Transient protection of azides by phosphazide formation [1]

Hosoya and Yoshida published a simple method for the azido group protection by phosphazide formation with di(tert-butyl)(4-(dimethylamino)-phenyl)phosphine (Amphos) as outlined in Scheme below. [2] [3] Deprotection is easily achieved by treatment with elemental sulfur.

It should be pointed out that phosphazide intermediates are stable under various conditions such as Pd/C under a hydrogen atmosphere, radical-mediated reduction with tri-butylstannane and 2,2’-azodiisobutyronitrile (AIBN), Staudinger reaction with triphenylphosphine, reduction with LiAlH? or in the presence of Grignard reagents.

[1] We are indebted to Professor Muriel Pipelier (Nantes Université) for calling our attention to this method.

[2] T. Aimi, T. Meguro, A. Kobayashi, T. Hosoya, S. Yoshida, Chem. Commun. 2021, 57, 6062-6065.

[3] T. Meguro, S. Yoshida, K. Igawa, K. Tomooka, T. Hosoya, Org. Lett. 2018, 20, 4126-4130.