Ionic and organometallic reductions with N-Heterocyclic carbene boranes

Article abstract of DOI:10.1002/chem.200902450

Surgical reduction: N-Heterocyclic carbene-borane complexes such as depicted are neutral, organic soluble analogues of borohydride anions with a weak hydridic character, compatible with organometallic catalysis. They are applicable for surgical reductions in complex, multifunctional molecules.

Full text of DOI:10.1002/chem.200902450

COMMUNICATION
DOI: 10.1002/chem.200902450
Ionic and Organometallic Reductions with N-Heterocyclic Carbene Boranes
Qianli Chu,[a] Malika Makhlouf Brahmi,[b] Andrey Solovyev,[a] Shau-Hua Ueng,[b]
Dennis P. Curran,*[a] Max Malacria,*[b] Louis Fensterbank,*[b] and Emmanuel Lacꢀte*[b]
Several groups have recently described syntheses of
borane complexes of N-heterocyclic carbenes (NHC–bor-
anes).[1] Such complexes are structurally interesting in their
own right, yet very little is known about their chemistry.[1e,2]
Given the importance of boron reagents in organic synthe-
sis,[3] the study of NHC–boranes as potential organic re-
agents is an important goal.
Figure 1. Structures of the N-heterocyclic carbene borane reagents.
In the first use of NHC–boranes as synthetic reagents, we
reduced xanthates and related derivatives to hydrocarbons
through a radical mechanism.[4] Accordingly, we immediate-
ly attempted to extend such radical reductions to organic
halides. Yet instead of encountering the expected radical
chain reductions, we quickly discovered that NHC–boranes
also behave as hydride donors in both ionic and organome-
tallic reactions.[5] These unprecedented transformations sug-
gest broad future potential for NHC–boranes as mild, selec-
tive reducing agents in diverse settings.
The two NHC–boranes used in this study are shown in
Figure 1. 1,3-Bis-(2,6-diisopropylphenyl)imidazol-2-ylidene
borane (1) and 2-phenyl-1,2,4-triazol-3-ylidene borane (2)
are readily prepared solids that are stable to air, alcohols,
weak acids, and moisture and therefore easily handled.[6]
In preliminary experiments, we were successful in reduc-
ing dodecyl iodide 3a to dodecane 4 with 1 in the presence
of assorted radical initiators (AIBN, Et3B/O2, peroxides) in
variable yields. However, control experiments without initia-
tors worked just as well or even better. Clearly, initiators
were not required to reduce dodecyl iodide under thermal
conditions.
Table 1 summarizes key results from a series of reductions
of dodecyl iodide 3a to dodecane 4 by heating in various
solvents in the absence of any initiator. Nearly quantitative
yields of 4 were obtained by heating 3a (1 equiv) and 1
(1 equiv) in benzene for 36 h in a sealed tube at 1258C or
for 2 h at 1808C (entries 1,2). The reaction was somewhat
faster (12 and 1 h) at the same temperatures in the more
polar trifluorobenzene (BTF) (entries 3,4). A preparative re-
action in refluxing toluene (1108C) was complete in 20 h
and provided dodecane in 95% GC yield and 89% isolated
yield after purification by flash chromatography (entry 5).
The reduction of 3a with 1 equiv of triazolylidene borane
2 was not as high yielding as 1, providing dodecane in 82%
yield after 48 h (entry 6). The transformation also proceeded
smoothly in o-dichlorobenzene (o-C6H4Cl2, 1258C) and o-
xylene (1408C) (entries 7,8). Further, the reduction occurred
in acetonitrile (1258C, 16 h, entry 9) and, remarkably, even
in methyl ethyl ketone (MEK, 1258C, 16 h, entry 10). The
absence of carbonyl reduction suggests that free borane (or
diborane, or a loose borane–solvent complex) is not in-
volved in the reduction.[7] That conclusion is further support-
ed by reduction of 3a in the presence of 1 equiv of 1-tetra-
decene (C12H25CH=CH2); product 4 was formed as usual
and the alkene was returned unreacted (entry 11).[8]
[a] Dr. Q. Chu, A. Solovyev, Prof. D. P. Curran
Department of Chemistry, University of Pittsburgh
Pittsburgh PA, 15260 (USA)
Fax : (+1)412-965-6447
E-mail: curran@pitt.edu
Homepage: http://radical.chem.pitt.edu/index.html
[b] M. Makhlouf Brahmi, Dr. S.-H. Ueng, Prof. M. Malacria,
Prof. L. Fensterbank, Dr. E. Lacꢀte
Institut Parisien de chimie molꢁculaire (UMR CNRS 7201), C. 229
UPMC Univ Paris 06, 4 place Jussieu, 75005 Paris (France)
Fax : (+33)144-27-73-60
E-mail: max.malacria@upmc.fr
louis.fensterbank@upmc.fr
To benchmark the new reagents, we briefly explored re-
ductions of 3a with triphenylphosphine borane (Ph3P–BH3)
and pyridine borane (Pyr–BH3),[9] but without comparable
emmanuel.lacote@upmc.fr
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200902450.
Chem. Eur. J. 2009, 15, 12937 – 12940
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
12937

Table 1. Reductions of dodecyl iodide 3a with NHC–boranes 1 and 2.
A study of the scope of leaving groups that can be re-
duced with 1 is summarized in Table 2. Dodecyl bromide 3b
was reduced in 94% yield after heating at 1408C for 16 h in
BTF (entry 1). The reduction of dodecyl chloride 3c was
also clean but rather slow, providing dodecane 4 in only
49% yield after 24 h at 1408C; the balance of the starting
chloride remained unreacted.
Entry
NHC–BH3
Solvent
T [8C][a]
t [h]
Yield 4 [%][b]
1
2
3
4
5
6
7
8
1
1
1
1
1
2
1
1
benzene
benzene
BTF[c]
125
180
125
180
110
110
125
143
125
125
125
125
36
2
12
1
20
48
18
16
16
16
16
8
99
98
95
99
BTF[c]
Table 2. Reductions of other functional groups with 1.
toluene
toluene
o-C6H4Cl2
o-xylene
MeCN
MEK[e]
BTF[c]
95 (89[d]
82
)
94
94
96
99
9
1
1
10
11
12
1[f]
1
98
BTF[c]
99 (1[g]
)
Entry
Substrate
Conditions[a]
Yield 4 or 9 [%]
[a] All reactions run above the solvent boiling point were conducted in
sealed tubes. [b] GC yield against an internal standard. [c] Trifluoro-
benzene. [d] Isolated yield after flash chromatography. [e] Methyl ethyl
ketone (2-butanone). [f] 1 equiv 1-tetradecene was added, but no conver-
sion was observed. [g] 1 equiv of 1-iodoadamantane was added and 1%
of adamantane formed.
1
2
3
4
5
6
7
8
9
n-C12H25Br, 3b
n-C12H25Cl, 3c
n-C12H25OTs, 3d
n-C12H25OMs, 3e
n-C12H25OTf, 3 f
n-C12H25OTf, 3 f
BTF, 1408C, 16 h
BTF, 1408C, 24 h
Tol, 1408C, 48 h
Tol, 1408C, 48 h
Tol, 808C, 17 h
dioxane, 258C, 24 h
Tol, 1408C, 48 h
Tol, 1408C, 48 h
Tol, 258C, 24 h[c]
Tol/tBuOOtBu 1:2,
258C, 24 h[d]
94[b]
49[b]
57
60
79[b]
76[b]
67
BnO
BnO
BnO
BnO
ACHTUNGTRENNUNG
A
61
64
77
N
success. Little conversion was obtained with Ph3P–BH3 (see
Supporting Information for details). In contrast, Pyr–BH3
did provide ~50% yield of dodecane in BTF, but this reduc-
tion was suppressed in methyl ethyl ketone. Pyridine borane
is well known to dissociate on heating,[9] so the latter experi-
ment indicates that borane may be the active reductant in
the Pyr–BH3 reduction.
10
U
[a] unless otherwise noted, all concentrations were 0.2m. [b] GC yield
against an internal standard. [c] c=0.1m. [d] c=0.04m.
As expected for ionic reactions, tosylates 3d, 8d and me-
sylates 3e, 8e could be reduced in acceptable yields by heat-
ing at 1408C for 48 h (57–67%, entries 3,4 and 7,8). In con-
trast to the heating required for the other leaving groups,
triflates 3 f and 8 f were reduced quickly at 808C and could
even be reduced at room temperature (entries 5, 6, and 9).
Each of the reactions of the halides or sulfonates with 1
also produced a boron-containing product NHC–BH2X 10,
where X=I, Br, Cl, OTs, OMs or OTf.[11] The 11B resonan-
ces of these compounds are well separated from that of 1, so
11B NMR spectroscopy is a convenient technique for follow-
ing reaction progress.
To probe the selectivity of the triflate reduction, we con-
ducted a reaction of 8 f with 1 in toluene in the presence of
a large excess (~85 equiv) of di-tert-butyl peroxide. Perox-
ides are strong oxidants that are readily reduced by most
metal hydrides in reactions that can be dangerous due to
exothermicity or potential explosion. Instead of derailing
the reduction, the peroxide additive actually increased the
yield of 9 from 64 to 77%, perhaps due to its polarity
(Table 2, compare entries 9 and 10). We do not recommend
using peroxides as additives; however, the results show that
1 could have use in very sensitive settings to address chal-
lenging chemoselectivity problems.
Several lines of evidence suggest that this thermal trans-
formation does not occur by a radical mechanism. First, ini-
tiators were not needed for the thermal reaction. Second, a
reduction of 3a in the presence of 1-iodoadamantane pro-
vided dodecane 4 in 99% yield along with 1% of adaman-
tane (entry 12).[10] Dodecyl iodide 3a was consumed, while
the bulk of the starting 1-iodoadamantane remained. In a
radical reduction with tributyltin hydride, dodecane and
adamantane were each produced in about 50% yield.
Finally, reduction of cyclizable probe iodide 5 provided
only the open chain product 6 in 58% isolated yield
(Scheme 1). Cyclized product 7 could not be detected by
GC in the crude reaction mixture. Previous experiments
have shown that 1 is a rather modest hydrogen donor,[4] so
any radical formed from 5 should have cyclized much more
rapidly than it was reduced. This result firmly rules out the
intermediacy of radicals in thermal reductions of primary io-
dides.
Two other selective reductions of triflates are shown in
Scheme 2. Triflation of keto alcohol 11 provided a very un-
stable triflate 12 that was quickly subjected to flash chroma-
tography. The eluted fractions (hexane/EtOAc) were ex-
Scheme 1. Reductions of cyclizable probe substrate 5.
12938
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 12937 – 12940

Ionic and Organometallic Reductions
COMMUNICATION
posed without concentration to 1 to provide 13 in 31% over-
all isolated yield. As expected, the ketone did not react. Tri-
flation of 14 gave 15 in 76% yield, then reduction with 1
provided 16 in 59% purified yield. No cyclized product was
detected.
complex 2, 10 mol% of PdACTHUNGTERNU(NG OAc)2 and dppf in refluxing
THF). The results of this series are summarized in Table 4.
Three other aryl iodides provided the reduced products in
yields ranging from 67–100% (entries 1–3). In particular, 4-
2
À
Table 4. Scope of the palladium-mediated reduction of Csp X bonds
with 2.
Entry
1
Substrate
Product, yield [%]
2
3
4
Scheme 2. Examples of triflate reductions.
Aryl iodides and triflates were not reduced under these
thermal conditions, either with or without radical initiators.
However, we speculated that the NHC–borane complexes
might donate hydride to metals and therefore be useful in
catalyzed reductions. A preliminary screening of conditions
was conducted with aryl iodide 17a, PdACTHNUTRGENUG(N OAc)2 and 1,1’-bis-
(diphenylphosphino)ferrocene (dppf) in THF. The iodide
was thus reduced by 1 without base to provide arene 18a in
44% yield along with 40% recovered 17a (Table 3, entry 1).
5
6
Table 3. Pd-mediated reduction of Aryl iodides with NHC–boranes.
[a] The product was too volatile to be satisfactorily isolated, but was the
only product detected by GC (see Supporting Information).
Entry
NHC–BH3
Equiv
Additive
Yield 18a [%]
1
2
3
4
5
1
2
2
2
2
1
1
0.5
0.34
0.34
–
–
–
44 (40% S.M.)[a]
90
55 (32% S.M.)
61 (13% S.M.)
70
iodoacetophenone 17d provided acetophenone 18d as the
only detectable product, with no trace of ketone reduction
(Entry 3).
NaOH
K2CO3
Aryl triflates were also reduced. For example, reduction
of the triflate ester 17e provided 18e in quantitative yield
without any reduction of the ester. (Table 4, entry 4). Repre-
sentative alkenyl triflate 17 f was also reduced to 18 f in
90% yield (entry 5). In contrast ortho,ortho’-bis-substituted
triflates failed to react. This limitation might be caused by
the failure of oxidative addition due to steric crowding.
Finally, reduction of 4-iodophenyl triflate 17g provided
phenyl triflate 18g in quantitative yield. (Table 4, entry 6).
The selectivity—iodide more reactive than triflate—is oppo-
site to that observed in the ionic reductions (see Table 2)
and presumably derives from the relative rates of oxidative
additions of palladium.[12] Because only one hydride is trans-
ferred from 2 in the absence of base, the chemoselectivity
for iodide reduction in 17g is total.
[a] S.M. = Starting material.
Complex 2 delivered 18a in a better yield (90%), again
without the help of a base (Table 3, entry 2). Seeking to de-
liver more than one hydride, we reduced 17a with 0.5 equiv
of 2. But the yield of 18a dropped to 55% and 17a was re-
covered in 32% yield (entry 3). Eventually we discovered
that better conversion and yield could be obtained in reac-
tions with less than 1 equiv of 2 when a wet solid base was
added (entries 4,5). For example, a reduction with 0.34 equiv
of 2 consumed all of 17a and provided 18a in 70% yield.
We next examined the scope of the metal-mediated reduc-
tion under the conditions of Table 3, entry 2 (1 equiv of
Chem. Eur. J. 2009, 15, 12937 – 12940
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
12939

E. Lacꢀte, D. P. Curran, M. Malacria, L. Fensterbank et al.
2009, 48, 4009–4012; e) T. Matsumoto, F. P. Gabbaꢄ, Organometallics
2009, 28, 4252–4253.
In conclusion, we have shown that complexation of bor-
anes with N-heterocyclic carbenes provides reagents that
can behave as hydride donors in ionic and organometallic
reactions. They also behave as hydrogen atom donors in rad-
ical reactions.[4] Based on these early experiments, the
chemistry of NHC–boranes seems to parallel that of re-
agents like tin hydrides rather than much more closely relat-
ed amine and phosphine boranes. Because of their weak hy-
dridic character, NHC–boranes can also be viewed as neu-
tral, organic soluble analogs of borohydride anions.[3] Their
reduced reactivity in ionic reactions compared to that of tra-
ditional borohydrides and the inherent selectivity of organo-
metallic catalysis may make NHC–boranes applicable for
surgical reductions in complex, multifunctional molecules.
[3] a) Science of Synthesis Organometallics: Boron Compounds, Vol. 6
(Eds.: D. E. Kaufmann, D. S. Matteson), Thieme, Stuttgart, 2004;
b) R. O. Hutchins, D. Kandasamy, C. A. Maryanoff, D. Masilamani,
B. E. Maryanoff, J. Org. Chem. 1977, 42, 82–91; c) R. O. Hutchins,
D. Kandasamy, F. Dux III, C. A. Maryanoff, D. Rotstein, B. Gold-
smith, W. Burgoyne, F. Cistone, J. Dalessandro, J. Puglis, J. Org.
Chem. 1978, 43, 2259–2267; d) For a recent report on the related ac-
À
tivation of B H bonds by a Lewis base, see: M. A. Dureen, A.
Lough, T. M. Gilbert, D. W. Stephan, Chem. Commun. 2008, 4303–
4305.
[4] a) S.-H. Ueng, M. Makhlouf Brahmi, E. Derat, L. Fensterbank, E.
Lacꢀte, M. Malacria, D. P. Curran, J. Am. Chem. Soc. 2008, 130,
10082–10083; b) S.-H. Ueng, A. Solovyev, X. Yuan, S. Geib, L. Fen-
sterbank, E. Lacꢀte, M. Malacria, M. Newcomb, J. C. Walton, D. P.
Curran, J. Am. Chem. Soc. 2009, 131, 11256–11262.
[5] Complexation of diborane allows boronate transfer to unsaturated
ketones, presumably through an ionic mechanism; see referen-
ce [2c].
[6] For example, imidazolylidene borane 1 survives heating for 24 h in
refluxing toluene and heating for 2 h at 1808C in benzotrifluoride
(BTF) in a sealed tube. It also survives GC-MS analysis and exhibits
a small molecular ion peak at m/z 402 and a larger fragment [MÀ3]
at m/z 399.
[7] In contrast, when a Lewis acid is added, carbene–borane complexes
do stereoselectively reduce carbonyl compounds. See D. Mc Arthur,
D. M. Lindsay, personal communications, manuscript under review.
[8] This control experiment shows that neither NHC–BH3 1 nor the de-
rived byproduct NHC–BH2I hydroborates the terminal alkene.
Amine complexes of BH3 also do not hydroborate alkenes, though
complexes of BH2I are postulated to do so. See, J. M. Clay, E.
Vedejs, J. Am. Chem. Soc. 2005, 127, 5766–5767.
Acknowledgements
We thank the US National Science Foundation, UPMC, CNRS, IUF
(M.M. and L.F.), l’ꢃtat et la Rꢁgion Ile-de-France (Chaire Blaise Pascal)
and the French Agence Nationale de la Recherche (ANR) for funding
(grant BLAN0309, Radicaux Verts and 08-CEXC-011-01, Borane). A.S.
thanks the University of Pittsburgh for a Graduate Excellence Fellow-
ship. Technical assistance (MS, elemental analyses) was generously of-
fered by ICSN (Gif sur Yvette, France) and FR 2769.
Keywords: aromatic substitution · boranes · N-heterocyclic
carbenes · palladium · reduction
[9] a) B. Carboni, L. Monnier, Tetrahedron 1999, 55, 1197–1248; b) B.
Carboni, F. Carreaux in Science of Synthesis Organometallics: Boron
Compounds, Vol. 6 (Eds.: D. E. Kaufmann, D. S. Matteson), Thieme,
Stuttgart, 2004, pp. 455–484; c) A.-C. Gaumont, B. Carboni in Sci-
ence of Synthesis Organometallics: Boron Compounds, Vol. 6 (Eds.:
D. E. Kaufmann, D. S. Matteson), Thieme, Stuttgart, 2004, pp. 485–
512.
[10] Interestingly, however, 1-iodoadamantane was reduced in 97% yield
to adamantane when it was heated with 1 in BTF at 1408C for 12 h.
[11] By way of example, the NHC·BH2I complex derived from 1 was iso-
lated in 90% yield from the reduction of dodecyl iodide. Detailed
studies on the preparation and characterization of this and other
boron-derived products will be published separately.
[1] a) N. Kuhn, G. Henkel, T. Kratz, J. Kreutzberg, R. Boese, A. H.
Maulitz, Chem. Ber. 1993, 126, 2041–2045; b) A. Wacker, H. Pritz-
kow, W. Siebert, Eur. J. Inorg. Chem. 1999, 789–793; c) T. Ramnial,
H. Jong, I. D. McKenzie, M. Jennings, J. A. C. Clyburne, Chem.
Commun. 2003, 1722–1723; d) Y. Yamaguchi, T. Kashiwabara, K.
Ogata, Y. Miura, Y. Nakamura, K. Kobayashi, T. Ito, Chem.
Commun. 2004, 2160–2161; e) Y. Wang, B. Quillian, P. Wei, C. S.
Wannere, Y. Xie, R. B. King, H. F. Schaefer III, P. von R. Schleyer,
G. H. Robinson, J. Am. Chem. Soc. 2007, 129, 12412–12413.
[2] a) D. Holschumacher, T. Bannenberg, C. G. Hrib, P. G. Jones, M.
Tamm, Angew. Chem. 2008, 120, 7538–7542; Angew. Chem. Int. Ed.
2008, 47, 7428–7432; b) P. A. Chase, D. W. Stephan, Angew. Chem.
2008, 120, 7543–7547; Angew. Chem. Int. Ed. 2008, 47, 7433-7437;
c) K.-s. Lee, A. R. Zhugralin, A. H. Hoveyda, J. Am. Chem. Soc.
2009, 131, 7253–7255; d) T. K. Wood, W. E. Piers, B. A. Keay, M.
Parvez, Angew. Chem. 2009, 121, 4069–4072; Angew. Chem. Int. Ed.
[12] Handbook of Organopalladium Chemistry for Organic Synthesis,
Vol. 1 (Eds.: E.-i. Negishi, A. de Meijere), Wiley Interscience, New
York, 2002, p. 132.
Received: September 4, 2009
Published online: November 4, 2009
12940
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 12937 – 12940