Pd-catalyzed allylic substitution between C-based nucleophiles and bicyclic aziridines João Oliveira 1 , Gredy Kiala 2 , Julie Oble 2 , Giovanni Poli 2 , Filipa Siopa 1,2 , Carlos Afonso 1 1 University of Lisbon, Portugal, 1 Sorbonne Université, France Aziridines are highly reactive three-membered heterocycles. They are well known to organic chemists for their great potential as building blocks for the synthesis of carbocycles with significant biological activity, such as aminocyclopentitols and beta-lactams. [1] A short route for the synthesis of these structures is the photochemical transformation of pyridinium salts to bicyclic-aziridines. The photochemical rearrangement forms a cis- fused cyclopenteno-aziridine allylic cation which reacts stereospecifically with poor nucleophiles/solvent devising a stable bicyclic-aziridine containing a new C-Nu bond in trans- position (Scheme 1). [2] In 2016, We reported the ring opening of these aziridines structures by performing a S N 2 reaction with nucleophiles such as azides, anilines, and thiols, forming new carbon-heteroatom bonds (Scheme 1). [3]
Considering the peculiar structure of the above described α-oxycyclopenten-aziridines in connection with our long-standing interest in Pd-catalyzed allylations, we were intrigued by the thought of investigating the behaviour of such cyclic substrates against soft carbon-based pro-nucleophiles under Pd(0) catalysis. Within this framework, we recently developed a palladium-catalyzed ring opening of vinyl aziridines. This process proceeds takes place through h 3 -allylpalladium complex formation via aziridine cleavage, and γ-reactivity of carbon-based nucleophiles leading to new carbon-carbon bonds (Scheme 2). [4] In this line, current efforts on asymmetric approach for aziridine opening via Pd catalysis, are also described with good progress.
Acknowledgements: The authors acknowledge Fundação para a Ciência e Tecnologia (FCT)(UIDB/04138/2020, UIDP/04138/2020, and PhD grant 2020.04589.BD)for financial support. The project leading to this application has received funding from the EuropeanUnion’sHorizon 2020 research and innovation programme under grant agreement No 951996. References 1. Vandekerckhove, M. D’hooghe, Bioorg. Med. Chem. 2013, 21 , 643. 2. Kaplan, L.; Pavlik, J. W.; Wilzbach, K. E. J. Am. Chem. Soc. 1972 , 94, 3283. 3. Vale, J. R.; Siopa, F.; Branco, P. S.; Afonso, C. A. M. Ring Opening of 6-Azabicyclo[3.1.0]hex-3-en-2-ols in Water under Mild Conditions. Eur. J. Org. Chem . 2016 , 2048−2053. 4. Oliveira, João; Kiala Gredy; Siopa, Filipa; Bernard, Aurélie; Gontard, Geoffrey; Oble, Julie; Afonso, C. A. M; Poli, Giovanni. Tetrahedron 2020, 51, 121182.
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