Spiro-cyclopropanation from oxoallylsilanes

Article abstract of DOI:10.1021/ja051967b

A novel highly stereoselective spiro-cyclopropanation reaction from oxoallylsilanes is described. Oxoallylsilanes are readily obtained by silylcupration of allene followed by conjugate addition to enones. The former oxoallylsilanes undergo a tandem cycliz

Full text of DOI:10.1021/ja051967b

Published on Web 05/12/2005
Spiro-Cyclopropanation from Oxoallylsilanes
Asuncio´n Barbero, Pilar Castren˜o, and Francisco J. Pulido*
Departamento de Qu´ımica Orga´nica, UniVersidad de Valladolid, 47011 Valladolid, Spain
Received March 28, 2005; E-mail: pulido@qo.uva.es
In the past years, organosilicon chemistry has become a
cornerstone of organic synthesis.1 Many valuable natural products
have frequently been prepared, taking advantage of the outstanding
chemical behavior of the silicon compounds.2 Among them, allyl-
and vinylsilanes are probably the most useful and widely used in
synthesis.3 It is not surprising, then, that a great deal of attention
has been directed to development of efficient routes for the synthesis
of these interesting building blocks. Silylmetalation of multiple
bonds is one of the best strategies and provides an easy access to
silicon-containing molecules.4 In a recent review, we have reported
the scope of the silylcupration of allenes, the relevancy of this
methodology for the preparation of functionalized allylsilanes,
and their application to the synthesis of naturally occurring
products.5
Allylsilanes bearing an electrophilic group are readily obtained
from allenes.6 They easily undergo intramolecular cyclization due
to the complementary electronic character of both functions, thus
providing useful strategies for cycloalkane annulations.6 Recently,
we found that Lewis acid-catalyzed cyclization of epoxyallylsilanes
follows an unusual rearrangement-cyclization pathway leading
stereoselectively to methylenecyclohexanols contained in many
terpenoid derivatives.7
In an effort to find new alternatives for the silicon-assisted
synthesis of natural products, we now report an unprecedented spiro-
cyclopropanation reaction from allylsilane-containing ketones car-
ried out in one step. Although huge advances have been made in
the stereoselective synthesis of cyclopropane derivatives,8 the recent
discovery of new antibiotics, amino acids, and oligo-unsaturated
fatty acids with linked cyclopropyl groups clearly demonstrates that
research in this area is far from over.9 Moreover, the spiro-
cyclopropyl moiety is present in the skeleton of many biologically
significant molecules such as illudin M and the taxane-AB
fragment.10
To optimize the procedure, a variety of combinations of solvent,
temperature, time, and reagent-to-substrate ratio was carefully tested
(Table 1). The use of different organometallics (Al or Zn) was also
considered. From examination of Table 1, it can be concluded that
conditions depicted in eq 2 seem to be the best choice. Times shorter
than 24 h do not lead to completion (compound 4, entry 2). Smaller
reagent-to-substrate ratios result in poor efficiency and larger
reaction times (entry 6). As revealed in Table 1, the Simmons-
Smith reagent (Et2Zn/CH2I2)11 is much less effective than the
Yamamoto version (Me3Al/CH2I2),12 the former leading to undesired
cyclopropanated open-chain products (entry 7). Higher temperatures
or nonpolar solvents reduce also the effectiveness of the process
Table 1. Reactions’ Conditions and Results
Oxoallylsilanes of type 2 are readily available from silylcupration
of allene (1,2-propadiene), followed by capture of the intermediate
cuprate with R,â-unsaturated ketones, at low temperature (eq 1).6a,7
A lower-order cuprate such as 1 is required to ensure the correct
regiochemistry of the addition to allene. The oxoallylsilane, in
DCM, was treated consecutively with 2 equiv of CH2I2 and Me3Al
at -60 °C; then the mixture was left to warm and was stirred at
room temperature around 48 h after workup to give the corre-
sponding spiro-cyclopropanes of type 3 (eq 2). The reaction (one
pot) proceeds under mild conditions and it is usually free from side
reactions.
a One equivalent used. b DMPSi ) PhMe2Si. c Yield determined by GC.
9
8022
J. AM. CHEM. SOC. 2005, 127, 8022-8023
10.1021/ja051967b CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Spiro-Cyclopropanes from Oxoallylsilanes
The procedure herein described is quite general, providing an
efficient route for the design and construction of hydroxylated bi-,
tri-, and tetracyclic systems bearing the spiro-cyclopropyl group
(Table 2). High levels of diastereoselectivity were found in all
cyclizations studied with the exception of 3e,f which were isolated
as a mixture of epimeric alcohols in 3:1 ratio.
The stereochemistry observed might indicate a preference for
the transition state I, where bulky groups attain an equatorial
conformation which minimizes steric repulsions. The high stereo-
control with which the reaction proceeds allows the preparation of
enantiomerically pure compounds such as 3h, starting from a chiral
building block such as (+)-pulegone. It should be noted that the
â-phenyl-substituted oxoallylsilane 2k affords the fused cyclopro-
pane 3k instead of the former spiro compound, maintaining the
silyl group unchanged. This interesting result seems to point to the
intermediacy of a stabilized â-silyl cation 8 in which the loss of a
proton competes favorably with the leaving of silyl group, perhaps
due to the formation of highly stabilized tetrasubstituted alkene.
This observation might be useful in the future for directing the
reaction in either sense, on the basis of the type of substitution.
Acknowledgment. We thank the Ministry of Science and
Technology of Spain (Project BQU2003/03035) and the JCyL
(Project VA050/2004) for financial support.
Supporting Information Available: Experimental procedures and
characterization data for all the new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
References
(1) (a) Auner, N.; Weis, J. Organosilicon Chemistry; Wiley-VCH: Weinheim,
2003. (b) Fleming, I. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds; Pergamon: Oxford, UK, 1991; Vol. 2. (c) Davies, A.
G. ComprehensiVe Organometallic Chemistry II; Pergamon: New York,
1995; Vol. 2.
(2) (a) Langkopf, E.; Schinzer, D. Chem. ReV. 1995, 95, 1375. (b) Fleming,
I.; Barbero, A.; Walter, D. Chem. ReV. 1997, 97, 2063.
(3) Fleming, I. Science of Synthesis: Houben-Weyl Methods of Molecular
Transformations; Thieme: Stuttgart, 2001; Vol. 4.
a Isolated pure compounds. b Reagent used: CH2I2/Et2Zn. c Epimeric ratio
3:1. d 3h: [R]D ) +12.4.
(4) Krause, N. Modern Organocopper Chemistry; Wiley-VCH: Dortmund,
Germany, 2002; Chapter 3, pp 93-102.
(5) Barbero, A.; Pulido, F. J. Acc. Chem. Res. 2004, 37, 817. For a recent
overview of the author’s work on metallocupration of multiple bonds,
see also: 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; Barbero,
A.; Pulido, F. J.; Rinco´n, J. A. J. Am. Chem. Soc. 2003, 125, 12049;
Barbero, A.; Blanco, Y.; Ferna´ndez, H.; Pulido, F. J. Synlett, 2004, 2833.
(6) (a) Barbero, A.; Garc´ıa, C.; Pulido, F. J. Tetrahedron (Symposium-in-
Print) 2000, 56, 2739. (b) Barbero, A.; Castren˜o, P.; Garc´ıa, C.; Pulido,
F. J. J. Org. Chem. 2001, 66, 7723. (c) Barbero, A.; Pulido F. J. Synthesis
2004, 779.
because of the increasing importance of organometallic addition
to the carbonyl group (entries 3 and 4).
Formation of spiro-cyclopropanes 3a-j (Table 2) seems to
proceed by a two-step pathway, involving silicon-assisted cycliza-
tion of the starting oxoallylsilane, followed by cyclopropanation
of the resulting methylenecyclopentanol (eq 2). The first step
(cyclization) is induced by the presence of the organoaluminum
compound; the second one (cyclopropanation) takes place by
reaction with an in situ formed iodomethylaluminum intermediate
(eq 2). The actual catalyst in the first step may be either Me3Al or
the iodomethylaluminum species.
This unique tandem mechanism is probably the most remarkable
feature of the reaction, enabling the construction of spiro-bicyclic
systems from open-chain allylsilanes in one step, a process of
undoubted interest from a synthetic point of view. Moreover, the
significance of the overall process becomes obvious when one
realizes that each component of the reagent (Me3Al or CH2I2) leads
separately to results different from the general reaction (Table 1,
entries 8-9, compare 5 and 7).
(7) Barbero, A.; Castren˜o, P.; Pulido, F. J. Org. Lett. 2003, 5, 4045.
(8) Kunz, R. K.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127, 3240
and references therein.
(9) Cyclopropanes and Related Rings; de Meijere, A., Ed; Chem. ReV. 2003,
103, Number 4, pp 931-1648.
(10) (a) Tokuzaki, K.; Kanemitu, Y.; Yoshimitsu, T.; Nagaoka, H. Tetrahedron
Lett. 2000, 41, 5923. (b) Primke, H.; Sarin, G. S.; Kohlstruk, S.;
Adiwidjaja, G.; de Meijere, A. Chem. Ber. 1994, 127, 1051. (c) Friese, J.
C.; Scha¨fer, H. J. Synlett 2002, 814. (d) Hashimoto, H.; Jin, T.; Karikomi,
M.; Seki, K.; Haga, K.; Uyehara, T. Tetrahedron Lett. 2002, 43, 3633.
(11) A modification of the original procedure due to Furukawa, see: Nishimura,
J.; Furukawa, J.; Kawabata, N.; Kitayama, M. Tetrahedron 1971, 27, 1799;
see also: Lorenz, J. C.; Long, J.; Yang, Z.; Xue, S.; Xie, Y.; Shi, Y. J.
Org. Chem. 2004, 69, 327.
(12) Maruoka, K.; Fukutani, Y.; Yamamoto, H. J. Org. Chem. 1985, 50, 4414.
JA051967B
9
J. AM. CHEM. SOC. VOL. 127, NO. 22, 2005 8023