Siloxycyclopropanes in Ugi Four-Component Reaction: A New Method for the Synthesis of Highly Substituted Pyrrolidinone Derivatives

Abstract

Reaction of methyl trimethylsiloxycyclopropanecarboxylates 3 with amino acids, tert-butylisonitrile and methanol furnished amino diacid derivatives 2 as the result of an Ugi 5-center 4-component reaction. This one-pot reaction involves β-formyl esters such as 1 as intermediate, which are liberated in situ. Adducts 2 could be thermally cyclized to provide γ-lactams 4 in good yields. The multi component reaction was combined with this cyclization process to a fairly efficient one-pot procedure. Thus, cyclopropane derivative 3a was converted into γ-lactam 4a in good yield. Two of the γ-lactams 4 were reduced with lithium aluminum hydride to give pyrrolidine derivatives 5. Based on an X-ray analysis of the major diastereomer of compound 5d, the diastereoselectivity of the 4-component reaction is discussed.

Key words

amino acids - cyclopropanes - pyrrolidines - lactams - Ugi reaction

References

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1

X-ray analysis.

17

This type of Ugi reactions with ketones has been reported mainly with sterically less hindered isonitriles. [9] [10]

18

The configuration of the new stereogenic center of an (S)-proline derived adduct was S-configured according to an X-ray analysis, whereas the corresponding formula of this compound was drawn as R-configured at this carbon. [4]