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The Development of a Stereoselective Method for the Synthesis of Tetrasubstituted Derivatives of α , β ‐Unsaturated Carboxylic Acids
Author(s) -
Rzymkowski Jan,
Piątek Anna
Publication year - 2016
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201600079
Subject(s) - chemistry , steric effects , alkyne , stereoselectivity , reagent , substituent , yield (engineering) , structural isomer , stereochemistry , combinatorial chemistry , catalysis , organic chemistry , materials science , metallurgy
Alkenes possessing four different carbon‐linked substituents are the main structural motif of many biologically active compounds. The derivatives of (2 E )‐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 CO 2 and an Et 2 Zn 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)Cl 2 was proposed as an alternative to widely used Ni(cod) 2 catalyst.