A. Loupy, B.Tchoubar

Salt Effects in Organic andOrganometallic 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 nthe 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 12 .1 .1

Ionization of C-X Bonds 1 12 .1 .1 .1 Electrophilic assistance 1 32 .1 .1 .2 Nucleophilic assistance by salts - effects of anions 1 62 .1 .2

Unimolcular Solvolysis Reactions (S N1, E 1 ) 1 62 .1 .2 .1 Common ion mass effect 1 82 .1 .2 .2 "Normal" and "special" salt effects 1 92 .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 42 .2 .1

SN2 Reactions Brought About by Anionic Nucleophiles [Scheme (2-23)] 2 42 .2 .1 .1 Effect of the cation accompanying the anionic nucleophile ; ionic associa-

tion or complexation of the electrophile 2 52 .2 .1 .2 Salt effects in SN2 reactions involving hard anionic reactants 2 62 .2 .1 .3 Salt effects in SN2 reactions involving soft anionic reactants 2 82 .2 .2

SN2 Reactions Involving Electrically Neutral Nucleophiles 3 02 .2 .2 .1 Effect according to the nature of the salt anion 3 12 .2 .2 .2 The case of alkali metal fluorides 3 42 .2 .2 .3 Use of tetraalkylammonium fluorides 3 62 .2 .2 .4 Use of fluorides on solid mineral supports 3 72 .2 .3 Other Cases of Heterolytic C-X Bond Cleavage 3 82 .2 .3 .1 Aromatic nucleophilic substitutions (SNAr) 3 82 .2 .3 .2 Elimination reactions 4 2

2 .3

Nucleophilic Reactions with a Hydrogen Atom Reactive Site 432 .3 .1 Cation Effects on C-H Bond Ionization caused by a Base Be 4 32 .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 53 .1 .1

Effect of the Cation Introduced with the Anionic Reagent : CarbonylComplexation or Ionic Association 56

3 .1 .1 .1 Carbonyl complexation : )C=O . • • M° 563 .1 .1 .2 Ionic association Nu°M ® 573 .1 .1 .3 Cation effects in AN. C=O reactions 5 8

3 .1 .2 Types of Salt Effects in AN C=0 Reactions 593 .1 .2 .1 Effects due to added salt cations : carbonyl complexation or associatio n

with the reactant 593 .1 .2 .2 Drying effects in protic media 603 .1 .3

Salt Effects in Alkaline Ester Hydrolysis 6 13 .1 .3 .1 Aliphatic esters 6 13 .1 .3 .2 Aromatic esters 623 .1 .3 .3 The case of phenyl acetate 633 .1 .3 .4 Explanation in terms of frontier orbitals 643 .1 .4 Examples of Salt Effects in AN C=0 Reactions 663 .1 .4 .1 Positive salt effects , .

. .,

. 663 .1 .4 .2 Negative salt effects

. .

.. . ._

. _ . 673 .1 .4 .3 Catalysis by trityl perchlorate 683 .1 .5 AN C=0 Reactions Caused by Electrically Neutral Reagents 683 .1 .6 Case of Other Unsaturated Compounds Having Electrophilic Character :

Nucleophilic Addition to Nitriles 70

3 .2

Double Activation : Bifunctional Catalysis 723 .2 .1

The Salt Taking Part as one of the Components in Double Activation 733 .2 .1 .1 As an electrophilic catalyst by means of M ®

733 .2 .1 .2 As nucleophilic catalyst by means of X ® _

763 .2 .2

The Salt Taking Part as a Bifunctional Catalyst 77

3 .3

Addition Reactions to C=C Double Bonds 793 .3 .1

General Points : Substituent Effects and Types of Addition 793 .3 .1 .1 Donor substituent effects 803 .3 .1 .2 Withdrawing substituent effects 803 .3 .1 .3 Particular case of C=C double bond a to C=0 803 .3 .2

Electrophilic Addition (AdE) 8 13 .3 .2 .1 Acceleration resulting from the cation effect 823 .3 .2 .2 Acceleration brought about by the anion 8 53 .3 .2 .3 Acceleration of olefin oxidation by thallic salts in aqueous media throug h

salt drying effects 8 83 .3 .3

Aromatic Electrophilic Substitution 8 83 .3 .3 .1 Anisole acylation

- : : ~,_ 8 83 .3 .3 .2 Mercuration of benzene ; salt drying effects 893 .3 .4 Nucleophilic Addition to Double Bonds a to C=0 903 .3 .4 .1 Accelerating effects due to the cation 903 .3 .4 .2 Inhibiting effects due tothe cation 923 .3 .4 .3 Salt effects 94

3 .3 .5 Particular Case of Halogen Addition to C=C-C=0 Conjugated Systems 9 5References 9 7

4

Effects of Salts on Reaction Orientation (Regioselectivity) 10 3

4 .1

Reactant Organization in the Vicinity of the Cation 10 34 .1 .1

Macrocycle Synthesis : the "Template Effect" 10 34 .1 .1 .1 Synthesis of macrocycles in basic media 10 34 .1 .1 .2 Acid catalyzed macrocycle synthesis 10 64 .1 .2

Effects of Salts on Intramolecular Cyclizations 10 74 .1 .2 .1 "Intramolecular self-solvation" effect 10 74 .1 .2 .2 Synthesis of benzo-18-crown-6 10 74 .1 .3

Effect of Salts on Metallation Regioselectivity 10 9

4 .2

Effects of Salts on Regioselectivity of Anionic Reactions 11 04 .2 .1

Effects involving Electrophilic Reactants 11 04 .2 .1 .1 Epoxide ring opening 11 04 .2 .1 .2 I3-Elimination reactions 11 54 .2 .1 .3 Reactions involving carbonyl compounds 12 14 .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 84 .2 .2 .2 Effect of salts on the O/C ratio in protic solvents 13 04 .2 .2 .3 Effect of salts on the O/C ratio in the case of aryloxy anions 13 14 .2 .2 .4 Effects of salts on the regioselectivity of alkylation of oximate s

()C=N-O°Mm) 1344 .2 .2 .5 Effects of salts on the ambident reactivity of aminoacid s

(0/N alkylation ratio) 13 54 .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 ReactionProducts

References 13 9

5

Effects of Salts on Reaction Stereochemistry 145

5 .1

Effects Concerning the Electrophilic Reactant 1455 .1 .1

Bimolecular Nucleophilic Substitutions 14 55 .1 .1 .1 Effects at carbon 1455 .1 .1 .2 Effects at silicon 1455 .1 .1 .3 Effects at germanium 14 75 .1 .1 .4 Effects at phosphorus 1485 .1 .2

Ring-opening of Epoxides 14 95 .1 .3

I3-Elimination (Syn vs. Anti Elimination) 15 05 .1 .4

Reactions of Addition to Carbonyl Compounds 15 15 .1 .4 .1 Stereochemistry of additions to cyclic ketones 15 15 .1 .4 .2 Stereochemistry of aldol condensations 15 75 .1 .4 .3 Stereochemistry of the Wittig-reaction 159

5 .1 .4 .4 Salt effects in asymmetric synthesis 1565 .1 .5 Nucleophilic Addition to Double Binds Conjugated with Electron With -

drawing Groups 169

5 .1 .5 .1 Stereochemistry of Michael-type reactions 1695 .1 .5 .2 Michael-type asymmetric synthesis 1725 .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 1805 .2 .1

C-Alkylation of Carbanionic Species 180

5 .2 .1 .1 Influence of association between the carbanion and its Mu counterion 18 15 .2 .1 .2 Role of the cation in the alkylation of carbanionic species a to a sulfoxid e

group; salt effects 18 45.2 .1 .3 Role of the cation in asymmetric alkylations 18 65.2 .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 55 .4 .1

Case of a-Haloketones Without a Mobile a' Hydrogen 19 65.4 .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 2005 .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 inEquilibria 21 1

6 .2

Specific Effects of Salts on Equilibria Preceding the Slow Step of VariousReactions 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 96 .4 .1

Reactions between Neutral Molecules to Give two Oppositely ChargedIons 220

6 .4 .1 .1 Acid-Base equilibria between neutral species 2206 .4 .1 .2 Equilibria for the acylation of neutral molecules 2226 .4 .2

Effects of Salts on Product Distribution for Reactions Taking Plac eWithin Ion Pairs 225

6 .4.2 .1 Reactions of "activated sulfoxides", S m -O-CO-R, X0 22 5

6 .4.2 .2 Epoxide ring opening in acid media 22 86 .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 06 .4 .2 .6 Carbon-Carbon bond formation in oxidizing media 23 16 .4 .3

Reactions Involving Radical Ions 23 2

6 .4 .3 .1 Photoisomerizations 23 36 .4 .3 .2 Photochemical organic reactions 23 46 .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 17 .1 .1 .1 Salt effects involving the organolithium reagent 24 17 .1 .1 .2 Salt effects onvolving the substrate 24 47 .1 .1 .3 Stabilization of a-halo organolithium reagents by lithium salts :

)C(X)Li (carbenoids) 2457 .1 .1 .4 Case of organolithium reagents of the type R(Li)C=O 24 77 .1 .1 .5 Structure and reactivity of lithium amides 24 97 .1 .2

Salt Effects in Grignard Reagent Chemistry 25 07 .1 .2 .1 Structure of Grignard reagents 25 07 .1 .2 .2 Salt effects 25 2

7 .2

Salt Effects in Transition Metal Chemistry 25 47 .2 .1

Anion Effects 25 47 .2 .1 .1 Anion effects on the structure of complexes 25 47 .2.1 .2 Effect of Xe anions on nucleophilicity of complexes 25 57 .2 .1 .3 Enhancement by anions of the reducing power of zerovalen t

metal complexes 2667 .2.1 .4 Anion effects on the stereo- and regioselectivity of reactions catalyzed

by palladium complexes 2697 .2 .2

Cation Effects 27 27 .2 .2.1 Cation participation in migratory insertions 27 37 .2.2 .2 Cation effects on the structure of anionic complexes 27 47 .2 .2 .3 Cation effects on the reactivity of anionic complexes 27 57 .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 98 .1 .1

Ionic Strength of a Solution 28 98 .1 .2

Acidity Functions 28 9

8 .2

Solvent Classification 29 18 .2 .1

Protic and Aprotic Solvents 29 18 .2 .2 Donor and Acceptor Solvents 291

8 .2 .2 .1 Donor solvents ; donor number scale 29 18 .2 .2 .2 Acceptor solvents ; acceptor number scale 29 2

8 .3

Ionic Associations 2928 .3 .1

Coulombic Interactions 2928 .3 .2

"Hard" and "Soft" Ions(HSAB Classification : Hard and Soft Acids and Bases) 293

8 .3 .3

Preferential Ionic Associations : "Symbiotic Effect" „ 2948 .3 .4 The Various Types of Ion Pair 2948 .3 .5 Concept of Aggregates 29 5

8 .4

Perturbation Theory Applied to Chemical Reactivity 29 58 .4 .1

Klopman Equation : Charge and Orbital Control 29 58 .4 .2

Applications to Reactivity 29 68 .4.2.1 Reaction kinetics 2968 .4 .2.2 Reaction regioselectivity 2978 .4.3

Application to the HSAB Principle : Interactions Between Soft Ion s(Symbiotic Effect) 297

8 .5

Concerning Transition Metal Chemistry 2988 .5 .1

Degree of Coordination Unsaturation of a Transition Metal in aComplex 298

8 .5 .2 Formal Oxidation State of a Transition Metal in a Complex 2998 .5 .3

Oxidative Addition and Reductive Elimination 2998 .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