1.3- Dipolar cycloaddition reactions chemistry

Studies from our laboratories by Pantarotto et al. (2004a, b), Wu et al. (2005) and Kostarelos et al. (2007) using covalently functionalised CNTs (1,3-dipolar cycloaddition reaction chemistry) have reproducibly described that CNTs were uptaken by cells via pathways other than endocytosis. This work has experimentally observed that CNTs were able to interact with plasma membranes and cross into the cytoplasm without the apparent need of engulfment into a cellular compartment... 

The 1,3-dipolar cycloaddition reaction of nitrones with alkenes gives isoxazolidines is a fundamental reaction in organic chemistry and the available literature on this topic of organic chemistry is vast. In this reaction until three contiguous asymmetric centers can be formed in the isoxazolidine 17 as outlined for the reaction between a nitrone and an 1,2-disubstituted alkene. The relative stereochemistry at C-4 and C-5 is always controlled by the geometric relationship of the substituents on the alkene (Scheme 8.6). 

For comprehensive reviews of 1,3-dipolar cycloaddition reactions, see R. Huisgen, R. Grashey and J. Sauer in The Chemistry of Alkenes, S. Patai, ed., Interscience London, 1965, pp. 806-878 G. Bianchi, C. DeMicheli, and R. Gandolfi, in The Chemistry of Double Bonded Functional Groups, Part I, Supplement A, S. Patai, ed., Wiley-Interscience, New York, 1977, pp. 369-532 A. Padwa, ed., 1,3-Dipolar Cycloaddition Chemistry, Wiley, New York, 1984. 

Click chemistry has been particularly active in various fields this year. For example, ample applications of click chemistry have been seen in carbohydrate chemistry. Various /weiido-oligosacchardies and amino acid glycoconjugates were synthesized via an intermolecular 1,3-dipolar cycloaddition reaction using easily accessible carbohydrate and amino acid derived azides and alkynes as building blocks <06JOC364>. The iterative copper(I)-catalyzed... 

S. Dedola, S. A. Nepogodiev, and R. A. Field, Recent applications of the Cul-catalysed Huisgen azide-alkyne 1,3-dipolar cycloaddition reaction in carbohydrate chemistry, Org. Biomol. Chem.., 5 (2007) 1006-1017. 

Dipolar cycloaddition reactions are of main interest in nitrile oxide chemistry. Recently, reviews and chapters in monographs appeared, which are devoted to individual aspects of these reactions. First of all, problems of asymmetric reactions of nitrile oxides (130, 131), including particular aspects, such as asymmetric metal-catalyzed 1,3-dipolar cycloaddition reactions (132, 133), development of new asymmetric reactions utilizing tartaric acid esters as chiral auxiliaries (134), and stereoselective intramolecular 1,3-dipolar cycloadditions (135) should be mentioned. Other problems considered are polymer-supported 1,3-dipolar cycloaddition reactions, important, in particular, for combinatorial chemistry... 

For reviews dealing with stereoselective 1,3-dipolar cycloaddition reactions, see (a) Martin JN, Jones RCF. In The Chemistry of Heterocyclic Compounds Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products, Padwa A, Pearson WH (Eds.), John Wiley Sons, New-York, Vol. 59, ch. 1, 1-81, 2002 ... 

Main Aspects of Chemistry and Stereochemistry of Cyclic Nitroso Acetals Chemistry of cyclic nitroso acetals or nitrosals (the term was introduced by Prof. Seebach) has attracted interest only after the discovery of the 1,3-dipolar cycloaddition reaction of nitronates with olefins in 1962 by the research group of Prof. Tartakovsky. (Principal data on nitroso acetals up to 1990 were summarized in the review by Rudchenko (395).)... 

Cycloaddition reactions are a fundamental class of processes in synthetic chemistry. Within this class, the 1,3-dipolar cycloaddition reaction (DCR) has found extensive use as an efficient method for the synthesis of different heterocyclic compounds. These type of reactions involve the addition of a 1,3-dipole to a multiple 7i-bond system (dipolarophile) leading to five-membered heterocycles (Scheme 1) [1]. 

Scheme 7.1 Click chemistry synthesis of 1,4-disubstituted-l,2,3-triazoles by a 1,3-dipolar cycloaddition reaction of organic azides with terminal acetylenes.

The rhodium( 11)-catalyzed formation of 1,3-dipoles has played a major role in facilitating the use of the dipolar cycloaddition reaction in modern organic synthesis. This is apparent from the increasing number of applications of this chemistry for the construction of heterocyclic and natural product ring systems. This chapter initially focuses on those aspects of rhodium(II) catalysis that control dipole formation and reactivity, and concludes with a sampling of the myriad examples that exist in the Hterature today. 

Due to space limitations, it is not possible to provide a comprehensive coverage of all 1,3-dipolar cycloaddition chemistry carried out using diazo compounds over the past two decades. Rather, attention will be given to the most significant developments, including the synthesis of novel heterocyclic systems, the preparation of well-established heterocycles (such as pyrazoles and pyrazolines) with novel functionalities, as well as stereoselective cycloadditions. A discussion of the theoretical, mechanistic, and kinetic aspects of these 1,3-dipolar cycloaddition reactions will be kept to a minimum, but references to important work in these areas will be given at appropriate places. Authoritative reviews dealing with the... 

The statement made in 1986 by Gingrich and Baum (10), with regard to miinchnones, that the most important reactions (of mtinchnones) from a synthetic point of view are 1,3-dipolar cycloaddition reactions, certainly applies to all mesoionic heterocycles and is more true today than it was in 1986. Although the factors governing the regioselectivity of unsymmetrical mesoionic cycloadditions are not always completely understood, the synthetic utility of this chemistry is enormous and indisputable. 

The reader was given a taste of the power of isomiinchnone dipolar cycloaddition chemistry in Section 10.2.1. As discussed by Potts (1) and Gingrich and Baum (10), the isomiinchnone ring system—a masked carbonyl dipole—is exceptionally reactive as a 1,3-dipole in 1,3-dipolar cycloaddition reactions. In the intervening years since these two excellent reviews the major research efforts in isomiinchnone chemistry have entailed synthetic applications to specific targets such as alkaloids and other natural and unnatural products. 

It is a major challenge to keep our coverage of this immense field up to date. One strategy is to publish Supplements or new Parts when merited by the amount of new material, as has been done, inter alia, with pyridines, purines, pyrimidines, quinazolines, isoxazoles, pyridazines and pyrazines. The chemistry and applications to synthesis of 1,3-dipolar cycloaddition reactions in the broad context of organic chemistry were first covered in a widely cited two-volume treatise edited by Prof. Albert Padwa that appeared in 1984. Since so much has been published on this fascinating and broadly useful subject in the intervening years, we felt that a Supplement would be welcomed by the international chemistry community, and we... 

The last comprehensive survey of this area dates back to 1984, when the two-volume set edited by Padwa, 1,3-Dipolar Cycloaddition Chemistry, appeared. Since then, substantial gains in the synthetic aspects of this chemistry have dominated the area, including both methodology development and a body of creative and conceptually new applications of these [3+ 2]-cycloadditions in organic synthesis. The focus of this volume centers on the utility of this cycloaddition reaction in synthesis, and deals primarily with information that has appeared in the literature since 1984. Consequently, only a selected number of dipoles are reviewed, with a major emphasis on synthetic applications. Both carbonyl ylides and nitronates, important members of the 1,3-dipole family that were not reviewed previously, are now included. Discussion of the theoretical, mechanistic, and kinetic aspects of the dipolar-cycloaddition reaction have been kept to a minimum, but references to important new work in these areas are given throughout the 12 chapters. 

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