Organocatalytic asymmetric α-aminomethylation of cyclohexanones

Article abstract of DOI:10.1055/s-2006-950346

The amino acid catalyzed direct asymmetric Mannich reaction between aminomethyl ether 1 and cyclohexanones is presented. The unprecedented reaction proceeds via an ionic transition state and gives the corresponding Mannich bases in moderate to high yields

Full text of DOI:10.1055/s-2006-950346

4060
SPECIAL TOPIC
Organocatalytic Asymmetric a-Aminomethylation of Cyclohexanones
A
symme
s
tric
a
-A
m
m
inomethylation of
C
a
yclohexa
n
i
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, 10691 Stockholm, Sweden
Fax +46(8)154908; E-mail: acordova@organ.su.se
Received 28 August 2006
lyzed by Shibasaki’s heterodimetallic complexes.8 Re-
Abstract: The amino acid catalyzed direct asymmetric Mannich re-
action between aminomethyl ether 1 and cyclohexanones is present-
ed. The unprecedented reaction proceeds via an ionic transition
state and gives the corresponding Mannich bases in moderate to
high yields with 75–99% ee.
cently, dinuclear zinc organometallic complexes were
reported that catalyze highly enantioselective Mannich-
type reactions between hydroxyaryl ketones and pre-
formed imines.9 Moreover, chiral copper(II) bisoxazoline
(BOX) complexes catalyze direct asymmetric Mannich
reactions involving activated ketones as donors.10 Recent-
ly, direct organocatalytic Mannich reactions that are cata-
lyzed by chiral Brønsted acids,11 chincona alkaloids,12
proline and its derivatives,13 peptide derivatives14 and
amino acids15 were developed. In this context, we report-
ed the amino acid catalyzed a-aminomethylation of ke-
tones (Equation 1).16 More recently, Gellman17 and we
independently reported the direct a-aminomethylation of
aldehydes (Equation 2).18
Key words: organocatalysis, Mannich reactions, aminomethyl-
ation, amino acids, asymmetric catalysis
The classical Mannich reaction,1 in which an aminometh-
yl group is introduced in the a-position to a carbonyl com-
pound, has found a multitude of applications in organic
chemistry.2 The resulting Mannich bases are of particular
interest due to their biological activities, such as analge-
sics, antioplastics, and antibiotics, and as synthetic build-
ing blocks and precursors for pharmaceutically valuable
g-amino alcohols.2 However, only a few stereoselective a-
aminomethylation reactions have been developed.3,4
Encouraged by these findings, we envisioned the possibil-
ity of developing a direct organocatalytic asymmetric
Mannich reaction between aminomethyl ethers and ke-
tones (Equation 3).
Several stoichiometrically indirect stereoselective Man-
nich transformations that utilize preformed enol equiva-
lents or imines are known.5 More recently, the first
successful examples of catalytic asymmetric additions of
enolates to imines were reported.6 This has led to an in-
tense research of catalytic indirect Mannich reactions.7
The first direct asymmetric Mannich reaction was cata-
R1 R1
N
Bn
Bn
R
N
O
N
O
H
+
R
R
MeO
R
Equation 3
Ar
O
HN
O
O
C
If successful, the reaction would give access to Mannich
products with protective groups that can be readily re-
moved by hydrogenolysis. Herein, we report the unprece-
dented organocatalytic enantioselective Mannich reaction
between dibenzyl aminomethyl ether 1 and ketones 2,
which furnish the corresponding Mannich bases in mod-
erate to high yields with 75–99% ee. In initial experi-
(S)-proline
r.t.
NH2
Ar
+
+
H
H
R1
R2
R1
R2
(aqueous)
up to >99% ee
yield 60–94%
Equation 1
N
H
Bn
Bn
Bn
Bn
R
Bn
Bn
R
O
H
N
N
O
N
OH
(20 mol%)
NaBH4
+
MeO
H
MeOH, –25 °C
DMF, –25 °C, 2 h
LiBr
R
AcOH
(20 mol%)
75–81% yield, 91–98% ee
Equation 2
SYNTHESIS 2006, No. 23, pp 4060–4064
x
x.
x
x
.
2
0
0
6
Advanced online publication: 06.11.2006
DOI: 10.1055/s-2006-950346; Art ID: C05006SS
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Asymmetric a-Aminomethylation of Cyclohexanones
4061
ments, we screened different chiral pyrrolidines (20
mol%) for their ability to catalyze the asymmetric reaction
between a-aminomethyl ether 1 (1 mmol) and cyclohex-
anone (2a) (2 mmol) in DMSO (2 mL) at room tempera-
ture (Table 1).
Table 1 Screening of Catalysts for Enantioselective Mannich Reac-
tions
Bn
Bn
Bn
Bn
O
N
N
O
catalyst
(20 mol%)
+
MeO
solvent
We found that all the tested chiral amines 4–7 catalyze the
asymmetric formation of 3a with high efficiency but low
to moderate enantioselectivity. (S)-Proline gave the high-
est asymmetric induction and was selected as the catalyst
to be further investigated. The efficiency and enantiose-
lectivity of the (S)-proline-catalyzed reaction was signifi-
cantly increased by heating or microwave irradiation.13j,19
For instance, Mannich base 3a was obtained in 53% yield
with 99% ee at 40 °C (entry 5). We also found that the re-
action was highly enantioselective in DMF. Notably, the
use of ten equivalents of 2a gave the Mannich product 3a
in 75% yield with 99% ee after three hours (entry 10). En-
couraged by this excellent result, we decided to investi-
gate the scope of the reaction for different cyclohexanones
(Table 2). We found that the reactions with ketones 2a–e
gave the corresponding a-aminomethylated ketones 3a–e
in good to high yields with high enantioselectivity (75–
99% ee). We also investigated the reaction for cyclohep-
tanone but the major product was the corresponding 2-
methylenecycloheptanone. The use of hydroxyacetone as
the donor enabled the asymmetric formation of Mannich
base 3f as the only regioisomer in 32% yield with 83% ee.
However, octan-2-one did only give trace amounts of
products. The Mannich bases 3 can also be converted in
one-pot to the corresponding amino alcohols (Scheme 1).
For instance, a one-pot tandem organocatalytic a-ami-
nomethylation/reduction sequence gave amino alcohol 8
(cis/trans = 1:1) in 74% yield with 99% ee. After that, a
Pseuomonas cepacia lipase-catalyzed kinetic resolution
gave acetylated trans-9 and remaining cis-8. The utiliza-
tion of dehydrogenation and acetylation sequences pro-
vided the corresponding diacetate 10.
1
2a
(2 equiv)
3a
HO
COOH
COOH
N
N
H
N
H
N
N
OH
H
H
4
5
6
7
Entry Catalyst Solvent
Temp
(°C)
Time
(h)
Yield
(%)a
ee
(%)b
1
2
4
5
6
7
4
4
4
4
4
4
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
r.t.
r.t.
r.t.
r.t.
40
60
100
40
40
40
4
45
60
70
40
53
70
30
60
40
75c
41
4
24
3
4
20
4
4
27
5
3
99
6
2
60
7
0.3
3
80
8
86
9
NMP
3
49
10
DMSO
3
99c
a Yield of pure compound after silica gel column chromatography.
b Determined by chiral-phase HPLC analyses.
c Ten equivalents of cyclohexanone (2a) were used.
Comparison with the literature revealed that the absolute
configuration at C2 of 3a was S.4b Based on this result, we
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
O
N
N
OH
N
OH
N
OAc
a
b
+
MeO
74%
+
1
2a
8
9
cis-8
trans-9
c
d,c
Ac
NH OAc
10
Scheme 1 Reagents and conditions: (a) (S)-proline (20 mol%), DMSO, 40 °C, 3 h; (b) P. cepacia lipase, isopropenyl acetate, CHCl3, 50 °C,
4 h; (c) Ac2O, cat. DMAP, CH2Cl2, r.t., 8 h; (d) Pd/C (10 mol%), MeOH, r.t., 16 h.
Synthesis 2006, No. 23, 4060–4064 © Thieme Stuttgart · New York

4062
Córdova, A.
SPECIAL TOPIC
Table 2 Organocatalytic Asymmetric a-Aminomethylation of
Ketones
R1
R1 = H or OH
Bn
Bn
Bn
Bn
Bn
(S)-proline
(20 mol%)
N
O
N
N
O
R
+
N
+
Bn
MeO
R
-O
O
DMSO, 40 °C, 3 h
R
R
R
R
Figure 1 Possible transition state for (S)-proline-catalyzed Man-
nich reaction.
1
2
3
Entry
Ketone Product
Yield (%)a drb
ee (%)c
99
In summary, we have described a highly regio- and enan-
tioselective organocatalytic Mannich-type reaction be-
tween a-aminomethyl ethers and cyclohexanones as well
as hydroxyacetone. Further development of this reaction
to the use of other acyclic ketones and molecular model-
ing studies are in progress.
NBn2
O
1
2a
2b
75d
–
3a
NBn2
O
73d
1:1
98
Chemicals and solvents were either purchased puriss p.A. from
commercial suppliers or purified by standard techniques. Aminom-
ethyl ether 1 was synthesized according to literature procedures.20
For TLC, silica gel plates Merck 60 F254 were used and compounds
were visualized by irradiation with UV light and/or by treatment
with a solution of phosphomolybdic acid (25 g), Ce(SO4)2·H2O
(10 g), concd H2SO4 (60 mL), and H2O (940 mL) followed by heat-
ing or by treatment with a solution of p-anisaldehyde (23 mL),
concd H2SO4 (35 mL), AcOH (10 mL), and EtOH (900 mL) fol-
lowed by heating. Flash chromatography was performed using sili-
2
3b
NBn2
O
3
4
2c
70d
1:1
n.d.e
ca gel Merck 60 (particle size 0.040–0.063 mm). 1H NMR and 13
C
3c
NBn2
NMR spectra were recorded on Varian AS 400. Chemical shifts are
given in d relative to TMS, and the coupling constants J in Hz. The
NMR spectra were recorded at r.t. in CDCl3 as solvent; TMS served
as internal standard (d = 0) for 1H NMR, and CDCl3 was used as in-
ternal standard (d = 77.0) for 13C NMR. HPLC was carried out us-
ing a Waters 2690 Millennium with photodiode array detector.
Optical rotations were recorded on a Perkin-Elmer 241 Polarimeter
(l = 589 nm, 1 dm cell) at 23 °C.
O
2d
43f
–
84
O
O
3d
NBn2
O
Mannich Bases 3; (–)-(S)-2-[(Dibenzylamino)methyl]cyclohex-
an-1-one [(S)-3a]: Typical Procedure
5
6
2e
2f
50f
–
–
75
83
To a mixture of (S)-proline [(23 mg, 0.2 mmol (20 mol%)] and ami-
nomethyl ether 1 (241 mg, 1 mmol) in DMSO (2 mL), was added
cyclohexanone (2a; 980 mg, 10 mmol) at 40 °C. After stirring vig-
orously for 3 h at this temperature, the mixture was directly loaded
onto a neutral aluminum oxide21 column and eluted with EtOAc–
toluene mixtures to furnish the pure Mannich base 3a; [a]D –20.2
(c = 1.0, CHCl3). The enantiomeric excess was determined by
HPLC with an AD column. Conditions: n-hexane–i-
PrOH (99.5:0.5), 0.5 mL/min; major isomer: tR = 26.5 min, minor
isomer: tR = 29.6 min.
1H NMR (400 MHz, CDCl3): d = 1.31 (m, 1 H), 1.52 (m, 1 H), 1.63
(m, 1 H), 1.72 (m, 1 H), 1.87 (m, 1 H), 2.20 (m, 1 H), 2.28 (m, 1 H),
2.34 (m, 1 H), 2.45 (m, 1 H), 2.55 (m, 1 H), 2.80 (dd, J = 5.4, 12.8
Hz, 1 H), 3.42 (d, J = 13.6 Hz, 2 H), 3.64 (d, J = 13.6 Hz, 2 H),
7.21–7.37 (m, 10 H).
O
O
3e
NBn2
O
32d
OH
3f
a Yield of pure compound after silica gel column chromatography.
b Anti/syn ratio determined by NMR analysis.
c Determined by chiral-phase HPLC analyses.
d Ten equivalents of the corresponding ketone 2 were used.
e n.d. = not determined.
f Two equivalents of the corresponding ketone 2 were used.
13C NMR (100 MHz, CDCl3): d = 24.2, 28.0, 32.1, 41.8, 49.1, 53.2,
59.2, 127.1, 128.4, 129.1, 140.0, 213.4.
propose that the (S)-proline-catalyzed reaction proceed
via an ionic transition state where the Si face of the chiral
enamine is approached by the in situ generated iminium
ion (Figure 1). This is in accordance with previous (S)-
proline-catalyzed a-aminomethylation of aldehydes with
aminomethyl ether 1 as the electrophile.17,18
3b
[a]D –10.8 (c = 1.0, CHCl3). The enantiomeric excess was deter-
mined by HPLC with an ODH column. Conditions: n-hexane–i-
PrOH (99.0:1.0), 0.5 mL/min; major isomer: tR = 17.6 min, minor
isomer: tR = 21.0 min.
1H NMR (400 MHz, CDCl3): d (mixture of two diastereo-
mers) = 0.89 (d, J = 6.2 Hz, 3 H), 0.99 (d, J = 6.5 Hz, 3 H), 1.32 (m,
2 H), 1.60 (m, 2 H), 1.80 (m, 2 H), 2.0 (m, 2 H), 2.12 (m, 2 H), 2.29
Synthesis 2006, No. 23, 4060–4064 © Thieme Stuttgart · New York

SPECIAL TOPIC
Asymmetric a-Aminomethylation of Cyclohexanones
4063
(m, 2 H), 2.50 (m, 2 H), 2.75 (m, 2 H), 2.82 (m, 2 H), 3.34 (d,
J = 13.5 Hz, 2 H), 3.44 (d, J = 13.3 Hz, 2 H), 3.63 (d, J = 13.3 Hz,
2 H), 3.74 (d, J = 13.5 Hz, 2 H), 7.20–7.38 (m, 20 H).
13C NMR (100 MHz, CDCl3): d = 21.0, 21.6, 26.6, 32.1, 35.0, 36.0,
38.0, 38.4, 41.0, 42.0, 47.5, 48.1, 53.7, 54.4, 58.6, 59.5, 127.0,
127.2, 128.3, 128.4, 129.0, 129.4, 139.6, 140.0, 213.2, 214.4.
was decreased to 0 °C, and MeOH (2 mL) and then excess NaBH4
(757 mg, 20 mmol) were added. After stirring for 5 min at this tem-
perature, the mixture was poured into a cold stirred mixture of
EtOAc (20 mL) and aq 1 M HCl (2 mL). The mixture was dried
(Na2SO4), evaporated and the residue was purified by column chro-
matography to afford the corresponding reduced alcohols 8 (cis/
trans = 1:1); yield: 229 mg (74%). The enantiomeric excess was de-
termined by HPLC with an ODH column. Conditions: n-hexane–i-
PrOH (99.5:0.5), 0.5 mL/min; major syn-isomer: tR 46.3 min, minor
syn-isomer: tR 33.0 min, major anti-isomer: tR 46.3 min, minor anti-
isomer: tR 77.7 min.
1H NMR (400 MHz, CDCl3): d (mixture of two diastereo-
mers) = 0.77 (m, 1 H), 1.12–1.53 (m, 10 H), 1.61–1.78 (m, 4 H),
1.94 (m, 2 H), 2.10 (m, 1 H), 2.22 (dd, J = 13.0, 4.2 Hz, 1 H), 2.30
(dd, J = 13.0, 2.8 Hz, 1 H), 2.62 (dd, J = 13.0, 11.6 Hz, 1 H), 2.85
(dd, J = 13.0, 19.9 Hz, 1 H), 3.11 (d, J = 13.2 Hz, 2 H), 3.21 (d,
J = 13.2 Hz, 2 H), 3.90 (d, J = 13.2 Hz, 2 H), 4.09 (d, J = 13.3 Hz,
2 H), 7.33–7.38 (m, 20 H).
3c
[a]D –12.4 (c = 1.0, CHCl3).
1H NMR (400 MHz, CDCl3): d = 0.86 (dd, J = 6.7–8.8 Hz, 6 H),
0.92 (dd, J = 1.24, 6.7 Hz, 6 H), 1.35 (m, 2 H), 1.47 (m, 2 H), 1.55
(m, 2 H), 1.64 (m, 2 H), 1.75 (m, 2 H), 1.83 (m, 2 H), 1.96 (m, 2 H),
2.13 (m, 2 H), 2.27 (m, 2 H), 2.42 (m, 2 H), 2.83 (m, 2 H), 3.35 (d,
J = 13.6 Hz, 2 H), 3.48 (d, J = 13.3 Hz, 2 H), 3.58 (d, J = 13.3 Hz,
2 H), 3.73 (d, J = 13.6 Hz, 2 H), 7.37–7.23 (m, 20 H).
13C NMR (100 MHz, CDCl3): d = 19.9, 20.1, 20.2, 20.4, 29.6, 31.0,
31.5, 32.3, 33.0, 35.7, 37.6, 38.5, 42.0, 43.1, 47.5, 48.2, 54.0, 54.5,
58.6, 59.7, 127.1, 127.2, 128.3, 128.4, 129.1, 129.3, 139.6, 140.0,
213.4, 214.7.
13C NMR (100 MHz, CDCl3): d = 24.3, 25.8, 27.4, 29.0, 31.7, 34.4,
37.0, 40.6, 59.2 (2 C), 59.3, 61.3, 70.3 (2 C), 127.5, 127.6, 18.7,
129.0, 130.0 (2 C), 138.0, 139.0.
3d
Two equivalents of ketone 2d were used in the reaction.
Enzyme-Catalyzed Kinetic Resolution of Amino Alcohol 8
To a solution of amino alcohol 8 [cis/trans (1:1), 278 mg, 0.9 mmol]
and isopropenyl acetate (135 mg, 1.35 mmol) in toluene was added
P. cepacia lipase (PS-C Amano II, 90 mg) at 50 °C. After 5.5 h,
50% conversion was reached and the enzyme was removed by fil-
tration. Purification by silica gel column chromatography (EtOAc–
pentane mixtures) gave cis-8 and trans-9 quantitatively.
[a]D –23.0 (c = 1.0, CHCl3). The enantiomeric excess was deter-
mined by HPLC with an AD column. Conditions: n-hexane–i-
PrOH (98.0:2.0), 0.5 mL/min; major isomer: tR 10.8 min, minor iso-
mer: tR = 12.8 min.
1H NMR (400 MHz, CDCl3): d = 1.44 (s, 3 H), 1.51 (s, 3 H), 2.74
(q, J = 8.0, 14.4 Hz, 1 H), 3.18 (dd, J = 2.7, 14.5 Hz, 1 H), 3.67 (d,
J = 13.7 Hz, 2 H), 3.77 (d, J = 13.7 Hz, 2 H), 3.96 (d, J = 16.9 Hz,
1 H), 4.24 (dd, J = 1.5, 16.9, 1 H), 4.51 (m, 1 H), 7.40–7.30 (m, 10
H).
(+)-(1S,2S)-cis-8
[a]D +8.1 (c = 1.0, MeOH).
1H NMR (300 MHz, CDCl3): d = 0.86 (m, 1 H), 1.10–1.41 (m, 3 H),
1.63 (m, 2 H), 1.83–1.90 (m, 2 H), 2.18 (m, 2 H), 2.83 (dd, J = 16.9,
4.9 Hz, 1 H), 3.14 (t, J = 15.4 Hz, 1 H), 3.40 (d, J = 13.6 Hz, 2 H),
3.63 (d, J = 13.6 Hz, 2 H), 7.28–7.38 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 22.8, 23.4, 27.4, 31.7, 37.0, 55.2,
59.3, 70.3, 127.5, 128.6, 129.4, 138.9.
13C NMR (100 MHz, CDCl3): d = 23.9, 24.3, 52.1, 59.0, 67.0, 75.1,
101.0, 127.2, 128.4, 129.0, 140.0, 208.9.
3e
Two equivalents of ketone 2e were used in the reaction.
[a]D –18.0 (c = 1.0, CHCl3). The enantiomeric excess was deter-
mined by HPLC with an ODH column. Conditions: n-hexane–i-
PrOH (97.0:3.0), 0.5 mL/min; major isomer: tR 38.5 min, minor iso-
mer: tR 42.3 min.
(–)-(1R,2S)-trans-9
[a]D –5.1 (c = 1.0, MeOH).
1H NMR (400 MHz, CDCl3): d = 0.78 (m, 1 H), 1.13–1.32 (m, 4 H),
1.62–1.87 (m, 3 H), 2.02 (s, 3 H), 2.19 (m, 2 H), 2.42 (dd, J = 12.7,
3.6 Hz, 1 H), 3.27 (d, J = 13.9 Hz, 2 H), 3.77 (d, J = 13.9 Hz, 2 H),
4.44 (m, 1 H), 7.29–7.40 (m, 10 H).
1H NMR (400 MHz, CDCl3): d = 1.90 (m, 1 H), 1.98 (m, 1 H), 2.30
(m, 1 H), 2.41 (m, 1 H), 2.49 (m, 1 H), 2.56 (m, 1 H), 2.61 (m, 1 H),
2.82 (d, J = 4.2 Hz, 1 H), 2.9 (m, 1 H), 3.31 (d, J = 13.6 Hz, 2 H),
3.72 (d, J = 13.6 Hz, 2 H), 3.99 (m, 4 H), 7.23–7.35 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 21.6, 24.3, 24.9, 29.4, 31.2, 31.6,
40.1, 56.1, 59.1, 75.6, 127.1, 128.4, 129.1, 140.0, 171.0.
13C NMR (100 MHz, CDCl3): d = 35.0, 38.5, 39.0, 45.0, 53.1, 59.0,
64.7, 65.0, 107.7, 127.1, 128.4, 129.1, 140.0, 211.5.
Diacetate 1022
3f
To a solution of acetate 9 (cis/trans-1:1, 0.9 mmol) in MeOH (2.0
mL) was added a catalytic amount of Pd/C. After hydrogenolysis
(90 MPa) for 17 h, the catalyst was filtered off on a pad of Celite
and the solvent was removed under reduced pressure. After that, the
intermediate amino alcohol was N-acetylated by addition of CH2Cl2
(2 mL), Et3N (101 mg, 1.0 mmol), Ac2O (102 mg, 1.0 mmol) and
DMAP (12.2. mg, 0.1 mmol). After stirring for 16 h, the mixture
was directly loaded onto a silica gel column and eluted with
pentane–EtOAc mixtures to give the pure known diacetate 10
(cis/trans = 1:1)22 as a clear oil; yield: 171 mg (89%).
[a]D –4.6 (c = 1.0, CHCl3). The enantiomeric excess was deter-
mined by HPLC with an ODH column. Conditions: n-hexane–i-
PrOH (97.0:3.0), 0.5 mL/min; major isomer: tR 23.0 min, minor iso-
mer: tR 29.4 min.
1H NMR (400 MHz, CDCl3): d = 1.92 (s, 3 H), 2.75–2.88 (m, 1 H),
3.45 (d, J = 13.4 Hz, 2 H), 3.84 (d, J = 13.4 Hz, 2 H), 4.2 (dd,
J = 2.6, 4.1 Hz, 1 H), 7.35–7.23 (m, 10 H).
13C NMR (100 MHz, CDCl3): d = 26.0, 55.3, 59.2, 76.1, 127.6,
128.6, 129.5, 139.0, 210.2.
1H NMR (400 MHz, CDCl3): d (mixture of two diastereo-
mers) = 0.76–1.00 (m, 2 H), 1.10–1.35 (m, 4 H), 1.40–1.54 (m, 4
H), 1.62–1.74 (m, 4 H), 1.80–1.96 (m, 4 H), 2.01 (s, 3 H), 2.02 (s, 3
H), 2.04 (s, 3 H), 2.05 (s, 3 H), 4.36–4.48 (m, 4 H), 4.93 (m, 2 H).22
Cis-8 and trans-8
One-Pot Preparation: To a mixture of (S)-proline [23 mg, 0.2 mmol
(20 mol%)] and aminomethyl ether 1 (241 mg, 1 mmol) in DMSO
(2 mL), was added cyclohexanone (2a; 980 mg, 10 mmol) at 40 °C.
After stirring vigorously for 3 h at this temperature, the temperature
Synthesis 2006, No. 23, 4060–4064 © Thieme Stuttgart · New York

4064
Córdova, A.
SPECIAL TOPIC
(8) Yamasaki, S.; Iida, T.; Shibasaki, M. Tetrahedron Lett.
1999, 40, 307.
(9) (a) Matsunaga, S.; Kumagai, N.; Harada, N.; Harada, S.;
Shibasaki, M. J. Am. Chem. Soc. 2003, 125, 4712.
(b) Trost, B. M.; Terrell, L. M. J. Am. Chem. Soc. 2003, 125,
338.
(10) (a) Juhl, K.; Gathergood, N.; Jørgensen, K. A. Angew. Chem.
Int. Ed. 2001, 40, 2995. (b) Marigo, M.; Kjaersgaard, A.;
Juhl, K.; Gathergood, N.; Jørgensen, K. A. Chem. Eur. J.
2003, 9, 2395.
(11) (a) Akiyama, T.; Itoh, J.; Yokota, K.; Fuchibe, K. Angew.
Chem. Int. Ed. 2004, 43, 1566. (b) Uraguchi, D.; Terada, M.
J. Am. Chem. Soc. 2004, 126, 5356.
Acknowledgment
We thank the Swedish National Research council and Medivir AB
for financial support.
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Synthesis 2006, No. 23, 4060–4064 © Thieme Stuttgart · New York