Of 1,3-dipolar cycloaddition reactions

The normal electron-demand principle of activation of 1,3-dipolar cycloaddition reactions of nitrones has also been tested for the 1,3-dipolar cycloaddition reaction of alkenes with diazoalkanes [71]. The reaction of ethyl diazoacetate 33 with 19b in the presence of a TiCl2-TADDOLate catalyst 23a afforded the 1,3-dipolar cycloaddition product 34 in good yield and with 30-40% ee (Scheme 6.26). 

The author has been involved for quite a long time in the study of Lewis acid catalysis of 1,3-dipolar cycloaddition reactions. From his research group, a series of methodologies directed to the Lewis acid-mediated stereochemical and regiochem-ical control of 1,3-dipolar cycloaddition reactions has been reported this includes ... 

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. 

To control the stereochemistry of 1,3-dipolar cycloaddition reactions, chiral auxiliaries are introduced into either the dipole-part or dipolarophile. A recent monograph covers this topic extensively 70 therefore, only typical examples are presented here. Alkenes employed in asymmetric 1,3-cycloaddition can be divided into three main groups (1) chiral allylic alcohols, (2) chiral amines, and (3) chiral vinyl sulfoxides or vinylphosphine oxides.63c... 

Attempts to Catalyze [3 + 2]-Cycloaddition of Nitronates to Olefins In Section 3.2.1.2.2.2, it was noted that [4+ 2]-cycloaddition reactions of nitro-alkenes and alkenes proceed much faster in the presence of LA. At the same time, in the presence of LA, nitronates can rapidly decompose (49) or undergo rearrangements (see Section 3.4.2.5.6 ). Hence, it is not surprising that catalysis of 1,3-dipolar cycloaddition reactions of nitronates with alkenes by LA has attracted little attention until very recent times. An exception is the study by the Japanese... 

In addition to the role of substituents in determining regioselectivity, several other structural features affect the reactivity of dipolarophiles. Strain increases reactivity. Norbomene, for example, is consistently more reactive than cyclohexene in 1,3-dipolar cycloadditions. Conjugated functional groups also usually increase reactivity. This increased reactivity has most often been demonstrated with electron-attracting substituents, but for some 1,3-dipoles, enamines, enol ethers, and other alkenes with donor substituents are also quite reactive. Some reactivity data for a series of alkenes with a few 1,3-dipoles are given in Table 6.3. Scheme 6.5 gives some examples of 1,3-dipolar cycloaddition reactions. 

Since the discovery of triazole formation from phenyl azide and dimethyl acetylenedicarboxylate in 1893, synthetic applications of azides as 1,3-dipoles for the construction of heterocychc frameworks and core structures of natural products have progressed steadily. As the 1,3-dipolar cycloaddition of azides was comprehensively reviewed in the 1984 edition of this book (2), in this chapter we recount developments of 1,3-dipolar cycloaddition reactions of azides from 1984 to 2000, with an emphasis on the synthesis of not only heterocycles but also complex natural products, intermediates, and analogues. 

Wilcox and co-workers (145) reported that the stereoselectivity of 1,3-dipolar cycloaddition reactions can be controlled in a predictable manner when ion pairs are located at a proper position near the reaction site (Scheme 11.40). He has employed an A-phenylmaleimide substrate having a chiral center in the substituent at ortho position of the phenyl group. Due to serious steiic hindrance, this phenyl group suffers hindered rotation around the aryl-nitrogen bond (rotation barrier 22 kcal/mol). Four diastereomeric cycloadducts are possible in the cycloaddition step with a nitrile oxide. When the cycloaddition reaction is carried out in... 

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... 

Similarly small rate factors were obtained for 1,3-dipolar cycloadditions between diphenyl diazomethane and dimethyl fumarate [131], 2,4,6-trimethylbenzenecarbonitrile oxide and tetracyanoethene or acrylonitrile [811], phenyl azide and enamines [133], diazomethane and aromatic anils [134], azomethine imines and dimethyl acetylenedi-carboxylate [134a], diazo dimethyl malonate and diethylaminopropyne [544] or N-(l-cyclohexenyl)pyrrolidine [545], and A-methyl-C-phenylnitrone and thioketones [812]. Huisgen has written comprehensive reviews on solvent polarity and rates of 1,3-dipolar cycloaddition reactions [541, 542]. The observed small solvent effects can be easily explained by the fact that the concerted, but non-synchronous, bond formation in the activated complex may lead to the destruction or creation of partial charges, connected... 

Xu, L. Doubleday, C. E. Houk, K. N. Dynamics of 1,3-dipolar cycloaddition reactions of diazonium betaines to acetylene and ethylene Bending vibrations facilitate reaction, Angew. Chem. Int. Ed. 2009, 48, 2746-2748. 

Some examples are known of 1,3-dipolar cycloaddition reactions of trifluoromethyl-substituted alkenes and alkynes with other dipoles (see Table 12), such as diazomethane.nitrile imines, " " nitronates," and munchones." Depending on reaction conditions, cycloadditions may occur via a two-step process. 

---