Methods of Non-a-Amino Acid Synthesis, 2nd Edition

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Contents

Preface to the Second Edition ...................................................................................ix

Preface to the First Edition .......................................................................................xi

Common Abbreviations ........................................................................................... xv

Introduction ............................................................................................................. xix

Chapter 1 Functional Group Exchanges ...............................................................1

1.1 Reactions with Ammonia, Amines, or Amine Surrogates ........1

1.1.1 Reaction with Ammonia ..............................................1

1.1.2 Reaction with Amines .................................................. 3

1.1.3 Reaction with Amine Surrogates .................................3

1.2 Conversion of Carbonyl Compounds to Amines ..................... 10

1.2.1 From β-Keto-Acids or β-Diketones ........................... 10

1.2.2 From Other Keto-Acids or Aldehyde Acids ...............12

1.3 Refunctionalization to Generate Carboxyl Groups ................. 15

1.3.1 Carboxyl Equivalents .................................................15

1.3.2 Carboxyl-Bearing Carbanions and Ylids ................... 19

1.3.3 Oxidative Methods ..................................................... 21

1.4 Refunctionalization of Amino Acids .......................................23

1.4.1 From α-Amino Acids .................................................23

1.4.2 From Other Non-α-Amino Acids ..............................29

1.4.3 N-Alkylation or N-Arylation ...................................... 31

1.5 Specialized Methods ............................................................... 35

1.5.1 Oxidation and Reduction ............................................35

1.5.2 Rearrangement Reactions ...........................................38

Chapter 2 Cyclic Precursors ............................................................................... 41

2.1 From Lactams or Imides ......................................................... 41

2.1.1 From β-Lactams ......................................................... 41

2.1.2 From Other Lactams ..................................................44

2.1.3 From Imides ...............................................................48

2.2 From Ketones ..........................................................................48

2.2.1 Direct Cleavage of Cyclic Ketones ............................49

2.2.2 Via Rearrangement Reactions .................................... 50

2.3 From Lactones and Anhydrides .............................................. 51

2.3.1 From Lactones ............................................................ 52

2.3.2 From Anhydrides........................................................53

2.4 From Heterocycles ................................................................... 54

2.4.1 Isoxazolidines, Isoxazoles, Oxazolidines,

andOxazine Derivatives ............................................54

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2.4.2 Pyrazole Derivatives ..................................................58

2.4.3 Pyridine, Hydropyridine, and Pyridone Derivatives.....59

2.4.4 From Uracil Derivatives and Cyclic Carbamates ....... 61

2.4.5 From Thiophene, Thiazolidine, and Oxathiolone

Derivatives .................................................................. 62

2.5 Diels-Alder Strategies ..............................................................62

Chapter 3 Conjugate Addition Reactions ............................................................65

3.1 Ammonia and Amine Nucleophiles ........................................ 65

3.2 Carbon Nucleophiles ...............................................................70

3.2.1 Nitro Enolates and Nitrile Enolates ............................70

3.2.2 Addition to Conjugated Nitro Derivatives ..................72

3.2.3 Addition of Enamines ................................................ 73

Chapter 4 Enolate Anion and Related Reactions ................................................ 75

4.1 Acid, Ester, and Malonate Enolate Anion Reactions .............. 75

4.2 Nitrile Enolate Anions ............................................................. 81

4.3 Nitroalkane Enolate Anions ....................................................83

4.4 Mukaiyama Type Condensations ............................................85

4.5 Condensation Reactions Involving Organozinc

Intermediates ........................................................................... 87

4.6 Ylid Reactions .........................................................................88

Chapter 5 Diastereoselective and Enantioselective Syntheses............................ 91

5.1 α-Amino Acid Templates ........................................................ 91

5.2 Non-α-Amino Acid Templates .............................................. 102

5.3 Synthesis from Other Starting Materials .............................. 105

5.4 Transformations Using Carbohydrates as Chiral Templates ....113

5.5 Enzymatic Transformations .................................................. 114

Chapter 6 Biologically Important Amino Acids ............................................... 119

6.1 Peptides and Proteins ............................................................ 119

6.1.1 As Residues in Peptides and Proteins ...................... 119

6.1.2 As Substrates for Peptides and Proteins ...................124

6.1.3 As Residues in Cyclic Peptides ................................129

6.2 β-Alanine and Aminopropanoic Acid Compounds .............. 131

6.3 GABA and Related Compounds ............................................ 135

6.4 GABOB and Carnitine .......................................................... 145

6.5 DAVA (Ava) and Ahx ............................................................ 153

6.6 Statine and Related Compounds ........................................... 156

6.7 Other Biologically Important Amino Acid Derivatives ........ 167

6.8 Non-α-Amino Acids in Catalysis .......................................... 172

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Chapter 7 Aminocyclic andHeterocyclic Amino Acids................................... 175

7.1 Aminocycloalkylcarboxylic Acids from Cyclic Precursors ..... 176

7.1.1 Lactam-Based Syntheses .......................................... 176

7.1.2 Dicarboxylic Acids and Related Precursors ............. 178

7.2 From Aromatic Precursors .................................................... 184

7.3 From Cyclic Ketones ............................................................. 187

7.4 Cycloaddition Strategies ........................................................ 191

7.5 Heterocyclic Amino Acids .................................................... 195