An efficient copper-mediated method for the oxidative alkynylation of diaryl imines with terminal alkynes is reported. This reaction provides the first catalytic and general synthesis of ynimines and allows for an easy preparation of these useful building blocks. An improved copper-catalyzed oxidative dimerization of imines to azines and the synthesis of dienes and azadienes from ynimines are also described.
This is not breaking news: copper acetylides, readily available polymeric rock-stable solids, have been known for more than a century to be unreactive species and piteous nucleophiles. This lack of reactivity actually makes them ideal alkyne transfer reagents that can be easily activated under mild oxidizing conditions. When treated with molecular oxygen in the presence of simple chelating nitrogen ligands such as TMEDA, phenanthroline or imidazole derivatives, they are smoothly oxidized to highly electrophilic species that formally behave like acetylenic carbocations and can therefore be used for the mild and practical alkynylation of a wide range of nitrogen, phosphorus and carbon nucleophiles.
Insights into the reactivity of ynimines under anionic conditions are reported. They were shown to be excellent precursors of metalated ketenimines, which can be generated in situ by the reaction of ynimines with organolithium reagents or strong bases. The metalated ketenimines can then be trapped with various electrophiles and, depending on their substitution pattern, afford original and divergent entries to various building blocks.
Copper acetylides, readily available reagents which are characterized by their lack of reactivity, can be simply activated by oxidation with oxygen in the presence of simple nitrogen ligands such as TMEDA or imidazole derivatives. Upon activation, these nucleophilic species undergo a formal umpolung and can transfer their alkyne subunit to a wide range of heteronucleophiles, including amides, oxazolidinones, imines, and dialkyl phosphites. This alkynylation, which provides one of the most practical entry to useful building blocks such as ynamides, ynimines, and alkynylphosphonates, proceeds under especially mild conditions and can be easily performed on a multigram scale.
Exploring the Anionic Reactivity of Ynimines, Useful Precursors of MetalatedKetenimines. -Ynimines are used as excellent precursors of metalated ketenimines generated in situ by the reaction with organolithium reagents or strong bases. The metalated ketenimines are further trapped with various electrophiles to afford generally highly substituted saturated and unsaturated nitriles. In contrast, silyl-substituted substrate (X) gives stable silylketenimines (XI) or, upon treatment with aromatic aldehydes, conjugated amides (XIII). -(LAOUITI, A.; COUTY, F.; MARROT, J.; BOUBAKER, T.; RAMMAH, M. M.; RAMMAH, M. B.; EVANO*, G.; Org. Lett. 16 (2014) 8, 2252-2255, http://dx.doi.org/10.1021/ol500749h ; Lab. Chim. Org., Univ. Libre Bruxelles, B-1050 Bruxelles, Belg.; Eng.) -S. Adam 42-085
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