Zinc Salt Promoted Diastereoselective Synthesis of Chiral Propargylamines Using Chiral Piperazines and Their Enantioselective Conversion into Chiral Allenes

Abstract

Zinc chloride catalyzed reactions of chiral piperazine derivatives 4a–d with 1‐alkynes and aldehydes give chiral propargylamines in 67–95 % yields with up to 99:1 dr. The chiral propargylamines are converted into chiral allenes by using zinc bromide in short reaction times (1–2 h) in high enantioselectivities (up to 99 % ee) in good yields (up to 89 %). The chiral piperazines are recovered in good yields (79–86 %) by reduction of the imine byproducts in situ by using NaBH4. Unexpectedly, the chiral aryl‐substituted allenes undergo facile cyclodimerization under neat conditions at 25 °C, in contrast to an earlier report that cyclodimerization takes place at 80 °C in benzene, which further illustrates the importance of the two‐step procedure reported herein because the chiral propargylamine may be converted into chiral allene when required.

Anchorage of Au3+ into Modified Isoreticular Metal–Organic Framework-3 as a Heterogeneous Catalyst for the Synthesis of Propargylamines

“…Among these synthetic strategies, A 3 coupling is the most efficient, and it permits construction of complex structures from simple starting materials with water as byproduct 10,11 . In recent years, various metals such as Au 9 , Cu 8 , Ag 12 , In 13 , Fe 14 , Zn 15 , and Ni 16 were extensively used to synthesize propargylamines. Among these metals, cationic gold species have received special attention because of their effective catalytic activity in A 3 coupling reactions 17,18 .…”

Iron oxide modified with pyridyl‐triazole ligand for stabilization of gold nanoparticles: An efficient heterogeneous catalyst for A3 coupling reaction in water

“…In addition, propargylamines have applications as therapeutic drug molecules in the treatment of Alzheimer's and Parkinson's diseases . Within the past few years, various transition metals such as copper, silver, iridium, iron, zinc, indium and nickel have been reported as catalysts for the preparation of propargylamines via A 3 coupling reaction under homogeneous or heterogeneous reaction conditions. In recent years, increasing attention has been paid to the catalytic performance of gold, which traditionally was considered as a poor and inactive metal .…”

Gold Nanoparticles Supported on Imidazole‐Modified Bentonite: Environmentally Benign Heterogeneous Catalyst for the Three‐Component Synthesis of Propargylamines in Water

“…One of the best examples of MCRs that reduce waste and increase safety is the catalytic coupling reaction of aldehydes, amines, and terminal alkynes (A3 coupling) via C−H activation of alkynes for the synthesis of propargylamines . Recently, many transition‐metal catalysts based on Ir, Ag, Cu, a Cu−Ru bimetallic system, Fe, Zn, and In [13] have been suggested as new catalysts for the preparation of propargylamines. Because of the well‐recognized catalytic properties of gold(I) and (III) in recent years, gold‐based catalysts have been identified as efficient catalysts in various organic transformations .…”