3986 Current Organic Chemistry, 2011, 15, 3986-4020 1385-2728/11 $58.00+.00 © 2011 Bentham Science Publishers Preparation of Stabilized Phosphorus Ylides via Multicomponent Reactions and Their Synthetic Applications Ali Ramazani * and Ali Reza Kazemizadeh Research Laboratory of MCRs, Department of Chemistry, Zanjan Branch, Islamic Azad University, P O Box 49195-467, Zanjan, Iran Abstract: Triphenylphosphine (TPP), dialkyl acetylenedicarboxylates (DAAD), and acids such as phenols, imides, amides, enols, oximes and alcohols react with each other via a multicomponent reaction to produce stabilized phosphorus ylides. The reactions take place easily, through formation of intermediate formed by the Michael addition of the triphenylphosphine to dialkyl acetylenedicarboxylates and concomitant protonation of the intermediate by an acid leads to vinyltriphenylphosphonium salts. The salts are unstable intermediates and undergo a subsequent Michael addition leads to stabilized phosphorus ylides. In some cases ylide products are stable, but in other cases they cannot be isolated and appear to occur as intermediates on the pathway to an observed product. The stabilized phosphorus ylides are able to take part in the normal intramolecular Wittig reactions and produce a variety of heterocyclic or carbocyclic compounds, but they are not able to participate in the intermolecular Wittig reactions. Keywords: Stabilized phosphorus ylides, triphenylphosphine, dialkyl acetylenedicarboxylates, multicomponent reaction, vinyltriphenylphos- phonium salts, intramolecular Wittig reaction. INTRODUCTION Organophosphorus compounds, i.e. those bearing a carbon atom directly bound to a phosphorus atom, are synthetic targets of interest, not least because of their value for a variety of industrial, biological, and chemical synthetic uses. Organophosphorus compounds have been extensively employed in organic synthesis [1-15] as useful reagents, as well as ligands in a number of transition metal catalysts [16]. Phosphorus ylides are a class of special type of zwitterions, which bear strongly nucleophilic electron rich carbanions. The electron distribution around the P + –C  bond and its consequent chemical implications had been probed and assessed through theoretical, spectroscopic and crystallographic investigations. The phosphorus ylides is an outstanding achievement in the chemistry of the twentieth century [17]. The versatile reactivity of phosphorus ylides enables their use as starting reactant in the synthesis of many important organic compounds. The synthetic utility of the phosphorus ylides as highly effective reagents for organic synthesis is most clearly shown by their reaction with carbonyl compounds. During recent years the chemistry of phosphorus ylides has been extensively developed, their chemical properties have been studied in details. Phosphorus ylides have found use in a wide variety of reactions of interest to synthetic chemists, especially in the synthesis of naturally occurring products, compounds with biological and pharmacological activity [18-24]. Proton affinity of these ylides can be used as a molecular guide to assess their utility as synthetic reagents and their function as ligands in coordination and organometallic chemistry [16, 18]. The nucleophilicity at the ylidic carbon is a factor of essential mechanistic importance in the use of these ylides as Wittig reagents. The development of the modern chemistry of natural and physiologically active compounds would have been impossible without the phosphorus ylides. Because of their unique molecular and electronic structure, phosphorus ylides undergo a wide variety of reactions. These compounds have attained great significance as *Address correspondence to these authors at the Research Laboratory of MCRs, Department of Chemistry, Zanjan Branch, Islamic Azad University, P O Box 49195-467, Zanjan, Iran; Tel: +98 241 4210735; Fax: +98 241 4261221; E-mail: aliramazani@gmail.com widely used reagents for linking synthetic building blocks with the formation of carbon-carbon double bonds, and this has aroused much interest in the study of the synthesis, structure and properties of P-ylides and their derivatives [23]. Phosphorus ylides were synthesized for the first time more than 100 years ago. At the end of the nineteenth century Michaelis and co-workers reported the synthesis of some phosphorus ylides, although they proposed an incorrect structure for them [25] and only 50-60 years later was it shown (Aksnes [26] , Ramirez and Dershowitz [27] ) that the first ylides were prepared by Michaelis. The work of Michaelis and Gimborn was an isolated occurrence and did not attract chemist's special attention to ylides. In 1919 Staudinger and Meyer synthesized and correctly characterized triphenylphosphonium diphenylmethylide [28, 29]. In work published in 1921, on the reaction of this ylide with diphenylketene and phenylisocyanate, they found for the first time, the reaction which was to be named the Wittig reaction. Unfortunately, Staudinger did not recognize the large synthetic possibility of the reaction of phosphorus ylides with carbonyl compounds and his work was not developed. In 1949 Wittig [30] observed that treatment of tetramethylphosphonium salts with phenyllithium led to the formation of trimethylphosphonium methylide and in 1953 Wittig and Geissler [31] discovered that triphenylphosphonium methylide reacts with benzophenone to form 1,1-diphenylethylene and triphenylphosphine oxide. This discovery led to the development of a new method for the preparation of alkenes which has since found widespread application in synthetic organic chemistry and is now universally known as the Wittig reaction. It was very soon shown that this reaction is generally applicable, and that high selectivity and proceeds without rearrangement and isomerization. After 1953 the chemistry of phosphorus ylides progressed intensively [32-38]. Phosphorus ylides are accessible compounds which can be obtained by simple methods from cheap chemical reagents. This accessibility of phosphorus ylides is the reason for the intensive studies of their chemical properties that have led to the wide extension of the ylides both in preparative chemistry and in industrial fine organic synthesis. Several methods have been developed for preparation of phosphorus ylides. These ylides are