The legacy of Gilbert Newton Lewis (1875-1946) pervades the lexicon of chemical bonding and reactivity. The power of his concept of donor-acceptor bonding is evident in the eponymous foundations of electron-pair acceptors (Lewis acids) and donors (Lewis bases). Lewis recognized that acids are not restricted to those substances that contain hydrogen (Bronsted acids), and helped overthrow the "modern cult of the proton". His discovery ushered in the use of Lewis acids as reagents and catalysts for organic reactions. However, in recent years, the recognition that Lewis bases can also serve in this capacity has grown enormously. Most importantly, it has become increasingly apparent that the behavior of Lewis bases as agents for promoting chemical reactions is not merely as an electronic complement of the cognate Lewis acids: in fact Lewis bases are capable of enhancing both the electrophilic and nucleophilic character of molecules to which they are bound. This diversity of behavior leads to a remarkable versatility for the catalysis of reactions by Lewis bases.

Lewis Base Catalysis in Organic Synthesis

Stereochemical Control in Organic-Synthesis Using Silicon-Containing Compounds

The aldol addition is one of the most important methods for stereoselective construction of carboncarbon bonds. New and powerful variants of these classical reactions have been developed in recent years.1 Two classes were mainly used for asymmetric induction in these reactions: the use of asymmetric modified enolates or electrophiles2 and the use of chiral Lewis acids.3 The chiral enolate or electrophile approach is much more general and gives high stereoselectivities due to the highly ordered nature of transition structures (“closed” transition models). The chiral center has to be removed after the completed aldol addition. To avoid this additional reaction step, a stategy is employed whereby achiral enolates can be reacted with achiral carbonyl compounds in the presence of additional chiral auxiliaries. This method requires the careful use of a chiral auxiliary.4 Unfortunately, however, stoichiometric amounts of the chiral information are necessary. Up to now and apart from enzymatic transformations, the so-called Mukaiyama reaction has opened an enantioselective and catalytic approach using chiral Lewis acids. This review covers the evolution of stereoselective Lewis-acid-mediated aldol-type addition up to the recent development of chiral Lewis acids. Mukaiyama et al. found that silyl enol ether reacts with carbonyl compounds in the presence of Lewis acids to give aldol products (for initial studies, see ref 5). The main advantages in the Mukaiyama approach are the chemoselectivity of the reaction and the possibility of stereoselective execution. Since the mid-1970s, the Mukaiyama reaction has become a useful method for chemoand regioselective carboncarbon bond formation.6 About 10 years later, investigations into stereochemical aspects of these reactions were initiated,7 and at the end of the 1980s, the development of chiral Lewis acids and thus the development of catalytic, enantioselective versions of the Mukaiyama reaction started.8 The reaction mechanism has not been explained yet. The most important fact is that Lewis acid enolates are not involved in this reaction.7 No transmetalation occurs. In this reaction, the Lewis acids coordinate with the carbonyl function leading to its activation.9 Two works published by Carreira and Shibasaki suggest the involvement of chiral metal enolates during the aldol addition (for copper enolates, see ref 10; for palladium enolates, see ref 11). Moreover, there is a marked stereochemical differRainer Mahrwald obtained his M.S. degree in chemistry from the MartinLuther-University, Halle, in 1973. In 1975 he joined the Institute “Manfred von Ardenne”, Dresden, where he obtained his Ph.D. in 1979 in the field of the synthesis of nuclesides. In 1980 he joined the Academy of Sciences in Berlin. There he worked in the field of total synthesis of prostaglandins. He pursued his formation as a postdoctoral fellow at Philipps-University, Marburg, in the group of Prof. M. T. Reetz (1991). Since 1994 he has been a lecturer at the Humbold-University. His main research interests have been associated with the development of catalytic stereoselective C−C bond formation. 1095 Chem. Rev. 1999, 99, 1095−1120

Diastereoselection in lewis-Acid-mediated aldol additions.

Trimethylsilyl nucleophiles (Me3SiNu), with silicon atoms attached to carbon, nitrogen, oxygen, or sulfur atoms, have long been recognized as effective alternatives for proton nucleophiles (HNu) in addition reactions to such electrophiles as aldehydes, ketones, imines, oxiranes, aziridines, nitrones, and polar conjugated systems. The number of examples of such additions has been growing steadily over the past 40 years, while the availability of trimethylsilyl nucleophiles was on the rise and new methods of transformation of silylated pronucleophiles into active nucleophiles were emerging. The interest in Me3SiNu additions was stimulated by the properties of the silicon atom, allowing the generation of active nucleophilic species (Nu), under different conditions in comparison to HNu sources. Activation of Me3SiNu by a Lewis base is primarily due to the affinity of silicon to fluorine or oxygen, facilitating the formation of a reactive pentacoordinate or hexacoordinate silicon intermediate, whereas HNu activation requires Brønsted or Lewis basemediated proton abstraction. Although activation of Me3SiNu and HNu may frequently be carried out with the same catalyst, deprotonation of weakly acidic carbon nucleophiles by strong bases in certain cases may be incompatible with the reaction conditions or with certain functional groups. Desilylative nucleophile activation occurs smoothly under catalytic conditions. Either 1,2-, 1,3-, or 1,4-additions can be carried out with trimethylsilyl nucleophiles, as shown in Scheme 1. The catalytic effect of the fluoride ion as well as polar N-oxide, P-oxide, and S-oxide bonds can be correlated with the dissociation energies of the Si-F and Si-O bonds (Figure 1), which are among the strongest single bonds and much stronger than the corresponding C-F and C-O bonds. Either anionic or neutral Lewis bases are suitable for activation of silylated nucleophiles. Both inorganic (especially CsF) and organic fluorides (most frequently tetra-nScheme 1. Catalytic Nucleophilic 1,2-Additions of Me3SiNu to Aldehydes, Ketones, and Imines (a) or to Epoxides and Aziridines (b), 1,3-Addition to Nitrones (c), and 1,4Additions to r, -Unsaturated Carbonyl Compounds (d) and Nitroalkenes (e) Chem. Rev. 2008, 108, 5227–5252 5227

Recent Progress in Lewis Base Activation and Control of Stereoselectivity in the Additions of Trimethylsilyl Nucleophiles

Lewis‐Base‐Katalyse in der organischen Synthese

Chiral quarternary ammonium fluoride. A new reagent for catalytic asymmetric aldol reactions

Catalytic enantioselective aldol reactions of silyl enol ethers with benzaldehyde in high enantiomeric excesses were realized by utilizing chiral quarternary ammonium fluoride.

T. Miura

Papers

Chiral quarternary ammonium fluoride. A new reagent for catalytic asymmetric aldol reactions

Chiral Quarternary Ammonium Fluoride. A New Reagent for Catalytic Asymmetric Aldol Reactions.

Use of Chiral Quaternary Salts in Asymmetric Synthesis