Organic Reactions Study Guide Summary

Typical First Year Organic Reactions Beauchamp 1
Organic Reactions Summary
For Use as a Study Guide
Beauchamp
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, SN-E, C=O, epoxides chem, with mechs.doc
Important acid/base reactions used in the examples below. Write out every one of these easy mechanisms.
sodium hydroxide
Na OH
H2 thiolates are good nucleophiles,
H2 Na
C H
Ka(RSH) C SN2 > E2 at Me, 1o and 2o RX,
Keq =
R S Ka(H2O) R S and strong bases, E2 > SN2 at
-8
Keq = 10 = 10+8 3oRX.
thiols -16 thiolates
10
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)
-37 course.
diisopropylamine Keq = 10 = 10+13
10-50 LDA = lithium diisopropylamide
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 -25 at 3oRX.
esters Keq = 10-37 = 10+12 ester enolates
10
O 2 eqs. Na NR2 O
Na enolates are good nucleophiles,
H C H Ka( O2CCH3) C Na SN2 > E2 at Me, 1o and 2o RX,
Keq =
O C Ka(HNR2) O CHR2 and strong bases, E2 > SN2
R2 at 3oRX.
10-25 = 10+12
carboxylic acids Keq = acid dianion
10-37
2 eqs. Na NR2
N N Na enolates are good nucleophiles,
C H Ka( O2CCH3) C SN2 > E2 at Me, 1o and 2o RX,
Keq =
C Ka(HNR2) CR2 and strong bases, E2 > SN2
R2 -30 at 3oRX.
nitriles Keq = 10-37 = 10+7 nitrile enolate
10
n-butyl lithium
H Li n-Bu
R R n-butyl lithium removes proton
C X Ka(HCR2SPh2) from sulfur salt and makes a
Keq = C
Ka(H-C4H9) good nucleophile at ketones and
R SPh2 R SPh2
10-33 = 10+17 aldehydes, forming epoxides.
Keq =
sulfur salt = ylid 10-50 betaine
n-butyl lithium removes proton
from dithiane and makes a
n-butyl lithium good nucleophile at all of our
Li n-Bu electrophiles. It can react once
or twice in SN2 reactions.
S S Ka(dithiane) S S Sulfur acetal forms carbonyl
Keq =
Ka(H-C4H9) C group after hydrolysis using
C
-33 Li Hg+2. Makes aldehydes and
H
dithiane
H Keq = 10-50 = 10+17 H
10 dithiane carbanion ketones.
Arrow-Pushing schemes for the above reactions
O Na O Na
Na H2 H2 Na
O H C O C H C
C H H H
R O R O H H R O R O H
carboxylic acids sodium hydoxide carboxylates alcohols sodium hydride alkoxides
H
H2 Na C Na C
H2 Na
C H O H C O C C Na
NR2
R S R S H H R R
thiols sodium hydoxide terminal alkynes sodium amide terminal acetylides
thiolates
H O O
Li Li Na
H2
N H2C C N
C CH3 C H NR2 C
H2 R C R CH2 Na
H2
LDA LDA
diisopropylamine n-butyl lithium lithium diisopropylamide ketones / aldehydes ketone enolates
O 2 eqs. O
O O
Na Na Na Na
R C H R C H C H C Na
NR2 NR2
O C O CR2 O C O CHR2
R2 R2
LDA ester enolates carboxylic acids LDA acid dianion
esters
N N Na Li
Na H2
C H C H2C C
C NR2 CR2 S S C CH3 S S
R2 C H2 CH
nitriles LDA nitrile enolate H H H Li
dithiane n-butyl lithium
dithiane carbanion
H H Li
Li H2
R H2 R R R
X H2C C X H2C C
C C C C CH3 C
C CH3
R PPh3 H2 R PPh3 R SPh2 H2 R SPh2
Wittig salt = ylid n-butyl lithium betaine sulfur salt = ylid n-butyl lithium betaine
Organometallics used in our course (Mg, Li and Cu)

Br Br
R Li R Br R Li
R Li
Li Li organolithium
bromohydrocarbons
discard reagents
Br +2
Mg Br Br R Mg Br
R R R
bromohydrocarbons Mg Mg R (MgBr)
Grignard reagents
(organomagnesium reagents)
Cu Br reacts with RBr (SN2)

Cu R
R Cu reacts with acid chlorides
R R Li R Li
Li reacts with ,-unsaturated C=O
dialkyl cuprates
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
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), azide (SN2 > E2) vs dialkylamides
(E2 > SN2) and metal hydrides (SN2 > E2) vs simple hydride (E2 > SN2). Higher basicity and steric hindrance in
either RX or the electron pair donor also favors E2 > SN2.
The following examples show 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.) It is the reactions at 2o RX
centers that are ambiguous.
2o RX structures are the most ambiguous.

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
Less basic, so SN2 > E2. More basic, so E2 > SN2. Less basic, so SN2 > E2. More basic, so E2 > SN2.
H Na H Li Na
H
N Na
H B H H Al H
N N K
H
N R R
Na H H hydrides
sodium borohydride
lithium aluminum hydride pKa of conjugate acid = 37
azide dialkyl amides
pKa of conjugate acid = 5 pKa of conjugate acid = 37 pKa of conjugate acid = ?
1. Making RBr from alkane and alkene hydrocarbons and alcohols
a. RBr from alkanes - mechanism using Br2 / h for free radical substitution of alkane sp3 C-H bonds to form sp3
C-Br bonds at the weakest C-H bond.
overall reaction Br
H2 h
C Br Br H Br
CH
H3C CH3
H3C CH3
1. initiation
h Br H = 46 kcal/mole
Br Br Br
weakest bond ruptures first
2a propagation
H BE = +95 kcal/mole
H H BE = -88 kcal/mole
Br C H Br
C H = +7 kcal/mole
H3C CH3 H 3C CH3 (overall) H = -15
2b propagation BE = +46 kcal/mole both steps
H H Br
BE = -68 kcal/mole
Br Br C Br
C H = -22 kcal/mole
H3C CH3 H3C CH3 (overall)
3. termination = combination of two free radicals - relatively rare because free radicals are at low concentrations
H
H Br
C Br
H3C CH3
C H = -68 kcal/mole
H3C CH3
CH3
H H
H3C CH H = -80 kcal/mole
C C
CH CH3
H3C CH3 H3C CH3
CH3 very minor product
Example reactions
CH4 Br2 / h
H3 C Br
achiral
Br2 / h achiral
Br
Br
Br2 / h enantiomers
(R and S)
Br2 / h Br
achiral
Br Br
2 Br2 / h can do E2 twice,
to make alkynes
Br
Br2 / h allylic substitution
b. 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 H3C C
H3C CH2 H2
1. initiation (two steps)

R O
h R O H = 40 kcal/mole
O R
O R
(cat.)
R BE = +88 kcal/mole
R H Br BE = -111 kcal/mole
O H Br
O H = -23 kcal/mole
reagent
2a propagation
H H
C BE = +63 kcal/mole
H3C CH2 Br BE = -68 kcal/mole
C Br
H3C C H = -5 kcal/mole
H2
2b propagation H
H2 BE = +88 kcal/mole H = -15
C Br C Br BE = -98 kcal/mole
H Br Br
H3C C H3C C both steps
H2 H2 H = -10 kcal/mole (2a + 2b)
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
H3C C H 3C C
H2 H2
CH3
H H H2
C CH Br H = -80 kcal/mole
Br C C Br
Br CH C
C CH3 H3C C H2
H2 H2
CH3 very minor products
Example reactions
H-Br / h
ROOR (cat.) Br achiral
Br2 / h
ROOR (cat.)
Br achiral
Br
Br2 / h
ROOR (cat.) R/S
enantiomers
Br
Br2 / h
ROOR (cat.) cis and trans
c. 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)
H2
overall reaction H 1. (BH3)2 C Br
C
2. Br2, CH3O H3C C
H3C CH2 H2
step 1 R
CH3 H3C H
H
B R B R
C C
H2C CH H2C C H
R
syn addition, with
H2C CH2 H at more substituted H2C CH2
C position and B at less C
H2 substituted position. H2
step 2
R
R R
H 3C H H3C H H3C H
B R
B R B R
C C C
H Br Br Br Br Br
H 2C C H2C C H2C C
H H
H 2C CH2 H2C CH2 H2C CH2 Br
C C C
H2 H2 H2
H3C O
R R
H3C H
R H3C H R
B B
C CH3 CH3
Br O C O
H2C C Br
H2C C
H
H2C CH2 H
H2C CH2
C
H2 C
H2
Example reactions
1. (BH3)2 Br
2. Br2, CH3O achiral
1. (BH3)2
2. Br2, CH3O Br achiral
Br
1. (BH3)2
2. Br2, CH3O R/S
enantiomers
1. (BH3)2 Br
2. Br2, CH3O
() or (dl) enantiomers
d. RBr from alcohols:
i. mechanism using HBr SN2 at methyl and 1o ROH; SN1 at 2o and 3o ROH, with possibility of rearrangements
acid H
H2 base H2 H2
C SN2 H
O H C O C Br
H3C C H Br Br H3 C C H O
H2 H3 C C
H2 H2
H
H
H H H H top
O O H Br H
acid H Br
H SN1
H3C C Br base H3C C
H3C C H3C C
CH CH3 CH CH3 C CH3 CH CH3
sp2 = flat
CH3 CH3 CH3 bottom CH3 S (top)
rearrangement
H Br
H2 H2
H3C C C H3C C
Br H3C
C CH3 C CH3 CH CH3
Br R (bottom)
CH3 achiral CH3 CH3
Example reactions
OH HI SN 2
I
OH Cl
SN2
HCl R/S
enantiomers
SN1
HBr
achiral
OH Br
R OH
SN 1
HBr
Br achiral
S rearrangement
OH Cl
HCl SN2 or SN1
achiral
Br
HO H Br H2
H3C C H3C CH
C C CH3 CH CH3
H3C
CH CH3 HBr CH3 major CH3 minor
achiral R/S
CH3 rearrangement enantiomers
CH3
CH3 Br
HBr Br
OH CH3
achiral (cis and trans)
ii. mechanism using PBr3 : SN2 at methyl and 1o ROH; SN1 at 2o and 3o ROH, with possibility of
rearrangements
H
H2 Br H2 H2 H
C O C O SN2 C Br
H3C C H P Br H3C C PBr2 O
H2 H2 H3C C
Br Br H2
PBr2
PBr2
H H
H H H H Br
O Br O SN1 H
H3C C C
H3C C H 3C C H3C
P C CH3
CH CH3 CH CH3 CH R CH3
Br Br
CH3 adds to CH3
CH3 CH3 Br both faces
rearrangement H Br
H2 H2 H3 C C
H3 C C C CH CH3
Br H3 C S
C CH3 C CH3
Br CH3
CH3 achiral
CH3
Example reactions
P/I2 = PI3 SN 2
OH I
OH Cl
SN 2
PCl3 R/S
enantiomers
SN1
PBr3
achiral
OH Br
R OH
PBr3 SN 1
Br achiral
S rearrangement
OH Cl
PCl3
SN2 or SN1
achiral
Br
HO H Br H2
H 3C C H3C CH
C C CH3 CH CH3
H3C
CH CH3 PBr3 CH3 major CH3 minor
SN 1 achiral R/S
CH3
CH3 Br
PBr3 Br
OH SN 1 CH3
iii. mechanism using SOBr2 SN2 at methyl and 1o ROH; SN1 at 2o and 3o ROH, with possibility of rearrangements
O
O Br
H2 O S
C O S H2
H2 Br
H3C C H S Br C O
H2 C O
Br Br H3 C C H
H3 C C H H2
H2
Br SN2
O O O
S H S H2
S C
Br Br Br
O O Br H3C C
O H2
H
H
O O
Br
H
S S H
H H O Br Br
O H H H C
O H O H3C
C CH3
H3C C S
H3C C H3C C
CH CH3 Br Br SN1
CH CH3 CH CH3 CH3 Br
CH3 adds to
CH3 CH3 both faces
rearrangement Br H
O O O H2 H3 C C
H2 H 3C C CH R CH3
S S S C Br
H3C C CH3
Br C CH3
O O CH3
O
H H Br CH3
CH3 achiral H Br
H
Br Br
H3C C
CH CH3
S
CH3
Example reactions
OH SOCl2 SN2
Cl
OH Cl
SN2
SOCl2 R/S
enantiomers
SOBr2 SN1
achiral
OH Br
R OH
SOBr2 S N1
Br achiral
S rearrangement
OH Br
SOBr2
SN2 or SN1
achiral
Br
HO H Br H2
H 3C C H3C CH
C C CH3 CH CH3
H3C SOBr2
CH CH3 CH3 major CH3 minor
SN1 achiral R/S
CH3
CH3 Br
SOBr2 Br
OH SN1 CH3
iv mechanism using 1. TsCl/pyridine 2. NaBr SN2 at methyl, 1o and 2o ROH, avoids rearrangements
O
O Ar N Ar
H H O N S
O S Cl
H H O
H H O
C Cl S O O
H3C
CH CH3 H3C C
H3C C
O CH CH3
CH3 CH CH3
avoids rearrangement
CH3
at 2o centers CH3
O
Ar
O H Br
Ar S N H
H3C C NaBr O H O
S
CH CH3 Cl
O O C
H3C
CH3 CH CH3
CH3 Br
Example reactions
1. TsCl / py.
OH 2. NaBr Br 1. acyl substitution
2. SN2
OH Br
1. TsCl / py. 1. acyl substitution
2. NaBr 2. SN2
R S
1. TsCl / py.
2. NaBr SN1
achiral
OH Br
R OH S I
1. TsCl / py. chiral
2. NaI
1. acyl substitution
S S 2. SN2
Br
OH 1. TsCl / py. achiral
2. NaBr
1. acyl substitution
2. SN2
HO H H Br
H3 C C 1. TsCl / pyridine H3C C

CH S CH3 2. NaBr CH R CH3
SN1 enantiomer
CH3 CH3
R S
OH I
1. TsCl / pyridine
R 2. NaI R
enantiomer
SN1
2. SN2 reactions using RBr compounds:
a. mechanisms using NaOH, SN2 at methyl and 1o RBr; E2 > SN2 at 2o and only E2 at 3o RBr,
H H H
SN2
O C Br O C Br
H H H
H H
D H D
SN2
O C Br O C S
Br
H H R S H
CH2 H2C
H3C CH3
H
H H
O C Br
H H C S O C R
H2 E2 > SN2 Br
CH3 CH3
Ha C E2 (-CH2-H) E2 (-CHa-H) H2C
E2 (-CHb-H) CH3
SN2
Hb
Example reactions
SN2
NaOH OH inversion of
Br configuration
E2 > SN2
Br OH
NaOH
R S
E2
NaOH
Br
R Br
E2 > SN2
NaOH
S S
OH
Br achiral
NaOH
SN2
b. mechanisms using NaOCH3, SN2 at methyl and 1o RBr; E2 > SN2 at 2o and only E2 at 3o RBr,
H H3C H
SN2
O C Br O C Br
H3C H H
H H
D H3C D
SN2
O C Br O C S Br
H3 C H R S H
CH2 H2C
H3C CH3
H
H3C H
O C Br
H3C H C S O C R
H2 E2 > SN2 Br
CH3 CH3
Ha C E2 (-CH2-H) E2 (-CHa-H) H2C
E2 (-CHb-H) CH3
SN2
Hb
Example reactions
CH3 SN2
NaOCH3 O inversion of
Br configuration
E2 > SN2
CH3
Br O
NaOCH3
R S
NaOCH3 E2
Br
R Br
NaOCH3 E2 > SN2
S S
CH3
O
Br achiral
NaOCH3
SN 2
c. mechanisms using NaO2CCH3, sodium carboxylates, SN2 at methyl 1o and 2o RBr; and only E2 at 3o RBr
Ester synthesis (can hydrolyze with NaOH (base) to ROH and RCO2H, providing an alternate approach to
secondary alcohols).
CH3
H O C H
H3C O H3C O SN2
O C Br O C Br
C H H C
H H
O O H H
O
D H3C C D H D
SN2
H3C O C Br S O C S
O C NaOH
C H R
H H
CH2 Br H2C H2C
O H3C CH3
CH3
H O
H3C O C Br H H H
H3C C
C H C S SN2 > E2 NaOH R
H2 R O C
O C
CH3 CH3
O Ha C CH3
H2C H2C
Br CH3
Hb CH3
Example reactions
O O
H 3C Br Na SN 2
C C CH3
R O R O
O
O
Br Na C R
C
O SN2 > E2
R O
achiral
C R
OH
O NaOH / H2O
acyl
2o alcohol substitution
O
Br Na
C E2
R O
O
O SN2
Na C
Br C O R
R O allylic and benzylic, very fast SN2 reactions
O
Na
C
Br no reaction
R O
d. mechanism using potassium t-butoxide, KOC(CH3)3, SN2 at methyl and E2 at 1o, 2o and 3o RBr,
H3C H SN2 H3C H

O
C C Br O C
H3C Br
H H
CH3 H H
D H H
E2 D
C Br C C D
H3C
O H R Z
CH3 C C E Br
C Ha C Hb H3C
H3C CH3 Ha
CH3 Hb
H
H3C
O C Br
C H C S E2 (-CH2-H)
H3 C H2 E2 Br
CH3 CH3
Ha C E2 (-CHb-H)
Hb E2 (-CHa-H)
Example reactions
E2 > SN2
KOC(CH3)3 anti
Br elimination
Br
KOC(CH3)3 E2
KOC(CH3)3 E2
Br
R Br
KOC(CH3)3 E2
S S
H3C
CH3
Br C
KOC(CH3)3 O CH3 S N2
no other
option
e. mechanism using NaSH, SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr,
H H H
SN2
S C Br S C Br
H H H
H H
D H D
SN2
S C Br S C Br
H H R S H
CH2 H2C
H3C CH3
H
H H
S C Br
H H C S SN2 S C Br
H2 R
CH3 H
Ha C H2C
CH3
Hb
Example reactions
SN 2
NaSH SH inversion of
Br configuration
Br SH
NaSH SN 2
R S
NaSH E2
Br
R Br S SH
NaSH
SN 2
S S
SH
Br achiral
NaSH
SN2
f. mechanism using NaSCH3, SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr,
H H3 C H
SN2
S C Br S C Br
H3C H H
H H
D H3C D
SN 2
S C Br S C Br
H3C H R S H
CH2 H2C
H3C CH3
H
H3C H
S C Br
H3C H C S SN2 S C Br
H2 R
CH3 H
Ha C H2C
CH3
Hb
Example reactions
SN 2
CH3
NaSCH3 S inversion of
Br configuration
CH3
Br S
NaSCH3
SN 2
R S
NaSCH3 E2
Br
R Br S S
CH3
NaSCH3
SN2
S S
CH3
Br S achiral
NaSCH3
SN2
g. mechanism using NaCN, SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr,
H H
SN2
C C Br N C C Br
N H H
H H
D D
SN2
C C Br N C C Br
N H R S H
CH2 H2C
H3C CH3
H
H
C C Br
N H C S SN2 N C C Br
H2 R
CH3 CH3
Ha C H2C
CH3
Hb
Example reactions
SN2
NaCN C inversion of
Br configuration
N
N
Br C
NaCN
SN 2
R S
NaCN E2
Br
N
R Br S C
NaCN SN 2
S S
Br C achiral
NaCN N
SN2
h. mechanism using NaCC-R, SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr,
H H
SN2
C C Br R C C C
C Br
H
R H
H H
D D
SN2
C C Br R C C C S Br
C H R
H
R CH2 H2C
H3C CH3
H
Br
D
C C Br
C H C S R
H2 E2 > SN2 R C C C
R
CH3 CH3
Ha C E2 (-CH2-H) E2 (-CHa-H) E2 (-CHb-H) H2C
S N2 CH3
Hb
Example reactions
SN2
NaCC-R inversion of
Br configuration
R
Br
NaCC-R
R E2 > SN2
NaCC-R E2
Br
R Br
NaCC-R E2 > SN2
S S
C achiral
Br NaCC-R C
R SN2
i. mechanism using 1. NaN3, SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr 2. LiAlH4 3. Workup,
makes 1o amines (RNH2)
H
H N
H
N N H H Al H
C Br SN2 N
N H H2N C
N C H Wk N
N H H
Br H H
H S N2
D N H
D D
N C Br SN2 N S N
N H R S H Al H H2N C
N C N
N CH2 H
H3C H H Wk
Br H2C H2C
CH3 CH3
SN2
H
C Br N
N H H N
N H C S N H Al H R
H2 SN2 N
N C H2N C
CH3 N
Ha C R H Wk
CH3 CH3
Br H2C H2C
Hb S N2
CH3 CH3
Example reactions
1. NaN3
2. LiAlH4 SN2
Br NH2 twice
3. workup
Br NH2
1. NaN3
2. LiAlH4
3. workup SN2
R S
1. NaN3
2. LiAlH4 E2
3. workup
Br
R Br S NH2
1. NaN3
2. LiAlH4 SN2
3. workup
S S
Br 1. NaN3 NH2 achiral

2. LiAlH4
3. workup SN 2
j. mechanism using 1. Na+ imidate, SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr 2. NaOH
O O 2 O
Br
Na 1
N H N N
acid/base
O H rxn Na SN 2
rxns
imidate
imide O O alkyl imide O
Ka1 -8
10 resonance stabilized makes
Keq = = = 10+8
Ka2 imidate less basic and a better
10-16 behaved nucleophile O H
3
acyl substitution #1 Na
O H reaction leads to
O O H
O O a primary amine O
acid/base
N
N
N N
H
H
O H
O
O acyl substitution #2 O O OH
O 10-5
O Keq = +10
= 10
10-15
O H
O
H N N
O O
H H
acid/base
-5 rxn
10 throw away primary amine
Keq = = 10+32 also made by
10-37
O 1. NaN3
O 2. LiAlH4
O
Look at similarities with ester hydrolysis, just above. O 3. workup
Example reactions
O
1. NaOH
N H 2. 1. SN2
Br 2. acyl substitution
NH2
O 3. NaOH (2 times)
O
1. NaOH NH2
2. Br
N H
R
SN2
O 3. NaOH S
O 1. NaOH
2.
N H E2
Br
O 3. NaOH
1. NaOH
O 2. R Br NH2
S
N H
S SN2
O 3. NaOH S
k. mechanism using ketone enolates, SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr (See acid/base reactions at
the beginning for synthesis of LDA.)
O
O O
N H H3C C H
Li
R R C SN 2
C H C Br H2C C
H3C C LDA H3C CH2 H
H2 H
H
-78oC H
O O
O
N Li D
SN 2 H3C C D
C H R R C C Br S
H3C C LDA
H3C CH2 H R H2C C
H2
-78oC CH2 H
H3C H2C
CH3
H
O O O
N Li
R R H3C C H
C H C C Br
LDA SN 2
H3C C CH2 H C S C
H2 H3C H2C
H2 R
-78oC CH3 CH3
Ha C H2C
CH3
Hb
Example reactions
O O
o SN2
1. LDA, -78 C
inversion of
2. configuration
Br
O
O 1. LDA, -78oC
2. Br
SN 2
R
S
O 1. LDA, -78oC
2.
E2
Br
O
O S
R Br
SN 2
S
S
1. LDA, -78 C o O
O
2. achiral
Br
SN2
l. mechanism using ester enolates, SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr,
O
O O
N H RO C H
Li
R R C SN2
C H C Br H2C C
RO C LDA RO CH2 H
H2 H
H
-78oC H
O O
O
N Li D
SN2 RO C D
C H R R C C Br S
RO C LDA
RO CH2 H R H2C C
H2
-78oC CH2 H
H3C H2C
CH3
H
O O O
N Li
R R RO C H
C H C C Br SN2
RO C LDA
H2 RO CH2 H C S H2C C
o
H2 R
-78 C CH3 CH3
Ha C H2C
CH3
Hb
Example reactions
O O
SN2
R 1. LDA, -78oC
R inversion of
O 2. O configuration
Br
O
O
1. LDA, -78oC
2. Br
R
O SN2
R
S
O 1. LDA, -78oC
2.
R E2
O
Br
O
1. LDA, -78oC
O
2. R Br S R
O
R
O SN2
S S
O
O 1. LDA, -78oC
2. R
Br O achiral
R
O S N2
m. mechanism using acid dianion enolates, SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr,
O
O O
N Li H HO C H
R R C SN2
C H C Br H2C C
O C LDA O CH2 H
H2 3. Wk H
H
-78oC H
O O
O
N Li D
SN2 HO C D
C H R R C C Br
LDA
O C O CH2 H R H2C C S
H2 3. Wk
-78 Co CH2 H
H3C H2C
CH3
H
O O O
N Li
R R HO C H
C H C C Br
LDA SN2
O C CH2 H C S C
H2 O H2C
o
H2 R
-78 C CH3 3. Wk CH3
Ha C H2C
CH3
Hb
Example reactions
O O
1. 2 eqs. LDA
2. SN2
H Br H
O 3. workup O
O 1. 2 eqs. LDA O
2. Br
OH
H SN 2
O R
3. workup S
1. 2 eqs. LDA
O 2.
H E2
O Br
3. workup
1. 2 eqs. LDA O
2. R Br
O
S H
O
H
O S SN2
3. workup S
1. 2 eqs. LDA O
O 2.
Br achiral
H OH
O SN2
3. workup
n. mechanism using nitrile enolates, SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr,
N N H C H
N Li
R R C SN 2
C H C Br H2C C
C LDA CH2 H
H2 Li H
H
-78oC H
N
N Li D
N N SN 2 C D
R R
C H C C Br
LDA S
C CH2 H R H2C C
H2
-78oC Li CH2 H
H3C H2C
CH3
H
N N
Li
N N H
R R C
C H C C Br SN2
LDA
C CH2 H C S H2C C
H2 H2 R
-78oC Li CH3 CH3
Ha C H2C
CH3
Hb
Example reactions
N 1. 2 eqs. LDA N SN2
C 2. inversion of
Br C
CH3 configuration
3. workup
1. 2 eqs. LDA
2. Br N
N C
C
CH3 R SN 2
3. workup S
1. 2 eqs. LDA
2.
N
C
E2
CH3 Br
3. workup
1. 2 eqs. LDA
2. R Br
N S
C C
CH3 N SN2
S S
3. workup
1. 2 eqs. LDA
2.
Br N
N C achiral
C
CH3 SN2
3. workup
o. mechanism using dithiane anions, SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr,
S H S H
H S Li
H2C H SN2
C Br CH C
C C H
H H
S S H S H
S D
H S SN2 S D
H2C H
C Br
C C CH C S
H R
H CH2 H
S S S
H3C H2C
Li CH3
H
S
H H2C S S H
H C Br SN2
C
C H C S CH C
H H2 R
S CH3 CH3
S Ha C S H2C
CH3
Li Hb
Example reactions
S S
1. n-BuLi SN2
2. inversion of
Br
S configuration
S
S 1. n-BuLi S
2. Br
S SN2
S R S
1. n-BuLi
S 2.
E2
S
Br
1. n-BuLi
S 2. R Br S S
S SN2
S S S
S 1. n-BuLi
2. S achiral
Br
S SN2
S
Hydrolysis of thioacetals (one as aldehyde and one as ketone)
Li
Li Br
Hg+
S S H2C Br Hg+2 S S
S S S S
C C
C C
H H 2. workup H
H H
1,3-dithiane Li
(also continued below to a ketone)
S S
S
Hg+ Hg+
Hg Hg+
S O S S S
S C H H C C
C H
O H O O
H H
O H H
H
H H
H
H H H
S
C resonance C C
Hg
O O H H O
S O
H aldehyde
H
Li Li
Br
S S H2C Br Hg+
Hg+2 S S
C S S S S
C C
C
H
2. workup
(from above) Li
S S
S
Hg +
Hg+ Hg+
S S
Hg
S O S C
S C H H C O
C
O H O H H
O
H H
H
S
C resonance C C
Hg
O O H H O
S O
H ketone
H
p. mechanism using LiAlH4 or NaBH4 (and deuterides), SN2 at methyl, 1o and 2o RBr and only E2 at 3o RBr,
D H H
Li
C Br S N2 D C
D Al D
H H
D H H
D D
H SN 2
Na C Br H C
H B H H R
H
CH2 H2C
H H3C becomes CH3
achiral
D H
Li C Br SN 2
D Al D H C S D C
H2 R CH3
CH3 H2C
D Ha C
CH3
Hb
Example reactions
SN2
LiAlD4 D inversion of
Br configuration
Br D
NaBD4
SN 2
R S
LiAlD4 E2
Br
R Br S D
NaBD4
SN 2
S S
Br D achiral
LiAlD4
SN 2
q. mechanism using diphenylsulfide to make diphenylsulfonium salt, SN2 at methyl, 1o and 2o RBr and only E2 at
3o RBr, used to make a diphenylsulfonium ylids, which are used to make epoxides with aldehydes and ketones.
Ph Ph
H Ph O
Br
S C S H CH2 1. n-BuLi
Ph Ph C 2. H2C=O S C
H H Ph CH2 H H
H H Li
Br
Ph = phenyl ylid salt
similar Ph Ph
mechanisms CH2 H2
S H2C S C
Ph O Ph C O
H2
H Br CH3
H Ph O
Ph Ph CH2
C Br 1. n-BuLi H2C
SN 2
S H R S C 2. H2C=O S C
CH2 H Li Ph C H H H
Ph Ph H2C
H3C
CH3
ylid salt
Ph
Ph
H2 H2
C CH2 S C
S Ph CH O
H3C HC
Ph
O
CH2
H3C
H
Ph Br CH3
H Ph O
C Br Ph CH2
S 1. n-BuLi H2C
H C S SN2 S C S
H2 2. H2C=O C
Ph R Li Ph C CH3
CH3 CH3 H H
Ha C Ph H 2C
CH3
Hb ylid salt
Ph
Ph
H2 H2
C CH2 S C
S Ph C O
H3C C
Ph H3C
O
H3C CH2
H3C
Example reactions
1. Br O
S SN2
2. n-BuLi inversion of
Ph Ph 3. H2C=O configuration
1. Br
R O
S
Ph Ph 2. n-BuLi SN 2
3. H2C=O S
1.
S Br
2. n-BuLi E2
Ph Ph
3. H2C=O
1. R Br O
S
Ph Ph S
2. n-BuLi SN 2
3. H2C=O
S
1.
Br O
S achiral
Ph Ph 2. n-BuLi SN 2
3. H2C=O
r. 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
Ph H Ph
Br Ph H O
SN2 Ph
Ph P C CH2 1. n-BuLi CH3
Ph P C 2. H2C=O P C
Ph H CH3 CH3 Li Ph C H CH3
Ph H H
ylid salt betaine
Ph = phenyl
H Ph O Ph O
Ph Ph Ph
C H H
H CH3 P C P C
Ph P O C Ph C CH3 CH3
Ph C
Ph Z alkenes
CH3 H CH3 H CH3
oxaphosphatane
Br H3 C
Ph H Ph O
Br Ph H
SN2 Ph
Ph P C CH2 1. n-BuLi CH2
P C P C
Ph 2. H2C=O
Ph C H CH3
Ph H3C CH2 CH2 Li
Ph CH3 CH3
H3 C ylid salt CH3 betaine
Ph = phenyl
H Ph O Ph O
Ph Ph Ph
C H H
H3C CH3 P C P C
Ph P O C Ph C CH3 CH3
Ph C
Ph Z alkenes
CH2 H3C CH2 H3C CH
2
H3C H3 C oxaphosphatane H3 C
Schlosser Modification of the Wittig reaction to make E alkenes
H OH2
H
H H H
O C
O C Ph3P O C O C
Ph3P acid/base Ph3P
R Ph3P
C H at -78oC R neutralize
R C R
C H C R
R The stereochemistry
R R H
betaine H2C of the alkene is
2 determined in this step.
flat sp carbon
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
Example reactions
1. Br
P
2. n-BuLi
Ph Ph Normal Wittig
3. CH3CH=O
Ph Z alkene preferred
1. Br
P R
Ph Ph 2. n-BuLi
Ph 3. CH3CH=O Normal Wittig
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. CH3CH=O Normal Wittig
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
P 3. CH3CH=O
4. -78oC, n-BuLi Schlosser modification
Ph Ph of the Wittig
Ph 5. HCl, warm
E alkenes preferred
3. SN1 reactions using RBr compounds:

a. RX compounds with water. SN1 conditions form carbocations with possible rearrangements. Alcohol
synthesis is the major product with E1 as minor product (unless reaction is run at high temperature).
H
H OH2
O H
Br O O
SN1 H H
top = bottom
H
H H2 O H2O H
H H top H O H H
Br O H H O
H
C H3C C H3C C
H3C H3C C
CH CH3 C CH3 CH CH3
CH CH3
S N1
sp2 = flat S (top) R (bottom)
CH3 CH3 bottom CH3
CH3
rearrangement
H2O
H2 H2 H2 O
H3C C H3C C O H
H2 H H O H
C CH3 H C CH3 H3C C
O O C CH3 H3C C
CH3 H3C C
CH3 CH CH3
H CH CH3
H achiral CH3
CH3 S (top)
CH3 R (bottom)
Example reactions
H2 O
H3 C Br no reaction
SN1 > E1
H2O OH
Br diastereomers
top & bottom
achiral
Br H2O OH SN1 > E1

top = bottom
H 2O SN 1
Br
Br
resonance stabilization of R+
H2O no reaction, vinyl

Br carbocation is too
unstable
b. RX compounds with alcohols. SN1 conditions form carbocations with possible rearrangements. Ether
synthesis is the major product with E1 as minor product (unless reaction is run at high temperature).
H
H OH2
O CH3
Br O O
SN1 CH3 CH3
top = bottom
H H
R
O H
Br H H top O
H
O H R R
H O H
C R H O R
H3 C H3C C
CH CH3 C CH3 C
H3C C
SN1 CH CH3 H3C
sp2 = flat CH CH3
CH3 CH3 bottom
CH3 S (top) R (bottom)
H CH3
R O rearrangement
H O
H2 H2
H3C C H3C C R O H
H2 R H O R
C CH3 H C CH3 H3C C
O O C CH3 H3C C
CH3 H3C C
CH3 CH CH3
R CH CH3
R achiral CH3
CH3 S (top)
CH3 R (bottom)
Example reactions
H3 C Br OH no reaction
SN1 > E1 diastereomers

top & bottom
Br OH achiral
O
Br O SN1 > E1
OH
top = bottom
OH SN1
Br O
OH no reaction
Br
c. RX compounds with liquid carboxylic acids. SN1 conditions form carbocations with possible
rearrangements. Ester synthesis is the major product with E1 as minor product.
OH
HO H O
O O
O
Br O O
SN1
top = bottom
HO
HO
O H
O
O
HO H O
Br H H top
O
H O H
H3 C C C H O
H3C
CH CH3 C CH3 C
H3C C
SN1 CH CH3 H 3C
sp2 = flat CH CH3
CH3 CH3 bottom
CH3 S (top) R (bottom)
CH3
HO
rearrangement
O
O
H2 H2
H3C C H3 C C O H
H2 H O
C CH3 C CH3 H3C C
O O C CH3 H3C C O
CH3 H 3C C
CH3 CH CH3
CH CH3
achiral H CH3
O O OH CH3 S (top)
CH3 R (bottom)
O
d. Oxidation of ROH with: CrO3 / pyridine (PCC). Synthesis of aldehydes or ketones.
O
O O
O N H
N Cr
H O H Cr O O
O O O
Cr H3C C
H3C C O O H3C C C H
C H C H H2 H
H2 H H2 H
E2
primary alcohols N
PCC = pyridinium chlorochromate oxidation O

of primary alcohol to an aldehyde (no water to O
hydrate the carbonyl group) N H O
H3C C
C H Cr
H2 O
aldehydes
H
CrO3 / pyridine
OH (PCC) oxidation
O
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. Oxidation of ROH with: CrO3 / acid / water (Jones). Synthesis of carboxylic acids or ketones.
H
O O
O O
O O
H H Cr Cr
O H H
O O O O O
Cr H H
O O
H 3C C H3C C H3C C
C H C H C H
H2 H H2 H H2 H
primary alcohols Jones = CrO3 / H2O / acid H
primary alcohols oxidize to carboxylic acids
(water hydrates the carbonyl group, O
which oxidizes a second time )
H H
H O
H
O O O
O O
Cr
H H
resonance H3C C O
H3 C C H3C C
C H C H hydration of C H
H2 H2 H2
the aldehyde
aldehydes (cont. in water)
O
H H H O
H H O
O O Cr
H H O H
O H H O O
H O O
H H Cr
H3C C O O O H3C C
H3C C O
C C O
H2 H H C H2
H2 H H H
H
second oxidation of the carbonyl hydrate
H
O O
O O O
Cr H H Cr
H O O O O
O H3C C H3C C
H
H H C O C O
H2 H2 H
carboxylic acids H
O
H H
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
d. Oxidation of ROH with: DMSO / ClOCCOCl / Et3N (Swern, many variations). Synthesis of
aldehydes or ketones.
O
O O O
O Et3N COCl C
Cl C C C Cl
O O
S C Cl
Cl
H3C CH3 S
O S
DMSO H3C CH3 H3C CH3 Cl
oxalyl chloride
CH3
Et3N
H
H S O
O O
O CH3
CH3 C C
H3C C H3C
H3C C S
C H
C H H2 O
H2 H
H Cl Cl
CH3 primary alcohols
S NEt3 CH3
H
O C
H2 O
S CH3
H3C C O CH2
C H H3C C
S
H2 H H3C C C H
H2 CH3
C H
H2 H aldehydes
H
DMSO / oxalyl chloride
(Swern) oxidation
OH
O
OH O
DMSO / oxalyl chloride
(Swern) oxidation
DMSO / oxalyl chloride no reaction

(Swern)
OH
OH DMSO / oxalyl chloride O

(Swern)
oxidation
OH DMSO / oxalyl chloride

(Swern) H
oxidation
e. RCO2H with thionyl chloride. Synthesis of esters. Amides, thioesters and anhydrides (Need to make
RCOCl with SOCl2 + acid.) There are a variety of approaches you could propose for this transformation.
O Cl O O
Cl Cl
O O S S S
Cl Cl Cl
O O O
C H S resonance resonance
R O Cl Cl C H C H C H Base
R O R O R O
O Cl
O
O S
Cl
O
Cl S
Cl O S
Cl C
O
C R C O R O
R C O
R O C
acylium ion Cl
R O H Base
resonance
ester synthesis from acid chloride and alcohols O

O Cl O Cl
H O R
O Cl O R
R O
R H
H
H
O
There are many variations of ROH and R
H
RCO2H joined together by oxygen. O
O
R H
amide synthesis from acid chloride and amines

O
Cl O Cl
O
R R
R H N N
N Cl R
H H H H
H2N
H
O
There are many variations of RNH2 or R2NH R
and RCO2H joined together by nitrogen. R
N
H3N
H
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
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. RNH2 with acid chlorides. Synthesis of amides. (Need to make RCOCl with SOCl2 + acid.)
O O
acyl
substitution
NH2 R Cl R N
H
O O acyl
NH2 substitution
R Cl R N
H
O O
acyl
substitution
R Cl R N
NH2 H
O O acyl
NH2 substitution
R Cl R N
H
O O
acyl
NH2 substitution
R N
R Cl H
h. RSH with acid chlorides. Synthesis of thioesters. (Need to make RCOCl with SOCl2 + acid.)
O O
acyl
substitution
R Cl R S
SH
O O acyl
SH substitution
R Cl R S
O O
acyl
SH substitution
R S
R Cl
i. RCO2H with acid chlorides. Synthesis of anhydrides. (Need to make RCOCl with SOCl2 + acid.)
O O O
O acyl
substitution
R Cl R O H
H OH
There is no 1C acid chloride, so the
anhydride works as a substitute.
j. ROH with sodium hydride, NaH. Synthesis of sodium alkoxides.
OH O Na
Na H acid/base
OH O Na
Na H acid/base
k. ROH with sulfuric acid / heat. Synthesis of alkenes (our only useful E1 reaction. Rearrangement is
possible).
H H
H O SO3H
O SO3H
H O H O H
H

(heat) H
O O E1
H H O SO3H H
slow step
H O SO3H
pKa = -10 water is a good H
secondary alcohol leaving group bp = +83oC
bp = +161oC alcohol alkene distills out
Tbp = 78oC
H  H H O
H CH3
O (heat) H H CH3
O H H
H O SO3H H3C C H3C C
C C C C
H rearrangement H
pKa = -5 slow step CH3 H H
CH3
alcohol 2o carbocation 3o carbocation
H3C
H
H3 C C
HO3S O H O H C CH3
alkene
(E1 mechanism) CH3
OH H2SO4 /  probably E2
OH
H2SO4 / 
E1
H2SO4 / 
E1
OH
OH
H2SO4 /  E1
OH
E1
H2SO4 / 
l. 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)
Br Br Br
2 eqs. Br2 H
h Na
H Na
N N
H R R N R R
H
R R 3rd equivalent
H most stable
a anion in mixture
O
H a H H Na
2. workup
H2 b
2.
H2 C
b Na
C X R
R
H
O SN2
c
O H c
CH H2O H 2.
b R CH C Na
R O R
b d d
HO 2.
H2O H O Na
O
The zipper reaction moves a triple bond in an unbranched linear chain to the end and allows all of the above
reactions.
H2
C CH2 CH2
C H Na C
N 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
C H H
R
C C
O
H H H H C
R
C
H2
j. Formation of conjugate base + addition of epoxide electrophile forms an alkynyl alcohol via SN2 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
Epoxide chemistry
a. Epoxides with aqueous hydroxide (followed by workup = neutralization).
O NaOH
H2O HO
OH achiral
2. WK
O NaOH HO R
H2O OH
chiral
R 2. WK
O NaOH OH
H2O OH achiral
2. WK
S OH
R
NaOH R OH
O H2O
2. WK S S OH
S S
S R OH
diastereomers
b. Epoxides with alcoholic alkoxide (followed by workup = neutralization).

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.

H2SO4 / ROH
O HO
(ROH2+) achiral
OR
2. WK
O H2SO4 / ROH S
(ROH2+) OH 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 R
NaCN C
DMSO chiral
R N
2. WK
O NaCN OH N
DMSO C achiral
2. WK
N
R
S C
NaCN
O DMSO and SRR
S S 2. WK
S S OH
diastereomers
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 achiral
HO
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.
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
2. WK CH3
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 2. WK S
S
S S OH
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
1. H3C organolithium reagent HO

O
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 achiral
O
3. NaOH
4. WK
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
3. NaOH achiral
NH2
4. WK
O
R 1. R NH2
NaOH R OH
O N H
S S
2. epoxide O S S OH S S NH2
3. NaOH
4. WK not stereoismers
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
(H3O+) OH
carbonyl hydrate
O OH
H2SO4 / H2O
(H3O+) OH
carbonyl hydrate
b. Aldehydes and ketones in aqueous base form carbonyl hydrates.

O
NaOH
HO OH
H2O
H carbonyl hydrate
H
O
NaOH
H2O HO OH
carbonyl hydrate
O OH
NaOH
H2O OH
carbonyl hydrate
O OH
NaOH
H2O 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
O
Zn / HCl
e. Aldehydes and ketones with hydrazine and base (Wolff-Kishner reduction).

O
H2NNH2 / RO / D
H Wolff-Kishner reduction
O
H2NNH2 / RO / D
Wolff-Kishner reduction
O
H2NNH2 / RO / D
O
H2NNH2 / RO / D
f. Aldehydes and ketones with LiAlH4 (LAH).

1. LiAlH4
O
2. WK
OH achiral
H
O OH
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
O OH
1. NaBH4
2. WK
O OH OH
1. NaBH4
2. WK
OH OH
O
1. NaBH4 R S
2. WK
chiral enantiomers
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
cyanohydrins
O HO N
C
1. NaCN
2. acid addition
cyanohydrins OH
O N
C
1. NaCN
2. acid addition
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
O OH R
Na
1. R
2. WK
O OH
Na
1. R R
2. WK
j. Aldehydes and ketones with LDA makes enolates (carbanion nucleophiles).

O
O Li enolate
N
R R
lithium diisopropylamide (LDA) H
H
O enolate O
N Li
R R
O enolate
O
N Li
R R
O
N Li O
R R enolate
k. Aldehydes and ketones with Grignard (Mg) reagents.

1. H2 OH
O 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
l. Aldehydes and ketones with organolithium reagents.

1. H3C OH
O
HC Li organolithium
reagent
H3C
H enantiomers (R & S)
2. WK
1. H3C OH
O
HC Li organolithium
reagent
H3C
O 1. H3C OH
HC Li organolithium
reagent
H3C
2. WK diastereomers (cis & trans)
O 1. H3C OH
HC Li organolithium
reagent
H3C
m. Aldehydes and ketones with cuprates.
1. (CH3)2Cu Li
O
cuprate Cuprates react slowly with
reagent ketones, esters and aldehydes.
2. WK
H
O
1. (CH3)2Cu Li
2. WK
O
1. (CH3)2Cu Li
2. WK
O O
1. (CH3)2Cu Li
cuprate
reagent
2. WK conjugate addition
to a,b-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
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
q. Aldehydes and ketones primary amine + NaBH3CN = secondary amine synthesis.

1.
O 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. NaH BCN
3
H 3. WK
O 1.
N
NH 2. NaH BCN
3
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
t. Aldehydes and ketones with 1. LDA 2. RX = alkylation of C=O.

O
O 1. Li
N
R R H
H achiral
2. RX (R = Me, 1o, 2o) R
O
1. Li
N O
R R
lithium diisopropylamide (LDA) R
2. RX (R = Me, 1o, 2o) achiral
enantiomers and diastereomers
O (RR, SS, RS, SR)
1.
N Li O
R R
2. RX (R = Me, 1o, 2o)
R
O R
1. Li
N
R R O
2. RX (R = Me, 1o, 2o)
u. Aldehydes and ketones with 1. LDA 2. epoxide = alkylation of C=O.

O
1. N Li
O R R H
O OH
H 2. epoxide
S
S
O
1. N Li
O R R
H
O
2. epoxide OH
S
1. N Li
O
R R
O
OH
O
2. epoxide
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 ,-unsaturated carbonyl compound.
Li O
1. 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
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.
Show the products of the following miscellaneous reactions.
other possible reactions
cuprates
Sulfur ylids
Phosphorous ylids (4 variations)
Ketals / acetals
Imines  amines  amides

Organic Reactions Study Guide Summary

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Organic Reactions Study Guide Summary

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Typical First Year Organic Reactions Beauchamp 1

Organic Reactions Summary

For Use as a Study Guide

LDA = lithium diisopropylamide

Arrow-Pushing schemes for the above reactions

Organometallics used in our course (Mg, Li and Cu)

Cu Br reacts with RBr (SN2)

SN2 versus E2 choices at 2oRX.

2o RX structures are the most ambiguous.

1. Making RBr from alkane and alkene hydrocarbons and alcohols

1. initiation (two steps)

() or (dl) enantiomers

d. RBr from alcohols:

H3 C C 1. TsCl / pyridine H3C C

2. SN2 reactions using RBr compounds:

NaOCH3 E2 > SN2

H3C H SN2 H3C H

NaCC-R E2 > SN2

Br 1. NaN3 NH2 achiral

Hydrolysis of thioacetals (one as aldehyde and one as ketone)

Schlosser Modification of the Wittig reaction to make E alkenes

3. SN1 reactions using RBr compounds:

Br H2O OH SN1 > E1

H2O no reaction, vinyl

SN1 > E1 diastereomers

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

PCC = pyridinium chlorochromate oxidation O

CrO3 / acid / H2O

OH CrO3 / acid / H2O O

OH CrO3 / acid / H2O

DMSO / oxalyl chloride no reaction

OH DMSO / oxalyl chloride O

OH DMSO / oxalyl chloride

ester synthesis from acid chloride and alcohols O

amide synthesis from acid chloride and amines

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

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

c. Epoxides with aqueous acid.

d. Epoxides with alcoholic sulfuric acid.

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

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

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

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

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

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

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

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

1. H3C organolithium reagent HO

1. H3C organolithium reagent

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

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

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

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

f. Aldehydes and ketones with LiAlH4 (LAH).

g. Aldehydes and ketones with NaBH4.

i. Aldehydes and ketones with terminal acetylides.

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

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

l. Aldehydes and ketones with organolithium reagents.

m. Aldehydes and ketones with cuprates.

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

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

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