Synthesis and use of 3,3′-bimorpholine derivatives in asymmetric Michael addition and intramolecular aldol reaction

Article abstract of DOI:10.1055/s-2007-965966

The synthesis of 3,3′-bimorpholine and its N-alkyl derivatives is described. These new diamine derivatives were revealed to be efficient organocatalysts for the asymmetric Michael addition of aldehydes to nitroalkenes with excellent enantioselectivity (up to 90% ee). The potential of these organocatalysts was also demonstrated for the highly enantioselective intramolecular aldol reaction affording the Wieland-Miescher ketone with tremendous enantioselectivity (up to 95% ee). Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-965966

PRACTICAL SYNTHETIC PROCEDURES
1729
Synthesis and Use of 3,3¢-Bimorpholine Derivatives in Asymmetric Michael
Addition and Intramolecular Aldol Reaction
Synthesis and
a
a
A
pplication
r
of 3,3
¢
-
a
Bimorphol
h
Department of Organic Chemistry, University of Geneva, Sciences II, 30, quai Ernest Ansermet,
1211 Geneva 4, Switzerland
Fax +41(22)3793215; E-mail: alexandre.alexakis@chiorg.unige.ch
Department of Chemistry, Tallinn University of Technology, Akadeemia tee 15,
Tallinn 12618, Estonia
b
PSP
Fax +3726202828; E-mail: kanger@chemnet.ee
Received 2 February 2007
No85
Abstract: The synthesis of 3,3¢-bimorpholine and its N-alkyl derivatives is described. These new diamine derivatives were revealed to be
efficient organocatalysts for the asymmetric Michael addition of aldehydes to nitroalkenes with excellent enantioselectivity (up to 90% ee).
The potential of these organocatalysts was also demonstrated for the highly enantioselective intramolecular aldol reaction affording the
Wieland–Miescher ketone with tremendous enantioselectivity (up to 95% ee).
Key words: diamine, asymmetric catalysis, organocatalysis, aldol reaction, Michael addition
MsO
HO
O
O
O
N3
N3
N3
N3
HO
HO
O
O
ref. 7
O
O
OEt
OEt
Procedure 1
Procedure 2
NH HN
O
MsO
HO
3
1
2
O
O
O
O
O
O
3
NH
N
NH
N
N
N
HX
6
4
5
O
R2
catalyst 5
(15 mol%)
O
R1
NO2
9a–g
Procedure 3
NO2
R2
H
H
CHCl3
R1
7a–d
8a–d
dr (syn:anti) up to 95:5
up to 90% ee
O
O
O
catalyst 6
(5 mol%)
Procedure 4
O
n
MeCN, reflux
O
n
12: n = 2
13: n = 1
up to 95% ee
10: n = 2
11: n = 1
Scheme 1
Organocatalytic methods for C–C bond formation have have a huge potential in this new area due to their activa-
become an important tool for stereoselective synthesis tion either of nucleophiles or of electrophiles during the
over the past few years.1 Asymmetric amino catalysts course of the catalytic cycle.2 Proline, as a cornerstone of
amino catalysts, was first used more than 30 years ago3
and is now the most widely used organocatalyst.4 In addi-
tion to proline a wide variety of analogues are used for ste-
reoselective synthesis.5 By analogy to bis-pyrrolidine,6a
we have designed and synthesized a new class of organo-
SYNTHESIS 2007, No. 11, pp 1729–1732
Advanced online publication: 28.02.2007
DOI: 10.1055/s-2007-965966; Art ID: Z02807SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
7

1730
S. Sulzer-Mossé et al.
PRACTICAL SYNTHETIC PROCEDURES
catalysts, bimorpholines 3.7 Herein we describe their promise as an amino catalyst for the asymmetric Michael
preparation, derivatization, and application in organocat- addition of aldehydes to nitroalkenes (Scheme 1, proce-
alytic Michael additions and intramolecular aldol reac- dure 3 and Table 1).9 The best asymmetric outcome for
tions.
the conjugate addition of isovaleraldehyde (7a) to b-ni-
trostyrene (8a) was reached with hydrochloride salt 6a at
the expense of reactivity and yield (entry 1). Hence, free
diamine 5 was considered to be the optimal catalyst in
terms of selectivity and reactivity (entry 2). Under these
conditions, a wide range of both branched or linear alde-
hydes 7a–d underwent reaction with nitrostyrene 8a in
high yields and selectivities (80–90% ee, entries 2–5).
Significantly, bimorpholine 5 displayed a marked bias to-
ward activation of moderately hindered aldehydes 7a–c
with high stereocontrol (entries 2–4). Likewise, diamine 5
was shown to be general with regard to aromatic nitroalk-
enes 8a–d (entries 5–8). The sterochemical outcome
could be explained by steric shielding according to See-
bach’s acyclic synclinal model.11
The first synthesis of the enantiomerically pure 3,3¢-bi-
morpholine was described by us some years ago.7 The key
intermediate 1 was derived from tartaric ester via a multi-
step procedure and was converted into bimorpholine 3 in
six steps in 32% yield. A substantial improvement in the
synthetic scheme was achieved by direct mesylation of the
primary hydroxy groups in compound 1 followed by re-
ductive cyclization of the thus obtained precursor 2
(Scheme 1, procedure 1). Both steps are high-yielding and
afford the target compound in 80% total yield. The cy-
clization reaction is regioselective and also stereoselec-
tive. No cross-cyclized seven-membered ring product was
formed and the enantiomeric purity of the bimorpholine 3
was high (98% ee). It is important to mention that the cy-
clization of the alternative intermediate, where the leaving The synthetic utility of the new organocatalyst was
groups are in the vicinal positions at the stereogenic car- demonstrated also by intramolecular aldol condensation
bon atoms and the nitrogen functionalities are at the w-po- of triketones 10 and 11 affording the synthetically useful
sition of the alkyl chains, leads to meso-bimorpholine.8
Wieland–Miescher ketone 12 or its nor analogue 13
(Scheme 1, procedure 4), (Table 2).10 It was found that the
mono salts of bimorpholine or its derivative were more ef-
ficient catalysts than the free amines. Hence, bimorpho-
line 5 was converted into its mono-salt with trifluoroacetic
acid 6a or trifluoromethanesulfonic acid 6b. Acid is need-
ed for the acceleration of the condensation and also for the
formation of the fixed conformation of the catalyst via hy-
drogen bonding thus providing higher stereoselectivity.12
To achieve monoderivatization (Scheme 1, procedure 2),9
we used our simple methodology based on aminal forma-
tion followed by reduction, as previously used for 2,2¢-bi-
pyrrolidine derivatives.6e The combination of the free
diamine 3 with acetone readily provided aminal interme-
diate 4 and the crude material was then reduced with sodi-
um borohydride in the presence of acetic acid. This
sequence afforded the mono-N-isopropyl-3,3¢-bimorpho-
line derivative 5 in 72% overall yield after Kugelrohr dis- Under our best conditions, Wieland–Miescher ketone 12
tillation. The corresponding salts 6 were formed in was obtained in the bimorpholine-catalyzed reaction in up
quantitative yield regardless of the acid used.9,10
to 84% isolated yield and with 91% ee. Thus, our catalyst
is more efficient and stereoselective than proline in this
reaction.3,13
In the course of our studies on enamine activation,6b–h N-
isopropyl-3,3¢-bimorpholine 5 was identified as holding
Table 1 Asymmetric Michael Addition of Aldehydes 7a–d to Nitroalkenes 8a–d Catalyzed by Bimorpholine Derivative 5
Entry
1e
Aldehyde
Nitroalkene
Product
9a
R1
R2
Yielda,b (%)
drc syn/anti
95:5
eed (%) (syn)
7a
7a
7b
7c
7d
7d
7d
7d
8a
8a
8a
8a
8a
8b
8c
8d
i-Pr
i-Pr
Ph
Ph
68
85
88
88
86
89
84
91
88
89
90
80
79
75
78
2
9a
Ph
94:6
3
9b
Ph
87:13
95.5
4f
9c
Cy
Me
Me
Me
Me
Ph
5g
6g
7g
8g
9d
Ph
90:10
89:11
80:20
84:16
9e
2-thienyl
4-ClC6H4
9f
9g
4-MeOC6H4 81
a Typical experiment: nitroalkene (0.335 mmol), aldehyde (3.35 mmol), catalyst 5 (15 mol%), CHCl3, r.t. 3 d.
b Isolated yields after column chromatography (silica gel).
c Determined by 1H NMR on the crude material.
d Determined by chiral SFC or chiral GC.
e Reaction was performed with 15 mol% of catalyst 6a (HX = HCl).
f Time: 13 d.
g Temperature: –3 °C.
Synthesis 2007, No. 11, 1729–1732 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Synthesis and Application of 3,3¢-Bimorpholine Derivatives
[a]D20 –29.4 (c 2.0, MeOH).
1731
Table 2 Cyclization of Triketones 10 and 11 in the Presence of Bi-
morpholines 5 or 6
IR (KBr): 3277, 2959, 2847, 1500, 1447, 1321, 1105, 960, 788, 668
cm–1.
Entry
Ketone
10
Catalyst
Product
12
Yielda (%) eeb (%)
1H NMR (CDCl3): d = 3.76 (m, 2 H), 3.75 (m, 2 H), 3.47 (m, 2 H),
3.30 (m, 2 H), 2.91 (m, 2 H), 2.89 (m, 4 H), 2.68 (m, 2 H).
13C NMR (CDCl3): d = 69.7 (C2), 67.8 (C6), 55.7 (C3), 45.6 (C5).
MS (EI): m/z = 172 [M]+, 114, 86, 58.
HRMS: m/z [M]+ calcd for C8H16N2O2: 172.1211; found: 172.1234.
1
2
3
4
5
5
45
84
60
83
68
rac
91
95
80
87
10
6a
6b
6a
6b
12
10
12
11
13
(3S,3¢S)-4-Isopropyl-3,3¢-bimorpholine (5)
11
13
To a soln of (3S,3¢S)-bimorpholine (3, 2.91 mmol) in Et2O (12 mL)
was added 4 Å molecular sieves (~ 0.5 g) and acetone (2.91 mmol).
The mixture was stirred overnight, then K2CO3 was added and the
mixture was stirred for 1 h and then it was filtered. The solvent was
removed to give the crude aminal 4 (586 mg, 95%). To a soln of
aminal 4 (586 mg, 2.76 mmol) in MeOH (10 mL) was added por-
tionwise at 0 °C NaBH4 (1.5 equiv) then AcOH (4 equiv). The soln
was stirred at 0 °C for 3 h and then diluted with Et2O (10 mL) and
hydrolyzed with 30% aq NaOH (5 mL) and H2O (10 mL). The soln
was decanted; the aqueous phase was extracted with EtOAc (2 ×).
The combined organic phases were washed with brine, dried
(K2CO3), filtered, concentrated under reduced pressure, and puri-
fied by Kugelrhor distillation (0.2 mbar/140 °C) to give a white sol-
id; yield: 449 mg (76%, 72% overall yield); GC/MS (program:
80 °C for 1 min, gradient 20 °C/min to 270 °C, hold 3 min):
tR = 8.95 min.
a Typical experiment: triketone (1 mmol), catalyst 5 or 6 (5 mol%),
MeCN, reflux, 69–216 h.
b Determined by chiral HPLC.
In conclusion, we have shown that 3,3¢-bimorpholine de-
rivatives are a new class of efficient bicyclic six-mem-
bered ring organocatalysts for the asymmetric Michael
addition, an operationally simple reaction that allows the
rapid access to enantioenriched g-nitroaldehydes. More-
over, we have further extended the scope of these organo-
catalysts to execute the highly enantioselective intra-
molecular aldol reaction providing Wieland–Miescher
ketone as highly versatile chiral building blocks.
[a]D20 +53.42 (c 1.1, CHCl3).
IR (KBr): 3307 (w), 2963 (m), 2851 (m), 1803 (m), 1448 (m), 1313
(m), 1296 (m), 1266 (m), 1178 (m), 1098 (s), 973 cm–1 (m).
(5S,6S)-5,6-Diazido-1,10-bis(methylsulfonyloxy)-3,8-dioxa-
decane (2)
1H NMR (400 MHz, CDCl3): d = 4.10–4.02 (m, 2 H), 3.73–3.52 (m,
2 H), 3.40–3.27 (m, 4 H), 3.15–3.09 (m, 1 H), 3.07–2.97 (m, 1 H),
2.67–2.60 (m, 1 H), 2.44–2.29 (m, 3 H), 2.20–2.14 (m, 1 H), 1.01
(br, 1 H), 0.83–0.81 (d, J = 6.56 Hz, 3 H), 0.71–0.69 (d, J = 6.56 Hz,
3 H).
13C NMR (100 MHz, CDCl3): d = 69.12 (CH2), 67.61 (CH2), 66.43
(CH2), 66.14 (CH2), 58.20 (CH), 53.27 (CH), 48.47 (CH), 46.85
(CH2), 42.60 (CH2), 21.70 (CH3), 16.05 (CH3).
MsCl (1.2 mL, 15.49 mmol) was slowly added to a cooled soln of
diol 1 (1.68 g, 6.45 mmol) and Et3N (2.7 mL, 19.35 mmol) in anhyd
CH2Cl2 (20 mL) at 0 °C. The mixture was allowed to warm to r.t.
over 3 h. H2O was added and the organic layer was separated and
the aqueous layer was extracted with EtOAc (3 × 40 mL). The com-
bined organic layers were washed with brine and dried (MgSO4).
Concentration in vacuum and purification of the crude product by
chromatography (silica gel, 50% EtOAc–petroleum ether) afforded
2 as a colorless oil; yield: 2.58 g (96%).
HRMS (ESI): m/z [M + H]+ calcd for C11H23N2O2: 215.1681; found:
215.1759.
[a]D20 –26.7 (c 2.66, CH2Cl2).
Bimorpholine Salts 6; General Procedure
To a soln of bimorpholine 5 (1 mmol) in Et2O (4 mL) corresponding
acid (1 mmol) was added at 0 °C. The precipitate was collected and
dried in vacuo.
IR (film): 3029, 2941, 2110, 1456, 1352, 1268, 1175, 1135, 1020,
974, 924, 809, 529 cm–1.
1H NMR (CDCl3): d = 4.36 (m, 4 H, CH2OS), 3.79 (m, 4 H,
SOCH2CH2O), 3.74 (m, 4 H, CHCH2O), 3.73 (m, 2 H, CHN), 3.05
(s, 6 H, CH3).
13C NMR (CDCl3): d = 70.8 (CHCH2O), 69.1 (SOCH2CH2O), 68.4
CH2OS), 60.6 (CHN), 37.5 (CH3).
(3S,3¢S)-4-Isopropyl-3,3¢-bimorpholine Trifluoroacetic Acid
Salt (6a)
Mp 113–115 °C.
[a]D21 +11.7 (c 2.24, MeOH).
MS (EI): m/z (%) = 417 [M + H]+ (3.99), 389 (15.04), 346 (8.25),
208 (22.27), 153 (86.73), 123 (100).
IR (KBr): 3427, 2493, 1672, 1623, 1208, 1129, 1107 cm–1.
1H NMR (500 MHz, CDCl3): d = 9.0 (br s, 2 H, NH), 4.11 (m, 1 H,
H2¢), 3.95 (m, 1 H, H6¢), 3.84 (m, 2 H, H2, H6¢), 3.77 (m, 2 H, H2¢,
H3¢), 3.65 (m, 1 H, H6), 3.58 (m, 1 H, H6), 3.54 (m, 1 H, H2), 3.31
(m, 1 H, H5¢), 3.22 (hept, J = 6.6 Hz, 1 H, i-Pr), 3.17 (m, 1 H, H5¢),
3.04 (m, 2 H, H3, H5), 2.73 (m, 1 H, H5), 1.12, 1.09 (2 d, J = 6.6
Hz, 6 H, i-Pr).
13C NMR (125 MHz, CDCl3): d = 162.2 (q, J = 35.1 Hz, COO),
116.6 (q, J = 292.8 Hz, CF3), 65.7 (C2¢), 64.9 (C6), 63.6 (C6¢), 63.0
(C2), 53.9 (C3), 52.0 (C3), 51.1 (i-Pr), 43.3 (C5¢), 41.5 (C5), 21.7,
20.0 (i-Pr).
Anal. Calcd for C10H20N6O8S2 (416.43): C, 28.84, H, 4.84; N,
20.18. Found: C, 28.65; H, 4.71; N, 20.10.
(3S,3¢S)-3,3¢-Bimorpholine (3)
To a soln of diazide 2 (17.98 g, 43.23 mmol) in a mixture of CH2Cl2
(45 mL) and MeOH (255 mL) was added PtO2 (1.48 g, 6.51 mmol).
The mixture was hydrogenated under a H2 atmosphere for 48 h. The
catalyst was removed by filtration through Celite and the filtrate
was evaporated affording the yellow solid of methanesulfonate salt
of bimorpholine (16.92 g). This crude product was purified by basic
treatment affording (S,S)-bimorpholine 3 as pale yellow crystals;
yield: 6.26 g (84%); 98% ee; mp 66–68 °C.
MS (EI): m/z (%) = 128 (100), 86 (68), 69 (30), 45 (51).
Synthesis 2007, No. 11, 1729–1732 © Thieme Stuttgart · New York

1732
S. Sulzer-Mossé et al.
PRACTICAL SYNTHETIC PROCEDURES
HRMS: m/z calcd for [C7H14NO]+: 128.1081; found: 128.1079; m/z
(2) For recent reviews on enamine and iminium catalysis, see:
(a) List, B. Chem. Commun. 2006, 819. (b) Palomo, C.;
Mielgo, A. Angew. Chem. Int. Ed. 2006, 45, 7876.
(c) Lelais, G.; MacMillan, D. W. C. Aldrichimica Acta 2006,
39, 79. (d) Sulzer-Mossé, S.; Alexakis, A. Chem. Commun.
2007, in press.
calcd for [C4H8NO]+: 86.0611; found: 86.0604.
(3S,3¢S)-4-Isopropyl-3,3¢-bimorpholine Trifluoromethane-
sulfonic Acid Salt (6b)
Mp 104–105 °C.
(3) (a) Eder, U.; Sauer, G.; Wiechert, R. Angew. Chem., Int. Ed.
Engl. 1971, 10, 496. (b) Hajos, Z. G.; Parrish, D. R. J. Org.
Chem. 1974, 39, 1615.
[a]D21 +13.4 (c 2.50, MeOH).
IR (KBr): 3437, 2860, 2525, 1279, 1245, 1153, 1103, 1031, 641,
519 cm–1.
(4) For pioneering findings, see (a) List, B.; Lerner, R. A.;
Barbas, C. F. III J. Am. Chem. Soc. 2000, 122, 2395. For
recent selected examples, see: (b) Tokuda, O.; Kano, T.;
Gao, W.-G.; Ikemoto, T.; Maruoka, K. Org. Lett. 2005, 7,
5103. (c) Ikishima, H.; Sekiguchi, Y.; Ichikawa, Y.;
Kotsuki, H. Tetrahedron 2006, 62, 311. (d) Pihko, P. M.;
Laurikainen, K. M.; Usano, A.; Nyberg, A. I.; Kaavi, J. A.
Tetrahedron 2006, 62, 317. (e) Alcaide, B.; Almenderos, P.;
Luna, A.; Torres, M. R. J. Org. Chem. 2006, 71, 4818.
(f) Calderón, F.; Doyagüez, E. G.; Fernández-Mayoralas, A.
J. Org. Chem. 2006, 71, 6258. (g) Suri, J. T.; Mitsumori, S.;
Albertshofer, K.; Tanaka, F.; Barbas, C. F. J. Org. Chem.
2006, 71, 3822. (h) Ibrahem, I.; Zou, W.; Xu, Y.; Córdova,
A. Adv. Synth. Catal. 2006, 348, 211.
1H NMR (500 MHz, CDCl3): d = 6.8 (br s, 2 H, NH), 4.10 (m, 1 H,
H2¢), 3.98 (m, 1 H, H6¢), 3.91 (m, 1 H, H6¢), 3.80 (m, 2 H, H2, H3¢),
3.74 (m, 1 H, H2¢), 3.60 (m, 2 H, H6), 3.58 (m, 1 H, H2), 3.34 (m,
1 H, H5¢), 3.28 (m, 2 H, H5¢, i-Pr), 3.02 (m, 1 H, H3), 3.01 (m, 1 H,
H5), 2.86 (m, 1 H, H5), 1.20, 1.19 (2 d, J = 6.5 Hz, 6 H, i-Pr).
13C NMR (125 MHz, CDCl3): d = 120.1 (q, J = 318.9 Hz, CF3), 65.2
(C2¢), 64.5 (C6), 63.6 (C6¢), 62.2 (C2), 52.3 (C3), 52.2 (i-Pr), 51.0
(C3¢), 42.4 (C5¢), 41.0 (C5), 22.0, 21.7 (i-Pr).
MS (EI): m/z (%) = 215 (2), 128 (100), 86 (54), 69 (12).
HRMS: m/z calcd for [C7H14NO]+: 128.1081; found: 128.1086; m/z
calcd for [C4H8NO]+: 86.0611; found: 86.0612.
(5) For recent highlights, see: (a) List, B. Acc. Chem. Res. 2004,
37, 548. (b) Notz, W.; Tanaka, F.; Barbas, C. F. III Acc.
Chem. Res. 2004, 37, 580. (c) Momiyama, N.; Torii, H.;
Saito, S.; Yamamoto, H. Proc. Natl. Acad. Sci. U.S.A. 2004,
101, 5374. (d) Huang, Y.; Walji, A. M.; Larsen, C. H.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127, 15051.
(e) Cobb, A. J. A.; Shaw, D. M.; Longbottom, D. A.; Gold,
J. B.; Ley, S. V. Org. Biomol. Chem. 2005, 3, 84.
(f) Maurigo, M.; Jørgensen, K. A. Chem. Commun. 2006,
2001. (g) Pihko, P. M. Angew. Chem. Int. Ed. 2006, 45, 544.
(h) Sundén, H.; Ibrahem, I.; Zhao, G.-L.; Eriksson, L.;
Córdova, A. Chem. Eur. J. 2007, 13, 574. (i) Enders, D.;
Grondal, C.; Hüttl, M. R. M. Angew. Chem. Int. Ed. 2007,
46, 1570.
(6) (a) Alexakis, A.; Tomassini, A.; Chouillet, C.; Roland, S.;
Mangeney, P.; Bernardinelli, G. Angew. Chem. Int. Ed.
2000, 39, 4093. (b) Alexakis, A.; Andrey, O. Org. Lett.
2002, 4, 3611. (c) Andrey, O.; Alexakis, A.; Bernardinelli,
G. Org. Lett. 2003, 5, 2559. (d) Andrey, O.; Vidonne, A.;
Alexakis, A. Tetrahedron Lett. 2003, 44, 7901. (e) Andrey,
O.; Alexakis, A.; Tomassini, A.; Bernardinelli, G. Adv.
Synth. Catal. 2004, 346, 1147. (f) Mossé, S.; Alexakis, A.
Org. Lett. 2005, 7, 4361. (g) Mossé, S.; Andrey, O.;
Alexakis, A. Chimia 2006, 60, 216. (h) Mossé, S.;Alexakis,
A. Org. Lett. 2006, 8, 3577.
Organocatalytic Michael Addition of Aldehydes 7 to Nitro-
alkenes 8; General Procedure
To a soln of organocatalyst 5 (0.05 mmol, 15 mol%) in CHCl3 (3
mL) was added at the appropriate temperature the aldehyde 7 (3.35
mmol, 10 equiv) and the nitroalkene 8 (0.335 mmol, 1 equiv). The
course of the reaction was followed by TLC until completion. The
soln was then hydrolyzed with 1 M HCl (2 mL). The layers were
separated and the aqueous phase was extracted with CH2Cl2 (2 × 3
mL). The combined organic phases were dried (MgSO4), filtered,
concentrated, and purified by flash column chromatography (silica
gel, cyclohexane–EtOAc); enantiomeric excess was determined by
chiral SFC or chiral GC.
Organocatalytic Aldol Condensation of Ketones 10 and 11;
General Procedure
Organocatalyst 5 or 6 (0.05 mmol) was added to a stirred soln of
triketone 10 or 11 (1.0 mmol) in anhyd MeCN (2.0 mL). The mix-
ture was refluxed for an appropriate time, monitoring the reaction
by capillary GC. When the reaction was complete, toluene (5 mL)
was added, the mixture was concentrated in vacuo and the crude
product was purified by chromatography (silica gel, 30% EtOAc–
petroleum ether); enantiomeric excess was determined by HPLC
(Daicel Chiralcel OD-H (250 × 4.6 mm), detection: 254 nm, eluent:
4% i-PrOH–hexane; flow rate: 0.8 mL/min).
(7) Kanger, T.; Kriis, K.; Pehk, T.; Müürisepp, A.-M.; Lopp, M.
Tetrahedron: Asymmetry 2002, 13, 857.
(8) Kanger, T.; Laars, M.; Kriis, K.; Kailas, T.; Müürisepp, A.-
M.; Pehk, T.; Lopp, M. Synthesis 2006, 1853.
(9) Mossé, S.; Laars, M.; Kriis, K.; Kanger, T.; Alexakis, A.
Org. Lett. 2006, 8, 2559.
Acknowledgment
The authors thank Estonian Science Foundation (grant no 6662) and
Ministry of Education and Science (grant no 0142725s06) for finan-
cial support.
(10) Kriis, K.; Kanger, T.; Laars, M.; Kailas, T.; Müürisepp, A.-
M.; Pehk, T.; Lopp, M. Synlett 2006, 1699.
References
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Chem. Int. Ed. 2005, 44, 1758. For a general review on
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