• 10.1021/jo8011368
  • The Journal of Organic Chemistry
  • Volume 73
  • September 2008
  • pp 7387-7389

Simple BINAM ligand synthesis,improvements made for scale-up

Details


Maruoka et al. developed a new synthetic route to access 3,3’-disubstituted BINAM compounds which are nitrogen derivatives of popular axial chiral ligands BINOL and BINAP. Their multi step approach involves in partial hydrogenation of BINAM to H8-BINAM, 3,3’-dihalogenation, and then Suzuki-Miyaura coupling followed by oxidative aromatization. 

I was particularly interested in the preparation of chiral 3,3’-aryl BINAM derivatives  to use as chiral ligands for catalytic C-H amination. I used this approach and synthesized 3,3’-ditolyl BINAM ligand similar to (R)-5. Reported procedures are reliable and reproducible; mainly the first 2 steps i.e. partial hydrogenation and halogenation are high-yielding as they reported. The most impressive part of this manuscript is the simple preparation of dihalo-BINAM derivatives which can be used to make diverse substituted BINAMs as the authors described.

However, the yield of Suzuki-Miyaura coupling step using Tolyl boronic acid is only 65 % (reported is 70 % for Phenyl boronic acid). I thought of improving this coupling step to get higher yields and to make it suitable for large scale synthesis. Then we replaced the PPh3 with Buchwald ligand X-Phos, a proven ligand for efficient Suzuki-Miyaura couplings. To our delight, the coupling reaction worked well and the yield was improved to 85%. Further solvent optimization led to 92 % (Dioxane) yield. It is also worth mentioning here that this modified procedure works well with gram scale synthesis as well. 



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