Ugi reaction

[14] One plausible reaction mechanism is depicted below:[15] Amine 1 and ketone 2 form the imine 3 with loss of one equivalent of water.

A second nucleophilic addition takes place at this intermediate with the carboxylic acid anion to 8.

The final step is a Mumm rearrangement with transfer of the R4 acyl group from oxygen to nitrogen.

[22] This approach relies on acyl transfer in the Mumm rearrangement to form the four-membered ring.

The reaction proceeds in moderate yield at room temperature in methanol with formaldehyde or a variety of aryl aldehydes.

For example, p-nitrobenzaldehyde reacts to form the β-lactam shown in 71% yield as a 4:1 diastereomeric mixture: Zhang et al.[23] have combined aldehydes with carboxylic acids and used the Ugi reaction to create lactams of various sizes.

These libraries can then be tested with enzymes or living organisms to find new active pharmaceutical substances.

The Ugi reaction
The Ugi reaction
Detailed Ugi mechanism
Detailed Ugi mechanism
An example of the use of the Ugi reaction to form a beta-lactam
An example of the use of the Ugi reaction to form a beta-lactam