1,3-dipolar cycloaddition reactions classification

In Chapter 10 of Part A, the mechanistic classification of 1,3-dipolar cycloadditions as concerted cycloadditions was developed. Dipolar cycloaddition reactions are useful both for syntheses of heterocyclic compounds and for carbon-carbon bond formation. Table 6.2 lists some of the types of molecules that are capable of dipolar cycloaddition. These molecules, which are called 1,3-dipoles, have it electron systems that are isoelectronic with allyl or propargyl anions, consisting of two filled and one empty orbital. Each molecule has at least one charge-separated resonance structure with opposite charges in a 1,3-relationship, and it is this structural feature that leads to the name 1,3-dipolar cycloadditions for this class of reactions.136... 

The 1,3-dipolar cycloaddition of organic azides with nitriles could give rise to two regioisomers. Since organic azides are Type II 1,3-dipoles on the Sustmann classification (approximately equal HOMO-LUMO gaps between the interacting frontier orbital pairs) the reactions could be dipole HOMO or LUMO controled and the regioselectivity should be determined by the orbital coefficients for the dominant HOMO-LUMO interaction. Such systems show U-shaped kinetic curves in their... 

Diels-Alder reactions are sometimes classified as [4+2] cycloadditions, and 1,3-dipolar cycloadditions as [3+2], where the numbers identify the number of atoms involved in the two chains. This classification is not as useful as the one used throughout this book, which is based on the number of electrons involved. In this classification, both Diels-Alder reactions and 1,3-dipolar cycloadditions are [4+2] cycloadditions—4 electrons from the diene or... 

The cationic site is of the immonium type, and is relatively iinreactive, but the radical site is reactive toward electron deficient alkenes such as acrylonitrile, yielding a 50 50 mixture of the diastereoisomeric pyrrolines, after being neutralized by back electron transfer from the sensitizer anion radical. The net result is an interesting example of a net 1,3-dipolar cycloaddition which, in the Huisgen method of classification of cycloadditions, is of the [3 -l- 2] type. The same general reaction had previously been carried out by Padwa, using direct photochemical excitation, a procedure which, in contrast, was highly diastereoselective (90 10, in favor of the trans isomer) [92]. 

This classification is illustrated in Scheme 365. The synthesis of imidazoles under this classification is rare mainly due to the difficulty of C-C bond formation. A palladium-catalyzed coupling of imines 1415, 1417 and acid chloride 1416 to synthesize substituted imidazoles 1418 belongs to this category of ring formation. AT-Alkyl and AT-aryl imines can be used, as can imines of aryl and even nonenolizable alkyl aldehydes. A plausible reaction mechanism involving 1,3-dipolar cycloaddition with miinchnones is illustrated in Scheme 366 <2006JA6050>. 

The past classification of the [4 + 2] cycloaddition reactions involving die 4it participation of a cationic heterodiene among the polar cycloadditions is derived not from an implied stepwise addition-cy-clization reaction mechanism but was terminology introduced to distinguish cycloadditions employing cationic or anionic components from those employing dipolar or uncharged components. Herein the reactions are simply referred to as [4 + 2] cycloaddition reactions. 

In 1893, Arthur Michael observed the formation of a 1,2,3-triazole derivative in the reaction of diazobenzolimid (i.e. Ph-Ns) with dimethyl acetylenedicarboxylate Michael - a future Harvard professor - worked with R. Bunsen and A.W. von Hofmann. Numerous cycloadditions of organic azides and HN3 to alkynes and alkenes were described in the sequel. In the general definition and classification azides belong to the 1,3-dipoles of propargyl-allenyl type (R. Huisgen, I960). 1,3-Dipolar cycloadditions share the 6 r-electron balance with Diels-Alder reactions - and the wide synthetic apphcation. Albert Padwa edited monographs on 1,3-dipolar cycloaddition chemistry in 1984 and 2003 -substantial chapters on azides were included. ... 

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