Alkylidenesilacyclopropanes derived from allenes: Applications to the selective synthesis of triols and homoallylic alcohols

Article abstract of DOI:10.1021/ol900456v

Several alkylidenesilacyclopropanes were prepared by silver-mediated silylene transfer to allenes. Oxasilacyclopentanes derived from allenes were prepared with high regio- and diastereoselectivity by a two-step, one-flask silacyclopropanation/carbonyl ins

Full text of DOI:10.1021/ol900456v

ORGANIC
LETTERS
2009
Vol. 11, No. 10
2173-2175
Alkylidenesilacyclopropanes Derived
from Allenes: Applications to the
Selective Synthesis of Triols and
Homoallylic Alcohols
Kay M. Buchner, Timothy B. Clark, Janice M. N. Loy, Thong X. Nguyen, and
K. A. Woerpel*
Department of Chemistry, UniVersity of California, IrVine, California 92697-2025
kwoerpel@uci.edu
Received March 4, 2009
ABSTRACT
Several alkylidenesilacyclopropanes were prepared by silver-mediated silylene transfer to allenes. Oxasilacyclopentanes derived from allenes
were prepared with high regio- and diastereoselectivity by a two-step, one-flask silacyclopropanation/carbonyl insertion reaction. Triols and
homoallylic alcohols were formed diastereoselectively by functionalizing the oxasilacyclopentanes. An optically active allene (>98% ee) was
utilized to synthesize an enantiopure homoallylic alcohol in 96% ee.
Allenes are unique scaffolds for organic synthesis because
they have axial chirality that can be transferred to the
products of subsequent reactions. Hydroamination,1 three-
component coupling,2 Pauson-Khand-type cycloaddition,3
and tandem coupling/cyclization4 have all been applied to
chiral allenes to give enantiopure products. The addition
reactions of carbenes5 and nitrenes6 with allenes have also
been employed in stereoselective synthesis. Silylene transfer
to allenes would combine the chirality inherent to the allene
with the high reactivity of the strained-ring silane7 to allow
the formation of enantiomerically pure products with new
carbon-carbon bonds. Photochemical silacyclopropanation
of allenes has been reported,8 but the alkylidenesilacyclo-
propane products were formed with low regio- and diaste-
reoselectivities.
In this paper, we demonstrate that metal-catalyzed silylene
transfer9 to allenes forms alkylidenesilacyclopropanes with high
regio- and diastereoselectivity. These highly reactive intermedi-
ates undergo insertions of carbonyl compounds to yield
synthetically useful oxasilacyclopentane products8,10 (Scheme
1). After manipulation of the exocyclic alkene or the C-Si bond,
(8) (a) Ando, W.; Saso, H. Tetrahedron Lett. 1986, 27, 5625–5628. (b)
Saso, H.; Ando, W.; Ueno, K. Tetrahedron 1989, 45, 1929–1940.
(9) (a) Driver, T. G.; Woerpel, K. A. J. Am. Chem. Soc. 2003, 125,
´
10659–10663. (b) Cirakovic´, J.; Driver, T. G.; Woerpel, K. A. J. Org. Chem.
2004, 69, 4007–4012. (c) Clark, T. B.; Woerpel, K. A. J. Am. Chem. Soc.
2004, 126, 9522–9523.
(1) Nishina, N.; Yamamoto, Y. Angew. Chem., Int. Ed. 2006, 45, 3314–
3317.
(10) (a) Marshall, J. A.; Ellis, K. C. Org. Lett. 2003, 5, 1729–1732. (b)
O’Neil, G. W.; Phillips, A. J. J. Am. Chem. Soc. 2006, 128, 5340–5341.
(c) Someya, H.; Kondoh, A.; Sato, A.; Ohmiya, H.; Yorimitsu, H.; Oshima,
K. Synlett 2006, 3061–3064. (d) Robertson, J.; Middleton, D. S.; O’Connor,
G.; Sardharwala, T. Tetrahedron Lett. 1998, 39, 669–672. (e) Robertson,
J.; O’Connor, G.; Sardharwala, T.; Middleton, D. S. Tetrahedron 2000,
56, 8309–8320. (f) Leighton, J. L.; Chapman, E. J. Am. Chem. Soc. 1997,
119, 12416–12417. (g) Hale, M. R.; Hoveyda, A. H. J. Org. Chem. 1992,
(2) (a) Ng, S.-S.; Jamison, T. F. J. Am. Chem. Soc. 2005, 127, 7320–
7321. (b) Ng, S.-S.; Jamison, T. F. Tetrahedron 2005, 61, 11405–11417.
(3) Brummond, K. M.; Kerekes, A. D.; Wan, H. J. Org. Chem. 2002,
67, 5156–5163.
(4) Ma, S.; Yu, F.; Gao, W. J. Org. Chem. 2003, 68, 5943–5949.
(5) Brandi, A.; Goti, A. Chem. ReV. 1998, 98, 589–635.
(6) Shipman, M. Synlett 2006, 3205–3217.
(7) Seyferth, D. J. Organomet. Chem. 1975, 100, 237–256.
57, 1643–1645.
10.1021/ol900456v CCC: $40.75
Published on Web 04/21/2009
 2009 American Chemical Society

Scheme 1
.
Formation of Oxasilacyclopentanes from Allenes
Table 1. Silacyclopropanation of Allenes
oxygenated compounds such as triols and homoallylic alcohols can
be formed.9c,11 When enantiomerically enriched allenes were
employed, enantioenriched products were formed.
Several alkylidenesilacyclopropanes were prepared with high
regio- and diastereoselectivity using silver-catalyzed silylene
transfer9 (Table 1). The reaction is general for a wide variety
of substitution patterns, including for a tetrasubstituted allene
(entry 7). Silylene transfer is regioselective for substrates that
have a steric difference between the substituents on the 1- and
3-positions of the allene (entries 1-6). For 1,3-disubstituted
allene 1e, the silacyclopropane was initially formed as a 70:30
mixture of regioisomers, but the more sterically hindered isomer
decomposed,12 and silacyclopropane 3e remained in 70% yield
(entry 5). Diastereoselectivity for these reactions, like
regioselectivity, was high when the two groups on the
newly formed exocyclic alkene were significantly different
in size. A decrease in diastereoselectivity was observed
for trisubstituted allene 1f, which provided a 3:1 mixture
of alkene isomers, favoring 3f (entry 6).
Alkylidenesilacyclopropanes participate in insertion reactions
with carbonyl compounds to yield oxasilacyclopentanes8 with
high regio- and diastereoselectivity. Silacyclopropane 3h un-
derwent allylic transposition with benzaldehyde and butyral-
dehyde to provide oxasilacyclopentanes 4a and 4b, respectively
(Table 2, entries 1-4). Cleavage of the Si-C(sp2) bond
occurred when silacyclopropane 3h was treated with ethyl
formate, resulting in oxasilacyclopentane 5 (entries 5 and 6).
Although these insertion reactions can be performed without
catalyst (22 to 100 °C), the use of a copper salt reduced both
the temperature and reaction time.12,13
Reaction conditions were developed for a two-step, one-flask
silacyclopropanation/carbonyl insertion method to avoid han-
dling sensitive alkylidenesilacyclopropanes. Oxasilacyclopen-
tane products like 6, 7, and 8 were synthesized (Scheme 2) with
silver salts catalyzing silylene transfer and copper and zinc salts
promoting insertion of carbonyl compounds.
a All regio- and diastereoselectivities were g93:7 except for 3b (83:17
dr), 3d (79:21 regioisomers) and 3f (78:22 dr). Details are provided as
Supporting Information. b As determined by 1H NMR spectroscopic analysis
of the product relative to an internal standard (PhSiMe3). c Details regarding
isolated yields are provided as Supporting Information.
asilacyclopentane 6 underwent epoxidation to form spiro-
epoxide 9 in 72% yield and 98:2 diastereoselectivity. Under
protodesilylation conditions, the epoxide was converted into
triol 10 as a single isomer in 84% yield (Scheme 3).14 The
triol is presumed to form by removal of the di-tert-butylsilyl
moiety under the protodesilylation conditions with concomi-
tant opening of the epoxide by adventitious water.
To determine the stereochemical course of the carbonyl
insertion with allylic transposition, silylene transfer to an
enantiopure allene was performed (Scheme 4). Allene (+)-
1d was prepared from an enantiopure (>98% ee) alcohol
The double bond of the oxasilacyclopentane can be
elaborated to provide highly functionalized products. Ox-
(11) Clark, T. B.; Woerpel, K. A. Org. Lett. 2006, 8, 4109–4112.
(12) More information is provided as Supporting Information.
(13) It is not clear how copper salts catalyze carbonyl insertion. The
mechanism of this reaction is currently being investigated.
(14) The relative stereochemistry of 10 was determined by X-ray
crystallography.
2174
Org. Lett., Vol. 11, No. 10, 2009

Table 2. Thermal vs. Cu-Catalyzed Carbonyl Insertion Reactions
Scheme 3. Functionalization to Form a 1,2,4-Triol
entry
R
conditions
product
timea
yieldb (%)
1
2
3
4
5
6
Ph
Ph
n-Pr
n-Pr
EtO
EtO
22 °C
Cul, 22 °C
60 °C
Cul, 22 °C
100 °C
Cul, 60 °C
4a
4a
4b
4b
5
1.5 h
30 min
15 h
30 min
7 d
82
90
82
89
82
90
5
21 h
a Time needed for the reaction to proceed to 100% conversion. b As
determined by H NMR spectroscopic analysis of the product relative to
1
an internal standard (PhSiMe3).
Scheme 4. Formation of an Enantiopure Homoallylic Alcohol
Scheme 2
.
Two-Step, One-Flask Silacyclopropanation/Carbonyl
Insertion Reactions
step, one-flask reaction with high regio- and diastereoselectivity.
The oxasilacyclopentanes were functionalized to form triols and
homoallylic alcohols diastereoselectively. An enantiopure ho-
moallylic alcohol was synthesized from optically active starting
material, which demonstrated the synthetic utility of this method.
This process could be used to make a variety of highly branched
homoallylic alcohols that cannot easily be made using existing
methods.17
Acknowledgment. This research was supported by the
National Institute of General Medical Sciences of the
National Institutes of Health (GM-54909). K.M.B. thanks
the Department of Education (GAANN) for a predoctoral
fellowship. K.A.W. thanks Amgen and Lilly for awards to
support research. We thank Dr. P. Dennison (UCI) for
assistance with NMR spectroscopy, Dr. J. W. Ziller and
M. K. Takase (UCI) for X-ray crystallography, and Dr. J.
Greaves and S. Sorooshian (UCI) for mass spectrometry.
following a known procedure,2a,15 then subjected to the two-
step, one-flask silacyclopropanation/carbonyl insertion reac-
tion to provide oxasilacyclopentane (R,S)-(-)-6 in 65% yield.
Oxasilacyclopentane (-)-6 underwent protodesilylation to
afford alcohol (R,S)-(+)-11 in 75% yield and 96% ee.16
These results indicate that upon allylic transposition, the new
carbon-carbon bond formation occurs on the face opposite
to the substituent of the three-membered ring.
Supporting Information Available: Experimental pro-
cedures, spectroscopic, analytical, and X-ray data for the
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
In conclusion, alkylidenesilacyclopropanes were synthesized
from allenes with high regio- and diastereoselectivity. Oxasi-
lacyclopentanes derived from allenes were prepared in a two-
OL900456V
(15) Myers, A. G.; Zheng, B. J. Am. Chem. Soc. 1996, 118, 4492–4493.
(16) Absolute stereochemistry was determined by X-ray crystallographic
analysis of a chiral carbamate derivative. Details are provided as Supporting
Information.
(17) (a) McNulty, J.; Nair, J. J.; Sliwinski, M.; Harrington, L. E.; Pandey,
S. Eur. J. Org. Chem. 2007, 5669–5673. (b) Evans, D. A.; Tedrow, J. S.;
Shaw, J. T.; Downey, C. W. J. Am. Chem. Soc. 2002, 124, 392–393. (c)
Abiko, A. Acc. Chem. Res. 2004, 37, 387–395.
Org. Lett., Vol. 11, No. 10, 2009
2175