Catalytic enantioselective synthesis of α-chiral azides

Abstract

The catalytic asymmetric synthesis of α-chiral azides is of current interest and three synthetic strategies have been developed. This review summarizes the recent progress in this research area, discusses the advantages and limitations of each strategy, and outlines synthetic opportunities for future research.

Towards an Asymmetric Organocatalytic α-Azidation of β-Ketoesters

“…Organic azides are an important and versatile class of molecules, and their syntheses and applications have attracted considerable interest [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Their potential lies in the fact that these compounds can serve as valuable building blocks for further transformations, e.g., the direct syntheses of heterocycles by means of a 1,3-dipolar cycloaddition with alkynes [ 3 , 4 , 5 ], or their straightforward reduction to free amines [ 6 , 7 , 8 ] (to mention only a few thoroughly investigated prominent applications of azides).…”

“…Their potential lies in the fact that these compounds can serve as valuable building blocks for further transformations, e.g., the direct syntheses of heterocycles by means of a 1,3-dipolar cycloaddition with alkynes [ 3 , 4 , 5 ], or their straightforward reduction to free amines [ 6 , 7 , 8 ] (to mention only a few thoroughly investigated prominent applications of azides). Keeping this high potential in mind, it is no surprise that a variety of strategies to introduce azide functionalities in organic molecules have been reported [ 1 , 7 , 8 , 9 , 10 ]. The classical way of installing an azide group is based on the displacement of leaving groups, e.g., halides, by nucleophilic azide sources, like NaN 3 or trimethylsilylazide (TMSN 3 ) [ 11 ].…”

Insight into the factors controlling the equilibrium of allylic azides

“…Organic azides are versatile substrates for use in reactions such us the Staudinger reaction, Schmidt reaction and Curtius rearrangement. [1][2][3] Also, since the introduction of copper(I) azidealkyne cycloaddition, thousands of compounds have been prepared. [4][5][6] Azide bioorthogonality has promoted this functional group's introduction on metabolites and proteins in many different studies.…”

“…Also, the distribution of the regioisomers is affected by the steric bulkiness and the conjugations of the double bonds. It has widely been assumed that the rearrangement of the allylic azides occurs through a concerted [3,3]-sigmatropic mechanism via a cyclic transition structure. 18,19 However, an ionic mechanism was recently proposed for the rearrangement of allylic azides at high temperatures or under Lewis acidic conditions.…”

Allylic azides: synthesis, reactivity, and the Winstein rearrangement

“…In particular, the Huisgen cycloaddition, Staudinger reaction, Schmidt reaction, and Curtius rearrangement have been used extensively in organic synthesis. [1][2][3][4][5][6][7][8][9][10] Additionally, azides have classically been used as protected primary amine equivalents. The utility of organic azides has been further extended because of the bioorthogonality exhibited in several classic reactions with azides.…”