Activation of sp3 and sp2 C-H bonds of oxygen containing heterocyclic molecules for alkylation and arylation reactions catalyzed by an iron complex

Article abstract of DOI:10.1016/j.molcata.2014.05.013

Activation of both sp³ and sp² CH bonds is reported using an efficient iron(III) complex (1) of a ligand (N2,N6-bis(2,6- diisopropylphenyl)pyridine-2,6-dicarboxamide: L). The iron(III) complex showed catalytic activity of CC coupling reaction of oxygen containing heterocycles, e.g. tetrahydrofuran (THF), with various alkyl, allyl and aryl Grignard reagents under ambient reaction conditions. Complex 1 demonstrated excellent activity and reactions were completed within 30 min to 1 h. A high turnover frequency (TOF) of 1700 h^-1 using a low catalyst loading of 0.02 mol% was obtained for the reaction. Interestingly, the catalyst was selective in activation of the CH bond adjacent to the oxygen in various oxygen containing heterocyclic molecules to yield 2-substitituted products.

Full text of DOI:10.1016/j.molcata.2014.05.013

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Accepted Manuscript
Title: Activation of sp3 and sp2 C-H bonds of oxygen
containing heterocyclic molecules for alkylation and arylation
reactions catalyzed by an iron complex
Author: Yashraj Gartia Punnamchandar Ramidi Sreevishnu
Cheerla Charlette M. Felton Darin E. Jones Bhaskar C. Das
Anindya Ghosh
PII:
S1381-1169(14)00210-6
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2014.05.013
MOLCAA 9113
To appear in:
Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
15-8-2013
5-5-2014
15-5-2014
Please cite this article as: Y. Gartia, P. Ramidi, S. Cheerla, C.M. Felton,
D.E. Jones, B.C. Das, A. Ghosh, Activation of sp3 and sp2 C-H bonds of
oxygen containing heterocyclic molecules for alkylation and arylation reactions
catalyzed by an iron complex, Journal of Molecular Catalysis A: Chemical (2014),
http://dx.doi.org/10.1016/j.molcata.2014.05.013
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Activation of sp3 and sp2 C-H bonds of oxygen containing
heterocyclic molecules for alkylation and arylation reactions
catalyzed by an iron complex
Yashraj Gartia,1 Punnamchandar Ramidi,1 Sreevishnu Cheerla,1 Charlette M. Felton,1
Darin E. Jones, 1 Bhaskar C. Das,2 and Anindya Ghosh*1
1Department of Chemistry, University of Arkansas at Little Rock, 2801 South University Avenue,
Little Rock, AR 72204, USA
2The University of Kansas Medical Center, 4801 Linwood Blvd. Room F5-100
Kansas City, MO 64128, USA
*Corresponding author: E-mail: axghosh@ualr.edu, Phone: 501 569 8827, Fax: 501 569 8838
Abstract
Activation of both sp3 and sp2 C-H bonds is reported using an efficient and iron(III)
complex (1) of a ligand (N2,N6-bis(2,6-diisopropylphenyl)pyridine-2,6-dicarboxamide: L). The
iron(III) complex showed catalytic activity of C-C coupling reaction of oxygen containing
heterocycles, e.g. tetrahydrofuran (THF), with various alkyl, allyl and aryl Grignard reagents
under ambient reaction conditions. Complex 1 demonstrated excellent activity and reactions
were completed within 30 min to 1 h. A high turnover frequency (TOF) of 1700 h-1 using a low
catalyst loading of 0.02 mol% was obtained for the reaction. Interestingly, the catalyst was
selective in activation of the C-H bond adjacent to the oxygen in various oxygen containing
heterocyclic molecules to yield 2-substitituted products.
Keywords: iron(III) complex; oxygen containing heterocyclics; Grignard reagents; sp3 and sp2
C-H bond activation; C-C coupling
Page 1 of 25

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1. Introduction
The use of atom efficient and economical methods for the development of complex
structures or molecules is always fascinating and challenging tasks for chemists. Various organic
synthetic processes strive to employ simple and readily available precursors for the generation of
more complex synthetic compounds. C-C coupling reactions by the transformation of
functionalities present in the precursor molecule structures are one such field of great scientific
interest [1, 2]. Based on the use of different coupling partners, several methods have been
established extensively for numerous synthetic applications. These well-defined reactions
generally employ compounds with various functionalities present within (or) introduced into the
precursor’s structure such as alkyl halides [3-7] and olefins [8, 9]. Such nucleophiles have been
reported to be easily functionalized with organometallic reagents, for example alkyl and aryl
boronic acid [10], tetraalkyltin reagents [11] and Grignard reagents [12]. However, the direct
activation of C-H bond and functionalization with Grignard reagent for the C-C coupling
reactions has not been exploited [13-15]. The ready availability of a C-H group, which is far
more abundant in general organic moieties over other functional groups, has vastly prompted the
study of C-H transformation for organic syntheses.
Extensive studies in the last four decades [16-31] has assisted in the better understanding
of C-H bond activation. Among these, the use of a transition metal and its complexes as catalysts
[32] for C-H bond activation is highly desirable. Transition metals like palladium [33], iridium
[34], rhodium [32], platinum [35], nickel [36], cobalt [12], etc. have been reported to play a
predominant role to facilitate efficient transformations through C-H activation. However, recent
use of 1st row transition metals has caught the attention for performing C-H transformation
reactions. Of these, the use of iron complexes as a virtue of their ready availability, low cost,
Page 2 of 25

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relatively low toxicity, and unique catalytic abilities has drawn much interest for the activation
and transformation of organic/inorganic substrates [37].
Tolman et al. first reported the use of an iron complex for such C-H bond cleavage in the
late 1970s. A transient 16-electron iron(0) species, iron(dmpe)2, was accounted for performing
the C-H bond cleavage [38]. Photolysis of the associated iron complex, iron(dmpe)2H2, was
found to activate C-H bonds of alkenes via generation of the same transient species, iron(dmpe)2
[24]. However, it was the activation of an aromatic C-H bond attained by irradiation of an iron
complex, which resulted in the first successful C-H functionalization through catalytic insertion
of isocyanide [39].
The use of an iron-based catalyst is even more attractive as iron is cheap and
environmentally benign. In 2008, Tatsumi and co-workers reported a half-sandwich iron
complex that could carry out reversible C-H bond activation of the 2-position of thiophenes and
furans under ambient conditions to produce the iron-heteroaryl complexes [40]. This iron
complex was successfully used to synthesize 2-boryl-heteroarenes intermediates upon treatment
with catecholborane. However, it was Nakamura et al. in 2008 who developed the first iron
based C-H activation for direct arylation. The use of zinc chloride and an aryl Grignard reagent
led to the in situ generation of an organozinc reagent that was oxidatively coupled with the help
of tetramethylenediamine (TMEDA) and 1,10-phenanthroline [34]. Afterwards, the same group
successfully functionalized the ortho C-H bond of an aromatic ketamine using an arylzinc
reagent [41].
The successful activation of C(sp2)-H bond using various transition metals [12, 33, 42],
including iron complexes, encouraged the researcher to investigate the possible use of iron for
the largely dormant field of C(sp3)-H activation and functionalization. However, the activation of
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