NDLI: Lithium Diisopropylamide-Mediated Ortholithiation of 2–Fluoropyridines: Rates, Mechanisms, and the Role of Autocatalysis

Content Provider	PubMed Central
Author	Gupta, Lekha Hoepker, Alexander C. Yun, Ma Viciu, Mihai S. Faggin, Marc F. Collum, David B.
Abstract	Lithium diisopropylamide (LDA)-mediated ortholithiations of 2–fluoropyridine and 2,6–difluoropyridine in tetrahydrofuran at −78 °C were studied using a combination of IR and NMR spectroscopic and computational methods. Rate studies show that a substrate-assisted deaggregation of LDA dimer occurs parallel to an unprecedented tetramer-based pathway. Standard and competitive isotope effects confirm post-rate-limiting proton transfer. Autocatalysis stems from ArLicatalyzed deaggregation of LDA proceeding via 2:2 LDA–ArLi mixed tetramers. A hypersensitivity of the ortholithiation rates to traces of LiCl derives from LiClcatalyzed LDA dimer–monomer exchange and a subsequent monomer-based ortholithiation. Fleeting 2:2 LDA–LiCl mixed tetramers are suggested to be key intermediates. The mechanisms of both the uncatalyzed and catalyzed deaggregations are discussed. A general mechanistic paradigm is delineated to explain a number of seemingly disparate LDA-mediated reactions, all of which occur in tetrahydrofuran at −78 °C.
Related Links	http://dx.doi.org/10.1021/jo302408r
Ending Page	4230
Page Count	17
Starting Page	4214
File Format	PDF
ISSN	00223263
e-ISSN	15206904
Journal	The Journal of organic chemistry
Issue Number	9
Volume Number	78
Language	English
Publisher Date	2013-05-03
Access Restriction	Open
Subject Keyword	Organic Chemistry Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry

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