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. 2020 May 1;22(9):3637-3641.
doi: 10.1021/acs.orglett.0c01124. Epub 2020 Apr 22.

Rh-Catalyzed Aziridine Ring Expansions to Dehydropiperazines

Hillary J Dequina  1 , Josephine Eshon  1 , William T Raskopf  1 , Israel Fernández  2 , Jennifer M Schomaker  1
Affiliations

Rh-Catalyzed Aziridine Ring Expansions to Dehydropiperazines

Hillary J Dequina et al. Org Lett. .

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Abstract

Piperazines are prevalent in pharmaceuticals and natural products, but traditional methods do not typically introduce stereochemical complexity into the ring. To expand access to these scaffolds, we report Rh-catalyzed ring expansions of aziridines and N-sulfonyl-1,2,3-triazoles to furnish dehydropiperazines with excellent diastereocontrol. Productive ring expansion proceeds via a pseudo-1,4-sigmatropic rearrangement of an aziridinium ylide species. However, the structural features of the carbene precursor are important, as pyridotriazoles undergo competing cheletropic extrusion to furnish ketimines.

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Figures

Figure 1.
Figure 1.
Ylide development and types of N-ylides.
Figure 2.
Figure 2.
Computed reaction profile for the process involving 1a' and dirhodium-bound carbene 5-Rh2. Relative free energies (ΔG, computed at 298.15 K and 1 M) and bond distances are given in kcal/mol and angstroms, respectively. All data have been computed at the SMD-B3LYP-D3/def2-SVP level.
Scheme 1.
Scheme 1.
Divergent reactivities of aziridinium ylides.
Scheme 2.
Scheme 2.
Cheletropic extrusion with pyridotriazole 2. Computed reaction profile with relative free energies (ΔG, computed at 298.15 K and 1 M) and bond distances in kcal/mol and Å, respectively. All data are computed at the SMD-B3LYP-D3/def2-SVP level.
Scheme 3.
Scheme 3.
Scope of the aziridine ring expansion.
Scheme 4.
Scheme 4.
One-pot synthesis from p-TsN3.
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References

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