Tin(IV) chloride catalyzed cycloaddition reactions between 3-ethoxycyclobutanones and allylsilanes

Article abstract of DOI:10.1021/ol901329c

Figur Presented Formal [4 + 2] cycloaddition between various 3-ethoxycyclobutanones and allyltrialkylsilanes proceeded to give 3-ethoxy-5-[(trialkylsilyl)methyl]cyclohexan-1-ones by catalysis with tin(VI) chloride. The use of allyl-fert-butyldiphenylsilan

Full text of DOI:10.1021/ol901329c

ORGANIC
LETTERS
2009
Vol. 11, No. 17
3822-3825
Tin(IV) Chloride Catalyzed Cycloaddition
Reactions between
3-Ethoxycyclobutanones and Allylsilanes
Jun-ichi Matsuo,* Shun Sasaki, Takaya Hoshikawa, and Hiroyuki Ishibashi
School of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health
Sciences, Kanazawa UniVersity, Kakuma-machi, Kanazawa 920-1192, Japan
jimatsuo@p.kanazawa-u.ac.jp
Received June 13, 2009
ABSTRACT
Formal [4 + 2] cycloaddition between various 3-ethoxycyclobutanones and allyltrialkylsilanes proceeded to give 3-ethoxy-5-[(trialkylsilyl)m-
ethyl]cyclohexan-1-ones by catalysis with tin(VI) chloride. The use of allyl-tert-butyldiphenylsilane induced 1,5-hydride transfer, which gave
2-[3-(tert-butyldiphenylsilyl)propyl]-6-methyltetrahydro-4-pyrones.
Substituted cyclohexenones are valuable compounds in
organic synthesis, and various methods for preparation of
these compounds have been developed. Reported methods
include a Diels-Alder reaction of siloxy diene with a
dienophile followed by acid treatment,1 Robinson annula-
tion,2 Birch reduction of o-methoxy-substituted benzoic acid
derivatives followed by alkylation and hydrolysis,3 and
alkylation of 3-alkoxycyclohex-2-en-1-ones followed by acid
hydrolysis.4,5 A highly substituted cyclohexane ring, which
is often seen in natural products and biologically active
compounds, can be constructed by using substituted cyclo-
hexenones, and efficient construction of multifunctionalizable
cyclohexenones remains an important task.
Recently, we found that 3-ethoxycyclobutanones reacted
with aldehydes or ketones to afford 2-ethoxytetrahydro-4-
pyrone derivatives in high yields by catalysis with boron
trifluoride etherate.6 Since the C-O double bond of alde-
hydes and ketones was efficiently inserted into the more
substituted C2-C3 bond of the cyclobutanone ring, we next
planned insertion of the C-C double bond into the cyclobu-
tanone ring. Allylsilanes7 have been employed as good
dipolarophiles for construction of four- and five-membered
carbocyclic compounds,8 and it was thought that 1,4-
(1) For leading references: (a) Danishefsky, S.; Kitahara, T. J. Am.
Chem. Soc. 1974, 96, 7807. (b) Danishefsky, S. Acc. Chem. Res. 1981, 14,
400. (c) Danishefsky, S. Chemtracts-Org. Chem. 1989, 2, 273. (d) Kozmin,
S. A.; Rawal, V. H. J. Org. Chem. 1997, 62, 5252. (e) Kozmin, S. A.;
Janey, J. M.; Rawal, V. H. J. Org. Chem. 1999, 64, 3039. (f) Kozmin,
S. A.; Rawal, V. H. J. Am. Chem. Soc. 1997, 119, 7165. (g) Kozmin, S. A.;
Rawal, V. H. J. Am. Chem. Soc. 1999, 121, 9562.
(2) Reviews:(a) Gawley, R. E. Synthesis 1976, 777. (b) Jung, M. E.
Tetrahedron 1976, 32, 3.
(6) Matsuo, J.; Sasaki, S.; Tanaka, H.; Ishibashi, H. J. Am. Chem. Soc.
2008, 130, 11600.
(3) (a) Taber, D. F. J. Org. Chem. 1976, 41, 2649. (b) Taber, D. F.;
Gunn, B. P.; Chiu, I.-C. Org. Synth. 1983, 61, 59, and references therein.
(4) (a) Woods, G. F.; Griswold, P. H.; Armbrecht, B. H.; Blumenthal,
D. I.; Plapinger, R. J. Am. Chem. Soc. 1949, 71, 2028. (b) Stork, G.;
Danheiser, R. L. J. Org. Chem. 1973, 38, 1775. (c) Stork, G.; Danheiser,
(7) General reviews for the use of allylsilanes in organic synthesis: (a)
Fleming, I. Chem. Soc. ReV. 1981, 10, 83. (b) Parnes, Z. N.; Bolestova,
G. I. Synthesis 1984, 991. (c) Blumenkopf, T. A.; Overman, L. E. Chem.
ReV. 1986, 86, 857. (d) Schinzer, D. Synthesis 1988, 263. (e) Fleming, I.;
Dunogues, J.; Smithers, R. Org. React. 1989, 31, 57. (f) Langkopf, E.;
Schinzer, D. Chem. ReV. 1995, 95, 1375.
R. L.; Ganem, B. J. Am. Chem. Soc. 1973, 95, 3414
.
(5) Another method:Stork, G.; Ponaras, A. A. J. Org. Chem. 1976, 41,
(8) Review:(a) Kno¨lker, H.-J. J. Prakt. Chem. 1997, 339, 304. (b) Masse,
C. E.; Panek, J. S. Chem. ReV. 1995, 95, 1293.
2939
.
10.1021/ol901329c CCC: $40.75
Published on Web 07/30/2009
 2009 American Chemical Society

zwitterionic species 2, generated by Lewis acid mediated
ring-opening of 3-ethoxycyclobutanones 1, would react with
allylsilanes 3 to give a formal [4 + 2] cycloadduct 5 via a
ꢀ-silyl cation9 intermediate 4 (Scheme 1). The product 5 has
a silyl group that can tolerate many organic reactions and
can be transformed to a hydroxyl group by Tamao oxida-
tion.10 [4 + 2] Cycloaddition to give six-membered car-
bocyclic compounds by using allylsilanes as a C2 unit haVe
not been reported to date.11-14 We report herein formal [4
+ 2] cycloadditions between 3-ethoxycyclobutanones and
allylsilanes and also report a unique cyclization via 1,5-
hydride transfer.
6a in 53% yield (entry 3). Catalysis with titanium(IV)
chloride gave product 8, which was formed by allylation of
the initial product 6a, in 23% yield along with cyclohexanone
derivative 6a (57%) and enone 7a, which was formed by
one-pot elimination of ethanol from 6a (entry 4). Enone 7a
was obtained as the major product when titanium(IV)
bromide was employed (entry 5). Tin(IV) chloride was found
to catalyze the desired [4 + 2] cycloaddtion most effectively
among Lewis acids we tested, and 6a was obtained in 80%
yield as a mixture of diastreomers (cis-6a/trans-6a ) 71:
29, entry 6). The present cycloaddition proceeded smoothly
also in toluene (entry 7), and a catalytic amount (20 mol %)
of tin(IV) chloride efficiently catalyzed the desired cycload-
dition to give 6a in 85% yield (entry 8). It was found that
the cis/trans ratio of 6a (cis/trans ) ca. 70:30) did not depend
significantly on the Lewis acid employed.
Scheme 1. Plan for Synthesis of Cyclohexanone Derivatives 5
by Lewis Acid (LA) Catalyzed Formal [4 + 2] Cycloaddition
between 3-Ethoxycyclobutanones 1 and Allylsilanes 3
Table 1. Optimization of Reaction Conditionsa
entry
Lewis acid
% yieldb 6a (cis/trans)
1c
2
Me3SiOTf
BF3·OEt2
EtAlCl2
TiCl4
TiBr4
SnCl4
SnCl4
SnCl4
SnBr4
0
1 (75:25)
53 (79:21)
57 (89:11)
6 (83:17)
80 (71:29)
78 (71:29)
85 (73:27)
16 (69:31)
3
4d
5e
6
First, we explored a suitable Lewis acid for the planned
[4 + 2] cycloaddition between cyclobutanone 1a and
allyltriisopropylsilane (Table 1). Allyltriisopropylsilane was
employed first because its sterically demanding silyl group
hasbeenreportedtosuppressallylationreactions(Hosomi-Sakurai
reaction15).16 It was found that the desired [4 + 2] cycload-
dition did not proceed by catalysis with trimethylsilyl triflate,
but dimerization of the starting material 1a to 9 took place
(entry 1). Only a trace amount (1%) of the desired product
6a was obtained by the use of boron trifluoride etherate (entry
2), whereas activation with ethylaluminum dichloride gave
7f
8g
9
a Cyclobutanone 1a (1.0 equiv), allyltriiropropylsilane (1.5 equiv), and
Lewis acid (1.2 equiv) were employed. Si ) Si(i-Pr3). b Combined yield of
1
cis- and trans-6a and cis/trans ratio of 6a were determined by H NMR
analysis. c Compound 9 was obtained in 50% isolated yield. d Compound
7a (2%) and 8 (23%) were obtained. e Compound 7a (57%) and 8 (16%)
were obtained. f Toluene was used as a solvent. g A catalytic amount of
SnCl4 (20 mol %) was used.
(9) Lambert, J. B.; Zhao, Y.; Emblidge, R. W.; Salvador, L. A.; Liu,
X.; So, J.-H.; Chelius, E. C. Acc. Chem. Res. 1999, 32, 183.
(10) (a) Tamao, K.; Ishida, N. J. Organomet. Chem. 1984, 269, C37.
(b) Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M. Organometallics 1983,
2, 1694. (c) Fleming, I.; Henning, R.; Plaut, H. J. Chem. Soc., Chem.
Commun. 1984, 29.
(11) Synthesis of tetahydropyrans: (a) Angle, S. R.; El-Said, N. A. J. Am.
Chem. Soc. 1999, 121, 10211. (b) Angle, S. R.; Belanger, D. S.; El-Said,
N. A. J. Org. Chem. 2002, 67, 7699. See also: (c) Angle, S. R.; El-Said,
The scope and limitations of the present cycloaddition
reaction were then investigated by employing tin(IV) chlo-
ride, various 3-ethoxycyclobutanones 1a-f and allyltriiso-
propylsilane in dichloromethane (Table 2). Several 2,2-
dialkyl-3-ethoxycyclobutanones 1a-c readily reacted with
N. A. J. Am. Chem. Soc. 2002, 124, 3608
.
(12) Synthesis of piperidine and tetrahydropyridine derivatives: (a)
Ungureanu, I.; Klotz, P.; Schoenfelder, A.; Mann, A. Chem. Commun. 2001,
958. (b) Horino, Y.; Kimura, M.; Naito, M.; Tanaka, S.; Tamaru, Y.
Tetrahedron Lett. 2000, 41, 3427
.
(13) Synthesis of tetrahydroqunolines and tetrahydroquinoxalines: (a)
Akiyama, T.; Suzuki, M.; Kagoshima, H. Heterocycles 2000, 52, 529. (b)
Shindoh, N.; Tokuyama, H.; Takasu, K. Tetrahedron Lett. 2007, 48, 4749.
(16) (a) Danheiser, R. L.; Dixon, B. R.; Gleason, R. W. J. Org. Chem.
1992, 57, 6094. (b) Kno¨lker, H.-J.; Foitzik, N.; Goesmann, H.; Graf, R.
Angew. Chem., Int. Ed. Engl. 1993, 32, 1081. (c) Akiyama, T.; Ishikawa,
K.; Ozaki, S. Chem. Lett. 1994, 627. (d) Akiyama, T.; Yasusa, T.; Ishikawa,
K.; Ozaki, S. Tetrahedron Lett. 1994, 35, 8401. (e) Kno¨lker, H.-J.; Foitzik,
N.; Goesmann, H.; Graf, R.; Jones, P. G.; Wanzl, G. Chem.sEur. J. 1997,
3, 538. (f) Akiyama, T.; Hoshi, E.; Fujiyoshi, S. J. Chem. Soc., Perkin
Trans. 1 1998, 2121. (g) Akiyama, T.; Ishida, Y. Synlett 1998, 1150. (h)
Sugita, Y.; Yamadoi, S.; Hosoya, H.; Yokoe, I. Chem. Pharm. Bull. 2001,
49, 657.
(c) Nair, V.; Vidya, R. D. N.; Devipriya, S. Synthesis 2006, 107
(14) Allylsilanes as C4 units: Organ, M. G.; Winkle, D. D.; Huffmann,
J. J. Org. Chem. 1997, 62, 5254
.
.
(15) (a) Hosomi, A.; Sakurai, H. J. Am. Chem. Soc. 1977, 99, 1673. (b)
Blumenkopf, T. A.; Heathcock, C. H. J. Am. Chem. Soc. 1983, 105, 2354.
(c) Sakurai, H. Pure Appl. Chem. 1982, 54, 1. (d) Hosomi, A. Acc. Chem.
Res. 1988, 21, 200. (e) Fleming, I.; Dunogues, I.; Smithers, R. Org. React.
1989, 37, 57.
Org. Lett., Vol. 11, No. 17, 2009
3823

allyltriisopropylsilane at -45 °C to afford [4 + 2] cycload-
ducts 6a-c in 79-96% yields (entries 1-3). Elimination
of ethanol from the initial product 6 proceeded by treatment
with trimethylsilyl triflate, and enones 7 were obtained in
good to high yields in two steps from cyclobutanone 1.
Spirocyclobutanones such as 1d,e also reacted smoothly to
afford 6d,e in 74% and 88% yields (entries 4 and 5).
3-Ethoxy-2-methylcyclobutanone 1f, which has a mono-
methyl substituent at the 2-position, also reacted readily with
allyltriisopropylsilane, and subsequent elimination gave
enone 7f in 61% yield (entry 6). In all examples described
above, allyltriisopropylsilane was regioselectively inserted
into the more substituted C2-C3 bond of cyclobutanones,
and other products formed by regioisomeric insertion of
allyltriiropropylsilane or noncyclized products were not
detected.
Table 3. Tin(IV) Chloride Catalyzed [4 + 2] Cycloaddition of
2-Diethyl-3-ethoxycyclobutanones to Various Allylsilanes
% yielda of 11 % yielda
entry
1
allylsilane 10
R1, R2 ) H,
(cis/trans)b
of 12
11ba
0
1
2
3
4
5
6
7
8
9
1b Si ) SiMe3 (10a)
80 (70:30)
11bb
72 (70:30)
11bc
75 (63:37)
11bd
55 (72:28)
11ad
Table 2. Tin(IV) Chloride Catalyzed [4 + 2] Cycloaddition of
Various 3-Ethoxycyclobutanones 1a-f to Allyltriisopropylsilane
R1, R2 ) H,
0
0
1b Si ) SiMe2Ph (10b)
R1, R2 ) H,
1b Si ) SiMe2CHPh2 (10c)
R1, R2 ) H,
12bd
22
12ad
16
12 cd
39
0
1b Si ) SiPh2t-Bu (10d)
1a 10d
53 (79:21)
11cd
1c 10d
50 (80:20)
11ae
R1 ) H, R2 ) Me,
1a Si ) SiMe3 (10e)
R1, R2 ) (CH2)4,
78 (52:48)c
11af
0
0
cyclobutanone 1
% yielda of 6
(cis/trans)
1a Si ) SiMe3 (10f)
64 (55:45)c
11ag
entry
R1, R2
6
7
% yieldb of 7
R1, R2 ) (CH2)3,
1a
6a
80
(71:29)
96
(72:28)
79
(70:30)
74
7a
78
1a Si ) SiMe3 (10g)
70 (57:43)c
1
2
3
4
5
6
R1, R2 ) Me
a Isolated yield. Determined by H NMR analysis. c Stereochemistry
was not determined.
b
1
1b
6b
6c
6d
6e
6f
7b
7c
7d
7e
7f
94
77
69
82
R1, R2 ) Et
1c
R1, R2 ) Bn
1d
2] cycloadducts 11bb and 11bc in 72% and 75% yields,
respectively (entries 2 and 3). It was found that the cis/trans
ratios of cyclohexanone derivative 11 did not depend on the
steric hindrance of silyl groups.
R1, R2 ) (CH2)4
1e
(68:32)
88
R1, R2 ) (CH2)5
1fc
(70:30)
ndd
61
Allyl-tert-butyldiphenylsilane 10d reacted with cyclobu-
tanone 1b to afford [4 + 2] cycloadduct 11bd in 55% yield
along with an unexpected product 12bd in 22% yield (entry
4). It is notable that only one distereomer (cis-product, 12)
was obtained. A possible mechanism for formation of 12bd
is shown in Scheme 2. 1,5-Hydride transfer18 of ꢀ-silyl cation
13, which is generated by tin(IV) chloride catalyzed addition
of 10d to 1b, gives a more stable zwitterionic intermediate
14 in which steric hindrance between two reaction sites is
reduced compared to that in the case of 13. Tetrahydro-4-
pyrone derivative 12bd is formed by cyclization of the
intermediate 14 with the six-membered chair transition
state.19
R1, R2 ) Me, H
(54:46)e
a Yield and cis/trans ratios were determined by 1H NMR analysis.
b Isolated yield for two steps from 1. c cis/trans ) 23:77. d Not determined.
e Diastereomer ratio.
Next, various allylsilanes 10a-d were employed instead
of allyltriisopropylsilane (Table 3). It is interesting that
cycloaddition between cyclobutanone 1b and allyltrimeth-
ylsilane 10a proceeded to afford the desired compound 11ba
in 80% yield (entry 1). This result suggests that formation
of a six-membered ring proceeds smoothly rather than
elimination of the trimethylsilyl group from intermediate 4,
and it is in contrast to the usual tendency of Lewis acid
catalyzed reaction of allyltrimethylsilane with carbonyl
compounds to give an allylation product (Sakurai product).
The reaction with allyldimethylphenylsilane 10b and allyl-
benzhydryldimethylsilane17 10c also gave the desired [4 +
(17) Peng, Z.-H.; Woerpel, K. A. Org. Lett. 2000, 2, 1379.
(18) 1,5-Hydride transfer: (a) Akiyama, T.; Nakano, M.; Kanatani, J.;
Ozaki, S. Chem. Lett. 1997, 385. (b) Choi, G. M.; Yoo, B. R.; Lee, H.-J.;
Lee, K.-B.; Jung, I. N. Organometallics 1998, 17, 2409.
3824
Org. Lett., Vol. 11, No. 17, 2009

butyldiphenylsilyl group20 and enolate moiety of the inter-
mediate 13 accelerates the 1,5-hydride transfer. The fact that
allyltriisopropylsilane did not induce 1,5-hydride transfer
suggests that the cation-stabilizing effect of the silyl group
may also play an important role in controlling the reaction
pathway (compare Table 2, entry 2 and Table 3, entry 4).21
Some substituted allyltrimethylsilanes 10e-g were em-
ployed in the present cycloaddition reaction with cyclobu-
tanone 1a (entries 7-9). The formal [4 + 2] cycloaddition
reaction proceeded to afford cycloadducts in good yields.
In summary, we have developed a formal [4 + 2]
cycloaddition between 3-ethoxycyclobutanones and allylsi-
lanes by catalysis with tin(IV) chloride. We have also found
the use of allyl-tert-butyldiphenylsilane induced 1,5-hydride
transfer, which gave a tetrahydro-γ-pyrone derivative. This
new method for the synthesis of cyclohexanones by employ-
ing a cycloaddition reaction between two easily accessible
small components, 3-ethoxycyclobutanone and allylsilane,
will have unique applicability in organic synthesis.
Scheme 2. Possible Mechanism for Formation of 12bd
To investigate the steric factors involved in inducing 1,5-
hydride transfer, cycloaddition of two cyclobutanones 1a,c
bearing dimethyl and dibenzyl groups at the 2-position of
3-ethoxycyclobutanone was examined (entries 5 and 6). It
was found that the yields of tetrahydro-4-pyrone derivatives
12 increased as the steric size of 2-alkyl groups became
larger. This suggests that steric hindrance between the tert-
Acknowledgment. This study was supported by a SUM-
BOR grant and a Grant-in-Aid for Scientific Research from
MEXT, Japan.
Supporting Information Available: Experimental pro-
cedures and characterization data of new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(19) 1,5-Hydride transfer/cyclization: (a) Verboom, W.; Reinhoudt,
D. N.; Visser, R.; Harkema, S. J. Org. Chem. 1984, 49, 269. (b) Nijhuis,
W. H. N.; Verboom, W.; Reinhoudt, D. N.; Harkema, S. J. Am. Chem.
´
Soc. 1987, 109, 3136. (c) Wo¨lfling, J.; Frank, E.; Schneider, G.; Tietze,
´
L. F. Eur. J. Org. Chem. 2004, 90. (d) Ma´tyus, P.; Ea´s, O.; Tapolcsa´nyi,
P.; Polonka-Ba´lint, A.; Hala´sz-Dajka, B. Synthesis 2006, 2625. (e) Pastine,
OL901329C
´
S. J.; McQuaid, K. M.; Sames, D. J. Am. Chem. Soc. 2005, 127, 12180. (f)
Pastine, S. J.; Sames, D. Org. Lett. 2005, 7, 5429. (g) Barluenga, J.; Fan˜ana´s-
Mastral, M.; Aznar, F.; Valdes, C. Angew. Chem., Int. Ed. 2008, 47, 6594.
(20) Hwu, J. R.; Wang, N. Chem. ReV. 1989, 89, 1599.
(21) Hagen, G.; Mayr, H. J. Am. Chem. Soc. 1991, 113, 4954.
Org. Lett., Vol. 11, No. 17, 2009
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