N-heterocyclic carbene boranes are good hydride donors

Article abstract of DOI:10.1021/ol202836p

The nucleophilicity parameters (N) of 1,3-bis(2,6-diisopropylphenyl) imidazol-2-ylidene borane and 1,3-dimethylimidazol-2-ylidene borane are 9.55 and 11.88. This places N-heterocyclic carbene boranes (NHC-boranes) among the most nucleophilic classes of neutral hydride donors. Reductions of highly electron-poor C=N and C=C bonds provide hydrogenation products along with new, stable borylated products. The results suggest that NHC-boranes have considerable untapped potential as neutral organic reductants.

Full text of DOI:10.1021/ol202836p

ORGANIC
LETTERS
2012
Vol. 14, No. 1
82–85
N-Heterocyclic Carbene Boranes are
Good Hydride Donors
†
,†
‡
§
^
Markus Horn, Herbert Mayr,* Emmanuel Lacote, Everett Merling,
Jordan Deaner,§ Sarah Wells,§ Timothy McFadden,§ and Dennis P. Curran*,§
€
€
Department Chemie, Ludwig-Maximilians-Universitat Munchen, Butenandtstr. 5-13,
D-81377 Mu€nchen, Germany, ICSN CNRS, Avenue de la Terrasse,
91198 Gif-sur-Yvette Cedex, France, and University of Pittsburgh,
Department of Chemistry, Pittsburgh, Pennsylvania 15260, United States
herbert.mayr@cup.uni-muenchen.de; curran@pitt.edu
Received October 25, 2011
ABSTRACT
The nucleophilicity parameters (N) of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene borane and 1,3-dimethylimidazol-2-ylidene borane are
9.55 and 11.88. This places N-heterocyclic carbene boranes (NHC-boranes) among the most nucleophilic classes of neutral hydride donors.
Reductions of highly electron-poor CdN and CdC bonds provide hydrogenation products along with new, stable borylated products. The results
suggest that NHC-boranes have considerable untapped potential as neutral organic reductants.
Knowledge about the chemistry of N-heterocyclic carbene
boranes (hereafter, NHC-boranes) has increased rapidly of
late.1 NHC-Trihydridoboranes (NHC-BH3) are typically
crystalline solids that are easy to make and handle.2 Many
are stable to air, strong bases,3 mild acids4 (including water
and acetic acid), and chromatography. Boranes such as
1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene borane5
Figure 1. Structures of N-heterocyclic carbene boranes 1 and 2
with formal charges shown.
(dipp-Imd-BH3, 1) and 1,3-dimethylimidazol-2-ylidene
†
€
Ludwig-Maximilians-Universitat M€unchen.
‡ ICSN CNRS.
§ University of Pittsburgh.
(1) Curran, D. P.; Solovyev, A.; Makhlouf Brahmi, M.; Fensterbank,
borane6 (diMe-Imd-BH3, 2) are useful reagents for
radical7,8 and organometallic reactions (Figure 1).9
^
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10317.
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^
D. P.; Fensterbank, L.; Lacote, E.; Malacria, M. J. Org. Chem. 2010, 75,
6983–6985.
^
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Curran, D. P. Org. Biomol. Chem. 2011, 9, 3415–3420. (b) Ueng,
S.-H.; Fensterbank, L.; Lacote, E.; Malacria, M.; Curran, D. P. Org.
ꢀ
(3) Monot, J.; Solovyev, A.; Bonin-Dubarle, H.; Derat, E.; Curran,
^
^
D. P.; Robert, M.; Fensterbank, L.; Malacria, M.; Lacote, E. Angew.
Chem., Int. Ed. 2010, 49, 9166–9169.
(4) Solovyev, A.; Chu, Q.; Geib, S. J.; Fensterbank, L.; Malacria, M.;
Lett. 2010, 12, 3002–3005. (c) Ueng, S.-H.; Makhlouf Brahmi, M.;
ꢀ
Derat, E.; Fensterbank, L.; Lacote, E.; Malacria, M.; Curran, D. P. J.
^
Am. Chem. Soc. 2008, 130, 10082–10083.
(8) (a) Tehfe, M.-A.; Monot, J.; Makhlouf Brahmi, M.; Bonin-
^
Lacote, E.; Curran, D. P. J. Am. Chem. Soc. 2010, 132, 15072–15080.
^
Dubarle, H.; Curran, D. P.; Malacria, M.; Fensterbank, L.; Lacote,
(5) Wang, Y.; Quillian, B.; Wei, P.; Wannere, C. S.; Xie, Y.; King,
R. B.; Schaefer, H. F.; Schleyer, P. v. R.; Robinson, G. H. J. Am. Chem.
Soc. 2007, 129, 12412–12413.
ꢀ
E.; Lalevee, J.; Fouassier, J.-P. Polym. Chem. 2011, 2, 625–631. (b)
Tehfe, M.-A.; Makhlouf Brahmi, M.; Fouassier, J.-P.; Curran, D. P.;
^
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ꢀ
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^
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r
10.1021/ol202836p
Published on Web 12/13/2011
2011 American Chemical Society

NHC-boranes have gained a reputation as weak ionic
hydride donors1 because of their stability under ambient
conditions and because of their tolerance of ketones and
other functional groups that are reduced by boron hydrides.
Much of this experience has been gained with dipp-
Imd-BH3 which reduces reactive primary halides and
sulfonates ionically at temperatures well over 100 °C.9
Only unhindered primary triflates are reduced near am-
bient temperature. The reductions of ketones by carbene-
boranes can be promoted by Lewis acids.10
Here we report that the reputation of NHC-boranes
as poor hydride donors may be undeserved. Measure-
ments of “nucleophilicity parameters (N)”11 place NHC-
boranes 1 and especially 2 among the most reactive neutral
hydride donors known.
A series of measurements with variable concentrations of
1 or 2 was performed for each electrophileꢀnucleophile
combination, and Figure 2 shows the results from a typical
run. The absorbance of E3 at λ = 643 nm decayed smoothly
upon addition of 2. A plot of the observed rate constants
(kobs) versus the concentration of the carbene-borane was
linear, as illustrated in the insert of Figure 2. Consequently,
the hydride transfer obeys the second-order rate law in eq 2,
with the rate constant k equaling the slope of the correlation
line exemplified by Figure 2. The rate constants measured in
this fashion are summarized in Table 2.
ꢀd[Ar2CHþ]=dt ¼ k[Ar2CHþ][Nu]
ð2Þ
Measurementof N Values:Benzhydrylium ions Ar2CHþ
with variable para- and meta-substituents span a broad
range of reactivity while the steric shielding of the reaction
center is kept constant. Accordingly, they have been used as
reference electrophiles for the construction of a comprehen-
sive nucleophilicity scale based on eq 1. Electrophiles are
characterized by E (electrophilicity), and nucleophiles are
characterized by the solvent-dependent parameters sN (sen-
sitivity, previously termed s) and N (nucleophilicity).11
log k20°C ¼ sN(N þ E)
ð1Þ
Figure 2. Absorbance decay at λ = 643 nm for the reaction of E3
(c0 = 1.38 ꢁ 10ꢀ5 mol Lꢀ1) with diMe-Imd-BH3 2 (c = 4.84 ꢁ
10ꢀ4 mol Lꢀ1), kobs = 2.45 ꢁ 10ꢀ2 sꢀ1, CH2Cl2, 20 °C. The insert
With the goals to incorporate N-heterocyclic carbene
boranes into the nucleophilicity scale andto predictpoten-
tial electrophilic reaction partners, we measured the rates
of reactions of 1 and 2 with the substituted benzhydrylium
ions E1ꢀE3 (Table 1) in CH2Cl2 at 20 °C.
is a plot of kobs versus [2], k = 5.05 ꢁ 101 L molꢀ1 sꢀ1
.
According to eq 1, the logarithms of k should correlate
linearly with the electrophilicity parameters E of the
benzhydrylium ions. This is confirmed by the plot in
Figure 3. The derived reactivity parameters N and sN
are 9.55 and 0.81 for 1 and 11.88 and 0.71 for 2.
Resonance interaction between the heterocyclic ring
and the N-aryl rings of 1 is negligible because these rings
are perpendicular.4,5,12 So the aryl groups in 1 influence
hydride transfer through the inductive effect. The smaller
electron-donating effect and the larger size of the di-
isopropylphenyl rings compared to methyl groups ex-
plain why 1 is considerably less reactive than 2.
Among the many NHC-boranes now available, dipp-
Imd-BH3 1 was chosen because its ionic reactivity had
already been demonstrated.9 To complement 1, we chose
diMe-Imd-BH3 2 because it has a much lower molecular
weight (110 compared to 402 g molꢀ1) and because its
BH3 group is much less sterically shielded.
Reaction progress was followed photometrically by
monitoring the absorbances of the benzhydrylium cations
E1ꢀE3. When 1 or 2 was added to solutions of the diaryl-
carbenium tetrafluoroborates in large excess ([1, 2] .
[Ar2CHþ]), monoexponential decays of the absorbances
were observed. This shows that there is a first-order
dependence of the rates on the electrophile concentrations.
Table 2. Second-Order Rate Constants for Hydride Transfers
from the Carbene-Boranes 1 and 2 to Benzhydrylium Ions
E1ꢀE3 (CH2Cl2, 20 °C), and the Derived Nucleophile-Specific
Parameters N and sN
Table 1. Diarylcarbenium Ions Used as Electrophiles and Their
Empirical Electrophilicity Parameters E (from ref 11c)
donor
acceptor
k/L molꢀ1 sꢀ1
N (sN)
1
E1
E2
E3
E1
E2
E3
1.16 ꢁ 102
1.04 ꢁ 101
1.27
2.64 ꢁ 103
4.05 ꢁ 102
5.05 ꢁ 101
9.55 (0.81)
2
11.88 (0.71)
(10) Lindsay, D. M.; McArthur, D. Chem. Commun. 2010, 46,
2474–2476.
Org. Lett., Vol. 14, No. 1, 2012
83

The second-order rate constant for a bimolecular pro-
cess with both reactants at 1 M should be greater than
10ꢀ4 L molꢀ1 sꢀ1 in order to achieve 50% conversion
within 3 h. Substitution of this value into eq 1 leads to the
rule of thumb that nucleophiles with sN ≈ 0.8 are likely to
react with electrophiles at rt if eq 3 is fulfilled.
N þ E g ꢀ 5
ð3Þ
Thus, 2 is not expected to react with typical alkyl- or
aryl-substituted aldehydes (E = ꢀ20 to ꢀ18),15 ketones,
or imines in aprotic solvents. Yet, it should react
with iminium ions and with CdN and even CdC double
bonds substituted with strong electron-withdrawing
groups.13
Figure 3. Plots of log k versus the electrophilicity parameters
E of the benzhydrylium ions. Correlation equations: log k = 0.707
E þ 8.40 for 2; log k = 0.807 E þ 7.70 for 1.
Figure 4 shows a scale of N parameters of represen-
tative neutral and anionic hydride donors.13 With an
N parameter of about 12, carbene borane 2 is less nucleo-
philic than borohydride anion BH4ꢀ in DMSO (N ≈ 15)
and roughly comparable to the cyanoborohydride anion
(BH3CNꢀ) in DMSO. Compared to neutral reference
hydride donors, 2 is more reactive than trialkylamine-
boranes, dihydropyridines, benzimidazolines, and even
stannanes. Indeed, carbene borane 2 has one of the high-
est N parameters of any neutral hydride donor measured
to date.14 Though less reactive than 2, 1 is still a reactive
hydride donor in the big picture for neutral reagents.
Reductions of iminium ions generated from imine 3
and acetic acid were conducted in dichloromethane
(Scheme 1). In the control reaction of 2 and 3 without
acid, no conversion occurred over 24 h (entry 1). Addition
of 1.3 equiv of acetic acid resulted in the rapid disappear-
ance of 2 over 1.5 h. p-Chlorobenzylaniline 4 was isolated
in 84% yield by flash chromatography (entry 2). The
amount of borane could be decreased to 0.5 equiv with little
change in yield (entries 3, 4), though the reaction time
increased. Even with 0.33 equiv of 2, an 86% yield of 4
was obtained (entry 5). Apparently, reagent 2 can donate
two and even three hydrides in iminium ion reductions.
For comparison, we reduced 3 with dipp-Imd-BH3 1
under the conditions of entry 2 (1 equiv 3, 1.3 equiv 1, 1.3
equiv HOAc). The reaction was slow at rt, so a prepara-
tive reaction was conducted at 80 °C for 2 days. This
provided p-chlorobenzylaniline 4 in 77% yield.16 Clearly,
2 is the better reagent for this reduction.
Scheme 1. Reductions of Preformed Imine 3 with 2
Figure 4. Nucleophilicity parameters N of some hydride donors
(in CH2Cl2 if not otherwise noted).
Preparative Reductions: Based on the high measured
N values, we undertook a preliminary survey of the poten-
tial to use the more readily available and more reactive
reagent 2 in preparative reductions.
Since 2 does not react rapidly with carbonyl com-
pounds, it should be possible to conduct one-pot reduc-
tive aminations starting from aldehydes and anilines. This
was accomplished by mixing the components (RCHO,
1 equiv; aniline, 1.3 equiv; 2, 0.5 or 1.3 equiv; HOAc,
1 equiv) in dichloromethane and then stirring for 1 h at rt.
The yield of 4 by the one-pot method (91%, Table 3,
entry 1) was comparable to the yield starting from the
preformed imine 3. Other pairs of partners also gave
(11) (a) Mayr, H.; Ofial, A. R. J. Phys. Org. Chem. 2008, 21, 584–595.
(b) Mayr, H.; Ofial, A. R. Nachr. Chem. 2008, 56, 871–877. (c) Mayr, H.;
Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker, B.; Kempf, B.;
Loos, R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. J. Am. Chem.
Soc. 2001, 123, 9500–9512.
(12) Maji, B.; Breugst, M.; Mayr, H. Angew. Chem., Int. Ed. 2011, 50,
6915–6919.
(13) The complete database is available at http://www.cup.
uni-muenchen.de/oc/mayr/Dbintro/html.
(14) At N = 14.6, only 4-dimethylaminopyridine borane (DMAP-BH3)
has a higher parameter. However, this has only been determined against a
single reference electrophile: Funke, M. A.; Mayr, H. Chem.;Eur. J. 1997,
3, 1214–1222.
(15) Appel, R.; Mayr, H. J. Am. Chem. Soc. 2011, 133, 8240–8251.
(16) Reaction with 1 gave 4 in 77% yield and dipp-Imd-BH2OAc in
69% yield.
84
Org. Lett., Vol. 14, No. 1, 2012

without acetic acid followed by flash chromatography
gave 40% of N-benzyltoluene sulfonamide 6 along with
26% of the reduced sulfonamide 7 containing the NHC-
borane.
Table 3. One-Pot Reductive Aminations
We added acetic acid in an effort to form more 6 at the
expense of 7. With 1 equiv of HOAc, the yield of 6
increased to 54% and that of 7 decreased to 19%, but a
new stable product 8 was isolated in 25% yield (entry 2).
Boron acetate 8 is apparently the product of an acid/base
reaction of 7 with acetic acid. Increasing the amount of
acetic acid gave more 6, and again less than 1 equiv of
borane could be used. Reduction of 5 with 10 equiv of
HOAc and only 0.33 equiv of 2 provided 6 in 79% yield
along with 17% of 7 (entry 3).
NHC-borane 2 did not react rapidly at rt with arylidene
or alkylidene malonic esters (E = ꢀ24 to ꢀ18), but it did
react with the corresponding malononitriles. Stirring of
2 and 9a (E = ꢀ9.4) for 15 min and then evaporation of
the solvent and flash chromatography provided the
stable reduced borylated malononitrile 10a in 57%
yield along with 13% of 11a (Scheme 3).
entry
R
Ar
C6H5
equiv 2
amine
1
2
3
4
5
6
7
8
p-ClC6H4
1.3
1.3
0.5
1.3
0.5
1.3
0.5
1.3
91%
98%
92%
73%
68%
76%
70%
57%
p-NO2C6H4
p-NO2C6H4
C6H5
p-BrC6H4
p-BrC6H4
o-IC6H4
C6H5
o-IC6H4
(E)-C6H5CH=CH
(E)-C6H5CH=CH
p-NO2C6H4
p-BrC6H4
p-BrC6H4
p-BrC6H4
amines with only slight decreases in isolated yield when
going from 1.3 to 0.5 equiv of 2. An imine derived from
cinnamaldehyde gave only the product of 1,2-reduction
(entries 6 and 7).
Sodium cyanoborohydride (NaBH3CN) is the classic
reagent for such one-pot reductive aminations,17 but
cyanide is a liability because of its toxicity. NaBH3CN
has been replaced by anionic reagents such as sodium
triacetoxyborohydride (NaBH(OAc)3)18 and amine-boranes
(R3NꢀBH3).19 Using 2 is convenient because water workup
and extractions can be omitted. Compared to amine-boranes,
carbene-borane 2 appears to be both more stable2 and
more reactive (higher N value). Both features are consis-
tent with the high Lewis basicity of the carbenes.12
In line with its electrophilicity parameter E of ꢀ11.5,15
the tosyl imine 5 is also reduced at rt by 2, with different
products forming depending on the stoichiometry. Scheme 2
shows that reduction of 5 by 2 in dichloromethane
Reduction of the corresponding ethylidene analog 9b
was much slower (18 h) and provided only the borylated
product 10b in 42% yield. Products 10a,b are hydrobora-
tion products where the boron atom resides exclusively on
the most substituted carbon atom.
Structures of the new types of carbene-boranes 7, 8, and
10a,b, were secured by a combination of NMR spectro-
scopy and mass spectrometry (see Supporting Information).
In summary, measurements of N parameters and re-
sults of preliminary reductions suggest that carbene-boranes
have considerable unrecognized potential as neutral,
organic hydride donors. 1,3-Dimethylimidazol-2-ylidene
borane 2 looks especially promising because it has a high
reactivity and a low molecular weight. It is stable, readily
available, and easy to handle. Interesting borylated pro-
ducts with potential for onward transformations are
isolated with some systems. Aqueous workups are not
needed, and removal of the boron byproducts by flash
chromatography is easy when nonborylated products are
targeted.
Scheme 2. Reduction of Tosyl Imine 5 with diMe-Imd-BH3 2
Acknowledgment. We thank the National Science Foun-
dation and the CNRS for support of this work, and we
thank Mr. Andrey Solovyev, University of Pittsburgh, for
help with assembling the Supporting Information.
Supporting Information Available. Includes complete
experimental details. This material is available free of
charge via the Internet at http://pubs.acs.org.
Scheme 3. Reductions of Ylidene Malononitriles with 2
(17) Baxter, E. W.; Reitz, A. B. Org. React. (N.Y.) 2002, 59, 1–714.
(18) Abdel-Magid, A. F.; Mehrman, S. J. Org. Process Res. Dev.
2006, 10, 971–1031.
(19) (a) Burkhardt, E. R.; Coleridge, B. M. Tetrahedron Lett. 2008,
49, 5152–5155. (b) Carboni, B.; Carreaux, F. In Science of Synthesis,
Organometallics: Boron Compounds; Kaufmann, D. E., Matteson, D. S.,
Eds.; Thieme: Stuttgart, 2004; Vol. 6, pp 455ꢀ484; (c) Kanth, J. V. B.
Aldrichimica Acta 2002, 35, 57–66.
Org. Lett., Vol. 14, No. 1, 2012
85