Highly regioselective functionalization of aliphatic carbon-hydrogen bonds with a perbromohomoscorpionate copper(I) catalyst

Article abstract of DOI:10.1021/ja0291484

The complex Tp^Br3Cu(NCMe) (1) is an excellent catalyst for the regioselective carbene transfer reaction to tertiary C-H bonds of hydrocarbons, at room temperature, using the readily available ethyl diazoacetate (EDA) as the carbene source. Copyright

Full text of DOI:10.1021/ja0291484

Published on Web 01/15/2003
Highly Regioselective Functionalization of Aliphatic Carbon-Hydrogen Bonds
with a Perbromohomoscorpionate Copper(I) Catalyst
†
†
†
†
Ana Caballero, M. Mar D ´ı az-Requejo, Tom a´ s R. Belderra ´ı n, M. Carmen Nicasio,
‡
,†
Swiatoslaw Trofimenko, and Pedro J. P e´ rez*
Departamento de Qu ´ı mica y Ciencia de Materiales, UniVersidad de HuelVa, Campus de El Carmen,
2
1071-HuelVa, Spain, and Department of Chemistry and Biochemistry, UniVersity of Delaware,
Newark, Delaware 19716
Received October 30, 2002 ; E-mail: perez@dqcm.uhu.es
Despite the many advances made in the past 20 years concerning
the stoichiometric activation of C-H bonds by transition-metal
complexes, there are few examples of catalytic transformations
feedstocks into valuable chemicals. Particularly interesting could
be the use of this procedure to functionalize hydrocarbon-based
polymers. This method would allow installation of a functional
group after polymer formation, avoiding the well-known problems
1
incorporating these activation reactions. Saturated hydrocarbons,
13
currently the most abundant feedstock, are particularly difficult to
functionalize using a C-H oxidation addition reaction.2 One
alternative methodology to functionalize alkanes consists of the
insertion of a transient metallocarbene species into the carbon-
hydrogen bond (eq 1)3
in the use of functionalized monomers.
6
In our previous contribution, the yields were high in the case
of cyclic ethers but moderate (50%) in the case of cycloalkanes
(cyclohexane and cyclopentane). Low conversions (<10%) were
observed when using acyclic alkanes. In search of a better catalyst
for such substrates, we have chosen to examine the novel perbromo
Br3 14
ligand Tp
,
that contains nine bromine atoms in the Tp
framework. This choice was based on the previous proposal by
several authors that the existence of electron-withdrawing groups
on ligands in the coordination sphere could favor the insertion
reaction, due to the enhancement in the electrophilicity of the
with the subsequent formation of a new carbon-carbon bond and
catalyst release to restart the catalytic cycle. The metallocarbene
species can be generated in situ by addition of a diazo reagent to
an appropriate transition-metal complex. Although the intramo-
lecular version of this reaction has been widely applied in organic
metal-carbene intermediate.7 The new complex Tp Cu(NCMe)
,8,12
Br3
Br3
(1) was prepared by the direct reaction of CuI and TlTp in
acetonitrile. Evidence for the decrease in electron density at the
metal center comes straightforwardly from the monocarbonyl adduct
3
synthesis, the intermolecular counterpart has not been studied as
Br3
-1
much. The reaction between ethyl diazoacetate (EDA) and cyclo-
Tp Cu(CO) (2) that displays a value of 2110 cm for ν(CO).
4
Ms
hexane was first reported by Scott et al. wherein low yields of the
The related derivative Tp Cu(CO) complex showed a ν(CO)
frequency of 2060 cm .
-
1 15
insertion product with copper salts as the catalyst were obtained.
The allylic C-H bond functionalization of cyclohexene induced
The expected enhancement of the catalytic activity with 1 was
by Cu(acac)
2
was later reported by Wulfman, again with very low
demonstrated upon reacting EDA and cyclohexane (eq 2):
conversions.5 To our knowledge, no more Cu-based catalytic
systems for this transformation have been reported until our recent
contribution describing the use of complexes of general formula
X
X
Tp Cu (Tp ) homoscorpionate ligand) as catalysts for the insertion
of ethyl diazoacetate into C-H bonds of cycloalkanes and cyclic
ethyl 2-cyclohexyl acetate was obtained in 90% yield (based in
EDA, [Cu]:[EDA]:[C H12], 1:20:1000). But, as mentioned above,
6
6
ethers. The decay of copper for this and other metallocarbene-
3
based reactions was mainly due to the work by Noels and co-
workers, that described Rh
acyclic substrates present more interest from the functionalization
2
(OAc)
4
as the catalyst of choice for those
16
point of view. A series of experiments have been carried out with
7
transformations. Related rhodium catalysts, later employed by
such molecules; the results are summarized in Table 1. The
8
9
10
Callot, Adams, and M u¨ ller, provided interesting results with a
range of substrates from hydrocarbons to cyclic ethers. However,
no doubt this alternative for C-H bond functionalization has gained
much interest in the past few years after the work from Davies and
co-workers with their chiral rhodium-based catalysts: in addition
chemoselectivity induced by 1 with EDA as the carbene source is
4,5
7,8
higher than that reported with other copper and rhodium
systems. This activity is somewhat unexpected, particularly after a
17
recent theoretical study by Nakamura et al. that predicted values
for the activation energy of this type of C-H insertion reaction:
the +5.7 kcal/mol calculated for the rhodium case is quite distinct
from the + 15.6 kcal/mol estimated for copper. Thus, tuning of
11
to the insertion of aryldiazoacetates into alkanes and cyclic ethers,
12a
the functionalization of C-H bonds of pyrrolidines,
allylic
12b
12c
12d
alkenes, alkoxysilanes, N-BOC-protected amines, allyl silyl
Br3
the metal center with the Tp ligand seems to be decisive in
ethers,1 or silyl enol ethers has been achieved in preparative
2e
12f
improving the catalytic activity in the copper system.
yields and with high degrees of asymmetric induction. However,
the application of this methodology to very unreactive alkane
substrates finds few reports in the literature.4
of catalytic systems that allow the functionalization of those C-H
bonds could provide a new method for converting inexpensive
Several trends can be inferred from the data inTable 1. First, no
primary C-H insertion has been observed, at least in the NMR
detection limit. This is in contrast with the previous reports of both
,5,7,8,11
The development
7
8
12
Noels and Callot, but similar to Davies’ results. The use of
-methylbutane provided a direct measure of the relative reactivities
2
between primary, secondary, and tertiary C-H bonds. NMR studies
showed a 80:20 tertiary:secondary molar ratio of products. A
†
Universidad de Huelva.
University of Delaware.
‡
1446
9
J. AM. CHEM. SOC. 2003, 125, 1446-1447
10.1021/ja0291484 CCC: $25.00 © 2003 American Chemical Society

C O MMU N I C A T I O N S
Scheme 1. Selective Functionalization of
Table 1. Insertion of Ethyl Diazoacetate into C-H Bonds of
Br3
a
Alkanes Catalyzed by Tp Cu(NCMe) (1)
2,6,10,14-Tetramethylpentadecane with EDA
insertion into the methylene groups are in good agreement with
the trends presented above.
In conclusion, we have found that the complex TpBr3Cu(NCMe)
(1) is an excellent catalyst for the regioselective carbene-transfer
reaction to tertiary C-H bonds of hydrocarbons. Applications to
other substrates, such as hydrocarbon polymeric chains, are currently
underway in our laboratories.
Acknowledgment. Dedicated to Professor Maurice Brookhart
on occasion of his 60th birthday. We thank the MCYT (Proyecto
BQU2002-01114) for financial support and the Universidad de
Huelva for the Servicio de Resonancia Magn e´ tica Nuclear. A.C.
thanks the MECD for a research fellowship.
Supporting Information Available: Syntheses and characterization
of complexes 1 and 2, and spectroscopic data for the monoesters
compounds (PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
a
b
See ref 16 for experimental details. Product distribution observed by
1
c
H NMR spectroscopy. EDA-based, determined after total consumption
of EDA. Diethyl fumarate, maleate, and ethyl glycidate account for 100%
of EDA. Selectivity for tertiary sites, normalized for the relative number
of hydrogen atoms. Selectivity for C2 secondary sites, also normalized.
d
e
statistical factor must be included to estimate the regioselectivity
per C-H bond,7d the tertiary selectivity for 2-methylbutane reaching
References
(
1) (a) Dyker, G. Angew. Chem., Int. Ed. Engl. 1989, 28, 1698. (b) Guari,
Y.; Sabo-Etienne, S.; Chaudret, B. Eur. J. Inorg. Chem. 1999, 1047. (c)
Arndtsen, B. A.; Bergman, R. G.; Mobley, T. A.; Peterson, T. H. Acc.
Chem. Res. 1995, 28, 154.
9
1%. Other branched alkanes such as 2-methylpentane, 2,3-
dimethylpentane, and 2,5-dimethylhexane have also been studied,
with the respective values for the tertiary selectivities of 87, >99,
and >99% being observed. This tertiary reaction site displays the
weakest C-H bond as well as the highest steric hindrance, and
thus electronic effects appear to dominate in this system. Additional
support came from a competition reaction between 2-methylbutane
and 1-bromo-3-methylbutane, for which only products derived from
the former were observed; the bromine atom deactivated both
tertiary and secondary sites in this substrate. This effect has also
been observed by Callot using rhodium-porphyrin catalysts.8
The situation varies when comparing the degree of functional-
ization for methylene groups. Given the similarities in electronics,
steric factors must be crucial. The methylene groups adjacent to
terminal methyl groups undergo activation in all cases, whereas
(
2) Shilov, A. E.; Shul’pin, G. B. ActiVation and Catalytic Reactions of
Saturated Hydrocarbons in the Presence of Metal Complexes; Kluwer:
Dordrecht, 2000.
(
3) (a) Doyle, M. P. In ComprehensiVe Organometallic Chemistry II; Abel,
E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Press: Oxford,
UK, 1995; Vol. 12, p 421. (b) Doyle, M. P.; McKervey, M. A.; Ye, T.
Modern Catalytic Methods for Organic Synthesis with Diazo Compounds;
John Wiley & Sons: New York, 1998.
(
(
4) Scott, L. T.; DeCicco, G. J. J. Am. Chem. Soc. 1974, 96, 322.
5) Wulfman, D. S.; McDaniel, R. S.; Peace, B. W. Tetrahedron 1976, 32,
1241.
(
6) D ´ı az-Requejo, M. M.; Belderrain, T. R.; Nicasio, M. C.; Trofimenko, S.;
P e´ rez, P. J. J. Am. Chem. Soc. 2002, 124, 896.
(
7) (a) Demonceau, A.; Noels, A. F.; Hubert, A.; Teyssi e´ , P. J Chem. Soc.,
Chem. Commun. 1981, 688. (b) Demonceau, A.; Noels, A. F.; Hubert,
A.; Teyssi e´ , P, Bull. Soc. Chim. Belg. 1984, 93, 945. (c) Demonceau, A.;
Noels, A. F.; Costa, J. L.; Hubert, A. J. Mol. Catal. 1990, 58, 21. (d)
Demonceau, A.; Noels, A. F.; Teyssie, P.; Hubert, A. J. Mol. Catal. 1988,
49, L13.
(
8) (a) Callot, H. J.; Metz, F. Tetrahedron Lett. 1982, 23, 4321. (b) Callot,
H. J.; Metz, F. NouV. J. Chem. 1985, 9, 167.
2
internal CH groups were activated to a lesser extent in linear
(
9) Adams, J.; Poupart, M.-A.; Schller, C.; Ouimet, N.; Frenette, R.
Tetrahedron Lett. 1989, 14, 1749.
alkanes or did not react at all when directly bonded to branched
carbons. As a result of this trend, high control of the selectivity
was achieved for 2,5-dimethylhexane, with no secondary activation
in the central CH
the level of regioselectivity displayed by this system with the readily
(
10) M u¨ ller, P.; Tohill, S. Tetrahedron 2000, 56, 1725.
(
11) (a) Davies, H. M. L.; Hansen, T.; Churchill, M. R. J. J. Am. Chem. Soc.
2
000, 122, 3063. (b) Davies, H. M. L.; Antoulinakis, E. G. J. Organomet.
2 2
-CH unit being observed. To our knowledge,
Chem. 2001, 617-618, 39.
(12) (a) Davies, H. M. L.; Venkaratamani, C. Org. Lett. 2001, 3, 1773. (b)
Davies, H. M. L.; Ren, P.; Jin, Q. Org. Lett. 2001, 3, 3587. (c) Davies,
H. M. L.; Antoulinakis, E. G. Org. Lett. 2000, 2, 4253. (d) Davies, H. M.
L.; Hansen, T.; Hoper, D. W.; Panaro, S. A. J. Am. Chem. Soc. 1999,
available EDA finds no precedent in the literature.
The catalytic properties of complex 1 toward the preferential
functionalization of tertiary C-H bonds can be expanded to more
elaborate substrates. We have explored the application of such
capabilities to higher alkanes such as 2,6,10,14-tetramethylpenta-
decane (TMPD). This molecule models the potential activation sites
of branched polymers with different tertiary as well as secondary
C-H bonds available. In this experiment, the diazo reagent has
been employed in excess. Thus, when 1 mmol of TMPD was
reacted1 with a 10-fold excess of EDA, 85% of the alkane was
converted into mono-inserted derivatives (Scheme 1); only tertiary
sites were activated with no secondary activation being observed
within the NMR detection limit. Two isomers T (terminal) and I
1
21, 6509. (e) Davies, H. M. L.; Antoulinakis, E. G.; Hansen, T. Org.
Lett. 1999, 1, 383. (f) Davies, H. M. L.; Ren, P. J. Am. Chem. Soc. 2001,
123, 2070.
(
(
13) Guyot, A. Polym. AdV. Technol. 1996, 7, 61 and references therein.
14) Rheingold, A. L.; Liable-Sands, L. M.; Incarvito, C. L.; Trofimenko, S.
J. Chem. Soc., Dalton Trans. 2002, 2297.
(
15) Schneider, J. L.; Carrier, S. M.; Ruggiero, C. E.; Young, V. G.; Tolman,
W. D. J. Am. Chem. Soc. 1998, 129, 11408-11418.
(16) Experimental: (a) All the operations were carried out inside a drybox. 1
(
2 2
0.05 mmol) was dissolved in CH Cl (5 mL) and the alkane (20 mL). A
solution of EDA (1 mmol) in the same alkane (10 mL) was added for 5
h with the aid of a syringe pump. No EDA was detected at the end of the
reaction by GC. After removal of volatiles, the crude product was
6b
1
investigated by H NMR spectroscopy. (b) In the case of TMPD, 1 mmol
of the alkane was dissolved in 20 mL of CH
2
Cl
2
, and 10 mmol of EDA
was added (10 mL of CH Cl ) over 5 h with the syringe pump.
2 2
(
17) Nakamura, E.; Yoshikai, N.; Yamanaka, M. J. Am. Chem. Soc. 2002, 124,
(internal) have been isolated and characterized in a 60:40 ratio
7181.
favoring the former. The activation of tertiary sites and the lack of
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