Self-regeneration of a silylium ion catalyst in carbonyl reduction

Article abstract of DOI:10.1039/c0cc02139c

The silylium ion-catalysed reduction of carbonyl compounds to the alcohol oxidation level is accomplished by exploiting the unique reactivity of a ferrocenyl-substituted silane.

Full text of DOI:10.1039/c0cc02139c

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Self-regeneration of a silylium ion catalyst in carbonyl reductionwz
Kristine Muther and Martin Oestreich*
¨
Received 28th June 2010, Accepted 10th August 2010
DOI: 10.1039/c0cc02139c
The silylium ion-catalysed reduction of carbonyl compounds to
the alcohol oxidation level is accomplished by exploiting the
unique reactivity of a ferrocenyl-substituted silane.
The crux of silylium ion catalysis is to keep the extremely
potent Lewis acid, that is the trivalent silicon cation1 itself,
alive. Strongly binding Lewis bases must be scrupulously
avoided, and any Lewis pair formation must be reversible.
There are a few examples of silylium ion-catalysed processes,
from which the silicon cation emerges indeed unchanged,2 but
there are also efficient catalytic reactions involving covalent
bond formation to the silicon atom of the silylium ion. To
maintain turnover in those, a silylium ion must be regenerated
from a suitable precursor in a subsequent step. That vital
self-regeneration was established by Lambert et al. in a
silylium ion-catalysed alkene hydrosilylation.3
A more
Scheme 1 The Kira–Piers mechanism of the silylium ion-catalysed
deoxygenation of carbonyl compounds (Do = donor and R = Et).
Counteranion [BAr4]ꢀ is omitted for clarity (Ar = 3,5-bis(trifluoromethyl)
phenyl8 or pentafluorophenyl9).
prominent example is the silylium ion-catalysed C–F bond
activation recently disclosed by Ozerov et al., a formal
Si–H/C–F metathesis.4 Both reactions, while appearing
unrelated, share however the regeneration of the solvent-
stabilised silylium ion catalyst, namely the hydride abstraction
from a silane5 by an intermediate carbenium ion.6
The situation is different in the silylium ion-catalysed
reduction of carbonyl compounds,7 resulting in deoxygenation
rather than reduction to the alcohol oxidation level. Kira et al.
had investigated that unexpected outcome almost two decades
ago,8 and an investigation by Piers et al. later corroborated the
suggested mechanism (Scheme 1).9 The catalysis commences
with the formation of silyloxycarbenium (or silylcarboxonium)
ion 3 through coordination of the Lewis basic carbonyl oxygen
of 2 to donor-stabilised silylium ion 1. The hydride affinity of
3 is not as pronounced as that of the previously discussed
carbenium ions,10 and hydride abstraction from silane 4 will
be less facile. Piers et al. had reasoned though that hydride
transfer is likely to be assisted by the oxygen atom in 3,9
proceeding through tentative transition state 5 (3 - 6).
Disiloxane 7 is a good leaving group, and oxonium ion 6
dissociates to produce carbenium ion 8, which in turn is
sufficiently reactive to directly regenerate silylium ion 1 upon
reaction with 4 (8 - 9). The net deoxygenation (2 - 9) was
experimentally verified at room temperature for benzophenone8
and acetophenone9 as substrates.11
Scheme 2 Facile generation of ferrocene-stabilised silylium ion at low
temperature.13
Aside from the hydride affinity of an intermediate silyl-
carboxonium ion, the hydride donor strength of the silane is
equally critical. Our laboratory recently introduced ferrocene-
stabilised silylium ion 11,12,13 which was accessed by an
exceptionally rapid Bartlett–Condon–Schneider hydride
transfer14 (10 - 11, Scheme 2).
We then anticipated that the unusual hydridic character of
10 could allow for the reduction of silylcarboxonium ion 12
without concomitant oxonium ion formation (12 - 13,
Scheme 3). Both the stabilisation of the trivalent silicon cation
through the ferrocenyl substituent and the steric bulk of the
reaction partners might account for immediate regeneration of
‘‘free’’ 11. In this communication, we report the silylium ion-
catalysed reduction of carbonyl compounds, which hinges
upon the self-regeneration of a catalytically active silicon
cation by that mechanism (2 - 13, Scheme 3).
Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat,
¨ ¨
Corrensstrasse 40, D-48149 Munster, Germany.
¨
E-mail: martin.oestreich@uni-muenster.de;
Fax: +49 (0)25183-36501; Tel: +49 (0)25183-33271
w This article is part of the ‘Emerging Investigators’ themed issue for
ChemComm.
z Electronic supplementary information (ESI) available: Preparation
and characterisation data as well as 1H, 13C, 19F and 29Si NMR
spectra of all new compounds. See DOI: 10.1039/c0cc02139c
In light of the deoxygenation observed for aryl-substituted
ketones (vide supra),8,9 we began our screening using these
carbonyl compounds. Catalyst 11 was generated in CH2Cl2 at
ꢀ60 1C from [Ph3C]+[B(C6F5)4]ꢀ (5.0 mol%) and a slight
excess of 10 prior to addition of the reactants (Scheme 4).y
The reaction of acetophenone was smooth, affording the
c
334 Chem. Commun., 2011, 47, 334–336
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Scheme 5 Deoxygenation—Friedel–Crafts sequence {[Ph3C]+[B(C6F5)4]ꢀ
(5.0 mol%) was used to initiate the reaction}.
the relative hydride affinities of silylcarboxonium ions 12a and
12b (cf. Scheme 3): two phenyl groups (as in 12b) lend more
stabilization to such intermediates than just one (as in 12a).
The same rationale applies to naphthyl- and other electron-
rich phenyl-substituted ketones (2c–2f, Table 1, entries 3–6).
Only 2g–2i displayed the reactivity of 2a (2g–2i - 13g–13i,
Table 1, entries 7–9), and the slightly more hindered substrates
2g and 2i showed a low level of diastereocontrol. The lack
of facial selectivity might be interpreted in support of the
hypothesis that silicon-to-carbon hydride transfer passes
through an acyclic transition state (12 - 13, Scheme 3),15
not involving the oxygen atom (cf. 4 - 5 - 6, Scheme 1).
The poor reactivity of ketones 2b–2f might be overcome at
elevated reaction temperatures. The upper temperature limit of
ꢀ30 1C is set by the chemical stability of silylium ion 11 in
CH2Cl2.12 However, even an increase from ꢀ60 1C to ꢀ45 1C
partially resulted in ipso alkylation of the ferrocene in several
cases (10 - 14, Scheme 5). We further analyzed this finding in
the reduction of acetophenone at ꢀ45 1C: the silicon ether
formed in the carbonyl-to-hydroxy reduction (2a - 13a) was
readily converted into the alkylated ferrocene in 55% isolated
yield (13a - 14a). Treatment of an independently prepared
sample of 13a under the standard reaction conditions at ꢀ45 1C
afforded 14a in 38% isolated yield. This set of data indicates to
us that reduction occurs at higher reaction temperatures,
followed by carbenium ion formation (cf. Scheme 1). The
thus formed strong electrophile is then attacked by any of
the present silylated ferrocenes, e.g., 13 or (tBuFcMeSi)2O
(Fc = ferrocenyl), to undergo a Friedel–Crafts reaction.
These experiments clearly reveal that the stability or, more
precisely, the hydride affinity of the intermediate silylcarboxonium
ion profoundly effects this catalysis. Electron-rich 4-MeOC6H4
(as in 2e) is deactivating, electron-poor C6F5 (as in 2h) is
activating (Table 1, entries 5 and 8). The majority of aryl-
substituted substrates forms unreactive 12 (Scheme 3 and
Table 1). Based on this understanding, we expected 12 derived
from purely alkyl-substituted carbonyls to be less stable and
more reactive, and this is indeed the case. All dialkyl ketones
surveyed performed very well (2j–2p - 13j–13p, Table 2).
Diastereoselectivity was again low (vide supra).15
Scheme 3 Proposed silylium ion-catalysed reduction of carbonyl
compounds. Counteranion [B(C6F5)4]ꢀ is omitted for clarity.
Scheme 4 Silylium ion-catalysed carbonyl reduction.
Table 1 Reduction of alkyl aryl and diaryl ketones 2a–2ia
Carbonyl compound 2
Silicon ether 13
No.
R1
R2
No. drb
Yieldc (%)
Entry
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2h
2i
Ph
Ph
Me
Ph
13a
13b
13c
13d
13e
13f
13g
13h
13i
51 : 49 82
—
—
—
—
No reaction
Tracesd
2-C10H7
1-C10H7
4-MeOC6H4
4-MeC6H4
2-ClC6H4
C6F5
Me
Me
Me
Me
Me
Me
Et
No reactione
No reaction
52 : 48 10d
78 : 22 97
52 : 48 85
78 : 22 82
Ph
a
All reactions were conducted using [Ph3C]+[B(C6F5)4]ꢀ (5.0 mol%) to
generate 11, and silane (1.2 equiv.) and carbonyl compound (1.0 equiv.)
with a ketone concentration of 0.2 M in CH2Cl2 at ꢀ60 1C. Reactions
b
were terminated after 212 h. Diastereomeric ratio determined by GLC
These results are in contrast to the work of Kira et al.;8
silylium ion-catalysed reduction of cyclododecanone (2l)
afforded neither 13l nor cyclododecane but cyclododecene in
high yield.11
c
analysis prior to purification. Combined yield of analytically pure
d
mixture of diastereomers after flash chromatography. Details are
e
discussed in the text (Scheme 5). Poor reactivity also due to steric
factors.
To recap, we disclosed here an unprecedented silylium ion-
catalysed reduction of carbonyl compounds, in which any
of the previously reported deoxygenation pathways8,9 are
suppressed. The hydride donor strength of our ferrocenyl-
substituted silane is the decisive feature, allowing for the
silicon ether in good yield (2a - 13a, Table 1, entry 1). No
defunctionalisation was detected. Conversely, benzophenone
was not participating in the catalysis at all (2b, Table 1,
entry 2). This rather unexpected result might be explained by
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 334–336 335

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Table 2 Reduction of dialkyl ketones 2j–2pa
Carbonyl compound 2 Silicon ether 13
(b) C. A. Reed, Acc. Chem. Res., 1998, 31, 325–332; (c) for a
recently developed silylium ion, see: S. Duttwyler, Q.-Q. Do,
A. Linden, K. K. Baldridge and J. S. Siegel, Angew. Chem., Int.
Ed., 2008, 47, 1719–1722.
2 H. F. T. Klare and M. Oestreich, Dalton Trans., 2010, 39, DOI:
10.1039/c003097j (Advance Article on April 19, 2010) and
references cited therein.
3 J. B. Lambert, Y. Zhao and H. Wu, J. Org. Chem., 1999, 64,
2729–2736.
4 (a) V. J. Scott, R. C¸ elenligil-C¸ etin and O. V. Ozerov, J. Am. Chem.
No.
R1
R2
No.
drb
Yieldc (%)
Entry
1
2
3
4
5
6
7
2j
2k
2l
2m
2n
2o
2p
–(CH2)4–
–(CH2)5–
13j
13k
13l
13m
13n
13o
13p
—
—
—
—
50 : 50
60 : 40
58 : 42
85
95
86
79
44
79
77
–(CH2)11
Et
Et
–
Et
Me
Me
Me
Soc., 2005, 127, 2852–2853; (b) R. Panisch, M. Bolte and
T. Muller, J. Am. Chem. Soc., 2006, 128, 9676–9682;
iBu
tBu
¨
(c) C. Douvris, C. M. Nagaraja, C.-H. Chen, B. M. Foxman and
O. V. Ozerov, J. Am. Chem. Soc., 2010, 132, 4946–4953.
5 H. Mayr, N. Basso and G. Hagen, J. Am. Chem. Soc., 1992, 114,
3060–3066.
a
All reactions were conducted using [Ph3C]+[B(C6F5)4]ꢀ (5.0 mol%)
to generate 11, and silane (1.2 equiv.) and carbonyl compound
(1.0 equiv.) with a ketone concentration of 0.2 M in CH2Cl2 at ꢀ60 1C.
b
Reactions were terminated after 221 h. Diastereomeric ratio determined by
6 Mukaiyama-type processes, where a trivalent silicon cation is
transferred between Lewis basic oxygen sites, are borderline cases.
(a) [Et3Si(toluene)]+[B(C6F5)4]–-initiated Mukaiyama aldol reac-
tion: K. Hara, R. Akiyama and M. Sawamura, Org. Lett., 2005, 7,
5621–5623; (b) [Ph3C]+[B(C6F5)4]–-initiated polymerisation:
Y. Zhang and E. Y.-X. Chen, Macromolecules, 2008, 41, 36–42.
7 For recent reviews of carbonyl hydrosilylation, see: (a) S. Rendler
and M. Oestreich, in Modern Reduction Methods, ed.
P. G. Andersson and I. J. Munslow, Wiley, Weinheim, 2008,
pp. 183–207; (b) G. L. Larson and J. L. Fry, in Organic Reactions,
ed. S. E. Denmark, Wiley, Hoboken, New Jersey, 2008, pp. 1–735.
8 M. Kira, T. Hino and H. Sakurai, Chem. Lett., 1992, 555–558.
9 D. J. Parks, J. M. Blackwell and W. E. Piers, J. Org. Chem., 2000,
65, 3090–3098.
c
GLC analysis prior to purification. Combined yield of analytically pure
mixture of diastereomers after flash chromatography.
hydride transfer onto rather unreactive silylcarboxonium ions
at low temperature. The reduction step itself regenerates the
catalytically active trivalent silicon cation.
K.M. thanks the Studienstiftung des deutschen Volkes for a
predoctoral fellowship (2009–2011). K.M. is a member of the
International Research Training Group Munster–Nagoya
¨
(GRK 1143 of the Deutsche Forschungsgemeinschaft).
10 Heteroatom-stabilisation of carbenium ions as in silylcarboxonium
ions is expected to be significant. We sincerely thank Professor
Ernst-Ulrich Wurthwein for a preliminary quantum-chemical
¨
Notes and references
y General procedure for the silylium ion-catalysed carbonyl reduction: in
a glove-box, a flame-dried 10 mL Schlenk tube equipped with a
magnetic stir bar is charged with [Ph3C]+[B(C6F5)4]ꢀ (9.2 mg,
0.010 mmol, 5.0 mol%). The Schlenk tube is transferred to a fume
cupboard and connected to an argon–vacuum manifold. Addition of
dry CH2Cl2 (1.0 mL) results in a yellow solution, which is subsequently
cooled to ꢀ60 1C using an ethanol cooling bath and a cryostat. After
silane addition (10, 11 mg, 0.040 mmol, 0.20 equiv.), the now brown
solution is stirred for 10 min, followed by successive addition of the
carbonyl compound 2 (0.20 mmol, 1.0 equiv.) and the silane 10 (57 mg,
0.20 mmol, 1.0 equiv.) dissolved in dry CH2Cl2 (0.5 mL each). The
reaction mixture is maintained at ꢀ60 1C for 212 h, and the reaction is
then terminated by the addition of dry hexane (10 mL), pre-cooled to
ꢀ60 1C. Filtration over a small pad of Celites and evaporation of the
solvents under reduced pressure affords crude 13, which is further
purified by flash chromatography on silica gel using cyclohexane as
eluent. The diastereomeric ratio is determined by GLC analysis prior
to purification.
analysis of their hydride affinities.
11 It is important to note that Kira et al. observed alkene instead of
alkane formation with cyclododecanone, indicating a b-elimina-
tion of the intermediate oxonium ion (cf. 6 in Scheme 1).8.
12 (a) H. F. T. Klare, K. Bergander and M. Oestreich, Angew. Chem.,
Int. Ed., 2009, 48, 9077–9079; (b) S. C. Bourke, M. J. MacLachlan,
A. J. Lough and I. Manners, Chem.–Eur. J., 2005, 11, 1989–2000.
13 The drawing of 11 is likely to be an oversimplified representation of
the true bonding situation. We are currently working on the
structural characterisation of 11, supported by quantum-chemical
calculations (in collaboration with S. Grimme and C. Muck-
¨
Lichtenfeld). For a related investigation in boron chemistry, see:
M. Scheibitz, M. Bolte, J. W. Bats, H.-W. Lerner, I. Nowik,
R. H. Herber, A. Krapp, M. Lein, M. C. Holthausen and
M. Wagner, Chem.–Eur. J., 2005, 11, 584–603.
14 P. D. Bartlett, F. E. Condon and A. Schneider, J. Am. Chem. Soc.,
1944, 66, 1531–1539.
15 Stereoinduction in the borohydride reduction of silicon-stereogenic
silylcarboxonium ions was also found to be low: D. T. Hog and
M. Oestreich, Eur. J. Org. Chem., 2009, 5047–5056.
1 For authoritative reviews, see: (a) J. B. Lambert, Y. Zhao and
S. M. Zhang, J. Phys. Org. Chem., 2001, 14, 370–379;
c
336 Chem. Commun., 2011, 47, 334–336
This journal is The Royal Society of Chemistry 2011