Enantioselective [2,3] sigmatropic rearrangement mediated by a butyllithium-chiral ligand complex

Article abstract of DOI:10.1039/a700906b

The first enantioselective [2,3] sigmatropic rearrangement of acyclic diprop-2-ynyl ethers and alkenyl benzyl ethers is achieved by a BuLi-chiral ligand complex.

Full text of DOI:10.1039/a700906b

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Enantioselective [2,3] sigmatropic rearrangement mediated by a
butyllithium–chiral ligand complex
Shino Manabe*†
Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan
The first enantioselective [2,3] sigmatropic rearrangement of
acyclic diprop-2-ynyl ethers and alkenyl benzyl ethers is
achieved by a BuLi–chiral ligand complex.
This chiral amino ether 1–BuLi complex is effective not only
for diprop-2-ynyl ether 2 but also for cis-but-2-enyl benzyl ether
4 (Scheme 1). The reaction gives syn alcohol 5 and anti alcohol
6
in a ratio of 9:1 in 50% yield.11 The ee of syn alcohol 5 was
The [2,3] sigmatropic rearrangement has been studied with
regard to its stereochemical course in view of its synthetic
application to the preparation of highly functionalized deriva-
64% and the ee of anti alcohol 6 was 80%. Relative
1
stereochemistries were determined by H NMR coupling
constants,12 and the ee and absolute configuration of the syn
1
1
tives. Asymmetric [2,3] sigmatropic rearrangement involving
alcohol were determined by H NMR after conversion to the
13
chiral auxiliaries has been investigated by Nakai and co-
workers and Enders and co-workers in order to achieve high
corresponding (R)-MTPA ester. ** The ee of anti alcohol 6
was determined directly by chiral HPLC [DAICEL CHIRAL-
2
i
3
21
diasteroselectivity. However, the enantioselective version of
CEL OJ, hexanes–Pr OH (50:1), 0.75 cm min , l = 254
this reaction has remained one of the unsolved problems in the
field of synthetic organic chemistry. Marshall and Lebreton
reported the first example of this reaction, in which a
nm].
Interestingly, the ee was sensitive to the substitution pattern
of the alkene. For instance, when trans-but-2-enyl benzyl ether
is used, the reaction gives 5 and 6 in the ratio 65:35 in 48%
yield. The ee of the syn alcohol 5 decreased to 16%, and the ee
of the anti alcohol 6 also decreased to 12%. In the case of
3-methylbut-2-enyl benzyl ether 7 (Scheme 2), the desired
product 8 was obtained in 68% yield and in 40% ee.††
In summary, the chiral ligand 1–BuLi complex is effective
for the enantioselective [2,3] sigmatropic rearrangement of
1
7
3-membered cyclic ether afforded the prop-2-ynylic alcohol in
0% ee by the use of a chiral lithium amide. But it has also been
3
reported that the same lithium amide was not effective for
acyclic substrates.3 Fujimoto and Nakai demonstrated an
enantioselective reaction for acyclic substrates via a boron ester
,4
5
enolate. Gladysz and co-workers reported the enantioselective
[
2,3] sigmatropic rearrangement of sulfur ylides using a chiral
6
3
rhenium complex. However, no examples of an enantio-
selective reaction of acyclic substrates involving an sp3
carbanion, which are the most typical substrates in this
rearrangement, have been demonstrated so far. We report herein
the first example of an enantioselective [2,3] sigmatropic
acyclic ethers involving an sp carbanion.
The author would like to thank Professor Kenji Koga for
helpful discussions.
3
7
Table 1 Rearrangement of 2 to give 3
rearrangement of acyclic ethers involving an sp carbanion.
Recently, this reaction was reported to proceed with complete
inversion of configuration at the carbanion carbon centre to give
the newly generated chiral centre. On the other hand, Hoppe
R
R
R
•
BuLi • 1
8
O
PhMe
et al. and Beak and co-workers have shown that asymmetric
HO
s
deprotonations can be effected with Bu Li–(2)-sparteine
R
complex to give a chiral dipole-stabilized carbanion which
reacts with electrofiles to give enantiomerically enriched
products.9 So it is expected that an enantioselective [2,3]
sigmatropic rearrangement could be possible if a chiral
carbanion can be generated by use of a BuLi–chiral ligand
complex. We have found that a complex of butyllithium with a
2
3
Yield (%)
of 3
R
C
Ee (%)
2
2
2c
2d
2e
a
b
7
H
15
50
51
29
57
37
61
62
59
48
46
c-Hex
10
t
chiral ligand 1 ठexerts a pronounced effect on this re-
arrangement.
Bu
Ph
Me Si
3
Initially acyclic diprop-2-ynyl ethers 2 were studied as they
have simple and symmetrical structures. The first attempt at
enantioselective [2,3] sigmatropic rearrangement of 2a medi-
ated by a complex of BuLi–(2)-sparteine was unsuccessful.
Although (2)-sparteine is known as a good chiral ligand in
many reactions, 3a was obtained in only 23% yield and 9% ee.
As a result the chiral amino ether 1 was designed, and was found
to work as a good chiral ligand for BuLi in this reaction.¶ Some
representative results are summarized in Table 1.∑
Me
Me
O
Ph
BuLi • 1
Ph
Ph
+
PhMe
Me
OH
OH
4
5
6
Scheme 1
Me
Ph
O
Me
O
Ph
Me
Me
BuLi • 1
Ph
Me2N
PhMe
Me
OH
MeO
7
8
1
Scheme 2
Chem. Commun., 1997
737

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Footnotes
OH
O
OSiMe2But
i, ii
CO2H
iii–v
*
†
E-mail: smanabe@postman.riken.go.jp
Present address: The Institute of Physical and Chemical Research
HO
C9H19
MOMO
C9H19
11
12
13
(RIKEN), Hirosawa, Wako-shi, Saitama 351-01 Japan.
vi
‡
§
All new compounds gave satisfactory spectroscopic data.
Compound 1 was prepared from (1R, 2R)-(2)-norpseudoephedrine in two
OMe
N
steps: (i) HCHO, HCO
2
2
H (100%); (ii) guaiacol, DEAD, PPh
3
, THF (25%).
C7H15
O
O
vii
Me
1
H NMR (270 MHz, [ H
6
]benzene): d 7.4–6.6 (9 H, m), 5.15 (1 H, d,
J = 6.6 Hz), 3.43 (3 H, s), 3.13 (1 H, dd, J = 6.6, 6.9 Hz), 2.40 (6 H, s);
mp 57 °C; [a] 279 (c 2.3, CHCl ). Mitsunobu reaction proceeded, with
net retention of configuration, via the azirizinium ion. The relative
configuration was determined by X-ray analysis. The kind assistance of Dr
Makoto Nakajima (Pharmaceutical Sciences, Hokkaido University) with
the X-ray analysis is gratefully acknowledged.
MOMO
C9H19
MOMO
C9H19
2
4
10
14
D
3
t
Scheme 4 Reagents and conditions: i, Bu Me
2
SiCl, Et
3
N, DMAP, CH
2
Cl
Cl,
2 2 2 4
Pr NEt, CH Cl , quant.; iv, Bu NF, THF, 82%; v, Jones’ reagent, acetone;
2
,
quant.; ii, octylmagnesium bromide, CuI, THF, 66%; iii, MeOCH
2
i
vi, MeNH(OMe)·HCl, Diethyl cyanophosphonate, Et
steps); vii, heptylmagnesium bromide, THF, 97%
3
N, DMF, 76% (2
¶
Typical procedure: To a solution of chiral ligand 1 (315 mg, 1.10 mmol)
3
3
in toluene (16 cm ), BuLi (0.63 cm , 1.67 m hexane solution, 1.05 mmol)
was added dropwise at 278 °C under Ar atmosphere. After 5 min diprop-
Me
Ph
Me
Me
Ph
Me
Me
Ph
Me
i
ii–iv
3
2
-ynyl ether 2a (290 mg, 1.0 mmol) in toluene (1 cm ) was added dropwise
CO2Me
to the resulting pale yellow solution via a cannula. The flask was rinsed with
OH
OAc
OH
3
toluene (1 cm ). The whole mixture was stirred at 278 °C for 5 h. The
8
15
Scheme 5 Reagents and conditions: i, Ac
ii, O , MeOH; iii, H , aq. NaOH; iv, CH
16
N, DMAP, CH
, Et O, 30% (3 steps)
3
reaction was quenched with 1 m HCl (20 cm ), and the aqueous layer was
2
O, Et
3
2 2
Cl , 91%,
3
extracted with ethyl acetate (30 cm 3 3). The organic layer was washed
3
3
3
2
O
2
N
2 2
2
3
with 1 m HCl (20 cm ), saturated aqueous NaHCO (20 cm ) and brine (20
2
3
2 4
cm ). After drying the mixture over Na SO , the mixture was concen-
trated. The residue was then purified by silica gel column chromatography,
References
and hydroxy allene 3a (145 mg, 50%) was obtained as a colourless oil.
1
1 For recent reviews see: T. Nakai and K. Mikami, Org. React., 1994, 46,
105; J. A. Marshall, in Comprehensive Organic Synthesis, ed. B. M.
Trost and I. Fleming, Pergamon, London, 1991, vol. 3, pp. 975–1014;
R. Br u¨ ckner, in Comprehensive Organic Synthesis, ed. B. M. Trost and
I. Fleming, Pergamon, London, 1991, vol. 6, pp. 873–908.
2 K. Mikami, O. Takahashi, T. Kasuga and T. Nakai, Chem. Lett., 1985,
1729; K. Mikami, K. Fujimoto, T. Kasuga and T. Nakai, Tetrahedron
Lett., 1984, 25, 6011; O. Takahashi, K. Mikami and T. Nakai, Chem.
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Int. Ed. Engl., 1994, 33, 2098; D. Enders and D. Backhaus, Synlett,
1995, 631.
∑
Spectroscopic data for 3a: H NMR: d 4.95 (1 H, d, J = 3.0 Hz), 4.93 (1
H, d, J = 3.0 Hz), 4.82 (1 H, dd, J = 1.9, 1.9 Hz), 2.23 (1 H, dt, J = 1.9,
7
1
8
2
.0 Hz), 2.22 (1 H, dt, J = 1.9, 7.0 Hz), 2.1–2.0 (2 H, m), 1.68 (1 H, brs),
1
3
.6–1.1 (20 H, m), 0.89 (6 H, t, J = 6.3 Hz); C NMR: d 204.37, 106.33,
6.38, 79.43, 79.03, 63.25, 31.81, 31.72, 29.27, 29.11, 28.77, 28.54, 27.68,
21
7.53, 22.59, 18.71, 14.04; nmax/cm 3400, 3000–2850, 2210, 1950, 850;
+
+
24
D
m/z 290 (M ), 289 (M 2 1); [a] + 18 (c 0.95, CHCl
ees were determined by HPLC analysis [DAICEL CHIRALCEL OD-H,
hexanes–Pr OH (300:1), l
trobenzoates. For 3c, the ee was determined by chiral HPLC analysis
3
). For 3a, 3b and 3c,
i
= 254 nm] of the corresponding p-ni-
i
[
DAICEL CHIRALCEL OD-H, hexanes–Pr OH (300:1), l = 254 nm] of
the corresponding 3,5-dinitrobenzoates. For 3d, the ee was determined by
3 J. A. Marshall and J. Lebreton, J. Am. Chem. Soc., 1988, 110, 2925.
4 J. A. Marshall and X. Wang, J. Org. Chem., 1992, 57, 2747.
5 K. Fujimoto and T. Nakai, Tetrahedron Lett., 1994, 35, 5019.
6 P. C. Cagle, A. M. Arif and J. A. Gladysz, J. Am. Chem. Soc., 1994, 116,
i
HPLC analysis [DAICEL CHIRALCEL OD-H, hexanes–Pr OH (300:1), l
254 nm]. Compound 3a could be converted to ketone 10 in four steps, as
shown in Scheme 3.
=
3
655; P. C. Cagle, O. Meyer, K. Weickhardt, A. M. Arif and
O
J. A. Gladysz, J. Am. Chem. Soc., 1995, 117, 11 730.
OH
C7H15
HO
•
C7H15
OH
C7H15
O
7 S. Matsui (Manabe), M. Nakajima and K. Koga, 7th IUPAC Symposium
on Organometallic Chemistry directed towards Organic Synthesis
(OMCOS 7), abstract 2B, Kobe, September, 1993; Nakai’s group has
also shown that this type of reaction proceeds in 70% ee: K. Tomooka,
N. Komine and T. Nakai, The Japan Chemical Society annual meeting,
abstract II 1208, Tokyo, March, 1996.
i, ii
iii–v
MOMO
MOMO
C9H19
C7H15
C7H15
3a
9
10
MOM = MeOCH2
8
R. Hoffman and R. Br u¨ ckner, Angew. Chem., Int. Ed. Engl., 1992, 31,
47; E. J. Verner and T. Cohen, J. Am. Chem. Soc., 1992, 114, 375;
K. Tomooka, T. Igarachi, M. Watanabe and T. Nakai, Tetrahedron Lett.,
992, 33, 5795.
Scheme 3 Reagents and conditions: i, MeOCH
ii, OsO , pyridine, PhH, 50%; iii, H , Pd(OH)
MeOH; v, NaIO , acetone, water, 30% (3 steps)
2
Cl, Pri
2
2 2
NEt, CH Cl , 70%;
6
4
2
2 4
–C, MeOH; iv, NaBH ,
4
1
9
S. T. Kerrick and P. Beak, J. Am. Chem. Soc., 1991, 113, 9718;
D. Hoppe, F.Hinze and P. Tebben, Angew. Chem., Int. Ed. Engl., 1990,
The absolute configuration of 3a was determined by comparison of the
optical rotation of 10, which was derived from commercially available
2
9, 1422; P. Beak and H. Du, J. Am. Chem. Soc., 1992, 115, 2516.
(R)-glycidol 11, as shown in Scheme 4.
1
0 M. Okuda and K. Tomioka, Tetrahedron Lett., 1994, 35, 4585.
For 3b–d, the absolute stereochemistries were assumed to be of the same
1
11 For transition state structure, see: K. Mikami, T. Uchida, T. Hirano,
Y.-D. Wu and K. N. Houk, Tetrahedron, 1994, 50, 5917 and references
cited therein.
2 K. Mikami, Y. Kimura, N. Kishi and T. Nakai, J. Org. Chem., 1983, 48,
79.
orientation as for 3a according to the H NMR spectra of the corresponding
(R)-O-methylmandelates. See J. A. Marshall and X. Xang, J. Org. Chem.,
1
*
990, 55, 2995.
1
* The absolute stereochemistry of the minor compound 12 was not
2
determined.
† Compound 8 was converted to 16 in four steps as shown in Scheme 5.
1
3 J. A. Dale, D. L. Dull, and H. S. Mosher, J. Org. Chem., 1969, 34,
†
2
4
2543.
The ee and the absolute configuration of compound 8 [[a] +22 (c = 0.84,
CHCl )] were determined by optical rotation of compound 16. The ee and
3
D
absolute configuration of 16 are known: M. Gette, J. Capillon and J. P.
Gette, Tetrahedron, 1973, 29, 3659.
Received in Cambridge, UK, 10th February 1997; Com.
7/00906B
738
Chem. Commun., 1997