A new route to silyl-substituted cyclobutenones and silylketenes

Article abstract of DOI:10.1016/j.tetlet.2010.10.130

2-Silyl-cyclobutene(di)ones are obtained by an addition/substitution approach on dimethyl squarate using silyl anions. The acetal and in particular the thioacetal derivatives readily undergo electrocyclic ring opening to reactive silyl(vinyl)ketenes.

Full text of DOI:10.1016/j.tetlet.2010.10.130

Tetrahedron Letters 52 (2011) 46–48
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Tetrahedron Letters
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A new route to silyl-substituted cyclobutenones and silylketenes
Konstantin Benda a, Tanja Knoth a, Rick L. Danheiser b, Ernst Schaumann a,
⇑
a Institut für Organische Chemie, Technische Universität Clausthal, Leibnizstraße 6, 38678 Clausthal-Zellerfeld, Germany
b Department of Chemistry, Masschusetts Institute of Technology, Cambridge, MA 02139, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
2-Silyl-cyclobutene(di)ones are obtained by an addition/substitution approach on dimethyl squarate
using silyl anions. The acetal and in particular the thioacetal derivatives readily undergo electrocyclic ring
opening to reactive silyl(vinyl)ketenes.
Received 31 July 2010
Revised 23 October 2010
Accepted 26 October 2010
Available online 31 October 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Silyl anions
Cyclobutenones
Silylketenes
Cyclopentenones
Cycloaddition reactions
1. Introduction
N2
R1Si
O
R1Si
3
1-Alkenyl(silyl)ketenes (‘silyl(vinyl)ketenes’) 11 show remark-
able stability, but are sufficiently reactive especially in cycloaddi-
tion chemistry to make them attractive synthetic building-
blocks,2–4 including in applications such as natural product
synthesis.5 Four main routes have been described for their synthe-
sis which, however, suffers from certain drawbacks (Scheme 1).
Thus, the dehydrohalogenation of appropriately substituted acyl
chlorides 2 is limited to produce vinylketenes in which R2 = H in
order to avoid regiochemical ambiguity.6 Similarly, the Wolff rear-
3
R3
O
Cl
R2
R2
R4
R3
NEt3
hν
R4
2
3
R1Si
3
O
R2
R4
1. Δ
2. hν
R3
1. Zn
2. Δ
R1Si
O
1
3
a
,b-unsaturated a0-diazoketones 3 works best for
SiR1
3
rangement of
R3
R4
purely aliphatic 1-alkenyl substitution.2 The outcome of the reac-
tion of silyl-substituted alkynes 4 with Fischer carbene complexes
5 depends on the size of the silyl substituent and is limited to the
preparation of vinylketenes in which R4 is an alkoxy group.5,7,8 Fi-
nally, the [2 + 2] cycloaddition of aryl(silyl)acetylenes 4 (R2 = aryl)
with dichloroketene and the subsequent dehalogenation give 2-si-
lyl-cyclobutenones and from there the corresponding silylketenes,
but the regioselectivity in the cycloaddition step can only be se-
cured when R2 is an aryl substituent.2 So it appeared attractive
to develop an independent method for regiospecific introduction
of a silyl substituent into the cyclobutenone ring.
Cl
R2
Cl
+
Cr (CO)5
R2
6
Zn/Cu
SiR1
5
4
Cl3C
Cl
3
R2 = Ar
O
+
R2
4
Scheme 1. Routes to silyl(vinyl)ketenes.
sequence, carbanions are first added to 7, the resulting alkoxide is
trifluoroacetylated to 8, and then a nucleophile is introduced in an
SN20 process to give intermediate 9 (Scheme 2).11–13 Thus, with
water as nucleophile cyclobutenediones are formed via the hemi-
acetal, the use of alcohols as nucleophile leads to acetals, and the
addition of amines produces cyclobutenimines.14 We reasoned
that this approach might be amenable to the introduction of a silyl
residue if a silyl anion15 is used as attacking nucleophile in the 1,2
2. Results and discussion
Dialkyl squarates 7 are excellent starting materials for the syn-
thesis of cyclobutene(di)ones.9,10 In a convenient one-pot reaction
⇑
Corresponding author. Tel.: +49 5323 72 2519; fax: +49 5323 72 2858.
E-mail address: ernst.schaumann@tu-clausthal.de (E. Schaumann).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.130

K. Benda et al. / Tetrahedron Letters 52 (2011) 46–48
47
1. R3Li
2. TFAA
3.H2O
R1O
R1O
O
O
Nu
O
R1O
R1O
O
1. R2M
2. TFAA
R1O
OMe
OMe
R3
Nu
OCOCF3
11a
R1O
R2
R2
-F3CCOO
9
Me2PhSi
O
7
8
R
1 = Alk
R2 = Alk, unsat. Alk, Ar
: R3 = Me (58%)
13a
13b: R3 = Ph (77%)
products
Scheme 2. Introduction of a substituent R2 into a squarate.
Scheme 4. Methoxy substitution in methoxy-cyclobutenone 11a.
addition step (R2 = silyl). In fact, silyl anions 10a–c turned out to
give a smooth addition to squarate 7 (R1 = Me) and, depending
on the method of work-up, provide diones of type 7 (one silyl in-
stead of MeO) or acetals 11a–c (Scheme 3).16 Isolated yields are
good for 11a and 11b, but probably due to steric reasons, 11c is
formed only in trace amounts (Table 1). Products 11 are stable at
room temperature and show no apparent tendency to undergo ring
opening to silylketenes 12.
HS(CH2)2SH
ZrCl4, CH2Cl2,O C
OMe
OMe
S
R3
Si
R3
Si
°
S
Ph
R1
Ph
R1
O
O
R2
R2
11,13
14
Interestingly, the remaining methoxy group in methoxy-
cyclobutenone 11a can be exchanged for a methyl or phenyl group
following the addition/substitution approach outlined in Scheme 2.
Thus, with methyl or phenyllithium and after aqueous work-up,
cyclobutenones 13a (57%) and 13b (77%) are formed (Scheme 4).
In a further modification, the acetal group in acetals 11a,b and
13a,b can be transformed into a thioacetal group which, if a dithio-
lane is formed, can be considered as a latent thione unit (Scheme
5).17 As in earlier studies,18,19 zirconium tetrachloride turned out
to be the most efficient Lewis acid catalyst for this transformation.
However, yields remain relatively low as in contrast to acetals 11
and 13, thioacetals 14 show, even at room temperature, a pro-
nounced tendency to undergo electrocyclic ring opening to give
silylketenes 15 which display variable stability. Thus, immediately
after chromatographic purification, products 14 already show the
characteristic ketene vibration at 2100 cmꢀ1 in the IR spectra.
The best yield is obtained for thioacetal 14c, followed by 14d, while
the methoxy-substituted derivative 14a is isolated in lower yield
and 14b only in trace amounts (Table 1). For 14c, complete conver-
sion into silylketene 15b20 is achieved by heating to 90 °C in tolu-
ene for 30 min. However, due to the limited stability of ketenes 15
and the corresponding species derived from acetals 13 it is advan-
tageous to use precursors 12–14 in reactions and generate the sily-
lketene in situ.
14,15a: R1 = R2 = Me, R3= OMe
b: R1 = Me, R2 = Ph, R2 = OMe
S
: R1 = R2 = R3 = Me
c
R3
Si
d: R1 = R2 = Me, R3 = Ph
S
Ph
R1
O
R2
15
Scheme 5. Formation of thioacetals 14 and electrocyclic ring opening to ketenes 15
(for yields see Table 1).
In previous studies, silylketenes have been shown to be useful
substrates for reaction with C1 transfer reagents to give cyclopen-
tenones in a [4 + 1] approach.21–23 A particularly smooth reaction
had been observed for (trimethylsilyl)diazomethane21 and this is
now confirmed for the reaction with the novel silylcyclobutenon-
es/silylketenes 11–14/15 (Scheme 6).24 Generally good yields
(50–74%)25 are obtained both from acetals 11 and 13 and from
thioacetals 14 implying that at temperatures above 90 °C ketene
intermediates of type 15 are also formed from acetals 11 and 13
which at room temperature are stable compounds with no appar-
ent tendency to undergo electrocyclic ring opening. However, only
trace amounts of cyclopentenone products 16c,f are formed from
silylcyclobutenones 13a and 14b where the corresponding ketene
intermediates 15 are apparently quite labile and preferably under-
go decomposition.
1. R1R2PhSiLi
OMe
(10)
2. TFAA
OMe
OMe
MeO
MeO
O
O
MeO
Ph
MeO
Ph
OMe
3. MeOH
The inherent 4
p system in vinylketenes 15 invites the use of
Si
precursors 11, 13, and 14 as dienes in Diels–Alder chemistry.2 Here
Si
O
O
R1
R2
R1
R2
7 (R1 = Me)
10 - 12a: R1 = R2 = Me
12
11
Me3SiCHN2
toluene,
95 °C, 12 h
R3
Si
X
X
X
b: R1 = Me, R2 = Ph
c: R1 = t-Bu, R2 = Ph
R3
Ph
SiMe3
X
Ph
R1
O
O
Si
R2
Scheme 3. Synthesis of silyl-substituted cyclobutenones (for yields see Table 1).
R1
R2
11a b 13a b 14a-d
, , , ,
16a: R1 = R2 = Me, R3 = X = OMe (51%)
Table 1
: R1 = Me, R2 = Ph, R3 = X = OMe (54%)
Starting materials, products, and yields in the reactions of Schemes 3 and 5
b
c: R1 = R2 = R3 = Me, X = OMe (trace)
Entry
Starting material
Product
Yield (%)
d: R1 = R2 = Me, R3 = Ph, X = OMe (77%)
e: R1 = R2 = Me, R3 = OMe, X = SCH2 (74%)
f: R1 = Me, R2 = Ph, R3 = OMe, X = SCH2 (trace)
g: R1 = R2 = R3 = Me, X = SCH2 (74%)
1
2
3
6
7
8
9
7 (R1 = Me)
7 (R1 = Me)
7 (R1 = Me)
11a
11b
13a
11a
11b
11c
14a
14b
14c
14d
82
49
Trace
29
Trace
57
h: R1 = R2 = Me, R3 = Ph, X = SCH2 (50%)
Scheme 6. 2,5-Bis-silylated cyclopentenones 16 from acetals 11, 13 or
thioacetals 14.
13b
32

48
K. Benda et al. / Tetrahedron Letters 52 (2011) 46–48
References and notes
S
S
S
R3
Si
R3
Me2PhSi
R4
NH
(c)
S
1. Reviews: (a) Tidwell, T. T. Ketenes, 2nd ed.; Wiley: Hoboken, NJ, 2006. pp 342–
361; (b) Pons, J.-M.; Kocienski, P. J. In Science of Synthesis; Fleming, I., Ed.;
Thieme: Stuttgart, Germany, 2002; Vol. 4, pp 657–668; (c) George, D. M.;
Danheiser, R. L. In Science of Synthesis in India; Danheiser, R. L., Ed.; Thieme:
Stuttgart, Germany, 2006; Vol. 23, pp 53–99; (d) Pommier, A.; Kocienski, P.;
Pons, J.-M. J. Chem. Soc., Perkin Trans. 1 1998, 2105–2118.
2. Loebach, J. L.; Bennett, D. M.; Danheiser, R. L. J. Org. Chem. 1998, 63, 8380–8389.
3. Bennett, D. M.; Okamoto, I.; Danheiser, R. L. Org. Lett. 1999, 1, 641–644.
4. Austin, W. F.; Zhang, Y.; Danheiser, R. L. Org. Lett. 2005, 7, 3905–3908.
5. Giese, M. W.; Moser, W. H. Org. Lett. 2008, 10, 4215–4218.
6. Danheiser, R. L.; Sard, H. J. Org. Chem. 1980, 45, 4810–4812.
7. Moser, W. H.; Sun, L.; Huffman, J. C. Org. Lett. 2001, 3, 3389–3391.
8. Li, Z.; Moser, W. H.; Zhang, W.; Hua, C.; Sun, L. J. Organomet. Chem. 2008, 693,
361–367.
9. Moore, H. W.; Yerxa, B. R. Chemtracts 1992, 5, 273–313; Adv. Strain Org. Chem.
1995, 4, 81–162.
10. Liebeskind, L. S. Tetrahedron 1989, 45, 3053–3060.
11. Reed, M. W.; Pollart, D. J.; Perri, S. T.; Foland, L. D.; Moore, H. W. J. Org. Chem.
1988, 53, 2477–2482.
12. Gayo, L. M.; Winters, M. P.; Moore, H. W. J. Org. Chem. 1992, 57, 6896–6899.
13. Liebeskind, L. S.; Fengl, R. W.; Wirtz, K. R.; Shawe, T. T. J. Org. Chem. 1988, 53,
2482–2488.
Ph
Me
Me
14c
O
O
or
d
: R3 = Me, R4= Ph (35%)
b: R3 = Me, R4 = CH=ChPh (18%)
19a
(b)
: R3 = R4 = Ph (16%)
c
(a)
d: R3 = Ph, R4 = CH=CHPh (53%)
S
S
CN
CN
CN
CN
R3
Me2PhSi
S
NO2
Ph
S
Me2PhSi
N
O
O
Me
17a: R3 = Me (99%)
: R3 = Ph (55%)
b
18
14. Oppermann, G.; Stranberg, M.; Moore, H. W.; Schaumann, E.; Adiwijaja, G.
Synthesis 2010, 2027–2038.
(40%)
15. Sekiguchi, A.; Lee, V. Y.; Nanjo, M. Coord. Chem. Rev. 2000, 210, 11–45.
16. Cyclobutenone 11a, Typical Procedure: Me2PhSiLi (70 mL, 0.5 M in THF,
35.0 mmol) was added dropwise to 7 (R1 = Me; 4.886 g, 34.4 mmol) in dry
THF (500 mL) at ꢀ78 °C. After 20 min, TFAA (5.5 mL, 34.4 mmol) was added
and after another 20 min dry MeOH (40 mL). The mixture was allowed to
warm to rt over 30 min with stirring and aq NaHCO3 (20%, 250 mL) added. The
product was extracted with ether (2 ꢁ 250 mL), the ethereal solution washed
with brine (2 ꢁ 150 mL), dried (MgSO4) and concentrated in vacuo. Purification
by flash chromatography (SiO2, petroleum ether/EtOAc = 101) yielded
cyclobutenone 11a (8.212 g, 46%). Yellow oil; 1H NMR (400 MHz, CDCl3):
d = 7.56 (m, 2H), 7.38 (m, 3H), 3.95 (s, 3H), 3.53 (s, 6H), 0.42 (s, 6H). 13C NMR
(100 MHz, CDCl3): d = 193.5, 192.1, 136.9, 133.7, 131.5, 129.5, 128.0, 115.0,
Scheme 7. Formal Diels–Alder reactions of silylketene precursors 14. Reagents and
conditions: (a) TCNE, toluene, 110 °C, 12 h (for 14c,d); (b) N-methyl-4-nitrobenz-
aldimine, toluene, 110 °C, 24 h (for 14d); (c) TMS–N@CH–Ph or TMS–N@CH–
CH@CH–Ph, cat. Zn(Otf)2, THF, rt, 24 h (for 14c,d); aq work-up.
we had little success with olefinic reaction partners. Only tetracy-
anoethylene gives a smooth reaction with thioacetals 14c,d, but no
cycloadduct 17 with 3-methoxy-cyclobutenone 14a (Scheme 7).
The alternative 2-alkenyl-cyclobutanone structure for 17 can be
ruled out because of a carbonyl vibration at relatively low wave-
60.2, 53.5, ꢀ2.5 ppm. IR (film):
m
= 1750 cmꢀ1. HRMS (ESI): [M+Na]+ found
315.1023, calcd 315.1023.
number around 1700 cmꢀ1
.
17. Schaumann, E.; Winter-Extra, S.; Rühter, G. J. Org. Chem. 1990, 55, 4200–4202.
18. Firouzabadi, H.; Iranpoor, N.; Karimi, B. Synlett 1999, 319–320.
[2 + 2] Cycloadditions of cyclobutenones 14 with C@N systems
turned out to be more successful. In particular, 14d undergoes a
smooth reaction with N-methyl-4-nitrobenzaldimine to give b-lac-
tam 18 in two diasteromeric forms with a characteristic carbonyl
absorption at 1740 cmꢀ1 (Scheme 7). Under the reaction condi-
tions, ketene 15a from cyclobutenone 14a apparently decomposes
and 14c/15c gives no reaction. In contrast, N-silyl-imines and sily-
lketene precursors 14c,d give d-lactams 19a–d,26 but to obtain the
indicated yields of 16–72% catalysis by zinc triflate is required; the
aqueous work-up leads to N-desilylation.
19. Regenhardt, W.; Schaumann, E.; Moore, H. W. Synthesis 2001, 1076–1080.
20. Selected data of compounds: Ketene 15b: slightly yellow liquid. 1H NMR
(400 MHz, CDCl3 = 7.26): d = 7.60 (m, 2H), 7.39 (m, 1H), 7.29–7.17 (m, 3H),
3.38 (m, 4H, SCH2), 1.77 (s, 3H), 0.49 (s, 6H). 13C NMR (125 MHz, CDCl3 = 77.4):
d = 198.6, 137.1, 133.8, 129.6, 85.3, 38.8, 38.1, 24.8, 0.9, ꢀ1.6. IR (film):
m
= 2958, 2086, 1589, 1428, 1252, 1115, 982, 813, 734, 701 cmꢀ1. HRMS (EI):
[M]+ found 306.0569, calcd 306.0568.
21. Loebach, J. L.; Bennett, D. M.; Danheiser, R. L. J. Am. Chem. Soc. 1998, 120, 9690–
9691.
22. Davie, C. P.; Danheiser, R. L. Angew. Chem. 2005, 117, 6017–6020; Angew. Chem.,
Int. Ed. 2005, 44, 5867–5870.
23. Li, Z.; Moser, W. H.; Deng, R.; Sun, L. J. Org. Chem. 2007, 72, 10254–10257.
24. Presented in part at the 21st International Symposium on the Organic
Chemistry of Sulfur (ISOCS XXI), Madrid, Spain, Jul 4, 2004; cf. Benda, K.;
Schaumann, E. Phosphorus, Sulfur Silicon Relat. Elem. 2005, 180, 1463–1464.
25. Cyclopentenone 16a: waxy solid, mp 74 °C. 1H NMR (200 MHz, CDCl3 = 7.26):
d = 7.37 (m, 1H), 7.21 (m, 4H), 3.47 (s, 3H), 3.28 (s, 3H), 3.14 (s, 3H), 2.41 (s, 1H),
0.06 (s, 3H), 0.04 (s, 3H), 0.00 (s, 9H). 13C NMR (125 MHz, CDCl3 = 77.4):
d = 206.7, 188.8, 140.6, 134.5, 130.0, 128.9, 116.0, 107.9, 62.4, 52.4, 52.3, 51.1,
3. Conclusion
The addition/substitution method (Scheme 2) offers convenient
access to silylcyclobutenones. Acetals 11 show no spontaneous
electrocyclic ring opening to silylketenes 12, but the ketene species
is apparently formed on heating with silyldiazomethane and
trapped to give cyclopentenones 16a–d. Thioacetals 14a–d are in
equilibrium with silylketenes 15, which can be trapped to 16–19,
but decomposition of 15 sometimes interferes.
0.1, 0.0. IR (film):
m = 2950, 2899, 2834, 1678, 1619, 1458, 1428, 1308, 1246,
1147, 1110, 1045, 970, 841, 816, 777, 734, 701, 650 cmꢀ1. HRMS (TOF-MS ES):
[M+Na]+ found 401.1591, calcd 401.1584.
26. d-Lactam 19c: colorless crystals, mp 205 °C. 1H NMR (200 MHz, CDCl3 = 7.26):
d = 7.91 (m, 2H), 7.56 (m, 2H), 7.24 (m, 11H), 6.42 (br s, 1H), 5.29 (s, 1H), 2.97
(m, 4H), 0.45 (s, 3H), 0.16 (s, 3H). 13C NMR (125 MHz, CDCl3 = 77.4): d = 177.4,
139.3, 137.0, 136.9, 133.0, 130.5, 129.5, 129.7, 129.5, 128.9, 128.5, 67.7, 48.2,
39.2, 38.4, 1.5, 0.0. IR (KBr):
m = 3166, 3056, 1676, 1491, 1445, 1427, 1374,
1348, 1303, 1246, 1111, 1018, 835, 818, 775, 730, 701, 652, 610, 544 cmꢀ1
HRMS (TOF-MS ES): [M+Na]+ found 496.1207, calcd 496.1201.
.
Acknowledgments
Support of our work by the Fonds der Chemischen Industrie,
Frankfurt, and the U.S. National Institutes of Health (GM 28273
to R.L.D.) is gratefully acknowledged.