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 GIABÀI TẬP TỔNG HỢP HÓA HỮU CƠ SINH VIÊN CHUYÊN NGÀNH HÓA HỌCBÀI TẬP TỔNG HỢP HÓA HỮU CƠ GIÁO VIÊN HÓA HỌCBÀI TẬP TỔNG HỢP HÓA HỮU CƠ LUYỆN THI HSG QUỐC GIABÀI TẬP TỔNG HỢP HÓA HỮU CƠ LUYỆN THI HSG QUỐC GIABÀI TẬP TỔNG HỢP HÓA HỮU CƠ LUYỆN THI HSG QUỐC GIA

BÀI TẬP

TỔNG HỢP HÓA HỮU CƠ LUYỆN THI HSG QUỐC GIA (tập 1) Thạc sĩ Phạm Công Nhân

Fukuyama Group - Group Meeting Problems

POCl3, Et3N

CH3CN

N N N H

3) liq NH3

CH3CN

45 °C4) 250 °C, neat

NBn

CNNC

H2N

CH2CH2OCOPh

OPhOMe

OPhOMeHO

H

+

major

hν (pyrex)MeOH

minor

HO

HO

+OHC

cat Pd (0)

Et3B (2.4 eq)

Et3N (1.2 eq)LiCl (1.0 eq)THFrt

OH

O

hν

H2Oacetone *

*) as acid scavenger

Cl carboxylic acid

C10H12O2

CN1) SOCl2, benzene;

Et3N, allyl amine2) PPh3, CCl4

Et3N, CH3CNO

O2N

ON

O2N

COOH1) CF3COCH3, NaHCO3, Oxone®

CH3CN-H2O, rt, pH7-7.52) 5% NaOH aq, MeOH

100 °C, 12 h

88%

Fukuyama Group - Group Meeting Problems

CO2Et

OHCN

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

110 °CHint: active catalyst = K2PdI4

3) BuLi, THF –78 °C to rt4) TMSCl (3 eq.), NaI (3 eq.)

CH3CN, rtO

N CO2H

MePh

O

N

N COCF3

MePh

1 TFAA, Py2

K2CO3, DMF

70 °C

H NH2NH·HCl

Fukuyama Group - Group Meeting Problems

CO (105 atm)benzene, 80 °C63%

OAc

CO2Me OBn

1) NaCN, DMSO, 130 °C2) 0.5 mol% [Rh(CO)2Cl]2 toluene, 110 °C, 30 min 93%

BnOH

1N HClTHF

N

OHPhPhOHPhPh

n-Bu

H

CO2Et

Fukuyama Group - Group Meeting Problems

N O O

OHO

78% (86%ee)

F3C CF3

OH

F3C OH HFIP TFE

C 13 H 13 ClO

1) LAH, Et2O, 0 °C2) KH (5 eq*), THF

0 °C to rt74%

76% (2 steps)

HH

(*$"&')#1%)

*TFE = trifluoroethanol

2 Ph3SnH, Et3B toluene

CO2MeMeO2C

Bu

OHO

NH

NHHN

NBn

Fukuyama Group - Group Meeting Problems

H

HHO

Me

1) SnCl4, toluene, –78 °C;

NaHCO3, toluene, 80 °C2) H2, RaneyNi, MeOH

160 psi, rt

NO2

NH

O

CO2Et

1) acetone, Ac2O ZnCl2, 48%

2)

n-BuLi, Et2O 85%

C 12 H 18 O 2

1) DIBAL, CH2Cl2 72%

2) (COCl)2, DMSO

Et3N, THF, 68%

3) DBU, CH2Cl2 89%

1) PhI(OAc)2

CF3CH2OH2) NaHCO3, MeOH

0 °C to rt 54% (2 steps)

3) MeMgBr, CuI (cat.) 60%

NO2

NH

P

;

Fukuyama Group - Group Meeting Problems

NOAc

O

NMeOTBS

40%

N3

6H4CHOcat AcOHEtOH , reflux

NN

1) PMe3 , Toluene , rt;

Ph2C=C=O2) Pd/C , Toluene,

p-Cl-C6H4

CHOMeO

1) PPh3, THF;

NaBH4, MeOH, rt2) I2, CH2Cl2, Et2O, rt N

OOH

HO

OMeOO

aq Na2CO3 N

OH

Fukuyama Group - Group Meeting Problems

O

NHN

CH3H

OHC(NMe2)3 (5 eq)

THF, reflux

5 h80%

CHOOTBS

FN

Et

EtMe

Me

Fukuyama Group - Group Meeting Problems

HO

Me3Si

1) Bu3SnH, AIBN benzene, ∆

2) MeLi

OPMBO

OH

OPMB

H1) SOCl2, imidazole, CH2Cl2

–78 °C to rt, 81%

2) PhMgBr, THF/CH2Cl2, –50 °C;

(MeO)3P, MeOH, 50 °C 83%

N

OSEM

+NMe

NH

N

MeH

HOH

N

H

N

OTBDPSMeO2C

HH

NH

N

Fukuyama Group - Group Meeting Problems

MeOMe

OEtTIPSO

OO1)

t-BuOK, DMF, 105 °C 2) hν, Vycor, CH3CN

TBSTMS

TMSTBSO

–80 to –30 °CTHF

1 Me2NNH2

2 MeI

3 NaH, THF

hν, Pyrex5% CH2=CHCN

(4 eq)

EtAlCl2

CH2Cl2rt

OSMeTBS90%

Fukuyama Group - Group Meeting Problems

NH

3) Cl3COCOCl, TEA4) CHCl3, aq NaOH, cat TEBAC5) H2, PtO2; (Boc)2O, TEA6) AgBF4, 40 °C

EDCI; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimideTEBAC; triethylbenzylammonium chloride

Cl

O,

NHEtO2C

Me CO2Et

MeNPh

CO2Me

CO2Me

OO

CNNC

O

hυ

MeCN

Fukuyama Group - Group Meeting Problems

OEt

1) ArSO2N3

i-Pr2NEt2) Rh2(OAc)4

CH2Cl2OBn

NO

O

NSwarmed to r.t

A

OBnBnO

OBn

OHBnO

BnO

OBn

Cp2ZrCl2, 2 eq n-BuLi

BF3•Et2O, THF65%

O

Ph

Ph

TMSOTfbenzene, CH2Cl2reflux, 7 hr98%

1) HOCH2SO3Na *

H2O, 40 °C2) RCO2H HOBt, DCC, Et3N

OR

R=

N NH O

O

Fukuyama Group - Group Meeting Problems

TMSI

1) LDA, THF –78 °C to rt;

o-NO2PhCOCl, Et3N;

2) TFA, CH2Cl2 54%

A

1) NaBH4, Cu(acac)2 EtOH, rt

2) NaNO2, HCl, CuCl MeOH, 0 °C to rt 74% (2 steps)

NHBzHMeO

+

OH

HOHO

1) I2, PhH

2) m-CPBA

3) t-BuOOH Ti(O-i-Pr)4

HCO2Hrt

NH

MeNEt

Cl2NCO2Me

1) SCl2, pyridine2)

CHCl3

H3CHC CHCH2CH3

3) KOH MeOH, rt4) LAH ether, reflux

NHMe2

H2, 20% Pd(OH)2/CMeOH, 59%

CO2Me

HO2CPPh3, DEAD

O

ClO

Me Br

NO

Boc

Me

NO

OH

NOOHH

OO

MeO2CMeO2C

OHH

4

11/21/2001

+

1) TiCl4 MeNO2

CH2Cl2, 2) LHMDS;

CO(OMe)2 98%

1)

K2CO3 acetone2) 1,2,4-trichlorobenzene reflux

1) CDCl3, 65 °C, 80%

2) KH (2 eq) 18-crown-6 (2 eq) THF, rt, 90%

NaN3

t-BuOH

reflux81%

NaOH, K2CO3NBu4+HSO4-toluene

80 °C91%

toluene

160 °C75%

>300 °C, 10 s

+

∆, 83%

Me S

CH2Cl2

rt, 20 min

Cl S CO2Me

1) 79%

OMe

N2Me

Me Me

Me

O

OMe

OTBS

R1OH

dil HCl

CH2Cl2, rt

TMSCH=C=O (2.2 eq)toluene

80 °C

4 hr79%

R1

NHPhOPh

iodobenzenePd(OAc)2 (5 mol%)NaOAc, LiClDMF, 100 °C60%

PPh3DMADdioxane

10 °C to reflux84%

S

1) BrCH2COCl, CH2Cl2, rt;

Et3N, CH2Cl2, reflux2) NaIO4

MeOH/dioxane/H2O, rt3) Ac2O, p-TsOH

toluene, reflux

S

HO

Til4 (3.0 eq)EtCN–78 to –20 °C

1) NBS, CH2Cl2, TFA2) AgBF4

3) H2O/THF

N COOMe MeO

N

OAc OH Me

Ph

OH

tBuO

NTsO

NH

NHCOOMeR

N CN

ArOHC

NH

NHCOOMeR

rt, 3h3) TFAA, CH2Cl2

2 hr, 70%

Cl

CO2Me

NN

OBn

100 °C, 2h

52% (2 steps)

toluene, 65 °C56%

1 MnO2, 96%

2 BnNHCH2CO2H toluene, reflux 68%

BzOO

OOBz

93%ee78%

N

Me

OMeO2C

NO2 CO2Me

CO2MeOMe

CO2Me

CO2MeOMe

MeO

NH

MeO2C1) PhN2BF4

aq pyridine2) NaBH4, MeOH3) H2, Pd-C, HCl

Me

TMSO

OMe