Catalytic asymmetric cyano-phosphorylation of aldehydes promoted by heterobimetallic YLi3tris(binaphthoxide) (YLB) complex

Article abstract of DOI:10.1055/s-2004-832821

A highly enantioselective cyano-phosphorylation of aldehydes catalyzed by YLi₃tris(binaphthoxide) complex (YLB, 1) is described. Slow addition of diethyl cyanophosphonate (4) to aldehydes 5 in the presence of 1 (10 mol%), H₂O (30 mol%), tris(2,6-dimethoxyphenyl)phosphine oxide (10 mol%, 3a), and BuLi (10 mol%) afforded cyanohydrin O-phosphates 6 in up to 98% yield and 97% ee.

Full text of DOI:10.1055/s-2004-832821

2
434
CLUSTER
Catalytic Asymmetric Cyano-Phosphorylation of Aldehydes Promoted by
Heterobimetallic YLi tris(binaphthoxide) (YLB) Complex
3
C
Y
atalytic
A
symme
u
tric Cyano-P
m
hosphorylation of
A
i
ldehydes Abiko, Noriyuki Yamagiwa, Mari Sugita, Jun Tian, Shigeki Matsunaga, Masakatsu Shibasaki*
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Fax +81(3)56845206; E-mail: mshibasa@mol.f.u-tokyo.ac.jp
Received 2 June 2004
Abstract: A highly enantioselective cyano-phosphorylation of al-
dehydes catalyzed by YLi tris(binaphthoxide) complex (YLB, 1) is
described. Slow addition of diethyl cyanophosphonate (4) to alde-
3
O
Li
O
O
Li
OMe
hydes 5 in the presence of 1 (10 mol%), H O (30 mol%), tris(2,6-
2
NC
NC
OEt
OEt
O
Y
dimethoxyphenyl)phosphine oxide (10 mol%, 3a), and BuLi (10
mol%) afforded cyanohydrin O-phosphates 6 in up to 98% yield
and 97% ee.
O
O
2
Li
P
O
O
3
O
P
OMe
Key words: asymmetric catalysis, cyanohydrins, Lewis acid, phos-
phorylation, yttrium
3a
OEt
4
YLi3tris[(S)-binaphthoxide]
S)-YLB 1
(
Catalytic asymmetric cyanation reaction of carbonyl com-
pounds is one of the most powerful tools available to sup-
ply useful chiral building blocks. Although various
methods have been developed over the last two decades,1
Figure 1 Structures of YLi tris(binaphthoxide) [YLB (1)], ethyl
cyanoformate (2), tris(2,6-dimethoxyphenyl)phosphine oxide (3a),
and diethyl cyanophosphonate (4)
3
(
CH ) SiCN (TMSCN) and/or HCN are most often used
3 3
as cyanide sources to afford cyanohydrins and their TMS Initially, we applied the optimized conditions for the cat-
ethers. The intrinsic instability of cyanohydrins and their alytic asymmetric cyano-ethoxycarbonylation reaction2
TMS ethers, however, is sometimes problematic for fur- to the cyano-phosphorylation reaction. The (S)-YLB (1,
ther transformations. Therefore, the development of a 10 mol%) catalyst with H O (30 mol%), Ar P(O) (3a, 10
a
2
3
one-pot cyanation–O-protection reaction with a stable mol%), and BuLi (10 mol%) promoted the reaction of 5a
2
protecting group is desirable. To address this issue, we
and 4 at –78 °C, affording cyanohydrin O-phosphate 6a in
3
,4
and others recently developed a catalytic asymmetric 66% yield and 86% ee with corresponding cyanohydrin
cyano-ethoxycarbonylation reaction of aldehydes and (11% yield, Table 1, entry 1). The results shown in entries
ketones using ethyl cyanoformate (2) as the cyanide 2–4 suggested that all three additives [H O, Ar P(O) 3a,
2
,3
4
2
3
source, affording the chiral cyanohydrin O-carbonates in and BuLi] were essential for good enantioselectivity. Dur-
5
one-pot. In our system, the YLi tris(binaphthoxide) com- ing optimization studies, we encountered reproducibility
3
plex [YLB (1), Figure 1] effectively promoted the reac- problems both in terms of reactivity and selectivity. We
tion in the presence of three additives; H O, tris(2,6- hypothesized that 4 might partially decompose the YLB
2
dimethoxyphenyl)phosphine oxide (3a), and BuLi. The complex (1), because 4 is a good phosphorylating reagent
9
cyanohydrin O-carbonates were obtained in high yield (up of phenolic OH groups. A slow addition of 4 was effec-
to 100% yield) and ee (up to 98% ee).
tive to overcome the problem. As shown in entry 5, both
chemical yield and enantiomeric excess were improved
when 4 was added slowly over one hour to the reaction
mixture at –78 °C. Cyanohydrin O-phosphate 6a was ob-
tained in 97% yield and 92% ee after two hours under the
optimized conditions.
To extend the utility of our catalyst system, we investigat-
ed the use of other cyanide sources. Cyanohydrin O-phos-6
phate is a useful building block found in pesticides.
Although efficient one-pot racemic syntheses of cyanohy-
drin O-phosphate were reported two decades ago using di-
7
ethyl cyanophosphonate (4) as the cyanide source, there Substituent effects of the phosphine oxide are summa-
is only one recent report of catalytic asymmetric cyano- rized in Table 2. Triphenylphosphine oxide (3b) resulted
phosphorylation reaction by Nájera, Saá and co-workers.8 in a slightly lower ee and reactivity (88% ee, 85% yield,
Herein, we disclose a catalytic asymmetric cyano-phos- entry 2). Tris(2,4,6-trimethoxyphenyl)phosphine oxide
phorylation reaction of aldehydes using YLB (1). Cyano- (3c) afforded comparable enantioselectivity and reactiv-
hydrin O-phosphates were obtained in up to 98% yield ity (95% yield, 91% ee, entry 3) On the other hand,
10
and 97% ee.
tris(2,4,6-trimethylphenyl)phosphine oxide (3d) pro-
duced worse results (75% yield, 79% ee, entry 4), indicat-
ing the importance of the MeO-group rather than steric
bulkiness at the ortho-position.
SYNLETT 2004, No. 13, pp 2434–2436
Advanced online publication: 24.09.2004
DOI: 10.1055/s-2004-832821; Art ID: Y03204ST
0
3
.1
1
.2
0
0
4
©
Georg Thieme Verlag Stuttgart · New York

CLUSTER
Catalytic Asymmetric Cyano-Phosphorylation of Aldehydes
2435
Table 1 Optimization of the Reaction Conditions
Linear and branched aliphatic aldehydes (entry 5–8) gave
good chemical yield (82–90%) and good enantiomeric ex-
cess (82–97% ee). Aldehyde 5h gave the highest enantio-
selectivity among the aldehydes examined (97% ee, entry
8). On the other hand, aldehyde 5i gave 6i in slightly lower
enantioselectivity, probably due to the steric factor (entry
(S)-YLB 1 (10 mol%)
O
P
H2O (30 mol%)
OEt
OEt
O
O
P
Ar3P=O 3a (10 mol%)
n-BuLi (10 mol%)
O
*
+
OEt
OEt
Ph
H
NC
Ph
CN
THF, –78 °C
5a
4
6a
9
). a,b-Unsaturated aldehydes 5j gave 6j in only 24% ee
entry 10), although high enantiomeric excess was ob-
tained in the cyano-ethoxycarbonylation reaction of 5j
1
.1 mol equiv
(
Additive (mol%)
H O
2
(
100% yield, 91% ee). The result shown in entry 10 indi-
Entry
Ar P=O BuLi
Time
(h)
Yield
(%)
ee
2
3
3a
(%)
86
19
29
75
92
cated that the catalytic cycle for the cyano-phosphoryl-
ation reaction might be different from that for the cyano-
1a
2
30
0
10
10
0
10
10
10
0
1
4
4
4
2
66
58
54
63
97
12
ethoxycarbonylation reaction.
Table 3 Catalytic Asymmetric Cyano-Phosphorylation of Alde-
hydes
3
30
30
30
(
S)-YLB 1 (10 mol%)
O
P
4
10
10
H2O (30 mol%)
Ar3P=O 3a (10 mol%)
n-BuLi (10 mol%)
OEt
OEt
5b
O
O
P
O
10
a
+
OEt
OEt
Cyanohydrin (11%) was obtained.
Compound 4 was slowly added over 1 h.
R
H
NC
R
CN
THF, –78 °C, 2 h
*
b
5
4
6
a
1
.2 mol equiv
Entry Aldehyde
Product
Yield ee
The scope and limitations of the substrates are summa-
rized in Table 3. In all entries, the reactions were per-
formed at –78 °C for two hours with the slow addition of
(
%)
(%)
1
1
1
2
CHO
5a 6a
97
92
4
. Aromatic aldehydes gave a high yield (95–98%) and
good enantiomeric excess (81–93% ee, entries 1–4).
CHO
CHO
5b 6b
98
93
Table 2 Effects of Phosphine Oxides
(
S)-YLB 1 (10 mol%)
O
P
Me
H2O (30 mol%)
Ar3P=O 3 (10 mol%)
n-BuLi (10 mol%)
OEt
OEt
3
5c
6c
98
95
81
89
O
O
P
O
*
+
OEt
OEt
Ph
H
NC
Ph
CN
THF, –78 °C
5a
4
6a
4b
5d 6d
1
.1 mol equiv
CHO
Entry Ar in Ar P=O
Yield (%) ee (%)
3
1
OMe
3a
97
92
5b
6
5e
5f
6e
6f
90
83
92
82
CHO
CHO
OMe
2
3
3b
3c
85
96
88
91
7
8
CHO
5g 6g
5h 6h
82
82
96
97
OMe
OMe
CHO
MeO
9
0
CHO
CHO
5i
5j
6i
6j
81
71
76
24
4
Me
3d
75
79
1
Me
Me
a
a
Compound 4 was slowly added over 1 h at –78 °C, and the reaction
Compound 4 was slowly added over 1 h at –78 °C.
mixture was stirred further 1 h at –78 °C.
b
Compound 3c was used instead of 3a.
Synlett 2004, No. 13, 2434–2436 © Thieme Stuttgart · New York

2
436
Y. Abiko et al.
CLUSTER
In conclusion, we developed a catalytic asymmetric cy-
ano-phosphorylation reaction promoted by the YLB com-
plex. Cyanohydrin O-phosphates were obtained with
good yield (up to 98%) and enantiomeric excess (up to
(8) Baeza, A.; Casas, J.; Nájera, C.; Sansano, J. M.; Saá, J. M.
Angew. Chem. Int. Ed. 2003, 42, 3143.
(9) Guzmán, A.; Díaz, E. Synth. Commun. 1997, 27, 3035; and
references therein.
(
10) The phosphine oxides 3 were synthesized form
corresponding phosphines: Kim, R. D.; Stevens, C. H.
Polyhedron 1994, 13, 727.
9
7% ee). Mechanistic studies are now in progress.
(
11) General Procedure for the Cyano-Phosphorylation
Reaction.
Acknowledgment
To 3a (164.6 mg, 0.3 mmol) in a test tube were added the (S)-
We thank financial support by Grand-in-Aid for Specially Promo-
ted Research and Grand-in-Aid for Encouragements for Young
Scientists (B) (for SM) from JSPS and MEXT.
2
YLB·H O solution (5.00 mL, 0.3 mmol, 0.06 M, THF) and
2
BuLi (0.3 mmol) in hexane at r.t. After dissolving 3a
completely, the mixture was cooled to –78 °C, and 5a (3.0
mmol) in THF (4.50 mL) was added to the catalyst mixture.
After stirring for 10 min at –78 °C, 4 (0.55 mL, 3.6 mmol) in
THF (0.50 mL) was slowly added to the reaction mixture
over 1 h, and the reaction mixture was stirred at –78 °C for
additional 1 h. Then, HOAc in THF cooled to –78 °C was
References
(
1) For recent reviews for catalytic asymmetric cyanation
reaction of carbonyl compounds, see: (a) Brunel, J. M.;
Holmes, I. P. Angew. Chem. Int. Ed. 2004, 43, 2752.
added to the solution, and the mixture was diluted with H O.
2
(
(
b) North, M. Tetrahedron: Asymmetry 2003, 14, 147.
c) Shibasaki, M.; Kanai, M.; Funabashi, K. Chem.
The organic component was extracted with EtOAc. The
organic layer was washed with sat. aq NaHCO , H O, brine,
3
2
Commun. 2002, 1989. (d) Gröger, H. Chem.–Eur. J. 2001,
and dried over Na SO . After evaporating solvent, the
2
4
7, 5246. (e) Shibasaki, M.; Kanai, M. Chem. Pharm. Bull.
2001, 49, 511. (f) Gregory, R. J. H. Chem. Rev. 1999, 99,
3949.
residue was purified by silica gel flash column
chromatography (hexane–EtOAc = 7:1) to give 6a (97%
yield, 92% ee, R); colorless oil. IR (neat): n = 1269, 1024
(
(
2) (a) Tian, J.; Yamagiwa, N.; Matsunaga, S.; Shibasaki, M.
Angew. Chem. Int. Ed. 2002, 41, 3636. (b) Tian, J.;
Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. Org. Lett.
–1 1
cm . H NMR (CDCl ): d = 1.16 (dt, J
= 0.6 Hz, J = 7.0
3
(H,P)
Hz, 3 H), 1.32 (dt, J( = 0.6 Hz, J = 7.0 Hz, 3 H), 3.92–
H,P)
3
.99 (m, 2 H), 4.12–4.17 (m, 2 H), 6.02 (d, J( = 8.6 Hz, 1
H,P)
13
2003, 5, 3021. (c) For other catalytic asymmetric reaction
H), 7.39–7.40 (m, 3 H), 7.49–7.50 (m, 2 H). C NMR
= 7.3 Hz), 16.0 (d, J(C,P) = 7.1
using YLB(1) complex, see: Yamagiwa, N.; Matsunaga, S.;
Shibasaki, M. J. Am. Chem. Soc. 2003, 125, 16178.
3) (a) Casas, J.; Baeza, A.; Sansano, J. M.; Nájera, C.; Saá, J.
M. Tetrahedron: Asymmetry 2003, 14, 197. (b) Belokon’,
Y. N.; Blacker, A. J.; Clutterbuck, L. A.; North, M. Org.
Lett. 2003, 5, 4505.
(CDCl ): d = 15.8 (d, J
3
(C,P)
Hz), 64.6 (d, J( = 6.3 Hz), 64.8 (d, J(C,P) = 6.1 Hz), 66.5 (d,
C,P)
J(C,P) = 4.1 Hz), 116.1 (d, J(C,P) = 6.3 Hz), 127.5, 129.2,
31
1
–
(
30.6, 132.4 (d, J(C,P) = 4.1 Hz). P NMR (CDCl ): d =
3
+
1.93. LRMS (ESI, MeOH): m/z = 292 [M + Na ]. HRMS
+
FAB): m/z [N + H ] calcd for C H NO P: 270.0890;
1
2
17
4
(
(
4) Tian, S.-K.; Deng, L. J. Am. Chem. Soc. 2001, 123, 6195.
5) For reviews on lanthanide heterobimetallic asymmetric
catalysis, see (a) Shibasaki, M.; Yoshikawa, N. Chem. Rev.
21.7
found: 270.0894. [a]D +18.9 (c 1.2, CHCl ; 92% ee, R);
3
®
HPLC (DAICEL CHIRALPAK ) AD-H, hexane–2-
PrOH = 9:1, flow rate = 1.0 mL/min, retention time 14.5
min (S)/17.1 min (R). The absolute configuration of 6a was
determined comparing retention time in HPLC analysis with
that of the authentic product synthesized from commercially
available (R)-mandelonitrile (Aldrich Co. Ltd.) with 4.
12) Detailed mechanistic studies of asymmetric cyanation
reaction using YLB(1) and the cyanide source 2 and 4 will
be reported elsewhere in due course.
2002, 102, 2187. (b) Shibasaki, M.; Sasai, H.; Arai, T.
Angew. Chem., Int. Ed. Engl. 1997, 36, 1236. (c) For the
preparation and property of YLB complex: Aspinall, H. C.;
Dwyer, J. L. M.; Greeves, N.; Steiner, A. Organometallics
1999, 18, 1366.
(
(6) Hodakowski, J. E.; Mohammed, A. H. Eur. Pat. Appl. 1981,
EP 44, 214.
(
7) (a) Harusawa, S.; Yoneda, R.; Kurihara, T.; Hamada, Y.;
Shioiri, T. Chem. Pharm. Bull. 1983, 31, 2932. (b) Review:
Kurihara, T.; Harusawa, S.; Yoneda, R. J. Synth. Org. Chem.
Jpn. 1988, 46, 1164. (c) For a review of 4 as a coupling
reagent: Shioiri, T. J. Synth. Org. Chem. Jpn. 1979, 37, 856.
(
d) For other methods to synthesize cyanohydrin O-
phosphates, see: Micó, I.; Nájera, C. Tetrahedron 1993, 49,
327; and references therein.
4
Synlett 2004, No. 13, 2434–2436 © Thieme Stuttgart · New York