Formal [3 + 2] and [3 + 3] additions of acceptor-substituted cyclopropylmethylsilanes to allenylsilanes

Article abstract of DOI:10.1021/ol047991w

(Chemical equation presented) 1,3-Dipolar synthons formed from vicinal TBDPS-substituted cyclopropyl alkyl/phenyl ketones on treatment with Lewis acids such as TiCl₄ and Et₂AlCl reacted with allenylsilanes to furnish [3 + 2] and [3 +

Full text of DOI:10.1021/ol047991w

ORGANIC
LETTERS
2004
Vol. 6, No. 24
4495-4498
Formal [3
Acceptor-Substituted
+ 2] and [3 + 3] Additions of
Cyclopropylmethylsilanes to
Allenylsilanes
Veejendra K. Yadav* and Vardhineedi Sriramurthy
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
Vijendra@iitk.ac.in
Received October 1, 2004
ABSTRACT
1,3-Dipolar synthons formed from vicinal TBDPS-substituted cyclopropyl alkyl/phenyl ketones on treatment with Lewis acids such as TiCl4
and Et2AlCl reacted with allenylsilanes to furnish [3
+
2] and [3
+
3] adducts with high regio- and stereocontrol.
The endeavor of carbon-carbon bond formation becomes
attractive when more than one bond is formed in a single
maneuver. Lewis acid promoted reactions of allenylsilanes
with 1,2- and 1,3-dipoles provide easy access to five- and
six-membered carbo- and heterocyclic rings where the
allenylsilane functions as the synthetic equivalent of a silyl-
substituted 1,2- and/or 1, 3-dipole.1 To explore the synthetic
applications of cyclopropylmethylsilanes,2 we have previ-
ously shown cyclopropyl ketones bearing a vicinal tert-
butyldiphenylsilylmethyl group to serve as excellent 1,3-
dipolar synthons under Lewis acid conditions to enable
formal [3 + 2] cycloadditions of arylacetylenes in a regio-
and stereoselective manner.2d To our knowledge, dipolar
additions of donor-acceptor substituted cyclopropanes to
allenylsilanes are hitherto unknown.1,3 However, allylation
and cycloaddition reactions of activated cylopropanes with
allylsilanes have been reported.3b,4 Herein, we report the first
application of allenylsilanes for cycloaddition with tert-
butyldiphenylsilylmethyl-substituted cyclopropyl ketones,
leading to the formation of [3 + 2] and [3 + 3] adducts.
The course of the reaction was modulated by both the
reaction temperature and the substitution profile of the
allenylsilane.
In principle, the donor-acceptor substituted cyclopropane
of type 1 could react first either a nucleophile through the
silicon-stabilized positive end of the dipole or with an
electrophile through the negative end, i.e., the enolate.3d The
reaction outlined in Scheme 1 falls under the former domain.
The vinyl cation A may rearrange to the vinyl cation B
entailing 1,2-migration of the allenylsilicon function.1,5 The
(1) (a) Miura, K.; Hosomi, A. Main Group Metals in Organic Synthesis;
Yamamoto, H., Oshima, K., Eds.; Wiley-VCH: Weinheim, 2004; Vol. 2,
pp 409-501. (b) Danheiser, R. L.; Carini, D. J.; Basak, A. J. Am. Chem.
Soc. 1981, 103, 1604. (c) Danheiser, R. L.; Kwasigroch, C. A.; Tsai, Y.-
M. J. Am. Chem. Soc. 1985, 107, 7233. (d) Becker, D. A.; Danheiser, R. L.
J. Am. Chem. Soc. 1989, 111, 389. (e) Danheiser, R. L.; Stoner, E. J.;
Koyama, H.; Yamashita, D. S.; Klade, C. A. J. Am. Chem. Soc. 1989, 111,
4407. (f) Angle, S. R.; Arnaiz, D. O. Tetrahedron Lett. 1991, 32, 2327. (g)
Evans, D. A.; Sweeny, Z. K.; Rovis, T.; Tedrow, J. S. J. Am. Chem. Soc.
2001, 123, 12095. (h) Denmark, S. E.; Gomez, L. Heterocycles 2002, 58,
129.
(2) (a) Yadav, V. K.; Balamurugan, R. Org. Lett. 2001, 3, 2717. (b)
Yadav, V. K.; Balamurugan, R. Chem. Commun. 2002, 514. (c) Yadav, V.
K.; Balamurugan, R. Org. Lett. 2003, 5, 4281. (d) Yadav, V. K.; Sriramurthy,
V. Angew. Chem., Int. Ed. 2004, 43, 2669. (e) Yadav, V. K.; Vijaya Kumar,
N. J. Am. Chem. Soc. 2004, 126, 8652.
(3) (a) Yu, M.; Pagenkopf, B. L. Org. Lett. 2003, 5, 5099. (b) Yu, M.;
Pagenkopf, B. L. Org. Lett. 2003, 5, 4639. (c) Yu, M.; Pagenkopf, B. L. J.
Am. Chem. Soc. 2003, 125, 8122. (d) Reissig, H.-U.; Zimmer, R. Chem.
ReV. 2003, 103, 1151. (e) Young, I. S.; Kerr, M. A. Angew. Chem., Int. Ed.
2003, 42, 3023. (f) Yu, M.; Pantos, G. D.; Sessler, J. L.; Pagenkopf, B. L.
Org. Lett. 2004, 6, 1057. (g) Young, I. S.; Kerr, M. A. Org. Lett. 2004, 6,
139.
(4) (a) Bambal, R.; Kemmett, R. D. W. J. Chem. Soc., Chem. Commun.
1988, 734. (b) Sugita, Y.; Yamadoi, S.; Hosoya, H.; Yokoe, I. Chem. Pharm.
Bull. 2001, 49, 657. (c) Bohm, C.; Schinnerl, M.; Bubert, C.; Zabel, M.;
Labahn, T.; Parisini, E.; Reiser, O. Eur. J. Org. Chem. 2000, 2955.
10.1021/ol047991w CCC: $27.50
© 2004 American Chemical Society
Published on Web 11/05/2004

Scheme 1. Working Mechanism for [3 + 2] and [3 + 3]
Table 1. [3 + 2] and [3 + 3] Additions of 1a-c with
Allenylsilanes
Additions
intramolecular capture of the cations A and B by the enolate
will then culminate in the formation of the five- and six-
membered carbocycles, 3 and 4, respectively. The olefin
geometry in 3 is likely to be controlled by the steric effects
arising from the terminal substituents on the olefinic bonds
in the allenylsilane and the enolate and also by the stereo-
electronic effects arising from the allenyl silicon during the
ring closure.
The phenyl ketone 1a6 underwent smooth ring opening
with TiCl4 in CH2Cl2 at - 78 °C and reacted subsequently
with the allene 2a to afford the [3 + 2] adduct 5 (Table 1,
entry 1). In contrast to the previous reports,1 the allenyl
trimethylsilicon was lost. Employment of Et2AlCl along with
TiCl4 (1.3 molar equiv each) at - 78 °C prevented this loss
(entry 2). The loss of the trimethylsilyl group under only
TiCl4 conditions must, therefore, be due to protodesilylation
caused by the adventitious HCl. Since Et2AlCl is an efficient
scavenger of protons,7 its application terminated the pro-
todesilylation channel completely. Application of anhydrous
K2CO3 as a suspension was not successful at preventing the
loss of the trimethylsilicon function, probably because of the
heterogeneous nature of the reaction mixture.
a Reaction was conducted using both TiCl4 and Et2AlCl, 1.3 equiv each.
b Reaction was conducted at -20 °C.
of several products. However, Et2AlCl worked very well at
25 °C, and interestingly, only the [3 + 3] adduct was formed
(Table 1, entry 3). The allenyl trimethylsilicon function was
retained in the product to arm it with the synthetically useful
vinylsilane motif.8 Bulky substituents on the silicon in
allenylsilane1c will also be expected to prevent its loss under
the TiCl4 condition. Indeed, when 1a was reacted with the
allenylsilane 2b at - 78 °C, both the [3 + 2] and [3 + 3]
adducts had formed in a 1.7:1 ratio (Table 1, entry 4).
Further, when the same reaction was conducted at - 20 °C,
significant migration of the allenyl silicon occurred to furnish
[3 + 2] and [3 + 3] adducts in a 1:3 ratio (Table 1, entry 5).
A complete silicon migration was noted when the reaction
was conducted at 25 °C using Et2AlCl (Table 1, entry 6).
The opening of the cyclopropane ring with Et2AlCl pro-
We studied next the effect of temperature on the mode of
addition arising from the migration of the allenyl silicon.
When the above reaction was conducted at 25 °C under TiCl4
conditions, the reaction was vigorous, resulting in a mixture
(5) For discussions on silyl-stabilized â-carbocations, see: (a) Fleming,
I. Frontier Orbitals and Organic Chemical Reactions; Wiley: London, 1976;
p 81. (b) Lambert, J. B. Tetrahedron 1990, 46, 2627. (c) 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.
(6) Cyclopropane derivatives 1a-c, 16, and 20 were prepared from a
rhodium-catalyzed carbene insertion reaction of the corresponding diazo-
compound with allyl tert-butyldiphenylsilane.
(7) Snider, B. B.; Rodini, David J.; Karras, M.; Kirk, T. C.; Deutsch, E.
A.; Cordova, R.; Price, R. T. Tetrahedron 1981, 37, 3927.
(8) (a) Moweri, M. E.; DeShong, P. Org. Lett. 1999, 1, 2137. (b)
Denmark, S. E.; Neuville, L. Org. Lett. 2000, 2, 3221. (c) Itami, K.; Nokami,
T.; Yoshida, J.-I. Org. Lett. 2000, 2, 1299. (d) Trost, B. M.; Ball, Z. T. J.
Am. Chem. Soc. 2001, 123, 12726. (e) Jankowski, P.; Plesniak, K.; Wicha,
J. Org. Lett. 2003, 5, 2789.
4496
Org. Lett., Vol. 6, No. 24, 2004

ceeded poorly at temperatures below 25 °C. Thus, the silicon
migration appears to be facile at higher temperatures.
The results from other cyclopropane derivatives are also
collected in Table 1. The reaction of the alleneylsilane 2a
with the n-butyl ketone 1b (entry 7) was similar to the
reaction with the phenyl ketone 1a. However, the cis:trans
selectivity had reduced from 3.2:1 to 1.9:1. Unlike the
reaction of the phenyl ketone 1a (entry 4), the tert-butyl
ketone 1c reacted with the allenylsilane 2b under TiCl4
conditions to afford the [3 + 3] adduct exclusively (entry
10). The relative stereochemistry of the substituents and the
geometry of the olefinic bond in the products were ascer-
tained from NOE measurements.
Scheme 2. Construction of [4.4]-, [4.5]-, and [5.5]-Spiro
Skeletons
In partial support of the reaction proceeding through
discrete vinyl cations as outlined in Scheme 1, we considered
studying reactions of the allenylsilane 2c. The transition state
corresponding to B (Scheme 1, R2 ) H) will be expected to
be higher in energy than the transition state corresponding
to A (Scheme 1, R2 ) H) as a result of the difference in the
substitution profile of the cationic center. Thus, one would
expect the [3 + 2] adduct to form in preference to the [3 +
3] adduct, irrespective of the reaction temperature and the
Lewis acid employed. The results are collected in Table 2.
as a single diastereomer. Likewise, trans-206 and cis-206
reacted with the allenylsilane 2b to generate a 1:1.1 mixture
of 21 and 22, each as a single diastereomer.10
The predominant cis-selectivity could be explained from
a consideration of the possible transition state structures for
the addition. Two transition structures, TS-I and TS-II (Figure
1), could be constructed for the [3 + 3] addition. TS-I,
Table 2. [3 + 2] Additions of 1a and 1c with Allenylsilane 2c
Figure 1. Transition states for [3 + 2] and [3 + 3] additions.
In the event that the reactions were conducted under the
standard conditions, the [3 + 2] adducts formed exclusively.
The alternate silirenium ion formation is unable to explain
the exclusive attack of the enolate on the internal allenic
carbon. The silirenium pathway cannot explain the observed
dependence of product distribution on temperature either.
As above, the relative stereochemistry of the substituents and
the geometry of the olefinic bond in the products were
ascertained from NOE measurements.
The [4.4]-, [4.5]-, and [5.5]-spiro skeletons9 were also
generated in good to excellent yields (Scheme 2). trans-166
and cis-166 reacted with the allenylsilane 2b to generate a
2:1 mixture of 17 and 18, each as a single diastereomer, and
with the allenylsilane 2c to generate 19 exclusively, again
leading to the trans-product, will be higher in energy than
TS-II for the steric interactions as shown. The cis-product
will therefore predominate. Likewise, two transition state
structures, TS-III and TS-IV, could be constructed for the
[3 + 2] addition. Since TS-III, leading to the trans-product,
will be higher in energy than TS-IV for the pseudo-1,3-
diaxial interaction as shown, TS-IV will generate the cis-
product predominantly.
It is easy to see for the E-enolate as well that the transition
states corresponding to TS-I and TS-III will be higher in
energy than the transition states corresponding to TS-II and
TS-IV, respectively, for the steric interactions arising from
R and the axial hydrogen on the carbon bearing the
silylmethyl function. The cis-product must therefore pre-
dominate again. The exclusive [3 + 3] addition in entry 10
(9) (a) Trost, B. M.; Sharma, S.; Schmidt, T. J. Am. Chem. Soc. 1992,
114, 7903. (b) Sannigrahi, M. Tetrahedron 1999, 55, 9007. (c) Knoelker,
H.-J.; Baum, E.; Graf, R.; Jones, P. G.; Spieb, O. Angew. Chem., Int. Ed.
1999, 38, 2583. (d) Alper, P. B.; Meyers, C.; Lerchner, A.; Siegel, D. R.;
Carreira, E. M. Angew. Chem., Int. Ed. 1999, 38, 3186. (e) Du, Y.; Lu, X.;
Yu, Y. J. Org. Chem. 2002, 67, 8901.
(10) The assignment of the relative stereochemistry of 17-19, 21, and
22 by NOE measurements was difficult because of the crowded nature of
the spectrum. Efforts are being made to secure the same through deriva-
tization and crystal structure illucidation.
Org. Lett., Vol. 6, No. 24, 2004
4497

(Table 1) could be explained through TS-IV wherein the
steric interactions of R () t-Bu) with the methyl group of
the allenyl reactant in the Z-enolate or the silicon function
of the allenyl reactant in the corresponding E-enolate retarded
the five-ring closure. This allowed the silicon to migrate to
attain the strain-free six-membered ring transition structure
TS-II.
form five- and six-membered carbocycles via formal
[3 + 2] and [3 + 3] additions with high regio- and
stereocontrol. The reaction with Et2AlCl at 25 °C generates
the six-membered ring product exclusively. The present
protocol has potential to find applications in the synthesis
of carbocyclic natural products and carbocyclic nucleosides.13
Acknowledgment. Authors thank DST, Government of
India, for financial support. This work is dedicated to
Professor R. P. Gandhi, a true inspirer.
In summary, vicinal tert-butyldiphenylsilylmethyl substi-
tuted cyclopropyl ketones reacted with allenylsilanes in the
11
12
presence of Lewis acids such as TiCl4 and Et2AlCl to
Supporting Information Available: Experimental details
and characterization data. This material is available free of
charge via the Internet at http://pubs.acs.org.
(11) General Procedure for the TiCl4-Assisted Reaction. A solution
of freshly distilled TiCl4 (61 mg, 0.326 mmol) in anhydrous CH2Cl2 (0.5
mL) was added slowly under N2 to the stirred solution of a cylopropyl-
methylsilane (0.251 mmol) and an allenylsilane (0.326 mmol) in anhydrous
CH2Cl2 (0.8 mL) at -78 °C. The reaction mixture turned deep red. After
stirring for 3 h at -78 °C, it was warmed slowly over 1 h to -40 °C. The
stirring was continued at this temperature for 2 h, and the reaction mixture
was taken up in Et2O (10 mL). The ethereal solution was washed with
water (1 × 7 mL). The aqueous washing was extracted with Et2O (2 × 5
mL). The combined organic extracts were washed with brine, dried, and
concentrated. Purification of the residue by silica gel column chromatog-
raphy (EtOAc/hexanes) furnished the pure product(s). The separation of
the cis- and trans-isomers was achieved by radial chromatography over
silica gel (EtOAc/hexanes).
OL047991W
reaction mixture was quenched with water at 0 °C and diluted with Et2O
(10 mL). The ethereal solution was washed with water (7 mL). The aqueous
washing was extracted with Et2O (2 × 5 mL). The combined organic extracts
were washed with brine, dried, and concentrated. Purification of the residue
by silica gel column chromatography (EtOAc/hexanes) furnished the pure
product.
(13) (a) Huldlicky, T.; Price, J. D. Chem. ReV. 1989, 89, 1467. (b)
Crimmins, M. T. Tetrahedron 1998, 54, 9229. (c) Trost, B. M.; Madsen,
R.; Guile, S. D.; Brown, B. J. Am. Chem. Soc. 2000, 122, 5947. (d) Gurjar,
M. K.; Maheshwar, K. J. Org. Chem. 2001, 66, 7552. (e) Moon, H. R.;
Kim, H. O.; Lee, K. M.; Chun, M. W.; Kim, J. H.; Jeong, L. S. Org. Lett.
2002, 4, 3501. (f) Hong, J. H.; Shim, M. J.; Ro, B. O.; Ko, O. H. J. Org.
Chem. 2002, 67, 6837.
(12) General Procedure for the Et2AlCl-Assisted Reaction. A solution
of Et2AlCl (54 mg, 0.375 mmol) in toluene (0.208 mL) was added slowly
under N2 to the stirred solution of a cylopropylmethylsilane (0.251 mmol)
and an allenylsilane (0.326 mmol) in anhydrous CH2Cl2 (1.3 mL) at 25 °C
when the reaction mixture turned pale yellow. After stirring for 6 h, the
4498
Org. Lett., Vol. 6, No. 24, 2004