Angewandte
Chemie
precipitate a yellowish orange solid. The collected precipitates were
might be held between two PhGly phenyl rings of 3 through a
cation–p interaction.[12]
A plausible mechanism is shown in Scheme 3 (nonpro-
ductive and minor pathways are not considered). The reaction
dissolved in CH2Cl2 (40 mL), washed with water (50 mL 3), and
dried over MgSO4. After filtration and removal of the solvent, the
residue was purified by preparative TLC (silica gel, eluent: ethyl
acetate, Rf = 0.45–0.61). A further precipitation with a mixture of
CH2Cl2 (10 mL) and pentane (100 mL) afforded (S,S,S)-3 (light
yellow powder, 787 mg, 74%). M.p 2238C (decomp); 1H NMR
(400 MHz, CDCl3): d = 2.45 (brs, 2H, NHH), 3.23 (brs, 2H, NHH),
3.63 (t, 2H, J = 8.3 Hz, 2PhCH), 6.24 (d, 2H, J = 9.3 Hz, ArH), 6.50
(m, 6H, ArH), 6.71 (m, 6H, ArH), 7.07–7.67 (m, 24H, ArH),
8.06 ppm (m, 4H, ArH); 31P NMR (161.7 MHz, CDCl3): d = 52.3 ppm
(s); HRMS (ESI): m/z calcd for C60H48N2O4P2Ru: 1024.21494 [M]+;
found: 1024.21231.
General procedure for the cyanosilylation of aldehydes: Caution:
(CH3)3SiCN must be used in a well-ventilated hood because of its high
toxicity. (CH3)3SiCN (1.19 g, 12.0 mmol) and aqueous Li2CO3 (0.10m,
10 mL, 1.0 mmol) were placed in a 40 mL Schlenk flask in an Ar
atmosphere, and the mixture was stirred for 20 min at 258C. (C2H5)2O
(10 mL) and (S,S,S)-3 (20 mm in THF, 50 mL, 1.0 mmol) were added to
the pale yellow solution, and the mixture was stirred for 30 min. The
resulting yellow solution was cooled down to À788C, and then 1a
(1.05 g, 9.9 mmol) was added, and the mixture was stirred for 12h.
After evaporation of the solvent and the volatile compounds under
reduced pressure at ambient temperature, the residue was purified by
a short-path distillation to give (R)-2a (colorless oil, 1.99 g, 98%,
97% ee). B.p. 688C/0.08 mmHg; [a]2D3 = + 28.4 degcm3 gÀ1 dmÀ1 (c =
1.12gcm À3, CHCl3); 1H NMR (400 MHz, CDCl3): d = 0.23 (s, 9H,
Si(CH3)3), 5.50 (s, 1H, CHCN), 7.37–7.50 ppm (m, 5H, ArH);
13C NMR (100 MHz, CDCl3): d = À0.3, 63.9, 119.2, 126.3, 128.9,
129.3, 136.2 ppm; HRMS (EI): m/z calcd for C11H15NOSi: 205.0923
[M]+; found: 205.0931. The ee value of 2a was determined by GC
analysis: column, CP-Chirasil-Dex (0.32mm 25 m, depth of film =
0.25 mm, Varian); carrier gas: helium (72.0 kPa); column temp.:
1108C; injection temp.: 2208C; retention time (tR) of (R)-2a: 14.7 min
(98.4%), tR of (S)-2a: 14.3 min (1.6%). The absolute configuration
was determined after conversion into 2-hydroxy-2-phenylacetonitrile.
Scheme 3. Plausible mechanism for the cycnosilylation of aldehydes.
of (CH3)3SiCN and Li2CO3 is expected to give the pentacoor-
dinated Si species 4, since the less Lewis basic salts LiCl and
LiOTf promote the cyanation only to a small extent. In the
presence of an excess amount of (CH3)3SiCN, the formation
of another pentavalent Si compound 5 is possible from the
reaction of (CH3)3SiCN with LiCN; 5 is reversibly released
from the 4. The Ru complex 3 and the Li salt 4 or 5 then form
a chiral [3·Li] species 6. The [3·Li]+ ion acts as an efficient
chiral Lewis acid, while the nucleophilic [(CH3)3Si(NC)X]À
ion (X = OCO2Li, NC) donates CNÀ ions effectively.[13] Thus,
the chiral compound 6 reacts smoothly with an aldehyde to
afford a cyanohydrin silyl ether and a chiral salt 7,[14] which
readily reacts with (CH3)3SiCN to regenerate 6.
[a]D25 = + 45.4 degcm3 gÀ1 dmÀ1 (c = 1.40 gcmÀ3, CHCl3); lit.[2c] [a]D24
+ 36.8 degcm3 gÀ1 dmÀ1 (c = 2.0 gcmÀ3, CHCl3), 85% ee (R).
=
Received: March 31, 2008
Published online: July 23, 2008
In summary, we have reported the highly reactive and
enantioselective cyanosilylation of aldehydes that is catalyzed
by a new [Ru(phgly)2(binap)]/Li2CO3 system. The combina-
tion of a chiral Ru complex and the Li salt is crucial to achieve
high catalytic activity. The reaction can be carried out with an
S/C ratio as high as 100000:1. A series of aromatic, aliphatic,
and a,b-unsaturated aldehydes were converted into the
silylated cyanohydrins with up to 98% ee. The high activity
and robustness of the catalyst system are notable, although
the low reaction temperature (À78 to À708C) is a disadvan
tage from a practical viewpoint. The ESIMS and NMR
measurements suggest the formation of an active chiral Ru-Li
bimetallic complex in the reaction system. The detailed
reaction mechanism is currently being studied.
Keywords: aldehydes · asymmetric catalysis · cyanosilylation ·
lithium · ruthenium
.
Comprehensive Asymmetric Catalysis, Vol. 2 (Eds.: E. N. Jacob-
sen, A. Pfaltz, H. Yamamoto), Springer, Berlin, 1999, pp. 983 –
Catalysts in Organic Synthesis (Eds.: M. Shibasaki, Y. Yama-
moto), Wiley-VCH, Weinheim, 2004, pp. 103 – 120; h) J.-M.
j) T. R. J. Achard, L. A. Clutterbuck, M. North, Synlett 2005,
Experimental Section
Preparation of (S,S,S)-3: [{RuCl2(benzene)}2] (258 mg, 0.52 mmol)
and (S)-binap (661 mg, 1.06 mmol) were placed in a 100 mL Schlenk
flask. After replacing the air in the flask with argon, degassed DMF
(15 mL) was added, and the mixture was heated at 1008C for 10 min
with stirring to give a reddish brown solution.[7] After the solution had
cooled to 258C, a degassed solution of sodium (S)-phenylglycinate
(533 mg, 3.08 mmol) in CH3OH (30 mL) was added and the mixture
was stirred for 12h. Water (50 mL) was added to the solution to
[2] For selected leading studies, see: a) M. T. Reetz, F. Kunisch, P.
Angew. Chem. Int. Ed. 2008, 47, 6643 –6646
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim