthesis.

O
1.
NH2 HN

2. NaH3BCN
H 3. WK

O
1.
NH2 HN

2. NaH3BCN
3. WK

r. Aldehydes and ketones secondary amine + NaBH3CN = tertiary amine synthesis.

1.
O
N

NH
2. NaH3BCN
H 3. WK

O 1.
N
NH
2. NaH3BCN
3. WK

s. Aldehydes and ketones ethylene glycol, acid, dehydration: ketal and acetal synthesis = protection).
O OH
HO O O acetal =
TsOH (-H2O) protected aldehyde
H H

O
OH ketal =
O O
HO protected ketone
TsOH (-H2O)

O
O
OH
HO
O
TsOH (-H2O)
ketal =
protected ketone

O O
OH
HO
TsOH (-H2O) O
ketal =
protected ketone

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t. Aldehydes and ketones with 1. LDA 2. RX = alkylation of C=O.

O

O 1.
N Li
R R H
lithium diisopropylamide (LDA)
H achiral
2. RX (R = Me, 1o, 2o) R

O
1. Li O
N
R R
lithium diisopropylamide (LDA) R
2. RX (R = Me, 1o, 2o) achiral
enantiomers and diastereomers
O (RR, SS, RS, SR)
1. Li O
N
R R
lithium diisopropylamide (LDA)
2. RX (R = Me, 1o, 2o)
R

O R
1. Li
N
R R O
lithium diisopropylamide (LDA)
2. RX (R = Me, 1o, 2o)
enantiomers (R and S)

u. Aldehydes and ketones with 1. LDA 2. epoxide = alkylation of C=O.

O

1.
N Li
O H
R R
lithium diisopropylamide (LDA)
O OH
H 2. epoxide
S
S

O
1.
N Li
O
R R H
lithium diisopropylamide (LDA)
O
2. epoxide OH

1.
O N Li
R R O
lithium diisopropylamide (LDA)
OH
O
2. epoxide

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v. Aldehydes and ketones with 1. LDA 2. another C=O = addition to C=O. Forms a beta hydroxyl
carbonyl, which can be dehydrated in acid or base (with heat) to an α,β-unsaturated carbonyl
compound.
O
1. Li O
N
O R R
lithium diisopropylamide (LDA) H
O H
acid
H
2. carbonyl
(-H2O)
OH

Li O
1. O
N
O R R
lithium diisopropylamide (LDA)
O
acid
2. carbonyl
(-H2O)

OH

1. Li
N O O
O R R
acid
lithium diisopropylamide (LDA) (-H2O)
O
2. carbonyl
OH

w. Aldehydes and ketones with mCPBA (Baeyer-Villigar oxidation) to form esters (cyclic = lactones).
O
O
H O
aldehyde forms
O O carboxylic acid
H
meta chloroperbenzoic acid
(mCPBA) OH

O
O O
H

O O
meta chloroperbenzoic acid O
(mCPBA) The better R+ group
migrates better.

O O
O
H

O O O
Cyclic esters
meta chloroperbenzoic acid are called
(mCPBA) lactones.

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7. Show the products of the following miscellaneous reactions.

O 1. NaOH O
2. RX (R = methyl, 1o, 2o)
R
OH O

O O
SOCl2

OH Cl

O O
R OH
R
Cl O

O O
NH3

Cl NH2

O
N
SOCl2 C

NH2

O
O
R NH2
R
N
Cl H

O
O
R
R
R NH
N
Cl
R

Z:\classes\316\Organic reactions overview\final exam option - rxn examples w answers.doc