Stereoselective synthesis of (Z)- and (E)-allylic silanes by copper- mediated substitution reactions of allylic carbamates with grignard reagents

Article abstract of DOI:10.1021/jo991312r

Both (Z)- and (E)-allylic silanes were prepared with high stereoselectivity by the copper-mediated substitution of allylic carbamates by organometallic reagents. The reaction of alkylmagnesium reagents with (E)- allylic carbamates provides (Z)-allylic silanes, whereas both alkylmagnesium and alkyllithium reagents react with (Z)-allylic carbamates to afford (E)- allylic silanes. Because Grignard reagents are often more facile to prepare than alkyllithium species, these reagents are the optimal nucleophiles for the synthesis of both (Z)- and (E)-allylic silanes. This method also allows readily available nonracemic allylic carbamates to be converted to chiral, nonracemic (Z)- and (E)-allylic silanes with high stereoselectivity.

Full text of DOI:10.1021/jo991312r

VOLUME 65, NUMBER 6
MARCH 24, 2000
© Copyright 2000 by the American Chemical Society
Articles
Ster eoselective Syn th esis of (Z)- a n d (E)-Allylic Sila n es by
Cop p er -Med ia ted Su bstitu tion Rea ction s of Allylic Ca r ba m a tes
w ith Gr ign a r d Rea gen ts
J acqueline H. Smitrovich and K. A. Woerpel*
Department of Chemistry, University of California, Irvine, California 92697-2025
Received August 18, 1999
Both (Z)- and (E)-allylic silanes were prepared with high stereoselectivity by the copper-mediated
substitution of allylic carbamates by organometallic reagents. The reaction of alkylmagnesium
reagents with (E)-allylic carbamates provides (Z)-allylic silanes, whereas both alkylmagnesium
and alkyllithium reagents react with (Z)-allylic carbamates to afford (E)-allylic silanes. Because
Grignard reagents are often more facile to prepare than alkyllithium species, these reagents are
the optimal nucleophiles for the synthesis of both (Z)- and (E)-allylic silanes. This method also
allows readily available nonracemic allylic carbamates to be converted to chiral, nonracemic (Z)-
and (E)-allylic silanes with high stereoselectivity.
In tr od u ction
determines the course of the reaction and the stereo-
chemistry of the product. The nature of the silicon group
controls whether the silyl group is eliminated from an
intermediate â-silyl carbocation (leading to allylation) or
whether the silicon group is retained (resulting in an-
nulation).4,10 Annulation reactions can be stereospecific
with respect to the olefin geometry of the allylic silane,
with (E)- and (Z)-allylic silanes leading to diastereomeric
products.9,11,12 Because allylic silane structure is closely
related to the efficiency and stereochemistry of annula-
tion reactions, the syntheses of these compounds must
be flexible to permit optimization of annulation processes.
Although many syntheses of allylic silanes have been
Allylic silanes are important reagents for the stereo-
selective construction of carbon-carbon bonds.1 The
Hosomi-Sakurai allylation reaction2,3 and annulation
reactions (both [3 + 2]4-6 and [2 + 2]7-9) provide access
to acyclic and cyclic products, respectively, with control
of stereochemistry. The structure of the allylic silane
(1) For a review discussing the use of chiral allylsilanes in synthesis,
see: Masse, C. E.; Panek, J . S. Chem. Rev. 1995, 95, 1293-1316.
(2) Hosomi, A.; Sakurai, H. Tetrahedron Lett. 1976, 17, 1295-1298.
(3) Fleming, I.; Dunogues, J .; Smithers, R. Org. React. 1989, 37, 57-
574 and references therein.
(4) For a review on [3 + 2] annulation reactions of allyltriiso-
propylsilane, see: Kno¨lker, H.-J . J . Prakt. Chem. 1997, 339, 304-314.
(5) Groaning, M. D.; Brengel, G. P.; Meyers, A. I. J . Org. Chem. 1998,
63, 5517-5522.
(11) Danheiser, R. L.; Takahashi, T.; Berto´k, B.; Dixon, B. R.
Tetrahedron Lett. 1993, 34, 3845-3848.
(6) Akiyama, T.; Yamanaka, M. Tetrahedron Lett. 1998, 39, 7885-
(12) Roberson, C. W.; Woerpel, K. A. J . Org. Chem. 1999, 64, 1434-
7888.
1435.
(7) Akiyama, T.; Kirino, M. Chem. Lett. 1995, 723-724.
(8) Akiyama, T.; Yamanaka, M. Synlett 1996, 1095-1096.
(9) Kno¨lker, H.-J .; Baum, E.; Schmitt, O. Tetrahedron Lett. 1998,
39, 7705-7708.
(10) Akiyama, T.; Ishikawa, K.; Ozaki, S. Chem. Lett. 1994, 627-
630.
(13) For a review of methods for the synthesis of allylsilanes, see:
Sarkar, T. K. Synthesis 1990, 969-983. Sarkar, T. K. Synthesis 1990,
1101-1111.
(14) For a method to prepare enantiomerically enriched (E)-allylic
silanes, see: Suginome, M.; Matsumoto, A.; Ito, Y. J . Am. Chem. Soc.
1996, 118, 3061-3062.
10.1021/jo991312r CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/01/2000

1602 J . Org. Chem., Vol. 65, No. 6, 2000
Smitrovich and Woerpel
reported,13,14 a general route that permits facile variation
of the structure (including the nature of the silyl sub-
stituent, olefin geometry, and absolute stereochemistry)
is lacking.
the Grignard reagent from magnesium to nickel. All
attempts to increase the yield by varying catalyst,
temperature, and solvent failed.
As part of our program investigating the [3 + 2]
annulation reactions of allylic silanes,12 we required a
stereo- and regioselective synthesis of silylmethyl-
substituted allylic silanes. Our initial experiments re-
vealed that standard methods for the synthesis of allylic
silanes gave low yields when applied to these structures.
The copper-mediated allylic displacement of carbamates
by organometallic reagents,15,16 however, proved to be a
general route for the synthesis of these compounds. The
reaction of alkylmagnesium reagents with (E)-allylic
carbamates provided (Z)-allylic silanes, whereas both
alkylmagnesium and alkyllithium reagents reacted with
(Z)-allylic carbamates to afford (E)-allylic silanes. We
report here the details of our allylic displacement method,
which can be applied to the synthesis of chiral, non-
racemic (Z)-17 and (E)-allylic silanes with high enantio-
selectivity.
We next focused on the synthesis of allylic silanes by
a Wittig reaction of an R-silylaldehyde,25 which was
prepared from imine 426 (eq 2). Deprotonation of 4 with
LDA followed by addition of (iodomethyl)dimethyl-
phenylsilane gave disilylimine 5, which was separated
from lower boiling impurities by bulb-to-bulb distillation
and subjected to hydrolysis without further purification
(eq 2). Upon hydrolysis26 of 5, a mixture of the desired
aldehyde 6 and R-desilylated aldehyde 7 was obtained.
Extensive variation of hydrolysis conditions did not
increase the yield of 6 above 22%.
Resu lts a n d Discu ssion
In itia l Ap p r oa ch es to Silylm eth yl-Su bstitu ted
Allylic Sila n es. Our first approach to silylmethyl-
substituted allylic silanes such as 3 relied upon Hayashi-
Kumada coupling of Grignard reagents with vinyl halides
(eq 1).18,19 This route was attractive because both (E)- and
(Z)-allylic silanes would be available by choice of the
appropriate vinyl halide coupling partner. Nickel and
palladium couplings of (silylmethyl)methylmagnesium
halides with vinyl halides have been used successfully
for the synthesis of unsubstituted allyl- and crotyl-
silanes,20,21 and the coupling of secondary silyl-substi-
tuted Grignard reagents by the Hayashi protocol has
been demonstrated in a few examples.19,22,23
The metal-catalyzed coupling reaction was unsuccess-
ful for the formation of the desired allylic silanes.
Chloride 2, the Grignard precursor, was prepared by
deprotonation of (chloromethyl)dimethylphenylsilane (1)
with sec-butyllithium24 followed by addition of a second
equivalent of 1 (eq 1). Treatment of the Grignard reagent
generated from chloride 2 with trans-3-bromopropene in
the presence of a nickel catalyst afforded the coupling
product 3a in low yield (eq 1). The other products of the
reaction arose from protonation of the Grignard reagent
and from â-hydride elimination after transmetalation of
Addition of aldehyde 6 to a solution of the ylide
generated from ethyltriphenylphosphonium iodide af-
forded the allylic silane 8a in low yield (33%) with high
(Z)-selectivity (E/Z ) 4:96, eq 3). Considering the low
yield obtained upon imine hydrolysis, the Wittig reaction
was not optimized, and production of allylic silanes by
this route was abandoned.
Develop m en t of th e Allylic Disp la cem en t Rou te.
The copper-mediated substitution of allylic derivatives
has been used for the synthesis of (E)-allylic silanes27,28
and appeared to be a viable route to 3. Inspection of the
requisite vinyl silane 9 (eq 4), however, revealed a
potential problem. Allylic acetate 9 bears a methyl group
R to the leaving group and a bulky silyl-group at the
γ-position. Reaction of 9 would be expected to occur with
delivery of the nucleophile to the less hindered allylic
terminus,29 which in this case is the R-position. Indeed,
(15) Gallina, C.; Ciattini, P. G. J . Am. Chem. Soc. 1979, 101, 1035-
1036.
(16) Goering, H. L.; Kantner, S. S.; Tseng, C. C. J . Org. Chem. 1983,
48, 715-721.
(17) Smitrovich, J . H.; Woerpel, K. A. J . Am. Chem. Soc. 1998, 120,
12998-12999.
(18) Tamao, K.; Sumitani, K.; Kiso, Y.; Zembayashi, M.; Fujioka,
A.; Kodama, S.; Nakajima, I.; Minato, A.; Kumada, M. Bull. Chem.
Soc. J pn. 1976, 49, 1958-1969.
(19) Hayashi, T.; Konishi, M.; Okamoto, Y.; Kabeta, K.; Kumada,
M. J . Org. Chem. 1986, 51, 3772-3781.
(20) Hayashi, T.; Kabeta, K.; Hamachi, I.; Kumada, M. Tetrahedron
Lett. 1983, 24, 2865-2868.
(25) Bhushan, V.; Lohray, B. B.; Enders, D. Tetrahedron Lett. 1993,
34, 5067-5070.
(21) Organ, M. G.; Murray, A. P. J . Org. Chem. 1997, 62, 1523-
1526.
(26) Hudrlik, P. F.; Kulkarni, A. K. J . Am. Chem. Soc. 1981, 103,
6251-6253.
(22) Hayashi, T.; Konishi, M.; Ito, H.; Kumada, M. J . Am. Chem.
Soc. 1982, 104, 4962-4963.
(27) Tanigawa, Y.; Fuse, Y.; Murahashi, S.-I. Tetrahedron Lett. 1982,
23, 557-560.
(23) Tamao, K.; Iwahara, T.; Kanatani, R.; Kumada, M. Tetrahedron
Lett. 1984, 25, 1909-1912.
(28) Fleming, I.; Higgins, D.; Lawrence, N. J .; Thomas, A. P. J .
Chem. Soc., Perkin Trans. 1 1992, 3331-3349.
(29) Kang, J .; Cho, W.; Lee, W. K. J . Org. Chem. 1984, 49, 1838-
1840.
(24) This procedure was developed by van Boom et al.: van Delft,
F. L.; de Kort, M.; van der Marel, G. A.; van Boom, J . H. J . Org. Chem.
1996, 61, 1883-1885.

Stereoselective Synthesis of (Z)- and (E)-Allylic Silanes
J . Org. Chem., Vol. 65, No. 6, 2000 1603
treatment of acetate 9 with bis[(trimethylsilyl)methyl]-
cuprate afforded vinylsilane 10 arising from R-substitu-
tion (eq 4). The desired allylsilane obtained from γ-sub-
1
stitution could not be detected by H NMR spectroscopic
analysis.
would provide valuable insight into the mechanism of
copper-mediated allylic displacement reactions. We
launched a systematic study of this reaction not only to
enhance the synthetic utility but also to investigate the
effect of reaction conditions on the control of alkene
geometry. Optimization of selectivity and yield was
accomplished by investigating the effects of copper salt,
equivalents of Grignard reagent, and nucleophile. The
reactions of both trans- and cis-allylic carbamates were
investigated. We also sought to use this method for the
synthesis of chiral, nonracemic (Z)- and (E)-allylic silanes
with high enantioselectivity.
P r ep a r a tion of Allylic Ca r ba m a tes. A synthesis of
the requisite allylic carbamates that would permit varia-
tion of the silyl group was desired. Alkyne starting
materials were attractive because both the (E)- and (Z)-
alkenes would be available by selective reduction of the
alkyne. The (E)-isomer was prepared from the THP ether
of 3-butyn-2-ol (14). Deprotonation of 14 with MeLi,
followed by treatment with 1 equiv of chlorosilane,
afforded propargylic derivatives 15a and 15b, in 70% and
94% yields, respectively (eq 7).35 After cleavage of the
THP ether, propargyl alcohols 16a and 16b were selec-
tively reduced to trans-allylic alcohols by Red-Al (E/Z )
98:2 by capillary GC).36 Treatment of the alcohols with
phenyl isocyanate gave the carbamates 13a and 13b in
good yield. The incorporation of the silyl group via the
silyl chloride allows easy variation of this substituent to
permit tuning of allylic silane reactivity.
Several methods for selective γ-substitution of biased
substrates have been developed, and these procedures
were investigated. Goering demonstrated that the regio-
chemistry of copper-catalyzed addition of Grignard re-
agents to allylic esters can be controlled by the choice of
the copper salt, with CuCN giving selective γ-alkylation.30
Reaction of pivalate ester31 11 with (dimethylphenylsilyl)-
methylmagnesium chloride in the presence of catalytic
CuCN provided a 61:39 mixture of the desired γ-substi-
tution product 3a (E/Z ) 40:60) and the R-substitution
product 12 (eq 5). Ba¨ckvall determined that slow addition
of the Grignard reagent to a mixture of substrate and
catalytic copper salts further increases γ-selectivity.32
Addition of (phenyldimethylsilyl)methylmagnesium chlo-
ride over 3 h to a solution of acetate 9 and 10 mol %
CuCN also afforded a mixture of the desired γ-product
(E/Z ) 64:36) and R-product in a 42:58 ratio. These
results demonstrate that R-substitution distal to the
silane moiety is competitive with γ-substitution of esters
9 and 11.
The poor γ-selectivity observed for the copper-mediated
allylic displacement reactions may also be overcome by
the use of allylic carbamates, which react with exclusive
γ-substitution and (E)-selectivity.15,16,28 This modification
proved to be successful for our purposes. Deprotonation
of carbamate 13a followed by complexation with CuI and
subsequent addition of (trimethylsilyl)methyllithium pro-
duced the (E)-allylic silane 3b with modest selectivity
(E/Z ) 60:40, eq 6). By simply changing the nucleophile
to the organomagnesium reagent, the allylic silane 3b
was obtained in higher yield, with high γ-selectivity and,
most notably, with high (Z)-selectivity (E/Z ) 5:95).33
The observation of high (Z)-selectivity upon the first
attempt to optimize the copper-mediated displacement
reaction was not anticipated. Allylic substitution reac-
tions, including both the traditional SN2′ reaction and the
copper-mediated processes, generally provide (E)-alk-
enes.34 The (Z)-selectivity was of interest to us because
it provided a route to allylic silanes that would otherwise
be difficult to access. We also felt that this transformation
The selective synthesis of the cis-allylic carbamate was
more challenging than that of its trans counterpart.
Semi-hydrogenation37 of propargylic alcohol 16a occurred
slowly and provided an inseparable mixture of the desired
(Z)-allylic alcohol, the (E)-isomer, and alkane. Successful
production of 18a with high (Z)-selectivity was achieved
by hydroboration38,39 of acetate 17 with dicyclohexyl-
(30) Tseng, C. C.; Paisley, S. D.; Goering, H. L. J . Org. Chem. 1986,
51, 2884-2891.
(31) Pivalate esters have been employed in the copper-catalyzed
allylic substitution reaction to disfavor attack of the Grignard reagent
on the carbonyl.
(35) This reaction sequence was adapted from that reported for the
synthesis of 3-(tert-butyldimethylsilyl)-2-propyn-1-ol: Myers, A. G.;
Zheng, B. Org. Synth. 1998, 76, 178-188.
(32) Ba¨ckvall, J .-E.; Selle´n, M.; Grant, B. J . Am. Chem. Soc. 1990,
112, 6615-6621.
(36) Denmark, S. E.; J ones, T. K. J . Org. Chem. 1982, 47, 4595-
(33) Alkene geometries were assigned by analysis of 1H NMR
coupling constants, by comparison of spectral data to reported data,
or by comparison to reference materials.
4597.
(37) Panek, J . S.; Clark, T. D. J . Org. Chem. 1992, 57, 4323-4326.
(38) Brown, H. C. Organic Synthesis via Boranes; Wiley: New York,
1975; pp 178-179.
(34) Magid, R. M. Tetrahedron 1980, 36, 1901-1930.

1604 J . Org. Chem., Vol. 65, No. 6, 2000
Smitrovich and Woerpel
Ta ble 1. Scr een of Cop p er Sa lts (Eq 10)
Ta ble 2. Effect of Equ iva len ts of Gr ign a r d Rea gen t
(Eq 12)
entry
CuX
E/Za
yieldb (%)
entry
equiv of i-BuMgCl
E/Z of 3ca
3c:20a
yieldb (%)
1
CuI
4:96
9:91
22:78
6:94
63
74
62
82
1
2
3
4
5
1.1
1.2
1.3
1.4
2.0
9:91
7:93
8:92
7:93
6:94
99:1
g95:5
95:5
93:7
88:12
55
69
70
71
77
2c
3
CuBr‚SMe2
CuCN‚2LiCl
CuI‚2LiCl
4
a
Determined by GC analysis of the unpurified reaction mixture.
b
Yields reported for material isolated after column chromatogra-
a
Determined by GC analysis of the unpurified reaction mixture.
phy. c MeLi-LiBr was employed as the base.
b
Yields reported for mixture of 3c and 20 isolated after column
chromatography.
borane38 and protonolysis with acetic acid (eq 8).40 Depro-
tection of the acetate followed by treatment with neat
phenyl isocyanate provided the allylic carbamate 18a . It
was later found that the THP ether 15b could be
submitted to the hydroboration/protonolysis procedure to
obtain the (Z)-alkene (eq 9), obviating the need for
manipulation of the protecting group.
The use of the soluble salt CuI‚2LiCl also permitted
the formation of the copper-carbamate complex to be
conducted at lower temperatures. With copper iodide, the
complex did not form at -78 °C, and warming to 0 °C
was necessary for complete formation of the complex (as
indicated by a homogeneous reaction mixture).16 Reac-
tions carried out from 0 °C to 22 °C, however, produced
10% of the unprotected alcohol corresponding to 13a (i.e.,
alcohol 19a ). The conjugate base of the carbamate could
be complexed to CuI‚2LiCl at -78 °C, which minimized
formation of 19a .
The use of a stoichiometric amount of copper is
necessary to obtain high γ-selectivity. In the absence of
copper, the allylic carbamate 13a was recovered (71%)
along with alcohol 19a (22%) and the vinylsilane 10 (5%)
arising from SN2 reaction of the Grignard reagent (eq 11).
No γ-substitution products were produced. The use of a
catalytic amount of copper results in loss of γ-selectivity.
The addition of 10 mol % CuI‚2LiCl to a cooled -78 °C
solution of the deprotonated carbamate, followed by
addition of 1 equiv of (trimethylsilyl)methylmagnesium
chloride afforded the vinylsilane 10 as the major product
(58%, γ/R ) 19:81). Presumably, the vinylsilane is
produced by reaction of the dialkylcuprate, which delivers
the nucleophile to the less-hindered allylic terminus.32
Therefore, the γ-substitution product cannot be obtained
in the presence of catalytic copper.
Op tim iza tion of Cop p er -Med ia ted Su bstitu tion .
Before the generality of the (Z)-selective allylic displace-
ment described in eq 6 could be probed, optimization of
the procedure was required. The most serious problem
encountered was that of reproducibility. Upon addition
of the deprotonated carbamate to a suspension of CuI in
THF at 0 °C, reduction of Cu(I) to Cu(0), which appeared
as a black suspension, occasionally occurred, and upon
addition of the nucleophile, starting material was recov-
ered. House reported a similar reduction of copper during
the formation of dialkylcuprates.41 He found that the use
of the more soluble CuBr‚SMe2 complex avoided reduc-
tion. A screen of copper salts was undertaken to deter-
mine if soluble salts would be less susceptible to reduction
(eq 10, Table 1). Of the copper sources investigated, the
soluble salt CuI‚2LiCl,42,43 prepared by stirring 1 equiv
of CuI and 2 equiv of LiCl in THF at 22 °C, gave
reproducibly high yields and eliminated the reduction of
the copper(I). The presence of the additional 2 equiv of
lithium introduced by the lithium chloride did not
significantly diminish the (Z)-selectivity (compare entries
1 and 4).
The number of equivalents of Grignard reagent em-
ployed in the reaction influences γ-selectivity and, to a
lesser extent, (Z)-selectivity. As the amount of the Grig-
nard reagent was increased, the amount of 20 arising
from R-substitution also increased (eq 12, Table 2). In
the presence of excess Grignard reagent, the dialkyl-
cuprate may be formed, leading to the R-substitution
product.32 The (Z)-selectivity of the γ-substitution product
also increased slightly as the equivalents of Grignard
reagent increased. Titration44 of the Grignard reagent
prior to use is critical for maintaining both high (Z)- and
γ-selectivity. The use of 1.2 equiv of Grignard reagent
provides optimal (Z)- and γ-selectivity (entry 2).
(39) Miller, R. B.; Reichenbach, T. Tetrahedron Lett. 1974, 15, 543-
546.
(40) Brown, H. C.; Zweifel, G. J . Am. Chem. Soc. 1961, 83, 3834-
3840.
(41) House, H. O.; Chu, C.-Y.; Wilkins, J . M.; Umen, M. J . J . Org.
Chem. 1975, 40, 1460-1469.
(42) For the introduction of CuCN‚2LiX, see: Knochel, P.; Yeh, M.
C. P.; Berk, S. C.; Talbert, J . J . Org. Chem. 1988, 53, 2390-2392.
(43) Lipshutz, B. H.; Segi, M. Tetrahedron 1995, 51, 4407-4420.
(44) Voskuil, W.; Arsens, J . F. Organic Syntheses; Wiley: New York,
1963; Collect. Vol. V, pp 211-214.

Stereoselective Synthesis of (Z)- and (E)-Allylic Silanes
J . Org. Chem., Vol. 65, No. 6, 2000 1605
Ta ble 3. Rea ction of 13a w ith Oth er Meta ls (Eq 13)
Ta ble 4. Com p a r ison of th e Rea ction s of tr a n s-13a ,b
w ith Gr ign a r d a n d Alk yllith iu m Rea gen ts (Eq 14)
c-e
yieldb
(%)
entry
RM
product
E/Za
γ/Ra
yieldb
1
2
3
4
5
Me2Ti(O-i-Pr)3Li
Et2Zn
AlMe3
Al(i-Bu)3
allylSnBu3
3d
3e
3d
3c
89:11
90:10
76:24
48:52
99:1
>99:1
>99:1
>99:1
82
77
76
73
NR
entry substrate
RM
MeMgCl
product E/Za
γ/Ra
(%)
1
2c
3
4
5
6
7
8
9
13a
13b
13a
3d
3c
8b
8c
3a
3f
3g
3h
3d
3c
8b
8c
3a
26:74 >99:1
6:94
7:93
6:94 >99:1
4:96 99:1
80
90
95
78
68
71
54
57
72
69
77
75
68
i-BuMgCl
95:5
97:3
Me3SiCH2MgCl
PhMe2SiCH2MgCl
i-PrMgCl
t-BuMgCl
PhMgCl
a
Determined by GC analysis of the unpurified reaction mixture.
Yields reported for material isolated after column chromatogra-
b
13:87 >99:1
7:93 100:0
phy.
58:42
92:8
91:9
91:9 >99:1
76:24 >99:1
72:28 >99:1
97:3
94:6
99:1
MeLi
i-BuLi
We were curious as to whether other organometallic
10
nucleophiles would exhibit a strong preference for alkene
stereochemistry and if the selectivities would be higher
than those observed for either lithium or magnesium
reagents. The metal used as the nucleophilic component
of the reaction with carbamate 13a was varied and the
(E/Z) ratio was determined (eq 13, Table 3). As with
alkyllithium reagents, dimethyltriisopropoxytitanate45
and diethylzinc46 both favored formation of the (E)-alkene
(entries 1 and 2) with selectivities comparable to that of
alkyllithium species. Trimethylaluminum47 exhibited
lower (E)-selectivity (76:24), while triisobutylaluminum
was unselective (entries 3 and 4). Allyltributyltin did not
react with the carbamate. The γ-selectivity was high in
all cases, but none of these alkylmetal reagents favored
formation of the (Z)-alkene. Grignard reagents appear
to be unique in their selectivity.
11
13b
13a
12
Me3SiCH2Li
PhMe2SiCH2Li
13d
a
Determined by GC analysis of the unpurified reaction mixture.
b
Yields reported for material isolated after column chromatogra-
phy. c Enantiomerically enriched 13a was employed (see eq 18).
d
CuI was used, and the reaction was performed at 0-22 °C.
Ta ble 5. Com p a r ison of th e Rea ction cis-18a ,b w ith
Gr ign a r d a n d Alk yllith iu m Rea gen ts (Eq 15)
yieldb
(%)
entry carbamate
RM
product E/ Za
γ/Ra
Rea ction of Tr a n s-Allylic Ca r ba m a tes w ith Gr ig-
n a r d a n d Alk yllith iu m Rea gen ts. The reversal of
selectivity observed with alkyllithium versus alkylmag-
nesium reagents is a general phenomenon with trans-
allylic carbamate 13a as substrate. Upon changing only
the metal in the nucleophile, in all cases alkyllithium
reagents showed (E)-selectivity, whereas use of alkyl-
magnesium reagents resulted in (Z)-selectivity (eq 14,
Table 4). Furthermore, γ/R-selectivity (SN2′/SN2) was
consistently high for both lithium and magnesium re-
agents. Methylmagnesium chloride gave the crotylsilane
3d with modest (Z)-selectivity (entry 1), but all other
alkylmagnesium chlorides exhibited high (Z)-selectivity.
Of the Grignard reagents examined, only phenylmagne-
sium chloride afforded the (E)-isomer as the major
product, albeit with low selectivity (entry 8). This modest
(E)-selectivity is not due to the steric bulk of the nucleo-
phile, because tert-butylmagnesium chloride affords the
(Z)-allylic silane 3g with high selectivity (entry 7). The
presence of the bulkier t-BuMe2Si group on carbamate
13b does not diminish either (Z)- or γ/R-selectivity as
1c
2e
3
18a d
18bf
18a
i-BuMgCl
Me3SiCH2MgCl
i-PrMgCl
MeLi
i-BuLi
PhLi
3c
3b
8d
3d
3c
3h
8c
97:3
98:2
93
78
85
73
93
55
91
93:7 >99:1
90:10 >99:1
100:0 >99:1
4
5c
6
>99:1
100:0
>99:1 >99:1
7
18bf
Me3SiCH2Li
98:2 >99:1
a
Determined by GC analysis of the unpurified reaction mixture.
b
Yields reported for material isolated after column chromatogra-
phy. c Enantiomerically enriched 18a was employed. The (E/ Z)-
ratio of 18a was 2:98 unless otherwise indicated. e The (E/ Z)-ratio
of 18a was 4:96. f The (E/ Z)-ratio of 18b was 11:89.
d
compared to carbamate 13a (entries 3 and 4). Thus, the
synthesis of (Z)-allylic silanes with primary, secondary,
and tertiary alkyl groups adjacent to silicon is possible
by this method.
Rea ction of Cis-Allylic Ca r ba m a tes. To investigate
whether the (Z)-selectivity exhibited by Grignard re-
agents would change upon reaction with cis-allylic car-
bamates, the reaction of cis-18 with both Grignard and
alkyllithium reagents (eq 15, Table 5) was compared to
the reactions with the trans carbamate (eq 14, Table 4).
The copper-mediated reaction of lithium reagents with
cis-allylic carbamates is known to occur with higher (E)-
selectivity than that of trans-allylic carbamates.28 As
expected, the reaction of 18a with isobutyllithium af-
forded the (E)-allylic silane 3c with high selectivity (E/Z
> 99:1, entry 5). The reaction of 18a with the corre-
sponding Grignard reagent also afforded (E)-3c with high
selectivity (E/Z ) 97:3, entry 1). With alkylmagnesium
reagents as nucleophiles, the degree of stereochemical
purity of the starting carbamates was preserved in the
products (entries 1-3). Comparison of the data in Tables
(45) For the copper-catalyzed reactions of terminal and cyclic allylic
phosphates and chlorides with titanate reagents, see: Arai, M.;
Nakamura, E.; Lipshutz, B. H. J . Org. Chem. 1991, 56, 5489-5491.
Arai, M.; Lipshutz, B. H.; Nakamura, E. Tetrahedron 1992, 48, 5709-
5718.
(46) For the copper-catalyzed reactions of allylic chlorides and
phosphates with organozinc reagents, see: (a) Sekiya, K.; Nakamura,
E. Tetrahedron Lett. 1988, 29, 5155-5156. (b) Nakamura, E.; Sekiya,
K.; Arai, M.; Aoki, S. J . Am. Chem. Soc. 1989, 111, 3091-3093. (c)
Zhu, L.; Wehmeyer, R. M.; Rieke, R. D. J . Org. Chem. 1991, 56, 1445-
1453.
(47) For the copper-catalyzed reactions of allylic phosphates and
halides with trialkylaluminum reagents, see: Flemming, S.; Kabbara,
J .; Nickisch, K.; Westermann, J .; Mohr, J . Synlett 1995, 183-185.

1606 J . Org. Chem., Vol. 65, No. 6, 2000
Smitrovich and Woerpel
4 and 5 indicates that, in all cases, the reactions of cis-
allylic carbamates lead to higher (E)-selectivity than
reactions of the trans-isomers.
elucidated. Tosylhydrazide reduction54 of 3c to the alkyl-
silane was followed by oxidation of the C-Si bond55 to
afford the known alcohol 21 ([R]D ) -11.9, lit.56 [R]D
)
-11.9). Since the oxidation of the C-Si bond occurs with
retention of configuration,55,57 these data indicate that
the alcohol 21 has predominately the (R)-configuration.
Analysis of the carbamate obtained from treatment of
alcohol 21 with (R)-(R-methyl)benzyl isocyanate by capil-
lary GC indicated a 94:6 ratio of diastereomers, which is
consistent with the ratio of alkene isomers of 3c. Thus,
reaction of trans-(R)-13a with alkylmagnesium chlorides
affords the (S)-enantiomer of (Z)-allylic silane (eq 18).
Ster eoch em istr y. The products of the copper-medi-
ated substitution of allylic carbamates with alkylmetal
nucleophiles possess two stereochemical features: the
geometry of the olefin and the stereochemistry of the
newly formed allylic center. Goering16 and Fleming28 have
demonstrated that the reactions of alkyllithium and
silyllithium reagents with acyclic allylic carbamates
produce (E)-alkenes and (E)-allylsilanes, respectively, by
addition of the nucleophile syn to the carbamate moiety.
This observation contrasts to the reaction of allylic
esters,48 halides,46 and phosphates,46 which undergo anti
substitution.49 We have demonstrated that alkylmagne-
sium reagents are unlike alkyllithium species in their
reactions with trans-allylic carbamates in that Grignard
reagents selectively afford (Z)-alkenes, whereas with cis-
substrates, both reagents give the (E)-isomer.
To determine the stereochemical relationship between
the carbamate leaving group and the incoming nucleo-
phile (i.e., syn or anti), nucleophilic substitutions on
nonracemic trans-13a and cis-18a were conducted. The
optically active carbamate (R)-13a was obtained in g 94%
ee by Sharpless kinetic resolution50,51 of racemic allylic
alcohol 19a followed by treatment with phenyl isocyanate
(eq 16). Nonracemic cis-allylic carbamate (R)-18a (eq 17)
was prepared from nonracemic propargylic alcohol 16a
(obtained in 96% ee by asymmetric transfer hydrogena-
tion of the corresponding ketone using Noyori’s ruthe-
nium catalyst52,53) as previously described for the racemic
compound.
This process was repeated for cis-carbamate (R)-18a .
Reaction of (R)-18a with isobutylmagnesium chloride
afforded (E)-3c with an (E/Z)-ratio of 97:3 in 93% yield
(eq 19). Analysis of alcohol 21, obtained as described
previously, indicated that the (R)-isomer predominated
with an enantiomeric ratio of 96:4, which compares
favorably to the (E/Z)-ratio of (E)-3c. Isobutyllithium also
gives (E)-3c (E/Z > 99:1, 93% yield) upon reaction with
(R)-18a (eq 20). Therefore, reaction of cis-18a with both
alkylmagnesium chlorides and alkyllithium reagents
gives the (S)-enantiomer of the (E)-crotylsilane.
These results indicate that the reactions of readily
available nonracemic trans- and cis-allylic carbamates
with alkylmagnesium reagents occur with high stereo-
chemical fidelity. The requisite allylic carbamates can be
prepared from propargylic and allylic alcohols, for which
numerous methods for asymmetric syntheses have been
reported.50,52,58 Thus, the allylic carbamates are attractive
precursors of both nonracemic (Z)- and (E)-allylic silanes.
Mech a n ism . Because the mechanism proposed by
Goering to explain the (E)-selective displacement reac-
tions of (E)-allylic carbamates with alkyllithiums did not
These nonracemic carbamates were submitted to cop-
per-mediated substitution reactions, and the enantio-
meric ratios of the product crotylsilanes were determined.
Reaction of trans-(R)-13a with isobutylmagnesium chlo-
ride afforded (Z)-allylic silane 3c with an E/Z ratio of 6:94
in 90% yield (eq 18).17 Chemical correlation allowed the
stereochemistry of the newly formed allylic center to be
(48) Goering, H. L.; Kantner, S. S. J . Org. Chem. 1984, 49, 422-
426.
(49) Corey, E. J .; Boaz, N. W. Tetrahedron Lett. 1984, 25, 3063-
3066.
(54) Suginome, M.; Iwanami, T.; Matsumoto, A.; Ito, Y. Tetrahedron:
Asymmetry 1997, 8, 859-862.
(50) Gao, Y.; Hanson, R. M.; Klunder, J . M.; Ko, S. Y.; Masamune,
H.; Sharpless, K. B. J . Am. Chem. Soc. 1987, 109, 5765-5780.
(51) Kitano’s procedure for Sharpless kinetic resolution of γ-silyl
allylic alcohols was followed: Kitano, Y.; Matsumoto, T.; Sato, F.
Tetrahedron 1988, 44, 4073-4086.
(52) Matsumura, K.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J . Am.
Chem. Soc. 1997, 119, 8738-8739.
(53) Haack, K.-J .; Hashiguchi, S.; Fujii, A.; Ikariya, T.; Noyori, R.
Angew. Chem., Int. Ed. Engl. 1997, 36, 285-288.
(55) Smitrovich, J . H.; Woerpel, K. A. J . Org. Chem. 1996, 61, 6044-
6046.
(56) Takenaka, M.; Takikawa, H.; Mori, K. Liebigs Ann. 1996, 1963-
1964.
(57) Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M. Organometallics
1983, 2, 1694-1696.
(58) For a review of methods available for the enantioselective
reduction of ketones, see: Singh, V. K. Synthesis 1992, 605-617.

Stereoselective Synthesis of (Z)- and (E)-Allylic Silanes
J . Org. Chem., Vol. 65, No. 6, 2000 1607
include a critical role of the counterion, it was not clear
why these reactions should be (Z)-selective when lithium
was exchanged with magnesium. Insight into these
reactions can be gained by consideration of both alkene
stereochemistry and the configuration at the allylic
stereocenter of the products.
oxidative addition would require that the higher energy
rotamer 23b leads to the major product (eq 24). This
analysis requires the reactivity of the reactant conforma-
tion to be a function of the organometallic reagent.
The copper-mediated substitution reactions of allylic
derivatives can occur by two modes of oxidative addition
of copper: either anti49 or syn15,16,59 to the leaving group.
In turn, each of these types of addition can occur through
two rotamers. Inspection of these four possible scenarios
for the reaction of (E)-allylic carbamate (R)-13a with an
organomagnesium reagent indicates that only one leads
to the observed (S)-enantiomer of the (Z)-allylic silane.
Analysis of the two possible manners for oxidative
addition of the magnesiocuprate anti to the carbamate
group demonstrates that neither mode would provide the
observed product. Anti oxidative addition of copper to
rotamer 22a followed by reductive elimination would
afford (S)-(E)-3, which is not observed (eq 21). Addition
of the copper reagent anti to the carbamate moiety in
rotamer 22b would provide the (Z)-allylic silane, but the
stereocenter would have the (R)-configuration, opposite
to what is observed (eq 22). Since neither mode of
addition accounts for the formation of (S)-(Z)-3, the
reaction cannot be occurring by addition of copper anti
to the carbamate moiety.
Since the relationship between the reactivity of the two
rotamers and the counterion of the cuprate was not
obvious, we originally proposed that the allylic displace-
ment with alkylmagnesium reagents to form (Z)-alkenes
proceeded by a fundamentally different mechanism than
that with organolithium nucleophiles.17 The alternative
model relied on anti carbometalation followed by anti
elimination (eq 25). If formation of the alkyl cuprate of
24 with organomagnesium reagents were disfavored,
carbometalation by the Grignard reagent anti to the
carbamate moiety of the copper complex, in its lower
energy conformer 24, becomes an alternative pathway
(eq 25). Anti-elimination from this acyclic intermediate
25 would afford the observed (Z)-alkene.
Since we first presented the carbometalation pathway
shown in eq 25,17 we have accumulated evidence that
argues against it. To determine if the Grignard reagent
transmetalates to copper prior to addition to the allylic
carbamate, a preformed alkylcopper complex was used
as the nucleophile. Addition of the deprotonated carbam-
ate to a solution of (trimethylsilyl)methylcopper,60 pre-
pared by addition of (trimethylsilyl)methylmagnesium
chloride to a solution of CuI‚2LiCl, afforded the allylic
silane 3b with high (Z)-selectivity (64%, E/Z ) 9:91, eq
26). This ratio is comparable to that obtained by the
standard protocol (E/Z ) 4:96). This result suggests that
the alkyl group is coordinated to copper prior to addition
to the carbamate and rules out an intermolecular attack
of alkylmagnesium reagent on the olefin (i.e., eq 25).
Therefore, the reaction of alkylmagnesium reagents with
The observed stereochemistry of the reaction of allylic
carbamates with Grignard reagents can be understood
by consideration of syn attack. Goering proposed that
trans-allylic carbamates react with alkyllithium reagents
to provide (E)-alkenes by a directed intramolecular
oxidative addition of copper syn to the carbamate moi-
ety.16 If this mechanism were also operative for organo-
magnesium reagents, then addition of the magnesium
reagent to the carbamate copper complex followed by
transmetalation from magnesium to copper would afford
23 (eq 23). Intramolecular oxidative addition via the
lower energy conformer 23a followed by reductive elimi-
nation would lead to (R)-(E)-3, which is not observed for
organomagnesium reagents (eq 23). Formation of the
observed (S)-enantiomer of the (Z)-alkene by a syn
(59) Goering, H. L.; Tseng, C. C. J . Org. Chem. 1985, 50, 1597-
1599.
(60) Foulon, J . P.; Bourgain-Commerc¸on, M.; Normant, J . F. Tet-
rahedron 1986, 42, 1389-1397.

1608 J . Org. Chem., Vol. 65, No. 6, 2000
Smitrovich and Woerpel
an Innovative Technologies nitrogen atmosphere drybox. KH
(26% dispersion in mineral oil) was purchased from Aldrich,
washed with hexanes, dried at 22 °C at 0.05 mmHg, and then
stored in an Innovative Technologies nitrogen atmosphere
drybox. Alkyllithium reagents were purchased from Aldrich
or were prepared by lithium-iodine exchange of the corre-
sponding alkyl iodide65,66 and were titrated using diphenyl-
acetic acid as an indicator. Grignard reagents were purchased
from Aldrich or were prepared from the corresponding alkyl
chlorides and were titrated with 2-butanol (1.00 M in xylenes)
using o-phenanthroline as an indicator.44
allylic carbamates likely occurs by transmetalation of the
Grignard reagent to copper followed by oxidative addition
of copper in rotamer 23b (eq 24). The enhanced reactivity
via the higher energy rotamer may be the result of
aggregation.
Cop p er -Med ia ted Rea ction of Allylic Ca r ba m a te 13a
Usin g Cu I: (()-(E)-2-(Dim eth ylp h en ylsilyl)-1-(tr im eth -
ylsilyl)-3-p en ten e [(E)-3b]. To a cooled (0 °C) solution of
carbamate 13a (1.58 g, 4.85 mmol) in 16 mL of THF was added
dropwise by syringe MeLi‚LiBr (1.2 M solution in hexanes, 4.1
mL, 4.8 mmol). After 5 min, the clear yellow-orange reaction
mixture was added dropwise by cannula to a suspension of
CuI (932 mg, 4.9 mmol). After 20 min, the brown reaction
mixture was cooled to 0 °C, and (trimethylsilyl)methyllithium
(1.0 M solution in Et2O/pentane, 4.9 mL, 4.9 mmol) was added
dropwise by syringe. The reaction mixture was allowed to
warm to 22 °C without removing the cold bath. After 16 h, 50
mL of 9:1 saturated aqueous NH4Cl/NH4OH and 75 mL of
methyl tert-butyl ether were added, and the mixture was
stirred until the aqueous layer became transparent blue. The
layers were separated, and the aqueous layer was extracted
with 3 × 50 mL of methyl tert-butyl ether. The combined
organic layers were washed with 50 mL of brine, dried
(MgSO4), filtered, and concentrated in vacuo to afford a golden
oil. Purification by flash chromatography (hexanes) provided
3b as a colorless oil (695 mg, 52%) with an E/ Z ratio of 60:40
and a γ/R ratio of >99:1 as indicated by capillary GC analysis
of the unpurified reaction mixture. The major isomer (E)-3b
was assigned as the (E)-alkene by the value of the coupling
constant of the olefinic protons (J ) 15.2 Hz). (E)-3b: GC tR
The syn-oxidative addition mechanism is further sup-
ported by the reaction of the nonracemic cis-allylic
carbamate 18a . The stereochemical studies revealed that
both alkylmagnesium reagents and alkyllithiums afford
the same enantiomer of the (E)-allylic silane. In the case
of the cis-allylic carbamate, the less favored rotamer 26b
suffers from such severe A1,3 strain61 that this rotamer
is prohibitively high in energy. Oxidative addition must
occur through the more favored rotamer 26a , leading to
the (E)-alkene as the (S)-enantiomer (eq 27) with both
alkyllithium and alkylmagnesium reagents.
1
5.2 min (DB-1, 150 °C, 16 psi); H NMR (CDCl3, 300 MHz) δ
7.47-7.52 (m, 2H), 7.33-7.36 (m, 3H), 5.18 (m, 2H), 1.73 (m,
1H), 1.62 (d, J ) 4.6 Hz, 3H), 0.49 (m, 2H), 0.24 (s, 3H), 0.22
Con clu sion
1
The copper-mediated substitution of allylic carbamates
by organometallic reagents provides a versatile method
for the synthesis of allylic silanes. The reaction of
alkylmagnesium reagents with (E)-allylic carbamates
provides (Z)-allylic silanes, whereas both alkylmagne-
sium and alkyllithium reagents react with (Z)-allylic
carbamates to afford (E)-allylic silanes with high selectiv-
ity. When an alkylmagnesium reagent was used as the
nucleophile, the stereoselectivity of the starting alkene
was transferred faithfully to the product. Considering
that Grignard reagents are often more facile to prepare
than alkyllithium species, Grignard reagents are the
preferred nucleophiles for the synthesis of both (Z)- or
(E)-allylic silanes with high selectivity. Furthermore, the
reaction of readily available nonracemic allylic carbam-
ates with alkylmagnesium reagents occurs in a highly
stereoselective fashion, affording chiral, nonracemic (Z)-
and (E)-allylic silanes.
(s, 3H), -0.08 (s, 9H); H NMR (C6D6, 500 MHz) δ 7.50-7.52
(m, 2H), 7.22-7.33 (m, 3H), 5.27 (ddq, J ) 15.2, 9.1, 1.2 Hz,
1H), 5.19 (dq, J ) 15.2, 5.8 Hz, 1H), 1.83 (ddd, J ) 12.1, 9.5,
2.2 Hz, 1H), 1.60 (d, J ) 6.2 Hz, 3H), 0.69 (dd, J ) 14.8, 2.3
Hz, 1H), 0.60 (dd, J ) 14.8, 12.2 Hz, 1H), 0.28 (s, 3H), 0.27 (s,
3H), 0.01 (s, 9H); 13C NMR (CDCl3, 125 MHz) δ 138.3, 134.2,
133.5, 128.7, 127.5, 120.3, 27.2, 18.0, 15.2, -0.8, -4.6, -5.5;
IR (thin film) 3008, 2954 cm-1; HRMS (EI-GCMS) m/z calcd
for C16H28Si2 (M+) 276.1729, found 276.1729. Anal. Calcd for
C
16H28Si2: C, 69.49; H, 10.20. Found: C, 69.34; H, 10.25.
(()-(Z)-2-(Dim et h ylp h en ylsilyl)-1-(t r im et h ylsilyl)-3-
p en ten e [(Z)-3b]. The procedure given for (E)-3b was fol-
lowed, except that the Grignard reagent was employed. The
product 3b was provided, after purification by flash chroma-
tography (pentane), as a colorless oil (136 mg, 82%) with an
E/ Z ratio of 5:95 and a γ/R ratio of >99:1 as indicated by
capillary GC analysis of the unpurified reaction mixture. The
major isomer (Z)-3b was assigned as the (Z)-alkene by the
value of the coupling constant of the olefinic protons (J ) 10.8
1
Hz): GC tR 5.9 min (DB-1, 150 °C, 16 psi); H NMR (CDCl3,
500 MHz) δ 7.51-7.53 (m, 2H), 7.35-7.36 (m, 3H), 5.29 (dq, J
) 10.8, 6.7 Hz, 1H), 5.12 (m, 1H), 2.11 (m, 1H), 1.46 (dd, J )
6.8, 1.6 Hz, 3H), 0.65 (dd, J ) 14.7, 2.0 Hz, 1H), 0.48 (dd, J )
14.7, 11.9 Hz, 1H), 0.28 (s, 3H), 0.25 (s, 3H), -0.07 (s, 9H);
13C NMR (CDCl3, 125 MHz) δ 138.1, 134.1, 133.9, 128.7, 127.4,
120.3, 22.4, 16.0, 13.2, -1.0, -4.8, -5.6; IR (thin film) 3005,
Exp er im en ta ls
Gen er a l Meth od s. All reactions were carried out under an
atmosphere of nitrogen in glassware that had been flame-dried
under a stream of nitrogen. THF was purified by filtration
through activated alumina according to the method of Grubbs.62
Diisopropylamine and N-methylpyrrolidinone were distilled
from CaH2. CuI was purified by a published method.63,64 LiCl
was dried at 150 °C at 0.05 mmHg for 8 h and then stored in
2954, 1642 cm-1
;
HRMS (CI/isobutane) m/z calcd for
C
C
16H28Si2 (M+) 276.1729, found 276.1724. Anal. Calcd for
16H28Si2: C, 69.49; H, 10.20. Found: C, 69.71; H, 10.22.
(64) Dieter, R. K.; Silks, I., L. A.; Fishpaugh, J . R.; Kastner, M. E.
(61) For a discussion of allylic strain, see: Hoffmann, R. W. Chem.
Rev. 1989, 89, 1841-1860.
(62) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.;
Timmers, F. J . Organometallics 1996, 15, 1518-1520.
(63) Kauffman, G. B.; Teter, L. A. Inorg. Synth. 1963, 7, 9-12.
J . Am. Chem. Soc. 1985, 107, 4679-4692.
(65) Bailey, W. F.; Punzalan, E. R. J . Org. Chem. 1990, 55, 5404-
5406.
(66) Negishi, E.; Swanson, D. R.; Rousset, C. J . J . Org. Chem. 1990,
55, 5406-5409.

Stereoselective Synthesis of (Z)- and (E)-Allylic Silanes
J . Org. Chem., Vol. 65, No. 6, 2000 1609
3330, 2175 cm-1
(()-2-[3-(Dim et h ylp h en ylsilyl)-1-m et h yl-2-p r op yn yl-
oxy]tetr a h yd r op yr a n (15a ).35 To a cooled (-78 °C) solution
of 1467 (5.85 g, 37.9 mmol) in 38 mL of THF was added MeLi
(1.1 M solution in Et2O, 36.0 mL, 40 mmol) dropwise by
addition funnel. After 10 min, the mixture was allowed to
warm to 0 °C. Chlorodimethylphenylsilane (6.6 mL, 40 mmol)
was added dropwise. The ice/H2O bath was removed, and after
15 min, 100 mL of brine and 100 mL of hexanes were added
to the reaction mixture. The layers were separated, and the
aqueous layer was extracted with 3 × 100 mL of hexanes. The
combined organic layers were dried (Na2SO4), filtered, and
concentrated in vacuo to provide a golden oil. Purification by
distillation (0.05 mmHg, 121-129 °C) provided 15a as a
colorless oil (7.71 g, 70%). 1H NMR spectroscopic analysis
indicated that the product was a 3:1 mixture of epimers: 1H
NMR (CDCl3, 500 MHz) major isomer δ 7.61-7.64 (m, 2H),
7.37-7.38 (m, 3H), 4.96 (m, 1H), 4.59 (q, J ) 6.7 Hz, 1H), 3.83
(m, 1H), 3.51 (m, 1H), 1.54-1.84 (m, 6H), 1.48 (d, J ) 6.7 Hz,
3H), 0.41 (s, 6H); minor isomer: δ 7.61-7.64 (m, 2H), 7.37-
7.38 (m, 3H), 4.81 (m, 1H), 4.49 (q, J ) 6.7 Hz, 1H), 4.00 (m,
1H), 3.51 (m, 1H), 1.54-1.84 (m, 6H), 1.46 (d, J ) 6.7 Hz, 3H),
0.41 (s, 6H); 13C NMR (CDCl3, 125 MHz) major isomer δ 136.9,
133.6, 129.33, 127.5, 107.4, 95.9, 87.0, 62.4, 61.7, 30.5, 25.4,
22.0, 19.4, -0.9; minor isomer (characteristic peaks): δ 137.0,
133.7, 129.27, 127.7, 108.4, 97.2, 86.1, 63.1, 62.0, 19.0; IR (thin
film) 3049, 2941, 2169 cm-1; HRMS (CI/isobutane) m/z calcd
for C17H25O2Si (M + H)+ 289.1623, found 289.1624.
;
HRMS (CI/isobutane) m/z calcd for
C
10H20OSi (M+) 184.1283, found 184.1281. Anal. Calcd for
C10H20OSi: C, 65.15; H, 10.94. Found: C, 64.91; H, 11.02.
(()-(E)-1-(Dim eth ylp h en ylsilyl)-1-bu ten -3-ol (19a ). To
a cooled (-20 °C) solution of Red-Al (65% weight solution in
toluene, 23.6 mL, 78.6 mmol) in 30 mL of Et2O was added a
solution of 16a (10.7 g, 52.4 mmol) in 20 mL of Et2O dropwise
by cannula. The reaction temperature was maintained at -25
to -15 °C over the course of the addition and was then allowed
to increase to 22 °C. After 3.5 h, the reaction mixture was
cooled to 0 °C, and H2SO4 (3.6 M, 30 mL, 108 mmol) was
cautiously added. The reaction mixture was diluted with 200
mL of Et2O. The layers were separated, and the aqueous layer
was extracted with 3 × 200 mL of Et2O. The combined organic
layers were washed with brine, dried (MgSO4), filtered, and
concentrated in vacuo to provide a golden oil. Purification by
flash chromatography (hexanes to 20:80 EtOAc/hexanes)
provided 19a as a colorless oil (9.45 g, 87%). Capillary GC
revealed that the product was formed as a 98:2 (E/Z) mixture
of alkene isomers. The spectral data were identical to that
reported in the literature:69 1H NMR (CDCl3, 500 MHz) δ 7.50-
7.53 (m, 2H), 7.34-7.37 (m, 3H), 6.17 (dd, J ) 18.7, 4.8 Hz,
1H), 5.97 (dd, J ) 18.7, 1.1 Hz, 1H), 4.32 (m, 1H), 1.56 (d, J )
3.2 Hz, 1H), 1.28 (d, J ) 6.5 Hz, 3H), 0.35 (s, 6H); 13C NMR
(CDCl3, 125 MHz) δ 151.4, 133.8, 129.0, 127.8, 125.9, 105.4,
70.4, 22.9, -2.8.
(()-(E)-1-(ter t-Bu t yld im et h ylsilyl)-1-bu t en -3-ol (19b ).
Using the procedure given for 19a with alcohol 15b provided
19b, after purification by flash chromatography (10:90 EtOAc/
hexanes), as a yellow oil (7.1 g, 100%). Only one stereoisomer
was formed as determined using 1H and 13C NMR spectros-
copy: 1H NMR (CDCl3, 500 MHz) δ 6.10 (dd, J ) 18.5, 5.1 Hz,
1H), 5.83 (dd, J ) 18.8, 1.4 Hz, 1H), 4.30 (m, 1H), 1.49 (br s,
1H), 1.27 (d, J ) 6.5 Hz, 3H), 0.87 (s, 9H), 0.03 (s, 6H); 13C
NMR (CDCl3, 125 MHz) δ 151.1, 125.2, 70.6, 26.4, 23.0, 16.4,
-6.2; IR (thin film) 3333, 2953, 1620 cm-1; HRMS (CI/
isobutane) m/z calcd for C10H22OSi (M+) 186.1440, found
186.1440. Anal. Calcd for C10H22OSi: C, 64.45; H, 11.90.
Found: C, 64.40; H, 11.94.
(()-2-[3-(ter t-Bu t yld im et h ylsilyl)-1-m et h yl-2-p r op yn -
yloxy]tetr a h yd r op yr a n (15b). The procedure given for 15a
was followed, except that the tert-butyldimethylsilyl chloride
was employed and the reaction mixture was stirred at 22 °C
for 1 h following the addition of tert-butyldimethylsilyl chloride.
Purification by distillation (0.05 mmHg, 83-93 °C) provided
15b as a colorless oil (4.69 g, 94%). 1H NMR spectroscopic
analysis indicated that the product was a 3:1 mixture of
epimers: 1H NMR (CDCl3, 500 MHz) major isomer δ 4.95 (m,
1H), 4.54 (q, J ) 6.7 Hz, 1H), 3.82 (m, 1H), 3.51 (m, 1H), 1.51-
1.87 (m, 6H), 1.45 (d, J ) 6.7 Hz, 3H), 0.93 (s, 9H), 0.10 (s,
6H); minor isomer δ 4.80 (m, 1H), 4.34 (m, 1H), 4.00 (m, 1H),
3.51 (m, 1H), 1.51-1.87 (m, 6H), 1.42 (d, J ) 6.7 Hz, 3H), 0.93
(s, 9H), 0.10 (s, 6H); 13C NMR (CDCl3, 125 MHz) major isomer
δ 106.0, 95.9, 87.2, 62.5, 61.2, 30.5, 26.0, 22.0, 19.5, 16.4, -4.7,
minor isomer (characteristic peaks) δ 107.1, 97.0, 86.4, 63.0,
(()-1-(E)-(Dim eth ylp h en ylsilyl)-1-bu ten -3-ol N-P h en yl-
ca r ba m a te (13a ).70 Phenyl isocyanate (0.875 mL, 8.0 mmol)
was added to neat alcohol 19a (1.66 g, 8.05 mmol). After the
mixture was stirred for 24 h, the resultant off-white solid was
diluted with hot hexanes, and the slurry was filtered. The
filtrate was concentrated in vacuo to provide an orange-yellow
oil. Purification by flash chromatography (2:98 to 5:95 EtOAc/
hexanes) provided 13a as a pale yellow oil that solidified on
62.0, 25.4, 22.1, 19.0, 16.5; IR (thin film) 2951, 2169 cm-1
;
HRMS (CI/isobutane) m/z calcd for C15H29O2Si (M + H)+
269.1937, found 269.1927. Anal. Calcd for C15H28O2Si: C,
67.11; H, 10.51. Found: C, 66.91; H, 10.66.
1
(()-4-(Dim eth ylp h en ylsilyl)-3-bu tyn -2-ol (16a ). To a
solution of 15a (925 mg, 3.21 mmol) in 12 mL of MeOH was
added TsOH (16 mg, 0.08 mmol). The reaction mixture was
stirred for 12 h and then concentrated in vacuo. The resultant
yellow oil was diluted with 50 mL of Et2O and washed with
25 mL of saturated aqueous NaHCO3. The layers were
separated, and the aqueous layer was extracted with 3 × 50
mL of Et2O. The combined organic layers were washed with
brine, dried (MgSO4), filtered, and concentrated in vacuo.
Purification by flash chromatography (2:98 to 10:90 EtOAc/
pentane) provided 16a as a colorless oil (528 mg, 81%). Spectral
data were identical to those reported in the literature:37,68 1H
NMR (CDCl3, 500 MHz) δ 7.61-7.63 (m, 2H), 7.36-7.40 (m,
3H), 4.56 (m, 1H), 1.83 (d, J ) 5.3 Hz, 1H), 1.48 (d, J ) 6.6
Hz, 3H), 0.42 (s, 6H); 13C NMR (CDCl3, 125 MHz) δ 136.6,
133.6, 129.4, 127.9, 109.4, 86.4, 58.7, 24.1, -1.0.
(()-4-(ter t-Bu tyld im eth ylsilyl)-3-bu tyn -2-ol (16b). Us-
ing the procedure given for 16a with 15b provided 16b, after
purification by flash chromatography (2:98 to 10:90 EtOAc/
pentane), as a colorless oil (524 mg, 76%): 1H NMR (CDCl3,
500 MHz) δ 4.52 (m, 1H), 1.78 (d, J ) 5.3 Hz, 1H), 1.45 (d, J
) 6.6 Hz, 3H), 0.93 (s, 9H), 0.10 (s, 6H); 13C NMR (CDCl3, 125
MHz) δ 108.4, 86.5, 58.7, 26.0, 24.3, 16.4, -4.7; IR (thin film)
standing (2.14 g, 82%): mp 56-57 °C; H NMR (CDCl3, 500
MHz) δ 7.50-7.52 (m, 2H), 7.26-7.49 (m, 7H), 7.02-7.04 (m,
1H), 6.71 (br s, 1H), 6.12 (dd, J ) 18.8, 4.6 Hz, 1H), 6.04 (dd,
J ) 18.8, 1.2 Hz, 1H), 5.39 (m, 1H), 1.36 (d, J ) 6.4 Hz, 3H),
0.34 (s, 6H); 13C NMR (CDCl3, 125 MHz) δ 152.8, 146.7, 138.2,
137.9, 133.8, 129.05, 129.01, 128.3, 127.8, 123.3, 118.6, 73.0,
20.0, -2.7; IR (thin film) 3321, 3068, 2957, 1706 cm-1; HRMS
(CI/NH3) m/z calcd for C19H27N2O2Si (M + NH4)+ 343.1842,
found 343.1845. Anal. Calcd for C19H23NO2Si: C, 70.11; H,
7.12; N, 4.30. Found: C, 70.06; H, 7.21; N, 4.29.
(()-1-(E)-(ter t-Bu t yld im et h ylsilyl)-1-b u t en -3-ol
N-
P h en ylca r ba m a te (13b). Using the procedure given for 13a
with alcohol 19b provided 13b, after purification by flash
chromatography (2:98 to 5:95 EtOAc/hexanes), as a white solid
1
(6.15 g, 58%): mp 103-104 °C; H NMR (CDCl3, 500 MHz) δ
7.35-7.39 (m, 2H), 7.28-7.32 (m, 2H), 7.04-7.07 (m, 1H), 6.54
(br s, 1H), 6.07 (dd, J ) 18.9, 5.0 Hz, 1H), 5.90 (dd, J ) 18.9,
1.4 Hz, 1H), 5.36 (m, 1H), 1.37 (d, J ) 6.5 Hz, 3H), 0.87 (s,
9H), 0.39 (s, 3H), 0.37 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ
152.8, 146.2, 138.0, 129.0, 127.8, 123.3, 118.6, 73.3, 26.4, 20.2,
16.4, -6.3; IR (thin film) 3296, 2952, 1702 cm-1; HRMS (CI/
NH3) m/z calcd for C17H27NO2Si (M+) 305.1811, found 305.1819.
(69) Panek, J . S.; Sparks, M. A. Tetrahedron: Asymmetry 1990, 1,
801-816.
(70) McElvain’s procedure for carbamate preparation was fol-
lowed: McElvain, S. M. The Characterization of Organic Compounds;
MacMillan: New York, 1953; p 199.
(67) Hickman, D. N.; Hodgetts, K. J .; Mackman, P. S.; Wallace, T.
M.; Wardleworth, J . M. Tetrahedron 1996, 52, 2233-2260.
(68) Fleming, I.; Takaki, K.; Thomas, A. P. J . Chem. Soc., Perkin
Trans. 1 1987, 2269-2273.

1610 J . Org. Chem., Vol. 65, No. 6, 2000
Smitrovich and Woerpel
Anal. Calcd for C17H27NO2Si: C, 66.84; H, 8.91; N, 4.58.
Found: C, 66.63; H, 8.98; N, 4.59.
diluted with 100 mL of Et2O. The layers were separated, and
the aqueous layer was extracted with 3 × 100 mL of Et2O.
The combined organic layers were washed with brine, dried
(Na2SO4), filtered, and concentrated in vacuo. The resultant
pale yellow slurry was diluted with 70 mL of MeOH, and TsOH
(81 mg, 0.43 mmol) was added. The reaction mixture was
stirred for 12 h and then concentrated in vacuo. The resultant
yellow oil was diluted with 100 mL of Et2O and washed with
50 mL of saturated aqueous NaHCO3. The layers were
separated, and the aqueous layer was extracted with 3 × 100
mL of Et2O. The combined organic layers were washed with
brine, dried (Na2SO4), filtered, and concentrated in vacuo.
Purification by flash chromatography (10:90 EtOAc/pentane)
provided 28b as a colorless oil (2.3 g, 58%) with an E/ Z ratio
of 11:89 as indicated by capillary GC analysis of the unpurified
reaction mixture: GC tR 7.3 min (DB-1, 60-150 °C at 5 °C/
min, 16 psi); 1H NMR (CDCl3, 500 MHz) δ 6.33 (dd, J ) 14.3,
9.1 Hz, 1H), 5.61 (dd, J ) 14.3, 0.7 Hz, 1H), 4.42 (m, 1H), 1.40
(br s, 1H), 1.26 (d, J ) 6.2 Hz, 3H), 0.89 (s, 9H), 0.12 (s, 3H),
0.11 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 152.1, 127.6, 68.5,
(()-(Z)-3-[1-(Dim eth ylp h en ylsilyl)-1-bu ten yl] Aceta te
(27). To a cooled (0 °C) solution of BH3‚SMe2 (0.340 mL, 3.58
mmol) in 3.6 mL of THF was added cyclohexene (0.725 mL,
7.16 mmol). The reaction mixture was allowed to warm to 22
°C and gradually became milky white. After 2.5 h, the reaction
mixture was cooled to 0 °C, and a solution of propargylic
acetate 1737 (586 mg, 2.38 mmol) in 2 mL of THF was added
dropwise. The reaction mixture was allowed to warm to 22 °C
and gradually became clear and colorless. After 3.5 h, the
reaction mixture was cooled to 0 °C, and AcOH (glacial, 0.340
mL, 5.94 mmol) was added dropwise. The reaction mixture
was allowed to warm to 22 °C. After 20 h, the reaction mixture
was poured into 20 mL of saturated aqueous NaHCO3 and
diluted with 50 mL of Et2O. The layers were separated, and
the aqueous layer was extracted with 3 × 50 mL of Et2O. The
combined organic layers were washed with brine, dried
(MgSO4), filtered, and concentrated in vacuo. Purification by
flash chromatography (5:95 EtOAc/pentane) provided 27 as a
colorless oil (543 mg, 92%) with an E/ Z ratio of 2:98 as
indicated by capillary GC analysis of the unpurified reaction
mixture. The spectral data were identical to that reported in
the literature:37 GC tR 4.2 min (DB-1, 150 °C, 16 psi); 1H NMR
(CDCl3, 500 MHz) δ 7.49-7.56 (m, 2H), 7.34-7.37 (m, 3H),
6.30 (dd, J ) 14.4, 8.8 Hz, 1H), 5.82 (dd, J ) 14.4, 0.8 Hz,
1H), 5.37 (dqd, J ) 8.8, 6.4, 0.8 Hz, 1H), 1.95 (s, 3H), 1.15 (d,
J ) 6.4 Hz, 3H), 0.41 (s, 6H); 13C NMR (CDCl3, 125 MHz) δ
170.0, 147.7, 138.7, 133.7, 130.1, 129.0, 127.8, 21.2, 20.5, -1.0,
-1.3.
(()-(Z)-1-(Dim eth ylp h en ylsilyl)-1-bu ten -3-ol (28a ). A
solution of 27 (540 mg, 2.17 mmol) in 10 mL of MeOH was
treated with K2CO3 (saturated, 2:1 MeOH/H2O, 1.2 mL). The
resultant mixture was stirred for 3 h. The reaction mixture
was concentrated in vacuo to an orange slurry that was diluted
with 50 mL of Et2O. The mixture was washed with 25 mL of
saturated aqueous NH4Cl. The layers were separated, and the
aqueous layer was washed with 3 × 50 mL of Et2O. The
combined organic layers were washed with brine, dried
(MgSO4), filtered, and concentrated in vacuo to provide a
yellow oil. Purification by flash chromatography (10:90 EtOAc/
hexanes) provided 28a as a colorless oil (404 mg, 90%). The
spectral data were identical to that reported in the literature:
37 1H NMR (CDCl3, 500 MHz) δ 7.51-7.56 (m, 2H), 7.35-7.38
(m, 3H), 6.36 (dd, J ) 14.1, 8.6 Hz, 1H), 5.76 (dd, J ) 14.1,
0.7 Hz, 1H), 4.30 (m, 1H), 1.36 (br s, 1H), 1.14 (d, J ) 6.3 Hz,
3H), 0.40 (s, 6H); 13C NMR (CDCl3, 125 MHz) δ 152.7, 139.3,
133.5, 129.1, 128.2, 128.0, 68.5, 22.8, -0.7, -0.8.
26.3, 23.0, 16.5, -3.9, -4.0; IR (thin film) 3341, 1613 cm-1
;
HRMS (EI-GCMS) m/z calcd for C6H13OSi (M - CMe3)+
129.0731, found 129.0733.
(()-(Z)-1-(ter t-Bu t yld im et h ylsilyl)-1-b u t en -3-ol
N-
P h en ylca r ba m a te (18b). Using the procedure given for 13a
with allylic alcohol 28b provided 18b, after purification by
flash chromatography (5:95 to 10:90 EtOAc/hexanes), as a
white solid (1.90 g, 96%): mp 98-99 °C; 1H NMR (CDCl3, 500
MHz) δ 7.37-7.40 (m, 2H), 7.28-7.31 (m, 2H), 7.03-7.07 (m,
1H), 6.54 (br s, 1H), 6.35 (dd, J ) 14.5, 9.2 Hz, 1H), 5.73 (d, J
) 14.5 Hz, 1H), 5.48 (m, 1H), 1.36 (d, J ) 6.3 Hz, 3H), 0.90 (s,
9H), 0.18 (s, 3H), 0.17 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ
152.7, 147.2, 138.0, 129.7, 129.0, 123.2, 118.6, 72.1, 26.3, 20.1,
16.5, -4.2, -4.5; IR (thin film) 3292, 2952, 1697 cm-1; HRMS
(LSIMS) m/z calcd for C17H28NO2Si (M + H)+ 306.1889, found
306.1884. Anal. Calcd for C17H27NO2Si: C, 66.84; H, 8.91; N,
4.58. Found: C, 66.99; H, 8.98; N, 4.63.
Cop p er -Med ia ted Rea ction of Allylic Ca r ba m a te 13a
Usin g Cu I‚2LiCl: (()-(Z)-2-(Dim eth ylp h en ylsilyl)-1-(tr i-
m eth ylsilyl)-3-p en ten e [(Z)-3b]. To a cooled (-78 °C) solu-
tion of carbamate 13a (150 mg, 0.46 mmol) in 1.2 mL of THF
was added dropwise by syringe n-BuLi (1.30 M solution in
hexanes, 0.355 mL, 0.46 mmol). After 5 min, the transparent
yellow-orange reaction mixture was added dropwise by can-
nula to a cooled (-78 °C) solution of CuI‚2LiCl [prepared by
stirring CuI (90 mg, 0.47 mmol) and LiCl (39 mg, 0.92 mmol)
in 2.3 mL of THF at 22 °C for 10 min]. After 30 min,
(trimethylsilyl)methylmagnesium chloride (0.69 M solution in
THF, 0.670 mL, 0.46 mmol) was added dropwise by syringe,
and the reaction mixture was allowed to warm to 22 °C without
removing the cold bath. After 16.5 h, the reaction mixture was
submitted to aqueous workup as described for the reaction of
13a using CuI. Purification by flash chromatography (pentane)
provided (Z)-3b as a colorless oil (105 mg, 82%) with an E/ Z
ratio of 6:94 and a γ/R ratio of >99:1 as indicated by capillary
GC analysis of the unpurified reaction mixture. The major
isomer was identical to a sample of (Z)-3b prepared from 13a
using CuI by 1H and 13C NMR spectroscopic analyses (vide
supra).
Rea ction of 13a w ith (Tr im eth ylsilyl)m eth ylm a gn e-
siu m Ch lor id e in th e Absen ce of Cop p er (I). To a cooled
(-78 °C) solution of carbamate 13a (254 mg, 0.78 mmol) in 3
mL of THF was added dropwise by syringe n-BuLi (1.34 M
solution in hexanes, 0.582 mL, 0.78 mmol). After 5 min,
(trimethylsilyl)methylmagnesium chloride (1.1 M solution in
THF, 0.730 mL, 0.8 mmol) was added dropwise by syringe,
and the reaction mixture was allowed to warm to 22 °C without
removing the cold bath. After 20 h, the reaction mixture was
submitted to aqueous workup as described for the reaction of
13a using CuI. Purification by flash chromatography (pentane
to 10:90 EtOAc/hexanes) provided vinylsilane 10 (11 mg, 5%),
recovered 13a (181 mg, 71%), and alcohol 19a (35 mg, 22%).
Vin ylsila n e 10: GC tR 6.6 min (DB-1, 175 °C, 16 psi); 1H NMR
(CDCl3, 500 MHz) δ 7.52-7.54 (m, 2H), 7.35-7.36 (m, 3H),
6.05 (dd, J ) 18.5, 7.0 Hz, 1H), 5.68 (dd, J ) 18.7, 1.2 Hz,
(()-(Z)-1-(Dim eth ylp h en ylsilyl)-1-bu ten -3-ol N-P h en yl-
ca r ba m a t e (18a ). Using the procedure given for 13a with
allylic alcohol 28a provided 18a , after purification by flash
chromatography (5:95 to 10:90 EtOAc/hexanes), as a white
solid (330 mg, 84%): mp 40 °C; 1H NMR (CDCl3, 500 MHz) δ
7.56-7.58 (m, 2H), 7.35-7.38 (m, 3H), 7.28-7.32 (m, 4H),
7.02-7.05 (m, 1H), 6.37 (dd, J ) 14.5, 8.2 Hz, 1H), 6.28 (br s,
1H), 5.85 (d, J ) 14.4 Hz, 1H), 5.40 (m, 1H), 1.23 (d, J ) 6.4
Hz, 3H), 0.48 (s, 3H), 0.43 (s, 3H); 13C NMR (CDCl3, 125 MHz)
δ 152.5, 147.9, 139.0, 137.9, 133.7, 129.8, 129.0, 128.9, 127.9,
123.2, 118.5, 71.9, 20.8, -0.97, -1.02; IR (thin film) 3292,
3050, 2958, 1725 cm-1; HRMS (EI-GCMS) m/z calcd for
C
C
19H23NO2Si (M+) 325.1498, found 325.1493. Anal. Calcd for
19H23NO2Si: C, 70.11; H, 7.12; N, 4.30. Found: C, 70.35; H,
7.15; N, 4.40.
(()-(Z)-1-(ter t-Bu t yld im et h ylsilyl)-1-b u t en -3-ol (28b).
To a cooled (0 °C) solution of BH3‚SMe2 (3.0 mL, 31.6 mmol)
in 30 mL of THF was added cyclohexene (6.5 mL, 64.2 mmol).
The reaction mixture was allowed to warm to 22 °C and
gradually became milky white. After 2.5 h, the reaction
mixture was cooled to 0 °C, and 15b (5.74 g, 21.4 mmol) was
added dropwise. The reaction mixture was allowed to warm
to 22 °C and gradually became clear and colorless. After 3.5
h, the reaction mixture was cooled to 0 °C and AcOH (glacial,
3.1 mL, 54.2 mmol) was added dropwise. The reaction mixture
was allowed to warm to 22 °C. After 20 h, the reaction mixture
was poured into 100 mL of saturated aqueous NaHCO3 and

Stereoselective Synthesis of (Z)- and (E)-Allylic Silanes
J . Org. Chem., Vol. 65, No. 6, 2000 1611
1H), 2.38 (m, 1H), 1.05 (d, J ) 6.8 Hz, 3H), 0.70 (dd, J ) 14.5,
7.4 Hz, 1H), 0.59 (dd, J ) 14.5, 7.0 Hz, 1H), 0.33 (s, 6H), 0.01
(s, 9H); 13C NMR (CDCl3, 125 MHz) δ 157.0, 139.4, 133.8,
128.8, 127.7, 123.0, 37.0, 24.7, 23.6, -0.6, -2.4; IR (thin film)
3069, 2955, 1612 cm-1; HRMS (CI/isobutane) m/z calcd for
E/ Z ratio of 4:96 and a γ/R ratio of 99:1 as indicated by
capillary GC analysis of the unpurified reaction mixture. The
major isomer was assigned as the (Z)-alkene by the value of
the coupling constant of the olefinic protons (J ) 10.8 Hz):
GC tR 6.6 min (DB-1, 200 °C, 16 psi); 1H NMR (CDCl3, 500
MHz) δ 7.44-7.46 (m, 2H), 7.39-7.41 (m, 2H), 7.30-7.34 (m,
6H), 5.25 (dqd, J ) 10.7, 6.8, 0.8 Hz, 1H), 5.09 (app tq, J )
10.8, 1.7 Hz, 1H), 2.07 (m, 1H), 1.34 (dd, J ) 6.8, 2.0 Hz, 3H),
0.90 (dd, J ) 14.7, 2.0 Hz, 1H), 0.68 (dd, J ) 14.9, 12.1 Hz,
1H), 0.24 (s, 3H), 0.21 (s, 3H), 0.20 (s, 3H), 0.18 (s, 3H); 13C
NMR (CDCl3, 125 MHz) δ 139.8, 138.0, 134.1, 133.7, 133.6,
128.8, 128.6, 127.6, 127.5, 120.7, 22.3, 15.3, 13.2, -1.8, -3.0,
-4.7, -5.7; IR (thin film) 3006, 2955 cm-1; HRMS (CI/
isobutane) m/z calcd for C21H30Si2 (M+) 338.1886, found
C
16H28Si2 (M+) 276.1729, found 276.1723. Anal. Calcd for
C16H28Si2: C, 69.49; H, 10.20. Found: C, 69.40; H, 10.26.
Op tim ized P r oced u r e for th e Cop p er -Med ia ted Rea c-
t ion of Allylic Ca r b a m a t e 13a : (()-(Z)-4-(Dim et h yl-
p h en ylsilyl)-2-m eth yl-5-h ep ten e [(Z)-3c]. To a cooled (-78
°C) solution of carbamate 13a (254 mg, 0.78 mmol) in 1.5 mL
of THF was added dropwise by syringe n-BuLi (1.26 M solution
in hexanes, 0.620 mL, 0.78 mmol). After 5 min, the transparent
yellow-orange reaction mixture was added dropwise by can-
nula to a cooled (-78 °C) solution of CuI‚2LiCl [prepared by
stirring CuI (151 mg, 0.79 mmol) and LiCl (67 mg, 1.6 mmol)
in 3 mL of THF at 22 °C for 10 min]. After 30 min,
isobutylmagnesium chloride (0.87 M solution in THF, 1.08 mL,
0.94 mmol) was added dropwise by syringe, and the reaction
mixture was allowed to warm to 22 °C without removing the
cold bath. After 16.5 h, the reaction mixture was submitted
to aqueous workup as described for the reaction of 13a using
CuI. Purification by flash chromatography (pentane) provided
(Z)-3c as a colorless oil (133 mg, 69%) with an E/ Z ratio of
7:93 as indicated by capillary GC analysis of the unpurified
reaction mixture. The γ/R ratio was determined to be g95:5
by the 1H NMR spectroscopic analysis of the unpurified
reaction mixture. The major isomer was assigned as the (Z)-
alkene by the value of the coupling constant of the olefinic
protons (J ) 10.9 Hz): GC tR 4.5 min (DB-1, 150 °C, 16 psi);
1H NMR (CDCl3, 500 MHz) δ 7.47-7.51 (m, 2H), 7.32-7.36
(m, 3H), 5.37 (dq, J ) 10.9, 6.7 Hz, 1H), 5.11 (m, 1H), 2.15
(app dt, J ) 11.6, 2.7 Hz, 1H), 1.53 (m, 1H), 1.46 (dd, J ) 6.8,
1.7 Hz, 3H), 1.30 (m, 1H), 1.12 (ddd, J ) 13.4, 10.4, 2.9 Hz,
1H), 0.82 (d, J ) 6.6 Hz, 3H), 0.76 (d, J ) 6.6 Hz, 3H), 0.27 (s,
3H), 0.25 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 138.1, 134.1,
132.2, 128.8, 127.5, 121.5, 38.8, 26.8, 25.5, 23.8, 20.7, 13.1,
-4.4, -5.2; IR (thin film) 3050, 2954, 1644 cm-1; HRMS (EI-
GCMS) m/z calcd for C16H26Si (M+) 246.1803, found 246.1805.
Anal. Calcd for C16H26Si: C, 78.29; H, 10.27. Found: C, 78.01;
H, 10.56.
338.1880. Anal. Calcd for
Found: C, 74.60; H, 8.96.
C21H30Si2: C, 74.48; H, 8.93.
(()-(E)-1,2-Bis(d im et h ylp h en ylsilyl)-3-p en t en e [(E)-
3a ]. Using the optimized procedure given for (Z)-3c with
carbamate 13a and (dimethylphenylsilyl)methyllithium pro-
vided (E)-3a , after purification by flash chromatography
(pentane), as a colorless oil (105 mg, 68%) with an E/ Z ratio
of 72:28 and a γ/R ratio of >99:1 as indicated by capillary GC
analysis of the unpurified reaction mixture. The major isomer
was assigned as the (E)-alkene by comparison of 1H NMR
spectroscopic and capillary GC data to that of the reference
compound prepared by Hayashi-Kumada coupling using
trans-bromopropene:71 GC tR 5.9 min (DB-1, 200 °C, 16 psi);
1H NMR (CDCl3, 500 MHz) δ 7.42-7.46 (m, 2H), 7.35-7.40
(m, 2H), 7.29-7.34 (m, 6H), 5.12 (m, 2H), 1.74 (m, 1H), 1.57
(d, J ) 4.9 Hz, 3H), 0.82 (dd, J ) 14.9, 2.2 Hz, 1H), 0.72 (dd,
J ) 14.9, 12.3 Hz, 1H), 0.22 (s, 3H), 0.20 (s, 3H), 0.19 (s, 3H),
0.18 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 140.1, 138.1, 134.1,
133.6, 133.3, 128.7, 128.5, 127.53, 127.49, 122.4, 27.1, 17.9,
14.4, -1.8, -2.7, -4.6, -5.7; IR (thin film) 3010, 2956 cm-1
;
HRMS (EI-GCMS) m/z calcd for C21H30Si2 (M+) 338.1886, found
338.1892. Anal. Calcd for C21H30Si2: C, 74.48; H, 8.93.
Found: C, 74.63; H, 8.83.
(()-(E)-4-(Dim eth ylph en ylsilyl)-2-m eth yl-5-h epten e [(E)-
3c]. Using the optimized procedure given for (Z)-3c with
carbamate 13a and isobutyllithium provided (E)-3c, after
purification by flash chromatography (pentane), as a colorless
oil with an E/ Z ratio of 91:9 and a γ/R ratio of 99:1 as indicated
by capillary GC analysis of the unpurified reaction mixture
(77 mg, 69%). The major isomer was assigned as the (E)-alkene
by the value of the coupling constant of the olefinic protons (J
) 15.2 Hz): GC tR 4.2 min (DB-1, 150 °C, 16 psi); 1H NMR
(CDCl3, 500 MHz) δ 7.47-7.51 (m, 2H), 7.32-7.36 (m, 3H),
5.22 (dq, J ) 15.2, 5.9 Hz, 1H), 5.19 (ddq, J ) 15.2, 8.9, 1.1
Hz, 1H), 1.77 (ddd, J ) 12.1, 9.1, 2.9 Hz, 1H), 1.64 (d, J ) 5.4
Hz, 3H), 1.57 (m, 1H), 1.32 (ddd, J ) 13.5, 12.3, 3.6 Hz, 1H),
1.04 (ddd, J ) 13.5, 10.3, 3.1 Hz, 1H), 0.82 (d, J ) 6.7 Hz,
3H), 0.74 (d, J ) 6.5 Hz, 3H), 0.24 (s, 3H), 0.23 (s, 3H); 13C
NMR (CDCl3, 125 MHz) δ 138.3, 134.1, 131.9, 128.7, 127.5,
122.9, 38.0, 30.2, 26.3, 23.9, 20.6, 18.1, -4.3, -5.1; IR (thin
film) 3050, 2954, 1657 cm-1; HRMS (EI-GCMS) m/z calcd for
C16H26Si (M+) 246.1803, found 246.1798. Anal. Calcd for
C16H26Si: C, 78.29; H, 10.27. Found: C, 78.01; H, 10.54.
(()-(Z)-3-(Dim eth ylph en ylsilyl)-2-m eth yl-4-h exen e [(Z)-
3f]. Using the optimized procedure given for (Z)-3c with
carbamate 13a and isopropylmagnesium chloride provided (Z)-
3f, after purification by flash chromatography (pentane), as a
colorless oil (142 mg, 71%) with an E/ Z ratio of 13:87 and a
γ/R ratio of >99:1 as indicated by capillary GC analysis of the
unpurified reaction mixture. Spectral data of the major isomer
were identical to those reported in the literature for the (Z)-
isomer:72 GC tR 4.0 min (DB-1, 150 °C, 16 psi); 1H NMR (CDCl3,
500 MHz) δ 7.51-7.53 (m, 2H), 7.32-7.34 (m, 3H), 5.49 (dq, J
) 11.0, 6.6 Hz, 1H), 5.35 (m, 1H), 2.01 (dd, J ) 11.9, 5.1 Hz,
1H), 1.84 (m, 1H), 1.45 (dd, J ) 6.7, 1.7 Hz, 3H), 0.84 (d, J )
2.3 Hz, 3H), 0.82 (d, J ) 2.4 Hz, 3H), 0.30 (s, 3H), 0.27 (s,
(()-(Z)-2-(Dim eth ylp h en ylsilyl)-3-p en ten e [(Z)-3d ]. Us-
ing the optimized procedure given for (Z)-3c with carbamate
13a and methylmagnesium chloride provided (Z)-3d , after
purification by flash chromatography (pentane), as a colorless
oil (163 mg, 80%) with an E/ Z ratio of 26:74 and a γ/R ratio of
>99:1 as indicated by capillary GC analysis of the unpurified
reaction mixture. Spectral data of the major isomer was
identical to that reported in the literature for the (Z)-isomer:
28
1
GC tR 4.6 min (DB-1, 125 °C, 16 psi); H NMR (CDCl3, 500
MHz) δ 7.48-7.53 (m, 2H), 7.32-7.37 (m, 3H), 5.33 (dqd, J )
10.7, 6.7, 0.8 Hz, 1H), 5.20 (tq, J ) 10.8, 1.7 Hz, 1H), 2.10
(dqd, J ) 10.9, 7.2, 0.6 Hz, 1H), 1.47 (dd, J ) 6.7, 1.7 Hz, 3H),
1.00 (d, J ) 7.2 Hz, 3H), 0.27 (s, 3H), 0.26 (s, 3H); 13C NMR
(CDCl3, 125 MHz) δ 138.0, 134.0, 133.6, 128.8, 127.5, 120.6,
21.2, 15.2, 13.1, -4.7, -5.5.
(()-(E)-2-(Dim eth ylp h en ylsilyl)-3-p en ten e [(E)-3d ]. Us-
ing the optimized procedure given for (Z)-3c with carbamate
13a and methyllithium provided (E)-3d , after purification by
flash chromatography (pentane), as a colorless oil (182 mg,
72%) with an E/ Z ratio of 92:8 and a γ/R ratio of 94:6 as
indicated by capillary GC analysis of the unpurified reaction
mixture. Spectral data of the major isomer (E)-3d was identical
to that reported in the literature for the (E)-isomer:28 GC tR
1
4.4 min (DB-1, 125 °C, 16 psi); H NMR (CDCl3, 500 MHz) δ
7.47-7.49 (m, 2H), 7.29-7.34, (m, 3H), 5.42 (dd, J ) 15.1, 8.0
Hz, 1H), 5.21 (dq, J ) 15.1, 6.4 Hz, 1H), 1.74 (m, 1H), 1.64 (d,
J ) 6.4 Hz, 3H), 1.00 (d, J ) 7.2 Hz, 3H), 0.24 (s, 6H); 13C
NMR (CDCl3, 125 MHz) δ 138.2, 134.0, 133.4, 128.8, 127.5,
121.3, 25.5, 18.2, 13.9, -4.8, -5.4.
(()-(Z)-1,2-Bis(d im et h ylp h en ylsilyl)-3-p en t en e [(Z)-
3a ]. Using the optimized procedure given for (Z)-3c with
carbamate 13a and (dimethylphenylsilyl)methylmagnesium
chloride provided (Z)-3a , after purification by flash chroma-
tography (pentane), as a colorless oil (136 mg, 68%) with an
(71) Details are provided as Supporting Information.
(72) Fleming, I.; Gil, S.; Sarkar, A. K.; Schmidlin, T. J . Chem. Soc.,
Perkin Trans. 1 1992, 3351-3361.

1612 J . Org. Chem., Vol. 65, No. 6, 2000
Smitrovich and Woerpel
3H); 13C NMR (CDCl3, 125 MHz) δ 139.2, 133.9, 128.8, 128.7,
127.5, 123.0, 35.0, 28.9, 23.9, 20.6, 13.0, -2.9, -3.7.
cm-1; HRMS (EI-GCMS) m/z calcd C14H32Si2 (M+) 256.2042,
found 256.2043. Anal. Calcd for C14H32Si2: C, 65.54; H, 12.57.
Found: C, 65.27; H, 12.41.
(()-(Z)-3-(Dim et h ylp h en ylsilyl)-2,2-d im et h yl-4-h ex-
en e [(Z)-3g]. Using the optimized procedure given for (Z)-3c
with carbamate 13a and tert-butylmagnesium chloride pro-
vided (Z)-3g, after purification by flash chromatography (pen-
tane), as a colorless oil (135 mg, 54%) with an E/ Z ratio of
7:93 and a γ/R ratio of >99:1 as indicated by capillary GC
analysis of the unpurified reaction mixture. The major isomer
was assigned as the (Z)-alkene by the value of the coupling
constant of the olefinic protons (J ) 11.0 Hz): GC tR 4.9 min
(DB-1, 150 °C, 16 psi); 1H NMR (CDCl3, 500 MHz) δ 7.50-
7.55 (m, 2H), 7.30-7.32 (m, 3H), 5.46 (dq, J ) 11.0, 6.3 Hz,
1H), 5.41 (m, 1H), 2.02 (d, J ) 9.9 Hz, 1H), 1.37 (d, J ) 5.0
Hz, 3H), 0.86 (s, 9H), 0.36 (s, 3H), 0.30 (s, 3H); 13C NMR
(CDCl3, 125 MHz) δ 140.2, 134.1, 129.8, 128.5, 127.4, 123.0,
40.3, 34.0, 30.5, 12.8, -1.4, -1.6; IR (thin film) 3010, 2955,
1642 cm-1; HRMS (EI-GCMS) m/z calcd for C16H26Si (M+)
246.1804, found 246.1815.
(()-1-(Dim eth ylph en ylsilyl)-1-ph en yl-2-bu ten e (3h ). Us-
ing the optimized procedure given for (Z)-3c with carbamate
13a and phenylmagnesium chloride provided 3h , after puri-
fication by flash chromatography (pentane), as a colorless oil
(151 mg, 57%) with an E/ Z ratio of 58:42 and a γ/R ratio of
97:3 as indicated by capillary GC analysis of the unpurified
reaction mixture. Spectral data were identical to that reported
in the literature for the (E)-isomer28 and (Z)-isomer:72 GC (E)-
3h : tR 7.9 min, (Z)-3h : tR 8.1 min (DB-1, 5 min at 150 °C then
ramped at 20 °C/min to 250 °C, 16 psi).
(()-(Z)-4-(t er t -Bu t yld im e t h ylsilyl)-2-m e t h yl-5-h e p -
ten e [(Z)-8b]. Using the optimized procedure given for (Z)-
3c with carbamate 13b and isobutylmagnesium chloride
provided (Z)-8b, after purification by flash chromatography
(pentane), as a colorless oil (140 mg, 95%) with an E/ Z ratio
of 7:93 and a γ/R ratio of 97:3 as indicated by capillary GC
analysis of the unpurified reaction mixture. The major isomer
was assigned as the (Z)-alkene by the value of the coupling
constant of the olefinic protons (J ) 10.8 Hz): GC tR 3.4 min
(DB-1, 125 °C, 16 psi); 1H NMR (CDCl3, 500 MHz) δ 5.32 (dq,
J ) 10.8, 6.7 Hz, 1H), 5.17 (m, 1H), 2.09 (m, 1H), 1.59 (d, J )
6.6 Hz, 3H), 1.51 (m, 1H), 1.33 (m, 1H), 1.20 (m, 1H), 0.91 (s,
9H), 0.86 (d, J ) 6.5 Hz, 3H), 0.81 (d, J ) 6.5 Hz, 3H), -0.07
(s, 3H), -0.09 (s, 3H);13C NMR (CDCl3, 125 MHz) δ 133.5,
120.6, 39.9, 27.4, 26.7, 24.1, 23.5, 20.8, 17.7, 13.3, -7.0, -7.3;
IR (thin film) 2954, 1645 cm-1; HRMS (EI-GCMS) m/z calcd
for C14H30Si (M+) 226.2117, found 226.2115. Anal. Calcd for
(()-(E)-2-(ter t-Bu tyld im eth ylsilyl)-1-(tr im eth ylsilyl)-3-
p en ten e [(E)-8c]. Using the optimized procedure given for
(Z)-3c with carbamate 13b and (trimethylsilyl)methyllithium
provided (E)-8c, after purification by flash chromatography
(pentane), as a colorless oil (192 mg, 75%) with an E/ Z ratio
of 76:24 and a γ/R ratio of >99:1 as indicated by capillary GC
analysis of the unpurified reaction mixture. The major isomer
was assigned as the (Z)-alkene by the value of the coupling
constant of the olefinic protons (J ) 15.1 Hz): GC tR 5.4 min
(DB-1, 100 °C to 250 °C at 5 °C/min, 16 psi); 1H NMR (CDCl3,
500 MHz) δ 5.23 (m, 1H), 5.19 (dd, H ) 15.1, 5.8 Hz, 1H), 1.71
(ddd, J ) 11.8, 9.1, 2.7 Hz, 1H), 1.62 (d, J ) 5.1 Hz, 3H), 0.89
(s, 9H), 0.63 (dd, J ) 14.9, 2.6 Hz, 1H), 0.56 (dd, J ) 14.8,
11.9 Hz, 1H), -0.04 (s, 9H), -0.09 (s, 3H), -0.10 (s, 3H); 13C
NMR (CDCl3, 125 MHz) δ 135.1, 121.4, 27.5, 25.9, 17.9, 17.8,
16.5, -0.7, -7.2, -7.6; IR (thin film) 2929, 1643 cm-1; HRMS
(EI-GCMS) m/z calcd C14H32Si2 (M+) 256.2042, found 256.2044.
Anal. Calcd for C14H32Si2: C, 65.54; H, 12.57. Found: C, 65.56;
H, 12.74.
(()-1-(Dim et h ylp h en ylsilyl)-1-p h en yl-4-b u t en e [(E)-
3h ]. Using the optimized procedure given for (Z)-3c with
carbamate 18a and phenyllithium provided (E)-3h , after
purification by flash chromatography (pentane), as a colorless
oil (121 mg, 55%) with an E/ Z ratio of >99:1 and a γ/R ratio
of >99:1 as indicated by capillary GC analysis of the unpurified
reaction mixture. 1H NMR and 13C NMR spectral data were
identical to that of a sample of 3h prepared from 13a and to
that reported in the literature28 for the (E)-isomer: 1H NMR
(CDCl3, 500 MHz) δ 7.26-7.36 (m, 5H), 7.15-7.18 (m, 2H),
7.05-7.07 (m, 1H), 6.90-6.95 (m, 2H), 5.71-5.81 (m, 1H), 5.33
(m, 1H), 3.06 (d, J ) 9.8 Hz, 1H), 1.66 (dd, J ) 6.4, 1.0 Hz,
3H), 0.24 (s, 3H), 0.22 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ
142.4, 137.1, 134.3, 129.9, 129.0, 128.1, 127.4, 124.5, 124.0,
42.5, 18.1, -4.3, -4.7.
(()-(E)-3-(ter t-Bu tyld im eth ylsilyl)-2-m eth yl-4-h exen e
[(E)-8d ]. Using the optimized procedure given for (Z)-3c with
carbamate 18b (11:89 ) E:Z) and isopropylmagnesium chloride
provided (E)-8d , after purification by flash chromatography
(pentane), as a colorless oil (180 mg, 85%) with an E/ Z ratio
of 90:10 and a γ/R ratio of >99:1 as indicated by capillary GC
analysis of the unpurified reaction mixture: GC tR 2.7 min
(DB-1, 5 min at 125 °C then ramped to 250 °C at 10 °C/min,
16 psi); 1H NMR (CDCl3, 500 MHz) δ 5.32 (m, 1H), 5.25 (dq, J
) 14.9, 5.9 Hz, 1H), 1.91 (m, 1H), 1.67 (d, J ) 5.8 Hz, 3H),
1.56 (dd, J ) 10.6, 3.3 Hz, 1H), 0.85-0.88 (m, 15H), -0.02 (s,
3H), -0.05 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 129.3, 125.3,
37.6, 28.5, 27.2, 23.9, 19.8, 18.1, 17.7, -5.7, -6.0; IR (thin film)
2856, 1472 cm-1; HRMS (EI-GCMS) m/z calcd for C13H28Si
(M+) 212.1960, found 212.1964. Anal. Calcd for C13H28Si: C,
73.50; H, 13.28. Found: C, 73.77; H, 13.36.
C
14H30Si: C, 74.25; H, 13.35. Found: C, 74.29; H, 13.39.
(()-(E )-4-(t er t -Bu t yld im e t h ylsilyl)-2-m e t h yl-5-h e p -
ten e [(E)-8b]. Using the optimized procedure given for (Z)-
3c with carbamate 13b and isobutyllithium provided (E)-8b,
after purification by flash chromatography (pentane), as a
colorless oil (175 mg, 77%) with an E/ Z ratio of 91:9 and a
γ/R ratio of >99:1 as indicated by capillary GC analysis of the
unpurified reaction mixture: GC tR 3.1 min (DB-1, 125 °C, 16
psi); 1H NMR (CDCl3, 500 MHz) δ 5.20 (m, 2H), 1.71 (m, 1H),
1.64 (d, J ) 4.8 Hz, 3H), 1.57 (m, 1H), 1.34 (m, 1H), 1.10 (m,
1H), 0.89 (s, 9H), 0.86 (d, J ) 6.7 Hz, 3H), 0.78 (d, J ) 6.5 Hz,
3H), -0.09 (s, 3H), -0.10 (s, 3H);13C NMR (CDCl3, 125 MHz)
δ 133.2, 122.3, 39.0, 28.7, 26.1, 24.1, 20.5, 18.0, 17.7, -7.1; IR
(thin film) 2956, 1659 cm-1; HRMS (EI-GCMS) m/z calcd for
(R)-(E)-1-(Dim et h ylp h en ylsilyl)-1-b u t en -3-ol
[(R)-
19a ].50,51 To a cooled (-23 °C) suspension of 4 Å molecular
sieves (crushed, 1.2 g) in 13 mL of CH2Cl2 was added Ti(O-i-
Pr)4 (1.23 mL, 4.20 mmol) followed by L-(+)-diisopropyl tartrate
(1.05 mL, 5.0 mmol). The resultant mixture was stirred for
30 min at -23 °C. A solution of (()-19a (4.3 g, 20.8 mmol) in
13 mL of CH2Cl2 (this solution was kept over molecular sieves
for 1 h prior to addition to the reaction mixture) was added to
the reaction mixture dropwise by cannula. After being stirred
for 1 h at -23 °C, the mixture was cooled to -40 °C, and tert-
butylhydroperoxide (4.55 M solution in CH2Cl2, 2.75 mL, 12.5
mmol) was added dropwise. The reaction mixture was allowed
to warm to -25 °C and stirred for 7 h. Dimethyl sulfide (0.920
mL, 12.5 mmol) was added, and the reaction mixture was
stirred for 30 min and then allowed to warm to 22 °C.
Saturated aqueous potassium sodium tartrate (2.4 mL), Et2O
(2.4 mL), sodium fluoride (14.5 g), and Celite (8.3 g) were added
sequentially, and the resultant slurry was stirred for 30 min.
The slurry was filtered and washed with 100 mL of CH2Cl2.
The filtrate was concentrated in vacuo to provide a yellow oil.
Purification by flash chromatography (5:95 to 20:80 EtOAc/
hexanes) provided (R)-19a as a pale yellow oil (1.89 g, 44%,
C
C
14H30Si (M+) 226.2117, found 226.2122. Anal. Calcd for
14H30Si: C, 74.25; H, 13.35. Found: C, 74.41; H, 13.44.
(()-(Z)-2-(ter t-Bu tyld im eth ylsilyl)-1-(tr im eth ylsilyl)-3-
p en ten e [(Z)-8c]. Using the optimized procedure given for
(Z)-3c with carbamate 13b and (trimethylsilyl)methylmagne-
sium provided (Z)-8c, after purification by flash chromatog-
raphy (pentane), as a colorless oil (198 mg, 78%) with an E/ Z
ratio of 6:94 and a γ:R ratio of >99:1 as indicated by capillary
GC analysis of the unpurified reaction mixture: GC tR 6.0 min
(DB-1, 100 °C to 250 °C at 5 °C/min, 16 psi); 1H NMR (CDCl3,
500 MHz) δ 5.21 (m, 2H), 2.10 (m, 1H), 1.59 (d, J ) 5.0 Hz,
3H), 0.91 (s, 9H), 0.73 (dd, J ) 14.8, 2.0 Hz, 1H), 0.54 (dd, J
) 14.8, 12.0 Hz, 1H), -0.03 (s, 9H), -0.07 (s, 3H), -0.10 (s,
3H); 13C NMR (CDCl3, 125 MHz) δ 135.4, 119.3, 27.6, 20.6,
17.9, 17.6, 13.6, -0.9, -7.2, -7.4; IR (thin film) 2929, 1643

Stereoselective Synthesis of (Z)- and (E)-Allylic Silanes
J . Org. Chem., Vol. 65, No. 6, 2000 1613
g94% ee by 1H NMR spectroscopic analysis of the Mosher
ester).71 The spectral data were identical to that reported in
the literature:69 1H NMR (CDCl3, 500 MHz) δ 7.51-7.54 (m,
2H), 7.34-7.37 (m, 3H), 6.14 (dd, J ) 18.7, 4.9 Hz, 1H), 5.97
(d, J ) 18.7 Hz, 1H), 4.32 (m, 1H), 1.55 (d, J ) 4.4 Hz, 1H),
1.28 (d, J ) 6.5 Hz, 3H), 0.36 (s, 6H); 13C NMR (CDCl3, 125
MHz) δ 151.4, 138.5, 133.8, 129.0, 127.8, 125.9, 70.4, 22.9,
1H NMR (CDCl3, 500 MHz) δ 3.71 (m, 1H), 1.8 (m, 1H), 1.34-
1.50 (m, 5H), 1.26 (m, 2H), 0.95 (m, 9H); 13C NMR (CDCl3,
125 MHz) δ 69.7, 46.8, 40.3, 24.6, 23.5, 22.0, 18.8, 14.1; [R]23
D
-11.9 (c 1.04, CH3OH); literature:56 [R]23 -11.9 (c 1.04, CH3-
D
OH).
(R)-3-[1-(Dim eth ylp h en ylsilyl)-1-bu tyn yl] a ceta te [(R)-
17]. To a solution of (R)-16a (2.4 g, 11.7 mmol) in 12 mL of
CH2Cl2 were added pyridine (0.093 mL, 1.15 mmol), 4-(N,N-
dimethylamino)pyridine (1 mg, 0.008 mmol), and acetic an-
hydride (0.108 mL, 1.15 mmol). After 12 h, 25 mL of saturated
aqueous NH4Cl and 25 mL of CH2Cl2 were added. The layers
were separated, and the aqueous layer was washed with 3 ×
25 mL of CH2Cl2. The combined organic layers were washed
with brine, dried (MgSO4), filtered, and concentrated in vacuo
to afford a yellow oil. Purification by flash chromatography
(5:95 EtOAc/hexanes) provided (R)-17 as a colorless liquid (2.68
g, 93%). The spectral data were identical to that reported in
the literature:37 [R]23D +104 (c 1.46, CH2Cl2) [lit.37 [R]23D +61.0
(c 1.45, CH2Cl2)]; 1H NMR (CDCl3, 500 MHz) δ 7.60-7.62 (m,
2H), 7.36-7.39 (m, 3H), 5.51 (q, J ) 6.7 Hz, 1H), 2.12 (s, 3H),
1.51 (d, J ) 6.9 Hz, 3H), 0.42 (s, 6H); 13C NMR (CDCl3, 125
MHz) δ 169.7, 136.5, 133.6, 129.5, 127.9, 105.3, 87.4, 60.6, 21.4,
21.1, -1.0; IR (thin film) 3070, 2982, 2179, 1748 cm-1; HRMS
(CI/isobutane) m/z calcd for C14H18O2Si (M+) 246.1076, found
246.1068. Anal. Calcd for C14H18O2Si: C, 68.25; H, 7.36.
Found: C, 68.37; H, 7.37.
-2.6; [R]23 -5.3 (c 0.8, CHCl3).
D
(R)-1-(Dim et h ylp h en ylsilyl)-1-b u t en e-3-ol N-p h en yl-
ca r ba m a te [(R)-13a ]. Using the procedure given for (()-13a
with (R)-19a (1.64 g, 8.0 mmol) and phenyl isocyanate (0.910
mL, 8.7 mmol) provided (R)-13a as a pale yellow oil (2.32 g,
89%). (R)-13a was identical to (()-13a by 1H NMR and 13C
NMR spectroscopic analyses: [R]23 +36.8 (c 1.0, CHCl3).
D
(S)-(Z)-4-(Dim eth ylph en ylsilyl)-2-m eth yl-5-h epten e [(S)-
(Z)-3c]. Using the optimized procedure given for (Z)-3c with
carbamate (R)-13a (1.23 g, 3.78 mmol), MeLi (1.3 M solution
in hexanes, 2.9 mL, 3.8 mmol), CuI (720 mg, 3.78 mmol), LiCl
(321 mg, 7.57 mmol), and isobutylmagnesium chloride (1.1 M
solution in THF, 4.3 mL, 4.7 mmol) provided (Z)-3c, after
purification by flash chromatography (pentane), as a colorless
oil (834 mg, 90%) with an E/ Z ratio of 6:94 and a γ:R ratio of
95:5 as indicated by capillary GC analysis of the unpurified
reaction mixture. The 1H and 13C NMR spectroscopic data
matched that of a sample of racemic material: [R]23 +85.1 (c
D
1.02, CHCl3).
(R)-2-Meth yl-4-(d im eth ylp h en ylsilyl)h ep ta n e [(R)-29].
To a solution of (S)-(Z)-3c (728 mg, 2.95 mmol) in 15 mL of
dioxane were added tosylhydrazide (5.5 g, 29.5 mmol) and
triethylamine (4.1 mL, 29.4 mmol). The reaction mixture was
heated at reflux for 11 h. After the reaction mixture was cooled
to 23 °C, additional tosylhydrazide (1.4 g, 7.5 mmol) and
triethylamine (1.0 mL, 7.2 mmol) were added, and the reaction
mixture was heated to reflux. After 14 h, the reaction mixture
was allowed to cool to 22 °C and was diluted with 50 mL of
Et2O. The mixture was washed with saturated aqueous Na2-
CO3. The layers were separated, and the aqueous layer was
washed with 3 × 50 mL of Et2O. The combined organic layers
were washed with H2O and brine, dried (Na2SO4), filtered, and
concentrated in vacuo. 1H NMR analysis of the unpurified
reaction mixture indicated that the reaction was incomplete.
The reaction mixture was submitted to flash chromatography
(pentane) to remove the sulfur containing impurities, and the
recovered material was resubmitted to the hydrogenation
conditions using the same amount of reagents listed above.
After being heated at reflux for 30 h, the reaction mixture was
allowed to cool to 22 °C and was worked up as described above.
Purification by flash chromatography provided (R)-29 as a
colorless oil (663 mg, 86%): 1H NMR (CDCl3, 500 MHz) δ
7.49-7.51 (m, 2H), 7.32-7.34 (m, 3H), 1.55 (m, 1H), 1.15-
1.38 (m, 6H), 0.87 (m, 1H), 0.81 (m, 6H), 0.77 (d, J ) 6.5 Hz,
3H), 0.25 (s, 6H); 13C NMR (CDCl3, 125 MHz) δ 139.4, 133.9,
128.6, 127.6, 39.5, 32.8, 26.7, 23.4, 22.4, 22.3, 21.9, 14.6, -3.8,
(R)-(Z)-3-[1-(Dim eth ylp h en ylsilyl)-1-bu ten yl] Aceta te
[(R)-27]. Using the procedure given for (()-27 with propargylic
acetate (R)-17 provided (R)-27 as a colorless liquid (2.41 g,
90%) with an E/ Z ratio of 7:93 as indicated by capillary GC
analysis of the unpurified reaction mixture. The product was
identical to (()-27 by 1H NMR and 13C NMR spectroscopic
analyses (vide supra).
(R)-(Z)-1-(Dim eth ylp h en ylsilyl)-1-bu ten -3-ol [(R)-28a ].
Using the procedure given for (()-28a with allylic acetate (R)-
27 provided (R)-28a , after two successive purifications with
6% AgNO3/SiO2, as a colorless liquid (1.35 g, 78%) with an E/ Z
ratio of 3:97 as indicated by capillary GC analysis. The product
was identical to (()-28a by 1H NMR and 13C NMR spectro-
scopic analysis: [R]23 +4.2 (c 1.45, CHCl3) [lit.37 [R]23 +2.76
D
D
(c 1.45, CHCl3)].
(R)-(Z)-1-(Dim eth ylp h en ylsilyl)-1-bu ten -3-ol N-P h en yl-
ca r ba m a te [(R)-18a ]. Using the procedure given for (()-13a
with alcohol (R)-28a provided (R)-18a as a white solid (1.80
g, 88%). The product was identical to (()-18a by 1H NMR and
13C NMR spectroscopic analyses (vide supra): [R]23 -76.1 (c
D
1.02, CHCl3).
(S)-(E)-4-(Dim eth ylph en ylsilyl)-2-m eth yl-5-h epten e [(S)-
(E)-3c]. Using the optimized procedure given for (Z)-3c with
carbamate (R)-18a (850 mg, 2.61 mmol), MeLi (1.1 M solution
in Et2O, 2.4 mL, 2.6 mmol), CuI (500 mg, 2.6 mmol), LiCl (223
mg, 5.3 mmol), and isobutylmagnesium chloride (1.0 M solu-
tion in THF, 2.6 mL, 2.6 mmol) provided (S)-(E)-3c, after
purification by flash chromatography (pentane), as a colorless
oil (600 mg, 93%) with an E/ Z ratio of 3:97 and a γ/R ratio of
98:2 as indicated by capillary GC analysis of the unpurified
reaction mixture. The product was identical to a sample of (()-
(E)-3c prepared from (()-18a by 1H and 13C NMR spectroscopic
-3.9; IR (thin film) 3069, 2956 cm-1; [R]23 +8.0 (c 1.01,
D
CHCl3); HRMS (EI-GCMS) m/z calcd for C15H25Si (M - CH3)+
233.1725, found 233.1725. Anal. Calcd for C16H28Si: C, 77.34;
H, 11.36. Found: C, 77.50; H, 11.28.
(R)-2-Meth yl-4-h ep ta n ol [(R)-21]. To a cooled (0 °C)
solution of tert-butylhydroperoxide (90%, 1.6 mL, 14.4 mmol)
in 1.5 mL of N-methylpyrrolidinone was added KH (powder,
580 mg, 14.5 mmol) cautiously in five portions.55 To the
resultant foamy reaction mixture was added by syringe a
solution of (R)-29 (627 mg, 2.52 mmol) in 1.5 mL of N-
methylpyrrolidinone. The reaction mixture was allowed to
warm to 22 °C and was heated at 90 °C for 16 h. After the
reaction mixture was allowed to cool to 22 °C, Na2S2O3
(anhydrous, 4.5 g, 27.0 mmol) and 1.0 mL of H2O were added.
After being stirred for 1 h, the reaction mixture was filtered
through a pad of SiO2, washing with 200 mL of 20:80 Et2O/
pentane. The filtrate was washed with 50 mL of 1 M NaOH,
dried (Na2SO4), filtered, and concentrated in vacuo. Purifica-
tion by flash chromatography (10:90 Et2O/pentane) provided
21 as a colorless, volatile oil (172 mg, 51%, 88% ee by 1H NMR
spectroscopic analysis of the R-methylbenzylcarbamate).71
Spectral data were identical to that reported in the literature:56
analysis (vide supra): [R]23 +28.3 (c 1.03, CHCl3).
D
(R)-2-Meth yl-4-(d im eth ylp h en ylsilyl)-h ep ta n e [(R)-29].
To a solution of (S)-(E)-3c (570 mg, 2.31 mmol) in 23 mL of
dioxane was added tosylhydrazide (4.3 g, 23.1 mmol) and
triethylamine (3.2 mL, 23.0 mmol).54 The reaction mixture was
heated at reflux for 24 h. After the reaction mixture was cooled
to 23 °C, additional tosylhydrazide (2.2 g, 11.5 mmol) and
triethylamine (1.6 mL, 11.5 mmol) were added, and the
reaction mixture was heated to reflux. After 10 h, the reaction
mixture was allowed to cool to 22 °C and was diluted with 75
mL of Et2O. The mixture was washed with saturated aqueous
NaHCO3 (20 mL). The layers were separated and the aqueous
layer was extracted with 3 × 50 mL of hexanes. The combined
organic layers were washed with H2O and brine (20 mL each),
dried (Na2SO4), filtered, and concentrated in vacuo. Purifica-
tion by flash chromatography (pentane) provided 29 as a
colorless liquid (556 mg, 97%). The product was identical to a

1614 J . Org. Chem., Vol. 65, No. 6, 2000
Smitrovich and Woerpel
sample of 29 prepared from (S)-(Z)-3c by 1H and 13C NMR
(R)-2-Meth yl-4-h ep ta n ol [(R)-21]. Using the procedure
given for (R)-21 derived from carbamate (R)-13a with silane
(R)-29 provided the product as a colorless, volatile oil (131 mg,
spectroscopic analyses (vide supra): [R]23 +13.2 (c 1.01,
D
CHCl3).
1
(R)-2-Meth yl-4-h ep ta n ol [(R)-21]. Using the procedure
given for (R)-21 derived from carbamate (R)-13a with silane
(R)-29 provided the product as a colorless, volatile oil (127 mg,
63%, 94% ee by H NMR spectroscopic analysis of the R-me-
thylbenzylcarbamate).71 1H and 13C NMR spectral data were
identical to that reported in the literature and to that of a
sample of (R)-21 derived from allylic carbamate (R)-12a (vide
1
45%, 92% ee by H NMR spectroscopic analysis of the R-me-
thylbenzylcarbamate).71 1H and 13C NMR spectral data were
identical to that reported in the literature56 and to that of a
supra): [R]23 -11.4 (c 1.05, CH3OH).
D
sample of (R)-21 derived from allylic carbamate (R)-13a : [R]23
-10.6 (c 1.03, CH3OH).
D
Ack n ow led gm en t. This research was supported by
a CAREER Award from the National Science Founda-
tion (CHE-9701622). J .H.S. thanks the American As-
sociation of University Women for an American Fellow-
ship. K.A.W. thanks the American Cancer Society, the
Research Corporation, Glaxo-Wellcome, and the Camille
and Henry Dreyfus Foundation for awards to support
research. We thank Dr. J ohn Greaves and Dr. J ohn
Mudd for mass spectrometric data.
(S)-(E)-4-(Dim eth ylph en ylsilyl)-2-m eth yl-5-h epten e [(S)-
(E)-3c]. The optimized procedure given for (Z)-3c with car-
bamate (R)-18a (793 mg, 2.44 mmol), MeLi (1.3 M solution in
Et2O, 1.9 mL, 2.5 mmol), CuI (465 mg, 2.4 mmol), LiCl (210
mg, 5.0 mmol), and isobutyllithium (0.5 M solution in Et2O/
pentane, 4.9 mL, 2.5 mmol) was used. The product (S)-(E)-3c
was obtained, after purification by flash chromatography
(pentane), as a colorless oil (561 mg, 93%) with an E/ Z ratio
of >99:1 and a γ/R ratio of 100:0 as indicated by capillary GC
analysis of the unpurified reaction mixture. The product was
identical to (()-(E)-3c prepared from (()-18a by 1H NMR and
Su p p or tin g In for m a tion Ava ila ble: Full experimental
and analytical data for the nickel-coupling and Wittig routes;
experimental details for reactions with allylic carboxylates and
for reactions described in Table 3; preparations of Grignard
and alkyllithium reagents; details of the determination of
enantiomeric ratios for reactions of nonracemic carbamates;
and 1H NMR data for select compounds; GC traces used to
determine stereoisomer ratios. This material is available free
of charge via the Internet at http://pubs.acs.org.
13C NMR spectroscopic analyses (vide supra): [R]23 +33.7 (c
D
1.03, CHCl3).
(R)-2-Meth yl-4-(d im eth ylp h en ylsilyl)h ep ta n e [(R)-29].
The procedure described for the previous synthesis of (R)-29
was used on the sample of (S)-(E)-3c prepared in the previous
procedure. Purification by flash chromatography (pentane)
provided (R)-29 as a colorless liquid (518 mg, 97%). The
product was identical to a sample of (R)-29 prepared from
allylic silane (S)-(Z)-3c by 1H and 13C NMR spectroscopic
analyses (vide supra): [R]23 +15.3 (c 1.01, CHCl3).
J O991312R
D