A catalytic aza-Nazarov cyclization between 3,4-dihydroisoquinolines and α,β-unsaturated acyl chlorides has been developed to access α-methylene-γ-lactam products in good yields (up to 79%) as single diastereomers. The reactions proceed efficiently when AgOTf is used as an anion exchange catalyst with a 20 mol % loading at 80°C. Computational studies were performed to investigate the reaction mechanism, and the findings support the role of the −TMS group in reducing the reaction barrier of the key cyclization step.

Room temperature ionic liquids continue to be at the forefront of chemistry, covering a broad spectrum of research areas from electrochemistry and energy to catalysis and green chemistry. Therefore, it is of great value to fully understand the chemical and electrochemical reactivity and stability of ionic liquids utilized in these applications. In this context, we have investigated the electrochemical generation of an N-heterocyclic carbene and its CS 2 adduct from the ionic liquid [bmim] [PF 6 ], and X-ray photoelectron spectroscopy (XPS) proved to be a highly effective spectroscopic tool to study such systems. Initially, the dithiocarboxylate adduct was chemically synthesized as a reference compound starting from both

We have developed a catalytic aza-Nazarov reaction of N-acyliminium salts generated in situ from the reaction of a variety of cyclic and acyclic imines with α,β-unsaturated acyl chlorides to afford substituted α-methylene-γ-lactam heterocycles. The reactions proceed effectively in the presence of catalytic (20 mol %) amounts of AgOTf as an anion exchange agent or hydrogen-bond donors such as squaramides and thioureas as anion-binding organocatalysts. The aza-Nazarov cyclization of 3,4-dihydroisoquinolines with α,β-unsaturated acyl chlorides gives tricyclic lactam products 7 in up to 79% yield with full diastereocontrol (dr = >99:1). The use of acyclic imines in a similar catalytic aza-Nazarov reaction with 20 mol % of AgOTf results in the formation of α-methylene-γ-lactam heterocycles 19 in up to 76% yield and with good to high diastereoselectivities (4.3:1 to 16:1). We have demonstrated the scalability of the reaction with a gram-scale example. The relative stereochemistry of the α-methylene-γ-lactam products 19 has been determined via the single-crystal X-ray analysis of lactam 19l. In order to shed light on the details of the reaction mechanism, we have performed carefully designed mechanistic studies which consist of experiments on the effect of β-silicon stabilization, the alkene geometry of the α,β-unsaturated acyl chloride reactants, and adventitious water on the success of the catalytic aza-Nazarov reaction.