• Ugi condensation products are often racemic• Enantiomerically pure amino acids are used as chiral building blocks

toward acylaminoamides

• Enantiopure substrates could be used for chiral induction in a diastereoselective Ugi-4CR

• the complexity of a four-component reaction system

• competition from the uncatalyzed background reaction

• the difficulty in achieving stereocontrol of the α-addition of an isocyanide to the imine

• competition from the Passerini reaction or other side reactions.

Design of a catalytic cycle which exploits the heterodimeric activation

Benjamin List, Angew. Chem. Int. Ed. 2014, 53, 7063–7067Synlett 2016, 27, A–N

the overlap of non-equivalent proton signals of the 3-3′ substituents is cleared in the presence of acetic acid, thus suggesting a lower rotational freedom of the C–C bond between the naphthalene backbone and the aryl moiety (2.5–3.0 ppm; 6.9–7.1 ppm).

扩散排序谱(DOSY)

Activation of Carboxylic Acids in Asymmetric Organocatalysis

Benjamin List, Angew. Chem. Int. Ed. 2014, 53, 7063–7067

Phosphoric Acid-Catalyzed Asymmetric Classic Passerini Reaction

J. Am. Chem. Soc. 2015, 137, 14039−14042

Mechanism studies

• The active catalyst is the chiral phosphoric acid itself rather than phosphate or other deprotonated species