Racemic α-acylphosphinates and formylphosphinate hydrate were used directly as the substrates in a proline derivative-catalyzed cross aldol reaction with ketones. Because of the preexisting the phosphorus stereogenic center, a mixture of two diastereomers of the corresponding α-hydroxyphosphinates were obtained in this reaction. Good to high enantioselectivities (up to 99% ee) were obtained simultaneously for both of these two diastereomers in good yields. Good diastereoselectivities were also obtained when the reaction generates an additional carbon stereogenic center.

MDO rocks! Proline and (2S,3aS,7aS)‐octahydro‐1H‐indole‐2‐carboxylic acid are both poor catalysts for the inverse‐electron‐demand hetero‐Diels–Alder reactions between aldehydes and electron‐deficient enones. However, forming modularly designed organocatalysts (MDOs) through their self‐assembly with cinchona alkaloid‐derived thioureas can dramatically improve the efficiency of these catalysts (see scheme; PCC=pyridinium chlorochromate).

The cross aldol reaction between enolizable aldehydes and α-ketophosphonates was achieved for the first time by using 9-amino-9-deoxy-epi-quinine as the catalyst. β-Formyl-α-hydroxyphosphonates were obtained in high to excellent enantioselectivities. The reaction works especially well with acetaldehyde, which is a tough substrate for organocatalyzed cross aldol reactions. The products were demonstrated to have anticancer activities.

The List-Barbas-Mannich reaction of ethyl (p-methoxyphenylimino)acetate (p-methoxyphenyl = PMP) with unmodified aldehydes or ketones catalyzed by modularly designed organocatalysts (MDOs) that are self-assembled from proline and cinchona alkaloid thioureas (such as a quinidine-derived thiourea) produces the corresponding γ-oxo-α-amino acid derivatives in high yields and excellent stereoselectivities. No solvent is necessary for this reaction. Aldehydes are especially good substrates for this reaction: The reaction takes only a few minutes to yield the corresponding List-Barbas-Mannich products in excellent dr (up to >99:1) and ee values (up to >99% ee).

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