Highly Stereoselective Synthesis of Terminal Chloro-Substituted Propargylamines and Further Functionalization

Abstract

The highly stereoselective addition of lithiated chloroacetylene, derived in situ from cis-1,2-dichloroethene and methyl lithium, to Ellman chiral N-tert-butanesulfinyl imines is reported. The reaction proceeds in high yield (up to 98%) and with excellent diastereoselectivity (up to >20:1) for a variety of aryl, heteroaromatic, alkyl, and α,β-unsaturated imine substrates. Transformations of the terminal chloro-substituted propargylamine products are described in which lithium-halogen exchange yields nucleophilic acetylides that can be quenched to yield terminal alkynes or intercepted by carbon electrophiles.

Chiral N‐tert‐Butylsulfinyl Imines: New Discoveries

“…In situ generated lithium chloroacetylide I from ( Z )‐1,2‐dichloroethylene 31 reacted with imines 16 , to give chlorinated propargyl amines 32 with high stereoselectivities (Scheme 13). [28] …”

Photochemical Properties of Propargylamine-based Polymers

“…Another method for the functionalization of propargylamines is the use of reductive amination reactions. Aldehydes and ketones are used in the presence of NaCNBH3 as a reducing agent [20]. Among other synthesis methods, multicomponent reactions and oxidation reactions of tertiary amines are less popular [21].…”

Zinc Oxide Sensitized Graphene Quantum Dots “ZnO‐GQDs”: A Hybrid Concept to Study Charge Transfer and its Catalytic Applicability to Synthesize Tetrasubstituted Propargylamines

“…Propargylamines scaffold are key intermediates in the synthesis of many bioactive compounds and several therapeutic drugs exhibiting widespread attention in academic research as well as industrial applications [21–24] . The classical synthesis of intrinsically valuable propargylamine is well known in literature involving nucleophilic attack of stoichiometric amounts organometallic agents namely Grignard reagents/metallated acetylide on substituted imines under anaerobic and anhydrous conditions [25–27] . The most widely known and straightforward approach to prepare trisubstituted propargylamines is the direct catalytic A3 three component coupling of an aldehyde, amines and alkynes [28,29] .…”