Intramolecular Alkyne Carbomercuration by Allylic Silanes: A New Carbon-Carbon Bond-Forming Reaction

Full text of DOI:10.1021/jo971478x

J . Org. Chem. 1997, 62, 8595-8599
8595
In tr a m olecu la r Alk yn e Ca r bom er cu r a tion
by Allylic Sila n es: A New Ca r bon -Ca r bon
Bon d -F or m in g Rea ction
5-8, respectively, each as a 1:1, E:Z alkene mixture
Scheme 1). Methyl- and trimethylsilyl-substituted
(
alkynes 9 and 10 were prepared from 8 in quantitative
yields, whereas terminally unsubstituted and methyl-
substituted alkynyl (Z)-allylic silanes (11 and 12, respec-
tively) were obtained in several steps from acetol.
Separate treatment of the alkynyl-tethered allylic
2
He Huang and Craig J . Forsyth*
Department of Chemsitry, University of Minnesota,
Minneapolis, Minnesota 55455
silanes (5-12) with HgCl (1.1 equiv) and HMDS (0.2
2 2
equiv) in CH Cl (0.2 M) at room temperature did indeed
Received August 7, 1997
promote intramolecular carbon-carbon bond formation
in all but one case (Table 1). After the indicated reaction
time, the vinyl mercurial products were isolated by silica
gel column chromatography in the yields indicated in
Table 1. Five-exo ring formation proceeded smoothly
(14-19 h) from 5 and 8-12 to give the exocyclic vinyl
mercurial products 13 and 16-18, respectively, in mod-
erate yields (entries 1 and 4-8). Six-exo ring formation
leading from 6 to 14 was lower yielding (36%, entry 2)
and accompanied by chloromercuration of the alkyne of
6. Attempted formation of a seven membered carbocycle
Intramolecular alkyne carbomercuration (IAC) of alky-
nyl-tethered enol silanes is a mild, versatile, and high-
yielding method for the formation of cyclic products
bearing a mercuric-functionalized exocyclic alkene â to
a carbonyl group.1 The vinyl mercurial moiety of the
products is synthetically valuable because it may be
stereoselectively transformed into a variety of additional
functional groups.2 This synthetic utility has been
demonstrated in the total syntheses of several structur-
ally diverse natural products.3-6 The configuration of the
(15) from 7 was unsuccessful. Instead, mercuric chloride
vinyl mercurial product, whether the mercuric substitu-
ent is syn or anti with respect to the carbonyl, is a
diagnostic indicator of plausible mechanistic pathways
leading from enol silane to carbomercuration product.
Strict syn addition of the R-carbon and mercuric salt to
the alkyne was originally postulated to occur from either
addition across the alkyne again occurred, while the
allylic silane moiety remained intact (entry 3).
In general, the standard conditions used for the IAC
reactions of silyl enol ethers provided the best results for
carbon-carbon bond formation of the allylic silanes
examined here. Attempts to increase the yields of the
cyclizations by heating the reaction mixtures or using
different types of mercuric salts or solvents (diethyl ether,
acetonitrile, or THF) were unsuccessful. The use of
hexamethyldisilazane was found to be beneficial, aiding
the suspension of the mercuric salt and serving as an
acid scavenger.1 Both the allylic silane and alkyne
an intermediate R-carbonyl mercurial or an O-mercury
enolate.1
,7
However, because only anti vinyl mercurial
products have since been observed from IAC reactions
of enol silanes containing terminally unsubstituted
alkynes,3
-5
R-carbonyl mercurial or O-mercury enolate
intermediates may be unnecessary. This suggested that
other types of latent carbon nucleophiles besides enol
derivatives might also undergo efficient intramolecular
alkyne carbomercuration to tethered, electrophilically
activated alkynes. In particular, replacement of the enol
silane oxygen by carbon provides a test for the interme-
diacy of enol derived organomercurials in the IAC
process. The utility of alkynyl-tethered allylic silanes for
unprecedented intramolecular carbon-carbon bond for-
mation upon mercuric salt activation was therefore
examined. This has resulted in the stereoselective
formation of functionalized carbo- and heterocycles and
means to control the E/Z configuration of the vinyl
mercurial products. Details of these initial studies are
reported here.
moiety of 5 were unreactive toward HgBr
under the standard reaction conditions. However, intro-
duction of HgF , either as the salt or generated in situ
from HgCl and TBAF, led to rapid (<5 min) addition of
2 2
and HgI
2
2
1
3
mercuric and fluoride ions to the triple bond but without
disruption of the allylic silane moiety. Methyl substitu-
tion of either the alkene or alkyne allowed the cycliza-
tions to proceed in yields comparable to those of the
unsubstituted substrates (entries 4-8). However, tri-
methylsilyl substitution of the alkyne (10) dramatically
impacted both the rate (45 h, entry 6) and stereoselec-
tivity of the reaction, yet provided a comparable yield of
cyclized product (18Z). Substrates bearing allylic prop-
argylic ether linkages (11 and 12) led to tetrahydrofuran
products (19 and 20, entries 7 and 8).
A few representative alkynyl-tethered allylic silanes
were synthesized conveniently from the corresponding
All of these reactions are highly stereoselective; each
carbomercuration product was obtained as only a single
alkene stereoisomer. Although direct spectroscopic evi-
dence to assign the vinyl mercurial configurations of 13
and 14 was not obtained, the vinyl configurations of 16-
ketones or aldehydes using a common key phosphine
8
intermediate, TMSCH
2
CH
2
dPPh
3
.
Treatment of alky-
9
10
11
12
nyl aldehydes 1, 2, and 3 or methyl ketone 4 with
in situ prepared TMSCH CH dPPh gave allylic silanes
2
2
3
2
0 were determined by NOE experiments using the
(1) Drouin, J .; Boaventura, M. A.; Conia, J . M. J . Am. Chem. Soc.
1
985, 107, 1726-1729.
allylic methyl substituent as a secure spectroscopic
handle. In the vinyl mercurial products 16E and 19,
derived from terminally unsubstituted alkynes 8 and 11,
respectively, the newly formed carbon-carbon bond and
mercuric salt are anti (entries 4 and 7). Terminal
methyl-substituted alkynes 9 and 12 also gave anti
products (entries 5 and 8), and it is therefore likely that
(
2) Larock, R. C. Tetrahedron 1982, 38, 1713-1754.
(
3) Forsyth, C. J .; Clardy, J . J . Am. Chem. Soc. 1990, 112, 3497-
3
505.
(
(
(
4) Huang, H.; Forsyth, C. J . J . Org. Chem. 1995, 60, 2773-2779.
5) Huang, H.; Forsyth, C. J . J . Org. Chem. 1995, 60, 5746-5747.
6) Frontier, A. J .; Raghavan, S.; Danishefsky, S. J . J . Am. Chem.
Soc. 1997, 119, 6686-6687.
(7) Boaventura, M. A.; Drouin, J .; Theobald, F.; Rodier, N. Bull. Soc.
Chim. Fr. 1987, 1006-1014.
1
3 and 14 are also anti vinyl mercurials. However,
(
8) Fleming, I.; Paterson, I. Synthesis 1979, 446-448.
(9) Adams, T. C.; Combs, D. W.; Daves, G. D., J r.; Hauser, F. M. J .
Org. Chem. 1981, 46, 4582.
(12) Peterson, P. E.; Kamat, R. J . J . Am. Chem. Soc. 1969, 91, 4521-
(
10) Ma, D.; Lu, X. Tetrahedron 1990, 46, 6319-6330.
4527.
(11) Kalabin, G. A.; Krivdin, L. B.; Proidakov, A. G.; Kushnarev, D.
(13) Larock, R. C. In Comprehensive Organometallic Chemistry II;
Elsevier Science: New York, 1995; Vol. 11; p 394.
F. Zh. Org. Khim. 1983, 19, 476.
S0022-3263(97)01478-3 CCC: $14.00 © 1997 American Chemical Society

8
596 J . Org. Chem., Vol. 62, No. 24, 1997
Notes
Sch em e 1
The anti selectivity in the cyclizations of methyl and
terminally unsubstituted alkynes 8, 9, 11, and 12 is
consistent with simple trans addition of the nucleophilic
â-allyl silane carbon to a mercuric salt-complexed alkyne,
3
-5
analogous to anti selective silyl enol ether IAC reactions.
It is interesting and synthetically useful that simple
trimethylsilyl substitution of the starting alkyne led
exclusively to a syn vinyl mercurial product (18Z).
Although further studies are required to define the basis
of this reversal in stereoselectivity, contributing factors
may include steric interactions or more unique silicon
characteristics such as relative electropositivity and
â-carbocation stabilization potential. Stereoselectivity
2
may derive from partitioning of an sp -like carbomer-
curinium intermediate between anti (21) and syn (22)
orientations with respect to the tethered nucleophile.
Minimization of steric interactions in this model would
help to define which conformer undergoes carbon-carbon
bond formation, via either cis or trans addition1 of carbon
and mercury across the activated alkyne. Because the
allyilc silane moiety of 7 was unchanged under prolonged
IAC reaction conditions, it is unlikely that an allylic
organomercurial is generated en route to 18Z.
4
Ta ble 1
Carbon-carbon bond formation using this novel nu-
cleophile-electrophile pair complements alternative meth-
1
5-17
ods available for the synthesis of similar carbocycles.
The dramatic silicon effect observed here provides a
practical means for controling the configuration of the
functionalized exocyclic alkene, and the synthetic versa-
2
18-20
tility of the vinyl mercurial and vinyl silane
products
may provide access to a wide range of additional func-
tionality. This work also suggests that electrophilically
activated alkynes may be useful in a broader variety of
carbon-carbon bond-forming reactions. Although the
yields of the allylic silane IAC reactions reported here
a
b
Standard reaction conditions were used (see text). Isolated
are modest when compared to those of analogous ketone
c
yields. Only chloromercuration adducts were obtained (see text).
silyl enol ether-based reactions,1
,3-5
substantial improve-
ments may result from modifying the substitution on
silicon to increase the nucleophilicity of the allylic silane
moiety.21 The results of these and further studies to
define basis of the observed stereoselectivity and extend
the scope of this methodology will be reported in due
course.
terminal substitution of the alkyne with a trimethylsilyl
group led to complete reversal of stereoselectivity (entry
6
, 10 f 18Z). Here, net syn addition of mercuric chloride
and the allylic moiety to the alkyne places the vinyl
trimethylsilyl group anti to the newly formed carbon-
carbon bond in 18Z. The (Z)-selectivity observed in the
carbomercuration of 10 is analogous to that reported
previously in the IAC reaction of a (trimethylsilyl)alky-
(14) Both cis and trans additions of nucleophiles and mercuric ions
nyl-tethered silyl enol ether.7
to alkynes are known.13
(
15) Takayama, Y.; Gao, Y.; Sato, F. Angew. Chem., Int. Ed. Engl.
997, 36, 851-853.
16) Trost, B. M.; Romero, D. L.; Rise, F. J . Am. Chem. Soc. 1994,
16, 4268-4278.
1
(
1
(
17) Trost, B. M. Acc. Chem. Res. 1990, 23, 34-42.
(18) Tamao, K.; Akita, M.; Maeda, K.; Kumada, M. J . Org. Chem.
1
987, 52, 1100-1106.
(
19) On, H. P.; Lewis, W.; Zweifel, G. Synthesis 1981, 999-1001.
20) Chan, T. H.; Lau, P. W. K.; Mychajlowskij, W. Tetrahedron Lett.
(
1
977, 18, 3317-3320.
21) Omoto, K.; Fujimoto, H. J . Am. Chem. Soc. 1997, 119, 5366-
372.
(
5

Notes
J . Org. Chem., Vol. 62, No. 24, 1997 8597
Exp er im en ta l Section
(E,Z)-1-(Tr im eth ylsilyl)-2-d ecen -9-yn e (7). Neat 1,3-di-
aminopropane (APA, 160 mL) was added to NaH (7.61 g, 317
mmol) under Ar, and the mixture was heated at 70 °C for 30
min. The resulting solution was cooled to rt, and 2-octyn-1-ol
(5.00 g, 39.6 mmol) was added dropwise. After 40 min, an ice-
water mixture was added, and the resulting mixture was
extracted repeatedly with ether. The combined ether extract
was washed with H O, dilute aqueous HCl, H O, and a saturated
Gen er a l P r oced u r es. Unless otherwise noted, all reactions
were carried out under Ar or N in oven-dried glassware using
standard syringe, cannula, and septa techniques. Diethyl ether
and THF were distilled under N from Na/benzophenone ketyl.
Hexamethyldisilazane and CH Cl were distilled under N from
CaH , and dimethylformamide was distilled from BaO. Other
solvents were used as received. NaI, HgCl , and triphenyl-
2
2
2
2
2
2
2
2
2
2 4
aqueous NaCl solution. Drying over Na SO , filtration, and
methylphosphonium bromide were dried under vacuum (0.3
Torr, ca. 6-12 h) immediately prior to use. Silica gel column
chromatography was performed using Baker flash silica gel 60
concentration gave crude 7-octyn-1-ol (4.51 g):
1
H NMR (200
MHz) δ 3.60 (t, J ) 6.60 Hz, 2H), 2.12 (m, 2H), 1.90 (t, J ) 2.2
Hz, 1H), 1.60-1.24 (m, 9H). To a rt solution of crude 7-octyn-
(
40 µm) or ICN Silitech 69 (63-200 µm) and the solvent systems
indicated. Analytic and preparative TLC was performed with
.25 or 0.50 mm EM silica gel 60 F254 plates, respectively. NMR
spectra were obtained in CDCl and are referenced to residual
1
-ol (2.52 g, ca. 20.0 mmol) in CH
2 2
Cl (50 mL) was added PDC
(15.0 g, 40.0 mmol). After 2 h, the mixture was filtered through
0
a pad of silica gel, the filtrate was concentrated, and the residue
3
purified by silica gel column chromatography to give 7-octynal
1
13
CHCl
spectrometers used show deviations of less than 5 ppm.
E,Z)-1-(Tr im eth ylsilyl)-2-octen -7-yn e (5). Pyridinium chlo-
rochromate (4.30 g, 20.0 mmol) was added to a stirred rt solution
of 5-hexyn-1-ol (982 mg, 10.0 mmol) in CH Cl (30 mL). After 1
3
at 7.24 ppm ( H) and 77.0 ppm ( C). The mass
1
(
(
3, 1.00 g, 8.00 mmol, 40% yield from 2-octyn-1-ol): H NMR
200 MHz) δ 9.82 (t, J ) 1.2 Hz, 1H), 2.49 (m, 2H), 2.23 (m,
(
2H), 1.96 (t, J ) 2.0 Hz, 1H), 1.81-1.21 (m, 6H). Using the same
procedure as described in the preparation of 5 above (ca. 1.3
equiv of phosphorylidene), 3 (911 mg, 7.33 mmol) gave 7 (1.15
g, 5.53 mmol, 30% yield) as a colorless oil after silica gel column
chromatography (hexanes-ethyl acetate, 10:1, v/v): IR (neat)
2
2
h, the mixture was filtered through a pad of silica gel, and the
9
filtrate was concentrated to give crude 5-hexynal (1 , 960 mg,
1
ca. 10.0 mmol) as an oil: H NMR (200 MHz) δ 9.83 (t, J ) 1.2
-1 1
3
5
1
(
2
309, 2118, 1647, 1248 cm ; H NMR (500 MHz, E/Z ) 1:1) δ
Hz, 1H), 2.50-2.20 (m, 4H), 1.97 (t, J ) 2.0 Hz, 1H), 1.60 (m,
.36 (m, 1H), 5.22 (m, 1H), 2.17 (m, 2H), 1.96 (m, 2H), 1.91 (m,
2
H). To a magnetically stirred 0 °C suspension of methyltriph-
H), 1.52 (m, 2H), 1.45-1.32 (m, 6H), -0.01 (s, 4.5H), and -0.02
enylphosphonium bromide (4.64 g, 13.0 mmol) in THF (10 mL)
was added n-BuLi (5.60 mL, 2.50 M in hexanes, 14.0 mmol)
under Ar. The resulting dark red solution was allowed to warm
to rt and stir for 1 h. A mixture of NaI (3.90 g, 13 mmol) and
+
s, 4.5H); HRMS calcd for C13
H
28NSi (M + NH
4
) 226.1991, found
26.1995.
(
E,Z)-1-(Tr im eth ylsilyl)-3-m eth yl-2-octen -7-yn e (8). To a
9
stirred solution of crude 1 (19.20 g, ca. 200 mmol, prepared from
-hexyn-1-ol as described in the synthesis of 5 above) in THF
250 mL) was added slowly a solution of methylmagnesium
(
chloromethyl)trimethylsilane (1.82 mL, 13.0 mmol) in THF (10
5
(
mL) was heated under reflux for 1 h and then cooled to rt before
the above phosphorylidene solution was added via cannula. The
resulting mixture was stirred at rt for 14 h under Ar and then
cooled to 0 °C before n-BuLi (5.20 mL, 2.50 M in hexanes, 13.0
bromide (80 mL, 3 M in ether, 240 mmol) at -78 °C and under
Ar. After 3 h, aqueous HCl (1 N) was added until the reaction
mixture was at neutral pH, and the mixture was extracted with
8
mmol) was added. After being stirred for 30 min, the mixture
ether. The combined organic extract was washed with
a
was cooled to -78 °C and a solution of crude 1 (960 mg, ca. 10.0
mmol) in THF (10 mL) was added slowly. The resulting mixture
was allowed to warm to rt and stir over 14 h. Aqueous NH Cl
4
was added, the mixture was extracted with hexanes, and the
combined organic extract was washed with a saturated aqueous
NaCl solution, dried over Na SO , filtered, and concentrated.
2 4
Silica gel column chromatography of the residue (hexanes-ethyl
acetate, 10:1, v/v) gave 5 (318 mg, 1.80 mmol, 18% yield ) as a
saturated aqueous NaCl solution, dried over Na
2
SO , filtered,
4
and concentrated to give crude 6-heptyn-2-ol (11.0 g, ca. 100
1
mmol, ca. 50% yield from 1): H NMR (200 MHz) δ 3.64 (m,
1
1
H), 2.20 (m, 2H), 1.80 (t, J ) 2.4 Hz, 1H), 1.65-1.30 (m, 5H),
.10 (d, J ) 6.4 Hz, 3H). To a rt solution of crude 6-heptyn-2-ol
2 2
(11.0 g, ca. 100 mmol) in CH Cl (200 mL) was added PDC (45.1
g, 120 mmol). After 14 h, the mixture was filtered through a
pad of silica gel, the filtrate was concentrated, and the residue
was purified by silica gel column chromatography to give
-
1
1
colorless oil: IR (neat) 3309, 2117, 1644, 1248 cm ; H NMR
(
2
2
500 MHz, E/Z ) 1:1) δ 5.43 (m, 1H), 5.24 (m, 1H), 2.19 (dt, J )
6
-heptyn-2-one (4, 3.90 g, 36.0 mmol, 36% yield) as a clear oil:
.5, 7.0 Hz, 2H), 2.09 (m, 2H), 1.94 (t, J ) 2.5 Hz, 1H), 1.59 (m,
1
H NMR (200 MHz) δ 2.52 (t, J ) 6.4 Hz, 2H), 2.11 (s, 3H), 1.83
t, J ) 2.4 Hz, 1H), 1.51 (m, 2H). Using the same procedure as
H), 1.47 (d, J ) 8.5 Hz, 2H), 0.00 (s, 4.5H), and -0.01 (s, 4.5H);
(
+
HRMS calcd for C11
H
20Si (M ) 180.1335, found 180.1329.
described for the preparation of 5 above (ca. 1.3 equiv of
phosphorylidene), 6-heptyn-2-one (4, 2.00 g, 18.0 mmol) gave 8
(
E,Z)-1-(Tr im eth ylsilyl)-2-n on en -8-yn e (6). Neat 1,3-di-
aminopropane (APA, 160 mL) was added to NaH (7.20 g, 300
mmol) under Ar, and the mixture was heated at 70 °C for 30
min. The resulting solution was cooled to rt, and 3-heptyn-1-ol
12.6 g, 100 mmol) was added dropwise. After 40 min, an ice-
water mixture was added, and the resulting mixture was
extracted repeatedly with ether. The combined ether extract
(1.30 g, 6.70 mmol, 37% yield) as a colorless oil after silica gel
column chromatography (hexanes-ethyl acetate, 10:1, v/v): IR
-
1 1
(
5
neat) 3313, 2120, 1247 cm ; H NMR (300 MHz, E/Z ≈ 1:1) δ
(
.17 (m, 1H), 2.13 (m, 2H), 2.08 (m, 2H), 1.93 (m, 1H), 1.65
and 1.52 (s, ∼1:1, 3H), 1.54 (m, 2H), 1.37 (d, J ) 8.4 Hz, 2H),
+
-
0.03 (bs, 9H); HRMS calcd for C12
94.1491.
H
22Si (M ) 194.1488, found
was washed with H
2
O, dilute aqueous HCl, H
2
O, and a saturated
, filtration, and
1
aqueous NaCl solution. Drying over Na
concentration gave crude 6-heptyn-1-ol (13.0 g, ca. 100%
2
SO
4
1
0
(E,Z)-1-(Tr im eth ylsilyl)-3-m eth yl-2-n on en -7-yn e (9). To
1
a 0 °C stirred solution of 8 (194 mg, 1.00 mmol) in THF (2 mL)
were added sequentially n-BuLi (420 µL, 2.50 M in hexanes, 1.05
mmol) and methyl iodide (125 µL, 2.00 mmol) under Ar. After
yield): H NMR (300 MHz) δ 3.65 (t, J ) 6.3 Hz, 2H), 2.22 (dt,
J ) 2.4, 6.6 Hz, 2H), 1.94 (t, J ) 2.4 Hz, 1H), 1.70-1.40 (m,
7
2
H). To a stirred rt solution of crude 6-heptyn-1-ol (2.82 g, ca.
1
4 h, the solution was diluted with hexanes (ca. 5 mL) and
2 2
5.0 mmol) in CH Cl (100 mL) was added PDC (18.8 g, 50.0
mmol). After 2 h, the mixture was filtered through a pad of silica
gel, the filtrate was concentrated, and the residue was purified
filtered through a pad of silica gel. Concentration of the filtrate
gave 9 (208 mg, 1.00 mmol, ca. 100% yield) as a colorless oil:
-1 1
1
0
IR (neat) 2170, 1247 cm ; H NMR (500 MHz, E/Z ≈ 1:1) δ 5.16
by silica gel column chromatography to give 6-heptynal (2, 1.75
1
(m, 1H), 2.11 (m, 2H), 2.04 (m, 2H), 1.77 (bs, 3H), 1.66 and 1.52
g, 16.1 mmol, 64% yield for two steps): H NMR (200 MHz) δ
(
s, ∼1:1, 3H), 1.55 (m, 2H), 1.39 (m, 2H), -0.02 (bs, 9H); HRMS
9
2
.80 (t, J ) 1.4 Hz, 1H), 2.49 (m, 2H), 2.23 (m, 2H), 1.96 (t, J )
.0 Hz, 1H), 1.80-1.50 (m, 4H).
+
calcd for C13
H
24Si (M ) 208.1649, found 208.1647.
Using the same procedure as described for the preparation
(E,Z)-1,8-Bis(tr im eth ylsilyl)-3-m eth yl-2-octen -7-yn e (10).
To a stirred 0 °C solution of 8 (194 mg, 1.00 mmol) in THF (2
mL) were added sequentially n-BuLi (420 µL, 2.50 M in hexanes,
1.05 mmol) and TMSCl (253 µL, 2.00 mmol) under Ar. After 14
h, the solution was diluted with hexanes (ca. 5 mL) and filtered
through a pad of silica gel. Concentration of the filtrate under
reduced pressure gave 10 (267 mg, 1.00 mmol, ca. 100% yield)
of 5 above (ca. 1.3 equiv of phosphorylidene), 2 (1.43 g, 13.0
mmol) gave 6 (1.81 g, 6.08 mmol, 46% yield) as a colorless oil
after silica gel column chromatography (hexanes-ethyl acetate,
1
0:1, v/v): IR (neat) 3311, 2119, 1645, 1248 cm-1; 1H NMR (500
MHz, E/Z ) 1:1): δ 5.39 (m, 1H), 5.24 (m, 1H), 2.19 (dt, J ) 2.5,
7
1
.0 Hz, 2H), 1.98 (m, 2H), 1.93 (t, J ) 2.5 Hz, 1H), 1.54 (m, 2H),
-1 1
.45 (m, 4H), 0.00 (s, 4.5H), and -0.01 (s, 4.5H); HRMS calcd
as a colorless oil: IR (neat) 2175, 1248 cm ; H NMR (300 MHz,
E/Z ≈ 1:1): δ 5.16 (m, 1H), 2.17 (m, 2H), 2.06 (m, 2H), 1.64 and
+
for C12
H
26NSi (M + NH
4
)
212.1834, found 212.1832.

8
598 J . Org. Chem., Vol. 62, No. 24, 1997
Notes
1
3
1
9
.52 (s, 3H), 1.56 (m, 2H), 1.38 (m, 2H), 0.12 (bs, 9H), -0.03 (bs,
C NMR (75 MHz) δ 128.9, 125.9, 81.9, 75.6, 67.6, 57.1, 21.6,
+
+
H); HRMS calcd for C15
H
30Si
2
(M ) 266.1886, found 266.1885.
18.7, 3.5, -1.8; HRMS calcd for C12
2
H
22OSi (M ) 210.1439, found
10.1434.
Vin yl Mer cu r ia l 13. To a stirred rt solution of 5 (87 mg,
82 µmol) and HMDS (20 µL, 96 µmol) in CH Cl (2 mL) was
1
-((ter t-Bu tyld im eth ylsilyl)oxy)p r op a n -2-on e (11a ). To
a stirred 0 °C solution of acetol (7.40 g, 100 mmol) in CH Cl
200 mL) were added sequentially TBSCl (16.6 g, 110 mmol),
imidazole (13.6 g, 200 mmol), and DMAP (122 mg, 1 mmol). After
h, saturated aqueous NH Cl was added and the mixture was
extracted with CH Cl The combined organic extract was
washed with a saturated aqueous NaCl solution, dried over
Na SO , filtered, and concentrated. Flash chromatography (170
g of silica gel, hexanes-ethyl acetate, 10:1, v/v) gave 11a (11.76
2
2
4
2
2
(
2
added HgCl (144 mg, 530 µmol). After 14 h, the reaction
mixture was concentrated and the residue subjected to prepara-
tive silica gel TLC (hexanes-ethyl acetate, 5:1) to give 13 (109
3
mg, 318 µmol, 65% yield) as a colorless gum: IR (CDCl ) 1640,
1
5
1
4
2
2
.
-
1 1
636, 1449, 1248, 905 cm ; H NMR (300 MHz) δ 5.69 (m, 1H),
.64 (m, 1H), 5.05 (ddd, J ) 10.8, 1.8, 0.6 Hz, 1H), 5.04 (ddd, J
2
4
-
1
) 16.2, 1.8, 0.9 Hz, 1H), 3.14 (m, 1H), 2.54 (m, 2H), 2.00 (m,
g, 62.0 mmol, 62% yield) as an oil: IR (neat): 1734, 1717 cm
;
1H), 1.80 (m, 1H), 1.60 (m, 2H); 13C NMR (125 MHz) δ 164.5,
1
H NMR (500 MHz) δ 4.13 (s, 2H), 2.15 (s, 3H), 0.91 (s, 9H),
1
3
140.0, 125.4, 115.5, 51.6, 37.5, 34.5, 24.3; HRMS calcd for C
8
H
11
-
0
1
.07 (s, 6H); C NMR (125 MHz) δ 209.2, 69.5, 25.9, 25.6 (3C),
+
HgCl (M ) 344.0255, found 344.0258.
+
8.2, -5.4 (2C); HRMS calcd for C
9
H
21
O
2
Si (M + H) 189.1310,
Vin yl Mer cu r ia l 14. To a stirred rt solution of 6 (194 mg,
.00 mmol) and HMDS (42 µL, 0.20 mmol) in CH Cl (3 mL)
was added HgCl (299 mg, 1.10 mmol). After 18 h, the reaction
found 189.1318.
Z)-2-Meth yl-4-(tr im eth ylsilyl)-2-bu ten -1-ol (11b). To a
stirred 0 °C suspension of methyltriphenylphosphonium bromide
14.28 g, 40.0 mmol) in THF (100 mL) was added n-BuLi (17.2
1
2
2
(
2
mixture was concentrated and the residue purified by silica gel
column chromatography (hexanes-ethyl acetate, 5:1, v/v) to give
1
ized mercuric salt-alkyne adducts (ca. 147 mg) as a colorless
gum: IR (CDCl
(
mL, 2.50 M in hexanes, 43.1 mmol) under Ar. The resulting
dark red solution was allowed to warm to rt and stir for 1 h. A
mixture of NaI (12.0 g, 40.0 mmol) and (chloromethyl)trimeth-
ylsilane (5.60 mL, 40.0 mmol) in THF (10 mL) was heated under
reflux for 1 h and then cooled to rt before the above solution
was added via cannula. The resulting mixture was stirred at
rt for 14 h under Ar and then cooled to 0 °C before n-BuLi (17.2
4 (ca. 129 mg, 360 µmol, ca. 36% yield) and partially character-
-1
1
3
) 1649, 1635, 1447, 1248, 901 cm ; H NMR
(
1
1
300 MHz) δ 5.95 (m, 1H), 5.40 (m, 1H), 5.13 (d, J ) 17.0 Hz,
H), 5.09 (d, J ) 10.5 Hz, 1H), 2.97 (m, 1H), 2.48 (m, 2H), 2.45-
.48 (m, 6H); HRMS calcd for C H13HgCl (M + H) 359.0490,
9
+
found 359.0491.
(E )-(2-M e t h y l-2-v i n y lc y c lo p e n t y li d e n e )m e t h y l]-
m er cu r ic Ch lor id e (16E). Treatment of 7 (97 mg, 0.50 mmol)
with HgCl (150 mg, 550 µmol) and HMDS (21 µL, 0.10 mmol)
in CH Cl (2 mL) and isolation as described for 13 above gave
16E (100 mg, 280 µmol, 56% yield) as a colorless gum: IR
(CDCl ) 1631, 1613, 1455, 905 cm-1
; H NMR (500 MHz) δ 5.80
8
mL, 2.50 M in hexanes, 40.0 mmol) was added. After being
[
stirred for 30 min, the mixture was cooled to -78 °C and a
solution of 11a (6.58 g, 35.0 mmol) in THF (100 mL) was added
slowly. The resulting mixture was allowed to warm to rt and
stir over 14 h. Saturated aqueous NH
mixture was extracted with hexanes, and the combined organic
extract was washed with a saturated aqueous NaCl solution,
dried over Na SO , filtered, and concentrated by rotary evapora-
2 4
tion. The residue was dissolved in methanol (100 mL), and 12
M aqueous HCl (0.5 mL) was added. After 10 min of stirring,
2
2
2
4
Cl was added, the
1
3
(dd, J ) 17.0, 10.5 Hz, 1H), 5.66 (t, J ) 2.5 Hz, 1H), 5.00 (dd, J
) 17.0, 1.0 Hz, 1H), 4.98 (dd, J ) 10.5, 1.0 Hz, 1H), 2.61 (dt, J
) 2.5, 7.5 Hz, 2H), 1.81 (m, 1H), 1.70 (m, 2H), 1.62 (m, 1H),
1.17 (s, 3H); NOE (500 MHz) irradiation of the (allylic methyl)
1
solid NaHCO
3
(ca. 5 g) was added, and the resulting mixture
H resonance at δ 1.17 gave a 2.5% NOE enhancement of the
1
13
was filtered and concentrated. Silica gel column chromatogra-
phy (hexanes-ethyl acetate, 5:1, v/v) of the residue gave 11b
(syn vinyl) H resonance at δ 5.66; C NMR (125 MHz) δ 168.1,
145.7, 125.0, 111.6, 51.3, 41.3, 37.7, 25.6, 22.1; HRMS calcd for
C
[(E)-1-(2-Meth yl-2-vin ylcyclop en tylid en e)-1-eth yl]m er -
cu r ic Ch lor id e (17E). Treatment of 8 (104 mg, 500 µmol) with
HgCl (150 mg, 550 µmol) and HMDS (21 µL, 0.10 mmol) in
CH Cl (2 mL) for 19 h and isolation as described for 13 above
+
(
3
3.70 g, 23.4 mmol, 67% yield) as a pale yellow oil: IR (neat)
9
H
13HgCl (M ) 358.0412, found 358.0388.
332, 1653, 1248 cm-1; H NMR (300 MHz) δ 5.30 (t, J ) 9.0
Hz, 1H), 4.06 (s, 2H), 1.77 (s, 3H), 1.44 (d, J ) 9.0 Hz, 2H), -0.03
s, 9H); NOE (500 MHz) irradiation of the C2-H methylene
protons resonance at δ 4.06 gave a 2.1% enhancement of the
1
(
2
2
2
1
3
C2-H methylene protons resonance at δ 1.44; C NMR (75 MHz)
gave 17E (74 mg, 0.20 mmol, 40% yield) and uncharacterized
alkyne addition products (18 mg, 38 µmol) as a colorless gum:
δ 131.6, 124.3, 61.3, 21.2, 18.6, -1.8; HRMS calcd for C
8
H
18OSi
+
IR (CDCl ) 1632, 1615, 1247, 902 cm-1
; H NMR (500 MHz) δ
1
(M ) 158.1127, found 158.1127.
3
5
4
3
.88 (dd, J ) 17.0, 10.5 Hz, 1H), 5.01 (dd, J ) 17.0, 1.5 Hz, 1H),
(
Z)-2-Met h yl-4-(t r im et h ylsilyl)-2-b u t en yl 2-P r op yn yl
.98 (dd, J ) 10.5, 1.5 Hz, 1H), 2.57 (m, 2H), 2.00 (t, J ) 2.0 Hz,
Eth er (11). To a stirred 0 °C solution of 11b (1.15 g, 7.28 mmol)
in THF (20 mL) were added sequentially NaH (239 mg, 9.46
mmol) and tetra-n-butylammonium iodide (37 mg, 0.10 mmol)
under Ar. After 1 h, propargyl bromide (1.45 mL, 80% solution
in toluene, 13.1 mmol) was added and the mixture was allowed
to warm to rt and stir for 14 h. Hexanes (ca. 30 mL) was added,
and the suspension was filtered through a pad of silica gel.
Concentration of the filtrate and silica gel column chromatog-
raphy (hexanes-ethyl acetate, 10:1, v/v) of the residue gave 11
H), 1.78-1.62 (m, 4H), 1.27 (s, 3H); NOE (500 MHz) irradiation
1
of the (allylic methyl) H resonance at δ 1.27 gave a 1.8% NOE
1
enhancement of the (syn vinyl methyl) H resonance at δ 2.00;
+
HRMS calcd for C10
H
15HgCl (M ) 372.0569, found 372.0574.
[
(Z)-(2-Me t h y l-2-v in y lc y c lo p e n t y lid e n e )(t r im e t h y l-
silyl)m eth yl]m er cu r ic Ch lor id e (18Z). Treatment of 10 (95
mg, 0.36 mmol) with HgCl (107 mg, 392 µmol) and HMDS (15
µL, 71 µmol) in CH Cl (2 mL) for 45 h and isolation as described
for 13 above gave 18Z (78 mg, 0.18 mmol, 50% yield) as a
2
2
2
(1.08 g, 5.51 mmol, 76% yield) as a pale yellow oil: IR (neat)
-1 1
3
colorless gum: IR (CDCl ) 1628, 1574, 1250 cm ; H NMR (500
310, 2119, 1248 cm-1; H NMR (300 MHz) δ 5.43 (t, J ) 9.0
1
3
MHz) δ 5.68 (dd, J ) 17.0, 10.5 Hz, 1H), 5.34 (d, J ) 10.5 Hz,
1
1
Hz, 1H), 4.08 (d, J ) 2.1 Hz, 2H), 4.02 (s, 2H), 2.41 (t, J ) 2.1
Hz, 1H), 1.74 (s, 3H), 1.50 (d, J ) 9.0 Hz, 2H), -0.00 (s, 9H);
H), 5.27 (d, J ) 17.0 Hz, 1H), 2.72 (m, 1H), 2.55 (m, 1H), 1.84-
.61 (m, 4H), 1.11 (s, 3H), 0.15 (s, 9H); NOE (500 MHz)
1
3
C NMR (75 MHz) δ 128.4, 126.4, 80.2, 74.0, 67.7, 56.5, 21.6,
1
irradiation of the (TMS) H resonance at δ 0.15 gave a 2.3% NOE
+
1
1
8.7, -1.8; HRMS calcd for C11
96.1287.
H
20OSi (M ) 196.1283, found
1
enhancement of the allylic methylene H resonances at δ 2.72
13
and 2.55; C NMR (125 MHz) δ 175.5, 148.1, 140.1, 118.0, 52.6,
(
Z)-2-Met h yl-4-(t r im et h ylsilyl)-2-b u t en yl 2-n -Bu t yn yl
40.4, 35.2, 24.4, 23.2, 1.29; HRMS calcd for C12H21SiHgCl:
430.0807, found 430.0806.
Eth er (12). To a stirred 0 °C solution of 11 (589 mg, 3.00 mmol)
in THF (10 mL) were added sequentially n-BuLi (1.26 mL, 2.5
M in hexanes, ca. 3.2 mmol) and methyl iodide (0.374 mL, 6.00
mmol) under Ar. After 14 h, hexanes (ca. 15 mL) was added
and the suspension was filtered through a pad of silica gel.
Concentration of the filtrate and silica gel column chromatog-
raphy (hexanes-ethyl acetate, 10:1, v/v) of the reside gave 12
[(E )-(4-Me t h yl-4-vin yl-3-fu r ylid e n e )m e t h yl]m e r cu r ic
Ch lor id e (19). Treatment of 11 (196 mg, 1.00 mmol) with
HgCl2 (299 mg, 1.10 mmol) and HMDS (42 µL, 0.20 mmol) in
CH Cl (2 mL) and isolation as described for 13 above gave 19
2
2
(173 mg, 482 µmol, 48% yield) as a colorless gum: IR (CDCl )
3
-
1 1
1653, 1558, 905 cm ; H NMR (500 MHz) δ 5.87 (dd, J ) 2.5,
2.5 Hz, 1H), 5.82 (dd, J ) 17.0, 10.5 Hz, 1H), 5.16 (d, J ) 17.0
Hz, 1H), 5.13 (d, J ) 10.5 Hz, 1H), 4.53 (dd, J ) 13.5, 2.5 Hz,
1H), 4.48 (dd, J ) 13.5, 2.5 Hz, 1H), 3.84 (d, J ) 8.5 Hz, 1H),
3.70 (d, J ) 8.5 Hz, 1H), 1.26 (s, 3H); NOE (500 MHz) irradiation
(631 mg, 3.00 mmol, 100% yield) as a pale yellow oil: IR (neat)
659, 1451, 1247 cm-1; H NMR (300 MHz) δ 5.38 (t, J ) 9.0
1
1
Hz, 1H), 4.00 (q, J ) 2.1 Hz, 2H), 3.96 (s, 2H), 1.83 (t, J ) 2.1
Hz, 3H), 1.71 (s, 3H), 1.48 (d, J ) 9.0 Hz, 2H), -0.03 (s, 9H);

Notes
of the (allylic methyl) H resonance at δ 1.26 gave a 2.1% NOE
J . Org. Chem., Vol. 62, No. 24, 1997 8599
1
Acknowledgment is made to the donors of The Petro-
leum Research Fund, administered by the American
Chemical Society, for partial support of this research.
We also thank the University of Minnesota for Graduate
Fellowship (H.H.) and McKnight Land-Grant Profes-
sorship (C.J .F.) support.
1
13
enhancement of the (vinyl) H resonance at δ 5.87; C NMR
125 MHz) δ 164.5, 141.4, 123.0, 114.1, 80.4, 73.6, 51.6, 22.4;
HRMS calcd for C 11OHgCl 359.0201, found 359.0194.
(E )-1-(4-Me t h yl-4-vin yl-3-fu r ylid e n e )-1-e t h yl]m e r cu -
r ic Ch lor id e (20). Treatment of 12 (210 mg, 1.00 mmol) with
HgCl (299 mg, 1.10 mmol) and HMDS (42 µL, 0.20 mmol) in
CH Cl (5 mL) for 15 h and isolation as described for 13 above
(
8
H
[
2
2
2
gave 20 (153 mg, 410 µmol, 41% yield) as a colorless gum: IR
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
-
1
1
(CDCl
3
) 1625, 905 cm
; H NMR (500 MHz) δ 5.83 (dd, J )
1
3
compounds 5-11a , 11b, 11-14, 16E, and 18Z-20 and
C
1
7.0, 10.5 Hz, 1H), 5.16 (d, J ) 10.5 Hz, 1H), 5.10 (d, J ) 17.0
Hz, 1H), 4.26 (m, 2H), 3.54 (d, J ) 11.0 Hz, 1H), 3.39 (d, J )
1
irradiation of the (vinyl methyl) H resonance at δ 1.84 gave a
2
δ 1.15; C NMR (125 MHz) δ 144.3, 143.4, 141.7, 114.7, 74.1,
7
3
NMR spectra for compounds 5-7, 11a , 11b, 11-13, 16, 18,
and 19 (27 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
1.0 Hz, 1H), 1.84 (m, 3H), 1.15 (s, 3H); NOE (500 MHz)
1
1
.0% NOE enhancement of the (allylic methyl) H resonance at
1
3
+
0.7, 44.8, 23.9, 20.0; HRMS calcd for C
75.0430, found 375.0393.
9
H14OHgCl [M + H]
J O971478X