Regio- and stereoselectivity in palladium-catalyzed cycloreductions of 1,6-enynes in the presence of formic acid or triethylsilane

Article abstract of DOI:10.1016/S0040-4020(01)00008-4

Palladium catalyzed 1,6-enyne cycloreductions in the presence of 1.2 equiv. of formic acid (method A) would involve cycloalkylpalladium formates which proceed via two consecutive steps: β-elimination of alkylpalladium intermediates and then reduction at t

Full text of DOI:10.1016/S0040-4020(01)00008-4

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 1723±1729
Regio- and stereoselectivity in palladium-catalyzed
cycloreductions of 1,6-enynes in the presence of
formic acid or triethylsilane
p
Chang Ho Oh, Hyung Hoon Jung, Hye Rhyan Sung and Jung Duk Kim
Department of Chemistry, Hanyang University, Haengdang-17, Sungdong-Gu, Seoul 133-791, South Korea
Received 30 October 2000; accepted 15 December 2000
AbstractÐPalladium catalyzed 1,6-enyne cycloreductions in the presence of 1.2 equiv. of formic acid (method A) would involve cyclo-
alkylpalladium formates which proceed via two consecutive steps: b-elimination of alkylpalladium intermediates and then reduction at the
less hindered ole®ns regio- and stereoselectivity. Triethylsilane, however, directly reduced the alkylpalladium intermediates to give the
corresponding cycloreduced products (method B). q 2001 Elsevier Science Ltd. All rights reserved.
7
1
. Introduction
formic acid was used. We have noted that even the alkyl-
palladium formates possessing a b-hydrogen also under-
went carbopalladation rather than b-elimination. Based on
these observations, we could postulate that use of an equiva-
lent of formic acid played a dual role in initiating the cata-
lytic reaction and also in reducing the alkylpalladium
Since functionalized carbocycles are very common struc-
tural subunits in many biologically active natural
compounds, their preparation becomes of paramount
1
interest in organic synthesis. Of particular signi®cance
are the palladium-catalyzed cycloisomerizations of
8
intermediate at the end of the catalytic cycle. In this
2
enediynes, dienynes, enynes and diynes. In the pioneering
paper, we report our results demonstrating the scope and
limitations of palladium-catalyzed enyne cycloreductions
in the presence of formic acid or triethylsilane.
work from the Trost group, various enynes were trans-
formed to the corresponding s-palladium species via hydro-
palladation of the terminal triple bond and subsequent
3
intramolecular carbopalladation. Iterative trapping of the
s-palladium species with tethered ole®ns allows for tandem
2. Results and discussion
4
cycloisomerizations. Direct reduction of the s-bonded
alkylpalladium intermediates by excess external hydrogen
donors such as triethylsilane or polymethylhydrosiloxane
Diethyl allylpropargylmalonate (1a) as an enyne substrate
was examined as shown in Eq. (1). Our initial hypothesis
was as follows. (1) The initially formed H±Pd±OOCH adds
to the terminal triple bond regioselectively, and adds to the
double bond to form an alkylpalladium intermediate. (2)
The alkylpalladium formate could undergo reductive
cleavage by the formate ligand more rapidly than
b-elimination. In fact, treatment of enyne 1a with 5 mol%
5
(
PMHS) would represent an useful process particularly.
Although this method was highly valuable with diverse
enyne substrates, one critical disadvantage is the require-
ment of a large excess of trialkylsilane, which should
cause puri®cation of the products to be problematic. An
alternative method, developed by the Stork group, involves
two-step processes: radical cyclization initiated by tributyl-
Pd(OAc)
, 10 mol% PPh
2
, and 2.5 equiv. of HCOOH in
3
6
tin radical and destannylation over silica gel. We have long
been interested in palladium-catalyzed cycloreductions of
enediynes and enynes, which could offer new or alternative
methodologies for constructing diverse carbocycles.
Recently, we reported a new variation of palladium-
catalyzed enediyne cyclization in which enediynes under
palladium catalysis selectively gave either [m,6,n]- or
ꢀ1†
[
m,5,n]-tricyclic compounds depending on how much
Keywords: formic acid; triethylsilane; cycloreductions.
Corresponding author. Tel.: 182-2-2290-0932; fax: 182-2-2299-0762;
e-mail: changho@email.hanyang.ac.kr
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)00008-4

1
724
C. H. Oh et al. / Tetrahedron 57 (2001) 1723±1729
toluene or 1,4-dioxane mainly furnished the cycloreduced
product 2a in 60±75% isolated yield along with a trace of
the diene 3a. This hypothesis was further supported from the
reaction of enyne 1b, since the alkylpalladium intermediate
derived from the enyne 1b under our conditions could not
undergo b-elimination due to the lack of b-hydrogen to the
alkylpalladium intermediate. The formation of cyclo-
reduced product 2b implied that direct reduction of the
9
alkylpalladium intermediates could occur rapidly. During
the course of extension of this palladium-catalyzed cyclo-
reduction methodology, we found that the enynes 4 conju-
gated with a carbonyl group (E) initially formed the dienes 5
via b-elimination of the alkylpalladium intermediates. The
dienes 5 underwent reduction to the g, d-unsaturated car-
bonyl compounds 6 for a prolonged period of reaction time
Scheme 2.
The enyne 7b was tested as a second substrate, since it is a
good model substrate for the natural product laurene and we
should revise and con®rm structural assignments for its
1
0
(
Eq. (2)).
1
4
cycloreduced products (Scheme 2). The enyne 7b under
method A was converted to the product 9b and its stereo-
isomer epi-9b in 52 and 25% isolated yields, respectively.
The enyne 7b under method B was converted to the product
ꢀ2†
1
0b and its stereoisomer epi-10b in 75 and 6% isolated
1
5
yields, respectively. With these products in hand, we
then determined their relative stereochemistries by analyz-
ing a series of NMR data including NOESY data. H, C-
NMR, DEPT, COSY, TOCSY, HETCOR experiments
Formation of the dienes 5 prompted us to reinvestigate Pd-
catalyzed cycloreductions of a variety of enynes and to
1
13
1
1
revise our proposed mechanism. When the enyne 7a was
heated at 608C with 5 mol% Pd(OAc) , 10 mol% PPh , and
1
13
2
3
enabled us to accomplish complete H and C NMR signal
assignments of compounds 9b, epi-9b, and 10b and to
con®rm the relative con®gurations of each compound.
Coupling constants given by DQF±COSY experiment
were analyzed to identify the orientation of J-coupled
proton networks and to observe possible ®ve-membered
ring puckering. In addition, temperature-dependent(220±
258C) and variable mixing times (tmˆ50, 100, 250,
500 ms) of NOESY experiments were carried out to observe
the direct NOE connectivities exhibiting the orientation of
1.2 equiv. of HCOOH in toluene (method A), we obtained
the compound 9a in 64% isolated yield along with a trace of
the isomer 10a (Scheme 1). We should understand how the
product 9a was formed in order to search an asymmetric
version of this method and its application to natural product
1
2
syntheses. Thus, when only 10 mol% of formic acid was
employed in method A, the enyne 7a was exclusively trans-
formed to the diene 8a, that was further reduced to the
product 9a by adding one equivalent of formic acid. Next,
we subjected enyne 7a to method B, a modi®ed Trost
1
6
side chains.
1
3
method. When the enyne 7a was heated at 608C with
5
1
mol% Pd(dppe)Cl2, 1.2 equiv. of HCOOH, and
.2 equiv. of triethylsilane in toluene, we obtained the
Then, we prepared structurally similar enynes 7c±j and
applied them to the present two methods. These results
are summarized in Table 1. Methods A and B worked
well for the substrates 7c±7f to afford the corresponding
cycloreduced products 9c±f (70±77% yields) and the
products 10c±f (60±85% yields), respectively. Like
substrate 7b, enyne 7d was cycloreduced to 9d (1:4) and
to 10d (1:9) as mixtures of diastereomers under the two
different conditions, respectively. The enynes 7e and 7f
for both methods did exhibit great stereoselectivities, up
to a 99:1 ratio, respectively. When the enynes 7g and 7h
were cyclized under method A, the products 10g and 10h
were isolated in 81 and 41% yields, respectively. The
enynes 7g and 7h under method B, however, were not
cyclized at all. When the enynes having a hydroxyl func-
tionality (7i and 7h) were applied to the two methods, the
corresponding products were formed with opposite relative
stereochemistry, indicating that the different mechanisms
might be operating.
product 10a in 70% isolated yield. Exclusive formation of
the product 10a implied that direct reduction of s-alkyl-
palladium intermediate I has predominantly occurred.
These experiments showed the possibility that palladium-
catalyzed enyne cycloreductions provide one of two
expected regioisomers selectively depending on the reaction
conditions. Then, the two methods (A and B) were applied
to several structurally diverse enynes.
2
.1. Proposed mechanism
While sterically bulky groups of the enynes seemed to be
associated with the regioselectivities of cycloreductions in
method A, those did not in method B. For example, the
Scheme 1.

C. H. Oh et al. / Tetrahedron 57 (2001) 1723±1729
Table 1. Palladium-catalyzed enyne cycloreductions under two methods
1725
a
Ratios mean trans:cis relations between substituents such as Me and Me, Me and OSiMe
2
(t-Bu), or Me and OH.
3
, 1.2 equiv. HCOOH, 1.2 equiv. Et SiH.
Method A: 5 mol% Pd(OAc) , 10 mol% PPh , 1.2 equiv. HCOOH. Method B: 5 mol% Pd(dppe)Cl
3
2
2
enynes 7a±e under method B were cycloreduced to the
products 10a±e, which could be formed via direct reduction
of the alkylpalladium intermediates by triethylsilane. Those
enynes under method A, however, initially formed the
dienes. When these dienes were reduced by HPdOOCH
under the similar reaction conditions, we obtained the
products 9a±e in high yields, respectively. Such regio-
selectivity could be con®rmed by control experiments
with the enynes 11a and 11b, which are regioisomers of
enynes 7a and 7b, respectively (Scheme 3). When the
enyne 11a was applied to method A, the reaction was slug-
gish to give the expected product 9a in 45% yield. The
enyne 11a under method B did not give any cyclized
experiments showed that cyclizations of the enynes 7a±j
and 11a±b under method A should involve the diene inter-
mediacy. Finally, a distinct stereochemical outcome has
been observed from cycloreductions of the enynes 7i and
1
7
products but reduced the triple bond to the double bond.
In contrast to the enyne 11a, the enyne 11b under method A
was cleanly transformed to the expected product 9b as a 3:1
mixture of diastereomers. The method B did give the same
product 9b but in a different ratio of isomers (2:1). These
Scheme 3. All reactions were carried out by method A under the following
conditions. (a) toluene, 608C, 2 h; (b) toluene, 608C, 1 h; (c) 1,4-dioxane,
408C, 3 h; (d) toluene, 508C, 4 h.

1
726
C. H. Oh et al. / Tetrahedron 57 (2001) 1723±1729
NMR spectrometer using tetramethylsilane as an internal
standard.
3
.2. Compound 9a. General procedure for method A
To a mixture of PPh (15.2 mg, 0.058 mmol) and Pd(OAc)2
3
(
6.5 mg, 0.029 mmol) in a 5 mL test tube was added a solu-
tion of enyne 7a (100 mg, 0.58 mmol) in dry toluene
1 mL). The mixture was stirred for 10 min under argon
atmosphere and then treated with formic acid (27 mL,
.69 mmol) via a gastight syringe. The mixture was stirred
(
0
for 2 h at 608C in a preheated oil bath. The reaction mixture
was cooled to room temperature and concentrated under
reduced pressure. Silica gel chromatography (1:9 EtOAc/
Scheme 4.
hexane) of the residue gave the product 9a (64.6 mg,
6
1
4%) as a colorless oil: H NMR (400 MHz, CDCl ): d
3
7
j. The method A afforded the predominant formation of the
trans isomer, since HPdOOCH could coordinate with the
OH functionality and therefore H-transfer occurred at the
7
.35 (t, Jˆ7.6 Hz, 2H), 7.22 (t, Jˆ7.2 Hz, 1H), 7.15 (d,
Jˆ7.6 Hz, 2H), 6.30 (d, Jˆ2.0 Hz, 1H), 4.67 (ABq,
Ddˆ33.6 Hz, Jˆ14.0 Hz, 2H), 4.08 (dd, Jˆ7.6, 8.0 Hz,
±
same face of the hydroxy group. The method B mainly
produced the cis isomer for both enynes. Such cis-relation-
ship might be understood by chelation effect of the vinyl-
palladium species with the pendant ±OH group, so that the
subsequent carbopalladation should occur at the same face
of ±OH group.
1
H), 3.39 (dd, Jˆ8.0, 8.0 Hz, 1H), 2.92 (m, 1H), 1.22 (d,
1
3
Jˆ6.8 Hz, 3H); C NMR (100 MHz, CDCl ): d 146.31,
3
1
3
1
37.22, 128.37, 127.74, 126.36, 119.78, 74.28, 70.31,
2
9.87, 16.51; FT-IR (neat, cm ): 3055, 3025, 2964, 2842,
1
662, 1492, 1447, 1374, 1081, 1063; HRMS calcd for
1
C H O (M ) 174.1044, found 174.1046.
1
2
14
1
.2.1. Compound 9b and epi-9b. 9b H NMR (400 MHz,
Following is a summary for the present two methods. First,
all enynes under both methods were hydro- and subse-
quently carbopalladated to the corresponding alkyl-
palladium intermediates. While triethylsilane could
directly reduce the intermediates to lead to the correspond-
ing cycloreduced products (method B), formic acid could
not (method A). In method A, the intermediates readily
underwent b-elimination to the dienes 8, which were
reduced to give the cycloreduced product 9 in excellent
yields and in excellent regio- and stereoselectivities.
Second, the regioselectivity in method A seemed to arise
from the steric factors of the dienes 8. The coordination of
the palladium catalyst with the dienes 8 at the sterically less
hindered double bond yielded the products as shown in
Scheme 4. In method B, the initially formed vinylpalladium
intermediates were carbopalladated to give the more stable
alkylpalladium intermediates, which were reduced by
triethylsilane to yield the products 10. The hydroxy
functionality in the enynes 7i and 7j might coordinate
with the palladium catalyst to control the regio- and stereo-
selectivities in both methods. We believe that the present
study will provide easy access to the regio- and stereo-
selective syntheses of exomethylenecyclopentane derivatives.
3
CDCl ): d 7.35 (d, Jˆ8.0 Hz, 2H), 7.11 (d, Jˆ8.0 Hz, 2H),
3
5
.06 (d, Jˆ2.8 Hz, 1H), 4.99 (d, Jˆ2.8 Hz, 1H), 4.05 (dd,
Jˆ8.0, 8.0 Hz, 1H), 3.47 (dd, Jˆ8.0, 8.0 Hz, 1H), 2.72 (m,
C
NMR (100 MHz, CDCl ): d 159.11, 142.77, 136.20, 128.62,
1
3
1
H), 2.32 (s, 3H), 1.59 (s, 3H), 1.13 (d, Jˆ6.8 Hz, 3H);
3
1
24.67, 104.53, 85.34, 71.86, 37.71, 28.25, 21.16, 16.33;
2
1
FT-IR (neat, cm ): 3079, 3024, 2971, 2928, 2870, 1664,
508, 1450, 1368, 1084, 1033; HRMS calcd for C H O
1
(
(
1
4
18
1
M ) 202.1357, found 202.1360.; epi-9b H NMR
1
400 MHz, CDCl ): d 7.38 (d, Jˆ8.4 Hz, 2H), 7.13 (d,
3
Jˆ8.4 Hz, 2H), 5.10 (d, Jˆ2.0 Hz, 1H), 5.03 (d,
Jˆ2.0 Hz, 1H), 4.10 (dd, Jˆ8.8, 8.8 Hz, 1H), 3.27 (dd,
Jˆ8.8, 8.8 Hz, 1H), 2.94 (m, 1H), 2.33 (s, 3H), 1.59 (s,
1
3
3
H), 1.02 (d, Jˆ6.8 Hz, 3H); C NMR (100 MHz,
CDCl ): d 159.03, 142.01, 136.26, 128.66, 125.39,
3
1
(
05.71, 85.46, 71.82, 38.93, 29.55, 21.12, 17.27; FT-IR
neat, cm ): 2973, 2928, 2870, 1662, 1508, 1450, 1373,
2
1
1
182, 1137, 1103, 1033, 1020.
1
3.2.2. Compound 9c. H NMR (400 MHz, CDCl ): d 7.36±
3
7.29 (m, 4H), 7.19 (m, 1H), 6.22 (d, Jˆ2.8 Hz, 1H), 4.18 (m,
4H), 3.29 (ABq, Ddˆ68.4 Hz, Jˆ17.6 Hz, 2H), 2.78 (m,
1
H), 2.59 (ddd, Jˆ12.4, 7.2, 1.2 Hz, 1H), 1.75 (dd,
Jˆ12.4, 11.6 Hz, 1H), 1.25 (t, Jˆ7.2 Hz, 3H), 1.23 (t,
1
3
3
. Experimental
Jˆ7.2 Hz, 3H), 1.22 (d, Jˆ7.2 Hz, 3H); C NMR
(100 MHz, CDCl ): d 171.76, 171.72, 146.23, 137.83,
128.19, 128.17, 126.06, 121.30, 61.56, 59.04, 41.36,
3
3.1. General procedure
2
1
9.09, 38.88, 18.33, 14.07, 14.05; FT-IR (neat, cm ):
3
All reactions were carried out under an atmosphere of dry
argon. Commercial reagents were used as received without
further puri®cation. All products were puri®ed by ¯ash
chromatography using silica gel 60 (70±230 mesh,
Merck) and/or by a Young-Lin M 930 HPLC employing a
Nova-Pak silica preparative column and a UV detector. The
3023, 2979, 2933, 2870, 1730, 1492, 1447, 1299, 1276,
1250, 1177, 1152, 1060, 1029; HRMS calcd for C H O
4
(M ) 316.1674, found 316.1669.
1
9
24
1
1
3.2.3. Compound 9d and epi-9d. 9d H NMR (400 MHz,
CDCl ): d 7.47 (d, Jˆ6.8 Hz, 2H), 7.31 (t, Jˆ6.8 Hz, 2H),
3
1
13
puri®ed products were identi®ed with H and C NMR
spectral data obtained from a Varian Mercury 400 MHz
7.22 (t, Jˆ6.8 Hz, 1H), 5.08 (d, Jˆ2.8 Hz, 1H), 5.01 (d,
Jˆ2.4 Hz, 1H), 4.07 (dd, Jˆ8.6, 8.6 Hz, 1H), 3.48 (dd,

C. H. Oh et al. / Tetrahedron 57 (2001) 1723±1729
1727
1
330.2365; cis-10h H NMR (400 MHz, CDCl ): d
Jˆ8.6, 8.6 Hz, 1H), 2.72 (m, 1H), 1.60 (s, 3H), 1.14 (d,
3
1
3
Jˆ6.8 Hz, 3H); C NMR (100 MHz, CDCl ): d 159.02,
7.3227.19 (m, 5H), 4.97 (d, Jˆ2.0 Hz, 1H), 4.92 (d,
Jˆ2.0 Hz, 1H), 4.37 (s, 2H), 3.86 (dd, Jˆ8.8, 6.4 Hz, 1H),
3.60 (dd, Jˆ8.8, 6.0 Hz, 1H), 2.95 (m, 1H), 2.94 (dd,
3
1
3
2
1
1
45.72, 127.97, 126.65, 124.77, 104.71, 85.43, 71.91,
2
1
7.65, 28.21, 16.23; FT-IR (neat, cm ): 3081, 2970,
929, 2870, 1663, 1560, 1491, 1446, 1369, 1215, 1066,
028; HRMS calcd for C H O (M ) 188.1201, found
1
3
Jˆ15.2, 5.2 Hz, 1H), 2.63 (dd, Jˆ15.2, 11.6 Hz, 1H);
C
1
NMR (100 MHz, CDCl ): d 151.09, 139.83, 128.64, 128.28,
3
1
3
16
1
88.1205; epi-9d H NMR (400 MHz, CDCl ): d 7.48 (d,
3
126.06, 104.01, 73.52, 71.62, 45.31, 38.82; FT-IR (neat,
2
1
Jˆ8.0 Hz, 2H), 7.31 (t, Jˆ8.0 Hz, 2H), 7.22 (t, Jˆ8.0 Hz,
cm ): 3062, 3026, 2938, 2848, 1665, 1495, 1453, 1182,
1063.
1
H), 5.11 (d, Jˆ2.4 Hz, 1H), 5.03 (d, Jˆ2.4 Hz, 1H), 4.11
(
(
(
dd, Jˆ8.4, 8.4 Hz, 1H), 3.28 (dd, Jˆ8.4, 8.4 Hz, 1H), 2.94
1
3
1
3.2.8. Compound trans-10i and cis-10i. trans-10i H NMR
m, 1H), 1.60 (s, 3H), 1.01 (d, Jˆ6.8 Hz, 3H); C NMR
100 MHz, CDCl ): d 159.03, 145.05, 128.03, 126.78,
3
(400 MHz, CDCl
3
): d 5.10 (dd, Jˆ2.8, 2.4 Hz, 1H), 4.97
1
(
25.50, 105.94, 85.54, 71.87, 38.86, 29.44, 17.24; FT-IR
(dd, Jˆ2.8, 2.0 Hz, 1H), 3.99 (dq, Jˆ8.8, 2.8 Hz, 1H), 2.56
(m, 1H), 1.73 (dd, Jˆ12.6, 8.4 Hz, 1H), 1.33 (d, Jˆ8.4 Hz,
1H), 1.09 (d, Jˆ7.2 Hz, 3H), 1.07 (s, 3H), 1.04 (dd, Jˆ12.6,
2
neat, cm ): 3059, 2961, 2926, 2854, 1738, 1490, 1447,
1
1373, 1137, 1071, 1026.
1
3
1
0.0 Hz, 1H), 0.78 (s, 3H); C NMR (100 MHz, CDCl ): d
3
1
.2.4. Compound 9e. H NMR (400 MHz, CDCl ): d 7.27
3
159.71, 106.35, 82.27, 44.87, 40.91, 33.31, 26.47, 21.32,
3
2
1
(
d, Jˆ8.8 Hz, 2H), 6.88 (d, Jˆ8.8 Hz, 2H), 5.20 (d,
19.42; FT-IR (neat, cm ): 3382, 2956, 2926, 2868, 1660,
1462, 1383, 1366, 1153, 1083, 1052; HRMS calcd for
Jˆ2.0 Hz, 1H), 4.96 (dd, Jˆ2.8, 2.8 Hz, 1H), 4.76 (dd,
1
16O (M ) 140.1201, found 140.1209.; cis-10i
1
Jˆ2.8, 3.2 Hz, 1H), 4.30 (dd, Jˆ8.4, 8.0 Hz, 1H), 3.80 (s,
C
NMR (400 MHz, CDCl
9
H
H
3
H), 3.41 (dd, Jˆ8.4, 9.6 Hz, 1H), 2.90 (m, 1H), 1.16 (d,
3
): d 5.15 (dd, Jˆ2.0, 2.0 Hz, 1H),
1
3
Jˆ6.8 Hz, 3H); C NMR (100 MHz, CDCl ): d 158.98,
4.96 (dd, Jˆ2.0, 2.0 Hz, 1H), 3.92 (d, Jˆ6.4 Hz, 1H), 2.54
(m, 1H), 1.73 (dd, Jˆ12.6, 9.4 Hz, 1H), 1.31 (dd, Jˆ12.6,
7.2 Hz, 1H), 1.29 (d, Jˆ6.4 Hz, 1H), 1.14 (d, Jˆ6.8 Hz,
3
1
5
56.90, 133.93, 128.17, 113.62, 105.38, 83.46, 74.53,
2
5.29, 38.69, 15.37; FT-IR (neat, cm ): 3076, 2963,
1
1
3
2
931, 2871, 2837, 1667, 1612, 1586, 1513, 1463, 1303,
3H), 0.98 (s, 3H), 0.90 (s, 3H); C NMR (100 MHz,
1
248, 1172; HRMS calcd for C H O (M ) 204.1150,
1
found 204.1138.
CDCl
26.57, 21.97, 20.74; FT-IR (neat, cm ): 3408, 2958,
929, 2869, 1659, 1460, 1365, 1279, 1175, 1106, 1076,
1028.
): d 160.37, 106.59, 82.79, 44.77, 40.31, 32.82,
3
1
1
3
16
2
2
2
1
.2.5. Compound 9f. H NMR (400 MHz, CDCl ): d 7.29
3
3
(
m, 1H), 7.18 (m, 3H), 5.48 (d, Jˆ2.0 Hz, 1H), 4.97 (dd,
1
Jˆ2.8, 2.8 Hz, 1H), 4.72 (dd, Jˆ2.4, 2.8 Hz, 1H), 4.32 (dd,
3.2.9. Compound trans-10j and cis-10j. trans-10j H NMR
(400 MHz, CDCl
Jˆ8.0, 8.0 Hz, 1H), 3.43 (dd, Jˆ9.6, 8.0 Hz, 1H), 2.96 (m,
3
): d 7.40 (d, Jˆ7.6 Hz, 2H), 7.31 (t,
1
3
1
(
1
1
2
H), 2.42 (s, 3H), 1.19 (d, Jˆ6.8 Hz, 3H); C NMR
100 MHz, CDCl ): d 159.28, 139.24, 136.14, 130.47,
3
Jˆ7.6 Hz, 2H), 7.19 (t, Jˆ7.6 Hz, 1H), 6.38 (t, Jˆ2.0 Hz,
1H), 4.44 (dt, Jˆ5.2, 2.0 Hz, 1H), 2.84 (m, 1H), 1.89 (dd,
Jˆ12.4, 8.8 Hz, 1H), 1.59 (d, Jˆ5.2 Hz, 1H), 1.24 (d,
Jˆ6.8 Hz, 3H), 1.12 (dd, Jˆ12.4, 8.8 Hz, 1H), 1.00 (s,
27.64, 127.53, 125.97, 105.25, 81.17, 74.58, 38.93,
9.54, 15.70; FT-IR (neat, cm ): 3075, 3024, 2964, 2929,
870, 1665, 1491, 1461, 1288, 1062, 1033; HRMS calcd for
2
1
1
3
3H), 0.97 (s, 3H); C NMR (100 MHz, CDCl ): d 152.03,
3
1
C H O (M ) 188.1201, found 188.1197.
1
137.11, 128.47, 128.27, 126.57, 124.76, 80.81, 45.15, 41.67,
3
16
2
5.84, 27.60, 21.53, 20.64; FT-IR (neat, cm ): 3584, 3436,
1
3
3057, 3024, 2956, 2868, 1598, 1494, 1447, 1382, 1074,
18
1
.2.6. Compound trans-10g . H NMR (400 MHz,
3
1
20O (M ) 216.1514, found
CDCl ): d 4.95 (dd, Jˆ0.8, 1.2 Hz, 1H), 4.86 (dd, Jˆ0.8,
1045; HRMS calcd for C15
216.1509; cis-10j H NMR (400 MHz, CDCl ): d 7.50 (d,
H
3
1
1
(
.2 Hz, 1H), 3.96 (td, Jˆ2.4, 2.4 Hz, 1H), 2.54 (m, 1H), 1.69
3
dd, Jˆ12.6, 8.8 Hz, 1H), 1.07 (d, Jˆ7.2 Hz, 3H), 1.00 (dd,
Jˆ7.2 Hz, 2H), 7.33 (t, Jˆ7.2 Hz, 2H), 7.22 (tt, Jˆ7.2,
2.0 Hz, 1H), 6.47 (d, Jˆ1.6 Hz, 1H), 4.13 (d, Jˆ4.4 Hz,
1H), 2.77 (m, 1H), 1.66 (dd, Jˆ12.2, 7.2 Hz, 1H), 1.48
(dd, Jˆ12.2, 11.2 Hz, 1H), 1.47 (d, Jˆ4.4 Hz, 1H), 1.25
Jˆ12.8, 9.6 Hz, 1H), 0.98 (s, 3H), 0.93 (s, 9H), 0.77 (s, 3H),
1
.09 (s, 3H), 0.08 (s, 3H); C NMR (100 MHz, CDCl ):
3
0
1
2
2
1
2
3
59.24, 105.85, 82.19, 44.89, 41.21, 33.15, 27.16, 26.09,
1.92, 20.27, 18.34, 24.01, 24.23; FT-IR (neat, cm ):
2
1
13
(d, Jˆ6.8 Hz, 3H), 1.12 (s, 3H), 0.82 (s, 3H); C NMR
(100 MHz, CDCl ): d 151.98, 137.29, 128.29, 128.26,
3
958, 2930, 2858, 1664, 1472, 1463, 1385, 1366, 1257,
116; HRMS calcd for C H OSi (M ) 254.2066, found
54.2083.
1
127.73, 126.69, 79.82, 44.83, 42.57, 37.14, 25.84, 22.61,
22.50; FT-IR (neat, cm ): 3583, 3469, 3057, 3025, 2956,
928, 2868, 1598, 1494, 1449, 1383, 1232, 1064, 1018.
1
5
30
2
1
2
1
.2.7. Compound trans-10h and cis-10h. trans-10h H
3
NMR (400 MHz, CDCl ): d 7.37±7.30 (m, 4H), 7.19 (t,
3
3.3. Compound 10a. General procedure for method B
Jˆ7.6 Hz, 1H), 6.37 (d, Jˆ1.6 Hz, 1H), 3.80 (s, 1H), 3.09
(
m, 1H), 1.76 (dd, Jˆ12.2, 8.4 Hz, 1H), 1.58 (dd, Jˆ13.4,
To a mixture of Pd(dppe)Cl (9.9 mg, 0.017 mmol) in a
2
7
9
.2 Hz, 1H), 1.15 (d, Jˆ6.8 Hz, 3H), 1.01 (s, 3H), 0.91 (s,
5 mL test tube was added a solution of enyne 7a
(96.5 mg, 0.56 mmol) in dry toluene (1 mL). The mixture
was stirred for 10 min under argon atmosphere and then
1
H), 0.85 (s, 3H), 0.12 (s, 3H), 0.11 (s, 3H); C NMR
3
(
100 MHz, CDCl ): d 152.67, 137.48, 128.25, 128.09,
3
1
2
26.15, 124.64, 87.33, 46.60, 41.60, 32.88, 26.23, 26.02,
2.98, 22.79, 21.05, 18.37, 23.49, 24.44; FT-IR (neat,
treated with Et SiH (110 mL, 0.69 mmol) and formic acid
3
(26 mL, 0.67 mmol) via gastight syringes. The mixture was
stirred for 3 h at 608C in a preheated oil bath. The reaction
mixture was cooled to room temperature and concentrated
under reduced pressure. Silica gel chromatography (1:9
2
1
cm ): 3059, 3026, 2957, 2930, 2859, 2365, 1602, 1494,
471, 1385, 1362, 1251, 1170, 1158, 1142, 1071, 1051;
HRMS calcd for C H OSi(M ) 330.2379, found
1
1
2
1
34

1
728
C. H. Oh et al. / Tetrahedron 57 (2001) 1723±1729
1
3
EtOAc/hexane) of the residue gave the product 10a
(
1.11 (d, Jˆ6.4 Hz, 3H); C NMR (100 MHz, CDCl ): d
3
1
68.2 mg, 70%) as a colorless oil: H NMR (400 MHz,
153.23, 138.36, 135.99, 130.36, 127.56, 126.23, 126.15,
102.98, 84.43, 71.16, 46.12, 19.49, 14.08; FT-IR (neat,
cm ): 3075, 3026, 2962, 2930, 1668, 1492, 1461, 1375,
CDCl ): d 7.32±7.19 (m, 5H), 4.97 (d, Jˆ2.0 Hz, 1H),
3
2
1
4
6
2
1
1
3
1
1
.92 (d, Jˆ2.0 Hz, 1H), 4.37 (s, 2H), 3.86 (dd, Jˆ8.8,
.4 Hz, 1H), 3.60 (dd, Jˆ8.8, 6.0 Hz, 1H), 2.95 (m, 1H),
.94 (dd, Jˆ15.2, 5.2 Hz, 1H), 2.63 (dd, Jˆ15.2, 11.6 Hz,
1
1057, 1039; HRMS calcd for C H O (M ) 188.1201,
1
3
16
found 188.1193.
1
3
H); C NMR (100 MHz, CDCl ): d 151.09, 139.83,
3
28.64, 128.28, 126.06, 104.01, 73.52, 71.62, 45.31,
8.82; FT-IR (neat, cm ): 3062, 3026, 2938, 2848, 1665,
2
1
Acknowledgements
1
495, 1453, 1182, 1063; HRMS calcd for C H O (M )
74.1044, found 174.1040.
1
2
14
We wish to acknowledge the ®nancial support of KOSEF
1999-1-123-001-5), Korea, made in the program year of
1999.
(
1
.3.1. Compound 10b. H NMR (400 MHz, CDCl ): d 7.37
3
3
(
d, Jˆ8.0 Hz, 2H), 7.16 (d, Jˆ8.0 Hz, 2H), 4.92 (d,
Jˆ2.4 Hz, 1H), 4.87 (d, Jˆ2.4 Hz, 1H), 4.52 (ABq,
Ddˆ50.4 Hz, Jˆ13.2 Hz, 2H), 2.67 (m, 1H), 2.34 (s, 3H),
References
1
3
1
.32 (s, 3H), 1.09 (d, Jˆ7.2 Hz, 3H); C NMR (100 MHz,
CDCl ): d 153.28, 143.19, 136.26, 128.71, 124.71, 103.11,
3
1. Widenhoefer, R. A.; Stengone, C. N. J. Org. Chem. 1999, 64,
8681±8692.
8
5.92, 69.03, 48.95, 21.14, 20.57, 12.73; FT-IR (neat,
2
1
cm ): 2971, 2924, 2858, 2361, 2342, 1669, 1514, 1459,
376, 1306, 1240, 1186, 1078, 1037; HRMS calcd for
C H O (M ) 202.1357, found 202.1362.
2. For reviews, see: (a) Trost, B. M. Science 1991, 254, 1471±
1477. (b) Trost, B. M. Acc. Chem. Res. 1990, 23, 34±42.
(c) Trost, B. M.; Krische, M. J. Synlett 1998, 1±16. (d) Lu,
X.; Zhu, G.; Wang, Z.; Ma, S.; Ji, J.; Zhang, Z. Pure Appl.
Chem. 1997, 69, 553±558.
1
1
1
4
18
1
.3.2. Compound 10c. H NMR (400 MHz, CDCl ): d
3
3
7
.31±7.19 (m, 5H), 4.99 (d, Jˆ2.4 Hz, 1H), 4.88 (d,
3. Trost, B. M.; Li, Y. J. Am. Chem. Soc. 1996, 118, 6625±6633.
4. (a) Yamada, H.; Aoyagi, S.; Kibayashi, C. Tetrahedron Lett.
1997, 38, 3027±3030. (b) Trost, B. M.; Lautens, M.; Chan, C.;
Jebaratnam, D. J.; Mueller, T. J. Am. Chem. Soc. 1991, 113,
636±644. (c) Grigg, R.; Loganathan, V.; Sridharan, V.;
Stevenson, P.; Sukirthalingam, S.; Worakun, T. Tetrahedron
1996, 35, 11479±11502.
Jˆ2.4 Hz, 1H), 4.37 (s, 2H), 4.16 (m, 4H), 3.03 (dd,
Jˆ13.6, 5.2 Hz, 1H), 3.01 (ABq, Ddˆ29.4 Hz,
Jˆ16.8 Hz, 2H), 2.87 (m, 1H), 2.50 (dd, Jˆ13.6, 10.4 Hz,
1
1
3
1
6
H), 2.36 (dd, Jˆ13.0, 7.6 Hz, 1H), 1.85 (dd, Jˆ13.0,
1
H); C NMR (100 MHz, CDCl ): d 171.56, 171.53,
51.36, 140.19, 128.71, 128.19, 125.87, 106.52, 61.54,
1.47, 53.24, 43.80, 41.05, 40.34, 39.62, 14.16, 14.13; FT-
0.4 Hz, 1H), 1.23 (t, Jˆ7.2 Hz, 3H), 1.21 (t, Jˆ7.2 Hz,
3
3
5. (a) Trost, B. M.; Fleitz, F. J.; Watkins, W. J. J. Am. Chem. Soc.
1996, 118, 5146±5147. (b) Ojima, I.; Donovan, R. J.; Shay,
W. R. J. Am. Chem. Soc. 1992, 114, 6580.
2
1
IR (neat, cm ): 2983, 2932, 1731, 1657, 1451, 1367, 1254,
1
181, 1072, 1019; HRMS calcd for C H O (M )
16.1674, found 316.1677.
1
3
6. (a) Stork, G.; Mook, Jr., R. J. Am. Chem. Soc. 1987, 109,
2829±2831. (b) Stork, G.; Mook, Jr., R. J. Am. Chem. Soc.
1
9
24
4
1
983, 105, 3720±3722. For extended works, see:
1
.3.3. Compound 10d. H NMR (400 MHz, CDCl ): d 7.49
3
(
(c) Beckwith, A. L. J.; O'Shea, D. M. Tetrahedron Lett.
1986, 27, 4525±4528. (d) Clive, D. L. J.; Magnuson, S. R.;
Manning, H. W.; Mayhew, D. L. J. Org. Chem. 1996, 61,
2095±2108.
3
d, Jˆ7.2 Hz, 2H), 7.35 (t, Jˆ7.2 Hz, 2H), 7.26 (t,
Jˆ7.2 Hz, 1H), 4.93 (d, Jˆ2.0 Hz, 1H), 4.88 (d,
Jˆ2.0 Hz, 1H), 4.53 (ABq, Ddˆ50.2 Hz, Jˆ13.2 Hz, 2H),
1
3
2
.68 (m, 1H), 1.34 (s, 3H), 1.10 (d, Jˆ6.8 Hz, 3H);
C
NMR (100 MHz, CDCl ): d 153.25, 146.23, 128.10,
7. Oh, C. H.; Kim, A.; Rhim, C. Y.; Kang, J. H.; Park, B. S. Bull.
Koran Chem. Soc. 1996, 17, 879±881.
3
126.79, 124.84, 103.25, 86.00, 69.07, 48.91, 20.45, 12.62;
FT-IR (neat, cm ): 3060, 2972, 2857, 1667, 1494, 1446,
8. For the use of formic acid or formates as a hydrogen equiva-
lent in palladium-mediated reactions, see: (a) Tsuji, J.
Palladium Reagents and Catalysts, Wiley: Chichester,
England, 1995. (b) Tsuji, J.; Mandai, T. Synthesis 1996, 1±24.
2
1
1
1
1
377, 1304, 1073, 1037; HRMS calcd for C H O (M )
13 16
88.1201, found 188.1208.
9
. (a) Oh, C. H.; Rhim, C. Y.; Kang, J. H.; Kim, A.; Park, B. S.;
Seo, Y. Tetrahedron Lett. 1996, 37, 8875±8878. (b) Oh, C. H.;
Jung, H. H. Tetrahedron Lett. 1999, 40, 1535±1538.
1
.3.4. Compound 10e. H NMR (400 MHz, CDCl ): d 7.31
3
(
3
d, Jˆ8.4 Hz, 2H), 6.90 (d, Jˆ8.8 Hz, 2H), 4.97 (d,
Jˆ2.8 Hz, 1H), 4.90 (d, Jˆ2.4 Hz, 1H), 4.55 (ABq,
10. Oh, C. H.; Jung, H. H.; Kim, J. S.; Cho, S. W. Angew. Chem.
Int., Ed. Engl. 2000, 39, 752±755.
Ddˆ107.6 Hz, Jˆ13.2 Hz, 2H), 4.22 (d, Jˆ9.6 Hz, 1H),
1
3
3
.82 (s, 3H), 2.49 (m, 1H), 1.06 (d, Jˆ6.8 Hz, 3H);
C
NMR (100 MHz, CDCl ): d 159.11, 153.06, 132.36,
11. Trost, B. M.; Edstrom, E. D.; Carter-Petillo, M. B. J. Org.
Chem. 1989, 54, 4489±4490.
3
1
27.71, 113.64, 102.85, 87.89, 71.17, 55.31, 46.37, 13.49;
12. (a) Wratten, S. J.; Faulkner, D. J. J. Org. Chem. 1977, 42,
3343±3349. (b) Irie, T.; Yasunari, Y.; Suzuki, T.; Imai, N.;
Kurosawa, E.; Masamune, T. Tetrahedron Lett. 1965, 6,
3619±3624. (c) Irie, T.; Suzuki, T.; Yasunari, Y.; Kurosawa,
E.; Masamune, T. Tetrahedron 1969, 25, 459±468. (d) Bailey,
W. F.; Jiang, X.-L.; McLeod, C. E. J. Org. Chem. 1995, 60,
7791±7795.
2
1
FT-IR (neat, cm ): 2961, 2836, 1666, 1613, 1515, 1462,
374, 1303, 1248, 1173, 1059, 1035; HRMS calcd for
C H O (M ) 204.1150, found 204.1143.
1
1
1
3
16
2
1
.3.5. Compound 10f. H NMR (400 MHz, CDCl ): d 7.43
3
3
(
4
d, Jˆ7.2 Hz, 1H), 7.20 (m, 3H), 4.98 (d, Jˆ2.4 Hz, 1H),
.91 (d, Jˆ2.4 Hz, 1H), 4.62 (d, Jˆ9.6 Hz, 1H), 4.58 (ABq,
Ddˆ97.4 Hz, Jˆ13.6 Hz, 2H), 2.65 (m, 1H), 2.38 (s, 3H),
13. Trost, B. M.; Rise, F. J. Am. Chem. Soc. 1987, 109, 3161±
3163.

C. H. Oh et al. / Tetrahedron 57 (2001) 1723±1729
1729
1
4. (a) Wratten, S. J.; Faulkner, D. J. J. Org. Chem. 1977, 42,
3
17. Yamada, H.; Aoyagi, S.; Kibayashi, C. Tetrahedron Lett.
1996, 37, 8787±8790.
343±3349. (b) Hall, J. G.; Reiss, J. A. Aus. J. Chem. 1986,
9, 1401±1409.
3
18. Full characterization of cis-10g has not been accomplished,
since the desilylated product of cis-10g and the cis-10i were
15. epi-10 Was not fully characterized due to a limited amount of
the isolated product.
1
identical in their H NMR spectra except some peaks corre-
sponding to impurities.
1
6. Oh, C. H.; Han, J. W.; Kim, J. S.; Um, S. Y.; Jung, H. H.; Jang,
W. H.; Won, H. S. Tetrahedron Lett. 2000, 53, 8365±8369.