Iridium-catalyzed reduction of alkyl halides by triethylsilane

Article abstract of DOI:10.1021/ja075725i

A highly active cationic Ir(III) hydride complex catalyzes the reduction of primary, secondary, and tertiary chlorides, bromides, and iodides as well as certain fluorides by Et₃SiH. The catalytic cycle appears to operate by a unique process in which an electrophilic iridium silane complex acts as a silylating reagent to produce a silyl-substituted halonium ion which is then readily reduced by the nucleophilic dihydride formed following silyl transfer. Copyright

Full text of DOI:10.1021/ja075725i

Published on Web 09/27/2007
Iridium-Catalyzed Reduction of Alkyl Halides by Triethylsilane
Jian Yang and Maurice Brookhart*
Department of Chemistry, UniVersity of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290
Received July 31, 2007; E-mail: mbrookhart@unc.edu
Table 1. Reduction of Alkyl Halides Catalyzed by 1a
Alkyl halides are generally reduced with trialkyl tin hydrides
via a radical chain mechanism.1 Alternative reduction procedures
are desired owing to the toxicity of the tin reagents and problems
separating tin byproducts from reduction products. Silanes are
thermodynamically capable of such reductions, but the Si-H bond
is too strong to support a radical chain reaction.2 Use of (TMS)3-
SiH possessing a weak Si-H bond circumvents this problem but
is not economically attractive.2 High loadings of Pd(II) salts have
been shown to induce Et3SiH reduction of certain classes of alkyl
halides.3 Strong Lewis acids (e.g., AlCl3) have been used in
combination with Et3SiH; skeletal rearrangements accompanying
reduction support a mechanism involving carbocation-like inter-
mediates.4 The combination of Et3SiH/Ph3C+BAr-4 (Ar- ) C6F5-)
can reduce alkyl fluorides via a mechanism involving generation
of carbocations through fluoride abstraction by Et3Si+ (formed from
Ph3C+ and Et3SiH) followed by hydride transfer to the carbocation
by Et3SiH.5 Similar chemistry has been described using a bissily-
lated onium salt.6 We report here a cationic Ir(III) hydride complex,
1, which is a versatile and highly active catalyst for reduction of a
broad spectrum of alkyl halides by Et3SiH.
catalyst
mol %
T,
t
conversionc
%
entry
halide
solventb
°
C
h
1
2
3
4
5
6
7
8
9
0.5
0.5
benzyl bromide
benzyl chloride
A
A
A
B
A
A
A
A
C
C
A
A
A
A
C
C
A
A
D
23
23
23
23
60
60
60
60
23
23
60
60
60
23
23
23
23
23
0.3
0.3
2.5
29
7
1.5
48
50
20
3.3
2.3
0.7
16
0.3
9
3.3
0.3
0.3
>99
>99
>99
32
>99
>99
>99
92d
0.075 benzyl bromide
0.01
0.5
0.5
0.5
2.0
0.5
benzyl chloride
1-chloropentane
1-bromopentane
1-iodopentane
1-fluoropentane
1-chloropentane
1-bromopentane
2-chloropentane
2-bromopentane
chlorocyclohexane
bromocycloheptane
2-chloropentane
2-bromopentane
trityl chloride
86
98
10 0.5
11 0.5
12 0.5
13 0.5
14 0.5
15 0.5
16 0.5
17 0.5
18 0.5
19 1.0
>99e
>99e
>99e
>99e
99e
98e
>99
>99e
>99f
tert-pentyl chloride
CD2Cl2
23 168
a Reaction conditions: 3 equiv. of Et3SiH. b Solvent: A, C6D5Cl; B,
C6D4Cl2; C, neat; D, CD2Cl2. c Determined by loss of alkyl halides by NMR.
d Products in addition to pentane are observed. e In addition to alkane, traces
of olefin and H2 were observed and converted to alkanes at longer reac-
tion times. f Catalyst loading and conversion refer to Et3SiH. The reduc-
tion product is CD2H2; only traces of CD2HCl are observed at 50%
reaction.
Synthesis of 1 is achieved in 94% isolated yield by treatment of
dihydride 27 with Ph3C+BAr- in acetone (eq 1). Complete
4
characterization including a single-crystal X-ray structural analysis
is in hand.8 Reductions of halides (eq 2) are conveniently carried
out either in chlorobenzene or in neat alkyl halide. Catalyst loadings
of 0.5 mol % are generally used (but can be much lower, see below)
together with 3 equiv of Et3SiH; temperatures of 23-60 °C are
employed depending on substrate.
1-bromopentane and 1-chloropentane at 23 °C are shown in entries
9 and 10. Again, the bromide is more reactive than the chloride.
Reductions of simple secondary halides are shown in entries
11-16. Like the primary halides, efficient reductions can be
accomplished in chlorobenzene or in neat alkyl halide at either 60
or 23 °C and bromides are reduced more rapidly than chlorides.
The tertiary chlorides, trityl chloride as well as tert-pentyl chloride
are reduced rapidly at 23 °C (entries 17 and 18).
To determine relative reactivities of primary and secondary
halides, competition experiments were run by treating a 1:1 molar
ratio of the two pentyl halides in C6D4Cl2 with 6 equiv Et3SiH and
1% 1 and monitoring initial rates of reduction of the halides at 23
°C. The following relative rates were determined: 1-chloropentane/
2-chloropentane ) 2.6:1.0, 1-bromopentane/2-bromopentane )
2.0:1.0, and 1-iodopentane/2-iodopentane ) 1.6:1.0.
Results in Table 1 show that, qualitatively, reactivities follow
the order RBr > RCl > RI when reductions are carried out in
separate flasks. Quite different results are seen when two different
halides compete for reduction in the same flask. The experimental
protocol is summarized in eq 3 and results are shown in Table 2.
In a representative experiment, 1-iodoheptane (1 equiv) and
1-bromohexane (80 equiv) were treated with 30 equiv of Et3SiH
and 5% 1. Analysis of heptane and hexane very early in the reaction
(less than 12.5% conversion of 1-iodoheptane) established a relative
reactivity ratio of 80:1 for primary iodide/primary bromide. Bromide
versus chloride and iodide versus chloride values are shown in the
Results of typical reductions are illustrated in Table 1. Conver-
sions are determined by NMR spectroscopy. Entries 1-2 show that
benzyl chloride and benzyl bromide are rapidly reduced at 23 °C,
0.5% catalyst loading. With 0.075% loading, complete reduction
of benzyl bromide (1330 TOs) is accomplished in 2.5 h at 23 °C.
At 0.01% loading 3200 TOs for reduction of benzyl chloride are
achieved after 29 h. Results of reduction of simple primary alkyl
halides are shown in entries 5-10. Rapid reduction of 1-bromopen-
tane occurs at 60 °C (0.5% 1) while under similar conditions
1-chloropentane requires ca. 7 h for complete reduction. Reduction
of 1-iodopentane is slow, requiring 48 h for complete conversion.
1-Fluoropentane can be reduced but exhibits only 92% conversion
at 2% catalyst loading after 50 h. Results of reductions of neat
9
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J. AM. CHEM. SOC. 2007, 129, 12656-12657
10.1021/ja075725i CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Proposed Catalytic Cycle for Iridium-Catalyzed
Table 2. Competition Experiments to Determine the Relative
Reactivities of Primary Chloride, Bromide, and Iodide
Reduction of Alkyl Halides by Triethylsilane
relative
reactivies
(RX/R
entry
RX
R
′
X
′
R
′
X
′
/RX
′
X
′
)
1
2
3
1-iodoheptane
1-bromoheptane
1-iodoheptane
1-chlorohexane
1-chlorohexane
1-bromohexane
250
200
80
1200
260
80
Table 2 and establish that in head-to-head competition RI > RBr
> RCl. These results show that highly chemoselective reductions
can be achieved.
of halides in separate flasks versus the same flask. Alkyl iodides
bind tightly to Ir and result in very low equilibrium concentrations
of the σ-silane complex thus retarding the overall rate, but the silane
complex reacts preferentially with iodides when offered the “same
flask” experiments.
In summary, iridium complex 1 is a highly effective catalyst for
reduction of a wide class of alkyl halides by triethylsilane. The
catalytic cycle appears to operate by a unique process in which an
electrophilic iridium silane complex acts as a silylating reagent to
produce a silyl-substituted halonium ion which is then readily
reduced by the nucleophilic dihydride formed following silyl
transfer. This mechanism has parallels to that proposed by Piers
for hydrosilylation of ketones using (C6F5)3B/Et3SiH wherein the
silane is activated by (C6F5)3B and transfers Et3Si+ to ketone.10
Indeed complex 1 catalyzes the reduction of other functional groups
and will be the subject of future publications.
Substantial mechanistic details were uncovered by in situ 1H and
31P NMR monitoring of working catalyst systems, with 31P NMR
data being the more useful. First, potential intermediates were
generated independently and their 31P NMR spectra recorded. The
31P chemical shifts for these species are summarized in Figure 1
and the means of generating them are described in Supporting
Information.
Exposure of the acetone complex 1 to Et3SiH results in rapid
formation of (CH3)2CHOSiEt3 and a highly reactive solvated
complex which initiates the reaction. Following the in situ reduction
of CH3I at 23 °C shows that the only Ir species present is the CH3I
complex, 3. However, following the reduction of either 1-chloro-
pentane or 1-bromopentane shows that the Ir species exist as a
mixture of the halide complex (6 or 7) and the σ-silane complex 4
with the ratio depending on the ratio of silane/halide and the nature
of the halide (the bromide binds tighter than the chloride). Low-
temperature NMR experiments show that the σ-silane complex is
in rapid equilibrium with the halide complexes and this equilibrium
is established rapidly relative to reduction.9 These results support
the catalytic cycle shown in Scheme 1.
The reactivity order, RI < RCl < RBr (separate flasks) and the
observation that CD2HCl is reduced much faster than CD2Cl2
are inconsistent with a radical mechanism. Reduction of iridium
halide complex A by Et3SiH is also inconsistent with the order RI
< RCl < RBr. Kinetic studies of the reduction of CH3I show that
the turnover frequency is zero-order in [CH3I] and first-order in
[Et3SiH], consistent with the proposed catalytic cycle where A,
[Ir]H(ICH3)+, is the dominant resting state. Data collected to date
cannot distinguish between step I or step II as the turnover-limiting
step, and this may well vary with the nature of the substrate. The
proposed mechanism also explains the differing relative reactivities
Acknowledgment. We acknowledge funding by the NSF-STC
under agreement No. CHE-9876674 and Dr. Peter White for
crystallography.
Supporting Information Available: CIF files containing X-ray
crystallographic data for complex 1, experimental details, and kinetics.
This material is available free of charge via the Internet at http://
pubs.acs.org.
References
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Figure 1. Characteristic 31P NMR shifts used to identify key Ir species.
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