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Diphenylprolinol silyl ether catalyst and MacMillan’s catalyst are widely used in reactions involving enamine or iminium ion intermediates. In this section, the reactivity of these catalysts will be discussed.

Mayr investigated the nucleophilicity (N) of enamines, and the electrophilicity (E) of iminium ions of several pyrrolidines and imidazolidinones (Figure 1.3) [11]. For enamines, the nucleophilicity is evaluated by the reaction with diarylcarbenium ions, and it correlates poorly with the Brønsted basicities. The enamine, which is derived from diphenylprolinol silyl ether catalyst 2, is almost two orders of magnitude less reactive than the corresponding enamine prepared from pyrrolidine. The reduction of the reactivity is primarily due to the electron‐withdrawing inductive effect of the trimethylsiloxybenzhydryl group in diphenylprolinol silyl ether catalyst. The reactivity of the enamine generated from MacMillan’s catalyst 1 is another two to three orders of magnitude less reactive relative to the enamine of diphenylprolinol silyl ether catalyst, because of the inductive electron‐withdrawing effect of the extra endocyclic amide group in the catalyst, the pyramidalization of the enamine nitrogen, and the steric shielding of both faces of the C=C bond by the two alkyl groups at the 2‐position of the imidazolidinone ring.

In the case of iminium ions, the iminium ion generated from diphenylprolinol silyl ether is 20 times more electrophilic than the iminium ion derived from the parent pyrrolidine because of the electron‐withdrawing substituents. The iminium ion of MacMillan’s catalyst, which is useful for the Diels‐Alder reaction, is more reactive than the iminium ion derived from diphenylprolinol silyl ether.

These investigations indicate that MacMillan’s catalyst is more electron deficient, and that its iminium ion is reactive because of the lower LUMO level. Diphenylprolinol silyl ether catalyst possesses suitable nucleophilicity and electrophilicity of its enamine and its iminium ion, respectively. Thus, this catalyst is effective for domino reactions (see Figure 1.3).

Figure 1.3. Nucleophilicity and electrophilicity of enamines and iminium ions.

Source: Based on [11].