Radical deoxygenation of xanthates and related functional groups with new minimalist N-heterocyclic carbene boranes

Article abstract of DOI:10.1021/ol101015m

Minimalist N-heterocyclic carbene boranes 1,3-dimethylimidazol-2- ylideneborane and 2,4-dimethyl-1,2,4-triazol-3-ylideneborane are readily available and have low molecular weights. They exhibit superior performance to first-generation NHC-boranes, providi

Full text of DOI:10.1021/ol101015m

ORGANIC
LETTERS
2010
Vol. 12, No. 13
3002-3005
Radical Deoxygenation of Xanthates and
Related Functional Groups with New
Minimalist N-Heterocyclic Carbene
Boranes
Shau-Hua Ueng,† Louis Fensterbank,‡ Emmanuel Lacoˆte,*,‡ Max Malacria,‡ and
Dennis P. Curran*,†
Department of Chemistry, UniVersity of Pittsburgh, Pittsburgh, PennsylVania 15260,
and 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
Minimalist N-heterocyclic carbene boranes 1,3-dimethylimidazol-2-ylideneborane and 2,4-dimethyl-1,2,4-triazol-3-ylideneborane are readily available
and have low molecular weights. They exhibit superior performance to first-generation NHC-boranes, providing improved yields in reductions
of xanthates and related functional groups.
Radical reactions are commonly used as key steps in modern
organic synthesis,1 and this has spurred research to provide
attractive alternatives to traditional radical reducing agents such
as tributyltin hydride.2,3 We have recently learned that
N-heterocyclic carbene-borane complexes 1 and 2 (hereafter
called NHC-boranes, Figure 1) can reduce xanthates and
related functional groups,4 and we have accumulated strong
evidence that these reductions occur through a radical
Figure 1. Structures of first-in-class N-heterocyclic carbene boranes
† University of Pittsburgh.
‡ Institut Parisien de Chimie Mole´culaire.
used in xanthate reductions. (Formal charges are shown here but
not in subsequent diagrams.)
(1) (a) Fossey, J.; Lefort, D.; Sorba, J. Free Radicals in Organic
Chemistry; Wiley: New York, 1995. (b) Giese, B.; Kopping, B.; Go¨bel, T.;
Dickhaut, J.; Thoma, G.; Kulicke, K. J.; Trach, F. Org. React. 1996, 48,
301–856. (c) Radicals in Organic Synthesis; Renaud, P., Sibi, M. P., Eds.;
Wiley-VCH: Weinheim, 2001. (d) Albert, M.; Fensterbank, L.; Lacte, E.;
Malacria, M. Top. Curr. Chem. 2006, 264, 1–62.
mechanism involving N-heterocyclic carbene boryl radicals
5-7
•
(NHC-BH2 ).
(2) Review of tin and related hydrides: Chatgilialoglu, C.; Newcomb,
M. AdV. Organomet. Chem. 1999, 44, 67–112
These NHC-boranes are attractive for radical, ionic,8 and
organometallic9 reactions because they are stable and easy
.
(3) Alternatives to tin hydrides: (a) Baguley, P. A.; Walton, J. C. Angew.
Chem., Int. Ed. 1998, 37, 3072–3082. (b) Studer, A.; Amrein, S. Synthesis
2002, 835–849. (c) Gilbert, B. C.; Parsons, A. F. J. Chem. Soc., Perkin
Trans. 2 2002, 367–387. (d) Darmency, V.; Renaud, P. Top. Curr. Chem.
(4) 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.
2006, 263, 71–106
.
10.1021/ol101015m  2010 American Chemical Society
Published on Web 06/10/2010

to handle and are built only from common second-row
elements. Although 1 and 2 are readily made, their carbene
precursors (an imidazolium or triazolium salt) are rather
expensive. The reagents are not ideally efficient in xanthate
reductions (often 2 equiv are used to maximize yield), and the
more well-studied reagent 1 has a relatively high molecular
weight of 402 g mol-1. Compare this to tributyltin hydride at
291 g mol-1 or tris(trimethylsilyl)silane at 249 g mol-1.
Herein we report that “minimalist” NHC-boranes 3 (110
g mol-1) and 4 (111 g mol-1) prepared from simple, readily
available imidazolium or triazolium salts are superior to first-
in-class reagents 1 and 2 in reductions of xanthates and
related functional groups.
characterized by the usual means (including 11B NMR
spectroscopy)10 and were stable to prolonged storage under
standard ambient conditions.
Imidazol-2-ylideneborane (1) is the most well understood
NHC-borane reagent to date, so we chose this as a
benchmark. In kinetic experiments described in the previous
paper,11 the rate constant for hydrogen abstraction from 3
by a primary alkyl radical was found to be kH ) 8 × 104
M-1 s-1 (See Figure 2). The measured rate constant for 4
1,3-Dimethylimidazol-2-ylideneborane (3) (hereafter called
diMe-Imd-BH3) was readily prepared by deprotonation of
1,3-dimethylimidazolium iodide (5) with NaHMDS followed
by addition of borane in THF (Scheme 1).5c Isolation by
Figure 2. Comparison of rate constants for generation and
termination of NHC-boryl radicals 1• and 3•. (The rate constants
kH and 2kT were measured in different experiments.)
Scheme 1. Synthesis of 1,3-Dimethylimidazol-2-ylideneborane
(3, diMe-Imd-BH3) and 2,4-Dimethyltriazol-3-ylideneborane (4,
diMe-Tri-BH3)
was comparable to 3. Contrast this to 1, which is about 4
times less reactive.5a
Like 1•, the NHC-boryl radical 3• generated by hydrogen
abstraction from 3 by t-BuO• was detected by EPR
spectroscopy.5c Boryl radical 3• reacted with itself (presum-
ably by dimerization) at rates approaching the diffusion
controlled limit (2kT > 1010 M-1 s-1). In contrast, boryl
radical 1• was persistent (2kT ) 9 × 106 M-1 s-1). Both of
these results can be understood by steric effects; the radical
3• is easier to generate and reacts more rapidly than 1•.
Based on these kinetic results, we undertook a series of
preparative experiments to evaluate the potential of 3 and 4
as radical reducing agents in more detail. The results of an
initial set of comparison experiments of diMe-Imd-BH3 (3)
with current standard 1 in the reduction of xanthate,
phenylthionocarbonate, and imidazolyl derivatives of several
secondary alcohols are summarized in Table 1.
In a typical pair of experiments under thermal conditions
(A), a benzene solution of xanthate 7a, NHC-borane 1 or 3
(1 equiv), and AIBN (1 equiv) was heated at reflux for 2 h.
The solvent was evaporated, and the crude product was
purified by flash chromatography to provide the isolated yield
of 10. In the reaction with 3, the xanthate was consumed,
and the reduced product 10 was isolated in 77% yield (entry
1). In contrast, the reaction with 1 provided only 15% yield
of 10 along with 73% of recovered xanthate 7a (entry 2).
Similar results were obtained in reductions of xanthates 8a
(78% of 11 compared 8%; entries 3 and 4) and 9a (88% of
12 compared to 42%; entries 9 and 10). In the reduction of
8a with 1, the major component was again recovered starting
material (64%). The yields with 1 are significantly lower
than previously reported because the reaction conditions are
flash chromatography was convenient on 1 g scale, and 3
was obtained in 79% yield as a white solid, mp 134-137
°C. A similar reaction of 2,4-dimethyl-1,2,4-triazolium iodide
(6) provided 2,4-dimethyl-1,2,4-triazol-3-ylideneborane (4)
(hereafter called diMe-Tri-BH3) in 61% yield after flash
chromatography, mp 57-58 °C. Both compounds were fully
(5) (a) 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. (b) Matsumoto, T.; Gabba¨ı,
F. P. Organometallics 2009, 28, 4252–4253. (c) 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. (d) 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.
(6) For pioneering work on amine and phosphine boryl radicals, see:
(a) Dang, H.-S.; Roberts, B. P. Tetrahedron Lett. 1992, 33, 6169–6172. (b)
Dang, H.-S.; Diart, V.; Roberts, B. P.; Tocher, D. A. J. Chem. Soc., Perkin
Trans. 2 1994, 1039–1045. (c) Roberts, B. P.; Steel, A. J. J. Chem. Soc.,
Perkin Trans. 2 1994, 2411–2422. (d) Barton, D. H. R.; Jacob, M.
Tetrahedron Lett. 1998, 39, 1331–1334. (e) Lucarini, M.; Pedulli, G. F.;
Valgimigli, L. J. Org. Chem. 1996, 61, 1161–1164. (f) Baban, J. A.; Roberts,
B. P. J. Chem. Soc., Perkin Trans. 2 1988, 1195–1200. (g) Sheeller, B.;
Ingold, K. U. J. Chem. Soc., Perkin Trans. 2 2001, 480–486. (h) Laleve´e,
J.; Tehfe, M. A.; Allonas, X.; Fouassier, J. P. Macromolecules 2008, 41,
9057–9062.
(7) These transformations are members of a larger class called
Barton-McCombie reactions: Crich, D.; Quintero, L. Chem. ReV. 1989,
89, 1413–1432.
(8) (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.
(10) The preparation and characterization of 3 are described in the
Supporting Information of ref 5c, while the corresponding information for
4 is in the Supporting Information of this paper.
(11) Solovyev, A.; Ueng, S.-H.; Monot, J.; Malacria, M.; Fensterbank,
L.; Lacoˆte, E.; Curran, D. P. Org. Lett. 2010, 12, DOI: 10.1021/ol101014q.
(9) Monot, J.; Makhlouf Brahmi, M. M.; Ueng, S.-H.; Robert, C.; Murr,
M. D.-E.; Curran, D. P.; Malacria, M.; Fensterbank, L.; Lacoˆte, E. Org.
Lett. 2009, 11, 4914–4917.
Org. Lett., Vol. 12, No. 13, 2010
3003

at room temperature with Et3B/air initiation (conditions B).
The progress of the reaction was followed by 11B NMR
spectroscopy, and Figure 3 shows a portion of the
Table 1. Preliminary Reductions of Xanthate and Related
Derivatives with diMe-Imd-BH3 (3) and dipp-Imd-BH3 (1)
(Control)
Figure 3.
Structure of 13 and a part of the 96.3 MHz 11B NMR
spectrum showing the evidence for its formation in the reaction of
7a and 3 after 10 min at room temperature.
product; SMb
NHC-BH3 conditionsa yieldb (%) (%)
entry substrate
X
1
7a
7a
8a
8a
8b
8b
8b
8b
9a
9a
9b
9b
9c
9c
C(dS)SMe
C(dS)SMe
C(dS)SMe
C(dS)SMe
C(dS)OPh
C(dS)OPh
C(dS)OPh
C(dS)OPh
C(dS)SMe
C(dS)SMe
C(dS)OPh
C(dS)OPh
C(dS)Imd
C(dS)Imd
3
1
3
1
3
1
3
1
3
1
3
1
3
1
A
A
A
A
A
A
B
B
A
A
B
B
Ac
Ac
10; 77
10; 15
11; 78
11; 8
n.d.
73
n.d.
64
12
spectrum at the first time point (10 min). The quartet
resonance of the starting borane at -36.4 ppm is already
substantially diminished, and a new triplet appears at
-25.9 ppm. Both the multiplicity and the chemical shift
of the peak are consistent with the proposed structure
diMe-Imd-BH2SC(dO)SMe (13).5a After 60 min, the
quartet of 3 disappeared, leaving the triplet of 13 as the only
significant resonance in the spectrum (see the Supporting
Information). We conclude that 13 is indeed the primary
boron-containing product of these reactions.
2
3
4
5
11; 74
6
11; n.d. 90
7
11; 81
14
8
11; n.d. 90
9
12; 88
12; 42
12; 83
12; 25
12; 67
12; 42
n.d.
10
11
12
13
14
n.d.
n.d.
n.d.
n.d.
n.d.
a A ) 1 equiv of AIBN, 80 °C, 2 h; B ) 1 equiv of Et3B, rt, 2 h,
ambient air. b Isolated yield after flash chromatography, n.d. ) not
determined. c AIBN initiation in toluene at 110 °C.
Next, we undertook a set of preparative deoxygenations
with 3 to explore the scope, and the results of these reactions
are shown in Table 2. As before, only 1 equiv of 3 was used
with either thermal (AIBN, conditions A) or room-temper-
ature (Et3B/air, conditions B) initiation. The reactions were
substantially complete after 2 h, and the products were
isolated by flash chromatography as usual. Reduction of 14
provided 19 in comparable yields (79% and 81%) under
thermal and rt conditions (entries 1 and 2).
Reductions of cyclopropylcarbinyl xanthate 15 provided
ring-opened products 20 and 21 (entries 3 and 4). The major
product under both thermal and rt conditions was reduced
20 (52% and 63%), while the minor product 21 (17% and
22%) resulted from a competing xanthate group transfer
reaction. In contrast, reduction of xanthate precursor 16 of
a hexenyl radical under both conditions (entries 5 and 6)
gave primarily ring closed, reduced product 22 (73% and
64%). There were also minor amounts of the directly reduced
product (4% and 10%; this product is not shown and was
not separated from 22) and the cyclized xanthate transfer
product 23 (5% in both reactions).12 The results of these
competitionsscomplete opening of a cyclopropylcarbinyl
radical, almost complete closing of a hexenyl radical, minor
xanthate transfer products from primary radicalssare all
qualitatively consistent with the intermediate value of the
rate constant for hydrogen transfer from 3.
different; optimal yields with 1 require an excess of reagent
and a longer reaction time.4
Likewise, the reduction of the thionocarbonate 8b under
fixed-time (2 h) thermal conditions with 3 provided 11 in
74% yield (12% recovered 8b; entry 5), while reduction with
1 provided substantially recovered 8b (90%, entry 6).
Reduction of imidazolyl derivative 9c under thermal condi-
tions in refluxing toluene with 3 and 1 provided 12 in 67%
and 42% yields, respectively (entries 13 and 14).
DiMe-Imd-BH3 reagent 3 was also superior to 1 in room-
temperature experiments (conditions B) with triethylborane
(1 equiv) and air (admitted through a narrow needle open to
the atmosphere). Again, the time was fixed at 2 h. Reduction
of thionocarbonate 8b with 3 provided 11 in 81% yield
alongside 14% recovered starting material (entry 7), while
1 provided only recovered starting material (90%; entry 8).
Likewise, 9b was reduced to 12 in 83% yield with 3 but
only 25% yield with 1 (entries 11 and 12). Taken together,
the data of the kinetic and preparative experiments show that
3 is a better radical reducing agent than 1.
According to the chain mechanism for reduction of
xanthates,7 the boron-containing product from the reductions
with 3 should be dithiocarbonate diMe-Imd-BH2SC(dO)SMe
(13).5a Attempts to isolate this compound by flash chroma-
tography were not successful, perhaps due to its instability
on silica gel.
Two syn-thionocarbonates 17 and 18 were also deoxy-
genated with 3. Reduction of monothionocarbonate 17
provided 24 in 68% yield under thermal conditions (entry
To learn about the nature of the boron products formed, a
reaction between 7a and 3 was conducted in an NMR tube
(12) Quiclet-Sire, B.; Zard, S. Z. Top. Curr. Chem. 2006, 264, 201–
236.
3004
Org. Lett., Vol. 12, No. 13, 2010

Table 2. Preparative Deoxygenations of Xanthates and
Thionocarbonates with 3 under Thermal (A) and
Room-Temperature (B) Conditions
Table 3. Comparison of Yields of 3 and 4 in Reductions of 8b
and 9a,b (Precursor and Product Structures Are Shown in Table
1)
entry substrate NHC-BH3 conditionsa product; yield (%)
1
2
3
4
5
6
8b
8b
9a
9a
9b
9b
3
4
3
4
3
4
A
A
B
B
A
A
11; 89
11; 87
12; 88
12; 86
12; 81
12; 80
a A ) 1 equiv of AIBN, 80 °C, 2 h; B ) 1 equiv of Et3B, rt, 2 h.
xanthates and thionocarbonates. (The results also show the
reproducibility in reductions with 3; entries 1, 3, and 5 in
Table 3 are repeat experiments of entries 5, 9, and 11 in
Table 1 and give comparable yields.)
We attempted to dissolve both 3 and 4 in water and found
that 2,4-dimethyl-1,2,4-triazol-3-ylideneborane 4 exhibits
considerable solubility. It is also stable in water, and an NMR
spectrum recorded in D2O is shown in the Supporting
Information. This suggests that 4 might be a useful reagent
either for conducting radical reactions in water or for
procedures involving aqueous workup.14
In summary, “minimalist” NHC-boranes 1,3-dimeth-
ylimidazol-2-ylideneborane (3) and 2,4-dimethyl-1,2,4-tria-
zol-3-ylideneborane (4) are attractive new reagents for
reduction of xanthates and related functional groups. They
are readily available and have low molecular weights, and
they provide good yields in both thermal and room temper-
ature reductions. Unlike the first-generation reagent 1, the
reactions with 3 and 4 are rapid, and excesses of the reagents
are not needed. These results clearly show that changing the
N-substituents on N-heterocyclic carbene boranes is a
valuable tool to alter reactivity in radical and presumably
other reactions.
a A ) 1 equiv of AIBN, 80 °C, 2 h. B ) 1 equiv of Et3B, rt, 2 h.
b Diastereomeric ratio 2.2:1. c Cyclization/reduction ratio 16.7:1.
d Diastereomeric ratio 2.7:1. e Cyclization/reduction ratio 5.7:1. f 2.6 equiv
of AIBN and 3 were used. g Yield determined by GC analysis with dodecane
as internal standard.
7), while reduction of bis-thionocarbonate 18 provided 25
in 40% isolated and 49% GC yield (entry 8).
Acknowledgment. This work was supported by grants
from the US National Science Foundation (CHE-0645998),
UPMC, CNRS, IUF, and the French Agence Nationale de
la Recherche (ANR, BLAN0309 Radicaux Verts, and 08-
CEXC-011-01 Borane). We thank Mr. E. A.-H. Yeh (Uni-
versity of Pittsburgh) for preparing substrates 17 and 18.
Technical assistance at UPMC (MS, elemental analyses) was
offered by FR 2769.
We briefly surveyed the ability of 3 to reduce several
primary xanthates and related derivatives. Such reductions
are much less common than with secondary derivatives. The
results of this series of experiments are shown in Table S1
of the Supporting Information. Though the yields are
moderate (typically 30-50%), they are comparable to other
examples of reductions of primary derivatives.13
Having a good understanding of the capabilities of reagent
3, we closed this preliminary study with a short series of
experiments comparing it to diMe-Tri-BH3 (4). Reductions
were done with 1 equiv of each reagent for 2 h under thermal
and room temperature conditions, as usual. The results for
reductions of thionocarbonates 8b and 9b and xanthate 9a
are summarized in Table 3 (see Table 1 for structures). The
yields of all three pairs of reactions were comparable and
were uniformly high (81-89%). Thus, it seems that 3 and 4
are roughly equivalent as radical reducing agents toward
Supporting Information Available: Procedures, charac-
terization of new compounds, and data on reduction of
primary xanthates. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL101015M
(14) A preliminary experiment with 4 and the xanthate of 2-propanol
was conducted, and the crude product was washed with water and then
assayed by 11B NMR spectroscopy. While the resonance for 4 was gone,
there was a large new triplet at -29.3 ppm, presumably diMe-Tri-
BH2SC(O)SMe. Apparently, the byproduct is less soluble in water than the
starting borane. Successful separations by aqueous washing with other
substrates will be reported in due course.
(13) Spiegel, D. A.; Wiberg, K. B.; Schacherer, L. N.; Medeiros, M. R.;
Wood, J. L. J. Am. Chem. Soc. 2005, 127, 12513–12515.
Org. Lett., Vol. 12, No. 13, 2010
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