Base‐Mediated Generation of Ketenimines from Ynamides: [3+2] Annulation with Azaallyl Anions

Abstract

Under basic conditions and heat, ynamides can serve as precursor to ketenimines, whose synthetic potential is often hampered by their difficulty of acces. Herein, we report that they can undergo a [3+2] cycloaddition with 2-azaallyl anions, obtained from benzylimines under the same reaction conditions. This reaction between two highly reactive intermediates, both generated in situ from bench stable starting materials, gives access to various nitrogen-rich heterocycles. The reaction usually proceeds with excellent diastereoselectivity, in favor of the cis adduct. Deuteration experiments and DFT calculation helped rationalize the regio and stereo-selectivity of the process as well as the formation of side-products..

Base‐Mediated Generation of Ketenimines from Ynamides: Addition of Hydrazones to Give Acetimidohydrazides**

“…We started our study with ynamide 1 a (Ar=Ph and R=H) but, whatever the conditions employed (see SI for details), no identifiable adduct could be observed when the reaction was attempted with either nitrone 5 or N −Ts‐ and N −Ac‐hydrazones 6 a and 6 b , respectively (Scheme 2). The heterodipole generally did not react or decomposed if the conditions were too harsh (100 °C, long reaction times), while the ketenimines seemed to be generated, as evidenced by the characterization of its adduct with dimethylamine coming from DMF [18] …”

“…The heterodipole generally did not react or decomposed if the conditions were too harsh (100 °C, long reaction times), while the ketenimines seemed to be generated, as evidenced by the characterization of its adduct with dimethylamine coming from DMF. [18] These disappointing results led us to reconsider our design. While we had chosen an electron poor (4-ClÀ C 4 H 6 ) aryl on the electrophilic moiety of the heterodipole, we had not fully considered the relative lack of nucleophilicity of the other moiety.…”

“…[6] For our part, we have recently explored the conversion of an ynamide [7][8][9][10][11][12][13][14] into a ketenimine [15] (including unsubstituted ones) and showed that they could be trapped by heterocyclic nucleophiles [16] or undergo cycloaddition reactions with imines [17] (Scheme 1b) and azallylanions (Scheme 1c). [18] In this latter example, the basic reaction conditions served to generate both the ketenimine 2 and the aza-allyl anion 4 from the ynamide 1 and the imine 3, respectively. Under microwave heating, the cycloaddition took place, giving rise to a series of 5-membered heterocycles.…”

“…One of the most widely used approach to generate ketenimines involves the combination of a sulfonylazide (such as tosylazide) and an alkyne, under copper catalysis, [4,5] akin to azide‐alkyne cycloaddition conditions (Scheme 1a) [6] . For our part, we have recently explored the conversion of an ynamide [7–14] into a ketenimine [15] (including unsubstituted ones) and showed that they could be trapped by heterocyclic nucleophiles [16] or undergo cycloaddition reactions with imines [17] (Scheme 1b) and azallylanions (Scheme 1c) [18] . In this latter example, the basic reaction conditions served to generate both the ketenimine 2 and the aza‐allyl anion 4 from the ynamide 1 and the imine 3 , respectively.…”

Quantum-Chemical Study of the Assembly Mechanism of 1-Pyrrolines from N-Benzylaldimines and Arylacetylenes in KOtBu/DMSO Superbasic Medium

“…This reaction is considered to start with the formation of 2-azaallyl anions from N -benzylimines under the action of a superbase. The involvement of such allyl species in cycloaddition reactions with unsaturated compounds is actively used as a direct route to obtain various five-membered carbo- and heterocycles. − The interaction of azaallyl anions with arylacetylenes, which we focus on here, can proceed via the mechanism of ( i ) a concerted cycloaddition or ( ii ) a two-step cycloaddition involving the formation of a 2-azadiene intermediate, which is similar to the product of the reaction of N -benzyl ketimines with unsubstituted acetylene (Scheme ).…”