Learning Group Problems 547
• Alkynes to alkenes• Alkenes and alcohols• Alcohols and alkyl halides• Alkenes and alkyl halides• Alcohols and ethers• Alkenes, epoxides, and 1,2-diols• Alkanes to alkyl halides• Alcohol silyl protecting group• Alcohols to carbonyl compounds
OHOH
(1) OsO4(2) NaHSO3(syn)
(1) Li, EtNH2(2) NH4
!
(anti) Markovnikov(1) Hg(OAc)2,THF/H2O(2) NaBH4orH2O, HA cat.
NaH or Na", K"
TsCl orMsCl, etc.
pyr
HA,heat
RO–, E2 elim.(best if RX is
2" or 3°, oruse bulky RO–)
I. HX(1" or 3")or if 1" or 2"II. PBr3orIII. SOCl2
HO–
(1" RX)orH2O(3" RX)
HX(Markov.)
HBr, ROOR,# (Anti-Markov.)
Br2, h$ or #(best if RH is 3")
Anti-Markovnikov(1) BH3:THF(2) H2O2, HO–
RCO3HC C
ONu:
H2O, HA or HO–
(anti)
TBSClimidazole
F–
H2, Ni2B (syn)or
CC
CC CC
C OHC
C O%C
C OTs(or Ms or Tf)
RX or ROTs(if RX or ROTs is 1")
R'O– (if RX or ROTs is 1")
C
C HC C XC C OR'C
OH
Nu
CC
C OTBSC
(a peroxy acid)
Oxidation/Reduction (Chapter 12)
(under acidic orbasic conditions)
C
O
Y
C
Y & H, R, or OH(also by alkeneoxidation, seeChapter 8)
Summary and Review Tools
Some Synthetic Connections of Alkenes, Alkynes, Alcohols, Alkyl Halides, and Ethers
Figure 11.4 Some synthetic connections of alkynes, alkenes, alcohols, alkyl halides, and ethers.
solom_c11_502-547hr2.qxd 15-10-2009 12:49 Page 547
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
Summary of Reactions 583
Summary of Reactions
Summaries of reactions discussed in this chapter are shown below. Detailed conditions for thereactions that are summarized can be found in the chapter section where each is discussed.
Substrate
Aldehydes
Ketones
Esters
Carboxylicacids
(Hydrogen atoms in blue are added during the reaction workup bywater or aqueous acid.)
Reducing agent
NaBH4 LiAlH4 (LAH)
[H]
!
1. Carbonyl Reduction Reactions
• Aldehydes to primary alcohols• Ketones to secondary alcohols• Esters to alcohols• Carboxylic acids to primary alcohols
[H]
[H]
[H]
Synthetic Connections of Alcohols and Carbonyl Compounds
Substrate
Primary alcohols
Secondary alcohols
Tertiary alcohols
Oxidizing agent [O]
PCC H2CrO4 KMnO4
2. Alcohol Oxidation Reactions
• Primary alcohols to aldehydes• Primary alcohols to carboxylic acids• Secondary alcohols to ketones
[O]
[O]
[O]
R H
O
R R¿
O
R R¿
O
R R¿
O
R R¿
O
R OR¿
O
R OH
O
R H
O
R OH
O
R OH
O
R H
OH
H
R R¿
OH
H
R H
OH
H
R¿¬ OH
R R¿
OH
H
R H
OH
H
R H
OH
H
R R¿
OH
R–
R OH
R R¿
OH
solom_c12_548-584hr.qxd 1-10-2009 17:52 Page 583
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
584 Chapter 12 Alcohols from Carbonyl Compounds
Synthetic Connections of Alcohols and Carbonyl Compounds
(1)
(2) H3O! (or NH4!)
(2) H3O! (or NH4!)
(2) H3O! (or NH4!)
HR
XR
MgXR
Li ! LiXR
"R
Nu:
Nu # alkynyl group, or alkyl groupfrom Grignard or alkyllithium
reagent
(a substituted orunsubstituted oxirane
!
3. Carbon-Carbon Bond Forming Reactions
• Alkynide anion formation• Grignard reagent formation• Alkyllithium reagent formation• Nucleophilic addition to aldehydes and ketones• Nucleophilic addition to esters• Nucleophilic ring-opening of epoxides
NaNH2(or other
strong base)
2 Li
Mg in ether
(1)
(1) R OR¿
O
R¿(H) R–(H)
O
R¿(H) R–(H)
OH
Nu
R R¿¬ OHNu
OH
Nu
O
Nu
OH
See First Review Problem Set in WileyPLUS
solom_c12_548-584hr1.qxd 14-10-2009 15:46 Page 584
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
Summary of Mechanisms 775
R"(
H)
R'
O
R"(
H)
R'
R"(
H)
R'
O
OH
R
R!
O!
!
AH
HO
H
H
R"(
H)
R'
O!R
"A
H
R"(
H)
R'
RO
H–
HO
H
AH
O
R"(
H)
R'
RO
HO
!
R"(
H)
R'
RO
RO
R"(
H)
R'O
OR
ROH
HR
"A
I. H
emia
ceta
l and
ace
tal f
orm
atio
n: r
eact
ion
with
alc
ohol
s
Man
y st
eps
are
near
ly th
e sa
me
in a
cid-
cata
lyze
d re
actio
ns o
f ald
ehyd
es a
nd k
eton
es w
ith a
lcoh
ols
and
amin
es.
Com
pare
the
mec
hani
sms
vert
ical
ly to
see
the
sim
ilarit
ies
and
diffe
renc
es.
Not
e di
ffere
nces
in c
ompl
etio
n of
the
mec
hani
sm fo
r ea
ch ty
pe o
f pro
duct
.
In a
ceta
l for
mat
ion,
the
oxon
ium
ion
isat
tack
ed b
y a
seco
nd a
lcoh
ol m
olec
ule.
In im
ine
form
atio
n, th
e pr
oton
on
the
initi
al im
iniu
m io
n is
rem
oved
,le
adin
g to
the
stab
le im
ine
prod
uct.
II. Im
ine
form
atio
n: r
eact
ion
with
pri
mar
y am
ines
Hem
iace
tal
Ace
tal
III. E
nam
ine
form
atio
n: r
eact
ion
with
sec
onda
ry a
min
es
SU
MM
AR
Y O
F M
EC
HA
NIS
MS
Ace
tals
, Im
ines
, and
Ena
min
es:
Com
mon
Mec
hani
stic
The
mes
in T
heir
Aci
d-ca
taly
zed
Form
atio
n fr
om A
ldeh
ydes
and
Ket
ones
R"(
H)
R'
O
R"(
H)
R'
R"(
H)
R'
O
NH
HH
R
R!
N!!
AH
HO
H
H
R"(
H)
R'
N!R
H
R"(
H)
R'
NR
"A
HH
R"(
H)
R'
RO
H"
HO
H
AH
N
H
N R"(
H)
R'
RO
H
Imin
e
Ena
min
e
"A
In e
nam
ine
form
atio
n, a
pro
ton
is r
emov
ed fr
om a
car
bon
adja
cent
to th
e im
iniu
m c
arbo
n (b
ecau
se n
o pr
oton
is a
vaila
ble
for
rem
oval
from
the
nitr
ogen
).
R"(
H)
R'
O
R"(
H)
R'
R"(
H)
R'
O
NH
HR
R
R!
N!!
AH
HO
H
R
R"(
H)
R'
N!N!
RR
R"(
H)
C
NR
R
"A
"
A
RH
R"(
H)
R'
RO
H"
HO
H
AH
N
R
N R"(
H)
R'
RO
H
R"(
H)
C H
RR
solom_c16_729-778hr.qxd 6-10-2009 14:43 Page 775
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
776 Chapter 16 Aldehydes and Ketones
SU
MM
AR
Y O
F M
EC
HA
NIS
MS
Nuc
leop
hilic
Add
ition
to A
ldeh
ydes
and
Ket
ones
Und
er B
asic
Con
ditio
ns
Gen
eral
ized
nuc
leop
hilic
add
ition
to a
n al
dehy
de o
r ke
tone
:
Pro
tona
tion
durin
gw
orku
p(in
mos
t rea
ctio
ns)
or b
y pr
otic
sol
vent
s
Ald
ehyd
e or
keto
ne
Exa
mpl
es:
Nuc
leop
hile
Hyd
ride
[e.g
., fr
omN
aBH
4 or
LiA
lH4
(LA
H)]
Tetr
ahed
ral i
nter
med
iate
R"(
H)
R'
Nu!
""
Nu
O
! H
Alk
ynid
e an
ion
! C
C
R
Alk
yllit
hium
Li
R
Gri
gnar
d re
agen
t
XM
g
R
OH
A
R"(
H)
R'
Pro
ductN
u
O
R"(
H)
R'H
R
O
R"(
H)
R'H
Alc
ohol
(with
C¬
C b
ond
form
atio
n)
Alc
ohol
(with
C¬
C b
ond
form
atio
n)
R
Alk
ynyl
alc
ohol
(C¬
C b
ond
form
atio
n)
O
R"(
H)
R'H H
Alc
ohol
(red
uctio
n)H
O
R"(
H)
R'H
H
O
R"(
H)
R'
R
O
R"(
H)
R'
A !
! !Li
"
R
O
R"(
H)
R'
!
CC
R
O
R"(
H)
R'
!
CC
R
O
H
R"(
H)
R'
Cya
nohy
drin
CN
O
R"(
H)
R'
CN
O
R"(
H)
R'
!
X!
Mg2"
Cya
nide
! C
N
!
solom_c16_729-778hr.qxd 6-10-2009 14:43 Page 776
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
Summary of Mechanisms 777
SU
MM
AR
Y O
F M
EC
HA
NIS
MS
Nuc
leop
hilic
Add
ition
to A
ldeh
ydes
and
Ket
ones
Und
er B
asic
Con
ditio
ns
Gen
eral
ized
nuc
leop
hilic
add
ition
to a
n al
dehy
de o
r ke
tone
:
Pro
tona
tion
durin
gw
orku
p(in
mos
t rea
ctio
ns)
or b
y pr
otic
sol
vent
s
Ald
ehyd
e or
keto
ne
Exa
mpl
es(c
ontin
ued)
:O
xaph
osph
etan
ein
term
edia
teW
ittig
pre
para
tion
of a
lken
es(w
ith lo
ss o
f tri
phen
ylph
osph
ine
oxid
e [(
C6H
5)3P
O])
Nuc
leop
hile
Tetr
ahed
ral I
nter
med
iate
R"(
H)
R'
Pho
spho
rus
ylid
e
Eno
late
(see
Cha
pter
18)
Nu!
"P
(C6H
5)3
""
Nu
OO
HA
R"(
H)
R'
Pro
ductN
u
O
R"(
H)
R'H
b-H
ydro
xy a
nd a
,b-u
nsat
urat
edca
rbon
yl c
ompo
unds
A !
! R
1
R2
P(C
6H5)
3
R1
R2
R'
R'
R"(
H)
R2
R1
O R"(
H)
R4
O
R"(
H)
R'H
HR
3
O
R4
R4
R3
R3
HH
O
! A
R4
R'
(H)R
"
R3
OO
!
R4
O
R"(
H)
R'
HR
3
O!
!
!
(plu
s di
aste
reom
er)
solom_c16_729-778hr.qxd 6-10-2009 14:43 Page 777
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
778 Chapter 16 Aldehydes and Ketones
Syn
the
tic
Co
nn
ec
tio
ns
Som
e S
ynth
etic
Con
nect
ions
of A
ldeh
ydes
, Ket
ones
, and
Oth
er F
unct
iona
l Gro
ups
Cl
R¿
O
OR
OH
R–(
H)
R¿
SR
SR
R–(
H)
R¿
H
H
R–(
H)
R¿
OR
OR
R–(
H)
R¿
CC
R
OH
R–(
H)
R¿
CN
OH
R–(
H)
R¿ R
¿
R–(
H)
R3
R4
R¿
R–
R–
R¿ C
lR
¿
O
R"
R¿
O
HR
¿
O
OH
R¿
OO
R–
R¿
O
R–(
H)
R–(
H)
R¿
RN
RR
N
Clo
ckw
ise
from
cen
ter,
botto
m:
I. Pr
epar
atio
n of
ald
ehyd
esan
d ke
tone
s:
• Nitr
ile, e
ster
, acy
l
halid
e re
duct
ion
• Alc
ohol
oxi
datio
n• O
zono
lysi
s• F
riede
l–C
rafts
acy
latio
n• G
rigna
rd w
ith n
itrile
• Ace
tal a
nd h
emia
ceta
l h
ydro
lysi
s
II. R
eact
ions
of a
ldeh
ydes
and
keto
nes:
• Hem
iace
tal a
nd a
ceta
l for
mat
ion
• Thi
oace
tal f
orm
atio
n a
nd re
duct
ion
• Alk
ynid
e an
ion
addi
tion
• Nitr
ile a
dditi
on (
cyan
ohyd
rin fo
rmat
ion)
• Witt
ig s
ynth
esis
of a
lken
es• E
nam
ine
synt
hesi
s• I
min
e sy
nthe
sis
• Red
uctio
n to
alc
ohol
s (
left,
cen
ter)
RO
H,
cat.
HA
RO
H,
cat.
HA
RS
H (
2 eq
uiv.
),ca
t. H
A
H2O
,ca
t. H
A
H2O
,ca
t. H
A
H2,
Ran
ey N
i
H2O
,ca
t. H
A
R2N
H,
cat.
HA
RN
H2,
cat.
HA
(1)
R–M
gBr
or R
–Li
(2)
H3O
!
(1)
CH
R3 R
4 Br,
(C
6H5)
3P(2
) R
Li (
as s
tron
g ba
se)
(1)
ArH
, AlC
l 3;
(2)
HO
H(le
ads
to R
–=A
r)
(1)
LiA
lH(O
-t-B
u)3
(2)
H2O
SO
Cl 2
(1)
DIB
AL-
H(2
) H
2O
(1)
DIB
AL-
H(2
) H
2O
(1)
O3
(2)
Me 2
S(p
rodu
cts
depe
ndon
R g
roup
s)
CN
R¿
CN
R¿
(1)
RC
C
"
(2)
H3O
!
(1)
CN
"
(2)
H3O
!
(whe
n R
¿ bor
e a
hydr
ogen
for
rem
oval
)
(E)
and
(Z )
H2C
rO4
or K
MnO
4
NaB
H4;
or
(1)
LAH
; (2)
H2O
PC
C
R–
R¿
OH
OH
R¿
solom_c16_729-778hr.qxd 6-10-2009 14:43 Page 778
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
818 Chapter 17 Carboxylic Acids and Their Derivatives
17.13 Summary of the Reactions of Carboxylic Acids and Their Derivatives
The reactions of carboxylic acids and their derivatives are summarized here. Many (but notall) of the reactions in this summary are acyl substitution reactions (they are principally thereactions referenced to Sections 17.5 and beyond). As you use this summary, you will findit helpful to also review Section 17.4, which presents the general nucleophilic addition–elim-ination mechanism for acyl substitution. It is instructive to relate aspects of the specific acylsubstitution reactions below to this general mechanism. In some cases proton transfer stepsare also involved, such as to make a leaving group more suitable by prior protonation or totransfer a proton to a stronger base at some point in a reaction, but in all acyl substitutionthe essential nucleophilic addition–elimination steps are identifiable.
Reactions of Carboxylic Acids
1. As acids (discussed in Sections 3.11 and 17.2C):
2. Reduction (discussed in Section 12.3):
3. Conversion to acyl chlorides (discussed in Section 17.5):
4. Conversion to esters (Fischer esterification) or lactones (discussed in Section 17.7A):
5. Conversion to amides (discussed in Section 17.8E):
O
RNH3!
OH
O
R O! NH4"
O
R NH2
! H2O
An amide
heat
R#! !OH H2OOR#OHR
O
R
OHA
SOCl2 or PCl5
R OH
O
R Cl
O
!(1) LiAlH4
(2) H3O+
R OH R OH
H HO
Na! ! H2O
Na! ! H2O ! CO2
R OH
OR O–
O
R O–
O
NaOH
NaHCO3
Nylon 6,6(A polyamide)
! H2O
n
O
NN
HO
H
Special Topic C continues our discussion of Step-Growth Polymers.
solom_c17_779-830hr1.qxd 14-10-2009 16:06 Page 818
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
17.13 Summary of the Reactions of Carboxylic Acids and Their Derivatives 819
6. Decarboxylation (discussed in Section 17.10):
Reactions of Acyl Chlorides
1. Conversion (hydrolysis) to acids (discussed in Section 17.5B):
2. Conversion to anhydrides (discussed in Section 17.6A):
3. Conversion to esters (discussed in Section 17.7A):
4. Conversion to amides (discussed in Section 17.8B):
5. Conversion to ketones (Friedel–Crafts acylation, Section 15.7–15.9):
Cl
O
R! R!NHR" (excess)
NR!R"
O
R! R!NH2R"Cl
R! and/or R" may be H.
# $
pyridine
Cl
O
R! R!9 OH
OR!
O
R! Cl$ ! pyr-H#
Cl
O
R O
O
RO$
O
R! R!
O! ! Cl$
Cl
O
R! H2O
OH
O
R! HCl
heatR OH
O O+ c
R CH3
O
heat
CO2
+ cCO2HO OH
O O
OH
O
ClR
O R
O
!AlCl3
6. Conversion to aldehydes (discussed in Section 16.4C):
Reactions of Acid Anhydrides
1. Conversion (hydrolysis) to acids (discussed in Section 17.6B):
2. Conversion to esters (discussed in Sections 17.6B and 17.7A):
OR!R
O
OHR
O
! R!OH !R RO
O O
R
O
OH! H2O 2
R RO
O O
ClR
O
HR
O
!(1) LiAlH(t-BuO)3
(2) H3O+
solom_c17_779-830hr.qxd 6-10-2009 15:44 Page 819
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
820 Chapter 17 Carboxylic Acids and Their Derivatives
3. Conversion to amides (discussed in Section 17.8C):
4. Conversion to aryl ketones (Friedel–Crafts acylation, Sections 15.7–15.9):
Reactions of Esters
1. Hydrolysis (discussed in Section 17.7B):
2. Conversion to other esters: transesterification (discussed in Review Problem 17.10):
3. Conversion to amides (discussed in Section 17.8D):
4. Reaction with Grignard reagents (discussed in Section 12.8):
5. Reduction (discussed in Section 12.3):
OR!R
OR9CH2OH ! R!OH
(1) LiAlH4
(2) H3O+
!OR!R
O
2 R"MgXEt2O H3O
!
R99R" ! R!OMgX
R"
R99R"
R"
OHOMgX
HN!
R"
R# N! HR"
R#
R!O
R" and/or R# may be H.
OR!R
O
R
O
OR!R
O
OR"R
O ! R"OH ! R!OH
HA
OR!R
O
OHR
O ! H2O ! R!OH
OR!R
O
O$R
O ! OH$ ! R!OH
H2O
HA
!AlCl3
O R
!R OH
O
R RO
O O
NR R
O
R! and/or R" may be H.
!H
R!
R"
NR!
R"
!OH
O
R RO
O O
solom_c17_779-830hr.qxd 6-10-2009 15:44 Page 820
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
Key Terms and Concepts 821
Reactions of Amides
1. Hydrolysis (discussed in Section 17.8F):
2. Conversion to nitriles: dehydration (discussed in Section 17.8G):
Reactions of Nitriles
1. Hydrolysis to a carboxylic acid or carboxylate anion (Section 17.8H):
2. Reduction to an aldehyde with (i-Bu)2AlH (DIBAL-H, Section 16.4C):
3. Conversion to a ketone by a Grignard or organolithium reagent (Section 16.5B):
R
(1) R!MgBr or R!Li
(2) H3O!
OR9C#N !
R!
HR
(1) (i-Bu)2 AlH
(2) H2O
OR9C#N
H3O!
R9C#N
HO"
H2O, heatR9C#N
OHR
O
O"R
O
heat
R9C#NNH2R
OP4O10
heat("H2O)
R, R!, and/or R# may be H.
!NR
O
O"R
O
OH"H2O ! N
R#R#
R!R!H
!NR
O
OHR
O
H3O$H2O ! H9N9R!
R#R#
$R!
H
Key Terms and ConceptsThe key terms and concepts that are highlighted in bold, blue text within the chapter aredefined in the glossary (at the back of the book) and have hyperlinked definitions in theaccompanying WileyPLUS course (www.wileyplus.com).
solom_c17_779-830hr.qxd 6-10-2009 15:44 Page 821
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
868 Chapter 18 Reactions at the aa Carbon of Carbonyl Compounds
Sum
mar
y of
Mec
hani
sms
Eno
late
s: a
-Sub
stitu
tion
X
XX
O–
Car
bony
l
I. H
O–
in H
2O o
r R
OH
;
or R
O–
in R
OH
;U
sefu
l for
rea
ctio
ns in
volv
ing
ther
mod
ynam
ical
ly fa
vore
den
olat
es a
nd e
quili
briu
m p
rodu
ctco
ntro
l
II. L
DA
(lit
hium
diis
opro
pyla
mid
e)
in T
HF
or
DM
E;
Use
ful,
in g
ener
al, f
or fo
rmin
gen
olat
es in
apr
otic
sol
vent
s(e
spec
ially
kin
etic
ally
favo
red
enol
ates
and
dire
ct a
lkyl
atio
n)
Som
e gr
oups
that
incr
ease
a-h
ydro
gen
acid
ity
Gen
eral
Rea
ctio
n
Typi
cal b
ases
(– :A
)an
d so
lven
ts fo
ren
olat
e fo
rmat
ion
Pos
sibl
e el
ectr
ophi
les
(E–A
)P
rodu
ct(s
)
O
R
OA
–
A–
RR
Ha
d+
d–
H
Nitr
ile(c
yano
gro
up)
(and
in g
ener
al, o
ther
grou
ps th
at c
an s
tabi
lize
an a
-car
bani
on)
CN
H
Sub
stitu
tion
of e
nola
tea
hyd
roge
n by
H, X
, or
R
O
R
H
EA
Dep
roto
natio
n–pr
oton
atio
n(m
ay le
ad to
rac
emiz
atio
nor
epi
mer
izat
ion)
O
R
X
Hal
ogen
atio
n
R´
O
R
R´
AH
Alk
ylat
ion
O
R
E
+
+ st
ereo
isom
er (
if a
car
bon
is, a
nd/o
r if
E c
onta
ins,
a s
tere
ogen
ic c
ente
r)
a
See Special Topic C in WileyPLUS
solom_c18_831-868hr1.qxd 14-10-2009 16:09 Page 868
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
19.9 Summary of Important Reactions 897
19.9 Summary of Important Reactions
1. Claisen Condensation (Section 19.2):
2. Crossed Claisen Condensation (Section 19.2B):
3. Aldol Reaction (Section 19.4)General Reaction
Specific Example
OH–
H2O
–H2O2 RH
O
H
O
R
OH
R
RH
O
R
(1) C6H5CO2Et/NaOEt
Et/NaOEt
Et/NaOEt
Et/NaOEt
(2) H3O!
H3O!
H3O!
H3O!
(1) EtOCO(2)
O
(1) HCO2
(2)
(1) EtO2CCO2
(2)
O
R
OEt
O
OEt
OR
R
O OEt
OEt
O
ROEt
O
O H
ROEt
O
OO
OEt
(1) NaOEt
(2) H3O!
OEt
O
R2 R
O
R
OEt
O
±OH–
10°C–H2O
H
O
H
O
H
OOH
H
O
solom_c19_869-910hr.qxd 6-10-2009 19:21 Page 897
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
898 Chapter 19 Condensation and Conjugate Addition Reactions of Carbonyl Compounds
4. Directed Aldol Reactions via Lithium Enolates (Section 19.5B)General Reaction
Specific Example
5. Conjugate Addition (Section 19.7)General Example
Specific Example
Specific Example (Michael Addition)
6. Mannich Reaction (Section 19.8):
R
O
H H
O
H NR!
R"R
O
NR!
R"
! !
O
C6H5 C6H5
OC6H5 C6H5
OO
, HO–
MeOH
C6H5 C6H5
O
C6H5
H
CN
C6H5
OCN–
EtOH, HOAc
R¿
R–
R
O
R¿ R
OR–
HNu
(1) Nu – (or Nu¬H)
(2) H ¬ A
$
Nu–
Nu¬H=1º or 2º amines; an enamine=CN–; an enolate (Michael addition); R‡MgBr
LDA
THF, –78°C
O O–Li+ (1)
(2) NH4Cl
H
O
OH O
LDA
THF, –78°C(formation ofthe kinetic enolate)
RH(R¿)
O (1)
(2) NH4Cl
R‡R–
O
RH(R¿)
O–Li+R
OHR–R‡
H(R¿)
O
solom_c19_869-910hr.qxd 6-10-2009 19:21 Page 898
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
Summary of Mechanisms 909
2. Steroids are an extremely important class of natural and pharmaceutical compounds. Synthetic efforts directed towardsteroids have been underway for many years and continue to be an area of important research. The synthesis ofcholesterol by R. B. Woodward (Harvard University, recipient of the Nobel Prize in Chemistry for 1965) and co-workers represents a paramount accomplishment in steroid synthesis, and it is rich with examples of carbonyl chem-istry and other reactions we have studied. Selected reactions from Woodward’s cholesterol synthesis and thequestions for this Learning Group Problem are shown in the WileyPlus materials for this chapter. Access thosematerials online to complete this problem.
CholesterolHO
H3
10A
9
C
B
13
20
17
14D
H
H
Me
8
H
Summary of Mechanisms
Enolate Reactions with Carbonyl Electrophiles
O–
O
Michael (conjugate) addition
Acyl substitution (addition–elimination), e.g., Claisen condensation when LG=OR
R¿ R‡
O
R¿R¿R–
R–
OR–
RR¿
R–
R‡
O O
R*
* *R¿
R–
R‡
* may be chirality centers
O–
R
O
R¿ LG
A –
(elimination ifa hydrogen
present)(E ) and (Z )
O
R R¿
R–
R¿
O
R
H
HO
R–
O–
R´
O
RLG
O O
R R´
Aldol reactions (addition and condensation)
O–
R
O–
R
O–
O
R
H A
solom_c19_869-910hr.qxd 6-10-2009 19:21 Page 909
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
910 Chapter 19 Condensation and Conjugate Addition Reactions of Carbonyl Compounds
HA
• E
nola
te fo
rmat
ion
• K
eto–
enol
taut
omer
ism
• H
alog
enat
ion
• A
lkyl
atio
n•
Acy
latio
n
Rea
ctio
ns o
f X a
s LG
, etc
.
(1)
R4M
gBr
or
R4L
i(2
) H
3O+
X2,
base
(1)
RO
–
(2)
R4X
(1)
RO
–
(2)
R3X
(3)
HO
–
(4)
H3O
+ , h
eat
(3)
H3O
+
(2)
(1)
LDA
The
n de
carb
oxyl
atio
nif
R2
= O
R
• C
lais
en c
onde
nsat
ion
• A
ldol
rea
ctio
ns•
Add
ition
of G
rigna
rd a
nd R
Li•
Mic
hael
add
ition
• C
onju
gate
add
ition
of H
CN
• C
onju
gate
add
ition
of a
min
es
O
R1
X
O
R1
OO
R1
R2
OO
R1
R2
R3
O
R1
R3
R4
CO
2!
R2
O
R2
LG
O
R2
R3
O
R1
O
Eno
late
s pr
ovid
e m
any
way
s to
func
tiona
lize
the a
-car
bon
of a
ca
rbon
yl c
ompo
und.
Mos
t im
port
antly
, eno
late
s pr
ovid
e w
ays
to fo
rm
new
car
bon–
carb
on b
onds
. Som
e of
thes
e sy
nthe
tic c
onne
ctio
ns a
re
show
n he
re. P
revi
ousl
y st
udie
d re
actio
ns o
f car
bony
l, al
coho
l, an
d al
kene
func
tiona
l gro
ups
(e.g
., re
duct
ion,
oxi
datio
n, a
dditi
on,
subs
titut
ion)
lead
to o
r fr
om s
ome
of th
ese
path
way
s.
Str
ong
base
(e.g
., LD
A)
Eno
late
res
onan
ce c
ontr
ibut
ors
R2
O
R
R3
NR
5R6
O
R1
R3 R
2
R3
O
R1
OH R
2
CN
O
R1
R3 R
2
+1,4
add
ition
Syn
thet
ic C
onne
ctio
ns
Som
e S
ynth
etic
Con
nect
ions
Invo
lvin
g E
nola
tes
R4
O
R1
OR
3 R2
R4
H
O(1
) LD
A,
(2)
H3O
+
HN
R5R
6H
CN
HA
or
wea
k A
–
–
–
(1)
LDA
(2)
R2X
(1)
LDA
(2)
O
RH
a
OH
R1
R1
R2
OH
R
R3
R4
See Special Topics D and E in WileyPLUS
solom_c19_869-910hr.qxd 13-10-2009 17:55 Page 910
Resumen de Reacciones Química Orgánica II, DC Angel A. Ramos O.
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