Zirconium-catalyzed site-selective deprotection of primary acetates by dibal-h

Session: 
S7.3 Catalytic glycan transformations
Code: 
OL7.3.3
Location (hall): 
Galactose
Start/end time: 
Wednesday, July 3, 2019 - 12:15 to 12:30
Thomas
Lecourt

Thomas Lecourt1

1Laboratory COBRA - UMR 6014 CNRS, Mont Saint Aignan Cedex, France

Carbohydrates, and other polyols, with a single free primary position and a polyacetylated framework are highly relevant synthetic intermediates for the preparation of numerous bioactive compounds, natural products, and biomaterials. However, their preparation suffers from several drawbacks. Indeed, classical approaches based on the manipulation of protecting groups have a high environmental impact and synthetic cost.[1] Moreover, alternative routes involving the regio- and chemoselective deprotection of peracetylated substrates have a relatively narrow scope, and require advanced technologies, like immobilisation of esterases on solid supports, to be amenable on large scales.[2]

We report herein that a mixture of Cp₂ZrCl₂ and DIBAL-H in THF at -20°C induce a site-selective deprotection of the primary position of peracetylated compounds. This transformation, relying on cheap, easy to handle, and commercially available reagents, de-O-acetylate pyranosidic and furanosidic scaffolds, as well as non-carbohydrate substrates, like amino-acids and terpene derivatives. Achieved under very mild reaction conditions, this reductive process is also tolerant towards numerous functional groups (acetals, ethers, benzoates and pivalates, NHAc, NHBoc, N₃, nitro, cyano…).[3] Mechanistic studies also reveal that this site-selective de-O-acetylation process is induced by a zirconium/aluminum mixed-metal hydride, and finally lead to the development of reaction conditions catalytic in zirconium.[4]

Zirconium-Catalyzed Site-Selective De-O-Acetylation by DIBAL-H

References: 
  1. Agoston, K.; Streicher, H. Fügedi, P. Tetrahedron: Asymmetry 2016, 27, 707-728.
  2. Kadereit, D.; Waldmann, H. Chem. Rev. 2001, 101, 3367-3396.
  3. Submitted for publication.
  4. Submitted for publication.

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