Ambiphilic dipole

Type II Because of the similar energy gap in either direction, HOMO of the dipole can interact with LUMO of the dipolarophiles or HOMO of the dipolarophile can interact with LUMO of the dipole. The situation is referred to as a HOMO—LUMO-controlled dipole or an ambiphilic dipole and includes nitrile imine, nitrone, carbonyl oxide, nitrile oxide, and azide. 

Type II (ambiphilic dipole) In such cases, the HOMO of the dipole can interact with the LUMO of the dipolarophiles or the HOMO of the dipolar-ophile can interact with the LUMO of the dipole. Therefore, any substituent on the either dipolarophile or dipole would accelerate the reaction by decreasing the energy gap between the two interacting frontier orbitals, i.e., an electron withdrawing group would decrease the energy of the LUMO while an EDO would increase the energy of the HOMO. For example, azides react with various electron-rich or electron-poor dipolarophiles with about a similar reactivity rate. 

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. 

An interesting series of compounds for which a fairly broad range of data exists is diazomethane, methyl diazoacetate, and diethyl diazomalonate, in which each additional ester group should make the 1,3-dipole successively more electrophilic. The data are given in Table 10.4. We see that diazomethane is primarily nucleophilic in character, dropping sharply in reactivity from electrophilic to nucleophilic dipolarophiles. The other two reactants clearly show an ambiphilic reactivity. These reagents show increased reactivity with both EWG and ERG dipolarophiles, with the diazomalonate shifted somewhat more toward electrophilic character. 

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