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

The development of some new synthetic reactions derived from nucleophilic addition of phosphines to electron-deficient carbon-carbon triple bonds is described. These reactions show that the phosphine plays the role of a nucleophile as well as an excellent leaving group. The central problem is to generate a 1,3-dipole from alkynoates or allenoates (2,3-butadienoates) by interaction with various phosphines. This study illuminates the unusual phenomena and shows how this understanding allows control of the reaction.

Reactions of electron-deficient alkynes and allenes under phosphine catalysis.

Construction of enantiopure pyrrolidine ring system via asymmetric [3+2]-cycloaddition of azomethine ylides.

Applications of NMR Spectroscopy in Organic Chemistry.

The sphingolipid bases, D-erythro- and D-threo-sphingosines, are the target molecules that have been synthesized to demonstrate the efficiency of a new methodology to control both absolute and relative configurations in acyclic systems. Tubulysins are compounds of extraordinary potency, rapidly degrading the tubulin cytoskeleton, with tubulysin D being the most active tubulin-modifier known so far. Among other isonitriles, isocyanoacetate derivatives occupy an important place in the field of synthetic application and reaction diversity, which makes them strongly attractive objects for investigation. The unique multifunctional nature of isocyanoacetic acid derivatives opens up a range of exciting reactions, especially tandem/cascade processes for the synthesis of complex cyclic and macrocyclic systems. Multicomponent chemistry of isocyanoacetates is also a powerful instrument to access different classes of biochemically relevant compounds such as peptides, peptide molecules, and nitrogen heterocycles.

Isocyanoacetate derivatives: synthesis, reactivity, and application.

A new synthesis of 9-hydroxy- and 9-(alkylamino)thiazolo[5,4-b]quinolines by cyclization of 4-(ethoxycarbonyl)-5-(arylamino)thiazoles and 5-(arylamino)-4-carbamoylthiazoles, respectively, is described. In vitro cytotoxicity of a large number of derivatives of these compounds has been tested against several cell lines. The highest activities observed are associated with the presence of a 2-[[(N,N-diethylamino)ethyl]amino] substituent at C-2 and a fluorine atom at the C-7 position of the tricyclic planar heteroaromatic framework. Three structural features seem to be essential for antitumor activities:  a positive charge density at carbon C-7, a side chain at position C-2 or C-9 of the thiazoloquinoline skeleton with two basic nitrogens and a pKa value of 7.5−10 in the most basic center, and a conformational flexibility of this basic side chain. These structural requirements must be simultaneously satisfied in order to ensure a significant antitumor activity.

Synthesis and antitumor evaluation of new thiazolo[5,4-b]quinoline derivatives.

Synthesis of gamma,delta-didehydrohomoglutamates by the phosphine-catalyzed gamma-addition reaction to acetylenic esters

Synthesis, Configurational Assignment and Conformational Analysis of .beta.-Hydroxy Sulfoxides, Bioisosteres of Oxisuran Metabolites, and their O-Methyl Derivatives

Carboxylates as pronucleophiles in the phosphine-catalyzed γ-addition reaction

Sm(III)-azomethine ylides 2 have been generated from ketones 1. Cycloaddition of ylides 2 with alpha,beta-unsaturated esters 3 through a transition state chelation-controlled by the metal allowed for the asymmetric synthesis of gamma-carboxypyroglutamates having a quaternary alpha-carbon that are potentially useful in the synthesis of neuroprotective agents.

Carlos Alvarez-Ibarra

Papers

Synthesis and antitumor evaluation of new thiazolo[5,4-b]quinoline derivatives.

Synthesis of gamma,delta-didehydrohomoglutamates by the phosphine-catalyzed gamma-addition reaction to acetylenic esters

Synthesis, Configurational Assignment and Conformational Analysis of .beta.-Hydroxy Sulfoxides, Bioisosteres of Oxisuran Metabolites, and their O-Methyl Derivatives

Carboxylates as pronucleophiles in the phosphine-catalyzed γ-addition reaction

Diastereoselective Synthesis of alpha,alpha-Disubstituted gamma-Carboxypyroglutamates via Sm(III)-Azomethine Ylide Cycloadditions.