Relative Reactivity, Regioselectivity, Stereoselectivity, and Transition Structures

Relative Reactivity, Regioselectivity, Stereoselectivity, and Transition Structures 

The bonding changes for 1,3-DPCA reactions involve four tt electrons from the 1,3-dipole and two from the dipolarophile. In most cases, the reaction is a concerted [ttIs-b Tr4s] cycloaddition. As in the D-A reaction, the reactants approach one another in parallel planes. There is interaction between the complementary HOMO-LUMO combinations, and depending on the combination, either reactant can be the electrophilic or the nucleophilic component. Generally speaking, the reactant 1,3-dipoles are more polar than the TS or the reaction product. The rate of reaction is not strongly sensitive to solvent polarity. 

The most widely applied interpretation of substituent effects on relative reactivity is based on FMO theory. According to FMO theory, interacting orbitals are most stabilized when they are closest in energy. Substituent effects on dipolar cycloadditions can be interpreted in terms of matching of HOMO and LUMO orbitals of the two reactants.This is the same concept used in applying FMO theory to D-A reactions (see p. 844-848). In the D-A reaction, it is fairly clear which reactant is electrophilic and which is nucleophilic, and the interpretation of substituent effects follows directly. This choice is not always so obvious for 1,3-DPCA reactions. In fact, for several of the 1,3-dipoles both EWGs and ERGs in the dipolarophile enhance reactivity. These 1,3-dipoles are called ambiphilic. Let us look carefully to see why they have this property. 

Much of the relative reactivity data on 1,3-DPCA reactions has been tabulated and discussed in reviews by R. Huisgen, a pioneer researcher in the field.Some representative data are presented in Table 10.3. The dipolarophiles are shown in decreasing order of electrophilicity. The data from these monosubstituted dipolarophiles should be relatively free of steric influences on reactivity. Note that for phenyl azide and benzonitrile oxide, reactivity is at a minimum for unfunctionalized alkenes and is increased by both donor and acceptor substituents. 

CH2=CHX Ph2CN2 PhN3= PhC=NO PhCH=NCH3 PhC=NNPH CHjNjS 

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