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An Efficient Synthesis of Substituted meta ‐Halophenols and Their Methyl Ethers: Insight into the Reaction Mechanism
Author(s) -
Khan Faiz Ahmed,
Choudhury Sumit
Publication year - 2010
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.201000071
Subject(s) - chemistry , bicyclic molecule , adduct , hydride , halogen , ether , deuterium , reaction mechanism , kinetic isotope effect , fragmentation (computing) , organic chemistry , combinatorial chemistry , stereochemistry , medicinal chemistry , catalysis , hydrogen , alkyl , physics , quantum mechanics , computer science , operating system
An expeditious synthetic methodology leading to substituted meta ‐halophenols and their corresponding methyl ether derivatives through acid‐mediated fragmentation of suitably substituted dihalonorbornyl ketones has been devised. The reaction sequence consists of TBTH‐mediated (TBTH is tri‐ n ‐butyltin hydride) selective bridgehead halogen reduction of easily accessible Diels–Alder adducts derived from 1,2,3,4‐tetrahalo‐5,5‐dimethoxycyclopentadiene and β‐substituted vinyl acetates, with subsequent conversion into the requisite bicyclic ketones by a two‐step hydrolysis/oxidation approach. An extensive mechanistic investigation based on isotope labeling and cross experiments has been carried out and plausible mechanistic pathways based on these results have been proposed. The absence of halogen atoms at the bridgehead positions steers the reaction through a novel pathway involving the incorporation of proton (or deuterium) followed by elimination of HX (or DX), so the described methodology also provides a reliable route to ortho‐para dideuteratedphenolic derivatives.