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. 2023 Jan 13;25(1):125-129.
doi: 10.1021/acs.orglett.2c03924. Epub 2022 Dec 29.

Accessing Chiral Pyrrolodiketopiperazines under Organocatalytic Conditions

Eider Duñabeitia  1 , Aitor Landa  1 , Rosa López  1 , Claudio Palomo  1
Affiliations

Accessing Chiral Pyrrolodiketopiperazines under Organocatalytic Conditions

Eider Duñabeitia et al. Org Lett. .

Abstract

The production of chiral pyrrolodiketopiperazines under organocatalytic conditions demonstrates the capacity of bicyclic acylpyrrol lactims to perform as pronucleophiles in direct carbon-carbon bond forming reactions. The good performance of ureidoaminal-derived Brønsted bases in the Michael addition to nitroolefins affords these heterocyclic scaffolds with high skeleton diversity.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Selected pyrrolodiketopyperazines and pyrrolopyrazinone compounds.
Figure 2
Figure 2
(A) Structural modularity of the pyrrolodiketopierazine skeleton for drug discovery. (B) Precedents for the synthesis of tetrasubstituted pyrrolodiketopierazines. (C) Present work: proof of concept.
Scheme 1
Scheme 1. Evaluation of Catalysts and Conditions for the Michael Addition
Reaction conditions: 1a (0.1 mmol), 2a (0.15 mmol), catalyst (10 mol %), solvent (0.3 mL). Isolated yields. Diastereomeric ratio and enantioselectivity determined by chiral HPLC.
Scheme 2
Scheme 2. Scope of the Enantioselective Michael Addition
Figure 3
Figure 3
Impact of concentration and catalyst loading on stereoselectivity. Most stable computed conformation of C7 in toluene.
Scheme 3
Scheme 3. (a) Production of the Target Chiral Pyrrolopyrazinones 4; (b) Modified Pyrrolopyrazinones 4 under Mild Conditions
See this image and copyright information in PMC

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