Estimated rate constants for hydrogen abstraction from n-heterocyclic carbene-borane complexes by an alkyl radical

Article abstract of DOI:10.1021/ol101014q

Rate constants for hydrogen abstraction by a nonyl radical from 20 complexes of N-heterocyclic carbenes and boranes (NHC-boranes) have been determined by the pyridine-2-thioneoxycarbonyl (PTOC) competition kinetic method at a single concentration point. The rate constants range from <1 × 10⁴ to 8 × 10⁴ M^-1 s^-1. They show little dependence on the electronic properties of the carbene core, but there is a trend for increasing rate constants with decreasing size of the carbene N-substituents. Two promising new reagents with small N-substituents (R = Me) have been identified.

Full text of DOI:10.1021/ol101014q

ORGANIC
LETTERS
2010
Vol. 12, No. 13
2998-3001
Estimated Rate Constants for Hydrogen
Abstraction from N-Heterocyclic
Carbene-Borane Complexes by an
Alkyl Radical†
Andrey Solovyev,‡ Shau-Hua Ueng,‡ Julien Monot,§ Louis Fensterbank,§
Max Malacria,§ Emmanuel Lacoˆte,*,§ and Dennis P. Curran*,‡
Department of Chemistry, UniVersity of Pittsburgh, Pittsburgh, PennsylVania 15260 USA,
UPMC UniV Paris 06, Institut Parisien de Chimie Mole´culaire (UMR CNRS 7201),
C 229, 4 Place Jussieu, 75005 Paris, France
emmanuel.lacote@upmc.fr; curran@pitt.edu
Received May 3, 2010
ABSTRACT
Rate constants for hydrogen abstraction by a nonyl radical from 20 complexes of N-heterocyclic carbenes and boranes (NHC-boranes) have
been determined by the pyridine-2-thioneoxycarbonyl (PTOC) competition kinetic method at a single concentration point. The rate constants
range from <1 × 104 to 8 × 104 M-1 s-1. They show little dependence on the electronic properties of the carbene core, but there is a trend
for increasing rate constants with decreasing size of the carbene N-substituents. Two promising new reagents with small N-substituents
(R ) Me) have been identified.
Interest in complexes of N-heterocyclic carbenes and main
group elements is rapidly increasing.1 Carbene-borane
complexes (NHC-boranes) are an emerging class of reagents
with potential applications in radical,2 ionic,3a-c and orga-
nometallic reactions.3d Much of the early work has focused
on the prototypical complex 1,3-bis(2,6-diisopropylphe-
nyl)imidazol-2-ylidene borane 1 (hereafter called dipp-Imd-
BH3). In a representative radical reaction (Scheme 1),
reduction of xanthate 2 with 2 equiv of 1 (80 °C, 2 equiv of
AIBN, 10 h) provided the reduced product 4 in 64% along
with dithiocarbonate borane complex 3.2b
Mechanistic studies of the xanthate deoxygenation with 1
support a standard two-step radical-chain reaction for this
new type of Barton-McCombie reaction4 in which 1 plays
the role of radical hydrogen atom donor (eq 1) and its derived
† Dedicated to the memory of Prof. Athelstan L. J. Beckwith, 1930-2010.
‡ University of Pittsburgh.
§ Institut Parisien de Chimie Mole´culaire.
(1) (a) Kirmse, W. Eur. J. Org. Chem. 2005, 237–260. (b) Chase, P. A.;
Stephan, D. W. Angew. Chem., Int. Ed. 2008, 47, 7433–7437. (c)
Holschumacher, D.; Bannenberg, T.; Hrib, C. G.; Jones, P. G.; Tamm, M.
Angew. Chem., Int. Ed. 2008, 47, 7428–7432. (d) Back, O.; Donnadieu,
B.; Parameswaran, P.; Frenking, G.; Bertrand, G. Nature Chem. 2010, 2,
369–373.
´
(2) (a) Ueng, S.-H.; Makhlouf Brahmi, M.; Derat, E.; Fensterbank, L.;
Lacoˆte, E.; Malacria, M.; Curran, D. P. J. Am. Chem. Soc. 2008, 130, 10082–
10083. (b) Ueng, S.-H.; Solovyev, A.; Yuan, X.; Geib, S. J.; Fensterbank,
L.; Lacoˆte, E.; Malacria, M.; Newcomb, M.; Walton, J. C.; Curran, D. P.
J. Am. Chem. Soc. 2009, 131, 11256–11262. (c) Matsumoto, T.; Gabba¨ı,
F. P. Organometallics 2009, 28, 4252–4253. (d) Walton, J. C.; Makhlouf
Brahmi, M.; Fensterbank, L.; Lacoˆte, E.; Malacria, M.; Chu, Q.; Ueng,
S.-H.; Solovyev, A.; Curran, D. P. J. Am. Chem. Soc. 2010, 132, 2350–
2358. (e) Tehfe, M.-A.; Makhlouf Brahmi, M.; Fouassier, J.-P.; Curran,
D. P.; Malacria, M.; Fensterbank, L.; Lacoˆte, E.; Laleve´e, J. Macromolecules
2010, 43, 2261–2267.
(3) (a) Chu, Q.; Makhlouf Brahmi, M.; Solovyev, A.; Ueng, S.-H.;
Curran, D. P.; Malacria, M.; Fensterbank, L.; Lacoˆte, E. Chem.sEur. J.
2009, 15, 12937–12940. (b) Lindsay, D. M.; McArthur, D. Chem. Commun.
2010, 46, 2474–2476. (c) Lee, K. S.; Zhugralin, A. R.; Hoveyda, A. H.
J. Am. Chem. Soc. 2009, 131, 7253–7255. (d) Monot, J.; Makhlouf Brahmi,
M.; Ueng, S.-H.; Robert, C.; Murr, M. D.-E.; Curran, D. P.; Malacria, M.;
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10.1021/ol101014q  2010 American Chemical Society
Published on Web 06/10/2010

experiments and analyzing results, we opted for single-point
comparisons in the reaction with a simple PTOC ester
2-thioxopyridin-1(2H)-yl decanoate (5).8
Scheme 1.
Typical Xanthate Reduction by dipp-Imd-BH3 1a
Scheme 2 shows the results of a typical kinetic experiment.
A solution of the pyridine-2-thioneoxycarbonyl (PTOC, 5),
Scheme 2. Results of a Typical Single-Point Kinetic Experiment
with PTOC Ester 5 and Hydrogen Donor dipp-Imd-BH3 (1)
dipp-Imd-BH3 (1), and dodecane (internal standard) in
benzene was irradiated with a sunlamp for 5 min. TLC
analysis verified that the PTOC ester 5 was consumed. Then
the yields of the nonane 6 (7%) and 2-nonylthiopyridine (7)
(57%) were determined by GC analysis of the crude product
against the internal standard.
Similar experiments were conducted for the other NHC-
borane complexes. Kinetic experiments were conducted in
duplicate with good reproducibility. Additional details are
provided in the Supporting Information.
a Formal charges are shown in this scheme only.
•
NHC-boryl radical (dipp-Imd-BH2 , 1•) adds back to the
xanthate to propagate the chain. In a careful series of kinetic
experiments, the rate constant for the hydrogen abstraction
reaction of a secondary cyclobutylcarbinyl radical probe with
1 was measured as kH ) 4 × 104 M-1 s-1 (eq 1).2b This rate
constant is in an interesting regime; it is lower than rate
constants of other popular hydrogen donors like tributyltin
hydride (Bu3SnH) or tris(trimethylsilyl)silane (TTMSH) but
higher than rate constant of reagents like triethylsilane that
do not propagate radical chains efficiently.5
Figure 1 shows the mechanistic framework for analysis
of the results. Nonyl radical 8 generated from PTOC ester 5
Substituent effects on the radical hydrogen donor ability
of the NHC-boranes are of fundamental interest because
the derived NHC-boryl radicals are a new class of boron-
centered radicals. In addition, benefits of such knowledge
could be reaped in synthesis. For example, 2 equiv or more
of both 1 and AIBN were needed to obtain optimal yields
in reductions of xanthates. This might be because the rate
constant for hydrogen transfer from 1 is on the low end of
the hydrogen-donor scale.6 NHC-boranes that are better
hydrogen donors might be better reagents in practice.
We have accumulated dozens of carbene boranes over the
last 2 years, and we decided to survey a subset of these as
potential radical hydrogen atom donors by measuring rate
constants for reactions with an alkyl radical. With so many
substrates, the usual method of conducting radical probe
experiments at multiple concentrations7 was deemed to be
too time-consuming. Instead, for ease of both conducting
Figure 1. Competing options for the nonyl radical 8 with known
(option 1) and unknown (option 2) rate constants.
has two competing options. It can react with the starting
PTOC ester 5 (so-called “self-trapping”) to provide 7 and
another nonyl radical 8 (option 1), or it can react with
NHC-borane 1 to provide nonane 6 and NHC-boryl radical
1• (option 2). By analogy to xanthate reactions, we assume
that the NHC-boryl radical 1• adds back to the starting
PTOC ester 5 to propagate the chain; however, we did not
attempt to isolate the expected product from that reaction
(5) Chatgilialoglu, C.; Newcomb, M. In AdVances in Organometallic
Chemistry; West, R., Hill, A. F., Eds.; Academic Press: San Diego, 1999;
Vol. 44, pp 67-112.
(7) (a) Newcomb, M. Tetrahedron 1993, 49, 1151–1176. (b) Newcomb,
M. In Radicals in Organic Synthesis, 1st ed.; Renard, P., Sibi, M., Eds.;
Wiley-VCH: Weinheim, 2001; Vol. 1, pp 317-336.
(8) (a) Barton, D. H. R.; Crich, D.; Motherwell, W. B. Tetrahedron 1985,
41, 3901–3924. (b) Newcomb, M.; Kaplan, J. Tetrahedron Lett. 1987, 28,
1615–1618.
(6) Additionally, dipp-Imd-BH2• proved to be a persistent radical, which
might suggest that its radical-molecule reactions with xanthates could also
be slow. See ref 2d.
Org. Lett., Vol. 12, No. 13, 2010
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Figure 2.
NHC-borane structures and rate constants kH (M-1 s-1) for hydrogen-atom transfer.
(NHC-BH2SPy). The rate constant for H-transfer (kH) is then
calculated in the usual way from the known rate constant
for self-trapping (kT)8b and the experimentally determined
product ratio, which was corrected for background reduction
as described in the Supporting Information.
described,10,11 and complete details for preparation and
characterization of the new complexes are contained in the
Supporting Information. Crystal structures were solved for
11, 15a, and 15b, and the Supporting Information provides
diagrams and data.
In this way, the rate constant kH for the reaction of a
primary alkyl radical 8 with 1 was determined to be 2 ×
104 M-1 s-1. This is two times lower than the more accurately
determined rate constant of 4 × 104 M-1 s-1 for the reaction
of a secondary radical with 1. Since primary alkyl radicals
are unlikely to be less reactive than secondary ones, the
difference in these numbers is presumably due to experi-
mental error. The yield of reduction product nonane 6 in
the experiments with 1 is low (7%), so background correction
is a possible source of error.
The background error will become more significant for
less reactive boranes, so we decided to use 1 as the cutoff
for rate constant estimation. Any boranes that are less reactive
than 1 are simply listed with rate constants <104 M-1 s-1.
To further validate the analysis, we conduced several more
control experiments with hydrogen donors that are both less
reactive (amine- and phosphine-boranes9) and more reactive
(Bu3SnH and TTMSH5) than 1. The measured rate constants
were in reasonable agreement with literature values (see the
Supporting Information).
Table S1 in the Supporting Information collects the
experimental data from which the rate constants in Figure 2
were calculated. We assume that the B-H bonds are the
primary source of hydrogen atoms in the reduced products.
In support of this assumption, radicals derived from several
of the boranes have already been observed by EPR
spectroscopy.2d The rate constants are not corrected for the
number of hydrogen atoms on boron (three for all boranes
except 3 and 10, which have two).
The structures in Figure 2 are collected into three groups
depending on whether they are less reactive than 1 (kH <104
M-1 s-1), similar in reactivity to 1 (kH 2-4 × 104 M-1 s-1),
or more reactive than 1 (kH 4-8 × 104 M-1 s-1). The global
impression is that the range of rate constants is small given
the diversity of different structures.
Selected comparisons of substrates based on NHC rings
and carbene ring substituents are shown in Figure 3. Compare
the carbene boranes 15c, 14b, and 19 with N,N-dimethyl
substituents. Despite the variation in carbene core (imidazol-
2-ylidene, benzimidazol-2-ylidene, 1,2,4-triazol-3-ylidene),
the rate constants are very similar. Analogously, inspection
of Figure 2 shows that the carbene boranes with bulky
The structures and rate constants for the 20 NHC-boranes
studied in this work are collected in Figure 2.
Most of the boranes were prepared by in situ deprotonation
of the corresponding salt by base, followed by addition of
BH3-THF. A few of the complexes have already been
(10) Complexes 3 (ref 2b), 14b (ref 2d), 15c (ref 2d), 16b (ref 2d), 17a
(ref 2d), 19 (ref 12) and 20 (ref 2a) are described in prior preparative or
EPR papers. Compound 12 was described by Lindsay and McArthur during
the course of this study (ref 3b).
(9) (a) Sheeller, B.; Ingold, K. U. J. Chem. Soc., Perkin Trans. 2 2001,
480–486. (b) Lucarini, M.; Pedulli, G. F.; Valgimigli, L. J. Org. Chem.
1996, 61, 1161–1164.
(11) Compound 15a has been prepared by a different route: Yamaguchi,
Y.; Kashiwabara, T.; Ogata, K.; Miura, Y.; Nakamura, Y.; Kobayashi, K.;
Ito, T. Chem. Commun. 2004, 2160–2161
.
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Org. Lett., Vol. 12, No. 13, 2010

1. Looking forward, two complexes stand out as potentially
useful reagents, 1,3-dimethylimidazol-2-ylideneborane (15c,
diMe-Imd-BH3) and 2,4-dimethyl-1,2,4-triazol-3-ylidenebo-
rane (19, diMe-Tri-BH3). These complexes are ideal candi-
dates for three reasons: (1) they come from very cheap
precursors, (2) they have the lowest molecular weights of
all the reagents in Figure 2 (110 and 111 g mol-1), and (3)
they are the best hydrogen donors (8 × 104 M-1 s-1). Indeed,
preparative experiments in the following paper12 suggest that
these two compounds above may indeed hit the reagent
trifecta.
In summary, we have implemented a simple kinetic
competition experiment with PTOC esters to measure rate
constants for radical hydrogen abstraction from NHC-boranes.
Experiments on several substrates are conveniently conducted
in parallel, and this has allowed us to provide rate constants
for 20 known and new NHC-boranes. The rate constants
fall in an interesting range, as summarized in Figure 4. They
Figure 3.
Selected comparisons of rate constants (M-1 s-1) based
on NHC ring (top) and nitrogen substituents (bottom).
N-substituents (1, 11-13) have similar rate constants (about
2 × 104 M-1 s-1). Likewise, the three carbenes 15c, 18a, and
18b with the same carbene core and N-substituents but different
substituents on C4 and C5 (H, CN, Cl) of the carbene ring show
about the same reactivity (top of Figure 3).
In contrast, the N-substituents play a more significant role.
Consider the series of imidazol-2-ylidene boranes with
different N-substituents in the lower part of Figure 3. As
the size of the pair of N-substituents decreases, the rate
constant increases from 2 × 104 to 8 × 104 M-1 s-1. It can
be difficult to change the hydrogen-donating ability of
reagents like tin hydrides through substituent effects, so the
ability modulate the reactivity of carbene boranes by chang-
ing N-substituents could be advantageous.
Figure 4. Scale of rate constants for donations of hydrogen atoms
to alkyl radicals.
are lower than those of tin hydrides, tris(trimethylsilyl)silicon
hydrides, and germanium hydrides yet still above the
threshold for conducting successful radical chain reactions.
There is limited information in Figure 2 on the effect of
boron substituents. However, both boron chloride 10 and
boron dithiocarbonate 3 are less reactive than 1, so it looks
like electron-withdrawing substituents may deactivate.
Substrates 17a and 17b bearing alkenyl groups (allyl and
homoallyl) were originally made to study the potential for
cyclization of the derived NHC-boryl radicals. However,
in a limited series of preparative experiments with Et3B and
air (25 °C) or AIBN (80 °C), we did not isolate any apparent
cyclized products.
There are important preparative ramifications of the data
in Figure 2, both looking backward and looking forward.
Looking backward, early work on reductions of xanthates
focused on reagents 1 and 20, and the 1,2,4-triazol-3-ylidene
derivative 20 often provided better performance either via
superior yield or faster reaction. This can now be understood
at least in part because 20 is a better hydrogen donor than
Acknowledgment. This work was supported by grants
from the US National Science Foundation (CHE-0645998),
UPMC, CNRS, and the French Agence Nationale de la
Recherche (ANR, BLAN0309 Radicaux Verts, and 08-
CEXC-011-01 Borane). We thank Drs. H. Rousselie`re and P.
Herson (IPCM, Paris) for solving the crystal structures and
acknowledge FR 2769 for technical assistance (NMR, MS).
Supporting Information Available: Procedures and
characterization of all new compounds, details of kinetic
experiments, copies of spectra of products, and crystal
structures (CIF). This material is available free of charge
via the Internet at http://pubs.acs.org.
OL101014Q
(12) Ueng, S.-H.; Fensterbank, L.; Malacria, M.; Lacoˆte, E.; Curran,
D. P. Org. Lett. 2010, 12, DOI: 10.1021/ol101015m.
Org. Lett., Vol. 12, No. 13, 2010
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