Current Organic Chemistry - Volume 10, Issue 15, 2006

Organoselenium chemistry continues to attract the attention of many researchers. Perhaps the underlying reason for this is the broad interest in the unique applications of selenium to inorganic, biological, and organic chemistries. Inorganic selenium complexes range from metal complexes and new materials (organic semiconductors) to quantum dots. Since the discovery of selenium as an essential trace element, the role of selenium in biological systems has been actively investigated. There are many selenium- containing proteins that have been discovered. A large number of these are involved in redox reactions and the most commonly encountered proteins are glutathione peroxidase, selenoprotiens and selenophosphate synthetase 2. Incorporation of selenium into proteins can be accomplished with selenocysteine and selenomethionine. In fact, selenocysteine is the 21st proteinogenic amino acid. The special role that selenium plays in many of these biological systems can be directly linked to its unique chemical and physical properties. New developments in organoselenium chemistry are a reflection of the diversity of reactions that are accessible. Anionic, cationic, and radical behaviors have been well studied and are usually represented in the initial strategies researchers use when devising a chemical transformation. Other reactions, such as rearrangements and eliminations, are frequently employed. The recent discovery of non-bonded interactions of the divalent selenium atom with heteroatoms has been instrumental in the development of novel chemistry in which this interaction plays a critical role in the outcome of the reaction. Many of these processes are attractive because of the ease of selenium introduction, access to multiple oxidation states, and ease of removal at the end of the sequence, giving rise to predictable chemo, regio, and stereoselectivity. Logical extensions of many of these novel chemistries have led to the development of asymmetric methods which, in many cases, have provided chemical manifolds to gain access to chiral compounds with excellent enantiomeric excesses. This issue of Current Organic Chemistry presents specific examples of new advances in asymmetric methods that employ selenium as a chiral controller unit. The reports authored by Professor T. Wirth and D. M. Browne (New Developments with Chiral Electophilic Selenium Regents), Professor C. Zhu and Y. Huang (Asymmetric Synthesis of Chiral Organoselenium Compounds), Professor A. L. Braga, D. S. L udtke, and F. Vargas (Enantioselective Synthesis Mediated by Catalytic Chiral Organoselenium Compounds), and Professor Y. Guindon, B. Cardinal-David, J-F. Brazeau, I. A. Katsoulis (Phenylselenoethers as Precursors of Acylic Free Radicals. Creating Tertiary and Quaternary Centers Using Free Radical-Based Intermediates) are excellent examples of the level of science that is moving this field forward. Professor T. Murai and T. Kimura present recent advances in the “Syntheses and Properties of Phosphinoselenoic Chlorides, Acids and Their Salts.” In this manuscript the synthesis and characterization of optically active phosphinoselenoic acid derivatives is described. This important work enables the steric and electronic tuning of organophosphorus compounds to improve on catalytic processes. The manuscript by Dr. D. Kimball and L. A. “Pete” Silks reviews the literature on this segment of aldol reactions and briefly describes the use of a chiral selenocarbonyl controller unit to promote such reactions. Finally, the report of Professor M. P. Cole (“Utilization of Nonbonded Interactions Involving Organoselenium Compounds”) includes a review of the literature that pertains to weak interactions involving the selenium atom. With the advances in methods to directly observe these weak interactions a general realization has emerged that, indeed, these interactions can be quantified, physically described, and more importantly utilized to design molecular complexes with defined reactivities. The author has assimilated the most recent developments in this area of organoselenium chemistry and biochemistry, specifically where the role of non-bonded interactions have been implicated, studied or used. This manuscript describes a physical basis for these types of interactions, links a number of areas of science to a common theme, and clearly demonstrates that these interactions are more prevalent than once ever imagined.

This review describes the development of enantiomerically pure selenium reagents as electrophiles in stereoselective synthesis. It outlines the addition of selenium electrophiles to alkenes, which can be used as part of key reactions in various transformations. Different nucleophiles can be employed in the addition reactions including oxygen, nitrogen and carbon nucleophiles. Furthermore, it has been shown that selenocyclisations can been performed using similar nucleophiles for the formation of different heterocycles. It has been established that the structure of the selenium electrophile, its counterion and the solvent all influence the course of these reactions. Most transformations use stoichiometric amounts of selenium containing reagents. Recently, selenenylation - deselenenylation reactions were discovered where only catalytic amounts of reagents are necessary.

Chiral organoselenium compounds can be attained from three types of asymmetric synthesis. Chiral substratecontrolled methods, chiral auxiliary-controlled methods, and chiral catalyst-controlled methods toward optically active organoselenium derivatives were illustrated. The strategy and classification of methods underlying all asymmetric synthesis therefore involve enantiomerically pure compounds to influence the stereochemical outcome of the reactions. In this review, the advances in asymmetric synthesis of some important classes of chiral organoselenium compounds were described.

Selenium-based methods have developed rapidly over the past few years and certain features of chiral selenium-containing compounds make these reagents particularly valuable for efficient stereoselective reactions. Recent advances in stereoselective transformations involving one-pot selenenylation-deselenylation sequences, which occur using only catalytic amounts of the optically active diselenides in the synthesis of valuable building blocks will be summarized. Additionally, recent results of catalytic reactions using chiral selenides and diselenides such as the enantioselective copper catalyzed conjugate addition of organometallic reagents to enones, diorganozinc addition to aldehydes, palladium-catalyzed enantioselective allylic alkylation, among other topics will also be addressed.

In the last two decades, enantioselective and diastereoselective free radical-based processes have started to emerge as viable methods to create stereogenic centers. To this end, chemists have taken advantage of the homolytic carbon-selenium bond cleavage as an efficient way to generate carbon-centered radicals. The reactivity of the radicals generated from β-hydroxy (or alkoxy) α-phenylseleno (or α-halo) esters in hydrogen transfer or allylation reactions will be reviewed. The minimization of the allylic-1,3 strain and the intramolecular dipole-dipole effect in the transition states are at the origin of the diastereoselectivities noted in these reactions (acyclic stereocontrol). The predominance of the anti isomer, in the hydrogen transfer reactions, has been shown to be enhanced by taking advantage of the exocyclic effect. Lewis acids were successfully used to create temporary cycles to the carbon-centered radical in order to induce the latter effect. Reversing the sense of the diastereoselectivity could be efficiently achieved using bidendate Lewis acids through the endocyclic effect. The synthesis of stereogenic quaternary centers using free radical-based allylation is described. The development of tandem reactions combining the Mukaiyama and the hydrogen transfer reactions, with various Lewis acids, led to the synthesis of propionates and polypropionate motifs. The use of novel phenylselenoenoxysilanes in the Mukaiyama reaction is described.

The synthetic methods for phosphinoselenoic chlorides, acids, and alkali metal and ammonium salts are overviewed. The addition of elemental selenium to trivalent chlorophosphines readily took place to give phosphinoselenoic chlorides. P-Chiral chlorides were efficiently prepared by the one-pot reaction of dichlorophenylphosphine or phosphorus trichloride with elemental selenium and Grignard reagents. The amination of the chlorides with optically active amines led to optically active phosphinoselenoic amides, which were applied to asymmetric synthesis as optically active ligands. The reaction of the chlorides with carbon nucleophiles occurred both at the phosphorus and selenium atoms, and the selectivity depended on the carbon nucleophiles used and the substituents at the phosphorus atom of the chlorides. The chlorides were used as key precursors leading to a variety of phosphinoselenoic, -selenothioic, -diselenoic acids and their alkali metal and ammonium salts. Finally, the stereochemical outcome at the phosphorus atom in the synthesis and substitution reaction of optically active P-chiral phosphinoselenoic chlorides is shown.

The aldol reaction of acetate and methyl ketone-based donors with aldehyde acceptors is reviewed. Emphasis is placed on major advances reported in the last 10-15 years. Several methods for inducing chirality at the newly formed stereogenic center are discussed, including popular alternate methods for equivalent syntheses. Different methods for stereospecific synthesis are compared in terms of yield, selectivity, ease of synthesis, and applicability to both small molecule and large macrolide production.

Nonbonded interactions involving selenium have been recognized for many years and are known to involve a number of groups and atoms that form close contacts to the chalcogen atom. With substantial improvements in high field NMR spectroscopy and single crystal X-ray diffraction, enabling such techniques to become ever more accessible, further understanding of the role that these interactions play in the chemistry of selenium has been gained in recent years. Given the well documented use of organoselenium compounds in organic chemistry and the recognition that certain enzymatic pathways utilize selenium within the active centre, the design of new systems that incorporate a group able to form nonbonded interactions of the type Se···Y forms an important field of research, with particular interest in how this affects the chemistry associated with the resultant selenium reagent. This article aims to bring together some of the more recent developments in the area of organoselenium chemistry, specifically where the role of nonbonded interactions have been implicated in affecting the outcome of the observed reactivity.