Basic Concepts in Organic Stereochemistry

Foreword
Preface
Acknowledgements
Structure Diagrams
Contents
About the Authors
1 Symmetry and Molecular Chirality. Conformation, Stability, and Physical Properties
1.1 Chirality. Symmetry Elements. Optical Rotation
1.1.1 Simple or Proper Axis of Symmetry
1.1.2 Plane of Symmetry
1.1.3 Center of Symmetry or Inversion Center
1.1.4 Alternating or Improper or Rotation-Reflection Axis (Sn)
1.1.5 Dissymmetric and Asymmetric Molecules. Chiral and Achiral Point Groups. Central Chirality
1.1.6 Symmetry Number, Order of Point Groups, Achiral Point Groups
1.1.7 Local Symmetry (or Site Symmetry). Desymmetrization
1.1.8 Optical Isomerism. Optical Rotation
1.1.9 Specific Rotation. Molecular Rotation. Units (Fig. 1.13)
1.2 Conformation of Simple Acyclic Molecules
1.2.1 Dihedral Angle. Torsion Angle. Torsional Strength
1.2.2 Klyne–Prelog Nomenclature for Torsion Angles. Conformational Chirality
1.2.3 Torsional Strain Curve (Potential Energy Diagram) of Ethane
1.2.4 Torsional Strain Curve of Propane
1.2.5 Torsional Strain Curve of Molecules ACX2CX2B, n-Butane
1.3 Configuration. Relative Configuration. Absolute Configuration
1.4 Relationship Between Two Molecules of Same Molecular Formula. Homomers, Constitutional Isomers, Stereoisomers, Enantiomers, Diastereomers, Configurational/Conformational Enantiomers/Diastereomers
1.5 Conformational Effect on Stability of Diastereomers (Fig. 1.25)
1.6 Conformation and Physical Properties of Acyclic Molecules and Some Cyclohexane Derivatives
1.6.1 Dipole Moment. Three Examples
1.6.2 Acid Strength Measurements. Cyclohexane-1,2-Dicarboxylic Acids, 4-T-Butylcyclohexanecarboxylic Acids (Fig. 1.29)
1.6.3 Different Affinity for Adsorbents of 4-t-Butyicyclohexanol Isomers
1.6.4 Physical Properties of Substituted Cyclohexanes; Von Auwers–Skita Rule or Conformational Rule, Van Arkel Rule
References
2 Configurational Nomenclature. Physical Properties of Geometrical Isomers
2.1 Fischer’s d,l Nomenclature
2.2 R,S Nomenclature for Absolute Configuration
2.2.1 R,S Nomenclature. Center of Chirality
2.2.2 Specification of Center/s of Chirality
2.2.3 Priority Sequence of the Application of the CIP Sub-rules
2.2.4 Modification of Sub-rule 3
2.2.5 R* and S* Nomenclature
2.2.6 Specification of Other Tetracovalent Chiral Atoms
2.2.7 Specification of Tricovalent Chiral Compounds (with Pyramidal Stereocenter)
2.3 Stereochemistry of Alkenes. E,Z Nomenclature [9–11]
2.4 Physical Properties of Geometrical Isomers [12]
2.4.1 Dipole Moments of Geometrical Isomers [13]
2.4.2 Physical Properties of Geometrical Isomers: Melting Points, Boiling Points, Densities, and Refractve Index [12]
2.4.3 Acid Strengths of Geometrical Isomers [16, 17]
References
3 Projection (Fischer, Newman, Sawhorse) and Perspective (Flying Wedge and Zigzag) Formulas, Working Out Stereoisomers
3.1 Molecules with Two Unlike (Unsymmetrical) Chiral Centers (AB Type)
3.1.1 Erythro and Threo Nomenclature
3.1.2 “Pref” and “Parf” Nomenclature
3.1.3 Syn and Anti System
3.1.4 Like (l) and Unlike (U) System
3.1.5 Brewster’s System of Nomenclature
3.2 Molecules with Two like (Symmetrical) Chiral Centers (AA Type)
3.3 Molecules with Three Unlike Chiral Centers (ABC Type)
3.4 Constitutionally Symmetrical Molecules Having Three Chiral Centers (ABA Type)
3.5 Stereogenecity and Chirotopicity (Fig. 3.12)
3.6 Molecules with Four (ABCD Type) or More Unlike Chiral Centers in a Chain
3.7 Constitutionally Symmetrical Molecules with Four or More like Chiral Centers in a Chain (ABBA, ABCBA, Etc., Types)
3.8 Chiral Compounds with Asymmetric Carbon Atoms in Branched Chains
3.9 Chirality and Dimension. One-, Two-, and Three-Dimensional Chiral Simplexes
References
4 Prochirality and Prostereoisomerism. Topicity of Ligands and Faces Nomenclature [1–5]
4.1 Introduction
4.2 Homotopic Ligands
4.3 Homotopic Faces
4.4 Enantiotopic Ligands
4.5 Nomenclature of Geminal Enantiotopic Ligands. Pro-R and Pro-S
4.6 Enantiotopic Faces
4.7 Nomenclature of Enantiotopic Faces
4.8 Diastereotopic Ligands
4.9 Nomenclature of Diastereotopic Ligands
4.10 Diastereotopic Faces. Nomenclature
4.11 Interesting Examples of Topicities of Homomorphic Ligands [8]
4.12 Interrelation of Topicity of Ligands with Isomerism
4.13 Molecules with Prostereogenic but Proachirotopic Center and Multiprochiral Centers
4.14 Topic Relationship of Ligands and Faces
4.15 Stereoheterotopic Ligands and NMR Spectroscopy
4.15.1 Anisochrony Arising Out of Diastereotopic Faces
References
5 Asymmetric Synthesis
5.1 Introduction. Principles of Stereoselection: Enantioselection. Diastereoselection
5.1.1 Lack of Stereoselection
5.1.2 Enantioselection
5.1.3 Diastereoselection
5.2 Asymmetric Synthesis. Definition. Stereoselective and Stereospecific Reactions. Product/Substrate Stereoselectivity. Regioselectivity
5.2.1 Enantiomeric Excess. Diastereomeric Excess. Optical Purity
5.3 Cram’s Rule
5.3.1 Cram’s Open Chain Model
5.3.2 Cram’s Chelate or Cyclic Model
5.3.3 Cram’s Dipolar Model
5.4 Felkin–Anh Models [8, 9]
5.4.1 Felkin–Anh Open Chain Model
5.4.2 Felkin–Anh Dipolar Model
5.5 Prelog’s Rule
5.5.1 Attempted Rationalization of Prelog’s Model
5.5.2 More Examples of the Application of Prelog’s Rule
5.5.3 Exception to and Anomalies of Prelog’s Rule
5.6 Horeau’s Rule
5.7 Sharpless Enantioselective Epoxidation
5.7.1 Kinetic Resolution of Racemate Allyl Alcohols
5.7.2 Mechanism of the Sharpless Reaction
References
6 Some Other Aspects of Dynamic Stereochemistry: Conformation and Reactivity
6.1 Introduction
6.2 Conformational Analysis of Chemical Reactions
6.2.1 Stereoelectronic Effects and Steric Effects
6.2.2 Conformationally Rigid Diastereomers
6.2.3 Conformational Energy: Anancomeric Systems
6.2.4 Conformation and Chemical Reactivity for a Conformationally Mobile Substrate Molecule: The Winstein–Holness Equation and the Curtin–Hammett Principle
6.2.5 Curtin–Hammett Principle. Case 1, Predominant Conformer Leading to Predominant Product (GoP2 > GoP1)
6.2.6 Elimination Reactions of Two Diastereomers trans- and Cis-2,3-Dibromobutane Leading to Two Diastereomeric Products
6.2.7 Curtin–Hammett Principle. Case 2. Energy Diagram for Predominant Conformer Leading to the Less Predominant Product. Derivation of C-H Principle
6.2.8 Curtin–Hammett Principle. Case 3. Different Conformers of Trans-2-Phenyl-Trans-3-t-Butylcyclohexan-r-1-ol Xanthate Having Same Free Energy Leading to Different Products. Chugaev Reaction
6.2.9 Quantitative Treatment of Mobile Systems. Winstein–Holness and Eliel Equations
6.2.10 Application of Winstein–Holness Equation. Examples 1 and 2
6.2.11 Application of Eliel Equation. Examples 1 and 2
6.2.12 Quaternization of 1-Methyl-2-Phenylpyrrolidine and 1-Methyl-2-Arylpyrrolidine. Product Ratio
6.2.13 The Conformational Preference of Substituents by 1H NMR Method. Calculation of Equilibrium Constant K (Cf. Kinetic Method) [18, 19]
6.2.14 Absolute Configuration of Allene Molecules (Figs. 6.18–6.22)
6.3 Baldwin’s Rules for Ring Closure
6.4 Conclusions
References
7 Conformation of Saturated Six-Membered Ring Compounds
7.1 Conformational Aspects of Cyclohexane
7.1.1 Geometry of Cyclohexane Chair. Bond Lengths. Bond Angles. Torsion Angles
7.1.2 Equatorial and Axial Bonds
7.1.3 Symmetry of Cyclohexane Conformations
7.1.4 Enthalpy (H) or Potential Energy (E) Difference
7.1.5 Cyclohexane Ring Inversion
7.1.6 Stable Boat or Skew–Boat Conformers
7.2 Monosubstituted Cyclohexanes. Conformational Energy
7.3 Conformational Energy
7.4 1,1-Disubstituted Cyclohexanes
7.5 Nongeminal Disubstituted Cyclohexanes
7.5.1 Some Typical Disubstituted Cyclohexanes (Fig. 7.10)
References
8 Cyclohexanone
8.1 Torsion Angles, Stability
8.2 Ring Inversion
8.3 Alkylketone Effects
8.3.1 2-Alkylketone Effect (Fig. 8.2)
8.3.2 3-Alkylketone Effect
8.3.3 4-Alkylketone Effect
8.4 Addition of Nucleophiles to Cyclohexanones. Stereochemical Aspects
8.4.1 PDC (PSC) and SAC (SSC)
8.4.2 Observations Against PSC
8.4.3 Torsional Strain. Role of C2 and C6 Axial Hydrogens. Burgi–Dunitz Trajectory
8.5 Cieplak Hypothesis
8.6 Highly Stereoselective Reduction of Saturated Cyclohexanones by Dissolving Metals. Birch Reduction
8.7 Alkylidene Cyclohexanes. Allylic(1,3) Strain
8.7.1 Conformational Preference
8.7.2 Synthetic Utility [24] of A(1,3) Strain. Stereochemistry of Exocyclic Enolate Anion Protonation
8.7.3 Another Example of the Use of A(1,3) Strain Concept
8.8 Cyclohexene. Conformation. A1,2 Strain
8.8.1 Conformation of Cyclohexene. Torsion Angles
8.8.2 Allylic 1,2-Strain (A(1,2)-Strain)
References
9 Fused Ring Systems
9.1 Decalins
9.1.1 Brief History
9.1.2 Trans-Decalin. Conformation. Torsion Angles. Symmetry
9.1.3 Cis-Decalin. Conformations. Torsion Angles. Symmetry (Fig. 9.2)
9.1.4 Ring Inversion in Cis-Decalin
9.1.5 Entropy Difference in Decalins
9.1.6 Enthalpy and Physical Constants. Auwers-Skita Rule
9.1.7 Free Energy Difference in Decalins
9.1.8 Effect of Introduction of Angular Methyl Group/s
9.1.9 Cis-Decalones and Trans-Decalones
9.1.10 Trans-2-Decalols. Conformational Analysis
9.1.11 Cis-2-Decalols. Conformational Analysis
9.2 Octalins (Octahydronaphthalenes)—Their Conformations
9.2.1 Six Octalins. ∆9,10-Octalin. ∆1,9-Octalin and Its Conformations and Torsion Angles. 2∆ Acetoxytestosterone (Fig. 9.10)
9.2.2 Trans-∆1,2-Octalin and Trans-∆2,3-Octalin. Torsion Angles at the Ring Junction and Their Relative Stability (Fig. 9.11)
9.2.3 Cis-∆1,2-Octalin and Cis-∆2,3-Octalin. Their Conformations and Relative Stability (Fig. 9.12)
9.3 Perhydrophenanthrenes (PHP’s). Stability. Point Groups. Optical Activity
9.3.1 Stereochemistry of Some Perhydrophenanthrones and All Perhydrodiphenic Acids (PHDPAs)
9.4 Perhydroanthracenes: Relative Stability. Torsion Angles. Point Group. Optical Activity
References
10 Stereoisomerism: Axial Chirality, Planar Chirality, (R, S) Notations. Helicity
10.1 Introduction
10.2 Stereochemistry of Allenes. Configurational Nomenclature
10.3 Chiral Spiranes and Analogs. Configurational Nomenclature
10.4 Chiral Adamantoids. Configurational Nomenclature
10.5 Chiral Catenanes. Configurational Nomenclature
10.6 Biphenyl Derivatives and Atropisomerism [8]
10.6.1 Introduction
10.6.2 Energy Profile Diagram
10.6.3 Examples of Atropisomerism
10.6.4 Orders of Steric Hindrance and of Buttressing Effect [11]
10.6.5 Configurational Nomenclature of Chiral Biphenyls (R, S or aR, aS)
10.6.6 Some Interesting Examples of Axially Chiral Molecules Exhibiting Atropisomerism
10.7 Planar Chirality
10.7.1 Introduction
10.7.2 The (R, S) Specification of Planar Chirality
10.8 Helicity and P,M-Designation
References
11 Chiroptical Properties I: Optical Rotation. ORD, CD
11.1 Origin of Optical Rotation. Circular Birefringence, Its Effect
11.2 Optical Rotatory Dispersion. Plain Curve
11.3 Circular Birefringence and Circular Dichroism. Cotton Effect
11.4 The Axial Haloketone Rule and Its Applications
11.4.1 Position of the Halogen Substituent
11.4.2 Absolute Configuration by Comparison Method
11.4.3 Absolute Configuration by Axial Haloketone Rule. Conformational Mobility
11.4.4 Boat Form of Ring A of a Steroid Bromoketone
11.5 The Octant Rule and Its Applications
11.5.1 Determination of the Preferred Conformation
11.5.2 Determination of Absolute Configuration of Trans-Decalones
11.5.3 Tricyclic Ketones: Perhydrophenanthrenones and Perhydroanthracenones
11.5.4 Tetracyclic Ketones: Steroids
References
12 Chiroptical Properties II: Helicity Rule or Chirality Rule
12.1 Introduction
12.2 Conjugated Dienes and Enones: Steroids
12.3 Biaryl Atropisomers and Helicenes
12.4 Correlation of Optical Rotation with Ligand Polarizability: Brewster’s Rule
12.5 Absolute Configuration of Chiral Allenes: Lowe’s Rule
12.6 The Exciton Chirality Method or the Dibenzoate Chirality Rule
12.7 Absolute Configuration of the 5α-Steroid Diols by Exciton Chirality Method
12.8 Absolute Configuration of Trans-Cyclohexane-1,2-Diol Enantiomers
12.9 Prediction of the First CE Signs of Vicinal and Nonvicinal Dihydroxy-5α-Steroid Diesters
12.10 Further Reading References on the Topics of This Monograph
References
Index