Rh-Catalyzed Aziridine Ring Expansions to Dehydropiperazines

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.

Continuous flow reactions in the preparation of active pharmaceutical ingredients and fine chemicals

“…As is well known, aziridines 96 have significant value in the pharmaceutical, agrochemical, and material sciences areas. [105][106][107][108][109][110][111] In 2021, Noe ¨l with a slight collaboration of our group, proposed an electrochemical aziridination method involving internal alkenes 94 and primary amines 95 (Scheme 20). 112 In a homemade electrochemical flow reactor, the process delivered the products in up to 93% yield, with a residence time of only 5 minutes.…”

Catalytic Synthesis of β‐(Hetero)arylethylamines: Modern Strategies and Advances

“…As a three membered ring, aziridine is a highly strained molecule that can be ring‐opened under mild conditions, a feature that has been extensively exploited in nucleophilic additions or cross‐coupling reactions [18] . Furthermore, aziridines are readily accessible from feedstock alkenes and their reactivity can be easily fine‐tuned in accordance with their substitution pattern [19] . Over the past decade, major strides in transition metal‐catalyzed ring‐opening of aziridines have expanded the applications of this transformation.…”

1,2,3-Triazole and Its Analogues: New Surrogates for Diazo Compounds

“…Fernández and Schomaker explored aziridine ring expansions with α-imino Rh carbenes to form dehydropiperazines in good yields with high diastereoselectivity (Scheme ). According to computational studies, the nitrogen atom in aziridine ring 76.1 first attacks the rhodium α-imino carbene of triazole 76.5 to generate ylide intermediate 76.6 .…”