Nucleophilic transformations of azido-containing carbonyl compounds via protection of the azido group

Abstract

Nucleophilic transformations of azido-containing carbonyl compounds are disclosed. The phosphazide formation from azides and di(tert-butyl)(4-(dimethylamino)phenyl)phosphine (Amphos) enabled transformations of carbonyl groups with nucleophiles such as lithium aluminum hydride and organometallic...

Kinetic and mechanistic studies of the Staudinger reduction: On the chemistry of aryl phosphazides

“…The formation of 2a from 1a and TPP is a second‐order process and proceeds too rapidly to be resolved on the timescales employed by the NMR experiment—nearly 90% conversion of azide occurs within the first five minutes of the experiment. Previous work has indicated that the formation of phosphazide may be a reversible process [ 9 ] —in this particular study, any putative reversibility cannot be observed or quantified from the kinetic traces with any reliability. The decomposition of 2a , and the growth of 3a and 4a are slower than the formation of 2a and may be approximated as temporally separable processes with reaction of 2a being overall rate‐determining.…”

“…For example, stable phosphazides may be generated using sterically demanding phosphines, [8] and such species can be used synthetically as protecting groups. [9,10] The phosphazide group is deprotected by species with a high affinity for phosphorus, such as sulfur.…”

Synthesis of 1,2,3-triazoles using Grignard reactions through the protection of azides

“…Previously, we found that amphos smoothly reacts with azides to furnish phosphazides without denitrogenation, and phosphazides can be transformed into azides through deprotection with elemental sulfur (Meguro et al, 2018). Azide protection realized various transformations, such as selective click reactions of diazides and Grignard reactions using carbonyl compounds having azide moieties due to the good stability of phosphazides as protected azides (Aimi et al, 2021). Herein, we describe an efficient method to prepare organomagnesium intermediates by Frontiers in Chemistry frontiersin.org iodine-magnesium exchange with a turbo Grignard reagent after the phosphazide formation of iodine-substituted azides, enabling facile synthesis of diverse 1,2,3-triazoles by Grignard reactions and following CuAAC reactions.…”

Amphos-Mediated Conversion of Alkyl Azides to Diazo Compounds and One-Pot Azide-Site Selective Transient Protection, Click Conjugation, and Deprotective Transformation

“…In the reports of azide protection studies, aryl azides were selectively protected in the presence of alkyl azides. − Therefore, we also investigated the azide selectivity with the α-azidocarbonyl compound (Scheme d). After treatments with silica gel followed by octasulfur, both azides 8 and 1a were obtained in good yields, with a minor diazo product 3a observed, demonstrating aryl azide-selective protection.…”

“…Yoshida, Hosoya, and co-workers reported an innovative method for azido group protection. − Using Amphos, a bulky and electron-rich phosphine, aryl azides were transiently protected as phosphazide structures without dinitrogen elimination via the Staudinger reaction. After click reactions of the unprotected alkyl azide moieties, the aryl azides were restored by treatment with octasulfur.…”