Efficient 1,3-asymmetric inductions during nucleophilic additions to imine and iminium ion derivatives

Article abstract of DOI:10.1055/s-1999-2756

Two new β-amino alcohols have been synthesized by a reaction between an organolithium compound 1 involving an allylsilane moiety with either an imine or an oxazolidine derived from (S)-phenylglycinol. These reactions occurred in good yields and with high

Full text of DOI:10.1055/s-1999-2756

1094
LETTER
Efficient 1,3-Asymmetric Inductions during Nucleophilic Additions to Imine
and Iminium Ion Derivatives
Claude Agami, Sebastien Comesse, Catherine Kadouri-Puchot*, Marie Lusinchi
Laboratoire de Synthèse Asymétrique associé au CNRS, case courrier 47, Université Pierre et Marie Curie, 4 place Jussieu, 75005 Paris,
France
Fax +33 (1) 44 27 26 20; E-mail: kadouri@ccr.jussieu.fr
Received 16 April 1999
astereoselectivity (see Scheme 1 and Table 1). As shown
Abstract: Two new b-amino alcohols have been synthesized by a
in the Table 1, allowing the reaction mixtures to reach
room temperature resulted in lower yields; this can be as-
cribed to the instability of the anionic intermediates prior
reaction between an organolithium compound 1 involving an allyl-
silane moiety with either an imine or an oxazolidine derived from
(S)-phenylglycinol. These reactions occurred in good yields and
with high diastereoselectivity. Both amino-alcohols were engaged to the hydrolytic workup.
in cyclization reaction with glyoxal to afford in two steps highly
functionalized bicyclic lactones.
OH
Key words: organolithium reagent, asymmetric synthesis, b-amino
alcohols
O
OH
a
a
R
N
H
N
R
Ph
NH
Ph
Ph
TMS
2 (R=Ph)
3 (R=Et)
R
The addition of organometallic reagents to imines derived
from phenylglycinol has recently begun to attract interest
of chemists.1 Pioneering works of Takahashi et al.2 report-
ed the diastereoselective addition of chiral imines and 1,3-
oxazolidines with MeMgBr and MeLi. This study prompt-
ed many groups to synthesize by this way chiral amines,3
optically pure b-amino alcohols 4 and various natural and
non-natural products.5 This interesting process is not re-
stricted to such simple organometallic reagents. This Let-
ter relates the reaction of b-amino alcohols-derived
4 (R=Ph)
5 (R=Et)
Scheme 1 a) TMSCH2C(=CH2)CH2Li (1), THF, -78 to -20 °C.
Table 1 Reactions of the Lithium Derivative 1 with Compounds 2
and 3.
substrates
with
[2-((trimethylsilyl)methyl)prop-2-
enyl]lithium 1, which has been recently synthesized by
Livinghouse and Ryter,6 from an allyl selenide. Kang et
al.7 described the reactivity of an analogous reagent with
various aldimines which afford racemic piperidines.
These two new b-amino alcohols 4 and 5 were engaged in
cyclization reaction11 with glyoxal to test, on the one
hand, whether our already described methodology could
be extended to those new substrates and, on the other
hand, to establish the absolute configurations of the ste-
reogenic centers (Scheme 2).
TMS
Li
1
In the course of our studies aimed at extending our meth-
odology that leads to derivatives of pipecolic acid,8 amino
alcohols presenting both a second chiral center and an al-
lylsilane side-chain were required. Chiral imine 2 and ox-
azolidine 3 were obtained quantitatively by stirring (S)-
phenylglycinol at room temperature with the correspond-
ing aldehyde in the presence of MgSO4. The structure of
the products was established by 1H NMR. The main prod-
uct derived from benzaldehyde was the trans imine 2 as
already described.2a The propanal-derived oxazolidine 3
was obtained as a mixture which was epimeric at C-2 (60/
40).9 Subsequent addition of the organolithium reagent 1
on the chiral compounds 2 and 310 afforded b-amino alco-
hols 4 and 5 respectively in good yields and with high di-
O
N
O
H
O
N
OH
H
4 (R=Ph)
5 (R=Et)
a
b
Ph
Ph
R
R
6(R=Ph)
7 (R=Et)
8 (R=Ph)
9 (R=Et)
Scheme 2 a) CHOCHO, THF/H2O, 93% and 95% from 4 and 5 re-
spectively; b) COCl2, DMSO, NEt3, 70% for 8 and 93% for 9.
Synlett 1999, No. 07, 1094–1096 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
1,3-Asymmetric Inductions onto Imine and Iminium Ion Derivatives
1095
The reaction of amino alcohols 4 and 5 with glyoxal af- use them in the total synthesis of cyclic and functionalized
forded hemiacetals 6 and 7 respectively in high yields. derivatives of amino acids.
Swern oxidation produced lactones 8 and 9, both as a
unique diastereomer.13, 14 A complete stereocontrol was
Acknowledgement
therefore achieved in the formation of the bicyclic lac-
tones. The configuration of compound 9 was established
from a NOESY experiment as depicted in Figure 1.
We thank M.N. Rager (ENSCP, Paris) who performed the NOESY
experiment.
References and Notes
H
H
O
N
O
H
(1) (a) Ager, D.J.; Prakash, I.; Schaad, D.R. Chem. Rev. 1996, 96,
835-875. (b) Bloch, R. Chem. Rev. 1998, 98, 1413-1421.
(2) (a) Higashiyama, K.; Inoue, H.; Takahashi, H. Tetrahedron
Lett. 1992, 33, 235-238. (b) (2) Higashiyama, K.; Inoue, H.;
Takahashi, H. Tetrahedron 1994, 50, 1083-1092.
(3) (a) Wu, M-J.; Pridgen, L.N. J. Org. Chem. 1991, 56, 1340-
1344. (b) Scialdone, M.A.; Meyers, A.I. Tetrahedron Lett.
1994, 35, 7533-7536. (c) Higashiyama, K.; Inoue, H.;
Yamauchi, T.; Takahashi, H. J. Chem. Soc. Perkin Trans 1
1995, 111-114. (d) Blanchet, J.; Bonin, M.; Chiaroni, A.;
Micouin, L.; Riche, C.; Husson, H-P. Tetrahedron Lett. 1999,
40, 2935-2938.
Ph
H
H
9
Figure 1
During the whole process, two chiral centers were created
owing to two 1,3-asymmetric inductions occurring in dif-
ferent steps. As regards the first stereogenic center, the ab-
solute configuration resulted from attack of the lithium
derivative 1 on the oxazolidine 3. In agreement with pre-
vious works,2b,3a,15 this stereoselectivity can be rational-
ized by a chelated intermediate 10 in which the less
hindered Si face of the imine E-double bond is attacked by
the organometallic moiety.
(4) Allin, S.M.; Button, M.A.C.; Baird, R.D. Synlett 1998, 1117-
1119.
(5) (a) Higashiyama, K.; Nakahata, K.; Takahashi, H. J.Chem.
Soc. Perkin Trans 1 1994, 351-353. (b) Carrillo, L.; Badia, D.;
Dominguez, E.; Vicario, J. L.; Tellitu, I. J. Org. Chem. 1997,
62, 6716-6721. (c) Poerwono, H.; Higashiyama, K.;
Yamauchi, T.; Kubo, H.; Ohmiya, S.; Takahashi, H.
Tetrahedron 1998, 54, 13955-13970. (c) Poerwono, H.;
Higashiyama, K.; Takahashi, H. J. Org. Chem. 1998, 63,
2711-2714.
(6) Ryter, K.; Livinghouse, T. J. Org. Chem. 1997, 62, 4842-
4844.
Li
(7) Kang, K-T.; Kim, E. H.; Kim, W. J.; Song, N. S.; Shin, J. K.;
Cho, B. Y. Synlett 1998, 921-923.
(8) Agami, C.; Bihan, D.; Morgentin, R.; Puchot-Kadouri, C.
Synlett 1997, 799-800.
O
Ph
Li
R
N
TMS
H
(9) The composition of the imine-oxazolidine equilibrium was
determined in CDCl3. The ratio reported above may not be the
same when this reagent was used in THF, but this does not
matter since the addition most probably takes place on the
imine.
(10) Typical procedure: A solution of imine 2 or oxazolidine 3
(4.8 mmol) in THF (10 ml). was added dropwise at –78° to a
freshly prepared solution of 1 (13.5 mmol) in THF (150 ml)
The mixture was stirred at this temperature for 30 minutes and
allowed to –20 °C within 30 minutes. Then, a saturated
aqueous solution of NH4Cl (50 ml) was added. The reaction
mixture was extracted with Et2O (2 x 50 ml) and the organic
layer was dried over K2CO3. After evaporation under reduced
pressure, the residue was chromatographed on silica gel
(petroleum ether/ethyl acetate:80/20) to afford the b-amino
alcohols.
10
The absolute configuration of the other stereogenic center
results from the attack of the allylsilane function on the
transient iminium ion 11 according to the same stere-
ochemical outcome that we already described: attack of
the allylsilane in an anti relationship with respect to the
phenyl group.16 In this case however, the diasteroselectiv-
ity was dictated by two stereogenic centers already
present in the substrate, both providing 1,3-asymmetric
induction.
(11) Typical procedure: Glyoxal (2.1 ml) was added to a solution
of compound 5 (3.2 mmol) in THF/H2O (v/v:1/1, 13 ml). The
mixture was stirred for 5 h. at rt and water (10 ml) was added.
Extraction with CH2Cl2 (2 x 10 ml) was followed by drying on
MgSO4. After evaporation under reduced pressure,
chromatography on silica gel (petroleum ether/ethyl
acetate:90/10) gave hemiacetal 7 (0.76 g, 95%). The same
procedure was applied when starting from compound 4
(reaction time:36 h.) in order to obtain hemiacetal 6 (93%).12
(12) In both cases, the minor diastereomer was eliminated during
the chromatography step.
O
OH
+
Ph
N
TMS
Ph
11
This work is in progress to extend the methodology to the
preparation of more substituted b-amino alcohols and to
Synlett 1999, No. 07, 1094–1096 ISSN 0936-5214 © Thieme Stuttgart · New York

1096
C. Agami et al.
LETTER
(13) Data for compound 8:1H NMR (250 MHz, CDCl3):7.42-7.00
(m, 10H), 4.90 (bs, 1H), 4.80 (bs, 1H), 4.51 (dd, J = 12 and 5.9
Hz, 1H), 4.29 (dd, J = 12 and 7.7 Hz, 1H), 3.99 (dd, J = 7.7
and 5.9 Hz, 1H), 3.96 (dd, J = 5.9 and 4.2 Hz, 1H), 3.72 (dd,
J = 8 and 4.9 Hz, 1H), 2.90 (dd, J = 13.7 and 4.2 Hz, 1H), 2.44
(dd, J = 13.7 and 5.9 Hz, 1H), 2.36 (m, 2H). 13C NMR
(62.5MHz, CDCl3):170.3, 140.9-140.1, 138.1, 128.1, 127.9,
127.2, 127.0, 126.9, 126.5, 110.9, 68.6, 64.4, 56.9, 54.9, 40.4,
32.3. [a]20D:-9 (c 0.7, CHCl3).
and 13.6 Hz, 1H), 1.70 (d, J = 13.6 Hz, 1H), 1.55-1.13 (m,
1H), 1.25-1.13 (m, 1H), 0.82 (t, J = 7.4 Hz, 1H).13C NMR
(100 MHz, CDCl3):170.5, 141.3, 136.4, 129.1, 128.8, 128.5,
110.8, 73.8, 56.0, 55.9, 55.7, 33.1, 32.7, 23.4, 10.7. [a]20D:+81
(c 1, CHCl3).
(15) Delorme, D.; Berthelette, C.; Lavoie, R.; Roberts, E.
Tetrahedron: Asymmetry 1998, 9, 3963-3966.
(16) Agami, C.; Couty, F.; Puchot-Kadouri, C. Synlett 1998, 449-
456.
(14) Data for compound 9:1H NMR (400 MHz, CDCl3):7.38-7.35
(m, 5H), 4.86 (d, J = 1.6 Hz, 1H), 4.70 (d, J = 1.6 Hz,1H), 4.44
(dd, J = 4.5 and 9.7 Hz, 1H), 4.32-4.24 (m, 2H), 4.02 (dd,
J = 3.8 and 11.9 Hz, 1H), 2.72 (t, J = 13.9 Hz, 1H), 2.68-2.61
(m, 1H), 2.43 (dd, J = 3.8 and 13.2 Hz, 1H), 2.29 (dd, J = 4.3
Article Identifier:
1437-2096,E;1999,0,07,1094,1096,ftx,en;G11999ST.pdf
Synlett 1999, No. 07, 1094–1096 ISSN 0936-5214 © Thieme Stuttgart · New York