Stereoselective synthesis of γ-aminoallyltins from vinyltin acetals

Article abstract of DOI:10.1016/S0022-328X(98)00663-9

γ-Aminoallyltins were obtained by reacting RCuCNMgCl/BF₃·Et₂O with aminoacetals derived from β-tributylstannylacrolein. The control of the stereochemistry of the double bond and of the absolute configuration of the newly created ally

Full text of DOI:10.1016/S0022-328X(98)00663-9

Journal of Organometallic Chemistry 567 (1998) 21–23
Stereoselective synthesis of k-aminoallyltins from vinyltin acetals
Franck Suzenet, Errol Blart, Mickae¨l Destouches, Jean-Paul Quintard *
Laboratoire de Synthe`se Organique, UMR 6513 du CNRS, Faculte´ des Sciences et des Techniques de Nantes, 2 rue de la Houssinie`re, BP 92208,
44322 Nantes Cedex 3, France
Abstract
k-Aminoallyltins were obtained by reacting RCuCNMgCl/BF3 ·Et2O with aminoacetals derived from i-tributylstannylacrolein.
The control of the stereochemistry of the double bond and of the absolute configuration of the newly created allylic carbon centre
was proved possible. © 1998 Elsevier Science S.A. All rights reserved.
Keywords: k-Aminoallyltins; Aminoacetals; i-Tributylstannylacrolein; Stereochemistry
1. Introduction
mer [1] or to the anti diastereoisomer in function of
the size of the substituent on the h-carbon related to tin
[4].
Accordingly, we have developed a new approach to
reach substituted k-alkoxyallyltins from vinyltin acetals
by reacting (E)-i-tributylstannylacrolein acetals with
organocopper reagents in the presence of boron tri-
fluoride etherate [5].
Functionalized allylmetals appear to be key reagents
to achieve the stereoselective allylation of organic sub-
strates [1] and in these series, special attention has been
devoted to the addition of h-, k-, l- or m-alkoxyallyltins
on aldehydes which opens interesting possibilities to
reach selectively polyoxygenated molecules [1,2]. In this
This approach has been proved efficient to obtain
enantioenriched chiral allyltins starting from the corres-
ponding acetals derived from chiral diols having a C2
symmetry axis [5].
Due to the importance of compounds like amino
sugars, we decided to attempt an extension of this
strategy in order to obtain k-aminoallyltins from N,O-
acetals of i-tributylstannylacrolein. The appropriate
precursors were obtained via transacetalisation of 1-
tributylstannyl-3,3-diethoxyprop-1-ene 1 [6–8] with N-
monoprotected aminoalcohols, the equilibrium being
shifted by azeotropic distillation of ethanol.
type of reaction a stereospecific process involving a
6-membered cyclic transition state is observed when the
reactions are performed thermally or under high pres-
sure [1], while stereoselective reactions are observed
when the allylations are achieved in the presence of
boron trifluoride [1–3]. Furthermore, in this last case, it
is possible to drive the reaction to the syn diastereoiso-
* Corresponding author. Tel.: +33 2 51125408; fax: +33 2
51125412; e-mail: quintard@chimie.univ-nantes.fr
0022-328X/98/$19.00 © 1998 Elsevier Science S.A. All rights reserved.
PII S0022-328X(98)00663-9

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F. Suzenet et al. / Journal of Organometallic Chemistry 567 (1998) 21–23
The allyltin 12 was obtained with the Z configura-
tion (3JHH=8.2 Hz) and probably as
single
in order to evaluate the different influences stemming
from the nature of the aminoacetals (perhydroxazine 2a
or oxazolidine 2b), the order of the cyanocuprates and
the temperature (Table 1).
In both series, the desired SN2% reaction was obtained
at low temperature (compounds 3–7), but competition
with an SN2 process was shown to be possible when
increasing the temperature from −100 to −5°C (com-
pounds 8–11).
a
diastereoisomer since we have been unable to discrimi-
nate between the two possible diastereoisomers due to
the benzylic and allylic asymmetric carbon atoms
1
on the basis of H-, 13C- and 119Sn-NMR spectra. Tak-
ing into account the optical rotation of 12 ([h]2D0=
−119.9°), those for N-t-Boc derivative of phenylglyci-
nol ([h]2D0= −46°) and the values of about +120°
While cyanocuprate order has minor influence both
on the rate of the SN2 side reaction and on the Z/E
ratio for the SN2% products, the temperature of the
reaction can be of crucial importance both on the SN2
contribution and on the isomeric distribution of SN2%
products (allyltins 3–7). In practice, the SN2 contribu-
tion is avoided at low temperature (−78 or −100°C)
but the stereochemical course of the desired SN2% reac-
tion is strongly modified in the perhydroxazine series
(2a) since reversed diastereoisomeric ratios were ob-
tained at −100°C (high preference for the Z-isomer)
and −5°C (high preference for the E-isomer). A simi-
lar result is not observed in the oxazolidine series (2b)
where the preference for the Z-isomer was always high
(Z/E=70/30 to 100/0).
Since products obtained in both series of reactions
are likely to be obtained under kinetic control, it would
mean that the transoid or cisoid conformation of the
transition state is highly dependent on the temperature
in the perhydroxazines series. Therefore, in order to
obtain more information related to the reaction mecha-
nism, chiral aminoacetals should be used in order to
clarify this point.
observed for k-alkoxyallyltins when the allylic carbon
atom has the S configuration [2,5], it seems likely to
assign the R configuration to the newly created allylic
centre in 12 on the basis of the similarities in the
polarisability of the bonds around the allylic carbon in
the h-position related to tin.
Naturally, this last result, which might mean an anti
SN2% reaction on a cisoid conformation as already ob-
served with organic analogues [10] and vinyltin acetals
[5], must be confirmed and extended to other examples
to allow a valuable discussion.
In spite of this, the above results demonstrate that
k-aminoallyltins are easily obtained from N-protected
aminoacetals derived from i-tributylstannylacrolein. A
possible control of the geometry of the double bond
can be obtained in the perhydroxazine series and the
use of the oxazolidine derived from (R) phenylglycinol
allows access to the corresponding enantioenriched chi-
ral k-aminoallyltins.
Work is in progress in order to improve the under-
standing of the observed reactions and to evaluate the
potential interest of this new class of functional allyltins
reagents [11,12].
Until now, we have just obtained a meaningful result
from (E,E)-2-(i-tributylstannylvinyl)-oxazolidine 2c
derived from N-protected (R)-phenylglycinol.

F. Suzenet et al. / Journal of Organometallic Chemistry 567 (1998) 21–23
23
Table 1
Reaction of RnCuCN(MgCl)n/BF3 ·Et2O with i-tributylstannylacrolein aminoacetals
Vinyltin reagenta
Experimental conditionsb
RnCuCN(MgCl)n
k-Aminoallyltinsa,c
No. (Z/E)
T (°C)
SN2%/SN2
Overall yieldd
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
BuCuCNMgCl
BuCuCNMgCl
−100
−5
−110
−5
−100
−10
−78
−78
−5
3 (90/10)
3 (10/90)
4 (75/25)
4 (20/80)
5 (70/30)
5 (20/80)
6 (90/10)
7 (80/20)
7 (100/0)
7 (93/7)
100/0
90/10
100/0
90/10
100/0
80/20
100/0
100/0
37/63
95/5
(50)
(90) 70
(\95)
(\95) 86
(\95) 85
(\95) 80
(\95) 75
(\95) 80
(80)
iPr2CuCN(MgCl)2
iPr2CuCN(MgCl)2
t-Bu2CuCN(MgCl)2
t-Bu2CuCN(MgCl)2
Bu2CuCN(MgCl)2
iPrCuCNMgCl
iPrCuCNMgCl
iPr2CuCN(MgCl)2
iPr2CuCN(MgCl)2
−78
−5
(\95) 90
(\95) 75
7 (70/30)
75/25
a Compounds 2–11 have been characterized on the basis of their physicochemical data.
b Typical experimental procedure for 7: in a Schlenk reactor containing 2b (100 mg) in dry degased ether (5 ml) were added 0.055 mmol of
BF3 ·Et2O (three equivalents) at −78°C before addition (cannula transfer), at the desired temperature, of a solution obtained by addition at
−50°C of the Grignard reagent (1.11 mmol, six equivalents) to a stirred suspension of dry copper cyanide (47 mg, three equivalents) in ether (5
ml) over 30 min. The obtained mixture is allowed to react at the desired temperature until complete disappearance of 2b (TLC monitoring). After
hydrolysis at −78°C and usual treatments, compound 7 was purified by flash chromatography [9].
c The assignment of the Z or E configuration for 3–7 and 12 is done on the basis of 1H, 13C and 119Sn-NMR spectra, the main argument being
3
3
the value of the coupling constant JHH across the double bond (3JHH ca. 7.5–8 Hz in the Z-isomer while JHH ca. 13.5–14 Hz in the E-isomer).
d Values in brackets are conversion rates (NMR evaluation) while underlined values are isolated yields.
[7] (a) I. Beaudet, J.-L. Parrain, J.-P. Quintard, Tetrahedron Lett.
Acknowledgements
32 (1991) 6333. (b) I. Marek, A. Alexakis, J. F. Normant,
Tetrahedron Lett. 32 (1991) 6337.
[8] V. Launay, I. Beaudet, J.-P. Quintard, Synlett (1997) 821.
The authors are grateful to Chemetall, Schering and
Rhoˆne-Poulenc Societies for gifts of organometallic
starting materials and to MESR and AGISMED for
financial support.
[9] k-Aminoallyltins 3–7 can be purified on silica gel using hexane/
ether (80/20) or hexane/ethyl acetate/triethylamine (83/15/2) as
eluent. Meaningful NMR signals for 7Z and for its isomers 7E
and 11E (obtained when the reaction was performed at higher
temperature): 7Z: 1H-NMR l (ppm): 2.73 (Hh, dd, 3J1H=13.3,
3J1H=8.7, superimposed with N–CH, 2JSnH=53); 5.67 (Hi, dd,
3
3J1H=13.3, 3J1H=7.5, 3JSnH=22); 5.03 (Hk, d, J1H
=
References
7.5,4JSnH=16.5); 13C-NMR l (ppm): Ch=38.1 (1JSnC=267/
278); Ci=140.1 (2JSnC=35.5); Ck=119.7 (3JSnC=49);
[1] (a) Y. Yamamoto, N. Asao, Chem. Rev. 93 (1993) 2207. (b) Y.
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[6] Pure (E)-1-tributylstannyl-3,3-diethoxyprop-1-ene was obtained
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isomer can be obtained by titanation of 1-tributylstannyl-3,3-di-
ethoxyprop-1-yne [8].
119Sn-NMR l (ppm): −13.1. 7E: 1H-NMR l (ppm): 2.01 (Hh,
3
dd, 3J1H=6.9, 3J1H=11.4); 5.16 (Hi, dd, 3J1H=13.6, J1H
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11.7, 3JSnH=22); 6.17 (Hk, d, 3J1H=13.6, 4JSnH=18); 13C-
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(ppm): −16.4. 11: 1H-NMR l (ppm): 5.87 (Hh, d, 3J1H=19,
2JSnH=73); 5.59 (Hi, dd, 3J1H=19, 3J1H=7, 3JSnH=63); 3.86
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–44.3.
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intramolecular additions are involved [12].
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Lett. 37 (1996) 2109. (b) I. Kadota, M. Kawada, Y. Muramatsu,
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.