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Enamines are generated from aldehydes or ketones upon reaction with secondary or primary amines, and the enamine can react with an electrophile to give an α‐functionalized derivative of the carbonyl compounds (Eq. 1.4).

α,β‐Unsaturated aldehydes or ketones also react with secondary or primary amines to generate an iminium ion, which has lower LUMO (lowest unoccupied molecular orbital) level compared with the parent α,β‐unsaturated carbonyl compound. A nucleophile reacts with the iminium ion to afford a β‐functionalized derivative of the carbonyl compound (Eq. 1.5).

(1.4)

(1.5)

Enamine and iminium ions are reactive species and many reactions involving these intermediates have been developed. Representative organocatalysts that have been used to generate enamines and iminium ions are presented in Figure 1.1.

Proline is a secondary amine catalyst that was first used in the intramolecular aldol reaction in the 1970s (Eq. 1.1). It is a bifunctional catalyst, possessing an amine moiety and an acid moiety (carboxylic acid) vide infra [3]. Imidazolidinone catalyst, which was developed by MacMillan, is a secondary amine catalyst prepared from phenylalanine [4]. Diarylprolinol silyl ether [7], which was developed by Jørgensen [8] and Hayashi [9] independently at the same time, is synthesized from proline; it is also a secondary amine catalyst. These two catalysts are not bifunctional catalysts, and do not possess an acid moiety. Cinchona amine‐based catalysts [10] are prepared from cinchona alkaloids, which are primary amines. This catalyst has several functional groups, and acts as a bifunctional catalyst.

Figure 1.1. Representative organocatalysts.

Figure 1.2. The reaction of enamines generated from diphenylprolinol silyl ether and proline.

The design concepts underlying bifunctional and monofunctional organocatalysts are different. Diphenylprolinol silyl ether, a monofunctional catalyst, reacts with an aldehyde to generate an enamine, in which one of the enantiofaces of the enamine is completely shielded by the bulky diphenyltrimethylsiloxymethyl moiety, and an electrophile approaches from the opposite side of this bulky substituent (Figure 1.2). Thus, the steric shielding of one of the enantiofaces is a key for the high enantioselectivity. Irrespective of the electrophile, high enantioselectivity is expected because the enantioface selectivity of the nucleophile is controlled by the catalyst. This is a contrast to bifunctional catalysts such as proline, in which an acid moiety activates the electrophile. Thus, the most suitable catalyst for a given reaction depends on the electrophile.