CHEM 330
Problem set 5
ANSWERS
1.
Predict the structure of the major product arising from the following reaction
sequences. Assume that aldehydes possessing an α-stereogenic carbon will react with
achiral enolates in accord with the Cram-Felkin or the Felkin-Anh model, as appropriate
(as briefly mentioned in class, this is not always the case).
Note: it is understood that each sequence ends with an aqueous workup.
1. LDA, THF /
HMPA, –78°C
O
a.
OEt
O
H
O
H
–78°C
2. Ph–CHO
O
c.
1. LDA,
THF
N
d.
OEt
O
Et3N
2. Ph–CHO
O
f.
H
Ph
Ph
H
Et3N
2. Et–CHO
N
2. O-TBS
CHO
Me
OEt (±)
OH O
(±)
H
OH O
H
Me
1. LDA, THF
–78°C
(±)
N
OH O
H
Me
1. 9-BBN-OTf
O
g.
–78°C
2. Et–CHO
(±)
H
H
(±)
N
OH O
–78°C
2. Me-CHO
1. Cy2BCl
e.
OH
H
Ph
H
1. LDA,
THF
O
OH O
2. Et–CHO
1. LDA,
THF
b.
H
Ph
TBSO
(±)
OH O
N
Problem set 5
p. 2
1. Cy2BCl
Et3N
O
h.
OH O
Ph
Ph
2.
Ph
MeO
CHO
OMe
1. LDA, THF
–78°C
O
i.
OEt
TBSO
OH O
2. O-TBS
CHO
OEt
Me
O
1. 9-BBN-OTf
Et3N
k.
OH O
O-TBS
CHO
2.
Me
1. LDA, THF /
HMPA, –78°C
O
l.
TBSO
OEt
OH O
OEt
2.
CHO
Me
O
1. LDA,THF
–78°C
m.
2.
HO
H
O
CHO
Me
n.
N
3. K2CO3
MeOH
Ph
N
Bn
Ph
OMe
H
1. Bu2BOTf,
Et3N
O
O
O
O
Me
o.
1. LDA
2. BnBr
O
O
O
2.
CHO
OMe
3. Aq. wrkp.
O
OH O
N
MeO
Bn
O
Problem set 5
2.
p. 3
Identify compounds A – E obtained as major products of the following reaction
sequences:
O
O
a.
DMSO,
(COCl)2
1. LDA
2. MeI
N
O
A
3. LiAlH4
4. Aq. wrkp.
Bn
B ;
O
A =
B =
H
O
b.
N
H
HO
O
D
E
3. cat. H+
heat
Et3N
3. K2CO3, MeOH
Bn
O
D =
3.
O
C =
H
1. BH3
2. H2O2,
NaOH
1. Bu2CuLi
2.
Br
C
2. B
3. Aq. wrkp.
then Et3N
HO
O
1. (Cy)2B-Cl,
Et3N
O
H
H
OMe
O
O
E =
The molecules shown below are fragments of known bioactive substances.
Propose a method to achieve their enantioselective chemical synthesis from the indicated
aldehydes. Be careful about protecting groups and relative/absolute configurations of
stereocenters. Assume the availability of all required reagents, chiral auxiliaries, etc.
OH OH
OH
a.
Bu
B
CHO
HO
O
O
N
Me
Bu
CHO
starting with
O
Ph
then aq. wrkp.
Ph
O
Xc
1. TBS-Cl
Et3N
TBSO
2. DIBAL
Ph
OH e.g., Pyr-SO3
DMSO, Et3N
Bu
TBSO
O
Ph
O
O
+
H
Bu
B
N
TBSO
(then aq.
O
OH O
1. DIBAL
Xc
workup)
2. TBAF
desired
product
Bn
OH
b.
starting with
O
CHO
O
Bu
Bu
B
CHO
O
O
N
Xc
then aq. wrkp.
O
HO
Bn
Bu
e.g., (COCl)2
DMSO, Et3N
H
TBSO
+
B
TBSO
(then aq.
Xc
workup)
O
TBSO
Bn
OH
TBSO
Xc
OMe
OH
OH
O
Xc
c.
O
OH O
same thing as . . .
TBAF
O
O
Bu
N
O
Xc
Et3N
O
O
O
TBS-Cl
desired
product
O
CHO
starting with
O
(hint – remember the Wittig reaction?)
Bu
O
H
Ph3P=CH-CHO
O
+
B
O
O
N
H
Bn
Bu
(then aq.
O
workup)
Xc
OH
2. Aq. LiOH
then mild H+
OH O
N
TBSO
1. TBS-Cl
Et3N
TBSO
N
O
CDI
(e.g.)
LDA
Li–O
O
desired
product
OMe
COOMe