Diastereoselective addition of silyl metals to γ-alkoxy substituted α,β-unsaturated esters

Article abstract of DOI:10.1016/j.tetlet.2004.12.064

Dimethylphenylsilyllithium adds to Z-γ-alkoxy-α,β- unsaturated esters to produce almost exclusively (i) the anti-adducts when the reaction is carried out in THF and (ii) the anti-adduct when carried out in the presence of HMPA. Poor stereocontrol is achieved with stereoisomeric E-γ-alkoxy-α,β-unsaturated esters.

Full text of DOI:10.1016/j.tetlet.2004.12.064

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 951–953
Diastereoselective addition of silyl metals
to c-alkoxy substituted a,b-unsaturated esters
Alain Krief,a,* Willy Dumonta and Diane Baillieula,b
a
´
Facultes Universitaires Notre-Dame de la Paix, Department of Chemistry, Lab de Chimie Organique de Synthese,
61 rue de Bruxelles, Namur 5000, Belgium
Fonds pour la Formation a la Recherche dans l’Industrie et l’Agriculture, 5 rue d’Egmont, Bruxelles 1000, Belgium
b
`
Received 7 June 2004; revised 29November 2004; accepted 10 December 2004
Available online 30 December 2004
´
Dedicated to Professor Leon Ghosez on the occasion of his 70th birthday for his valuable contribution to organic chemistry
Abstract—Dimethylphenylsilyllithium adds to Z-c-alkoxy-a,b-unsaturated esters to produce almost exclusively (i) the anti-adducts
when the reaction is carried out in THF and (ii) the anti-adduct when carried out in the presence of HMPA. Poor stereocontrol is
achieved with stereoisomeric E-c-alkoxy-a,b-unsaturated esters.
Ó 2004 Published by Elsevier Ltd.
As continuation of work aimed to produce methyl chry-
santhemate by tandem addition of stannyl- and silyl-
metals 2 and acetone to a,b-unsaturated esters,1 we
became interested in extending this reaction to related
c-alkoxy-a,b-unsaturated esters such as methyl 3-(2,
2-dimethyl-[1,3]dioxolan-4-yl)-acrylate 1 derived from
D-glyceraldehyde acetonide2 (Scheme 1). We expected
to favour asymmetric induction leading to the enantio-
selective synthesis of the desired compound.3
(Re) face
CO2Me
a) R3SiM 2, Solvent, -78°C
b) aq. NH4Cl, -78°C
O
Me
Me
(Si ) face
O
1
R3Si
CO2Me
R3Si
O
CO2Me
O
Me
Me
Me
+
Me
O
O
3Re
3Si
We first reacted trimethylsilyllithium 2a4a with the eno-
ate 1 and found that it adds quite selectively to the
Si-face of the Z-stereoisomer Z-1 to produce the anti-
adduct 3aSi (7 equiv HMPA, THF, À78 °C, de 62%;
Scheme 1, entry a) and with very poor stereocontrol
from the Re-face of its E-diastereoisomer leading to
the syn-adduct 3aRe (7 equiv HMPA, THF, À78 °C, de
12%; Scheme 1, entry e).
Entry
Yield 3Si/3Re
3 (%)
1
2
R3SiM
Me3SiLi,HMPA
anti/syn
a
b
c
d
e
f
Z
Z
Z
Z
E
E
E
E
60
81/19
95/05
05/95
02/98
44/56
54/46
37/63
36/64
2a
2b
2b
2c
2a
2b
2b
2c
PhMe2SiLi, HMPA
PhMe2SiLi
55
60
PhMe2Si Zn(Et2)Li
Me3SiLi,HMPA
PhMe2SiLi, HMPA
PhMe2SiLi
78
53
Although the carbon framework of the silyllithium is
similar to that of its tin analogue (compare Scheme 1,
entry a to Scheme 2, entry a), we felt that it was not se-
cure to compare these results. In fact due to synthetic
constraints, the presence of HMPA in the reaction
involving the silyl derivative is required which is not
the case with trimethylstannyllithium.
56
g
h
60
PhMe2Si Zn(Et2)Li
79
Scheme 1.
We have therefore prepared dimethylphenylsilyllithium
2b which, unlike trimethylsilyllithium 2a, can be gener-
ated in THF alone.4b We observed that, contrary to
*
Corresponding author. Tel.: +32 81 724539; fax: +32 81 724536;
e-mail: alain.krief@fundp.ac.be
0040-4039/$ - see front matter Ó 2004 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2004.12.064

952
(Re) face
A. Krief et al. / Tetrahedron Letters 46 (2005) 951–953
of HMPA prior to the aqueous quench ((i) THF,
À78 °C, 1 h (ii) HMPA, À78 °C, 3 h (iii) aq NH4Cl).
CO2Me
a) R3SnM 4, Solvent, -78°C
O
O
Me
Me
b) aq. NH4Cl, -78°C
(Si) face
It is even more interesting to compare the behaviour of
the trialkylsilyl metals to that of trialkylstannylmetals3
which belong to the same family of compounds.
1
R3Sn
CO2Me
R3Sn
O
CO2Me
O
Me
Me
Me
Both silyl-4a,b and stannyl-5a,b lithiums react in THF
with extremely high stereocontrol on methyl Z-3-(2,2-di-
methyl-[1,3]dioxolan-4-yl)-acrylate 1 but from different
faces (Re and Si, respectively; Scheme 1, entry c and
Scheme 2, entries a,b). The presence of HMPA in the
reaction medium reverses the face of attack in the for-
mer case (Scheme 1, entries b,c) whereas as we have dis-
covered in the present study it has no effect on the
reaction involving tributylstannyllithium (Scheme 1,
compare entries b,c).
+
Me
O
O
5Re
5Si
Yield
5 (%) anti/syn
5Si/5Re
Entry
1
R3SnM
4
a
b
c
d
e
f
Z
Z
Z
Z
E
E
Me3SnLi
74
58
67
84
73
50
100/00
100/00
100/00
0/100
(n-Bu)3SnLi
(n-Bu)3SnLi,HMPA
(n-Bu)3Sn(Et2)ZnLi
(n-Bu)3Sn(Et2)ZnLi
(n-Bu)3SnLi
Silyl-4c and stannyl-3 zincates however both add to the
same Re-face of methyl Z-3-(2,2-dimethyl-[1,3]dioxo-
lan-4-yl)-acrylate 1 (Scheme 1, entry d; Scheme 2, entry
d) and this trend is not reversed with its E-stereoisomer
although the stereofacial differentiation is poorer
(Scheme 1, entry h; Scheme 2, entry e).
10/90
74/26
Scheme 2.
the previous case, it generates the syn-adduct 3bRe in
good yield from the Z-enoate 1, and with extremely high
de (Scheme 1, entry c; compare to entry a).
The stereochemistry of each of the two diastereoisomers
of 3, has been ascertained by transforming them to the
corresponding
4-(dimethylphenylsilanyl)-5-hydroxy-
We performed, in order to confirm the important role of
HMPA in this facial stereocontrol, the reaction of 2b
with the Z-enoate Z-1 in THF-HMPA (7 equiv., THF,
À78 °C, 4 h). We found, as expected that it produces
the anti-adduct 3bSi resulting from the stereoselective at-
tack on its Si-face (Scheme 1, entry b). The stereoselec-
tivity proved to be much better than that observed from
2a under the same experimental conditions (Scheme 1,
compare entries a,b).
methyldihydrofuran-2-ones 6anti and 6syn on tandem
acid catalyzed dioxolane ring opening c-hydroxyester
ring closure (CF3CO2H, THF, 20 °C, 3 h, Scheme 3).6
The 1H NMR spectra of 6anti compares successfully with
that already described in the literature for the same com-
pound prepared from the silylcuprate and 5-hydroxy-
methyl-5H-furan-2-one.6 That of its stereoisomer 6syn
is as expected (Ha: d = 2.22 ppm, JHAÀHB = 8.4 Hz;
Hb d = 4.674 ppm, JHAÀHB = 8.4 Hz).
Diethylzincate4c 2c behaves as its lithium analogue 2b
when the reactions are performed in THF. It reacts by
the Re-face of the Z-enoate Z-1 and offers the advantage
of providing the syn-adduct 3bRe with even higher ste-
reocontrol (de 96 % instead of 90 %) and higher yield
(Scheme 1, entry d, compare to entry c).
Our results compare favourably with those already
described by Smadja and co-workers, involving the
tris(trimethylsilyl)silyl radical,7 since they allow the stereo-
selective synthesis of each of the two stereoisomers
of 3.
We were rather surprised to find that silyl metals react
with very poor stereocontrol with the E-enoate E-1,
whatever are the conditions used (de 8–28%; Scheme
1, entries e–h). This contrasts with the results reported
above for the Z-diastereoisomer Z-1 (de 62–96%;
Scheme 1, compare entries e–h to a–d).
At present, we are unable to rationalize the whole set of
results involving addition and cycloaddition reactions
on c-alkoxy-a,b-unsaturated esters bearing a chiral
c-carbon on the basis of any known model (degenerated
H
a
PhMe2Si
PhMe2Si
O
CO2Me
This whole set of these results is quite exceptional,
especially, the high control of the face of attack of sily-
llithium 2b towards methyl Z-3-(2,2-dimethyl-[1,3]-
dioxolan-4-yl)-acrylate 1 in THF and the remarkably
completely reversed facial stereocontrol found if the
reaction is carried out in the presence of HMPA. We
have ascertained, at least in the latter case that the reac-
tion occurs under kinetic control. This has been
achieved by determining the structures of the mixtures
of products generated as described in Scheme 1, entry
c ((i) THF, À78 °C, 4 h (ii) aq NH4Cl) or after addition
Hb
CF3CO2H, aq. THF,
20°C, 3h
Me
O
O
O
Me
O
OH
96 %
3Si
6anti
H
a
PhMe2Si
CO2Me
PhMe2Si
O
Hb
CF3CO2H, aq. THF,
20°C, 3h
Me
O
Me
O
OH
93 %
3Re
6Syn
Scheme 3.

A. Krief et al. / Tetrahedron Letters 46 (2005) 951–953
953
phenylsilyl chloride and elemental lithium in THF: (b)
George, M. V.; Peterson, D. J.; Gilman, H. J. Am. Chem.
Soc. 1960, 82, 403; Fleming, I.; Newton, T. W.; Roessler, F.
J. Chem. Soc., Perkin Trans. 1 1981, 2527; Fleming, I.;
Roberts, R. S.; Smith, S. C. J. Chem. Soc., Perkin Trans. 1
1998, 1209; From dimethylphenylsilyllithium4b and diethyl
zinc: (c) Crump, R. A. N. C.; Fleming, I.; Urch, C. J. J.
Chem. Soc., Perkin Trans. 1 1994, 701.
non-chelated Felkin-Anh or chelated Cram model or
another one).8 We are working towards this end.
References and notes
1. (a) Krief, A.; Dumont, W.; Provins, L. Synlett 1995, 121;
(b) Krief, A.; Provins, L. Synlett 1997, 505.
5. From tin hydrides and LDA: (a) Still, W. C. J. Am. Chem.
Soc. 1978, 100, 1481; From distanannes and alkyllithiums:
(b) Still, W. C. J. Am. Chem. Soc. 1977, 99, 4836.
6. Schneider, M.; Fazio, F., DE Patent 2001, 10020275.
7. Smadja, W.; Zahouily, M.; Malacria, M. Tetrahedron Lett.
1992, 33, 551.
8. (a) Krief, A.; Froidbise, A. Tetrahedron 2004, 60, 763, and
references cited; (b) Yechezkel, T.; Ghera, E.; Ramesh, N.
G.; Hassner, A. Tetrahedron: Asymmetry 1996, 7, 2423; (c)
Leonard, J. Contemp. Org. Synth. 1994, 1, 387; (d)
Yamamoto, Y.; Chounan, Y.; Nishii, S.; Ibuka, T.;
Kitahara, H. J. Am. Chem. Soc. 1992, 114, 7652.
2. (a) Katsuki, T.; Lee, A. W. M.; Ma, P.; Martin, V. S.;
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F. J. J. Org. Chem. 1982, 47, 1373; (b) Minami, N.; Ko, S.
S.; Kishi, Y. J. Am. Chem. Soc. 1982, 104, 1109; (c) Krief,
A.; Dumont, W.; Pasau, P.; Lecomte, P. Tetrahedron 1989,
45, 3039; See also Ando, K. J. Org. Chem. 1997, 62, 1934;
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3. Krief, A.; Provins, L.; Dumont, W. Angew. Chem., Int. Ed.
Engl. 1999, 38, 1946–1948.
4. From hexamethyldisilane and methyllithium in HMPA: (a)
Still, W. C. J. Org. Chem. 1976, 41, 3063; From dimethyl-