Acid-Catalyzed Cyclization of Epoxyallylsilanes. An Unusual Rearrangement Cyclization Process

Article abstract of DOI:10.1021/ol035297v

(Equation presented) A new route for the synthesis of epoxyallylsilanes bearing the phenyldimethylsilyl group is reported that involves silylcupration of allene, conjugate addition to enones, and sulfur-ylide-mediated epoxidation. The Lewis acid-catalyzed

Full text of DOI:10.1021/ol035297v

ORGANIC
LETTERS
2003
Vol. 5, No. 22
4045-4048
Acid-Catalyzed Cyclization of
Epoxyallylsilanes. An Unusual
Rearrangement Cyclization Process
Asuncio´n Barbero, Pilar Castren˜o, and Francisco J. Pulido*
Departamento de Qu´ımica Orga´nica, UniVersidad de Valladolid,
47011 Valladolid, Spain
pulido@qo.uVa.es
Received July 15, 2003
ABSTRACT
A new route for the synthesis of epoxyallylsilanes bearing the phenyldimethylsilyl group is reported that involves silylcupration of allene,
conjugate addition to enones, and sulfur-ylide-mediated epoxidation. The Lewis acid-catalyzed cyclization of these substrates is presented.
The expected normal products derived from 5-exo and/or 6-endo attack are not observed; instead, methylenecyclohexanols resulting from a
tandem rearrangement−cyclization process are formed.
The use of organosilicon compounds as useful reagents in
the construction of natural products has become a powerful
tool in organic synthesis.1 In particular, allylsilanes have
proved to be one of the most versatile silicon-containing
synthons in allylation reactions.2 It is well-known that Lewis
Acids promote the reaction of allylsilanes with carbonyl
compounds (Sakurai-Hosomi reaction),2a,3 enones,2a,4 R,â-
unsaturated esters,5 and iminium ions.2a,6 The corresponding
intramolecular process, often called allylsilane-terminated
cyclization, is an easy entry to ring formation.
Despite its synthetic potential, the cyclization of epoxy-
allylsilanes has not been widely explored. It has been reported
that the stabilization of the incipient charge in the Lewis
acid-mediated intramolecular process overrides entropic and
stereoelectronic factors. Under Lewis acid conditions, nu-
cleophilic substitution usually takes place at the most
substituted carbon center of the epoxide7 unless the presence
of electron-withdrawing groups next to the epoxide desta-
bilizes the developing carbocation.8
Epoxyallylsilanes have been previously prepared by Wittig
reaction of an aldehyde with Ph3PdCHCH2SiMe3 followed
(1) Langkopf, E.; Schinzer, D. Chem. ReV. 1995, 95, 1375.
(2) (a) Fleming, I.; Barbero, A.; Walter, D. Chem. ReV. 1997, 97, 2063.
(b) Denmark, S. E.; Fu, J. Chem. Commun. 2003, 167. (c) Organ, M. G.;
Winkle, D. D.; Huffmann, J. J. Org. Chem. 1997, 62, 5254. (d) Suginome,
M.; Iwanami, T.; Yamamoto, A.; Ito, Y. Synlett 2001, 1042.
(3) (a) Hosomi, A.; Sakurai, H. J. Am. Chem. Soc. 1977, 99, 1673. (b)
Heathcock, C. H. J. Am. Chem. Soc. 1983, 105, 2354. (c) Schlosser, M.;
Franzini, L.; Bauer, C.; Leroux, F. Chem. Eur. J. 2001, 7, 1909. (d) Yadav,
J. S.; Chand, P. K.; Anjaneyulu, S. Tetrahedron Lett. 2002, 43, 3783.
(4) For selected examples, see: (a) Jeroncic, L. O.; Cabal, M.-P.;
Danishefsky, S. J.; Shulte, G. M. J. Org. Chem. 1991, 56, 387. (b) Kraus,
G. A.; Bougie, D. Tetrahedron 1994, 50, 2681. (c) Kno¨lker, H.-J.; Wanzel,
G. Synlett 1995, 378. (d) Brengel, G. P.; Meyers, A. I. J. Org. Chem. 1996,
61, 3230. (e) Wu, M.-J.; Yeh, J.-Y. Tetrahedron 1994, 50, 1073. (f) Yadav,
J. S.; Reddy, B. V. S.; Sadasiv, K.; Satheesh, G. Tetrahedron Lett. 2002,
43, 9695.
(5) (a) Kno¨lker, H.-J.; Baum, G.; Graf, R. Angew. Chem., Int. Ed. Engl.
1994, 33, 1612. (b) Organ, M. G.; Dragan, V.; Miller, M.; Froese, R. D. J.;
Goddart, J. D. J. Org. Chem. 2000, 65, 3666.
(6) (a) Katagiri, N.; Okada, M.; Kaneko, C.; Furuya, T. Tetrahedron
Lett. 1996, 37, 1801. (b) Amat, M.; Llor, N.; Bosch, J. Tetrahedron Lett.
1994, 35, 2223. (c) Burgess, L. E.; Gross, E. K. M.; Jurka, J. Tetrahedron
Lett. 1996, 37, 3255. (d) Burgess, L. E.; Meyers, A. I. J. Am. Chem. Soc.
1991, 113, 9858. (e) Stahl, A.; Steckham, E.; Nieger, M. Tetrahedron Lett.
1994, 35, 7371. (f) Kaptein, B.; Schoemaker, H. E. Tetrahedron Lett. 1994,
35, 1087.
(7) (a) Wang, D.; Chan, T.-H. J. Chem. Soc., Chem. Commun. 1984,
1273. (b) Armstrong, R. J.; Weiler, L. Can. J. Chem. 1986, 64, 584. (c)
Tan, T. S.; Mather, A. N.; Procter, G.; Davidson, A. H. J. Chem. Soc.,
Chem. Commun. 1984, 585. (d) Overman, L. E.; Renhowe, P. A. J. Org.
Chem. 1994, 59, 4138.
10.1021/ol035297v CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/30/2003

by epoxidation9 and by cross metathesis of alkenyl epoxides
and allylsilanes.10 We now report a new route for the
synthesis of epoxyallylsilanes by silylcupration of allene,
followed by capture of the intermediate cuprate with enones
and final formation of the epoxide.
unsaturated oxocompounds affords oxoallylsilanes of type
2 (Scheme 2), which are useful building blocks for cyclo-
pentane annelations.13
In this paper, we describe the synthesis and cyclization of
epoxyallylsilanes of type 3, carrying the phenyldimethylsilyl
group. As it is shown below, Lewis acid-catalyzed intra-
molecular cyclization occurs with concomitant rearrangement
of the epoxy group (Table 2), thus showing that the behavior
Scheme 1
Table 1. Synthesis of Oxo- and Epoxyallylsilanes
For the past decade, we have been involved in the study
of the metallocupration reactions of allenes and acetylenes
and their synthetic applications.11,12 These reactions involve
the addition of copper to one end of a multiple bond and a
metal (Si or Sn) to the other, allowing the formation of
intermediates of type 1 (Scheme 2).
Scheme 2
a THF was used as a solvent. b BF3‚Et2O was used as a catalyst. c TMSCl
was used as a catalyst.
of phenyldimethylsilyl derivatives is perceptibly different
from that observed for the trimethylsilyl analogues (Scheme
1).
The intermediate cuprate 1 can be captured by a great
variety of electrophiles.11,12 In particular, the use of R,â-
Phenyldimethylsilylcopper13 reacted readily with allene at
-40 °C to give a vinyl copper intermediate 1, which was
smoothly added to the R,â-unsaturated ketones 4-7 and the
enals 8-10 to afford compounds 11-17 in good yield. All
the reactions were carried out in the presence of BF3‚OEt2
or TMSCl, which considerably increased the yield (Table
1). The oxoallylsilanes thus obtained were treated with
dimethylsulfonium methylide to give in good yield the
(8) (a) Proctor, G.; Russell, A. T.; Murphy, P. J.; Tan, T. S.; Mather, A.
N. Tetrahedron 1988, 44, 3953. (b) Molander, G. A.; Andrews, S. W. J.
Org. Chem. 1989, 54, 3114.
(9) Seyferth, D.; Wursthorn, K. R.; Mammarella, R. E. J. Org. Chem.
1977, 42, 3104.
(10) Langer, P.; Holtz, E. Synlett 2002, 110.
(11) SiCu of allenes and acetylenes: (a) Cuadrado, P.; Gonza´lez, A. M.;
Pulido, F. J.; Fleming, I. Tetrahedron Lett. 1988, 29, 1825. (b) Fleming, I.;
Rowley, M.; Cuadrado, P.; Gonza´lez, A. M.; Pulido, F. J. Tetrahedron 1989,
45, 413. (c) Barbero, A.; Cuadrado, P.; Gonza´lez, A. M.; Pulido, F. J.;
Fleming, I.; Sa´nchez, A. J. Chem. Soc., Perkin Trans. I 1995, 1525. (d)
Blanco, F. J.; Cuadrado, P.; Gonza´lez, A. M.; Pulido, F. J. Synthesis 1996,
42. (e) Barbero, A.; Blanco, Y.; Garc´ıa, C.; Pulido, F. J. Synthesis 2000,
1223. (f) Barbero, A.; Garc´ıa, C.; Pulido, F. J. Synlett 2001, 824.
(12) SnCu of allenes and acetylenes: (a) Barbero, A.; Cuadrado, P.;
Gonza´lez, A. M.; Pulido, F. J.; Fleming, I. J. Chem. Soc., Chem. Commun.
1990, 1030. (b) Barbero, A.; Cuadrado, P.; Gonza´lez, A. M.; Pulido, F. J.;
Fleming, I. J. Chem. Soc., Perkin Trans. 1 1992, 327. (c) Barbero, A.;
Cuadrado, P.; Gonza´lez, A. M.; Pulido, F. J.; Fleming, I. J. Chem. Res.
1990, 291. (d) Barbero, A.; Cuadrado, P.; Gonza´lez, A. M.; Pulido, F. J.;
Fleming, I. J. Chem. Soc., Chem. Commun. 1992, 351. (e) Barbero, A.;
Cuadrado, P.; Gonza´lez, A. M.; Pulido, F. J.; Rubio, R.; Fleming, I. J. Chem.
Soc., Perkin Trans. 1 1993, 1657. (f) Barbero, A.; Cuadrado, P.; Garc´ıa,
C.; Rinco´n, J. A.; Pulido, F. J. J. Org. Chem. 1998, 63, 7531. (g) Barbero,
A.; Pulido, F. J.; Rinco´n, J. A.; Cuadrado, P.; Galisteo, D.; Mart´ınez-Garc´ıa,
H. Angew. Chem. Int. Ed. 2001, 40, 2101.
(13) (a) Blanco, F. J.; Cuadrado, P.; Gonza´lez, A. M.; Pulido, F. J.;
Fleming, I. Tetrahedron Lett. 1994, 35, 8881. (b) Barbero, A.; Garc´ıa, C.;
Pulido, F. J. Tetrahedron Lett. 1999, 40, 6652. (c) Barbero, A.; Garc´ıa, C.;
Pulido, F. J. Tetrahedron 2000, 56, 2739. (d) Barbero, A.; Castren˜o, P.;
Garc´ıa, C.; Pulido, F. J. J. Org. Chem. 2001, 66, 7723.
4046
Org. Lett., Vol. 5, No. 22, 2003

Table 2. Cyclization of Epoxyallylsilanes
corresponding epoxides 18-24 as mixtures of diastereo-
isomers (Table 1).
silanes. The nature of the silyl group clearly is playing an
important role in these reactions since structurally similar
epoxiallylsilanes bearing a trimethylsilyl group, instead of
the phenyldimethylsilyl group, give the normal product of
5-exo or 6-endo attack16 (Scheme 1).
The former observation seems to indicate that in the case
of epoxyallylsilanes with a phenyldimethylsilyl group, re-
arrangement of the epoxide occurs much faster than nucleo-
philic substitution on the epoxy group. In this sense, the fact
that cyclization of 18a and 18b gives the same result when
For compound 18, both diastereomers (18a and 18b) could
be separated by chromatography, and their stereochemistry
was assigned by X-ray analysis of one of them (Figure 1).
In the other cases, they were used as a mixture of diaster-
eomeric epoxides in the subsequent cyclization, which
apparently does not represent a limitation since it was verified
that both diastereomers 18a and 18b lead separately to the
same result.
The most noteworthy feature of the epoxyallylsilane
cyclization is the absence of products derived from 5-exo or
6-endo attack. Instead, we selectively obtained methylenecy-
clohexanols 25-35 from a rearrangement-cyclization pro-
cess (Table 2). The rearrangement of epoxides to carbonyl
compounds is a well-known reaction.14 However, this is the
first time that this sequential type of process has been
observed15 in the acid-catalyzed cyclization of epoxyally-
(14) (a) Rickborn, B. ComprehensiVe Organic Synthesis; Pergamon
Press: Oxford, 1991; Vol. 3, pp 733-771. (b) Kita, Y.; Furukawa, A.;
Futamura, J.; Ueda, K.; Sawama, Y.; Hamamoto, H.; Fujioka, H. J. Org.
Chem. 2001, 66, 8779. (c) Marson, C. M.; Campbell, J.; Hursthouse, M.
B.; Abdul Malik, K. M. Angew. Chem., Int. Ed. 1998, 37, 1122.
(15) Products of epoxide rearrangement have been obtained in a similar
cyclization reaction: Xiao, X.-Y.; Park, S.-K.; Prestwich, G. D. J. Org.
Chem. 1988, 53, 4869.
(16) (a) Corey, E. J.; Staas, D.D. J. Am. Chem. Soc. 1998, 120, 3526.
(b) Molander, G. A.; Shubert, D. C. J. Am. Chem. Soc. 1987, 109, 576.
Org. Lett., Vol. 5, No. 22, 2003
4047

C(Si) and CdO bonds, which would be parallel as it is shown
in the transition state II. This point has been recently
rationalized by Schlosser et al.3c A comparative inspection
of transition states II and III (Scheme 3) shows that II fits
Scheme 3
better with that geometry, whereas in III, the above-
mentioned bonds occupy a skew position.18 The use of a
bulkier Lewis acid such as titanium tetrachloride (Table 2,
entries 4 and 6), leads to the 1,2-trans isomer as the major
one, suggesting the intervention of transition state III with
both the R and the carbonyl-LA groups equatorial for
minimal steric repulsions (Scheme 3).
Figure 1. X-ray crystal structure of 18a (2R*,4R*).
In summary, a new route for the synthesis of epoxyallyl-
silanes having the PhMe2Si group is described and their acid-
catalyzed cyclization has been studied. The so-called normal
products derived from 5-exo or 6-endo attack were never
obtained. On the contrary, an interesting rearrangement-
cyclization was observed, which led to methylenecyclohex-
anols selectively.
treated with Lewis acids points out that the reaction proceeds
through common intermediates, and it could be considered
evidence that rearrangement takes place prior to cyclization.
A two-step pathway involving rearrangement to intermediate
I and cyclization seems to be the most feasible mechanism
for the general reaction we have reported. The degree of
concertedness between the two steps is still uncertain.17 The
cyclization reaction was examined with several Lewis acids
under a variety of solvents and temperature conditions (Table
2). The diastereomeric pairs collected in Table 2 could be
adequately separated by chromatography.
The diastereoselectivity and product outcome of the
process depends on the Lewis acid used. Aluminum-based
Lewis acids give low yields of the cyclized products. By
way of contrast, boron trifluoride etherate gives good yields
of methylenecyclohexanols. The results obtained with boron
trifluoride show that, except for entry 1, the ratio of
diastereomers formed is in favor of the 1,2-cis isomer (Table
2, entries 2, 3, 5). The preference for the cis isomer could
be due to the countercurrent flow of electrons in the Csp2-
Acknowledgment. We thank the Ministry of Science and
Technology of Spain (BQU2000/0867) and the “Junta de
Castilla y Leo´n” (VA023/2001) for financial support. We
are very much indebted to Prof. D. Miguel (Universidad de
Valladolid) for X-ray crystallographic help.
Supporting Information Available: Typical experimen-
tal procedures for the synthesis of oxoallylsilanes and
epoxyallylsilanes, experimental procedure for the cyclization
of epoxyallylsilanes, and characterization data for compounds
11, 13, 16, 18, 20, 23, 25, 26, 29, 30, 34, and 35. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL035297V
(17) We were not able to isolate or detect aldehydes resulting from
isomerization of the starting epoxiallylsilane.
(18) A better picture can be obtained using molecular models.
4048
Org. Lett., Vol. 5, No. 22, 2003