BÀI TẬP - BÀI GIẢI TỔNG HỢP HÓA HỮU CƠ LUYỆN THI HSG QUỐC GIA (tập 1 - 2021)

BÀI TẬP
TỔNG HỢP HÓA HỮU CƠ

LUYỆN THI HSG
QUỐC GIA (tập 1)
Thạc sĩ Phạm Công Nhân

TAXOL


Fukuyama Group - Group Meeting Problems
2001/08/22

1
O

1) SOCl2, benzene;
Et3N, allyl amine
carboxylic acid

hν

Cl

C10H12O2

H2 O
acetone
O *

CN

2) PPh3, CCl4
Et3N, CH3CN

*) as acid scavenger

2

cat. Pd (0)
Et3B (2.4 eq)
Et3N (1.2 eq)
LiCl (1.0 eq)

HO
OHC

OH

+
THF
rt

HO

3
H2NOC

CONH2

1) NaNO2

6 N HCl
–45 °C to rt
2)

H 2N

N
Bn

N

3) liq NH3
CH3CN
45 °C

NC

4) 250 °C, neat
N
H

N

H 2N

POCl3, Et3N
CH3CN

4

CH2CH2OCOPh
hν (pyrex)

HO

O
Ph
OMe

minor

5

O 2N

COOH

1) CF3COCH3, NaHCO3, Oxone®
CH3CN-H2O, rt, pH7-7.5
2) 5% NaOH aq, MeOH
100 °C, 12 h

Ph
OMe

+

major

O

N
Bn

O
H

MeOH

N

CN

O 2N
88%


Fukuyama Group - Group Meeting Problems
08/29/2001

1
Me
N

Ph

CO2H

2. H

O

2

N

1. TFAA, Py
Ph

NH2

NH·HCl
K2CO3, DMF
70 °C

MeO

N
Me

COCF3

PdI2 (0.2 mol%)
KI (2 mol%)
CO/air (3:1, 600 psi )

O

MeO

CO2Me
CO2Me

MeOH
110 °C

O

O

O

Hint: active catalyst = K2PdI4

3

3) BuLi, THF
OH

O
–78 °C to rt

1) NBS

4) TMSCl (3 eq.), NaI (3 eq.)
CH3CN, rt

2) NaH, TsCl

4

1.

Br

CO2Et

NOH
Na2CO3
2. aq. NaOH, 20 °C
3. 150 °C

CN
OH

5
MeO O
O

N
N

CO2Me

toluene
reflux

O

OMe CO Me

2

A
A

30 h, 74%
(C6H8O2)
A : transient intermediate

OH

O








Fukuyama Group - Group Meeting Problems
09/05/2001

1
1) NaCN, DMSO, 130 °C
OAc

2) 0.5 mol% [Rh(CO)2Cl]2
toluene, 110 °C, 30 min
93%

CO2Me OBn

H
BnO

2
t-BuLi (5.5 eq), Et2O, –78 °C;
TMEDA, –78 °C to rt;

Br Br

PhCOCOPh

N
Ph

N
Ph

OH
Ph
Ph
OH

3
LTA (1.5 eq)
CO (105 atm)
OH

4

O

O
O

benzene, 80 °C
63%

O

O
Cu powder

1N HCl

PhH
reflux
3.5 h

THF
65 °C
1h

O
+

N2

O

5

n-Bu

O

CO2Et

Br Br

O
:

9
t-BuLi (4 eq)
A

THF
–78 °C

O
CO2Et

n-Bu

1) A
THF, –78 °C

CO2Et

+

2) H (silica gel)
benzene, reflux

H

1


Fukuyama Group - Group Meeting Problems
09/12/2001
O

1

n-BuLi
THF, –78 °C, 20 min;
O
O

then

HO

O

·

N
O

F3C

CF3

F3C

OH
HFIP

–78 °C to –30 °C, 1 hr;
then HCl / HFIP-TFE
–78 °C to rt

OH
TFE

2

CH2N2, Et2O
0 °C, 2 h;
evap;
H
O

H
Cl

Cl

cyclopentadiene (10 eq*)
Et3N (3 eq*)
TFE /Et2O (1 : 1)
–78 °C to rt

78% (86%ee)

1) LAH, Et2O, 0 °C

C13H13ClO

H
H

2) KH (5 eq*), THF
0 °C to rt

74%
76% (2 steps)

(two isomer 10.4 : 1)

TFE = trifluoroethanol

*

ϓϙ Rκ☰aR✤⒴a

3
O

OH

CF3CO3H (8eq*)

O

+

O

CF3CO2H, CH2Cl2

*

ϓϙ Rκ☰aR✦⒴a

OH

4
MeO2C

1. propargyl alcohol
PhI(OAc)2, CH3CN

OH

MeO2C

Bu

O

CO2Me
MeO2C
Bu

2. Ph3SnH, Et3B
toluene
3. 1 M HCl, Et2O

O
OH
O

5

Bn
R
N
H

N

CHO

HN

Bn
CO2Me

H
CHO

benzoic acid, benzene
reflux, 10 hr

R=

N
H
79%

R
CO2Me


Fukuyama Group - Group Meeting Problems
09/19/2001

1

1) COCl2, DMAP, DMF
25 °C, 1 hr

P

NO2

HN

2) NH2CH2CH2NH2, DMAP
CH2Cl2, 25 °C, 1 hr
3) hν (lamp equipped with pyrex filter)
THF

N
H

2

i-PrO

Br

O

OCH3

NH
NO2

N
H

O

i-PrO HO

;

tert-BuLi;
i-PrO

P

O

i-PrO
H

Li
CH3

3

O CH3

; aq NH4Cl

CO2Me

OH
H

1) SnCl4, toluene, –78 °C;
NaHCO3, toluene, 80 °C
NO2

H

2) H2, RaneyNi, MeOH
160 psi, rt

Me

Me

HO
H
NH
O

4
1) acetone, Ac2O
ZnCl2, 48%

O
CO2Et

5

2)

PPh3Br
n-BuLi, Et2O
85%

C12H18O2

1) DIBAL, CH2Cl2
72%

CHO

2) (COCl)2, DMSO
Et3N, THF, 68%
3) DBU, CH2Cl2
89%

OH

H

CO2H

NHCbz

1) PhI(OAc)2
CF3CH2OH

3) MeMgBr, CuI (cat.)
60%

2) NaHCO3, MeOH
0 °C to rt
54% (2 steps)

4) PhI(OAc)2, I2
CH2Cl2, 80 %

O
CO2Me
O

N H
AcO Cbz


Fukuyama Group - Group Meeting Problems
09/26/2001

1

O

CO2Me

O

N3

MeO

1) PPh3, THF;
NaBH4, MeOH, rt

O

2) I2, CH2Cl2, Et2O, rt

O
MeO

H
N

H O

O

CHO

OAc

2

AgOTf
CH3CN, 70 °C;

C CCH2OTBS
O
NMe

BnMe3NCN
rt

N

I

OAc

OTBS

N

NMe

O
40%

3

NH2

p-Cl-C6H4CHO

1) PMe3 , Toluene , rt;
Ph2C=C=O

N3

cat. AcOH
EtOH , reflux

2) Pd/C , Toluene,
reflux

p-Cl-C6H4
N
Ph

N

CH3
HO CH
3

4

1) Eu(fod)3 (10 mol%), toluene, 80 °C, 36 h, 84%
H 3C

2) hν, Corex, 19 h, 79%
3) LiDBB, THF, –78 °C to 10 °C, 35 h, 57%

O
CH3
H 3C

H 3C

LiDBB; lithium di-tert-butylbiphenylide

5
1) MCPBA
N

2) (CF3CO)2O;
aq. Na2CO3

N
OH

H
CH3