21529-68-0Relevant academic research and scientific papers
The Development of a Stereoselective Method for the Synthesis of Tetrasubstituted Derivatives of α,β-Unsaturated Carboxylic Acids
Rzymkowski, Jan,Pi?tek, Anna
, p. 665 - 673 (2016)
Alkenes possessing four different carbon-linked substituents are the main structural motif of many biologically active compounds. The derivatives of (2E)-3-(3-methoxyphenyl)-2-methylpent-2-enoic acid ((E)-2c) are suitable precursors for the synthesis of Tapentadol, a novel centrally acting analgesic. It was found that the Ni-carbometallation reaction of disubstituted alkyne 8 with CO2and an Et2Zn allows for efficient and practical preparation of (E)-2c as a single (E)-regioisomer in 89% of isolated yield. The influence of the size of the aliphatic substituent of alkyne and the steric hindrance of the organozinc reagent on stereochemical course of the carbometallation reaction was evaluated. Finally, air-stable Ni(dme)Cl2was proposed as an alternative to widely used Ni(cod)2catalyst.
