Publication of the week, number 6, 3 January 2014

Here is an interesting piece of work by Narbonne, Retailleau, Maestri and Malacria from the CNRS and the University of Paris detailing the synthesis of dibenzoazepines via a three component reaction catalysed by palladium/norbornene complexes.

benzos01

Using the following conditions: Pd(OAc)2 5 mol %, 0.02 M, ligand 10 mol %, norbornene 60 mol %, Ar−I 0.29 mmol, 1.1 equiv, olefin 2 equiv, K2CO3, 2.2 equiv in DMF under Ar at 130 °C for 36 h. When the ligand is a tri-isopropylphosphine the yields are around 75%, unfortunately determined by H-NMR!

The paper goes into great mechanistic detail to account for the observed  diastereoselectivity. Interestingly when the olefin is methyl vinyl ketone, an enolisable ketone, a retro-Mannich reaction occurs delivering the second of the two products shown above. The selectivity is due to a chelated Pd(IV) complex that allows atroposelective aryl-aryl coupling, simultaneously a kinetic resolution of the intermediates takes place resulting in the observed selectivity.

This is a nice method to rapidly access biologically interesting dibenzo[c,e]azepines as well as generating novel organocatalysts. However, I would like to see a scale-up of this sequence and a better determination of the yield. NMR yields can be taken with a pinch of salt. Otherwise some interesting chemistry here.

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4 thoughts on “Publication of the week, number 6, 3 January 2014

  1. Many thanks for the kind presentation of our recent work.
    A friend of mine send me the link to your nice blog.
    I just wished to note that troughout the paper yields, figures presenting the scope refers to isolated yields. During optimization, presented in first table, NMR-yield was a more efficient tool to evaluate conditions.

    Thanks again,

    Giovanni Maestri

    1. Thank you for your comment. Point noted about the yields. I hope someone pick up on your versatile methodology.
      regards

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