Enantioselective pinacol coupling of aryl aldehydes catalyzed by chiral Salan-Mo(IV) complexes

Article abstract of DOI:10.1021/jo701842r

(Chemical Equation Presented) Reported herein is the asymmetric pinacol coupling of aromatic aldehydes with chiral Salan-Mo(VI) dioxo complex as an effective precatalyst. Chiral diols were obtained with high diastereoselectivity and enantioselectivity up

Full text of DOI:10.1021/jo701842r

Enantioselective Pinacol Coupling of Aryl Aldehydes Catalyzed by
Chiral Salan-Mo(IV) Complexes
Hongwei Yang,† Hongsong Wang,† and Chengjian Zhu*,†,‡
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing
UniVersity, Nanjing 210093, China, and State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
cjzhu@netra.nju.edu.cn
ReceiVed August 28, 2007
Reported herein is the asymmetric pinacol coupling of aromatic aldehydes with chiral Salan-Mo(VI)
dioxo complex as an effective precatalyst. Chiral diols were obtained with high diastereoselectivity and
enantioselectivity up to 92/8 and 95%, respectively. The possible mechanism of the pinacol coupling
reaction with the catalytic system was investigated. The X-ray crystal structure of the precatalyst Mo-
(L3)O2 was determined and the oxidation state of the intermediate C was confirmed as +4 with X-ray
photoelectron spectroscopy study. The proposed mechanism speculated the stereochemical outcome of
the reaction, and a working model for the radical coupling of E was proposed, which explained the
absolute configuration of the favored (S,S)-enantiomer of the dl isomer.
Introduction
the asymmetric pinacol coupling reaction4 was found to be one
of the most direct methods to prepare chiral 1,2-diol. Although
different metals such as Ce,5 Ti,6 U,7 Sm,8 Cr,9 V,10 Ru,11 and
In12 have been shown to efficiently catalyze pinacol coupling
Chiral 1,2-diols, especially hydrobenzoins, are very useful
chiral ligands1 and auxiliaries2 in stereoselective organic
syntheses. Besides the asymmetric dihydroxylation reaction,3
(3) For reviews, see: (a) Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless,
K. B. Chem. ReV. 1994, 94, 2483. (b) Johnson, R. A.; Sharpless, K. B.
Catalytic Asymmetric Dihydroxylation-Discovery and Development. In
Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH:
Weinheim, Germany, 2000; pp 357-398.
(4) (a) Robertson, G. M. In Comprehensive Organic Synthesis; Trost,
B, M., Fleming, I., Eds.; Pergamon: Oxford, UK, 1991; Vol. 3, pp 563-
611. (b) Wirth, T. Angew. Chem., Int. Ed. Engl. 1996, 35, 61.
(5) (a) Groth, U.; Jeske, M. Angew. Chem., Int. Ed. 2000, 39, 574. (b)
Groth, U.; Jeske, M. Synlett 2001, 129. (b) Villiers, C.; Ephritikhine, M.
Chem.-Eur. J. 2001, 7, 3043.
(6) Selected references for Ti-based reagents. (a) Wang, K.; Wang, S.-
X.; Gao, M.-Z.; Li, J.-T. Synth. Commun. 2006, 36, 1391. (b) Oller-Lopez,
J. L.; Campana, A. G.; Cuerva, J. M.; Oltra, J. E. Synthesis 2005, 2619. (c)
Gansa¨uer, A.; Bluhm, H. Chem. ReV. 2000, 100, 2771. (d) Tsuritani, T.;
Ito, S.; Shinokubo, H.; Oshima, K. J. Org. Chem. 2000, 65, 5066. (e) Li,
T.; Cui, W.; Liu, J.; Zhao, J.; Wang, Z. Chem. Commun. 2000, 139. (f)
Yamamoto, Y.; Hattori, R.; Miwa, T.; Nakagai, Y.; Kubota, T.; Yamamoto,
C.; Okamoto, Y.; Itoh, K. J. Org. Chem. 2001, 66, 3865.
* Address correspondence to this author. Phone: 0086-25-8359-4886. Fax:
0086-25-8331-7761.
† Nanjing University.
‡ Chinese Academy of Sciences.
(1) (a) Tomioka, K. Synthesis 1990, 541. (b) Prasad, K. R. K.; Joshi, N.
N. Tetrahedron: Asymmetry 1996, 7, 1957. (c) Shindo, M.; Koga, K.;
Tomioka, K. J. Org. Chem. 1998, 63, 9351. (d) Donnoli, M. I.; Superchi,
S.; Rosini, C. J. Org. Chem. 1998, 63, 9392. (e) Ishimaru, K.; Monda, K.;
Yamamoto, Y.; Akiba, K. Tetrahedron 1998, 54, 727. (f) Ishihara, K.;
Nakashima, D.; Hiraiwa, Y.; Yamamoto, H. J. Am. Chem. Soc. 2003, 125,
24.
(2) (a) Whitesell, J. K. Chem. ReV. 1989, 89, 1581. (b) Halterman, R.
L.; Jan, S. T.; Nimmons, H. L.; Standlee, D. J.; Khan, M. A. Tetrahedron
1997, 53, 11257. (c) Kim, K. S.; Park, J. I.; Ding, P. Tetrahedron Lett.
1998, 39, 6471. (d) Superchi, S.; Contursi, M.; Rosini, C. Tetrahedron 1998,
54, 11247. (e) Tunge, J. A.; Gately, D. A.; Norton, J. R. J. Am. Chem. Soc.
1999, 121, 4520. (f) Ray, C. A.; Wallace, T. W.; Ward, R. A. Tetrahedron
Lett. 2000, 41, 3501. (g) Andrus, M. B.; SomaSekhar, B. B. V.; Meredith,
E. L.; Dalley, N. K. Org. Lett. 2000, 2, 3035.
(7) Maury, O.; Villier, C.; Ephritikhine, M. New J. Chem. 1997, 21, 137.
10.1021/jo701842r CCC: $37.00 © 2007 American Chemical Society
Published on Web 11/29/2007
J. Org. Chem. 2007, 72, 10029-10034
10029

Yang et al.
SCHEME 1. Synthesis of Salan-Mo(VI) Dioxo Complexes
in diastereoselectivity study, attention was mainly focused on
chiral titanium catalysts in the field of enantioselective pinacol
coupling reaction.13 More recently, Yamamoto’s group devel-
oped the highly enantio- and diastereoselective pinacol coupling
reaction with a chiral chromium complex TBOxCr(III)Cl as
precatalyst.14 However, other chiral metal complex catalysts but
chiral chromium and titanium complexes used in asymmetric
pinacol coupling reaction have not been reported.
cis-Dioxo complexes dominate the chemistry of molybdenum-
(VI), and their prevalence, ease of synthesis, and chemical
attributes have led to their exploitation as oxidation catalysts,
models for enzymes and surface oxides, sensors, and drug
targets.15 Although application for chiral Mo(VI) dioxo com-
plexes in asymmetric reaction dated back the 1970’s, all study
was focused on oxygen atom transfer reactions, the olefin
epoxidation,16 and oxidation of sulfides.17 To the best of our
knowledge, no optically active chiral Mo(VI) dioxo complexes
were used in asymmetric reactions other than the oxidative
reaction.
Herein we describe the highly enantioselective pinacol
coupling of aromatic aldehydes with characterized Salan-Mo-
(VI) dioxo complexes as precatalysts and the reaction mecha-
nism was also investigated.
Results and Discussion
The readily obtainable tetradentate Salan ligands, which are
derived from (R,R)-1,2-diphenylethane, were chosen as the
requisite ligands. As shown in Scheme 1, treatment of the chiral
ligand with 1 equiv of MoO2(acac)2 in refluxing methanol
provided the chiral Salan-Mo(VI) dioxo complexes in very high
yield. Attempts to apply the Salan-Mo(VI) dioxo complexes
in oxygen atom transfer reactions were not succeed. We found
these complexes were completely ineffective in both the olefin
epoxidation and oxidative reaction of sulfides. This may be
attributed to the enhanced stability of the molybdenum-oxo
moiety afforded by the chelate effect of the quadridentate
ligands, which prevents the metal-oxo moiety from coordinat-
ing with substrates.18
Asymmetric Pinacol Coupling of Aryl Aldehydes Cata-
lyzed by Chiral Salan-Mo (IV) Complexes. Following the
protocol of the Ti-catalyzed pinacol coupling reaction, in which
Me3SiCl was used as a mediator and a second metal was
employed as a co-reductant. We studied the asymmetric pinacol
coupling of aromatic aldehydes with the Salan-Mo(IV) com-
plexes as precatalysts. In our preliminary investigation, we
carried out the coupling of benzaldehyde using three different
Salan-Mo(IV) complexes as precatalysts in THF with 10 mol
(8) (a) Dahlen, A.; Prasad, E.; Flowers, R. A., II; Hilmersson, G. Chem.-
Eur. J. 2005, 11, 3279. (b) Aspinall, H. C.; Greeves, N.; Valla, C. Org.
Lett. 2005, 7, 1919. (c) Matsukawa, S.; Hinakubo, Y. Org. Lett. 2003, 5,
1221. (d) Nomura, R.; Matsuno, T.; Endo, T. J. Am. Chem. Soc. 1996,
118, 1666. (e) Fukuzawa, S.; Yahara, Y.; Kamiyama, A.; Hara, M.; Kikuchi,
S. Org. Lett. 2005, 7, 5809. (f) Miller, R. S.; Sealy, J. M.; Shabangi, M.;
Kuhlman, M. L.; Fuchs, J. R.; Flowers, R. A. J. Am. Chem. Soc. 2000,
122, 7718.
(9) (a) Svatos, A.; Boland, W. Synlett 1998, 549. (b) Takai, K.; Morita,
R.; Matsushita, H.; Toratsu, C. Chirality 2003, 15, 17.
(10) (a) Wang, S.-X.; Wang, K.; Li, J.-T. Synth. Commun. 2005, 35,
2387. (b) Xu, X.-L.; Hirao, T. J. Org. Chem. 2005, 70, 8594. (c) Hirao, T.;
Hasegawa, T.; Muguruma, Y.; Ikida, I. J. Org. Chem. 1996, 61, 366. (d)
Hirao, T.; Asahara, M.; Muguruma, Y.; Ogawa, A. J. Org. Chem. 1998,
63, 2812. (e) Hirao, T.; Hatano, B.; Imamoto, Y.; Ogawa, A. J. Org. Chem.
1999, 64, 7665. (f) Hirao, T.; Takeuchi, H.; Ogawa, A.; Sakurai, H. Synlett
2000, 1658.
(11) Shimada, H.; Qu, J. P.; Matsuzaka, H.; Ishii, Y.; Hidai, M. Chem.
Lett. 1995, 671.
(12) (a) Mori, K.; Ohtaka, S.; Uemura, S. Bull. Chem. Soc. Jpn. 2001,
74, 1497. (b) Wang, C.-Y.; Pan, Y.-J.; Wu, A.-X. Tetrahedron 2006, 63,
429. (c) Nair, V.; Ros, S.; Jayan, C. N.; Rath, N. P. Tetrahedron Lett. 2002,
43, 8967. (d) Lim, H. J.; Keum, G.; Kang, S. B.; Chung, B. Y.; Kim, Y.
Tetrahedron Lett. 1998, 39, 4367.
(13) (a) For a review on pinacol coupling reactions see: Chatterjee, A.;
Joshi, N. N. Tetrahedron 2006, 62, 12137. Chiral Ti catalysts. See: (b)
Wen, J. W.; Zhao, J.; You, T. P. J. Mol. Catal. A 2006, 245, 278. (c) Bandini,
M.; Cozzi, P. G.; Morganti, S.; Umani-Ronchi, A. Tetrahedron Lett. 1999,
40, 1997. (d) Dunlap, M. S.; Nicholas, K. M. Synth. Commun. 1999, 29,
1097. (e) Halterman, R. L.; Zhu, C.; Chen, Z.; Dunlap, M. S.; Khan, M.
A.; Nicholas, K. M. Organometallics 2000, 19, 3824. (f) Bensari, A.;
Renaud, J. L.; Riant, O. Org. Lett. 2001, 3, 3863. (g) Chatterjee, A.; Bennur,
T. H.; Joshi, N. N. J. Org. Chem. 2003, 68, 5668. (h) Li, Y.-G.; Tian,
Q.-S.; Zhao, J.; Feng, Y.; Li, M.-J.; You, T.-P. Tetrahedron: Asymmetry
2004, 15, 1707.
(15) For a review on molybdenum(VI) dioxo complexes see: (a) Stiefel,
E. I. In Comprehensive Coordination Chemistry; Wilkinson, G., Gillard,
R. D., McCleverty, J. A., Eds.; Pergamon: Oxford, UK, 1987; Chapter
36.5, pp 1375-1420. (b) Young, C. G. In Comprehensive Coordination
Chemistry II; McCleverty, J. A., Meyer, T. J., Eds.; Elsevier Pergamon:
Amsterdam, The Netherlands, 2004; Chapter 4.7, pp 415-527. (c) Ku¨hn,
F. E.; Zhao, J.; Herrmann, W. A. Tetrahedron: Asymmetry 2005, 16, 3469.
(d) Ku¨hn, F. E.; Santos, A. M.; Herrmann, W. A. J. Chem. Soc., Dalton
Trans., 2005, 2483. (e) Ku¨hn, F. E.; Santos, A. M.; Abrantes, M. Chem.
ReV. 2006, 106, 2455.
(16) Selected references for enantioselective epoxidation of alkenes,
see: (a) Barlan, A. U.; Basak, A.; Yamamoto, H. Angew. Chem., Int. Ed.
2006, 45, 5849. (b) Zhao, J.; Zhou, X.-G.; Santos, A. M.; Herdtweck, E.;
Roma˜o, C. C.; Ku¨hn, F. E. J. Chem. Soc., Dalton Trans. 2003, 3736. (c)
Ku¨hn, F.; Zhao, J.; Herrmann, W. A. Tetrahedron: Asymmetry 2005, 16,
3469. (d) Gonclaves, I.; Santos, A.; Romao, C.; Lopes, A.; Rodriguez-
Borges, J.; Pillinger, M.; Ferriera, P.; Rocha, J.; Kuhn, R. J. Organomet.
Chem. 2001, 626, 1. (e) Wang, X.-Y.; Shi, H.-C.; Sun, C.; Zhang, Z.-G.
Tetrahedron 2004, 60, 10993. (f) Fridgen, J.; Herrmann, W. A.; Eickerling,
G.; Santos, A. M.; Kuhn, F. E. J. Organomet. Chem. 2004, 689, 2752.
(17) Enantioselective oxidation of sulfides, see: (a) Basak, A.; Barlan,
A. U.; Yamamoto, H. Tetrahedron: Asymmetry 2006, 17, 508. (b) Bellemin-
Laponnaz, S.; Coleman, K. S.; Osborn, J. A. Polyhedron 1999, 18, 2533.
(18) Tarafder, M. T. H.; Khan, A. R. Polyhedron 1991, 10, 819.
(14) Takenaka, N.; Xia, G.-Y.; Yamamoto, H. J. Am. Chem. Soc. 2004,
126, 13198.
10030 J. Org. Chem., Vol. 72, No. 26, 2007

Asymmetric Pinacol Coupling Reaction
TABLE 1. Asymmetric Pinacol Coupling Reaction of
Benzaldehyde under Different Conditionsa
TABLE 2. Asymmetric Pinacol Coupling Reaction of Various
Aromatic Aldehydesa
reaction
time (h)
yield
(%)b
ee (%)
reaction yields
time (h)
eed
entry
aldehyde (Ar)
dl/mesoc
(config.)f
entry
catalst (%)
sol.
THF
(%)b dl/mesoc (%)
1
2
3
4
5
6
7
8
9
Ph
48
48
48
48
36
36
48
36
48
90
84
80
95
88
78
88
65
60
92/8
74/26
82/18
93/7
73/27
75/25
42/58
78/22
66/34
95d (S,S)
85e (S,S)
76d (S,S)
90e (S,S)
72e (S,S)
72e (S,S)
84d (S,S)
66e (S,S)
47e (S,S)
1
2
3
4
5% Mo(L3)O2
36
36
36
48
76
80
82
90
63/35
66/34
90/10
92/8
25
68
86
95
o-CH3C6H4
m-CH3C6H4
p-CH3C6H4
p-BrC6H4
m-BrC6H4
o-ClC6H4
p-FC6H4
10% Mo(L3)O2 THF
15% Mo(L3)O2 THF
15% Mo(L3)O2 THF
+7.5%H2L3
5
6
7
15% Mo(L3)O2 hexane
+7.5% H2L3
48
48
48
62
74
58
48/52
66/34
88/12
23
74
30
15% Mo(L3)O2 CH3CN
+7.5% H2L3
o-CF3C6H4
a Reaction conditions: RCHO/Mo(L3)O2/H2L3/Zn/Me3SiCl ) 1:0.15:
0.075:4:2, reaction was performed at 0 °C. b Isolated yields. c Determined
by 1H NMR. d The ee values were determined by HPLC with a Daicel
Chiralcel OJ-H. e The ee values were determined by HPLC with a Daicel
Chiralcel AD-H. f Absolute configuration was assigned by comparison of
optical rotation reported in the literature.
15% Mo(L3)O2 CH2Cl2
+7.5% H2L3
a Reaction conditions: PhCHO/Zn/Me3SiCl ) 1:4:2, reaction was
1
performed at 0 °C. b Isolated yields. c Determined by H NMR or HPLC.
d The ee values were determined by HPLC with a Daicel Chiralcel OJ-H.
% loading, 2 equiv of Me3SiCl, and 4 equiv of Zn powder as
co-reductants. Mo(L1)O2 and Mo(L2)O2 complexes as precata-
lysts were not further studied for providing lower diastereose-
lectivity and enantioselectivity less than 30% ee. Complex
Mo(L3)O2 can give moderate diastereoselectivity (dr ) 66/34)
and enantioselectivity (ee ) 43%). Change in precatalyst loading
from 5, to 10, to 15 mol % was explored in the reaction (Table
1, entries 1-3). The enantioselectivity increased from 25%, to
68%, to 86% and the yield was not enhanced obviously. By
further increasing the catalyst loading to 20 mol %, improvement
of the enantioselectivity and yield could not be obtain. Therefore
as for the concentration parameter, 15 mol % precatalysts
loading was the optimal reaction condition. To our delight, the
mixture of 7.5 mol % H2L3 and 15 mol % Mo(L3)O2 as
precatalyst can afford a much better result than 15 mol % Mo-
(L3)O2 only. Both enantioselectivity and diastereoselectivity
were improved from 86% to 95% ee and 90/10 to 92/8 dr,
respectively (Table 1, entries 3 and 4). In addition, a further
survey of solvent revealed that THF was the most favorable
solvent among all those examined. Extensive exploration showed
the optimized conditions of the catalytic pinacol coupling
reaction as PhCHO/Mo(L3)O2/H2L3/Zn/Me3SiCl ) 1:0.15:
0.075:4:2 at 0 °C with THF.
On the basis of the optimal conditions established, we
investigated the coupling of a variety of aromatic aldehydes to
examine the scope of this catalytic system. The results are shown
in Table 2. As can be seen from Table 2, steric hindrance caused
a negative effect on the enantioselectivity. All the substituted
aryl aldehydes (Table 2, entries 2-9) showed lower ee values
than the benzaldehydes (Table 2, entry 1). Various substituted
aryl aldehydes exhibited a crucial electronic effect on enanti-
oselectivity. All benzaldehydes substituted by CH3 at different
positions, ortho, meta, and para, can give higher diastereose-
lectivity and enantioselectivity (Table 2, entries 2-4). With the
enhancement of a groups’ electron-withdraw capability from
Br, F, and CF3, the optical reactivity was reduced (Table 2,
entries 5, 6, 8, and 9). It was noteworthy that the o-chloroben-
zaldehyde afforded higher optical reactivity with enantioselec-
tivity up to 84%, but lower diastereoselectivity (Table 2, entry
7). In most cases, the reaction’s optical reactivity of aromatic
FIGURE 1. ORTEP diagram of Mo(L3)O2 with 30% probability
ellipsoids. Hydrogen atoms are omitted for clarity.
aldehydes with electron-donating groups was higher than that
with electron-withdraw groups in this catalytic system. In
addition, the absolute configuration of the major isomers of the
dl products was determined as (S,S).
Studied Reaction Mechanism of Pinacol Coupling Cata-
lyzed by Salan-Mo(IV) Complexes. For better understanding
of the reaction mechanism, the X-ray crystal structure of the
precatalyst Mo(L3)O2 was determined. Complexes Mo(L3)O2
and NH4PF6 were dissolved in ethanol. Single crystals suitable
for X-ray diffraction analysis were grown by slow evaporation
from their ethanol solution for several days. The molecule
structure of Mo(L3)O2 is a monomer and the ORTEP diagram
of Mo(L3)O2 is shown in Figure 1. The X-ray structure of Mo-
(L3)O2 exhibited that the coordination around the molybdenum
atom was a highly distorted octahedral geometry in the R-cis
(19) Six-coordinate molybdenum complexes have three geometric iso-
mers:
J. Org. Chem, Vol. 72, No. 26, 2007 10031

Yang et al.
SCHEME 2. The Possible Reaction Course of Me3SiCl with Molybdenum-Dioxo Complexes and Co-reductant Zn
SCHEME 3. Proposed Mechanism for Pinacol Coupling
Reaction
configuration,19 with the N atoms trans to the terminal double
bonded oxygen atoms.
On the basis of X-ray analysis of Mo(L3)O2 precatalyst, the
possible mechanism of the pinacol coupling reaction catalyzed
by Salan-Mo(VI) complexes was investigated.
It has been reported that the treatment of the dioxomolyb-
denm(VI) complex with chlorosilane formed monoxomolyb-
denm dichloride through a two-step procedure involving a 1,2-
monoaddition of the chlorosilane to a ModO bond and the
subsequent halogenation reaction.20 The formation of the active
species in our catalytic system, based on this result, was
proposed in Scheme 2. Reaction of Mo(L3)O2 with 1 equiv of
Me3SiCl gave the intermediate A, which transferred to B after
reacting with another equivalent of Me3SiCl by nucleophilic
substitution of OSiMe3 with chloride. The active catalytic
species C could be formed through the reduction of B with Zn
metal.
X-ray photoelectron spectroscopy (XPS) has been used
extensively to elucidate the electronic structure of transition
metal compounds.21 To confirm the oxidation state of the
intermediate C, we carried out the XPS study with this catalyst
system.
To the solution of Mo(L3)O2 (0.115 g, 0.15 mmol) in 4 mL
of anhydrous THF was added Zn powder (0.26 g, 6 mmol) under
nitrogen atmosphere. The yellow mixture was stirred for 10 min
at room temperature. After Me3SiCl (254 µL, 2 mmol) was
added, the suspension turned red. The mixture was stirred for
12 h, and the suspension was filtered through a glass funnel.
Then the solvent and excess Me3SiCl were removed in vacuum.
After being dried in vacuum, the sample was ground into powder
for XPS study.
spectrum, and a low-intensity additional peak at a binding energy
of 229.4 eV was present, which indicated the presence of mixed
states of molybdenum. We then deconvoluted the Mo 3d
envelope to obtain the oxidation state distribution of molybde-
num. The Mo 3d photoelectron spectrum of the dominant species
exhibited the Mo 3d3/2 line situated at 234.6 eV and the Mo
3d5/2 component at 231.4 eV, which were accordant to the
binding energy of Mo6+ 3d (Figure 2, curve b).23 The Mo 3d5/2
peak and Mo 3d3/2 peak of the minority species were centered
at a binding energy of 229.4 and 232.5 eV, respectively, which
were in a agreement with the value reported for Mo4+ (Figure
2, curve c).22,20b This indicated the sample was composed of
both Mo6+ and Mo4+ species. The corresponding Zn 2p3/2 peak
would be located at 1023.3 eV, which was assigned to Zn2+
The results of the XPS study on the catalyst system were
shown in Figures 2 and 3, which showed the analysis of the
Mo 3d and the Zn 2p spectra, respectively. Curve a in Figure
2 showed the Mo 3d experimental spectra. The peaks in the
experimental spectrum were broader than that in the Mo6+
(22) (a) Lo´pez-Carrenˇo, L. D.; Ben´ıtez, G.; Viscido, L.; Heras, J. M.;
Yubero, F.; EspinoÄ s, J. P.; Gonza˜lez-Elipe, A. R. Surf. Interface Anal.
1998, 26, 235. (b) Oshikawa, K.; Nagai, M.; Omi, S. J. Phys. Chem. B
2001, 105, 9124.
(23) Schroeder, T.; Zegenhagen, J.; Magg, N.; Immaraporn, B.; Freund,
H.-J. Surf. Sci. 2004, 552, 85.
(20) (a) Teruel, H.; Moret, Y. Y.; Perillo, B. Polyhedron 1998, 18, 419.
(b) Arzoumanian, H.; Krentzien, H.; Corao, C.; Lopez, R.; Agrifoglio, G.
Polyhedron 1995, 14, 2887. (c) Fernandes, A. C.; Fernandes, R.; Romao,
C. C.; Royo, B. Chem. Commun. 2005, 2, 213.
(21) Jeng, S.-P.; Zhang, Z.; Henrich, V. E. Phys. ReV. B 1991, 44. 3266.
10032 J. Org. Chem., Vol. 72, No. 26, 2007

Asymmetric Pinacol Coupling Reaction
FIGURE 4. Proposed molecular model for E (formation of the (S,S)-
product was favored).
SCHEME 4. Proposed Mechanism for the
Diastereoselective Pinacol Coupling Reaction
FIGURE 2. Deconvoluted Mo 3d spectra for the intermediate catalyst
C: (a) experimental spectra, (b) deconvoluted curve for Mo6+, and (c)
deconvoluted curve for Mo4+
.
FIGURE 3. XPS spectra of Zn 2p for the intermediate catalyst C.
(Figure 3).24 These results show that the oxidation state of
molybdenum in Mo(L3)OCl2 (B) has been partly reduced from
+6 to +4, while Zn powder was oxidized to Zn2+ in ZnCl2.
On the basis the XPS study, the oxidation state of molybdenum
in C was confirmed as +4.
The proposed catalytic mechanism for the pinacol coupling
reaction was shown in Scheme 3. Unlike the one-electron
reducing agent such as Ti(III), Cr(II), etc. employed in the
pinacol coupling reaction,13a the intermediate C was a unique
two-electron reducing species. The oxygen atoms of 2 equiv of
aldehydes formed a bond with molybdenum atom of the
intermediate catalyst C to give diketyl radical intermediate D.
The diketyl radicals were generated through two simultaneous
electron transfers from the molybdenum atom to two carbonyl
substrates. The oxidation state of molybdenum was changed
from +4 to +6. After the coupling of the diketyl radical, and
subsequently cleavage of the Mo-O bonds with Me3SiCl, the
diol silyl ether was formed and the intermediate B was
regenerated.
The dl and meso diastereoisomers were possibly formed by
different coupling patterns of the ketyl radicals as indicated in
Scheme 4. (i) The dl isomers should be produced through the
intramolecular coupling of the carbon radicals (Scheme 4, Path
A). The intramolecular coupling of two ketyl radicals in D might
be more favorable to form the cyclic metal-bridged intermediate
E, in which two aryl groups are oriented trans to each other, and
resulted in the formation of the dl stereochemistry in the product.
(ii) The intermolecular coupling of the carbon radicals should
lead to the formation of the meso isomer, through an acyclic
bimetallic intermediate (Scheme 4, Path B). The cis transition
state was favorable in this case. As the intramolecular reaction
of carbon radical coupling was more accessible than the
intermolecular reaction, the dl product was predominant.
By the way, the absolute configuration (R,R)-form of the
chiral ligand played a key role in the enantioselectivity. We
(24) (a) Hunsicker, R. A.; Klier, K. Chem. Mater. 2002, 14, 4807. (b)
Srinivasan, V.; Stiefel, E. I.; Elsberry, A.; Walton, R. A. J. Am. Chem.
Soc. 1979, 101, 2611.
J. Org. Chem, Vol. 72, No. 26, 2007 10033

Yang et al.
) 15 Hz), 6.70-7.38 (14H) ppm; 13C NMR (75 MHz, CDCl3) δ
29.69, 30.48, 34.67, 35.67, 52.31, 63.91, 120.48, 126.60, 125.21,
127.61, 129.20, 129.52, 136.61, 138.39, 143.17, 157.35 ppm; IR
(KBr) 2952, 1466, 1236, 909, 844, 760, 699, 555, 478 cm-1. Anal.
Calcd for C44H56MoN2O4: C, 68.38; H, 7.30; N, 3.62. Found: C,
68.43; H, 7.30; N, 3.91. Yellow solid and NH4PF6 were dissolved
in ethanol. Crystals suitable for X-ray diffraction were grown by
slow evaporation from solution for several days.
proposed a working model for the radical coupling of E, which
explained the absolute configuration of the favored enantiomer
of the dl isomer, as shown in Figure 4. The aryl group of
aldehyde oriented away from the phenyl group at the backbone
of the ligand as far as possible owing to steric hindrance. This
situation led to the formation of the (S,S) enantiomer of the dl
pinacol products, and was consistent with the experimental
results.
General Procedure for Pinacol Coupling Reaction. To a
mixture of Mo(L3)O2 (57.8 mg, 0.075 mmol), H2L3 (24 mg, 0.0375
mmol), and Zn powder (130 mg, 3 mmol) was added anhydrous
THF (2 mL) under nitrogen atmosphere. The yellow mixture was
stirred for 10 min at room temperature, and then cooled to 0 °C.
The freshly distilled Me3SiCl (127 µL, 1 mmol) was added and
the suspension turned red. After 20 min, aldehyde (0.5 mmol) was
added. The mixture was stirred at 0 °C for a specified length of
time. The suspension was filtered through a glass funnel, then the
filtrate was treated with 2 M HCl (5 mL) and stirred until the silyl
ether was completely desilylated (monitored by TLC). The mixture
was extracted with EtOAc (3 × 10 mL) and the organic phase was
washed with a saturated NaHCO3 solution (2 × 10 mL) and then
dried over anhydrous Na2SO4. After removal of solvent under
vacuum, the crude product was purified by flash chromatography
on silica gel (5:1; petroleum ether/EtOAc).
Conclusions
The highly diasteroselective and enantioselective pinacol
coupling reaction with the optically active Salan-Mo dioxo
complex as an effective precatalyst was developed. The mo-
lecular structure of the precatalyst Mo(L3)O2 was characterized
with X-ray analysis as a monomer, with R-cis configuration
coordination around the molybdenum atom. The XPS study
exhibited the oxidation state of the key intermediate is +4. The
possible mechanism was proposed with a two-electron reducing
process. The stereochemical outcome of the reaction was
speculated by the possible mechanism. Our study will provide
the basis for studies on the application of chiral Mo dioxo
complexes.
Acknowledgment. We gratefully acknowledge the National
Natural Science Foundation of China (20472028, 20332050, and
20672053) and the National Basic Research Program of China
(2007CB925103) for their financial support. The Program for
New Century Excellent Talents in the University of China is
also acknowledged.
Experimental Section
Synthesis of R,R-Mo(L3)O2. R,R-H2L3 (2.73 g, 5 mmol) was
dissolved in methanol (40 mL), followed by the addition of MoO2-
(acac)2 (1.79 g, 5.5 mmol). The resulting brown mixture was
refluxed for about 6 h with magnetic stirring. After completion of
the reaction (monitored by TLC), the solvent was removed in
vacuum. The crude product was purified by column chromatography
on silica gel (5:1; petroleum ether/EtOAc). Yellow crystals were
obtained (3.67 g, 95%). ESI-MS m/z 774 [Mo(L3)O2 + H]+ (40);
1H NMR (300 MHz, CDCl3) δ 1.33 (s, 18H), 1.57 (s, 18H), 3.64-
3.69 (d, 2H, J ) 15 Hz), 3.88-3.92 (m, 2H), 5.18-5.23 (d, 2H, J
Supporting Information Available: Experimental procedures,
spectral data for all new compounds, and crystallographic data and
an X-ray crystallographic file (CIF format). This material is
available free of charge via the Internet at http://pubs.acs.org.
JO701842R
10034 J. Org. Chem., Vol. 72, No. 26, 2007