Chiral terminal bromo-substituted propargylamines are highly functionalized small molecules that are useful synthetic intermediates in organic and medicinal chemistry. Despite their usefulness, current methods to prepare these molecules require multiple synthetic steps. To address this limitation, a new synthetic method to prepare chiral terminal bromo-substituted propargylamines in good chemical yield and chiral selectivity was developed. Reaction optimization efforts focused on varying the reaction base, solvent, and temperature, and resulted in the discovery of optimal reaction conditions that could produce a range of aryl, heteroaryl, alkyl, and α,β-unsaturated terminal bromo-substituted propargylamines in modest to good yields (43 – 85%) and chiral selectivity (dr = 3:1 to &gt;20:1). Finally, the utility of compounds produced with this method was demonstrated by use of these products in the Cadiot-Chodkiewicz coupling to produce functionalized diynes. This new method is gram-scale compatible and expands the range of chiral terminal bromo-substituted propargylamines that can be efficiently synthesized.

Stereoselective synthesis of terminal bromo-substituted propargylamines

ACS Fall 2021

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