Palladium‐Catalyzed Silylcyanation of Ynamides: Regio‐ and Stereoselective Access to Tetrasubstituted 3‐Silyl‐2‐Aminoacrylonitriles

Abstract

The palladium-catalyzed silylcyanation of ynamides is described. This reaction is fully regioselective, delivering tetrasubstituted 2-aminoacrylonitriles derivatives exclusively. Unexpectedly, the nature (aryl or alkyl) of the substituent located at the β-position of the ynamide directly controls the stereoselectivity. The reaction tolerates a number of functional groups and can be considered as the first general access to fully substituted 2-aminoacrylonitriles. Given the singular reactivity observed, a computational study was performed to shed light on the mechanism of this intriguing transformation. Relying on the specific reactivity of the newly installed vinylsilane functionality, the scope of 2aminoacrylonitriles has been enlarged by postfunctionalization.

Redox-Neutral Synthesis of α-Iminonitriles, α-Cyanoenamines, and N-Acyl Derivatives from Amides

“…These two cases constitute excellent examples reflecting the relevance between drug discovery and astrobiology, a topic highlighted by Weber and Tran in a recent perspective article . In spite of the significant progress and of the primordial importance and long history of those reactions on the early earth, − the chemistries of multifunctional α-iminonitriles ( 1 ) and α-cyanoenamines ( 2 ) are underexplored. , …”

Silylium-Catalyzed Regio- and Stereoselective Carbosilylation of Ynamides with Allylic Trimethylsilanes

“…Very recently, a palladium catalyzed silylcyanation was described; the reaction proceeds in a stereo-and regioselective way through a β-palladium enamide intermediate II (Figure 1C). 20 On the other hand, the precedented reactions of allylsilanes with C−C multiple bonds catalyzed by Brønsted or Lewis acids 21−23 and the possibility of self-regeneration of catalytic silylium moved us to choose allylsilane derivatives as carbon nucleophile counterparts for our study on the catalytic carbosilylation of ynamides (Figure 1D). Therefore, herein we develop a regio-and stereoselective allylsilylation of ynamides, using catalytic silylium ion, an alternative to other species such as metal salts and transition metal complexes.…”

“…Apart from the silylmetalation approach, β-silyl-( Z )-enamides can also selectively be obtained by hydrosilylation of ynamides using a rhodium complex or tris­(pentafluorophenyl)­borane as catalyst; in both cases, the hydride abstraction from the silane by the corresponding catalyst leads to a silylium ion, responsible for the formation of a β-silyl ketenimonium intermediate I (Figure B). Very recently, a palladium catalyzed silylcyanation was described; the reaction proceeds in a stereo- and regioselective way through a β-palladium enamide intermediate II (Figure C) …”

“…Very recently, a palladium catalyzed silylcyanation was described; the reaction proceeds in a stereo- and regioselective way through a β-palladium enamide intermediate II ( Figure 1 C). 20 …”

Direct Access to 2,3-Disubstituted Amido-Indenones through Annulation of 2-Iodobenzaldehydes with Ynamides

“…Despite a great potential for the synthesis of 2,3-disubstituted indenone derivatives, annulations involving alkynes and 2-halo-benzaldehydes, first reported by Heck and then extended by Larock, remain moderately investigated and they are almost limited to carbon substituted, often symmetrical or with a strong dissymmetry in terms of steric hindrance ( t- Bu vs primary alkyl for instance), internal alkynes. If we consider electron-rich alkynes bearing a heteroatom, a unique report including two examples with different ynol ethers has been made by Zhu et al In this context and based on our experience of carbonylation reactions applied to polarized alkynes, we have decided to investigate this transformation using readily accessible ynamides (i.e., alkynes substituted with an electron-depleted nitrogen), as this approach would represent a direct and versatile strategy to 2,3-disubstituted amido-indenones. However, while this reaction appeared to be mastered for nonpolarized alkynes, some uncertainty remained with respect to its regioselectivity in the case of polarized CC triple bonds.…”