Room temperature Ni-catalyzed reduction of aryl tosylates by borane hydrides

Article abstract of DOI:10.1016/j.tetlet.2006.08.085

Mild Ni-catalyzed homogeneous reductions of aryl tosylates are described for the first time. The catalytic system Ni(PPh₃)₂Cl₂ and PCy₃ is shown to be general for hydrogenolysis of a wide range of tosylates, including hindered, deactivated, heterocyclic, and bifunctional examples.

Full text of DOI:10.1016/j.tetlet.2006.08.085

Tetrahedron Letters 47 (2006) 7515–7518
Room temperature Ni-catalyzed reduction of aryl tosylates
by borane hydrides
Vladimir Kogan
Department of Chemistry and Biochemistry, University of California at Santa Barbara, CA 93106, USA
Koffolk Fine Chemicals, Ltd., Ramat-Hovav 84874, Israel
Received 8 May 2006; revised 15 August 2006; accepted 23 August 2006
Abstract—Mild Ni-catalyzed homogeneous reductions of aryl tosylates are described for the first time. The catalytic system
Ni(PPh ) Cl and PCy is shown to be general for hydrogenolysis of a wide range of tosylates, including hindered, deactivated,
3
2
2
3
heterocyclic, and bifunctional examples.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
ature. Palladium acetate and Pd (dba) in the presence
2 3
of 4 equiv of triphenylphosphine gave good yields
(81% and 85%, respectively) of naphthalene in DMF
only at 75 °C. Bidentate ligands (2 equiv): dppf, dppb,
dppe, and dppp in combination with palladium acetate
resulted in similar conversions of 2-naphthyl tosylate.
These results were consistent with previously published
data describing Pd-catalyzed reduction of strongly acti-
Deoxygenation of phenols has aroused considerable
scientific interest, as it is an important transformation
in synthetic organic chemistry. This interest is certainly
1
well-grounded: replacement of the hydroxy group on an
aryl ring with hydrogen was a key step in the synthesis
2
a
2b
2c
of the vancomycin aglycon, linarin, angelecin, cal-
2
d
2e
6
othrixin B, metacyclophanes, and partially reduced
vated aryl sulfonates.
2
f
2g
polysubstituted calixarenes, liquid crystals dopands,
etc. To date, almost all reports have described palladium
catalyzed deoxygenation of phenols via triflates or
nonaflates, usually employing ammonium formate
as the reducing agent. Aryl tosylates have not been
reported as synthetically useful substrates for the deoxy-
genation of phenols. However, aryl tosylates are more
stable, operationally convenient, and cheaper than
triflates.
In the present study, we report a novel method for the
Ni-catalyzed hydrogenolysis of aryl tosylates using the
borane hydrides NaBH4 and dimethylamine–borane
complex under mild conditions.
3
Commercially available Ni(PPh ) Cl was used in this
3
2
2
research. PCy was found to be the best ligand leading
3
to excellent conversions as shown in Table 1. Surpris-
ingly, electron-rich ligands (entries 7 and 12) were less
effective; triarylphosphines, PPh and P(o-tolyl) demon-
It has been shown that tosylates can serve as coupling
partners in Suzuki–Miyaura cross-coupling reactions
3
3
strated low activity. The bidentate ligands dppb, dppe,
dppp, and dppf afforded low conversions of the model
tosylate (10–23%).
4
catalyzed by Ni complexes, however, palladium
catalyzed coupling processes of tosylates have been
5
investigated in detail. In this letter, we demonstrate
Ni-catalyzed reduction of aryl tosylates.
Among the solvents screened, THF and DMF were
found to be the best. In acetonitrile the reaction time
was slightly longer and nonpolar solvents (toluene, diox-
ane and dichloromethane) also gave slow reactions. The
borane hydrides play a dual role: they reduce the Ni(II)
complex to a Ni(0) complex in situ and serve as a hydro-
gen donor in the hydrogenation process. A number of
2
. Results and discussion
Pd complexes were found to be ineffective for the reduc-
tion of 2-naphthyl tosylate with NaBH at room temper-
4
7
hydride donors reported for triflate reductions were
E-mail: vladimir.kogan@koffolk.co.il
also examined: tributyltin hydride, triethylsilane, and
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.08.085

7516
V. Kogan / Tetrahedron Letters 47 (2006) 7515–7518
a
Table 1. Room temperature Pd(0) and Ni(0)-catalyzed reduction of 2-naphthyl tosylate with sodium borohydride
OTos
7
mol% cat
+
NaBH4
THF, rt,14 h
Entry
Metal source
Ligand
Conversion (%)
1
2
3
4
5
6
Pd
PdCl
PdCl
Pd(CH
Ni(PPh
Ni(PPh
2
(dba)
3
PPh
dppe, PPh
PPh , PCy
dppf, PPh
PPh
P(o-tolyl)
3
, PCy
3
, dppe, dppf
0
0
0
0
7
2
3
2
(PPh
3
)
2
3
3
3
COO)
2
3
3
)
)
2
2
Cl
Cl
2
3
3
2
3
11
2 2
PCy NMe
7
Ni(PPh
3
)
2
Cl
2
45
8
9
0
1
2
3
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
Ni(PPh
3
)
3
)
3
)
3
)
3
)
3
)
2
2
2
2
2
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
dppf
10
12
15
23
57
dppe
dppp
dppb
1
1
1
1
t-Bu
PCy
3
P
3
100
a
Reaction conditions: aryl tosylate (1 mmol), 2–4/1 ratios ligand:metal, sodium borohydride (5 mmol), THF (4 ml); conversion determined by GC,
using tetrahydronaphthalene as the internal standard.
sodium cyanoborohydride were found to be inactive
under these conditions.
Due to the strong electron-withdrawing features of these
groups, substrates are activated toward insertion of Ni
into the C–O bond and a low loading of the reductant
(3–3.5 mmol) was sufficient in order to obtain high
yields. Thus, using this reagent, chemoselective reduc-
tions can be achieved.
In general the reactions with NaBH were slow due to
4
the low reactivity of the tosylates and 5 equiv of the
reductant were needed to complete this hydrogenolysis.
Using sodium borohydride with mild heating permitted
decreasing the borohydride loading to 4.2–4.5 equiv.
These amounts of reductant are comparable to those
During the preparation of this manuscript, a report
describing heterogeneous hydrogenolysis was pub-
1
,2,6
9
reported for triflate reductions.
lished. Being one of the authors of this paper and rec-
ognizing the attraction of a heterogeneous process I
note certain drawbacks of this process: (1) harsh reac-
tion conditions (120 °C), (2) hydrolysis and not hydro-
genolysis of certain tosylates (substrates 5–7, Scheme
6. Ref. 9). However, tosylate hydrolysis was never ob-
served using mild homogeneous catalysis. So, for exam-
ple, (substrate 6, Scheme 6, Ref. 9) was smoothly
reduced obtaining 2-(2-hydroxyphenyl) benzothiazole).
As shown in Table 2, a variety of neutral and electron-
rich substrates were examined. Entries 1–8 show very
high conversions, and products were isolated by flash
chromatography. Entries 9–13 demonstrated good con-
versions as well, despite deactivation by electron-donat-
ing substituents on the aromatic ring. In the case of
deactivated substrates (entries 10 and 13–15), low con-
versions were obtained. On reacting these tosylates at
6
0 °C, moderate to excellent conversions were obtained.
In conclusion, a novel, efficient and convenient synthetic
route for mild dehydroxylation of a wide range of phe-
nols via Ni-catalyzed reduction of their tosylate deriva-
tives is described. Current mechanistic studies on this
process as well as a search for new synthetic pathways
Bifunctional tosylates (entries 6 and 7) as well as a
heterocyclic tosylate (entry 5) were found to be reactive.
In the case of a hindered bistosylate (entry 6), a small
amount of mono-reduced product was isolated, but
this product was undetectable at 60 °C. Reduction of
bistosylates needed almost a double loading of the
reductant as expected. Using this protocol competitive
catalyzed by this Ni(0)/PCy system are underway.
3
6
Pd-catalyzed hydrolysis of tosylates was never
3. Experimental
observed.
General method for tosylates hydrogenolysis
For a variety of electron-deficient aryl tosylates, the use
of sodium borohydride was unsuitable due to the com-
petitive reduction of the carbonyl substituents. For these
substrates (entries 1–4 in Table 3) and for nitrile- and
ester-containing substituents (entries 5 and 6), dimethyl-
amine–borane complex was used at ambient tempera-
ture as the reducting agent. The modified Lipshutz
protocol for nonaflate reduction (Ni instead of Pd,
A solution of 2-naphthyl tosylate (0.298 g, 1 mmol) in
4 ml of DMF was treated with Ni(PPh ) Cl (0.017 g,
3
2
2
0.07 mmol) and tricyclohexylphosphine (0.011 g,
0.28 mmol) and after stirring for 5 min NaBH4
(0.190 g, 5 mmol) was added in one portion. The mix-
ture was stirred at room temperature and the progress
of the reaction was monitored by TLC (hexane:ethyl
acetate, 8:2). After consumption of the starting material
8
DMF as solvent, room temperature) was applied.

V. Kogan / Tetrahedron Letters 47 (2006) 7515–7518
7517
Table 2. Room temperature Ni(0)-catalyzed reduction of aryl tosylates
with sodium borohydride
Table 3. Room temperature Ni-catalyzed reduction of aryl tosylates
with dimethylamine–borane complex
a
a
7
%Ni(PPh ) Cl /28%PCy
7 %Ni(PPh ) Cl /28%PCy
3
3
2
2
3
3
2
2
Ar-OTos
+
NaBH4
Ar-H
Ar-OTos
Entry
+
BH3
.
N(CH3)2
Ar-H
THF, rt,14 h
DMF,K CO , rt,14 h
2
3
Entry
1
Ar-OTos
Yield (%)
Ar-OTos
Yield (%)
OTos
93
b
1
2
H CCO
OTos
OTos
100
3
CH CO
3
OTos
90
2
3
90
O
b
OTos
3
4
100
b
100
OTos
CF3
OTos
89
4
5
90
87
O
OTos
O
OTos
c
5
6
NC
OTos
87
H CCOO
OTos
92
3
c,d
6
7
8
9
81
a
Reaction conditions: aryl tosylate (1 mmol), dimethylamine–borane
complex (3 mmol), DMF (4 ml).
GC yield, tetrahydronaphthalene used as the internal standard.
3.5 mmol of dimethylamine–borane complex, 20 h.
OTos OTos
b
c
c
TosO
OTos
88
the reaction mixture was diluted with water, extracted
OTos
with ethyl acetate, dried over MgSO and evaporated.
b
4
95
The residue was chromatographed on silica gel with
hexane–ethyl acetate mixture (99:1) as eluent to give
0.119 g, 93% of naphthalene.
OTos
90
Acknowledgement
OTos
e
1
0
1
93
I thank Professor B. H. Lipshutz who encouraged my
interest in organonickel chemistry and in whose labora-
tory the preliminary results were obtained.
OTos
b
1
100
References and notes
1
2
3
OTos
90
81
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4
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