BÀI TẬP -BÀI GIẢI TỔNG HỢP HÓA HỮU CƠ LUYỆN THI HSG QUỐC GIA (tập 3 2021)

BÀI TẬP
TỔNG HỢP HÓA HỮU CƠ

LUYỆN THI HSG
QUỐC GIA (tập 3)
Thạc sĩ Phạm Công Nhân

TAXOL


Fukuyama Group - Group Meeting Problems
01/08/2003
1
O
Ph

NO2

N
H

O

O

SOCl2 (ex.)

Ph

N
H

rt, 52%

N

O

N

N
H

Ph

O

2
O

O
O

80~110 °C, 5 h

NHMe

Ph

O

OEt

74%

EtO2C
Ph

O

NMe
O

O

3
H
N

NH2

AcCl, Et3N
55%

4

SMe
O

H
N

BrCN, Et2O, 0 °C;

NHAc

diphenyl ether
190 °C, 2.5 h

N

76%

1) I2, THF, 69%
2) Na2CO3
THF/dioxane/H2O, reflux, 71%

NEt

3) 0.5 N NaOH
EtOH/H2O, reflux, 64%

NHEt
OH

(racemic)

5

O

N
N
PhO2S

H

1) KOt-Bu, O2, P(OEt)3
HOt-Bu, DME, 79%

O
N

2) NaBH4, THF, 76%
3) NaIO4, 53%

H
N
PhO2S


Fukuyama Group - Group Meeting Problems
01/15/2003
1
O

O

OH

1) LDA, THF, –78 °C

2) CF3SO3Me, CH2Cl2, 0 °C to rt
3) t-BuOK, THF

O

2
(NH4)2SO3·H2O

OH
OH

NH2
OH

NH3·H2O
200 °C, 5 d
91%

3

1) n-Bu3P, DMF, 0 °C

then

S S

O

47%
N

H

N
H

H
N

Br

H
N

O

O

O

Br

2) 1,2,2,6,6-pentamethylpiperidine (cat)
toluene, reflux, 72%

N
H

N
H

4
Me

O

O
O

O MeCO2Me
CO2Me

t-BuNC, DMAD
CH2Cl2, rt, 24 h
94%

O
O

NHt-Bu

5
O

CO2Et
SnCl2 (5 eq)

S
NO2

S

EtOH
reflux, 2 h
98%

S
S
N
H


Fukuyama Group - Group Meeting Problems
01/22/2003
1
n-BuLi (1 eq), THF;
B(n-Bu)3 (1.1 eq);
BCl3 (1.1 eq);

Ph
OMOM

MeOH;
30% aq. H2O2-NaOH

Ph
OH

n-Bu
89%

2
CO (2-3 bar), Pd(PPh3)4
K2CO3, n-Bu4NBr

I

O

NHTs

3

O

N
Ts

CH3CN
70-80 °C
61%
NH4Cl
toluene
rt, 1 hr;

CO2Me
+

OHC C6H13

NH2

O
MeO2C

O

O
CN

N

N
N

O
Ph
reflux, 1.5 hr

C6H13

4
SO2Ph
O

+

O

1) t-BuOLi, –60 °C
2) DDQ

O
O

3) toluene, reflux
O

5

O

O
O

OTIPS

SnBu3
MeO
MeO

NHTs

2) KF on Al2O3
1) PhI(CN)OTf
(under air)
CH2Cl2, –40 °C;
LHMDS
DME, –40 °C

MeO

MeO

N









Fukuyama Group - Group Meeting Problems
02/12/2003
1
18O

hn

MeO2C

MeO

dioxane/H218O

O

HO
H

O

2
S

OPh

N
Me

S

1) mCPBA, CHCl3
2) CHCl3, reflux

OPh

3) 20% aq. KOH

O

N
Me

O

O

3

OMe
Mo(CO)5
O

OMe

THF, 67 ºC

+

CO2Me

MeO2C
O

2 hr, 71%

O

O

4

NO2
Cl

NaOH,
N

O2N

acetone, ~60%
OH

O

NO2

PhH, reflux
6 hr, 74%

NO2

N
O2N

NO2

5
O
DBU, NIS
OH

CH2Cl2, rt
73%

"tricyclic compound"

Bu3SnH, AIBN

t-BuOH, reflux
50%

O

H

H

O


Fukuyama Group - Group Meeting Problems
02/19/2003
1
O

O

Lawesson's rgt (1.1 eq)
NO2

N
H

2

toluene, 100 °C, 15 min
68%

1)
NH2, H2O, 81%
2) Tf2O (2 eq.), py
CH2Cl2, 83%

O
O

NH2

N
H

S

Me
N
SO2CF3

3) toluene, reflux
Me

3
OH
N

DPPA
DBU

Cy2BH, THF

0 ° C to rt, 12 h;

toluene
rt

MeOH
N
85%

90%

4

H

Ph
O
O

H

N
H

+

PPh3CHCO2Bn

r.t, CH2Cl2, 3 days

H

Ph
H

BnO2C

95%

H

Ph

COPh

Me

5
MeO

N,N-diethylaniline
O

O

225 °C, 12 h

MeO

MeO

MeO

O

OH
40%

Me

1) PIDA, MeOH
2) p-TsOH, MeOH
reflux, 1.5 h

MeO

MeO

O
O

MeO

49% (2 steps)

PIDA = phenyliodonium diacetate

Fukuyama Group - Group Meeting Problems
03/05/2003
1

1) n-BuLi (2 eq), TMEDA;
RCHO, THF, 62%
2) PPTS, toluene, 85%

HO
O

OH

O

O

3) Pd/C, H2, EtOH, 90%
4) BF3•Et2O, THF, 85%

O

O

R=

O

2
1) Rh(II)
benzene, rt
10 min, 94%

N2
O

N
O

Ph

O

H

O

O

2) xylene, 145 °C
13 hr, 68%

O

N
Ph

[Rh(II) = Rh2(pfb)4]

3
Mo(CO)5
Bu
W W

Me

OMe

NO2

W

benzene
40 °C

W = CO2Me

4

W

OMe

Bu

54%

(0.5 eq :

theoretical amount)

O2N

O

N

O
+

CHCl3 - MeNO2
rt, 10 min

O2N
2 : 3 mixture

5
1) n-BuLi, –78 °C
Cl

O

Cl

2) n-BuLi, 0 °C

OH

N

Fukuyama Group - Group Meeting Problems
03/12/2003
1
1) Lawessons' reagent
2) COCl2 (2 M in tol.), cat. DMF
0 °C,to rt, 1 h; evaporation;

O
N
Me

CO2Me

Ph
Cbz-L-Phe

Cbz

N
H

CH3CN
rt, 19 h

DABCO, THF, rt, 20 min;
filtration;
NaN3, 46%

H
N
O

83%

2

O
O
Me

1) PhNMe2
180 °C, 6 h, 87%

O

2) cat. Zr(acac)4, TBHP (2 eq)
CH2Cl2
20 °C, 6 h, 71%

Me

3
1) BrCH2CO2Ph
i-Pr2NEt, MeCN

OH

OH

TIPSO

2) TIPSOTf, Et3N
benzene
3) LiAlH4

NHBn

OH

N
Bn

4
O

Me3Si

1) Br2, MeOH
2) AgNO3, MeOH

CO2Me

3) TFAA, DMSO

CO2Me

CO2Me
CO2Me

5
CO2Me
Cl

+

CO2Me

1) CH2Cl2, rt
5 days, 70%
N
O

2) DMSO, 100 °C
3 hr, 73%

N
O

O
N
Me

CO2Me

Fukuyama Group - Group Meeting Problems
04/09/2003
1

O

O

O

1) LDA (3 eq), THF
–78 °C to reflux
2) toluene, 80 °C

O

3) EtAlCl2, CH2Cl2
0 °C to rt

2

NaH (2.4 eq),
O

O

Me
Me

I
S
Me
O

H
(2.4 eq)
O

DMF, rt

O

H

OH O

54%

3

R

R
HO

OAc

OH OH

R=

[CF3CO2ReO3·2MeCN]
TFAA

PCC

R

CH2Cl2-MeCN (9:1 v/v)
–40 °C, 1.5 hr, 84%

CH2Cl2
30 min, 47%

HO

4

H

O

OAc

1) TsNCO, Et3N
THF, rt, 94%

O

2)

OH

O

Br

N
Ts

Pd(OAc)2 (5 mol%)
P(o-tol)3 (11 mol%)
Na2CO3, n-Bu4NCl
CH3CN, 90 °C, 77%

5
COCl
+
ClOC

1) benzene, rt
overnight, 93%
2) CH2N2, overnight
34%

H

3) benzene, 170 ºC
85%

H

O

OH

O

R
H

OH