A. Loupy, B.Tchoubar Salt Effects in Organic and Organometallic Chemistry
1 Introduction - Classification of Specific Salt Effects 1 1.1 Specific Salt Effects Involving the Salt's Lewis Acid or Base Character 2 1.2 Salt Effects Arising from Exchange Reactions between Two Ion Pairs 3 1.3 Salt Effects Connected with the Position of Ionic Dissociation Equilibria 4 1.4 Specific Salt Effects Affecting the Structure of the Activated Complex i n the Transition State: Effect on the Stereo- and Regioselectivities 5 1.5 Salt Effects Arising from Specific Associations with Protic Solvent s (Drying Effect) 6 References 8 2 Effects of Salts on the Rates of Single Bond Cleavage Reactions 1 1 2.1 Specific Salt Effects Concerning the Heterolytic Cleavage of C-X Bonds 1 1 2.1.1 Ionization of C-X Bonds 1 1 2.1.1.1 Electrophilic assistance 1 3 2.1.1.2 Nucleophilic assistance by salts - effects of anions 1 6 2.1.2 Unimolcular Solvolysis Reactions (S N 1, E 1) 1 6 2.1.2.1 Common ion mass effect 1 8 2.1.2.2 "Normal" and "special" salt effects 1 9 2.1.2.3 Retardation by the drying salt effect : S N1 reactions in mixed solvents 2 2 2.2 Specific Salt Effects in Bimolecular Nucleophilic Reactions 2 4 2.2.1 SN2 Reactions Brought About by Anionic Nucleophiles [Scheme (2-23)] 2 4 2.2.1.1 Effect of the cation accompanying the anionic nucleophile ; ionic association or complexation of the electrophile 2 5 2.2.1.2 Salt effects in SN2 reactions involving hard anionic reactants 2 6 2.2.1.3 Salt effects in SN2 reactions involving soft anionic reactants 2 8 2.2.2 SN2 Reactions Involving Electrically Neutral Nucleophiles 3 0 2.2.2.1 Effect according to the nature of the salt anion 3 1 2.2.2.2 The case of alkali metal fluorides 3 4 2.2.2.3 Use of tetraalkylammonium fluorides 3 6 2.2.2.4 Use of fluorides on solid mineral supports 3 7 2.2.3 Other Cases of Heterolytic C-X Bond Cleavage 3 8 2.2.3.1 Aromatic nucleophilic substitutions (SN Ar) 3 8 2.2.3.2 Elimination reactions 4 2 2.3 Nucleophilic Reactions with a Hydrogen Atom Reactive Site 43 2.3.1 Cation Effects on C-H Bond Ionization caused by a Base Be 4 3 2.3.2 C-H Bond Ionization Caused by Alkali Metal Fluorides 4 6 References 47
3 Effects of Salts on Rates of Addition Reactions to Multiple Bonds 55 3.1 Anionic Nucleophilic Addition (AdN) to )C=O and Similar Bonds 5 5 3.1.1 Effect of the Cation Introduced with the Anionic Reagent: Carbonyl Complexation or Ionic Association 56 3.1.1.1 Carbonyl complexation : )C=O. M 56 3.1.1.2 Ionic association Nu M 57 3.1.1.3 Cation effects in AN. C=O reactions 5 8 3.1.2 Types of Salt Effects in AN C=0 Reactions 59 3.1.2.1 Effects due to added salt cations : carbonyl complexation or associatio n with the reactant 59 3.1.2.2 Drying effects in protic media 60 3.1.3 Salt Effects in Alkaline Ester Hydrolysis 6 1 3.1.3.1 Aliphatic esters 6 1 3.1.3.2 Aromatic esters 62 3.1.3.3 The case of phenyl acetate 63 3.1.3.4 Explanation in terms of frontier orbitals 64 3.1.4 Examples of Salt Effects in AN C=0 Reactions 66 3.1.4.1 Positive salt effects,...,. 66 3.1.4.2 Negative salt effects......_. _. 67 3.1.4.3 Catalysis by trityl perchlorate 68 3.1.5 AN C=0 Reactions Caused by Electrically Neutral Reagents 68 3.1.6 Case of Other Unsaturated Compounds Having Electrophilic Character : Nucleophilic Addition to Nitriles 70 3.2 Double Activation : Bifunctional Catalysis 72 3.2.1 The Salt Taking Part as one of the Components in Double Activation 73 3.2.1.1 As an electrophilic catalyst by means of M 73 3.2.1.2 As nucleophilic catalyst by means of X _ 76 3.2.2 The Salt Taking Part as a Bifunctional Catalyst 77 3.3 Addition Reactions to C=C Double Bonds 79 3.3.1 General Points : Substituent Effects and Types of Addition 79 3.3.1.1 Donor substituent effects 80 3.3.1.2 Withdrawing substituent effects 80 3.3.1.3 Particular case of C=C double bond a to C=0 80 3.3.2 Electrophilic Addition (AdE) 8 1 3.3.2.1 Acceleration resulting from the cation effect 82 3.3.2.2 Acceleration brought about by the anion 8 5 3.3.2.3 Acceleration of olefin oxidation by thallic salts in aqueous media throug h salt drying effects 8 8 3.3.3 Aromatic Electrophilic Substitution 8 8 3.3.3.1 Anisole acylation - : : ~,_ 8 8 3.3.3.2 Mercuration of benzene ; salt drying effects 89 3.3.4 Nucleophilic Addition to Double Bonds a to C=0 90 3.3.4.1 Accelerating effects due to the cation 90 3.3.4.2 Inhibiting effects due tothe cation 92 3.3.4.3 Salt effects 94
3.3.5 Particular Case of Halogen Addition to C=C-C=0 Conjugated Systems 9 5 References 9 7 4 Effects of Salts on Reaction Orientation (Regioselectivity) 10 3 4.1 Reactant Organization in the Vicinity of the Cation 10 3 4.1.1 Macrocycle Synthesis : the "Template Effect" 10 3 4.1.1.1 Synthesis of macrocycles in basic media 10 3 4.1.1.2 Acid catalyzed macrocycle synthesis 10 6 4.1.2 Effects of Salts on Intramolecular Cyclizations 10 7 4.1.2.1 "Intramolecular self-solvation" effect 10 7 4.1.2.2 Synthesis of benzo-18-crown-6 10 7 4.1.3 Effect of Salts on Metallation Regioselectivity 10 9 4.2 Effects of Salts on Regioselectivity of Anionic Reactions 110 4.2.1 Effects involving Electrophilic Reactants 11 0 4.2.1.1 Epoxide ring opening 11 0 4.2.1.2 I3-Elimination reactions 11 5 4.2.1.3 Reactions involving carbonyl compounds 12 1 4.2.2 Effects Arising from the Nucleophilic Reagen t (Case of Mesomeric Anions) 12 7 4.2.2.1 Effect of salts on the O/C ratio in an aprotic solvent 12 8 4.2.2.2 Effect of salts on the O/C ratio in protic solvents 13 0 4.2.2.3 Effect of salts on the O/C ratio in the case of aryloxy anions 13 1 4.2.2.4 Effects of salts on the regioselectivity of alkylation of oximate s ()C=N-O Mm) 134 4.2.2.5 Effects of salts on the ambident reactivity of aminoacid s (0/N alkylation ratio) 13 5 4.2.2.6 The case of allylic carbanions a to SPh 13 5 4.3 Effects of Salts on the Nature and Distribution of AdE2 Reactio n Products References 13 9 5 Effects of Salts on Reaction Stereochemistry 145 5.1 Effects Concerning the Electrophilic Reactant 145 5.1.1 Bimolecular Nucleophilic Substitutions 14 5 5.1.1.1 Effects at carbon 145 5.1.1.2 Effects at silicon 145 5.1.1.3 Effects at germanium 14 7 5.1.1.4 Effects at phosphorus 148 5.1.2 Ring-opening of Epoxides 14 9 5.1.3 I3-Elimination (Syn vs. Anti Elimination) 15 0 5.1.4 Reactions of Addition to Carbonyl Compounds 15 1 5.1.4.1 Stereochemistry of additions to cyclic ketones 15 1 5.1.4.2 Stereochemistry of aldol condensations 15 7 5.1.4.3 Stereochemistry of the Wittig-reaction 159
5.1.4.4 Salt effects in asymmetric synthesis 156 5.1.5 Nucleophilic Addition to Double Binds Conjugated with Electron With - drawing Groups 169 5.1.5.1 Stereochemistry of Michael-type reactions 169 5.1.5.2 Michael-type asymmetric synthesis 172 5.1.5.3 Salt effects in asymmetric Michael reactions 17 5 5.1.6 Salt Effects on the Steric Course of Nucleophilic Addition of Halogens 17 8 5.2 Effects on the Anionic Nucleophilic Reactant 180 5.2.1 C-Alkylation of Carbanionic Species 180 5.2.1.1 Influence of association between the carbanion and its Mu counterion 18 1 5.2.1.2 Role of the cation in the alkylation of carbanionic species a to a sulfoxid e group; salt effects 18 4 5.2.1.3 Role of the cation in asymmetric alkylations 18 6 5.2.1.4 a-alkylation of ketones 18 6 5.2.2. 0-Alkylation of Enolates of ß-Dicarbonyl Compounds 19 0 5.3 Electrophilic Additions : Effects of Salts on Stereochemistry 19 2 5.4 Salt Effects on the Steric Course of the Favorskii Rearrangement 19 5 5.4.1 Case of a-haloketones Without a Mobile a' Hydrogen 19 6 5.4.2 Case of a-haloketones with a Mobile a' Hydrogen 19 6 5.5 Medium Effects on the Stereochemistry of Enolate Ketonizatio n (Protonation) 20 0 5.5.1 Dissociating Protic Medium ; Effect of ph 200 5.5.2 Cation Effects on Ketonization Stereochemistry in Inert Solvents 202 References 203 6 Specific Effects of Salts on Equilibria 21 1 6.1 Concepts of Activity and Activity Coefficients. Their Significance in Equilibria 21 1 6.2 Specific Effects of Salts on Equilibria Preceding the Slow Step of Various Reactions 21 3 6.3 Some Examples Illustrating the Effects of Salts on Uncatalyzed Pre - Equilibrated Reactions 21 6 6.4 Salt Effects resulting from Equilibria between Ion Pairs 21 9 6.4.1 Reactions between Neutral Molecules to Give two Oppositely Charged Ions 220 6.4.1.1 Acid-Base equilibria between neutral species 220 6.4.1.2 Equilibria for the acylation of neutral molecules 222 6.4.2 Effects of Salts on Product Distribution for Reactions Taking Plac e Within Ion Pairs 225 6.4.2.1 Reactions of "activated sulfoxides", S m -O-CO-R, X 0 22 5 6.4.2.2 Epoxide ring opening in acid media 22 8 6.4.2.3 Electrophilic additions to alkenes 229
6.4.2.4 Aromatic electrophilic substitutions 23 0 6.4.2.5 Reductions by silanes in acid media 23 0 6.4.2.6 Carbon-Carbon bond formation in oxidizing media 23 1 6.4.3 Reactions Involving Radical Ions 23 2 6.4.3.1 Photoisomerizations 23 3 6.4.3.2 Photochemical organic reactions 23 4 6.4.3.3 Reactivity of aromatic radical cations 23 7 References 23 8 7 Salt Effects in Organometallic Chemistry 24 1 7.1 Main Group Metals : Li, Mg 24 1 7.1.1 Salt Effects in Organolithium Chemistry 24 1 7.1.1.1 Salt effects involving the organolithium reagent 24 1 7.1.1.2 Salt effects onvolving the substrate 24 4 7.1.1.3 Stabilization of a-halo organolithium reagents by lithium salts : )C(X)Li (carbenoids) 245 7.1.1.4 Case of organolithium reagents of the type R(Li)C=O 24 7 7.1.1.5 Structure and reactivity of lithium amides 24 9 7.1.2 Salt Effects in Grignard Reagent Chemistry 25 0 7.1.2.1 Structure of Grignard reagents 25 0 7.1.2.2 Salt effects 25 2 7.2 Salt Effects in Transition Metal Chemistry 25 4 7.2.1 Anion Effects 25 4 7.2.1.1 Anion effects on the structure of complexes 25 4 7.2.1.2 Effect of Xe anions on nucleophilicity of complexes 25 5 7.2.1.3 Enhancement by anions of the reducing power of zerovalen t metal complexes 266 7.2.1.4 Anion effects on the stereo- and regioselectivity of reactions catalyzed by palladium complexes 269 7.2.2 Cation Effects 27 2 7.2.2.1 Cation participation in migratory insertions 27 3 7.2.2.2 Cation effects on the structure of anionic complexes 27 4 7.2.2.3 Cation effects on the reactivity of anionic complexes 27 5 7.2.3 Reactions Taking Place Within a Contact Ion Pair 27 9 References 27 9 8 Appendix 28 9 8.1 Revision of Some General Concepts 28 9 8.1.1 Ionic Strength of a Solution 28 9 8.1.2 Acidity Functions 28 9 8.2 Solvent Classification 29 1 8.2.1 Protic and Aprotic Solvents 29 1 8.2.2 Donor and Acceptor Solvents 291
8.2.2.1 Donor solvents; donor number scale 29 1 8.2.2.2 Acceptor solvents ; acceptor number scale 29 2 8.3 Ionic Associations 292 8.3.1 Coulombic Interactions 292 8.3.2 "Hard" and "Soft" Ions (HSAB Classification : Hard and Soft Acids and Bases) 293 8.3.3 Preferential Ionic Associations : "Symbiotic Effect" 294 8.3.4 The Various Types of Ion Pair 294 8.3.5 Concept of Aggregates 29 5 8.4 Perturbation Theory Applied to Chemical Reactivity 29 5 8.4.1 Klopman Equation : Charge and Orbital Control 29 5 8.4.2 Applications to Reactivity 29 6 8.4.2.1 Reaction kinetics 296 8.4.2.2 Reaction regioselectivity 297 8.4.3 Application to the HSAB Principle : Interactions Between Soft Ion s (Symbiotic Effect) 297 8.5 Concerning Transition Metal Chemistry 298 8.5.1 Degree of Coordination Unsaturation of a Transition Metal in a Complex 298 8.5.2 Formal Oxidation State of a Transition Metal in a Complex 299 8.5.3 Oxidative Addition and Reductive Elimination 299 8.5.4 Intramolecular Insertions 300 8.6 Hydrophobic and Hydrophilic Effects ; Salting-In and Salting-Out Effects 30 1 References 302 9 Supplement - Recent Publications 30 5 Index 311