Synthesis of Non-Symmetrical and Atropisomeric Dibenzo[1,3]diazepines: Pd/CPhos-Catalysed Direct Arylation of Bis-Aryl Aminals

Abstract

Pd/CPhos-catalysis provides direct arylation/cyclisation of methylene-linked bis-anilines to dibenzo[1,3]diazepines v, which are both non-(C2)-symmetrical and axially chiral. Synthesis of the direct arylation substrates commences with substitution of (N-acyl)anilines to methylene methyl sulfide derivatives, followed by halogenation/de-thiomethylation to N-(chloromethyl)anilines. These are substituted with a second aniline derivative, allowing modular preparation of (ortho-halo)aryl-aminal-linked arenes 4. The C–H functionalising direct arylation conditions were adapted from Fagnou and co-workers: substrates and potassium carbonate were heated in dimethylacetamide in the presence of palladium acetate and an electron-rich and sterically hindered biarylphosphine ligand, here CPhos 5. These conditions delivered the C1-(a)symmetric dibenzo[1,3]diazepine targets, which, due to torsion around the axis of the newly formed biaryl bond, are also intrinsically atropisomeric. The axially twisted scaffold is known to impart special properties to ligands/catalysts when the products are further converted into the corresponding seven-membered ring-containing N-heterocyclic carbenes (e.g. xii and xiv).

Metal‐Catalyzed Routes to Dibenzodiazepines (DBDAs) and Structural Analogues: Recent Advances

“…[36] They used a novel Pd/CPhos-catalyzed direct arylation of bisaryl aminals in an attempt to find a more flexible route to this compound class. [36] They used a novel Pd/CPhos-catalyzed direct arylation of bisaryl aminals in an attempt to find a more flexible route to this compound class.…”

“…[36] They used a novel Pd/CPhos-catalyzed direct arylation of bisaryl aminals in an attempt to find a more flexible route to this compound class. [36] The first protected aniline used did not contain a halogen in the aromatic ring whilst the second protected aniline did in the ortho position relative to the N-acetyl functional group.…”

“…In 2015, non-symmetrical atropoisomeric dibenzo[1,3]diazepines were synthesized by Masters' group (Scheme 9). [36] They used a novel Pd/CPhos-catalyzed direct arylation of bisaryl aminals in an attempt to find a more flexible route to this compound class. The crucial part of the synthesis was not the ring closure of the [1,3]diazepine, but the preparation of the methylene-linked bis-anilines.…”

“…Pd-catalysed C-H arylation leading to 1,3-dibenzodiazepines as reported by Masters and co-workers. [36]…”

Synthesis of Tetracyclic 2,3-Dihydro-1,3-diazepines from a Dinitrodibenzothiophene Derivative

“…Since the last comprehensive survey of their synthesis 31 only a handful of new synthetic approaches have been reported for monocyclic, [32][33][34][35] singly- [36][37][38][39] or doubly-ringfused 1,3-diazepines. [40][41][42][43][44][45][46][47][48][49] In this work the introduction of sterically hindered nitro groups at the 1-and 9-positions of a dibenzothiophene-5,5-dioxide derivative provides access to a new two-electron accepting molecule, which is a precursor to luminescent four-ring-fused 2,3-dihydro-1,3-diazepines 6-8 using facile protocols in synthetically viable yields. To our knowledge these molecules represent the first examples of tetracyclic 1,3-diazepine derivatives.…”