Kinetic and Dynamic Kinetic Resolution of Racemic Tertiary Bromides by Pentanidium‐Catalyzed Phase‐Transfer Azidation

Abstract

We have developed a method to afford enantiomerically enriched tertiary azides and bromides through pentanidium‐catalyzed kinetic resolution (KR) of racemic tertiary bromides under base‐free conditions. We found that the absence of water is crucial to attain a high selectivity factor (s). On the other hand, new experimental observations and DFT modeling led us to propose that enantioconvergent azidation of tertiary bromides proceeded through dynamic kinetic resolution (DKR). The investigations particularly identified the crucial roles of base and water in the enantioconvergent process, thus supporting the proposal that the tertiary bromide isomerizes in the presence of base and water through a SN2X pathway.

Pentanidium-Catalyzed Direct Assembly of Vicinal All-Carbon Quaternary Stereocenters through C(sp 3 )–C(sp 3 ) Bond Formation

“…Shortly thereafter, a more in-depth investigation of the azide-substitution with tertiary bromide, revealed that it is a dynamic kinetic resolution, modulated by base present in the reaction. 32 Herein, we report our recent progress into the use of nucleophilic substitutions to construct vicinal all-carbon quaternary stereocenters, using insights from our previous works, through direct coupling of racemic tertiary electrophiles with racemic tertiary nucleophiles using chiral cations as catalysts (Figure 1c).…”

Stereospecific and stereoconvergent nucleophilic substitution reactions at tertiary carbon centers

“…Following this work, the same group also reported an enantioselective azidation of tertiary bromides using NaN 3 as the nucleophile (Scheme 48B). 96 It was found in this azidation reaction, tertiary azides 218 can be obtained either through kinetic resolution (KR) or dynamic kinetic resolution (DKR) under different reaction conditions. Base-free conditions resulted in KR (up to 50% yield with high ees) and basic conditions resulted in DKR (high yields and ee values).…”

Kinetic resolution of cyclic benzylic azides enabled by site- and enantioselective C(sp3)–H oxidation

“…Catalytic nonenzymatic kinetic resolution (KR) of racemates is one of the most powerful and practical tools to prepare valuable enantiopure targets, especially in cases where other methods are not possible or provide insufficient enantiocontrol 1 – 5 . Chiral organic azides are versatile synthetic precursors for a range of nitrogen-containing molecules and have found dramatically expanded utility in medicine, biology, and material science 6 – 15 .…”