Asymmetric hydrogenation of aromatic, aliphatic, and α,β- unsaturated acyl silanes catalyzed by tol-binap/pica ruthenium(II) complexes: Practical synthesis of optically active α-hydroxysilanes

Article abstract of DOI:10.1002/anie.200704696

(Chemical Equation Presented) A catalytic system of Ru^II complex (see scheme; Ar = 4-CH₃C₆H₄; R = H, t-C ₄H₉) and t-C₄H₉OK or NaBH ₄ activator has been used in the hydrogenation of aromatic and aliphatic acyl silanes to give α-hydroxysilanes with high enantioselectivity (R¹ = aryl, alkyl, alkenyl; R² = t-C₄H₉, C₆H₅). Optically active allylic α-hydroxysilanes are obtained in the 1,2-reduction of α,β-unsaturated acyl silanes. These chiral α-hydroxysilanes are converted into 4-substituted 2-cyclopentenones without loss of enantioselectivity.

Full text of DOI:10.1002/anie.200704696

Communications
DOI: 10.1002/anie.200704696
Asymmetric Hydrogenation
Asymmetric Hydrogenation of Aromatic, Aliphatic, and a,b-
Unsaturated Acyl Silanes Catalyzed by Tol-binap/Pica Ruthenium(II)
Complexes: Practical Synthesis of Optically Active a-Hydroxysilanes**
Noriyoshi Arai, Ken Suzuki, Satoshi Sugizaki, Hiroko Sorimachi, and Takeshi Ohkuma*
Optically active a-hydroxysilanes are regarded as a kind of
chiral organometallic compound with a functional group.
These molecules and their derivatives have been utilized for
Benzoyl-tert-butyldimethylsilane (1a; Scheme 1), pre-
pared by a reported procedure,[3c] was selected as a typical
substrate for screening the reaction conditions. Hydrogena-
tion of 1a (0.42 g, 0.48m) in ethanol with [RuCl2{(S)-Tol-
À
stereocontrolled C C bond formation and rearrangement,
which resulted in a variety of chiral organic compounds.[1–5]
Asymmetric reduction of acyl silanes is a straightforward
method to produce the chiral secondary a-hydroxysilanes.
Hydroboration
with
B-chlorodiisopinocampheylborane
(Ipc2BCl) is the most widely used method for this important
transformation.[1,3a,4d–h,5–7] The chiral oxazaborolidine reagent
is effective for the reaction of acetylenic acyl silanes.[4i,j,5]
A
chiral lithium amide reduces a,b-unsaturated acyl silanes with
excellent enantioselectivity.[8] However, these procedures
require more than one equivalent of the chiral reagent to
the substrate.
A recently reported transfer hydrogenation catalyzed by
an arene/N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine
(Ts-dpen) RuII complex using 2-propanol as a reducing agent
is effective for aromatic acyl silanes.[3c] Although this is the
only catalytic chemical process for this reaction, the substrate-
to-catalyst molar ratio (S/C) of 33–200 is not satisfactory for
practical use. Asymmetric microbial reductions are reported
to exhibit high stereoselectivity merely for specific acyl silane
substrates.[3b,9] Thus, the development of an efficient proce-
dure for the catalytic asymmetric reduction of acyl silanes is
highly desirable. Hydrogenation possesses advantages over
many other reduction methods from the atom-economical
and practical points of view.[10]
Herein, we disclose for the first time the highly enantio-
selective hydrogenation of acyl silanes catalyzed by Tol-
binap/pica RuII complexes.[11,12] The reaction is conducted
with a S/C value as high as 10000 under 10 atm of H2. A series
of benzylic, aliphatic, and allylic a-hydroxysilanes is obtained
in up to 99% ee.
Scheme 1. Asymmetric hydrogenation of acyl silanes.
binap}(pica)] [(S)-3a;[13] 0.94 mg, 0.24 mm, S/C = 2000] and t-
C4H9OK (1.0m in tert-butyl alcohol, 40 mL, 10 mm) at 248C
under H2 (10 atm) was completed in 1 h to afford the (R)-a-
hydroxysilane (R)-2a in 96% ee and 96% yield of isolated
product (Scheme 1 and Table 1, entry 1). When the concen-
tration of base was increased to 50 mm, the yield of 2a was
slightly decreased with formation of the benzyl silyl ether as a
by-product (Table 1, entry 2). This is because cleavage of the
À
Si C(OH) bond of 2a through a Brook-type rearrangement
occurred under the conditions of higher base concentra-
[*] Prof. Dr. N. Arai, K. Suzuki, S. Sugizaki, H. Sorimachi,
Prof. Dr. T. Ohkuma
tion.[14]
Division of Chemical Process Engineering
Graduate School of Engineering, Hokkaido University
Sapporo 060-8628 (Japan)
Fax: (+81)11-706-6598
E-mail: ohkuma@eng.hokudai.ac.jp
The 1m m concentration of base was not enough to
activate the precatalyst 3a for conversion to the active RuH
species (Table 1, entry 3).[11,15] KOH was usable instead of t-
C4H9OK (Table 1, entry 4), but employment of the less basic
K2CO3 or DBU decreased the reactivity, even at a higher
concentration of base (40 mm; Table 1, entries 5 and 6).
NaBH4, a metal hydride, also activated 3a, although the
efficiency was much less than that of t-C4H9OK (Table 1,
entry 7).[11,16] The Ru complex 3b with 4,5-di-tert-butylpicolyl-
[**] This work was supported by a Grant-in-Aid from the Japan Society
for the Promotion of Science (JSPS) (No. 18350046). Tol-
binap=2,2’-bis(di-4-tolylphosphanyl)-1,1’-binaphthyl; pica=a-
picolylamine.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Chemie
Table 1: Asymmetric hydrogenation of 1a.[a]
Table 2: Asymmetric hydrogenation of acyl silanes.[a]
Entry Ru catalyst S/C[b] Activator [mm] t [h] Yield [%][c] ee [%][d]
(R)-2
1
Ru catalyst
S/C[b]
t [h]
Yield [%][c]
ee [%][d]
1
2
3
4
5
6
7
8
9
(S)-3a
(S)-3a
(S)-3a
(S)-3a
(S)-3a
(S)-3a
(S)-3a
(S)-3b
[i]
2000 tBuOK (10)
2000 tBuOK (50)
1000 tBuOK (1)
1600 KOH (10)
30 K2CO3 (40)
1
1
1
1
6
6
10
6
96
96
92[e]
<1[f]
94
95
1a[e]
1b
1c
1d
1e
1 f
(S)-3a
(S)-3a[f]
(S)-3a
(S)-3a
(S)-3a
(S)-3a
(S)-3b
(S)-3a[g]
(S)-3a
(S)-3a
(S)-3b[h]
(S)-3a
(S)-3a
(S)-3a
(S)-3a
(S)-3a
(S)-3a
10000
900
1000
500
1600
2000
800
1100
600
1200
500
900
600
600
2.5
1
3.5
5
1.5
3
3
1
1
6
6
4
1
1.5
1
1
96
80
90
90
96
88
99
85
88
99
97
77
83
94
84
82[i]
54
95
96
96
96
96
98
98
93
97
91
95
99
98
99
89
87[j]
90
nd[g]
96
92
94
94
91
95
96
97
400 DBU (40)[h]
300 NaBH4 (10)
1200 tBuOK (10)
500 tBuOK (20)
97
1 f
3
1
nd[g]
1g
1h
1i
1i
1j
1k
1l
1m
1n
1o
[a] Unless otherwise stated, reactions were conducted using 1.0–
2.1 mmol of 1a (0.4–0.5m) in ethanol containing a Ru catalyst and an
activator at 20–258C under 10 atm of H2. [b] Substrate/catalyst molar
ratio. [c] Yield of isolated (R)-2a. [d] Data for (R)-2a determined by chiral
HPLC analysis. [e] A benzyl silyl ether was obtained as a by-product.
[f] Conversion determined by 1H NMR analysis. [g] Not determined.
[h] DBU=1,8-diazabicyclo[5.4.0]undec-7-ene. [i] [RuCl2{(S)-binap}{(S,S)-
dpen}] was used as a catalyst in 2-propanol.
350
300
350
1
[a] Unless otherwise stated, reactions were conducted using 0.9–
1.4 mmol of ketone 1 (0.4–0.7m) in ethanol containing a Ru catalyst 3
and t-C4H9OK (10 mm) at 20–268C under 10 atm of H2. [b] Substrate/
catalyst molar ratio. [c] Yield of isolated product. [d] Chiral GC or HPLC
analysis. [e] Reaction using 18.4 mmol (4.05 g) of 1a. [f] The concen-
tration of t-C4H9OK was 5 mm. [g] NaBH4 (15 mm) was used as catalyst
activator. [h] CH3OH/t-C4H9OH (3:7) was used as solvent. [i] Deter-
mined by 1H NMR analysis. [j] Determined after conversion to the N-
phenylcarbamate.
amine (DTB-pica) instead of the original pica showed
comparably high enantioselectivity, while the activity was
relatively lower (Table 1, entry 8).
Notably, a catalyst system consisting of trans-[RuCl2{(S)-
binap}{(S,S)-dpen}] and t-C4H9OK in 2-propanol, which
shows high activity and enantioselectivity for the hydro-
genation of simple ketones, was virtually inert for this
transformation (Table 1, entry 9).[17,18] The flat pyridine
moiety of the pica ligand is crucial to achieve high reactivity
for the hydrogenation of sterically hindered acyl silanes. Thus,
we chose the following standard reaction conditions: preca-
talyst, 3; activator, t-C4H9OK (10 mm); solvent, ethanol; H2
pressure, 10 atm; temperature, 20–258C.
The catalyst system hydrogenated aromatic, aliphatic, and
a,b-unsaturated acyl silanes with high reactivity and enantio-
selectivity. Absolute configurations of new hydroxysilanes
were estimated by a modified Mosher method (see the
Supporting Information).[19] Hydrogenation of 1a (0.75m)
with (S,S)-3a at a S/C value of 10000 in ethanol containing t-
C4H9OK (10 mm) at 238C under H2 (10 atm) produced (R)-2a
in 95% ee and 96% yield of isolated product (Table 2).
Although benzoyldimethylphenylsilane (1b) is more base-
labile than 1a, it was also hydrogenated with high enantio-
selectivity under a lower concentration of base (5 mm).
Benzoyl substrates with an electron-donating CH3O
group or an electron-attracting F atom at the meta or para
position of the phenyl ring (1c–e) were converted to the a-
hydroxysilanes 2c–e in the same ee of 96%. The electronic
features of the aromatic moieties did not affect the enantio-
selectivity, while introduction of the electron-withdrawing
function accelerated the reaction rate. Hydrogenation of
acetyl-tert-butyldimethylsilane (1 f), a simple aliphatic sub-
strate, mediated by (S)-3a in base-containing ethanol
afforded the (R)-a-hydroxysilane (R)-2 f in 98% ee. The
sense of enantioselection was the same as that in the reaction
of benzoylsilane 1a. The Tol-binap/DTB-pica Ru complex 3b
showed the same enantioselectivity.
3a using NaBH4 (15 mm) as an activator to give (R)-2g in
93% ee and 85% yield of isolated product. Hydrogenation of
pentanoyldimethylphenylsilane (1h) afforded the hydroxysi-
lane 2h in 97% ee; t-C4H9OK (10 mm) could be used as an
activator in this reaction. Hexanoyl-tert-butyldimethylsilane
(1i) was hydrogenated with 3a in 91% optical yield. When the
reaction was conducted with complex 3b, the optical yield was
increased to 95%. Use of a CH3OH/t-C4H9OH (3:7) mixed
solvent gave slightly better stereoselectivity. The “remote
effect” of tert-butyl groups on the pyridine ring (see the
catalyst structure) may originate from suitable fixation of the
catalyst conformation for enantioface selection of this sub-
strate. Hydrogenation of secondary alkyl acyl silanes 1j–l in
the presence of (S)-3a afforded the (R)-a-hydroxysilanes (R)-
2j–l in > 98% ee. Tri-n-butyl(propanoyl)stannane,[20] a tin
analogue of 1, was not converted under the standard hydro-
genation conditions.
Complex 3a also effects asymmetric hydrogenation of
a,b-unsaturated acyl silanes to the optically active allylic a-
hydroxysilanes, although these conjugated acyl silanes readily
undergo 1,4-reduction in general.[1,3c] Hydrogenation of (E)-
2-hexenoyl-tert-butyldimethylsilane (1m) in the presence of
(S)-3a (S/C = 350) and t-C4H9OK (10 mm) in ethanol under
H2 (10 atm) was completed in 1 h to afford the R allylic a-
hydroxysilane (R)-2m in 89% ee and 84% yield of isolated
product (Table 2). The 1,2-reduction occurred exclusively
over the 1,4-reduction, while conjugate addition of ethoxide
occurred as a side reaction in less than 5% yield. Such
predominant 1,2-reduction selectivity for a,b-unsaturated
acyl silanes is achieved only by this hydrogenation catalyzed
Acetyldimethylphenylsilane (1g), which is extremely
labile in basic alcoholic media, was hydrogenated with (S)-
by
a
Tol-binap/pica Ru complex, hydroboration with
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Communications
Ipc2BCl,[1,3a,4d–h] and a chiral lithium amide[8] reduction. In the
silica-gel column chromatography with ethyl acetate/hexane (1:20) as
eluent to give (R)-2a (faintly yellow oil, 3.94 g, 96% yield, 95% ee).
The ee of 2a was determined by HPLC analysis: column, Chiral-
same manner, hydrogenation of (E)-2-decenoyl-tert-butyldi-
methylsilane (1n) afforded (R)-2n in 87% ee and 82% yield.
When (E)-2-hexenoyldimethylphenylsilane (1o) was hydro-
genated with (S)-3a under the standard conditions, (R)-2o
was obtained in 90% ee and 54% yield accompanied by
messy by-products as a result of the extreme lability of 1o.[21]
The chiral allylic a-hydroxysilane (R)-2n was readily
converted to (R)-4-n-heptyl-2-pentenone [(R)-6n][22] through
the Ireland–Claisen rearrangement[4a] without loss of enan-
tioselectivity (Scheme 2). Acetylation of (R)-2n in 87% ee
cel OD-H; eluent, hexane/2-propanol (9:1); flow rate, 0.5 mLminÀ1
;
column temperature, 408C; retention time (tR) of (R)-2a, 17.5 min
(97.6%); tR of (S)-2a, 11.4 min (2.4%). [a]2D0 = + 95.4 (c = 1.08,
CH2Cl2); literature[3c] [a]D24 = À81.6 (c = 1.02, CH2Cl2), 82% ee (S).
Received: October 11, 2007
Published online: January 21, 2008
Keywords: asymmetric catalysis · enantioselectivity ·
.
hydrogenation · ruthenium · silanes
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diisopropylamide; TBSCl=tert-butyldimethylsilyl chloride; HMPA=
hexamethylphosphoramide.
under standard conditions gave (R)-4n in 92% yield.
Deprotonation of 4n with LDA followed by treatment with
t-C4H9(CH3)2SiCl in the presence of HMPA at À788C,
warming to room temperature, and hydrolysis with an acid
afforded the chiral 5-silyl-4-pentenonic acid (R)-5n in 82%
yield. Intramolecular vinylation of the acid anhydride of 5n
mediated by AlCl3 resulted in the chiral enone (R)-6n in
86% ee and 79% yield (see the Supporting Information).[23]
In conclusion, we report here the first example of the
highly reactive and enantioselective hydrogenation of acyl
silanes catalyzed by Tol-binap/pica RuII complexes 3 with a
base or a metal hydride activator in ethanol. A series of
aromatic, aliphatic, and a,b-unsaturated acyl silanes is con-
verted to the corresponding a-hydroxysilanes in excellent ee.
Allylic a-hydroxysilanes with high enantio- and regioselec-
tivity are obtained in the reaction of a,b-unsaturated com-
pounds. Thus, this method provides a new, efficient, and
practical route to producing chiral silane compounds.
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Experimental Section
General procedure for hydrogenation of acyl silanes: Hydrogenation
of 1a illustrates the typical reaction procedure using standard Schlenk
techniques. A degassed (three freeze–thaw cycles) solution of solid
(S)-3a (1.7 mg, 1.8 mmol), t-C4H9OK (24.5 mg, 0.22 mmol), and 1a
(4.05 g, 18.4 mmol) in ethanol (20 mL) was placed in a 100-mL glass
autoclave equipped with a teflon-coated magnetic stirring bar.
Hydrogen was introduced into the autoclave at a pressure of
10 atm, and then the reaction mixture was vigorously stirred at
238C for 2.5 h. After carefully venting the hydrogen gas, the solvent
was removed under reduced pressure. The residue was purified by
[12] For
transfer
hydrogenation
of
ketones
with
[RuCl2(diphosphine)(pica)], see: W. Baratta, E. Herdtweck, K.
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[13] Complex 3a was obtained as a mixture of five diastereomers (see
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acyl silane hydrogenation were independent of the initial
diastereomeric ratio.
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