Diastereoselective Synthesis of Terminal Bromo-Substituted Propargylamines via Generation of Lithium Bromoacetylide and Addition to Chiral N-tert-Butanesulfinyl Aldimines

Abstract

The stereoselective synthesis of terminal bromosubstituted propargylamines via in situ generation of lithium bromoacetylide from 1,2-dibromoethene and addition to Ellman chiral N-tert-butanesulfinyl aldimines is reported. Modest to good yields (43− 85%) and diastereoselectivity (dr = 3:1 to >20:1) were achieved for a range of aryl, heteroaryl, alkyl, and α,β-unsaturated substrates. Terminal bromo-substituted propargylamines prepared via this method can be directly used in the frequently employed Cadiot−Chodkiewicz coupling to produce functionalized diynes. The method reported here increases the structural diversity of chiral terminal bromo-substituted propargylamines that can be readily synthesized as previous methods for the stereoselective synthesis of these compounds rely on amino acid precursors from the chiral pool.

Palladium/Brønsted-Acid-Catalyzed Diastereoselective Cyclization with Chiral Sulfinamides as Nucleophiles

“…1−3 In particular, diastereoselective nucleophilic addition to chiral sulfinimines, aldimines, or ketimines derived from Ellman's reagents has been extensively studied with various nucleophilic reagents, exhibiting excellent stereocontrol. 3 By contrast, methods for stereoselective reactions with N-tertbutyl sulfinamide derivatives as chiral nucleophiles remain limited. 4 Fustero and del Pozo reported intramolecular aza-Michael addition with tethered chiral sulfinamides as nucleophiles, which yielded various cyclized products (Scheme 1a).…”