Catalytic asymmetric reaction with water: Enantioselective synthesis of α-hydroxyesters by a copper-carbenoid O-H insertion reaction

Article abstract of DOI:10.1002/anie.200704651

(Chemical Equation Presented) Taking on water: A novel catalytic asymmetric metal-carbenoid insertion reaction with water has been developed with copper complexes of chiral spiro bisoxazoline ligands as catalysts. This reaction provides an efficient and practical procedure for preparing chiral α-hydroxyesters and acids starting from readily available materials in high yields and enantioselectivities. BAr_F^- = [B{3,5-(CF₃)₂C₆H₃)} ₄]^-.

Full text of DOI:10.1002/anie.200704651

Communications
DOI: 10.1002/anie.200704651
Asymmetric Catalysis
Catalytic Asymmetric Reaction with Water: Enantioselective Synthesis
À
of a-Hydroxyesters by a Copper–Carbenoid O H Insertion Reaction**
Shou-Fei Zhu, Chao Chen, Yan Cai, and Qi-Lin Zhou*
As one of the most abundant, safe, environmentally benign,
and cost-efficient resources, water has been widely used in
chemical synthesis and production.[1] However, catalytic
various ligands developed by us and by others were briefly
investigated (Table 1). The bisoxazoline ligands such as
asymmetric transformations using water as
a reactant
remain a great challenge to chemists, and successful examples
are very limited.[2] Transition-metal-catalyzed asymmetric
À
insertion of a-diazoesters into the O H bond of water
provides an extremely simple approach for the synthesis of
chiral a-hydroxyesters in an efficient and atom-economical
way.[3] Although great efforts have been devoted toward the
development of efficient catalysts for this important reaction,
only two examples of catalytic asymmetric insertions of a-
diazoesters into water with low enantioselectivities have been
documented.[4] In 1997, Landais and co-workers[5] reported
the Rh-catalyzed asymmetric insertion of a-diazoester with
water in moderate yield (59%) and very low enantioselectiv-
ity (8% ee). Maier and Fu[6] also attempted the catalytic
asymmetric insertion reaction of methyl a-diazophenylace-
tate with water using chiral copper/bisazaferrocene com-
plexes as catalysts, and obtained the corresponding a-
hydroxyesters in 55% yield with 15% ee. We recently
demonstrated that the copper complexes of chiral spiro
bisoxazoline ligands (spirobox, 1) are highly efficient catalysts
Scheme 1.
Table 1: Optimization of the reaction conditions for the asymmetric
insertion of methyl a-diazophenylacetate with water.[a]
Entry [M]
Ligand
Solvent
T
Yield
ee
[8C] [%][b]
[%][c]
1
2
3
4
5
6
7
CuCl
(Sa,S,S)-1a
(Ra,S,S)-1a
(Sa,S,S)-1b
(Sa,S,S)-1c
(S,S)-Ph-box
(S,S)-iPr-pybox
(Sa,S,S)-Ph-bina- CH2Cl2 10
box
(Ra,S,S)-Ph-bina- CH2Cl2 10
box
CH2Cl2 10
CH2Cl2 10
CH2Cl2 10
CH2Cl2 10
CH2Cl2 10
CH2Cl2 10
76
36
62
53
81
51
71
42
13
20
14
11
0
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
À
for the asymmetric insertions of a-diazoesters into the N H
[7]
À
bonds of anilines and O H bonds of phenols. As a part of
our continuing efforts on this compelling research topic, we
report herein our investigations on the enantioselective
insertion reaction of a-diazoesters with water catalyzed by
Cu/spirobox complexes.
0
8
CuCl
69
0
The insertion reaction of methyl a-diazophenylacetate
(2a) with water was performed in dichloromethane at 108C
with a copper catalyst generated in situ from 5 mol% CuCl,
9
10
11
12
13
14
15
16
17
18
19
20
21
CuCl2
CuBr2
(Sa,S,S)-1a
(Sa,S,S)-1a
CH2Cl2 10
CH2Cl2 10
CH2Cl2 10
CH2Cl2 10
CH2Cl2 10
CH2Cl2 10
CH2Cl2 30
CH2Cl2 30
CH2Cl2 30
CHCl3 10
DCE
toluene 10
THF 10
CHCl3 25
CHCl3 40
CHCl3 60
95
81
61
95
66
79
50
50
44
85
82
38
trace
90
91
67
45
49
44
44
26
72
20
54
38
81
80
19
–
Cu(OTf) (Sa,S,S)-1a
CuPF6 (Sa,S,S)-1a
Cu(OAc)2 (Sa,S,S)-1a
CuSO4 (Sa,S,S)-1a
Ag(OTf)2 (Sa,S,S)-1a
NiCl2
AuCl
CuSO4
CuSO4
CuSO4
CuSO4
[8]
6 mol% ligand, and 6 mol% NaBArF (Scheme 1). First,
[*] Dr. S.-F. Zhu, Y. Cai, Prof. Q.-L. Zhou
State Key Laboratory and Institute of Elemento-organic Chemistry
Nankai University
(Sa,S,S)-1a
(Sa,S,S)-1a
(Sa,S,S)-1a
(Sa,S,S)-1a
(Sa,S,S)-1a
(Sa,S,S)-1a
(Sa,S,S)-1a
(Sa,S,S)-1a
(Sa,S,S)-1a
Tianjin 300071 (China)
Fax: (+86)22-2350-6177
E-mail: qlzhou@nankai.edu.cn
10
C. Chen
22[d] CuSO4
23[e] CuSO4
24[f] CuSO4
85
90
25
Institute of Fine Chemicals
East China University of Science and Technology
Shanghai 200237 (China)
[**] We thank the National Natural Science Foundation of China, the
Major Basic Research Development Program (Grant No.
2006CB806106), the “111” project (B06005) of the Ministry of
Education of China, and Merck Research Laboratories for financial
support.
[a] Reaction conditions: [M] (0.015 mmol), ligand (0.018 mmol), NaBArF
(0.018 mmol), and solvent (3 mL) were stirred under argon at room
temperature for 2 h to 4 h, then water (1.5 mmol) and methyl a-
diazophenylacetate (0.3 mmol) were sequentially introduced, and the
reaction mixture was stirred for 2 h to 24 h. [b] Yield of isolated product.
[c] Determined on SFC using a Chiralcel OD-H column. [d] Reaction
time: 30 min. [e] Reaction time: 15 min. [f] Reaction time: 5 min.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
932
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Chemie
spirobox 1, Ph-box,[9] iPr-pybox,[10] and Ph-binabox[11] showed
good reactivity in the reaction, but only the spiro bisoxazoline
ligand (Sa,S,S)-1a gave a moderate level of enantioselectivity
(42% ee, Table 1, entry 1). Phosphine-containing ligands
including binap,[12] sdp,[13] phox,[14] and siphox[15] were also
investigated. The reactions using these ligands require a
higher temperature (308C) and exhibit no enantioselectivity
(data not shown).
Table 2: Substrate scope for the asymmetric insertion of a-diazoesters
with water.[a]
Entry
R1
R2
Product
Yield [%]
ee [%]
To improve the enantioselectivity of the insertion of
methyl a-diazophenylacetate (2a) with water, the reaction
conditions were carefully optimized by using ligand (Sa,S,S)-
1a. A variety of copper salts were compared as precursors of
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Ph
Ph
Ph
Me
Et
iPr
3a
3b
3c
3d
3e
3 f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
91
91
81
83
87
90
83
86
87
89
85
88
92
91
81
71
90
76
70
78
90 (R)
88 (R)
86 (R)
92 (R)
92
92 (R)
92 (R)
91 (R)
92
91 (R)
89
88 (R)
88
94 (R)
89
50 (R)
36 (R)
90 (R)
90
4-MeC6H4
4-PhC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
3-MeC6H4
3-MeOC6H4
3-FC6H4
3-ClC6H4
3-BrC6H4
3,4-Cl2C6H3
2-MeC6H4
2-MeOC6H4
2-ClC6H4
2-naphthyl
3-thienyl
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Bn
À
the catalyst. All tested copper compounds gave O H
insertion products in good yields and moderate enantiomeric
excesses, with CuSO4 showing the highest enantioselectivity
(72% ee, Table 1, entry 14). In addition to copper, other
metals such as Ag, Ni, and Au can also be applied as catalyst
precursors for the insertion reaction although the reactivities
and enantioselectivities are lower compared to those obtained
with CuSO4 (Table 1, entries 15–17). Variation of the solvent
showed that CHCl3 and 1,2-dichloroethane (DCE) are better
solvents, affording insertion products in higher enantiomeric
excesses (Table 1, entries 18 and 19). In the coordinating
solvent THF, the insertion reaction was prevented (Table 1,
entry 21). Further studies revealed that the reaction is
sensitive to temperature. Increasing the reaction temperature
from 108C to 408C resulted in improvements in both yield
and enantioselectivity (Table 1, entries 22 and 23 vs. entry 18).
However, as the reaction temperature was further elevated to
608C, both yield and ee value of the insertion product
dramatically dropped (Table 1, entry 24). The insertion reac-
tion can be carried out in the presence of 2 to 100 equivalents
water, giving methyl a-hydroxyphenylacetate in 87–91%
yield with 90% ee.[16]
3s
3t
78 (R)
[a] The reaction conditions are the same as those in Table 1, entry 23. All
reactions were completed within 30 min. For details of operation and
analysis, see the Supporting Information.
the corresponding a-hydroxyester in good yield and enantio-
selectivity (Table 2, entry 20).
We also conducted a carbenoid insertion with deuterated
water. The reaction of a-diazophenylacetate and D2O gave
methyl a-deutero-a-hydroxyphenylacetate in 87% yield with
A wide range of a-diazoesters was examined in the
insertion reaction with water under optimal reaction con-
ditions, and the results were summarized in Table 2. The ester 88% ee. Moreover, in a comparative reaction between H2O
moiety of the diazo compounds has a slight effect on the
and D2O, a predominant H2O insertion product (72%) was
obtained (Scheme 2), which is similar to the observation by
reaction, with a smaller R2 group being preferable for high
yield and enantioselectivity (Table 2, entries 1–3). All tested Maier and Fu in the insertion of carbenoids into alcohols.[6]
a-diazophenylacetate substrates having para or meta sub-
À
stituents on the phenyl rings gave O H insertion products in
high yields (81–92%) and high enantioselectivities (88–
94% ee) regardless of the electronic properties and steric
hindrance of the substituents (Table 2, entries 4–14). In the
reaction of ortho-substituted a-diazophenylacetates, the sit-
uation is very different. The insertion of a-diazo-2-methyl-
phenylacetate (2o) with water had an enantioselectivity of
89% ee (Table 2, entry 15), which was similar to that in the
reaction of a-diazophenylacetate. However, the reactions of
a-diazo-2-methoxyphenylacetate (2p) and a-diazo-2-chloro-
Scheme 2.
À
phenylacetate (2q) gave O H insertion products in very low
enantioselectivities (50% and 36% ee, Table 2, entries 16 and prepared by hydrolysis of the insertion products 3. For
Optically pure mandelic acid derivatives can be readily
À
17). Additionally, a-diazo-2-naphthylacetate (2r) and a-
diazo-3-thienylacetate (2s) were also suitable substrates for
example, the hydrolysis of O H insertion products 3a and 3n
in aqueous NaOH gave the acids 4a and 4n (Scheme 3).[17]
À
the O H insertion reaction with water (Table 2, entries 18 After recrystallization from DCE the optically pure mandelic
and 19). The benzyl a-diazopropionate (2t) smoothly under-
acids were obtained.
went the asymmetric insertion reaction with water to afford
In summary, the first highly enantioselective carbenoid
insertion into water has been realized with Cu/spirobox
Angew. Chem. Int. Ed. 2008, 47, 932 –934
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Communications
F. Kakiuchi, E. N. Jacobsen, Science 1997, 277, 936; d) A. El-
Qisairi, O. Hamed, P. M. Henry, J. Org. Chem. 1998, 63, 2790.
[3] For reviews on non-asymmetric catalytic insertion of a-diazo-
esters with water, see: a) M. P. Doyle, M. A. McKervey, T. Ye,
Modern Catalytic Methods for Organic Synthesis with Diazo
compounds, Wiley, New York, 1998, chap. 8; b) T. Ye, M. A.
McKervey, Chem. Rev. 1994, 94, 1091; c) D. J. Miller, C. J.
Moody, Tetrahedron 1995, 51, 10811.
[4] For diastereoselective carbenoid insertion into water, see: a) Y.
Landais, D. Planchenault, V. Weber, Tetrahedron Lett. 1994, 35,
9549; b) E. Aller, D. S. Brown, G. G. Cox, D. J. Miller, C. J.
Moody, J. Org. Chem. 1995, 60, 4449; c) M. P. Doyle, M. Yan,
Tetrahedron Lett. 2002, 43, 5929.
Scheme 3. Reaction conditions: 1) 1.25m NaOH, EtOH, 08C to RT,
2 h. 2) Recrystallization from DCE. Optical rotation is shown in
degcm3 gÀ1 dmÀ1 and concentration in gcmÀ3
.
complexes as catalysts. This reaction represents one of few
catalytic asymmetric procedures using water as a reactant and
provides an efficient method for preparing chiral a-hydroxy-
esters and acids starting from readily available materials
under mild reaction conditions.
[5] P. Bulugahapitiya, Y. Landais, L. Parra-Rapado, D. Planche-
nault, V. Weber, J. Org. Chem. 1997, 62, 1630.
[6] T. C. Maier, G. C. Fu, J. Am. Chem. Soc. 2006, 128, 4594.
[7] a) B. Liu, S.-F. Zhu, W. Zhang, C. Chen, Q.-L. Zhou, J. Am.
Chem. Soc. 2007, 129, 5834; b) C. Chao, S.-F. Zhu, B. Liu, L.-X.
Wang, Q.-L. Zhou, J. Am. Chem. Soc. 2007, 129, 12616.
[8] BArFÀ = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate.
[9] Ph-box = 2,2’-bis(4,5-dihydro-4-phenyloxazol-2-yl)propane.
[10] iPr-pybox = 2,6-bis(4,5-dihydro-4-isopropyloxazol-2-yl)pyridine.
[11] Ph-binabox = 2,2’-bis(4,5-dihydro-4-phenyloxazol-2-yl)-1,1’-
binaphthyl.
[12] binap = 2,2’-bis(diphenylphosphino)-1,1’-binaphthyl.
[13] sdp = 7,7’-bis(diphenylphosphino)-1,1’-spirobiindane.
[14] phox = 2-(2-diphenylphosphinophenyl)-4,5-dihydro-4-isoprop-
yloxazole.
Received: October 9, 2007
Published online: December 14, 2007
Keywords: asymmetric catalysis · carbenoids · hydroxyesters ·
.
insertion · water
[1] For general reviews, see: a) “Special Issue: Water”, Chem. Rev.
2002, 102, 2625; b) G. W. Robinson, S. B. Zhu, S. Singh, M. W.
Evans, Water in Biology, Chemistry, and Physics, World Scien-
tific, Singapore, 1996; c) C.-J. Li, T.-H. Chen, Organic Reactions
in Aqueous Media, Klewer Academic Publisher, Dordrecht,
1997.
[15] siphox = 7-diphenylphosphino-7’-(4,5-dihydro-4-phenyloxazol-
2-yl)-1,1’-spirobiinane.
[16] Because the reaction is biphasic, the amount of water used has a
negligible influence on the yield and enantioselectivity.
[17] a) U. Felfer, U. T. Strauss, W. Kroutil, W. M. F. Fabian, K. Faber,
J. Mol. Catal. B 2001, 15, 213; b) Y. Sun, X. Wang, J. Wang, Q.
Meng, H. Zhang, L. Jiang, Z. Zhang, Org. Lett. 2005, 7, 5425.
[2] For a review, see: a) Comprehensive Asymmetric Catalysis (Eds.:
E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer, Heidelberg,
1999, chap. 11 and 35; for examples, see: b) H. Alper, N. Hamel,
J. Am. Chem. Soc. 1990, 112, 2803; c) M. Tokunaga, J. F. Larrow,
934
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