Enantioselective conjugate addition of diethylzinc to enones catalyzed by a copper complex of chiral aryl diphosphite

Article abstract of DOI:10.1039/a807997h

The 1,4-conjugate addition of diethylzinc to cyclohex-2-enone and cyclopent-2-enone catalyzed by a copper complex of a chiral aryl diphosphite gave the desired products with 90.2 and 76.6% ee respectively.

Full text of DOI:10.1039/a807997h

Enantioselective conjugate addition of diethylzinc to enones catalyzed by a
copper complex of chiral aryl diphosphite
Ming Yan, Li-Wei Yang, Kwok-Yin Wong and Albert S. C. Chan*
Union Laboratory of Asymmetric Synthesis and Department of Applied Biology and Chemical Technology,
The Hong Kong Polytechnic University, Hong Kong, China. E-mail: bcachan@polyu.edu.hk
Received (in Cambridge, UK) 15th October 1998, Accepted 16th November 1998
The 1,4-conjugate addition of diethylzinc to cyclohex-
-enone and cyclopent-2-enone catalyzed by a copper
complex of a chiral aryl diphosphite gave the desired
products with 90.2 and 76.6% ee respectively.
In 1991 Pringle et al. reported the synthesis of (R,R,R)-1 from
trichlorophosphine and (R)-binaphthol. A Ni0 complex of
(R,R,R)-1 was used in the hydrocyanation of norbornene, giving
a product with 38% ee.11 It is noticeable that the structure of 1
is entirely based on chiral binaphthol. (S,S,S)-1 is fairly stable to
oxygen in the solid state but is somewhat air- and moisture-
sensitive in solution.
2
The enantioselective conjugate addition of chiral organome-
tallic reagents to enones is an attractive method for C–C bond
formation. A number of successful methods for stereoselective
The addition of Et
model (Scheme 2). The effects of reaction temperature, solvent
and the ratio of (S,S,S)-1 to Cu(OTf) were investigated and the
2
Zn to cyclohex-2-enone 3b was used as a
1
,4-addition based on chiral auxiliaries or stoichiometric
organometallic reagents have been developed, but a highly
enantioselective catalytic version is still rare. Ni and Co
2
1
II
II
results are summarized in Table 1. In most cases complete
conversion and good enantioselectivity were obtained. No
1,2-addition product was detected by GC analysis. The reaction
was strongly dependent on the choice of solvents. The best
solvent was found to be toluene (90.2% ee, 100% conversion).
Coordinative solvents such as THF and MeCN gave sub-
stantially lower conversion rates and enantioselectivities
(22.4% conversion, 72.2% ee and 6.5% conversion, 0% ee,
respectively). The use of 2 equiv. (S,S,S)-1 increased the
enantioselectivity from 83.2 to 90.2% ee (entry 2 vs. entry 3).
catalysts containing chiral amino alcohol ligands are of
substantial interest, but they show enantioselectivity only for
2
3
acyclic enones. The copper complexes of chiral phosphites,
phosphorus amidites, phosphines,5 thiols6 and aminophos-
phines have been used in the catalytic conjugate addition of
4
7
Et
2
Zn or Grignard reagents to enones with low to moderate
enantioselectivity. Recently several chiral phosphorus ami-
8
9
dites and phosphite oxazolines have been used in the copper-
catalyzed conjugate addition of dialkylzinc to cyclohex-
2
-enone with excellent enantioselectivity. These ligands shared
2
Further increase of the ratio of (S,S,S)-1 to Cu(OTf) decreased
a common feature of a bridging of binaphthol with a chiral
amine through a phosphorus center. The active catalyst in the
the catalytic activity (entry 1). When less than 1 equiv. (S,S,S)-1
was used, the enantioselectivity decreased but the catalytic
activity was still high (entry 4). The optimum reaction
temperature was found to be ca. 0 °C. When the reaction
temperature decreased to 240 °C, the reaction became sluggish
and far less enantioselective (entry 8). Although the use of a low
catalyst:substrate ratio was rather ineffective, it is of interest to
note that increasing the concentration of the catalyst lowered the
enantioselectivity (entries 9–11). The preliminary results re-
I
reaction has been proposed by Feringa et al. to be an alkyl–Cu
species coordinated with two ligand molecules.8 The C
2
-
symmetric bidentate ligands in these reactions are of substantial
interest.4a Here we report the catalytic conjugate addition of
Et
Cu(OTf)
catalytic activity.
Optically pure aryl diphosphite (S,S,S)-1 was prepared by the
reaction of the (S)-chlorophosphite 2 and (S)-binaphthol in the
presence of Et
2
Zn to enones using a C
2
-symmetric chiral aryl diphosphite–
2
complex with good enantioselectivity and high
vealed that a catalyst concentration of 0.0008–0.0012
M
was
optimum. The copper complexes at different concentrations
may form different catalytic species. Similar results had been
reported by Feringa et al.4a When EtMgCl was used in place of
3
N (Scheme 1). The crude product was easily
Cl –EtOH. The structure of
purified by recrystallization in CH
2
2
the compound was supported by elemental analysis and spectral
data.10
Et
small amounts of 1,2-addition product were observed (entry
2).
The 31P NMR spectrum of the catalyst solution (L:Cu = 2:1,
2
Zn only racemic 4b was obtained as the major product and
1
OH
OH
O
O
toluene-d ) showed two peaks at d 231.6 and 149.0. The peak at
d 149.0 corresponded to free (S,S,S)-1 and the low field peak at
8
P
Cl
+
2
d 231.6 is expected to be (S,S,S)-1–Cu(OTf) . When excess
2
2
Et Zn was added at room temperature, the peak at d 231.6
disappeared quickly and a new peak at d 124.0 was observed.
This new species may be postulated to be an Et–Cu complex
Et3N
toluene, 0 °C
I
2
containing a molecule of (S,S,S)-1. The electron-rich nature of
I
31
Et–Cu caused the significant P NMR shift. Coordinative
solvents such as THF or MeCN competed with the enone
I
substrates for the coordinating site of the Cu catalyst and
O
O
O
O
O
O
P
P
(S,S,S)-1 (2 mol%)
Cu(OTf)2 (1 mol%)
toluene, 3 h, 0 °C
O
O
+
Et2Zn
n
n
*
3
a
b
c
n = 0
n = 1
n = 2
4a n = 0
b
c
n = 1
n = 2
(S,S,S)-1
Scheme 1
Scheme 2
Chem. Commun., 1999, 11–12
11

Table 1 Enantioselective 1,4-addition of diethylzinc to cyclohex-2-enone 3b catalyzed by (S,S,S)-1–Cu(OTf) a
2
Entry
2
Cu(OTf) /3b
1/Cu(OTf)
2
T/°C
Conversion (%)b
Ee (%)b
Configurationc
1
2
3
4
5
6
7
8
9
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.01
0.001
0.05
0.2
4
2
1
0.5
2
2
2
2
2
0
0
0
81.7
100 (92.0 )
88.3
90.2
83.2
79.1
70.9
87.7
84.6
39.4
67.5
57.1
45.2
0
S
S
S
S
S
S
S
S
S
S
S
—
d
100
100
100
100
100
24.1
54.5
100
100
0
40
20
220
240
0
0
0
278
1
1
1
0
1
2
2
2
2
e
f
0.01
100
a
.5 equiv. of diethylzinc was used and the reactions were carried out in toluene for 3 h. b The conversions and ee values were determined by GC with a
1
c
Chiraldex A-TA column (30 m 3 0.25 mm); no 1,2-addition product was observed. The absolute cofiguration was determined by optical rotation (ref. 12).
d
e
f
Isolated yield. Ethylmagnesium chloride was used. A small amount of 1,2-addition product was observed.
decreased the rate of reaction as well as the enantioselectiv-
ity.
The Cu complex of (S,S,S)-1 was also tested in the conjugate
We thank the Hong Kong Polytechnic University and the
Hong Kong Research Grants Council (Project number
PolyU34/96P) for financial support of this study.
II
addition of diethylzinc to cyclopent-2-enone 3a, cyclohept-
2
-enone 3c and chalcone 5, and the results are summarized in
Notes and references
Table 2. Up to now the catalytic conjugate addition of
organometallic reagents to 3a has been relatively unsuccess-
1
2
3
Reviews: R. Noyori, Asymmetric Catalysis in Organic Synthesis, VCH,
New York, 1993; P. Prelmutter, Conjugate Addition Reactions in
Organic Synthesis, Pergamon, Oxford, 1992; Advanced Asymmetric
Synthesis, ed. G. R. Stephenson, Chapman & Hall, London, 1996;
Advances in Catalytic Processes, ed. M. P. Doyle, JAI Press,
Greemwich, Connecticut, 1995, vol. 1; B. E. Rossiter and H. M.
Swingle, Chem. Rev., 1992, 92, 771; N. Krause, Angew. Chem., Int. Ed.,
4c,8,9
ful.
With the (S,S,S)-1–Cu(OTf)
2
catalyst system, the
conjugate addition of Et
2
Zn to 3a gave a good yield of the
desired product with 76.6% ee (entry 1). To the best of our
knowledge, this enantioselectivity was the best one so far
obtained for this reaction. Interestingly the absolute configura-
tion of the product was opposite to that from the conjugate
addition to 3b. The reversal of enantiofacial selectivity for 3a
was also observed previously by Rossiter et al.13 The conjugate
addition of Et Zn to 3c gave a lower conversion rate and
2
enantioselectivity than the reaction with 3b and 3a (entry 2,
Scheme 2).
1
998, 37, 283.
(a) C. L. Gibson, Tetrahedron: Asymmetry, 1996, 7, 3357; (b) A. H. M.
de Vries and B. L. Feringa, Tetrahedron: Asymmetry, 1997, 8, 1377; (c)
A. H. M. de Vries, R. Imbos and B. L. Feringa, Tetrahedron:
II
Asymmetry, 1997, 8, 1467; (d) Recently Ni catalysts containing chiral
diphosphine ligands were used in asymmetric addition of Grignard
reagents to unsaturated cyclic acetals with moderate enantioselectivity:
see E. Gomez-Bengoa, N. M. Heron, M. T. Didiuk, C. A. Lachaco and
A. H. Hoveyda, J. Am. Chem. Soc., 1998, 120, 7649.
A. Alexakis, J. Vastra, J. Burton and P. Mangency, Tetrahedron:
Asymmetry, 1997, 8, 3193.
Table 2 The addition of diethylzinc to enones 3a,c and 5 catalyzed by
(S,S,S)-1–Cu(OTf)
2
Conversion
Entry Substrate Solvent T/°C (%)a
Ee (%)a Configuration
4 (a) A. H. M. de vries, A. Meetsma and B. L. Feringa, Angew. Chem., Int.
Ed. Engl., 1996, 35, 2374; (b) F. Y. Zhang and A. S. C. Chan,
Tetrahedron: Asymmetry, 1998, 9, 1179; (c) E. Keller, J. Maurer, R.
Naasz, T. Schader, A. Meetsma and B. L. Feringa, Tetrahedron:
Asymmetry, 1998, 9, 2409.
5
6
7
8
9
100 (71.3b) 76.6
Rc
1
2
3
4
a
3a
3c
5
Toluene
Toluene
Toluene
THF
0
0
0
0
d
40.0
45
56.0
9.3
nd
e
R
R
A. Alexakis, J. Burton, J. Vastra and P. Mangency, Tetrahedron:
Asymmetry, 1997, 8, 3987.
D. Seebach, G. Jaeschke, A. Pichota and L. Audergon, Helv. Chim.
Acta., 1997, 80, 2515.
T. Mori, K. Kosaka, Y. Nakagawa, Y. Nagaoka and K. Tomioka,
Tetrahedron: Asymmetry, 1998, 9, 3175
B. L. Feringa, M. Pineschi, L. A. Arnold, R. Imbos and A. H. M. de
Vries, Angew. Chem., Int. Ed. Engl., 1997, 36, 2620.
A. K. H. Knobel, I. H. Escher and A. Pfaltz, Synlett, 1997, 1429.
5
62
16.5
The ee value of 4a and the conversion were determined by GC with a
Chiraldex A-TA Column (30 m 3 0.25 mm). The ee value of 4c and the
conversion were determined by GC with a Chrompack CP-Chirasil-Dex CB
(
25 m 3 0.25 mm). The ee value of 6 and the conversion were determined
by HPLC with a Diacel-OD column. Isolated yield. c The absolute
b
d
configuration was determined by optical rotation (ref. 14).
determined. Comparison of the retention time of 6 in HPLC with known
Not
e
data (ref. 9).
1
0 Selected data for (S,S,S)-1 containing 0.5EtOH (solvent of crystalliza-
tion): Calc. for C60 ·0.5C O: C, 78.12; H, 4.16%. Found: C,
) 145.7; d (CDCl3, 400MHz) 7.97 (d, J 8.8,
H), 7.90 (d, J 8.0, 2H), 7.82 (dd, J 8.0, J 8.8, 4H), 7.73 (d, J 8.0, 2H),
H
36
O
6
P
2
2 6
H
7
P
8.13; H, 4.16%; d (CDCl
3
H
2
The conjugate addition of Et Zn to chalcone gave 6 with poor
2
1
2
enantioselectivity and low conversion (entries 3 and 4, and
Scheme 3). The high specificity of the matching of substrate and
7.52 (d, J 8.8, 2H), 7.37 (m, 8H), 7.16–7.31 (m, 14H), 6.53 (d, J 8.8,
2H), 3.72 (q, J 6.8, 1H), 2.36 (s, 0.5H), 1.24 (t, J 6.8, 1.5H); d (CDCl
147.2, 147.0, 146.5, 134.2, 132.7, 132.2, 131.4, 131.0, 130.8, 130.2,
C
3
)
catalyst had been found in many other catalyst systems.2
c,8,9
1
1
30.0, 129.5, 128.3, 128.2, 128.1, 126.9, 126.8, 126.2, 126.0, 125.8,
The chiral match of the three binaphthol rings is very
important for efficient enantiocontrol. (S,R,S)-1 was prepared
25.1, 124.9, 124.6, 124.2, 122.4, 121.8, 121.7, 121.1; m/z (ESI) 915
+
20
(M
+ 1, 100%); Mp 196–198 °C (decomp.); [a]
D
+346.6 (c 1.085,
and used for the addition of Et
reaction conditions [1 mol% Cu(OTf)
toluene]. Compound 4b was obtained with only 30.6% ee (S).
2
Zn to 3b using the optimum
20
THF) [a rather different [a]
1)].
1 M. J. Baker and P. G. Pringle, J. Chem. Soc., Chem. Commun., 1991,
292.
D
value was reported by Pringle et al. (ref.
2
, 2 mol% (S,R,S)-1, 0 °C,
1
1
1
1
1
2 G. H. Posner and L. L. Frye, Isr. J. Chem., 1984, 24, 88.
3 B. E. Rossiter, M. Eguchi, G. B. Miao, N. M. Swingle, A. E. Hernandez,
D. Vickers, E. Fluckiger, R. G. Patterson and K. V. Reddy, Tetrahedron,
1993, 49, 965.
(
S,S,S)-1 (2 mol%)
O
Cu(OTf)2 (1 mol%)
O
+
Et2Zn
Ph
Ph
solvent, 3 h, 0 °C
Ph
*
Ph
1
4 R. K. Dieter and M. Tokles, J. Am. Chem. Soc., 1987, 109, 2040.
5
6
Scheme 3
Communication 8/07997H
12
Chem. Commun., 1999, 11–12