Alpha- vs ortho-lithiation of N-alkylarylaziridines: probing the role of the nitrogen inversion process.
The lithiation reaction of monophenyl- and diphenylaziridines has been investigated in detail in an effort to understand why the former undergo exclusively or mainly ortho-lithiation while the latter are lithiated exclusively at the alpha-position. Evidence is reported that ruled out the possibility that the alpha-lithiation, observed for the diphenylaziridines, is the result of an ortho- to alpha-translocation phenomenon, thus substantiating a direct alpha-deprotonation process. The role of the aziridine nitrogen lone-pair has been considered: dynamics at the aziridine nitrogen as well as complex-induced proximity effects seem to be responsible for the observed regioselectivity in both monophenyl and diphenylaziridines. It turns out that, by tuning the reaction conditions for the lithiation of trans-1-alkyl-2-methyl-3-phenylaziridines, it is possible to generate with high regioselectivity alpha- and/or ortho-lithiated aziridines, which can be stereoselectively functionalized by electrophilic trapping. A regioselective ortho-functionalization of diphenylaziridines is made possible by halogen- or tin-lithium exchange and by deprotonation of bis-deuterated aziridines.
Affortunato
Francesco
F
Dipartimento Farmaco-Chimico, Università di Bari, Consorzio Interuniversitario Nazionale Metodologie e Processi Innovativi di Sintesi C.I.N.M.P.I.S., Via E. Orabona 4, I-70125, Bari, Italy.
Florio
Saverio
S
Luisi
Renzo
R
Musio
Biagia
B
D001388:Aziridines / Q000737:chemistry*; D002625:Chemistry, Organic / Q000379:methods*; D004563:Electrochemistry / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009584:Nitrogen / Q000737:chemistry*; D013696:Temperature
D001388:Aziridines; D009584:Nitrogen