Lewis acid-promoted carbonyl addition of 1,3-bis(silyl)propenes

Article abstract of DOI:10.1016/j.tetlet.2008.09.099

A novel synthetic protocol for Lewis acid-promoted addition of 1,3-bis(silyl)propenes to N-phenyl glyoxylamide and ethyl glyoxylate is developed. The reaction does not appear to be influenced by the steric bulk of the 1,3-bis(silyl)propenes, and represents a new approach to vinylation of glyoxylates; the products are obtained in good yields.

Full text of DOI:10.1016/j.tetlet.2008.09.099

Tetrahedron Letters 49 (2008) 6882–6884
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Tetrahedron Letters
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Lewis acid-promoted carbonyl addition of 1,3-bis(silyl)propenes
Pavel Tuzina a, Peter Somfai a,b,
*
a Organic Chemistry, KTH Chemical Science and Engineering, SE-100 44 Stockholm, Sweden
b Institute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 July 2008
Revised 10 September 2008
Accepted 17 September 2008
Available online 20 September 2008
A novel synthetic protocol for Lewis acid-promoted addition of 1,3-bis(silyl)propenes to N-phenyl
glyoxylamide and ethyl glyoxylate is developed. The reaction does not appear to be influenced by the
steric bulk of the 1,3-bis(silyl)propenes, and represents a new approach to vinylation of glyoxylates;
the products are obtained in good yields.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Vinylation
Allylsilane
[1,3]-Brook rearrangement
N-Phenyl glyoxylamide
Ethyl glyoxylate
Tin tetrachloride
Allylsilanes are synthetically versatile precursors to enantioen-
riched building blocks for natural product synthesis.1 Lewis acid-
promoted addition of allylsilanes to aldehydes and ketones is an
efficient method for stereoselective C–C bond formation,2-4 and
they can also be used as a synthetic equivalent of 1,2-5,6 and
1,3-7-9 dipoles in stereoselective annulation reactions. Recently,
we reported an expansion of allylsilane technology, namely that
1,3-bis(silyl)propene 1a can participate in a highly stereoselective
1a to glyoxylamide 3a14 and glyoxylate 3b, which represents a
conceptually distinct approach to vinylation of glyoxylates, as well
as providing access to functionalized allylsilanes (Scheme 2).
Initial attempts were directed toward developing optimal reac-
tion conditions for the successful addition of silane 1a to N-phenyl
glyoxylamide 3a (Table 1). In view of our previous success in pro-
moting the [3+2] annulation reaction of silane 1a with
a-amino
aldehydes, we began our investigation by employing MeAlCl2 as
the Lewis acid. Disappointingly, neither aluminum-based biden-
tate Lewis acids nor BF3ÁEt2O furnished the desired product (en-
tries 1 and 2).
[3+2] annulation reaction with a-amino aldehydes to provide den-
sely functionalized pyrrolidines 2 (Scheme 1).10
In contrast, the use of vinylsilanes as nucleophiles in addition to
carbonyl compounds is relatively rare,11,12 presumably due to their
low inherent nucleophilicity. Based on this precedent, we were
interested in examining the efficiency of silane 1a13 as a nucleo-
phile recognizing that its structural features include both vinyl-
and allylsilane moieties and that this dual reactivity would allow
for an efficient addition to carbonyl compounds. To this end, we re-
port a novel Lewis acid-catalyzed addition of 1,3-bis(silyl)propene
Further screening15 of both monodentate and chelating Lewis
acids revealed that excess SnCl4 successfully promoted addition
of silane 1a to glyoxylamide 3a to give 4a together with O-desily-
lated product 5 in low yield (entry 3). Both prolonged reaction time
and increased reaction temperature resulted in the formation of 6,
the result of a protodesilylation16 of 1a followed by addition of
the so-formed allylsilane to amide 3a. In order to preclude this
HO
SiMe2Ph
O
[3+2]-Annulation
PhMe2Si
SiMe2Ph
R
H
R
N
NHTs
Ts
SiMe2Ph
1a
2
Scheme 1. [3+2]-Annulation of a-amino aldehydes.
* Corresponding author. Tel.: +46 8 7906960; fax: +46 8 7912333.
E-mail address: somfai@kth.se (P. Somfai).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.09.099

P. Tuzina, P. Somfai / Tetrahedron Letters 49 (2008) 6882–6884
6883
O
OSiMe2Ph
R
SnCl4
R
PhMe2Si
SiMe2Ph
PhMe2Si
H
4Å MS,
CH2Cl2, -78 °C
O
O
1a
3a, R = NHPh
3b, R = OEt
4
Scheme 2. Addition of silane 1a to glyoxylamide 3a and glyoxylate 3b.
Table 1
Optimization of the reaction conditions for the addition of 1a to N-phenyl glyoxylamide 3aa
OR
OH
O
LA
PhMe2Si
NHPh
NHPh
PhMe2Si
SiMe2Ph
NHPh
H
cond.
O
O
O
1a
6
3a
4a, R = SiMe2Ph
5, R = H
Entry
Lewis acid
Equiv
T (°C)
Time (h)
Product
Yieldb (%)
1
2
3
MeAlCl2
BF3ÁEt2O
SnCl4
SnCl4
SnCl4
2
1
1.2
1
0.15
À78
À78
À78
24
24
2.5
18
1
—
—
4a (5)
6 (5)
4a
—
—
32 (12)
69 (17)
89
4
À78 to À20
À78
5c
a
Reaction conditions: to a solution of 3a (1.2 equiv) and 1a (1 equiv) in CH2Cl2 at À78 °C was added Lewis acid, and the reaction mixture was stirred for the indicated time,
see Ref. 17.
b
c
Isolated yield.
Reaction was conducted in the presence of 4 Å MS.
Ln
M
[1,3]-Brook
rearrangement
nucleophilic
addition
OSiMe2Ph
NHPh
MLn
O
O
O
O
PhMe2Si
PhMe2Si
SiMe2Ph
H
NHPh
O
NHPh
[Si]
[Si]
1a
3a
4a
7
Scheme 3. Proposed mechanism for allylsilane formation.
undesired side reaction, it was found that addition of 4 Å molecular
sieves to the reaction mixture together with a low reaction tem-
perature could effectively suppress protodesilylation of silane 1a,
and using this protocol allylsilane 4a could be obtained as the sole
product in an excellent yield (entry 5).17
A plausible mechanism for the formation of 4a commences with
nucleophilic addition of silane 1a to the Lewis acid-activated elec-
trophile 3a, furnishing the b-silicon-stabilized carbocation 7,18 and
subsequent [1,3]-Brook rearrangement19 yields allylsilane 4a
(Scheme 3). Thus, this reaction represents a rare example of viny-
lation of glyoxylates.11 Since 1a is a rather poor nucleophile com-
pared to the corresponding allylsilane,20 it is believed that
bidentate Lewis acid activation of 3a is required to promote the
addition. With optimized conditions at hand, we then turned our
attention to the reaction scope. Despite the fact that glyoxylamide
3a has been used successfully in asymmetric glyoxylamide-ene
reactions,21 Sakurai allylations,14 and vinylsilane11 and proparg-
ylsilane22 additions, it is not commercially available, and has to
be prepared via a tedious procedure.21 Consequently, we were
interested to see whether the present reaction protocol could be
applied for the addition of silane 1a to commercially available
ethyl glyoxylate 3b, thus making it more suitable for future
Table 2
SnCl4-catalyzed additions of silanes 1a–c to 3a, ba
O
O[Si]
SnCl4
[Si]
[Si]
[Si]
R
R
H
CH2Cl2, -78 °C, 4Å MS
O
O
1a-c
3a, b
4a-d
Entry
1 ([Si])
3 (R)
Equiv (SnCl4)
Yield of 4b (%)c
1
2
3
4
a (SiMe2Ph)
a (SiMe2Ph)
b (SiMe3)
a (NHPh)
b (OEt)
b (OEt)
b (OEt)
0.15
0.3
0.3
a (89)
b (84)
c (71)
d (85)
c (SiPh2t-Bu)
0.3
a
For reaction conditions, see Ref. 24.
b
c
All new compounds were fully characterized by IR, 1H, and 13C NMR.
Isolated yield.

6884
P. Tuzina, P. Somfai / Tetrahedron Letters 49 (2008) 6882–6884
16. Fleming, I.; Langley, J. A. J. Chem. Soc., Perkin Trans. 1 1981, 1421–1423.
17. A typical experimental procedure for the preparation of 4a is described (Table
1, entry 5). To a solution of 3a (23.4 mg, 0.156 mmol) and silane 1a (40.4 mg,
0.130 mmol) in CH2Cl2 at À78 °C containing 4 Å MS (100 mg/mmol) was added
applications. To our delight, increasing the catalyst loading to 30%
of SnCl4 together with a prolonged reaction time afforded allylsi-
lane 4b in 84% yield (Table 2, entry 2). Finally, the effect of different
silicon substituents on the reaction outcome was investigated.23
Interestingly, neither the less bulky silane 1b ([Si] = SiMe3) nor
the more bulky silane 1c ([Si] = SiPh2t-Bu) showed significant ef-
fects on the product distribution, and the corresponding allylsi-
lanes 4c and 4d were obtained in good yields (Table 2, entries 3
and 4).24
In summary, we have developed a novel protocol for addition of
1,3-bis(silyl)propenes to Lewis acid-activated glyoxylates resulting
in vinylation. The reaction proceeds in high yields and the outcome
does not appear to be influenced by the steric bulk of the trialkyl-
silyl moieties in silanes 1. Further studies on the presented reac-
tion, including asymmetric protocols, are currently underway.
SnCl4 (13 lL, 0.1 mmol, 1 M solution in CH2Cl2) in one portion. The resultant
mixture was stirred at À78 °C until the reaction was judged complete by TLC
analysis (typically 1 h for additions to 3a, Rf (1a) = 0.84, 7:1 heptane/EtOAc).
The reaction mixture was then quenched at À78 °C with Et3N (0.2 mL)
followed by addition of H2O (10 mL). The mixture was extracted with EtOAc
(3 Â 15 mL), the organic phases dried (MgSO4), and the resultant crude
material purified by flash chromatography (SiO2, 7:1 pentane/EtOAc) to
provide 4a as a colorless oil (53.2 mg, 89%). 1H NMR (500 MHz, CDCl3) dH
8.43 (s, 1H), 7.58–7.54 (m, 2H), 7.54–7.49 (m, 4H), 7.46–7.30 (m, 8H), 7.15–
7.10 (m, 1H), 5.81 (dtd, J = 1.2, 8.2, 15.3, 1H), 5.43 (ddt, J = 1.1, 6.2, 15.1, 1H),
4.62 (d, J = 6.2, 1H), 1.75 (d, J = 8.3, 1H), 0.44 (s, 3H), 0.44 (s, 3H), 0.30 (s, 3H),
0.28 (s, 3H). 13C NMR (126 MHz, CDCl3) dC 170.26, 138.48, 137.63, 136.69,
133.82, 133.52, 130.67, 130.36, 129.18, 128.34, 127.98, 126.53, 124.46, 119.75,
75.45, 22.18, À0.94, À1.37, À3.08, À3.15. HRMS (ESI+): exact mass calcd for
C27H33NO2Si2 [M+H]+, requires m/z: 460.2122, found m/z: 460.2121.
18. Lambert, J. B. Tetrahedron 1990, 46, 2677–2689.
19. Moser, W. H. Tetrahedron 2001, 57, 2065–2084.
20. Restorp, P.; Dressel, M.; Somfai, P. Synthesis 2007, 1576–1583.
21. Evans, D. A.; Wu, J. J. Am. Chem. Soc. 2005, 127, 8006–8007.
Acknowledgments
22. Evans, D. A.; Aye, Y. J. Am. Chem. Soc. 2007, 129, 9606–9607.
This work was financially supported by the Swedish Research
Council and the Knut and Alice Wallenberg Foundation.
23. All 1,3-bis(silyl)propenes used in this investigation 1a–c were prepared from
the corresponding allylsilanes see: Knolker, H. J.; Foitzik, N.; Goesmann, H.;
Graf, R.; Jones, P. G.; Wanzl, G. Chem. Eur. J. 1997, 3, 538–551. by a known
method see Ref. 16.
References and notes
24. A typical experimental procedure for the preparation of 4b is described (Table
2, entry 2). To
containing 4 Å MS (100 mg/mmol, activated) was added freshly distilled ethyl
glyoxylate (263 L, 1.97 mmol, 80% solution in toluene, [see Evans, D. A.;
MacMillan, D. W. C.; Campos, K. R. J. Am. Chem. Soc. 1997, 119, 10859–10860] at
À78 °C followed by SnCl4 (164 L, 0.1 mmol, 1 M solution in CH2Cl2) and the
resulting mixture was stirred for 1 h at À78 °C. Each hour, for 2 h, an additional
portion of SnCl4 (2 Â 164 L, 0.2 mmol, 1 M solution in CH2Cl2) was added. The
a solution of silane 1a (509.8 mg, 1.64 mmol) in CH2Cl2
1. Chabaud, L.; James, P.; Landais, Y. Eur. J. Org. Chem. 2004, 3173–3199.
2. Fleming, I. Org. React. 1989, 37, 57.
l
3. Masse, C. E.; Panek, J. S. Chem. Rev. 1995, 95, 1293–1316.
4. Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97, 2063–2192.
5. Angle, S. R.; El-Said, N. A. J. Am. Chem. Soc. 2002, 124, 3608–3613.
6. Kiyooka, S. .; Shiomi, Y.; Kira, H.; Kaneko, Y.; Tanimori, S. J. Org. Chem. 1994, 59,
1958–1960.
7. Mertz, E.; Tinsley, J. M.; Roush, W. R. J. Org. Chem. 2005, 70, 8035–8046.
8. Panek, J. S.; Jain, N. F. J. Org. Chem. 1994, 59, 2674–2675.
9. Roberson, C. W.; Woerpel, K. A. J. Org. Chem. 1999, 64, 1434–1435.
10. Restorp, P.; Fischer, A.; Somfai, P. J. Am. Chem. Soc. 2006, 128, 12646–
12647.
l
l
resulting solution was stirred at À78 °C until the silane 1a was completely
consumed (1.5–2 h) as determined by TLC (Rf (1a) = 0.84, 7:1 heptane/EtOAc).
The reaction mixture was then quenched at À78 °C with Et3N and after
warming to rt, was filtered through Celite 521, and concentrated. The crude
product was purified by flash chromatography (aluminium oxide 90 active
basic, 7:1 pentane/EtOAc) to provide 4b as a colorless oil (569 mg, 84%). 1H
NMR (500 MHz, CDCl3) dH 7.66–7.50 (m, 2H), 7.50–7.43 (m, 2H), 7.43–7.29 (m,
6H), 5.74 (dtd, J = 1.2, 8.2, 15.3, 1H), 5.40 (ddt, J = 1.1, 6.7, 15.1, 1H), 4.54 (d,
J = 6.6, 1H), 4.20–4.00 (q, 2H), 1.72 (d, J = 8.3, 2H), 1.20 (t, J = 7.1, 3H), 0.39 (s,
3H), 0.38 (s, 3H), 0.25 (s, 6H).
11. Evans, D. A.; Aye, Y. J. Am. Chem. Soc. 2006, 128, 11034–11035. and references
therein.
12. Tomita, D.; Wada, R.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2005, 127,
4138–4139.
13C NMR (126 MHz, CDCl3) dC 174.18, 145.43,
13. de Dios, M. A. C.; Fleming, I.; Friedhoff, W.; Woode, P. D. W. J. Organomet. Chem.
2001, 624, 69–72.
14. Evans, D. A.; Aye, Y.; Wu, J. Org. Lett. 2006, 8, 2071–2073.
15. Lewis acids: BBr3, TiCl4, Sc(OTf)3, Sn(OTf)2.
139.95, 138.38, 133.73, 133.15, 131.49, 129.41, 129.27, 127.94, 127.86, 125.34,
71.93, 61.99, 22.23, 14.31, 1.01, À3.29. HRMS (ESI+): exact mass calcd for
C23H32O3Si2 [M+Na]+, requires m/z: 435.1782, found m/z: 435.1781.