The Development of a Stereoselective Method for the Synthesis of Tetrasubstituted Derivatives of α,β‐Unsaturated Carboxylic Acids

Abstract

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 CO2 and 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)Cl2 was proposed as an alternative to widely used Ni(cod)2 catalyst.

Interpol review of controlled substances 2016–2019

“…Precursors: 2016 Stereoselective method for the synthesis of derivatives of (2E)-3-(3-methoxyphenyl)-2-methylpent-2-enoic acid ((E)-2c, precursors for the synthesis of Tapentadol [ 1673 ]; impacts of US sodium permanganate and Mexico pseudoephedrine controls [ 1674 ]; effect of precursor control on retail street price [ 1675 ]; single analyzer precursor scans using an ion trap [ 1676 ]; 2017 capacitive biosensor was developed to monitor trace amounts of an amphetamine precursor in aqueous samples [ 1677 ]; data-driven machine learning approach to detect drug- and explosives-precursors using colorimetric sensor technology for air-sampling [ 1678 ]; combined colorimetric and gravimetric CMUT sensor for detection of Phenylacetone [ 1679 ]; portable infrared laser for the identification of psychoactive substances and of their main precursors [ 1680 ]; 2018 a sensor system consisting of a capacitive micromachined ultrasonic transducer and a colorimetric array for detection of benzyl methyl ketone [ 1681 ]; a polyacrylonitrile nanofiber-based quartz crystal microbalance for detecting safrole, the main precursor for producing MDMA [ 1682 ];…”