Highly Anti-Selective One-Pot Multicomponent Synthesis of Mannich-Type N-Acylated β-Amino Acid Derivatives by Copper or Sodium Salt Catalysis

Abstract

A stereo-defined process has been developed for the synthesis of Mannich-type products using readily available copper sulfate or sodium chloride as catalyst. Good to excellent diastereoselectivity has been achieved for a broad array of substrates. The observed diastereoselectivity is explained on the basis of the steric interaction between the acyloxy group of the aldehyde carbon and the more hindered α-substituted enolate anion. This steric interaction helps the addition to take place through the less-hindered face to produce the anti-isomers predominantly.

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GRAPHICAL ABSTRACT

Keywords:

• Amido ketone
• common salt
• Mannich-type
• multicomponent reaction
• stereoselectivity

Notes

^a All reactions were carried out at room temperature.

^b Isolated yield, all products were identified by comparing their NMR and IR values with those for authentic samples.^[6a,6b]

^c Assigned based on comparison with literature value for the coupling constants of methine proton.^[6a]

^a All reactions were carried out at room temperature using dichloromethane as solvent.

^b Isolated yield.

^c Product was identified by comparing its NMR and IR values with those for authentic samples.^[6b]

^a All reactions were carried out at room temperature.

^b Isolated yield.

^c Products were identified by comparing their NMR and IR values with those for authentic samples.^{[ 6 ]}