Enhancing Reactivity and Selectivity of Aryl Bromides: A Complementary Approach to Dibenzo[b,f]azepine Derivatives

Abstract

Dihydrodibenzo [b,f]azepines and dibenzo [b,f]azepines can be efficiently synthesized from aryl bromides, o-bromoanilines and norbornene or norbornadiene by means of palladium catalysis. This protocol gives access to dibenzo[b,f]azepine core containing a variety of electron-withdrawing substituents on both aromatic rings and complements the previously reported methodology where electron rich aryl iodides were preferentially used. The presence of KI, even in sub-stoichiometric amount, is crucial for this three-component reaction. The proper addition of iodide anions has a dramatic effect on reaction rate and selectivity. A formal three-step synthesis of the tricyclic antidepressant Clomipramine (Anafranil ) is also described.

Palladium/Norbornene Cooperative Catalysis

“…Interestingly, the addition of 20 mol % CsI improved the selectivity for the desired product ( 168a ), which indicated that the halide anion might influence the steps after the ortho amination with ANP. Later, the Della Ca’ group also observed that the presence of potassium iodide was crucial for improving the yield with aryl bromides …”

Palladium/Norbornene Chemistry: Synthesis of Norbornene-Containing Arylsilanes Involving Double C–Si Bond Formation

“…Subsequently, sequential reaction with electrophiles and nucleophiles gives straightforward access to polyfunctionalized arenes. Alternatively, palladium-catalyzed ortho C–H functionalization of aryl iodides using norbornene as the reaction substrate has also been reported. − However, most of the efficient transformations have focused on C–C/C–N bond formation (Scheme , reaction 2a) , and multiple C–C bond formation (Scheme , reaction 2b). , Very recently, two papers reported on transformation of C–H bond toward C–Si bond. The Cheng group devoloped a palladium-catalyzed ortho-silylation of aryl iodides/aryl-silylation of oxanorbornadiene reaction for assembling functionalized ( Z )-β-substituted vinylsilanes .…”

PdI2 as a Simple and Efficient Catalyst for the Hydroamination of Arylacetylenes with Anilines

“…Moreover, iodide anions display a superior ability to stabilize palladium(II) species, compared to other counteranions, such as acetates [39]. Efforts at understanding the effect of iodide anions in this transformation are underway in our laboratories [40]. Not surprisingly, imine products 3 were unstable under acidic conditions and the isolated yields after column chromatography were very low.…”