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One‐Pot Three‐Component Heteroannulation of β‐Oxo Dithioesters, Amines and Hydroxylamine: Regioselective, Facile and Straightforward Entry to 5‐Substituted 3‐Aminoisoxazoles
Author(s) -
Samai Subhasis,
Chanda Tanmoy,
Ila Hiriyakkanavar,
Singh Maya Shankar
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201300038
Subject(s) - hsab theory , chemistry , regioselectivity , hydroxylamine , nucleophile , structural isomer , amine gas treating , combinatorial chemistry , aryl , alkyl , organic chemistry , intramolecular force , medicinal chemistry , catalysis
Abstract An efficient and highly regioselective one‐pot three‐component synthesis of previously inaccessible and synthetically demanding 3‐(cycloalkyl/alkyl/arylamino)‐5‐aryl/alkylisoxazoles has been achieved by the cyclocondensation of β‐oxo dithioesters, amines and hydroxylamine in ethanol at reflux. This transformation proceeds via an in situ generated β‐oxothioamide by the reaction of the β‐oxo dithioester and amine, which undergoes nucleophilic attack by hydroxylamine followed by intramolecular cyclization with the oxo functionality and subsequent dehydration to give 5‐substituted 3‐aminoisoxazoles as a single regioisomer in good yields. Furthermore, the mechanism of the reaction has been established experimentally and shown to be in agreement with the hard and soft (Lewis) acid and base (HSAB) theory.