Chemistry - The nitro group in organic synthesis - Willey (2

Chemistry - The nitro group in organic synthesis - Willey (2

Also in the Series:

Noboru Ono

NewYorkChichesterWeinheim Brisbane SingaporeToronto

Series Forewordix Preface xi Acknowledgments xiii Abbreviations xv 1. Introduction1

2. Preparation of Nitro Compounds3

2.1 Nitration of Hydrocarbons / 3

2.2 Synthesis of Nitro Compounds by Oxidation / 20

3. The Nitro-Aldol (Henry) Reaction30

3.1 Preparation of β-Nitro Alcohols / 31 3.2 Derivatives from β-Nitro Alcohols / 38

3.3 Stereoselective Henry Reactions and Applications to Organic Synthesis / 51

4. Michael Addition70 4.1 Addition to Nitroalkenes / 70

4.2 Addition and Elimination Reaction of β-Heterosubstituted Nitroalkenes / 100 4.3 Michael Addition of Nitroalkanes / 103

4.4 Asymmetric Michael Addition / 115

5. Alkylation, Acylation, and Halogenation of Nitro Compounds126

5.1 Alkylation of Nitro Compounds / 126 5.2 Acylation of Nitroalkanes / 128 5.3 Ring Cleavage of Cyclic α-Nitro Ketones (Retro-Acylation) / 131 5.4 Alkylation of Nitro Compounds via Alkyl Radicals / 133 5.5 Alkylation of Nitro Compounds Using Transition Metal Catalysis / 138

5.6 Arylation of Nitro Compounds / 147 5.7 Introduction of Heteroatoms to Nitroalkanes / 149

6 . Conversion of Nitro Compounds into Other Compounds159

6.1 Nef Reaction (Aldehydes, Ketones, and Carboxylic Acids) / 159

6.2 Nitrile Oxides and Nitriles / 167 6.3 Reduction of Nitro Compounds into Amines / 170

7. Substitution and Elimination of NO2 in R–NO2182

7.1 R–Nu from R–NO2 / 182 vi CONTENTS

8. Cycloaddition Chemistry of Nitro Compounds231

8.1 Diels-Alder Reactions / 231

9. Nucleophilic Aromatic Displacement302

9.1 SNAr / 302 9.2 Nucleophilic Aromatic Substitution of Hydrogen (NASH) / 309

10. Synthesis of Heterocyclic Compounds325

10.1 Pyrroles / 325 10.2 Synthesis of Indoles / 338 10.3 Synthesis of Other Nitrogen Heterocycles / 346

Index 365

CONTENTS vii

Professors Kornblum and Ono. xiii

, %  8&&8$

xvi ABBREVIATIONS

366 SUBJECT INDEX

$ 

SUBJECT INDEX 367

368 SUBJECT INDEX

SUBJECT INDEX 369

370 SUBJECT INDEX

SUBJECT INDEX 371

372 SUBJECT INDEX

1 INTRODUCTION

RN O2 Ar NO2

Ar–NH2 CH NOHR

NO2 CH3NO2

RN3

X = Br, I, OTs

Ar–H R–H

R–NH2

Scheme 1.1. Preparation of nitro compounds

Ar NO2 RNu, alkenes

RN H2 Ar NH2

Michael addition Cyclo addition

Nitro-aldol reaction

Scheme 1.2. Reaction of nitro compounds

2 INTRODUCTION

2.1 NITRATION OF HYDROCARBONS 2.1.1 Aromatic Compounds

FHNO3, Ac2OFF FNO2

NO2 NO2

NO2 NO2

NO2

Zeolite-β, 20 ºC, 30 min

++ Zeolite-β,

NO2 NO2

NO2 NO2

NO2

++ ClCH2CH2Cl

4 PREPARATION OF NITRO COMPOUNDS

NO2

NO2

NO2N2O5, HNO3N2O5, HNO3 25 ºC, 10 min5 ºC, 5 min <#

CO2Me CO2Me

CO2Me

CO2Me

2.1 NITRATION OF HYDROCARBONS 5

  )

O NO2-O3 O

NO2

–10 ºC

Me Me CH2Cl2, 0°C

6 PREPARATION OF NITRO COMPOUNDS

2.1.2 Alkanes

N Cl

N CO2R

N Cl

N CO2R

N Cl

N CO2R

Br S

NO2

OMeOMe OMe OMe

NO2

2.1 NITRATION OF HYDROCARBONS 7

CH3

CH3

CH3 CH3

CH3 NHAc

CH3

CH3 NHAc

CH3 NO2

CH3 NO2

CH3 NO2

CH3 NO2

CH3 NO2

NHAc NO2

Cl NO2

CH3 NO2

CH3 NO2

NHAc NO2

8 PREPARATION OF NITRO COMPOUNDS

COMe Cl

CO2H OCOMe

CH2OMe

COMe

NO2 Cl

NO2

NO2 OCOMe

NO2

CH2OMe NO2

NO2-O3 NO2ONO2

MeSO3H 0 ºC, 1 h

DMSO, 17 ºC56%

2.1 NITRATION OF HYDROCARBONS 9

2.1.3 Activated C-H Compounds

1) LDA

CH2CO2HMeO

CH2NO2

1) LDA

H3C CN

CH2NO2

NO2

NO2

Na NO2

NO2

NO2

NO2

10 PREPARATION OF NITRO COMPOUNDS

2.1.4 Alkenes

NO2

CH2Cl2 1 h, 25 ºC

2) AcONaH O2NH

NO2

OMe 1) t-BuLi, –78 ºC

2.1 NITRATION OF HYDROCARBONS 1

SnMe3

NO2 NO2

NO2

NO2

NO2 NO2

CH3 NO2

NO2 NO2

NO2 NO2

NO2 NO2

NO2

12 PREPARATION OF NITRO COMPOUNDS

NO2

NO NO2 acidic Al2O3

NO H-zeolite

84% Ph Ph NO2

NHAc NO2BF4

2.1 NITRATION OF HYDROCARBONS 13

2) pyridine

Me3Si Me3Si NO2

O2N SePhO2N2) AgNO2/ HgCl2

1) PhSeBr

1) PhSeBr

MeO OMe OMe

CH3

MeO OMe OMe

HBF4, CH2Cl2 20 ºC, 15 h

14 PREPARATION OF NITRO COMPOUNDS

SiMe3 AcONO2 ONO2

NO2

SnMe3 NO2

SiMe3 AcONO2 NO2

2.1 NITRATION OF HYDROCARBONS 15

2.1.5 Synthesis of -Nitro Ketones

 = )#4&

DMSO O NO2

OSiMe3

OAc (CF3CO)2O

OO2N

OAc

HNO3-Ac2O

16 PREPARATION OF NITRO COMPOUNDS

2.1.6 Nitration of Alkyl Halides

NO2O O2NC O2RROH

NO2Me OH NO2Me NO2Me

Me3SiONO2 O

DMSO 73

2.1 NITRATION OF HYDROCARBONS 17

CH2BrCO2HC H2NO2RT NaNO2 NaNO2

DMF –16 ºC

18 PREPARATION OF NITRO COMPOUNDS

O Br O O NO2

O Si

Me CO EtNCMe

NO Et

O Si Si

ONBr Ph

OTs

O Si

Me CO EtNCMe

Br Et

OH (CH ) Br

Si Si

2.1 NITRATION OF HYDROCARBONS 19

2.2 SYNTHESIS OF NITRO COMPOUNDS BY OXIDATION 2.2.1 Oxidation of Amines

RN H2 RN O2OO acetone

20 PREPARATION OF NITRO COMPOUNDS

2.2.2 Oxidation of Oximes

O AcO

AcO AcO

NH2

OAc

O AcO

AcO AcO

NO2

OAcm-CPBA CHCl3

NH2 NO2 KMnO4

H2N OEt OEt O2N OEt

OEt t-BuOOH

Zr(Ot-Bu)4

NH2

2.2 SYNTHESIS OF NITRO COMPOUNDS BY OXIDATION 21

.+)%@!% "& (" C<4 L+ .+)%@!" 21 74

NO2

MeO NOH MeO

2 PREPARATION OF NITRO COMPOUNDS

"   

Cl NO

NOH NO2

BzOMoO(O2)2 –

C2H5 CN P O Oi-Pr

Oi-Pr

OOi-Pr

Oi-Pr

NO2

65% m-CPBA

RT, 72 h 2&# n-Bu4NHSO4 NaClO

NO2Cl NO2

H2/ Pd-CHClO, pH 5.5 benzene

NOH Cl

NO2 OXONE, NaCl

Scheme 2.1.

2.2 SYNTHESIS OF NITRO COMPOUNDS BY OXIDATION 23

=  22C2@#

CH3CN

Ph3CO O Ph3CO O

NO2

PhCO2 O

PhCO2

1) pyridine, Cr2O7 2) H2NOH

RCO2

RCO2 O

NO2

24 PREPARATION OF NITRO COMPOUNDS

N O OCH2CCl3

NaN3 DMF Ph3P

O3 X = I

X = NO2

50% (overall) X = N=PPh3

O NO2 O2NH2O, acetone

1) SOCl2

REFERENCES 25

! :+% !  K @@7

26 PREPARATION OF NITRO COMPOUNDS

REFERENCES 27

28 PREPARATION OF NITRO COMPOUNDS

REFERENCES 29

+ R′CHObase

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