N-heterocyclic carbene-catalyzed hydrosilylation of styryl and propargylic alcohols with dihydrosilanes

Article abstract of DOI:10.1002/chem.201101822

Reducing alkenes to tears: Addition of structurally diverse N-heterocyclic carbenes (NHCs) to silicon allows the reduction of propargylic and styryl alcohols through an organocatalyzed silylation/direct hydride transfer tandem reaction (see scheme). Catalytic turnover is enabled by the switch to and from hypervalent silicon. This provides a new synthetic application of NHC-main group element complexes. Copyright

Full text of DOI:10.1002/chem.201101822

COMMUNICATION
DOI: 10.1002/chem.201101822
N-Heterocyclic Carbene-Catalyzed Hydrosilylation of Styryl and Propargylic
Alcohols with Dihydrosilanes
Qiwu Zhao,[a] Dennis P. Curran,[b] Max Malacria,[a] Louis Fensterbank,*[a]
Jean-Philippe Goddard,*[a] and Emmanuel Lacꢀte*[a, c]
The catalytic reduction of nonactivated olefins is an im-
portant synthetic process.[1] However, the principal methods
reported so far involve late transition metals as the active
species. Organocatalytic reductions have been reported,[2]
but generally involve electron-poor olefins and are best de-
scribed as the Michael addition of hydride. As a result, new
Scheme 1. The NHC-catalyzed reduction of olefins.
organocatalyzed reduction reactions would be very helpful.
We considered N-heterocyclic carbene (NHC)–borane com-
plexes as potential candidates for this role.[3] However, the
bonds, whereas the tBuOK-catalyzed reaction is limited to
some activated alkynes. We wanted to expand the reaction
scope to other alkynes and to alkenes. We reasoned that in-
tramolecular delivery of the hydride could be facilitated and
thus decided to examine olefins containing a hydroxyl group
in the allylic position, in the hope that NHC catalysis would
also be effective in the initial silylation step of the suggested
tandem reaction.[9]
À
NHC boron bond is generally too strong to allow decom-
plexation of the NHC from boron and catalytic turnover of
the NHCs.[4]
It has been suggested that tert-butoxide addition at silicon
triggers the hydrosilylation of alkynes through direct hy-
dride transfer from hypervalent silanes generated in situ.[5]
NHCs can also bind to silicon and generate hypervalent ad-
ducts that are known to transfer hydrides or nucleophiles to
carbonyl compounds.[6] It appeared to us that NHCs were
structurally and electronically diverse Lewis base candidates
to replace strong Brønsted bases such as tBuOK
(Scheme 1).
Carbenes A–F (dipp=2,6-diisopropylphenyl; Bn=benzyl)
were chosen as potential catalysts. This collection forms an
Hypervalent silicon compounds are also better Lewis
acids than regular silanes,[7] which may assist the hydrosilyla-
tion step by interacting with the p-system before the hydride
transfer.[8] From the perspective of this dual activation, the
versatility offered by NHCs was attractive. The hydrosilyla-
tion would be the first step towards the organocatalyzed
one-pot reduction of nonactivated carbon–carbon multiple
array of NHCs with a large structural, stereochemical, and
electronic diversity.
In a typical experiment, a solution of 4-phenyl-2-butenol
(1a) and Ph2SiH2 in DMF was added at room temperature
to a solution of catalyst A (10 mol%), which was prepared
separately by treatment of the corresponding azolium salt
with NaH in DMF. A solution of tetra-n-butylammonium
fluoride (TBAF) in THF was added after 6 h to quench all
traces of the silicon derivative. To our delight, this delivered
fully reduced 2a in 82% isolated yield (Table 1, entry 1)
after 30 min of stirring with TBAF.
[a] Dr. Q. Zhao, Prof. Dr. M. Malacria, Prof. Dr. L. Fensterbank,
Dr. J.-P. Goddard, Dr. E. Lacꢀte
Institut Parisien de Chimie Molꢁculaire (UMR CNRS 7201)-FR 2769
UPMC Univ Paris 06, 4 place Jussieu, C. 229, 75005 Paris (France)
Fax : (+33)1-44-27-73-60
E-mail: louis.fensterbank@upmc.fr
jean-philippe.goddard@upmc.fr
[b] Prof. Dr. D. P. Curran
Department of Chemistry, University of Pittsburgh
4200 Fifth Avenue, Pittsburgh, Pennsylvania 15260 (USA)
NHCs B and E led to similar results (Table 1, entries 2
and 5). On the other hand, the more electron donating
IBiox NHC (C)[10] gave only 20% conversion after 12 h, al-
though with no trace of degradation (Table 1, entry 3). Fur-
thermore, the reaction was not limited to NHCs, since cyclic
alkylaminocarbene (CAAC) F[11] also allowed a smooth re-
action (88%, Table 1, entry 6). Overall, the best yield was
[c] Dr. E. Lacꢀte
Present address: ICSN CNRS, Avenue de la Terrasse
91198 Gif-sur-Yvette Cedex (France)
E-mail: emmanuel.lacote@icsn.cnrs-gif.fr
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101822.
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Table 1. Optimization of the reduction of 1a.
Table 2. The reduction of 3-aryl allyl alcohols.
Entry
Carbene[a]
Silane
Conversion [%][b]
Yield [%]
Entry Substrate
R
R1
R2
Product Yield [%]
1
2
3
4
A
B
C
D
E
F
D
D
D
H2SiPh2
H2SiPh2
H2SiPh2
H2SiPh2
H2SiPh2
H2SiPh2
H2SiMePh
99
95
20
97
94
90
93
82
20
82
1[a]
2
3
1b
1c
1d
1e
1 f
1 f
1g
1h
1i
Ph
Ph
Ph
Ph
Ph
Ph
H
H
H
H
H
2b
2c
2d
2e
78
94
81
75
99
99
65
96
99
70
99
82
iPr
tBu
Ph
Me
Me
Me
Me
20[b]
92
4
5
85[b]
88
5[b]
6[b,c]
7[d]
8
Me 2 f
Me 2 f
6[c]
7
60[b]
75[b]
20[b]
4-(MeO)C6H4
4-ClC6H4
4-(CO2Me)C6H4 Me
2-furyl
3-pyridyl
vinyl
H
H
H
H
H
H
2g
2h
2i
2j
2k
8
9
H2Si
ACHTUNGERTN(NUNG tBu)2
ACHTUNGRTEN(NUNG HSiMe2)2O
9
10
11
12
1j
1k
1l
Me
Me
Ph
[a] Generated by deprotonation of the azolium salts with NaH. [b] Calcu-
lated from H NMR spectroscopy by using methyl cinnamate as the inter-
nal standard. [c] 20 mol% of NaH was used.
1
starting material
13
14
1m
1n
Me
H
starting material
reached with triazolidinene D,[12] which delivered a 92%
yield of 2a (Table 1, entry 4). Consequently, we selected this
NHC to assess the scope of the reduction reaction.
Ph
vinyl
H
2n
85
[a] Reaction took 12 h. [b] Reaction run on a 10 mmol scale. [c] 1 mol%
of D was used. [d] Reaction took 6 h.
Screening of the hydride source identified diphenylsilane
to be the best silane for the reaction (Table 1, entry 4 vs. 7–
9). It is worth noting that the very bulky di-tert-butylsilane
still gave a 75% yield of 2a (Table 1, entry 8), but only 20%
conversion was observed with tetramethyldisiloxane after
12 h (Table 1, entry 9). In addition, the best results were ob-
tained in DMF or DMSO and with NaH as the base used
for carbene generation (see the Supporting Information).
Control experiments showed that all reagents were re-
quired for conversion (see the Supporting Information). Use
of the methyl ether of 1a (Me-1a) resulted in no product
formation (the starting material was recovered intact). This
indicates that the OH group plays the pivotal role that we
had anticipated in the reaction (Scheme 2).
10). On the other hand, substrates with p-Cl (1h) and p-
CO2Me (1i) substituents or a pyridyl ring (1k) gave nearly
quantitative yields (Table 2, entries 8, 9, and 11). Pyridines
are strong transition metal ligands and thus 1k might not be
a suitable reagent for metal-mediated hydrogenation, which
is not a problem under the reported conditions.
Dienyl derivatives 1l and m were not reduced, suggesting
that an aryl substituent was required for the reduction reac-
tion (Table 2, entries 12 and 13). Finally, alcohol 1n yielded
85% of 2n, in which the arylolefin had been reduced with
complete chemoselectivity (Table 2, entry 14).
The reduction of 4-arylhomoallyl alcohol 1o was less effi-
cient, giving only a 50% yield of 2o after 6 h, together with
35% unreacted 1o (Scheme 3). High chemoselectivity was
again observed in the reduction of 1p, delivering a 78%
yield of 2p.
Propargylic alcohols were stereoselectively reduced to E
alkenes in the presence of one equivalent of diphenylsilane
(Table 3). For example, phenyl-substituted alkynes 3a and b
gave 1a and b in 92 and 78% yield, respectively (Table 3,
entries 1 and 2). The yield was again slightly reduced for pri-
mary alcohol 3b (compare with Table 2, entry 1).
Scheme 2. The reduction of the methyl ether of 1a.
With the optimized conditions in hands, we investigated
the scope of the reduction reaction with substrates 1b–n
(Table 2). The reaction tolerated a variety of alcohols
(Table 2, entries 1–6). In particular, primary (78% yield
after 12 h, Table 2, entry 1) and tertiary (Table 2, entries 5
and 6) styryl alcohols were efficiently reduced. The reduc-
tion of 1 f was carried out on a 10 mmol scale (vs. 1 mmol
for the standard test reactions) without loss of yield (99%).
On this scale a much lower loading of NHC D (1 mol%)
proved equally efficient (Table 2, entry 6).
The influence of the aryl group was examined next. Sub-
strates with a p-methoxy substituent (1g) or an electron-rich
heteroaromatic ring (1j) gave lower yield and, in the former
case, required a longer reaction time (Table 2, entries 7 and
Scheme 3. The reduction of a homoallylic alcohol and the chemoselectivi-
ty of the reaction in the presence of a second olefin.
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Chem. Eur. J. 2011, 17, 9911 – 9914

NHC-Catalyzed Hydrosilylation
COMMUNICATION
Table 3. Reduction of propargylic alcohols.
Reduction of trisubstituted allyl alcohol 6 delivered 48%
of the known compound anti-7[14] (70% conversion, insepa-
rable from recovered 6, 15:1 diastereoselectivity (d.s.),
Scheme 4c), suggesting that the reaction is sensitive to steric
hindrance. The relative configuration of 2a-D was deter-
mined to be syn by analogy.
Entry
Substrate
R1
R2
R3
t [h]
Product
Yield [%][c]
Taken together, these results show that the silane pro-
motes the reduction, which presumably also proceeds
through intramolecular hydrosilylation for alkenes. Howev-
er, all attempts to isolate the cyclic saturated siloxanes from
the reaction of alkenes failed due to the instability of these
heterocycles, which react further under NHC catalysis.[15]
In conclusion, we have introduced a new NHC-catalyzed
tandem reaction that has led to the chemoselective reduc-
tion of olefins and alkynes containing an a-hydroxyl sub-
stituent through silyl ether formation and intramolecular hy-
drosilylation. This adds to the armory of organic transforma-
tions and should be useful in organic synthesis. Further
work will focus on developing an asymmetric version of this
new reduction of carbon–carbon multiple bonds.
1
2
3
4
5
6
3a
3b
3c
3r
3s
3t
H
H
Me
H
Ph
Ph
Ph
Ph
H
2
2
3
3
3
6
1a
1b
1q
1l
1s
1t
92
78
-(CH2)5-
H
-(CH2)5-
-(CH2)5-
99
Ph
60[a]
72
nBu
61[a,b]
[a] The TBAF quench was carried out at 608C. [b] 38% of 3t was recov-
ered.
Gratifyingly, the reduction also worked with unsubstituted
propargyl alcohols (Table 3, entries 4 and 5), as well as with
a 3-alkyl-substituted propargyl alcohol (Table 3, entry 6).
However, reduction of n-butyl propargyl alcohol 3t was
much slower and the starting material was recovered in
38% yield after 6 h. In some cases, the silicon-containing ad-
ducts were more stable and quenching with TBAF had to be
carried out at 608C (Table 3, entries 4 and 6, see also
Scheme 4).
Experimental Section
General procedure for the reduction of styryl alcohols: Triazolium chlo-
ride salt (0.1 mmol, 24.4 mg, 0.1 equiv) was added to a suspension of
NaH (0.1 mmol, 4 mg, 60% in mineral oil, 0.1 equiv) in dry DMF (1 mL)
at room temperature to afford catalyst D. After stirring for 30 min, a so-
lution of H2SiPh2 (1 mmol, 203 mg, 1.1 equiv) and the substrate (1 mmol)
in dry DMF (1 mL) was added to the reaction mixture. The reaction was
monitored by TLC until no substrate was left. TBAF (1 mmol, 1 mL,
1.0m in THF, 1 equiv) was then added to the resulting mixture, which
was stirred for a further 30 min and quenched with H2O (10 mL). The
mixture was extracted with EtOAc (3ꢃ10 mL) and the combined organic
layers were washed with brine (10 mL), dried with anhydrous Na2SO4, fil-
tered, and the solution was concentrated under vacuum. The crude prod-
uct was purified by flash column chromatography over silica gel.
When TBAF was omitted after the reaction of 3r, we iso-
lated cyclic siloxane 4 in 60% yield (Scheme 4a). This
strongly suggests that the reaction proceeds through NHC-
catalyzed hydrosilylation of the initially formed silane 5.[13]
As expected, compound 5 must in turn be formed by an
NHC-catalyzed reaction.
The reduction of 1a has been conducted with D2SiPh2 (D
content: 97%). Alcohol 2a-D was obtained in 95% yield as
a single diastereomer (Scheme 4b). Deuterium incorpora-
tion (>95%) was observed exclusively at the homobenzylic
position and the relative configuration of 2a-D was found to
be syn (see below).
Acknowledgements
This work was supported by grants from UPMC, CNRS, IUF (L.F. and
M.M.), the US National Science Foundation and ANR (ANR 08-CEXC-
011–01 Borane). Technical assistance was generously offered through FR
2769.
Keywords: carbenes · hydrogenation · hydrosilylation. ·
organocatalysis · silicon
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Published online: July 27, 2011
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Chem. Eur. J. 2011, 17, 9911 – 9914