A novel 1-glycosyl-1H-triazole-based P,N ligand for rhodium-catalyzed asymmetric hydrosilylation of ketones

Article abstract of DOI:10.1002/hlca.201000093

A novel class of chiral glycosyl-triazole-based P,N ligands were synthesized by 'click chemistry' and were applied to the Rh-catalyzed asymmetric hydrosilylation of a range of substituted acetophenones. Enantioselective hydrosilylation of acetophenone gav

Full text of DOI:10.1002/hlca.201000093

Helvetica Chimica Acta – Vol. 93 (2010)
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A Novel 1-Glycosyl-1H-triazole-Based P,N Ligand for Rhodium-Catalyzed
Asymmetric Hydrosilylation of Ketones
by Chao Shena)b), Peng-Fei Zhang*a), and Xin-Zhi Chen*b)
a) College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University,
Hangzhou 310036, P. R. China (phone: þ 86-571-85996586; fax: þ 86-571-88484468;
e-mail: pfzhang@hznu.edu.cn)
b) College of Material Chemistry and Chemical Engineering, Zhejiang University, Hangzhou 310027,
P. R. China
A novel class of chiral glycosyl-triazole-based P,N ligands were synthesized by ꢀclick chemistryꢁ and
were applied to the Rh-catalyzed asymmetric hydrosilylation of a range of substituted acetophenones.
Enantioselective hydrosilylation of acetophenone gave (S)-1-phenylethanol in moderate enantioselec-
tivity (72% ee) and in good conversion (93%).
1. Introduction. – Over the last few decades, the asymmetric Rh-catalyzed
hydrosilylation of ketones has been recognized as a versatile method for the synthesis
of enantiomerically enriched alcohols and amines [1]. The chiral catalysts for
asymmetric hydrosilylation were based on neutral cationic Rh precursors in combi-
nation with chiral bidentate diphosphines and amines to mixed donor-atom moieties
[2], such as phosphino ethers [3], phosphino thioethers [4], and aminophosphines [5].
These catalytic systems have been applied to asymmetric hydroformylation, hydro-
genation, hydrosilylation, and allylic alkylation reactions. Numerous configurations of
phosphorus,nitrogen (P,N) ligands have been reported [6]. The P,N ligands can be
generically divided into two categories, namely those based on structurally rigid sp2-N-
centers, unsaturated pyridine or imine groups [7], and the other are sp3-N-centers,
which constitute saturated amine functionalities [8]. ꢀClick chemistryꢁ has recently
attracted considerable attention as a powerful and efficient way to synthesize desired
compounds in high yields by using a simple and benign procedure [9]. Recently, we
were interested in the CuI-catalyzed 1,3-dipolar ꢀclickꢁ azide – alkyne cycloaddition
[10], since the resulting 1,4-disubstituted 1,2,3-triazoles can be a part of bidentate P,N-
type ligands that have been applied in various catalytic transformations [11][12].
ClickFerrophos, ferrocenyl, and P,P and P,N ligands have been prepared by Fukuzawa
et al. by ꢀclick chemistryꢁ, and their Rh complexes have been demonstrated to work
effectively in asymmetric hydrogenation and allylic alkylation reactions [13]. Carbo-
hydrates are readily available and highly functionalized compounds with several
stereogenic centers. This allows a systematic regio- and stereoselective introduction of
different functionalities in the course of the synthesis of a series of chiral ligands that
can be screened in the search for high activities and enantioselectivities [14]. Prompted
by our interest in carbohydrates as an inexpensive and highly modular chiral sources for
ꢂ 2010 Verlag Helvetica Chimica Acta AG, Zꢃrich

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Helvetica Chimica Acta – Vol. 93 (2010)
the glucose-mediated asymmetric Strecker reaction [15], we herein report the
preparation of triazole-based P,N ligands (sp3 type), which are derived from (þ)-d-
glucose for Rh-catalyzed asymmetric hydrosilylation. To the best of our knowledge,
triazole-based P,N ligands have not been tested in this process.
2. Results and Discussion. – 2.1. Ligand Design. On the basis of the efficient
formation of the disubstituted triazoles, a straightforward two-step synthesis of the
several ligands has been developed (Scheme 1). 1-Azido-2,3,4,6-tetra-O-pivaloyl-b-d-
glucopyranose (1) was subjected to click chemistry under Sharpless conditions to give
the corresponding 1,2,3-triazoles 3a – 3e in good yields. Then, reaction of carbohydrate-
derived triazoles 3a – 3e with 1 mol-equiv. of BuLi in THF at ꢀ 788, followed by
trapping with 1.1 mol-equiv. of Ph2PCl, gave the desired ligand 4b only. The presence of
other groups in the carbohydrate-derived triazoles did not allow the synthesis of
corresponding chiral P,N ligands, even upon exposure to a large excess of BuLi. The
ligand 4b was stable during purification on neutral alumina under an Ar atmosphere
1
and isolated as white solid. The H-, 31P-, and 13C-NMR spectra were as expected for
this type of ligands (see Exper. Part).
Scheme 1. Preparation of 1-Glycosyl-triazole-Based Chiral Ligand 4
2.2. Asymmetric Hydrosilylation of Ketones. We first investigated the Rh-catalyzed
hydrosilylation of acetophenone, which is widely used as a model substrate. The
catalysts were generated in situ by adding the corresponding ligand to the catalyst

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precursor. The effect of the solvent, temperature, and catalyst precursor was
investigated. The results are summarized in Table 1.
Table 1. Hydrosilylation of Acetophenone (5a) Using Chiral Ligand 4b under Various Conditionsa)
Entry
Silane
T [8]
Solvent
Time [h]
Conv. [%]b)
ee [%]c)
1
2
3
4
5
6
7
PhSiH3
PhSiH3
Ph2SiH2
Ph2SiH2
(1-Np)PhSiH2
(1-Np)PhSiH2
(1-Np)PhSiH2
ꢀ 20
ꢀ 20
ꢀ 20
ꢀ 20
r.t.
CH2Cl2
THF
Et2O
THF
THF
THF
THF
2
5
2
2
2
2
5
45
52
87
87
87
78
89
11 (S)
15 (S)
23 (S)
40 (S)
52 (S)
66 (S)
68 (S)
d
)
ꢀ 20
ꢀ 20
a) Reaction conditions: 5a (1 mmol), silane (1.1 mmol), ligand 4b (0.011 mmol), 4b/Rh ¼ 1.1, solvent
c
(2 ml). b) Conversion after 2 h determined by GC using undecane as internal standard. ) Enantiomeric
excess determined by GC. d) 1-Np ¼ Naphthalen-1-yl.
A preliminary optimization was carried out by studying the effect of various
solvents and temperature on both conversion and enantioselectivity. According to
Table 1, THF gave the best results regarding both conversion and enantiomeric excess,
as well as short reaction time. We had applied the monosubstituted silane, i.e., PhSiH3
(Entry 1), and obtained the product with an enantioselectivity lower than when ligand
4b was used. Previous studies by Fu have shown that the size of the aromatic group on
the silane has a significant effect on enantioselectivity [5]. Therefore, we prepared
more sterically demanding silanes than Ph2SiH2 and applied (naphthalen-1-yl)phenyl-
silane with ligand 4b. The (1-Np)PhSiH2 was found to give lower conversion (78%)
than Ph2SiH2, although a slight increase in enantioselectivity to 66% was observed
(Table 1, Entry 4 vs. 6). We next studied how the steric and electronic properties of the
ketone affected the outcome of the reaction. For this purpose, a series of substituted
benchmark aryl ketones 6a – 6f were tested. The results are summarized in Table 2. We
found that para-substitution (substrate 6f) resulted in higher selectivities in the
hydrosilylation, while ortho-substitution (substrate 6d) gave lower selectivities.
2.3. Mechanism. Here, we propose the catalytic mechanism for this reaction. For the
Piv4Glc skeleton, which played a primary impact in controlling the diastereoselectivity,
influencing the metal coordination according to Scheme 2, in which Rh is coordinated
to one of the O-atoms of the 2’-PivO group and the P-atoms of the Ph2P group.
However, the 1,2,3-triazole moiety could also interact with the catalytic metal and
trigger non-enantioselective reaction pathways, whereas formation of chelates like B-
or C-type would decrease the coordination between N-atom of the triazole and P-atoms
and lead to low enantiomeric excess. From the experimental results, we found that A-
type chelates are favored over the B- and C-type chelates, and are facilitating

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Table 2. Asymmetric Hydrosilylation of Various Prochiral Ketones in the Presence of Chiral Ligand 4ba)
Entry
Ketone
R
Conv. [%]b)
ee [%]c)
1
2
3
4
5
6
5a
5b
5c
5d
5e
5f
Ph
78
72
60
75
83
82
66 (S)
50 (S)
52 (S)
55 (S)
69 (S)
72 (S)
4-MeOꢀC6H4
4-MeꢀC6H4
3-MeꢀC6H4
4-BrꢀC6H4
4-NO2ꢀC6H4
a) Reaction conditions: ketones 5a – 5f (1 mmol), (1-Np)PhSiH2 (1.1 mmol), ligand 4b (0.011 mmol),
4b/Rh ¼ 1.1, solvent (2 ml). b) Conversion after 2 h determined by GC using undecane as internal
standard. c) Enantiomeric excess determined by GC.
Scheme 2. Possible Pathways in Metal Catalysis with the Chiral Ligand 4b
enantiomerically selective pathways which gave (S)-1-phenylethanol in moderate
enantioselectivity (72% ee).
A novel triazole-based P,N ligand has been developed and tested in the Rh-
catalyzed asymmetric hydrosilylation of aryl ketones. High activities and moderate
enantiomeric excesses (ee up to 72%) were obtained. Although the enantioselectivities
remain still modest for the reduction of various ketones, this study shows that new
family of chiral ligands can be effectively used for the enantioselective hydrosilylation
of prochiral ketones. Further applications of the 1-glycosyl-triazole-based P,N ligand
approach to other transformations catalyzed by organometallic reagents, including
asymmetric allylic alkylation reaction, are currently underway.

Helvetica Chimica Acta – Vol. 93 (2010)
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Experimental Part
General. 1-Azido-2,3,4,6-tetrakis-O-pivaloyl-b-d-glucopyranose (1) was prepared according to [15].
Other chemicals and solvents were either purchased or purified by standard techniques. Anal. TLC:
Merck precoated TLC (silica gel 60 F 254) plates. GC: Varian 3900 gas chromatograph with an octakis(6-
o-methyl-2,3-di-o-pentyl)-r-CD column of Chrompack CP-9000 (CP-Sil-8, 30 m ꢁ 0.32 mm; 75 kPa of
H2) under the condition given. M.p.: X4-Data microscopic melting-point apparatus; uncorrected. Optical
rotations: ADP 440 polarimeter in CH2Cl2. IR Spectra: Nicolet 380 FT-IR spectrophotometer; KBr discs.
1H-, 13C-, and 31P-NMR spectra: Bruker Avance 400 spectrometer in CDCl3 with TMS or H3PO4 as
internal standard. ESI-MS: Bruker Esquire 3000 plus spectrometer. Elemental analyses: Carlo-Erba 1106
instrument.
General Procedure for the Preparation of the 1H-[1,2,3]Triazole 3. To a mixture of 1 (541 mg,
1.0 mmol) and alkynes 2 (1.0 mmol) in t-BuOH (1 ml), 0.5 ml of an aq. soln. of CuSO4 (50 mg, 0.2 mmol)
and 0.5 ml of an aq. soln. of sodium ascorbate (79.2 mg, 0.4 mmol) were added. The mixture was stirred
vigorously for 24 h. The suspended product was filtered and washed with H2O. The crude product was
purified by column chromatography (CC; SiO2; hexane/AcOEt mixtures of increasing polarity) to afford
the triazole products.
4-Phenyl-1-[2,3,4,6-tetrakis-O-(2,2-dimethylpropanoyl)-d-glucopyranosyl]-1H-[1,2,3]triazole (3a).
Yellow solid. Yield: 92.3%. M.p. 216 – 2208. IR: 2970, 2077, 1744, 1637, 1481, 1400, 1368, 1280, 1140,
1037. 1H-NMR: 8.05 (s, 1 H); 7.85 (d, J ¼ 7.6, 2 H); 7.46 (d, J ¼ 7.6, 2 H); 7.38 (t, J ¼ 7.2, 1 H); 5.87 (d, J ¼
4.0, 1 H); 5.55 (t, J ¼ 4.4, 1 H); 5.36 (t, J ¼ 5.6, 1 H); 4.71 – 4.74 (m, 1 H); 4.55 – 4.59 (m, 1 H); 4.31 – 4.35
(m, 1 H); 0.92 – 1.25 (m, 12 Me). 13C-NMR: 177.8; 176.5; 147.4; 144.6; 129.0; 127.9; 127.6; 125.0; 85.1;
74.6; 71.1; 69.2; 66.2; 60.4; 37.8; 25.8; 26.1. ESI-MS: 643.2 ([M þ H]þ). Anal. calc. for C34H49N3O9: C
63.43, H 7.67, N 6.53; found: C 63.44, H 7.66, N 6.55.
2-{1-[2,3,4,6-Tetrakis-O-(2,2-dimethylpropanoyl)-d-glucopyranosyl]-1H-[1,2,3]triazol-4-yl}pyridine
(3b). Yellow solid. Yield: 95.3%. M.p. 179 – 1818. 1H-NMR: 8.60 (s, 1 H); 8.37 (d, J ¼ 3.6, 1 H); 8.11 (t,
J ¼ 6.8, 1 H); 7.78 (t, J ¼ 6.0, 1 H); 7.27 (d, J ¼ 12.2, 1 H); 5.97 (d, J ¼ 8.2, 1 H); 5.54 – 5.56 (m, 2 H); 5.32 –
5.37 (m, 1 H); 4.19 – 4.21 (m, 2 H); 4.05 (d, J ¼ 2.4, 1 H); 1.87 – 1.89 (m, 1 H); 0.94 – 1.21 (m, 12 Me).
13C-NMR: 177.7; 177.1; 177.1; 155.3; 149.2; 137.2; 131.4; 129.5; 123.6; 97.6; 78.2; 73.7; 69.2; 69.8; 62.4; 36.8;
25.79; 26.12. IR: 3431, 2974, 1742, 1601, 1479, 1400, 1281, 1141, 1034. Anal. calc. for C33H48N4O9: C 61.55,
H 7.82, N 8.78; found: C 61.58, H 7.80, N 8.75.
4-(4-Bromophenyl)-1-[2,3,4,6-tetrakis-O-(2,2-dimethylpropanoyl)-d-glucopyranosyl]-1H-[1,2,3]tri-
azole (3c). Yellow solid. Yield: 88.1%. M.p. 220 – 2228. IR: 3422, 2974, 1742, 1637, 1481, 1403, 1368, 1140,
1040. 1H-NMR: 7.97 (s, 1 H); 7.70 (d, J ¼ 5.6, 2 H); 7.56 (t, J ¼ 7.2, 2 H); 5.99 (d, J ¼ 7.6, 1 H); 5.52 – 5.55
(m, 2 H); 5.36 (d, J ¼ 4.2, 1 H); 4.18 – 4.21 (m, 2 H); 4.06 – 4.09 (m, 1 H); 0.92 – 1.25 (m, 12 Me).
13C-NMR: 177.7; 176.7; 131.9; 129.7; 127.2; 122.4; 85.9; 77.2; 71.8; 69.9; 66.9; 61.1; 38.8; 25.53; 26.92. Anal.
calc. for C34H48BrN3O9: C 56.62, H 6.73, N 5.93; found: C 56.65, H 6.70, N 5.91.
4-(4-Fluorophenyl)-1-[2,3,4,6-tetrakis-O-(2,2-dimethylpropanoyl)-d-glucopyranosyl]-1H-[1,2,3]tri-
azole (3d). White solid. Yield: 89.1%. M.p. 190 – 1928. IR: 3436, 2976, 1740, 1641, 1485, 1406, 1360, 1141,
1039. 1H-NMR: 8.02 (s, 1 H); 7.82 (d, J ¼ 7.2, 2 H); 7.82 (t, J ¼ 6.0, 2 H); 5.96 (d, J ¼ 6.6, 1 H); 5.54 – 5.58
(m, 2 H); 5.38 (d, J ¼ 2.4, 1 H); 4.11 – 4.20 (m, 2 H); 4.11 (d, J ¼ 12.4, 1 H); 0.95 – 1.26 (m, 12 Me).
13C-NMR: 178.7; 176.9; 132.1; 129.7; 127.2; 122.4; 85.9; 77.2; 71.9; 69.9; 66.9; 61.2; 38.7; 25.5; 26.9. Anal.
calc. for C34H48FN3O9: C 61.76, H 7.22, N 6.43; found: C 61.73, H 7.20, N 6.45.
4-(4-Methylphenyl)-1-[2,3,4,6-tetrakis-O-(2,2-dimethylpropanoyl)-d-glucopyranosyl]-1H-[1,2,3]tri-
azole (3e). White solid. Yield: 92.6%. M.p. 208 – 2108. IR: 3443, 2352, 2118, 1746, 1649, 1540, 1398, 1280,
1146. 1H-NMR: 8.00 (s, 1 H); 7.74 (d, J ¼ 5.6, 2 H); 7.25 (t, J ¼ 6.8, 2 H); 5.86 (d, J ¼ 11.6, 1 H); 5.55 (d,
J ¼ 4.2, 1 H); 5.31 – 5.34 (m, 1 H); 4.71 (m, 2 H); 4.45 (d, J ¼ 2.2, 1 H); 4.30 (d, J ¼ 6.2, 1 H); 2.39 (s,
1 H); 0.92 – 1.25 (m, 12 Me). 13C-NMR: 177.4; 176.2; 176.2; 144.3; 137.9; 129.1; 126.5; 126.2; 115.9; 86.2;
76.8; 76.2; 66.0; 65.9; 60.0; 38.4; 29.19; 26.47. Anal. calc. for C35H51N3O9: C 63.86, H 7.74, N 6.50; found: C
63.86, H 7.74, N 6.50.
General Procedure for the Preparation of the Ligand 4b (¼2-{5-(Diphenylphosphanyl)-1-[2,3,4,6-
tetrakis-O-(2,2-dimethylpropanoyl)-b-d-glucopyranosyl]-1H-[1,2,3]triazol-4-yl}pyridine). In a 20-ml
Schlenk tube containing a magnetic stirring bar were charged triazole 3b 1.28 g (2.0 mmol) and dry

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Helvetica Chimica Acta – Vol. 93 (2010)
THF (5 ml) under a slight pressure of N2. The flask was cooled to ꢀ 788, and a hexane soln. of BuLi (1 ml,
2.0 mmol, 2m) was then added using a syringe through the septum with magnetic stirring. After 10 min,
Ph2PCl (460 ml, 2.5 mmol) was injected into the mixture at ꢀ 788, and stirred for 1 h. When the addition
was completed, the mixture was allowed to warm to r.t. and then stirred for an additional 2 h. The
reaction was quenched with sat. NH4Cl, and the soln. was then extracted with Et2O (3 ꢁ 30 ml). The
combined extracts were washed (brine), dried (Na2SO4), filtered, and the solvent was removed on a
rotary evaporator to leave a yellow solid. The crude product was purified by recrystallization from
hexane/CH2Cl2: 1.16 g (69.8%). White solid. M.p. 189 – 1928. 1H-NMR: 8.47 (s, 1 H); 7.88 (d, J ¼ 5.6,
1 H); 7.74 (t, J ¼ 7.2, 1 H); 7.78 (t, J ¼ 4.0, 1 H); 7.17 – 7.46 (m, 10 H); 5.59 – 5.62 (m, 1 H); 5.35 – 5.36 (m,
2 H); 5.28 – 5.32 (m, 1 H); 4.17 – 4.19 (m, 2 H); 3.90 – 3.95 (m, 1 H); 0.94 – 1.21 (m, 12 Me). 13C-NMR:
205.6; 177.9; 176.9; 176.2; 149.1; 148.7; 145.2; 142.0; 136.8; 134.4; 131.6; 130.3; 128.8; 128.4; 128.3; 127.7;
122.7; 84.9; 78.3; 76.7; 74.4; 67.5; 45.5; 38.7; 27.2; 26.49. 31P-NMR: ꢀ 11.70. ESI-MS: 828.9 ([M þ H]þ).
Anal. calc. for C45H57N4O9P: C 62.50, H 6.93, N 6.76; found: C 62.52, H 6.95, N 674.
General Procedure for Asymmetric Hydrosilylation Reactions. To a soln. of the desired catalyst
precursor (0.01 mmol Rh) in the corresponding solvent (2 ml), the ligand (0.011 mmol) was added. The
mixture was stirred for 30 min. Ketone (1 mmol), Ph2SiH2 (1.1 mmol), and undecane as the GC internal
standard (0.1 ml) were then added. After the desired reaction time, the reaction was quenched with
MeOH (7 ml) and 2.5m aq. NaOH (5 ml). The mixture was extracted with Et2O (3 ꢁ 5 ml), and the
combined Et2O phases were dried (Na2SO4) and filtered. The conversion percentages and ee values were
determined by GC.
This work was supported by the Natural Science Foundation of Zhejiang Province (No. Y4090052)
and the National Science and Technology Ministry of P. R. China (No. 2007BAI34B05).
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Received March 8, 2010