Paper Info
Title
Organocatalytic Asymmetric Halocyclization of Allylic Amides to Chiral Oxazolines Using DTBM-SEGPHOS-Mechanistic Implications from Hammett Plots
Abstract
The intramolecular halocyclization of alkenes possessing an internal heteroatom nucleophile leads to multifunctional heterocycles which are useful versatile intermediates in organic synthesis. The asymmetric chlorocyclisation of 2-substituted allylic amides gives access to chiral oxazolines bearing a chloromethyl moiety for further synthetic manipulation. The literature reports on this transformation involve complex syntheses of the 2-substituted allylic amides and cryogenic temperatures for achieving high enantioselectivities in the organocatalyzed halocyclization step. Based on the Heck reaction of aryl bromides and Boc-protected allylamine or allylamine benzamides, we developed a practical synthesis of 2-substituted allylic amides that does not require chromatography and accomplished their asymmetric halocyclization reaction with 24-92%ee under practical conditions (5 degrees C, CpME) catalyzed by (S)-(+)-DTBM-SEGPHOS. In addition, using appropriately substituted substrates, we generated Hammett plots and formulated a consistent mechanism for the halocyclization reaction which involves two competing modes of formation of the haliranium intermediate whose relative kinetics are governed by the electronic properties of the substrate.
Year
DOI
Venue
2022
10.3390/sym14050989
SYMMETRY-BASEL
Keywords
DocType
Volume
organocatalysis, halocyclization, 2-substituted allylic amides, 1, 3-oxazolines, chiral diphosphines, Hammett plots
Journal
14
Issue
ISSN
Citations 
5
2073-8994
0
PageRank 
References 
Authors
0.34
0
6
Name
Order
Citations
PageRank
Fotini Moschona100.34
Christina Misirlaki200.34
Nikolaos Karadimas300.34
Maria Koutiva400.34
Ioanna Savvopoulou500.34
Gerasimos Rassias600.34