Stereo-defined synthesis of differentially all-carbon tetrasubstituted alkenes derived from (E)-1-bromo-2-iodoalkenes

Article abstract of DOI:10.1016/j.tet.2017.08.013

An intuitive approach to differentially all-carbon tetrasubstituted olefins from a scaffold of (E)-1-bromo-2-iodoalkenes is described. The iodine atom of the scaffold selectively undertook CuTC-mediated cross-coupling reactions with organotin reagents, suppressing a side-reaction of β-halogen elimination. The resultant vinyl bromides were successfully subjected to various transformations into tetrasubstituted olefins bearing four different carbon-linked groups. The crystallographic analysis revealed that the configuration of the double bonds is fully retained in those two steps. Thus, the template strategy would provide a new entry for preparing stereo-defined tetrasubstituted alkenes.

Full text of DOI:10.1016/j.tet.2017.08.013

Accepted Manuscript
Stereo-defined synthesis of differentially all-carbon tetrasubstituted alkenes derived
from (E)-1-bromo-2-iodoalkenes
Naoki Endo, Tetsuo Iwasawa
PII:
S0040-4020(17)30833-5
10.1016/j.tet.2017.08.013
TET 28907
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 29 June 2017
Revised Date: 2 August 2017
Accepted Date: 10 August 2017
Please cite this article as: Endo N, Iwasawa T, Stereo-defined synthesis of differentially all-carbon
tetrasubstituted alkenes derived from (E)-1-bromo-2-iodoalkenes, Tetrahedron (2017), doi: 10.1016/
j.tet.2017.08.013.
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Stereo-defined synthesis of differentially all-
carbon tetrasubstituted alkenes derived from
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(E)-1-bromo-2-iodoalkenes.
Naoki Endo, Tetsuo Iwasawa*
Department of Materials Chemistry, Ryukoku University, Otsu, Shiga, 520-2194, Japan

1
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Tetrahedron
journal homepage: www.elsevier.com
Stereo-defined synthesis of differentially all-carbon tetrasubstituted alkenes derived
from (E)-1-bromo-2-iodoalkenes.
a
a,
Naoki Endo , Tetsuo Iwasawa 
a
Department of Materials Chemistry, Ryukoku University, Otsu, Shiga, 520-2194, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An intuitive approach to differentially all-carbon tetrasubstituted olefins from a scaffold of (E)-
1-bromo-2-iodoalkenes is described. The iodine atom of the scaffold selectively undertook
CuTC-mediated cross-coupling reactions with organotin reagents, suppressing a side-reaction of
-halogen elimination. The resultant vinyl bromides were successfully subjectd to various
transformations into tetrasubstituted olefins bearing four different carbon-linked groups. The
crystallographic analysis revealed that the configuration of the double bonds is fully retained in
those two steps. Thus, the template strategy would provide a new entry for preparing stereo-
defined tetrasubstituted alkenes.
Available online
Keywords:
Alkene geometry
Differentially all-carbon tetrasubstituted olefins
Vicinal hetero-dihaloalkenes
Molecular diversity
2
009 Elsevier Ltd. All rights reserved.
Platform synthesis
1
. Introduction
substrates follow. This unpleasant side-reaction provides
chemists continuing challenge toward stereo-controlled
synthesis of tetrasubstituted olefins.
a
Efficient regio- and stereoselective synthesis of differentially
1
all-carbon tetrasubstituted olefins still remains
challenge, although their significance lies in medicinal and
material chemistry. Even monumental approaches including
carbometallation of alkynes, carbonyl olefination, elimination
a
3,g4rand
1
,2
5
,6
7
8
9
10
reaction, and olefin metathesis, would give E/Z or regio-
isomeric mixtures. Based on these limitations, the use of diverse
1
1
scaffold strategies seems to be an attractive option:
differentially substituted olefin templates enable forming various
and stereo-defined tetrasubstituted olefins, provided that the
configuration of the double bond is fully retained during the
1
2
transformations.
Recently, we have reported regio- and stereoselective
iodobromination of internal alkynes; the triple bonds reacted with
1
3
in situ IBr to yield anti-IBr adduct, like 1, as a single isomer. To
establish 1 as a stereo-defined alkenyl template for a synthesis of
differentially all-carbon tetrasubstituted olefins, 1 was subjected
to conventional transformations using palladium catalyzed
reaction (Scheme 1 (a)); however, the reaction didn’t work and
caused -halogen elimination to yield numerous amounts of 1-
Scheme 1. (a) -Halogen elimination of 1 on palladium-
catalyzed reaction condition; (b) Reactivity of 1 on a vinylic
Rosenmund-von Braun cyanation; (c) Iodine-selective reaction of
1 with tributyl(thiophen-2-yl)stannane to give the corresponding
full-substituted vinyl bromide 2.
1
3
phenyl-1-butyne. A CuCN-mediated cyanation of 1 was also
unworkable, giving side-products of bromine migration, double
1
4
cyanation, and -halogen elimination (Scheme 1 (b)). For the -
1
5
16
halogen elimination, Rathore group and Ogilvie group
Herein we describe a scaffold strategy for synthesis of
differentially all-carbon tetrasubstituted olefins utilizing a key
compound of (E)-1-bromo-2-iodoalkene template (Scheme 1 (c)).
reported similar observations: vicinal dihaloalkenes readily
undertook this type of side-reactions, whatever mechanism the
—
——

Corresponding author. Tel.: +81-77-543-7461; fax: +81-77-543-7483; e-mail: iwasawa@rins.ryukoku.ac.jp

2
Tetrahedron
ACCEPTED MANUSCRIPT
First, the template took on CuTC-mediated carbon-carbon bond
forming reactions with organotin reagents just at the iodine site,
suppressing the -halogen elimination side-reaction. Then, the
following substitution reactions at the Br site yielded the
corresponding tetrasubstituted alkenes as single isomeric
compounds with full retention of stereochemistry. We carefully
investigated reactivities of vinylic iodine and bromine for taking
basic information to construct future synthetic chemistry of
tetrasubstituted alkenes.
ratio. When the use of 2 was scaled up in 6 mmol (2.05 g), 4 was
21
given in 91% (2.63 g) with
a 96:4 isomeric ratio.
Recrystallization from CH CN purified the sample, giving a
3
perfect pure 4 in 60% (1.75 g). The molecular structure of the
2
2
pure 4 was determined by crystallographic analysis (Figure 1),
which disclosed that nearly full retention of the stereochemistry
throughout from 1 to 4 was accomplished.
2
. Results and Discussion
We started investigation with a CuTC-mediated cross-
1
7, 18
coupling of 1 undertaken as shown in Scheme 1(c)
and the
preliminary research after several tests reached initial criterion of
entry 1 in Table 1: the combination of CuTC with PPh in toluene
3
solvent at 90 ºC consumed the starting 1, yielding 76% of desired
2
along with <5% of side-product 3 derived from halogen
elimination. To our surprise, any other products like as non-
selective mono- or double-substituted molecules were not found
even in crude states: the reaction was impressively clean. Rf
values of 1, 2, and 3 were 0.52, 0.35, and 0.38 on TLC
monitoring eluted with hexane only, respectively; the separation
of 2 from 3 was not easy but careful chromatographic column
Scheme 2. Synthesis of 4 from 2 via palladium-catalyzed
reaction.
isolated 2. For entry 2, no use of PPh made the reaction slow and
3
1
9
gave 2 in 56%. For entry 3, lowering the temperature to 70 ºC
needed overnight reaction time, and yielded 1 in 68% along with
3
% of 2. It appeared to us that the condition of entry 1 (90 ºC, 3
h, CuTC/PPh ) would be effective. For entry 4, even in 1.5 h of
3
the reaction time, the reaction yielded 2 in 81% with trace
amount of 3 This selective reaction was amenable to scale-up
synthesis (entry 5); finally, 9 mmol of 1 afforded 2.1 g of 2 in
8
0% yield (entry 6). Thus, this unwavering transformation means
that (E)-1-bromo-2-iodoalkene would be a template for singly
constructing diverse tetrasubstituted olefins.
Table 1. Evaluation of the reactivity of 1 conducted via
Scheme 1(c).
[
a]
Scale of 1
mmol (g)
%Yields
Entry
Time/h
/
2
3
1
0
1
0.5 (0.17)
0.5 (0.17)
0.5 (0.17)
1.0 (0.34)
3.0 (1.0)
9.0 (3.0)
3
3
Figure 1. ORTEP drawing of 4 with thermal ellipsoids at the 50% probability
level. Hydrogen atoms are omitted for clarity. Selected bond lengths [Å] and
angles [º] for 4: C17-C18 1.354, C17-C21 1.499, C17-C1 1.496, C18-C27
7
6
6
8
1
7
<5
3
[b]
2
5
6
8
7
17
0
[c]
3
20
1.5
2
1
.462, C18-C19 1.520, C18-C17-C21 123.86, C1-C17-C21 115.17, C1-C17-
C18 120.96, C17-C18-C27 124.42, C19-C18-C27 115.17, C17-C18-C19
20.31.
3
4
5
6
trace
trace
trace
trace
0
1
2
[d]
8
0
0
With a viable protocol in hand, we surveyed the reactivity of
the vinylic iodine in (E)-1-bromo-2-iodoalkenes (Table 2): for
entries 1-10, organotin was fixed, and reactivities of ortho-tolyl
a
b
c
d
Isolated yields.
The reaction was conducted without PPh
The reaction was conducted at 70 ºC.
3
.
5
a, para-methoxyphenyl 5b, 9-anthryl 5c, para-benzonitrile 5d
were evaluated. The starting 5a, 5b, and 5d showed moderate
reactivities, yielding 7a, 7b, and 7d in around 60%. The side-
production of the corresponding alkynes 8 were recognizably
observed in 10-20%. For the starting 5c in entries 6 and 7, TLC
monitoring of the reaction process gave multi spots, and the yield
of 7c was low presumably due to the bulky 9-anthryl moiety. For
entries 11-15, substrate 1 was fixed, and reactivities of sp-
2
.1 g of 2 was isolated.
As illustrated in Scheme 2, the resultant vinylic bromine atom
in 2 served as a convenient handle for forming carbon-carbon
bonds, which yielded a differentially all-carbon tetrasubstituted
olefin. The vinyl bromide 2 of 0.3 mmol under the condition of
Suzuki-Miyaura cross-coupling with pyren-1-ylboronic acid
afforded 4 of 115 mg in 93% yield: the H NMR spectrum
showed the product is practically single with a >99:1 isomeric
2
0
2
1
hybridized carbon-stannane 6a, sp -hybridized carbon-stannane
3
6
b and 6c, sp -hybridized carbon-stannane 6d were evaluated.
The 6a and 6b showed acceptable yields, 51% of 7e and 75% of

3
ACCEPTED MANUSCRIPT
entries 14 and 15, the reaction was not regulated as we expected,
7
f (entries 12 and 13). However, for phenyl-6c and allyl-6d of
proved to be not perfect but rather effective for decreasing
alkynes, which has not been reported so far.
and the desired 7g and 7h were not obtained. The reaction system
[
a]
Table 2. Evaluation of reactivities of vinylic iodines in (E)-1-bromo-2-iodoalkenes.
[b]
Substrate
Product
%Yield
Entry
Organotin
Temp./ºC
Time/h
5
or 1
5a
7
7
8
5 or 1
1
2
3
85
90
23
17
5
7a
7b
65
11
trace
0
[c]
[c]
5b
48
58
24
[c]
[c]
70
15
4
[
d]
4
70
19
25
23
20
11
2
61
11
11
0
0
5
6
7
8
9
r.t.
90
68
14
0
tributyl(2-
thienyl)tin
[e]
5c
7c
25
21
35
17
11
34
9
110
90
10
60
56
36
12
5d
7d
0
90
5
1
0
1
2
3
70
20
20
20
2
10
16
4
1
1
1
1
6a
90
7e
[f]
110
90
51
10
3
[
g]
6b
6c
6d
7f
75
0
6
[h]
1
4
5
110
110
17
17
7g
7h
-
-
[h]
1
0
-
-
a
Conditions: substrate (0.5 mmol), organotin (0.75 mmol), toluene (4 mL). Stereochemistry of 7 was inferred from evidence of the ORTEP drawing in Figure 1.
b
Isolated yields, unless otherwise noted.
c
NMR yields as a mixture of 7 and 8 after chromatographic purification.
d
Each 3 equiv of CuTC, 2, and PPh
5% purity.
3
was used.
e
9
f
Average of two runs. In this entry, numerous amounts of homo-coupling adducts of 6a were observed.
g
7f was totally decomposed in ca. 4 h right after the purification.
h
NMR spectra in the crude showed terribly messy peaks, although the slight peaks of apparently desired 7 appeared along with clear peaks of 8a and 1.
Bu) ] was effectual for not only high-yielding transformation but
3
2
also consumption of 2 (entry 6). Although the additional P(t-Bu)3
was indispensable for the completion, the reaction was relatively
Next, we studied reactivity of the resultant vinylic bromine
that is the second tag for synthesizing diverse tetrasubstituted
olefins. As shown in Scheme 3, bromine 2 was evaluated in
Sonogashira reaction that is known as a powerful tool for
2
3
installation of alkynyl sp-hybridized carbon, and the results
were summarized in Table 3. For entries 1-3, conventional
PdCl (PPh ) and Pd(PPh ) catalyzed the cross-coupling to give
2
3 2
3 4
9
as a single isomer, but the unreacted 2 remained anyhow. Even
2
4
2
5
though Fu’s protocol (entry 4) and Alami’s method (entry 5)
were attempted, the reactions didn’t complete. These
shortcomings would be caused by numerous amounts of side-
clean on TLC monitoring.
products
that
were
homo-coupling
adducts
of
Scheme 3. Sonogashira cross-coupling reaction between 2 and
triisopropylsilylacetylene.
2
6
triisopropylsilylacetylenes. We finally found the use of Pd[P(t-

4
Tetrahedron
a
ACCEPTED MANUSCRIPT
Conditions: 1 (0.3 mmol), tributyl(thiophen-2-yl)stannane (0.45 mmol),
toluene (0.5 mL), unless otherwise noted. Stereochemistry of 10 was inferred
Table 3. Evaluation of the reactivity of 2 conducted via
from evidence of the ORTEP drawing in Figure 1.
[
a]
Scheme 3.
b
Isolated yields in 2 steps.
[
b]
%Yield
PdL
n
, additive, CuI, solvent/amine (1/1
v/v), temp./ºC, time/h
c
Entry
Without additional 10 mol% P(t-Bu)3.
9
2
1
10 mol% PdCl
2
(PPh
3
)
2
, 10 mol% PPh
3
,
4
4
6
7
7
8
37
43
22
14
40
0
1
0 mol% CuI, toluene/Et
3
N, 70 ºC, 8 h
2
3
10 mol% PdCl (PPh , 10 mol% CuI,
2
3 2
)
toluene/Et N, 70 ºC, 13 h
3
3 4
10 mol% Pd(PPh ) , 20 mol% CuI,
toluene/Et N, 70 ºC, 13 h
3
[c]
[
e]
4
2
2
3
3 mol% PdCl (PhCN) , 6 mol% P(t-Bu) ,
<
83
6
mol% CuI, dioxane/HN(iPr) , r.t., 20 h
2
Scheme 5. Vinylic Rosenmund-von Braun cyanation of 2 to give
11.
5
5 mol% PdCl (PhCN) , 10 mol% CuI,
2
2
5
9
0
piperidine, 70 ºC, 3 h
[
d]
6
5 mol% Pd[P(t-Bu) , 10 mol% P(t-Bu)
]
3 2
3
,
The vinyl bromide 2 was also subjected to vinylic
5
1
0 mol% CuI, toluene/Et N, 70 ºC, 4 h
3
Rosenmund-von Braun cyanation that attaches sp-hybridized
carbon (Scheme 5). Although the high temperature of 135 ºC was
needed for smooth reaction completion, desired 11 was singly
a
Conditions: 2 (0.5 mmol), triisopropylsilylacetylene (0.75 mmol), solvent
0.5 mL), unless otherwise noted. Stereochemistry of 9 was inferred from
(
2
7, 28
evidence of the ORTEP drawing in Figure 1.
formed in 91% yield.
b
Isolated yields.
Negishi reaction is known as one of the most convenient
c
2
3
The reaction was conducted at 70 ºC.
methods for installation of sp - and sp -carbon into the vinylic
bromine, which proceeds under neutral condition unlike Suzuki-
Miyaura reaction utilizing basic condition. We evaluated the
reactivity of 2 on Negishi cross-coupling (Scheme 6). For the
part of (a), the use of Pd(PPh ) didn’t consume all of the starting
d
1
mmol of 2 was used.
e
Inseparable impurities were included.
3
4
2
(entries 1 and 2), but Pd[P(t-Bu) ] was effective for using up 2
3 2
As illustrated in Scheme 4, this Sonogashira protocol was
successfully applicable to labile 7f that was obtained in Table 2;
and the results were summarized in Table 4. The vinyl bromide
f decomposed totally within 4 h after chromatographic
purification; so, right after the crude 7f was filtered through a
short-plugged silica-gel column chromatography, the sample was
provided to the next coupling step. The reaction at 70 ºC didn’t
completed (entry 1), but the raise to 85 ºC consumed the starting
f and yielded 10 in 79% (entry 2). Luckily, the full-substituted
0 was stable as we expected. No use of additional P(t-Bu)3
although the aid of additional 10 mol% P(t-Bu) was required
3
(entry 4). The reaction gave 2•H as a side-product that was not
observed in Suzuki protocol of Scheme 2. For part (b), sec-
butylzinc(II) bromide was employed as a reaction partner. The
conventional condition utilizing Pd(PPh ) as well as Fu’s
method were attempted;
1
with other unidentified side-products. We also tried reactions
utilizing alkylboronic acids instead of alkylzinc halides, which
ended up in complicated mixtures including 2•H.
7
3
4
29, 30
however, these didn’t afford desired
3, and gave numerous amounts of de-halogenated 2•H along
7
1
decreased the yield to 21% (entry 3). As the temperature went up
to 95 ºC, the production of 10 was suppressed owing to large
Scheme 6. Evaluation of reactivity of 2 in Negishi cross-coupling
side-production
of
homo-coupling
adduct
of
triisopropylsilylacetylene (entry 4). Thus, the reactivity of the
vinylic bromine in Sonogashira reaction seems to be relatively
sensitive toward the reaction temperature.
Scheme 4. A through-process for use of labile 7f: synthesis of
tetrasubstituted 10.
Table 4. Evaluation of the reactivity of 7f conducted via
Scheme 4.
[
b]
%Yield
Entry
amine
temp./ºC
time/h
1
3
7
2
4
0
7
9
1
8
unreacted 7f
1
2
Et
Et
Et
3
3
3
N
N
N
70
85
85
95
15
17
15
15
36
0
[c]
3
33
19
4
EtN(iPr)
2

5
ACCEPTED MANUSCRIPT
reaction employing a) p-tolylzinc iodide, and b) sec-butylzinc
(E)-1-bromo-2-iodoalkene templates. Particularly, the reagent
bromide.
combination of CuTC/PPh /organotin in the first step plays an
3
important role in this “differentially substituted olefin template
strategy”. The results suggest that the strategy provides three
salient features: One, the use of CuTC and organostannane
selectively substitutes a carbon group for the vinylic iodine. Two,
the copper-mediated reaction greatly suppresses unpleasant side-
reaction of -halogen elimination. Three, the template retains its
configuration during these two-step conversions, exclusively
giving singly defined tetrasubstituted alkenes. Clearly, these
features would constitute an illustration of the high potential of
(E)-1-bromo-2-iodoalkene template for general use to synthesize
new tetrasubstituted olefins. On the other hand, it is certain that
this sequential approach doesn’t yet reach mature level. There are
Alternatively, lithium-halogen exchange is one of the most
monumental, reliable and established protocols for replacement
of the vinylic bromine with sp -hybridized carbon. As
illustrated in Scheme 7, the bromide 2 could be activated with
tert- or n-butyl lithium, and its resultant vinyl lithium was
exposed to allyl bromide. The results were summarized in Table
3
31
5
. For entry 1, the conventional method employing tert-BuLi in
THF solvent at low temperature consumed all of the starting 2,
but unfortunately gave many side-products including 2•H. The
1
H NMR ratio of 14/2•H after short-plugged silica-gel column
chromatography showed 3.5/1. For entries 2 and 3, the lithiation
in toluene solvent was found to proceed at 0 ºC, and the addition
of THF (4 eq) drastically improved the productivity of 14 with up
to 30/1 ratio of 14/2•H. Although the separation of 14 from 2 was
laborious, use of many amounts of silica-gel barely isolated 14 in
two major points needing improvement: poor reactivity of
3
PhSnBu
and CH
=CHCH
SnBu
, and difficult induction of sp -
3
2
2
3
3
2, 33
hybridezed carbons to the vinylic bromine.
Our progress
reported herein about the synthetic route is the decisive evidence
showing the template utility of (E)-1-bromo-2-iodoalkene that is
a simple, small, and intuitive molecule. Further synthetic
development and improvement is ongoing and will be reported in
due course.
5
0% yield. We expected that more convenient n-BuLi supplies
the place of tert-BuLi (entries 4 and 5); however, the obtained
crude products consisted of many side-products.
4
. Experimental section
.1 General
All reactions sensitive to air or moisture were carried out
4
Scheme 7. Substitution of allyl moiety for the vinylic bromine of
under an argon atmosphere and anhydrous conditions unless
otherwise noted. Dry solvents were purchased and used without
further purification and dehydration. All reagents were purchased
and used without further purification. Analytical thin layer
chromatography was carried out on Merck silica 60F254. Column
chromatography was carried out with silica gel 60N (Kanto
Chemical Co.). LRMS and HRMS were reported on the basis of
TOF (time of flight)-MS (LCMS-IT-TOF; Shimadzu), and
2
through lithium–halogen exchange reaction to synthesize 14.
Table 5. Evaluation of the reactivity of 2 conducted via
[
a]
Scheme 7.
NMR
Isolated
yields[%]
14
1
1
BuLi
eq)
Add.
(eq)
temp. /ºC, time /h
[b]
1
13
Entry
Solv.
ratios
4/2•H
DART (Direct Analysis in Real Time)-MS. H and C NMR
spectra were recorded with a 5 mm QNP probe at 400 MHz and
2
2
(
temp. /ºC, time /h
1
1
00 MHz, respectively. Chemical shifts are reported relative to
1
tBuLi
2.2)
tBuLi
2.2)
tBuLi
2.2)
nBuLi
1.1)
nBuLi
1.1)
-78, 0.25
r.t., 1
residual solvent signals [ H NMR: CHCl (7.26), C H (2.08),
3 7 8
13
1
2
THF
toluene
toluene
toluene
THF
-
-
3.5/1
0/100
30/1
-
-
C H (7.16), CH Cl (5.32); C NMR: CDCl (77.0)]. Signal
6
6
2
2
3
(
patterns are indicated as s, singlet; d, doublet; t, triplet; q, quartet;
m, multiplet; br, broad.
0, 0.25
0, 1
(
4
.2 General procedure of (E)-2-(1-bromo-1-phenylbut-1-en-2-
THF
(4)
0, 0.25
0, 1
[
c]
3
50
-
yl)thiophene 2, for Table 1, entry 6: Under an argon
(
atmosphere, to a solution of 1 (3.03 g, 9.00 mmol) and PPh (3.54
3
g, 13.5 mmol) in toluene (60 mL) was added tributyl(2-
thienyl)tin (4.3 mL, 13.5 mmol), and then Copper (I) thiophene-
THF
(4)
r.t., 0.25
r.t., 2
4
5
2.1/1
4.7/1
(
2
-carboxylate (2.57 g, 13.5 mmol), namely CuTC, was
suspended. After stirred at 90 ºC for 2 h, the reaction mixture was
allowed to cool to ambient temperature, and followed by
filtration through a pad of celite and frolisil, and evaporation. The
resultant residue was dissolved into toluene (100 mL), and
washed with brine (40 mL), and dried over Na SO , and
-78, 0.2
r.t., 2
-
-
(
a
0
.3 mmol of 2 was used, unless otherwise noted.
2
4
b
The ratios were determined on the basis of the crude sample that was
concentrated in vacuo to give a crude product as a mixture of
orange oil and brown solid. The crude was washed with hexane
(3.3 mL/g) at room temperature, and the filtrate was concentrated
in vacuo to give a yellow oil. Purification with silica gel column
chromatography (hexane only) afforded 2.10 g of 2 as a yellow
oil in 80% yield. Analytical data are listed in the section below.
purified through a short-plugged silica-gel (eluent, hexane/EtOAc = 50/1).
c
1
mmol of 2 was used.
3
. Conclusion
4
.2.1. (E)-2-(1-bromo-1-phenylbut-1-en-2-yl)thiophene (2). 80%
1
In summary, we demonstrated a straightforward synthesis of
differentially all-carbon tetrasubstituted olefins in two steps from
yield (2.1 g); yellow oil; H NMR (400 MHz, CDCl ) 7.27-7.22
3
(m, 5H), 6.92 (dd, J = 5.1 Hz, 1.0 Hz, 1H), 6.76 (dd, J = 5.1 Hz,

6
Tetrahedron
ACCEPTED MANUSCRIPT
3
.6 Hz, 1H), 6.64 (dd, J = 3.6 Hz, 1.0 Hz, 1H), 2.86 (q, J = 7.5
4.2.6.
(E)-(1-bromo-2-ethylbut-1-en-3-yne-1,4-diyl)dibenzene
1
3
1
Hz, 2H), 1.17 (t, J = 7.5 Hz, 3H) ppm; C NMR (100 MHz,
(7e). 51% yield (95 mg); yellow oil; H NMR (400 MHz, CDCl )
3
CDCl ) 141.9, 141.8, 137.1, 130.1, 128.6, 128.4, 127.7, 126.7,
7.65 (d, J = 7.0 Hz, 2H), 7.39-7.20 (m, 8H), 2.63 (q, J = 7.5 Hz,
3
1
3
1
25.9, 121.4, 33.7, 12.5 ppm; MS (DART-TOF) m/z: 294
2H), 1.27 (t, J = 7.5 Hz, 3H) ppm; C NMR (100 MHz, CDCl3)
140.7, 131.6, 130.0, 129.9, 128.9, 128.6, 128.5, 128.0, 126.3,
123.5, 94.1, 88.6, 31.4, 12.6 ppm; MS (DART-TOF) m/z: 313
+
[
M(Br81)] (100%); IR (neat): 3072, 2967, 2927, 2867, 1595,
-
1
1
439, 1217, 1072, 1016, 855, 678 cm ; HRMS (DART-TOF)
+
+
calcd for C H Br(81)S: 293.9901 [M(Br81)] , Found 293.9881;
[M(81)+H] ; IR (neat): 3048, 2969, 2873, 2337, 2210, 1947,
1
4
13
-
1
Anal. Calcd for C H BrS: C, 57.35; H, 4.47. Found: C, 57.30;
1800, 1597, 1487, 1441, 752, 687 cm ; HRMS (DART-TOF)
1
4
13
+
H, 4.33.
calcd for C H Br(81): 313.0415 [M(81)+H] , Found 313.0412;
1
8
16
Anal. Calcd for C H Br(79): C, 69.47; H, 4.86. Found: C,69.50;
H, 4.82.
1
8
15
4
6
.2.2. (E)-2-(1-bromo-1-(o-tolyl)oct-1-en-2-yl)thiophene (7a).
5% yield (235 mg); pale yellow viscous materials; H NMR
1
(
400 MHz, CDCl ) 7.24-7.20 (m, 1H), 7.18-7.17 (m, 3H), 7.04
4.2.7. (E)-2-(1-bromo-1-phenylbut-1-en-2-yl)furan (7f). This
3
(dd, J = 5.1 Hz, 1.2 Hz 1H), 6.77 (dd, J = 5.1 Hz, 3.7 Hz, 1H),
compound is very labile; actually, its decomposition was
6
.71 (dd, J = 3.7 Hz, 1.2 Hz, 1H), 2.21 (s, 3H), 2.89 (dt, J = 13.3
observed within 4 h after chromatographic purification.
Hz, 5.4 Hz, 1H), 2.87 (dt, J = 15.1 Hz, 5.4 Hz, 1H), 1.67 (tt, J =
Identification of this molecule was ensured in this derivative 10
7
=
.8 Hz, 2H), 1.49-1.42 Hz (m, 2H), 1.37-1.33 (m, 4H), 0.91 (t, J
shown in Scheme 4, which is described in the section below.
1
3
1
7.0 Hz, 3H) ppm; C NMR (100 MHz, CDCl ) 141.5, 141.1,
75% yield (101 mg); yellow oil; H NMR (400 MHz, CDCl )
3
3
1
3
36.9, 135.9, 130.9, 130.2, 129.2, 126.9, 126.5, 126.1, 120.9,
7.32-7.24 (m, 5H), 7.18 (m, 1H), 6.16-6.14 (m, 1H), 5.61 (d, J =
8.9, 32.0, 29.6, 28.5, 23.0, 19.6, 14.4 ppm; MS (DART-TOF)
3.4 Hz, 1H), 2.81 (q, J = 7.5 Hz, 2H), 1.16 (t, J = 7.5 Hz, 3H)
+
13
m/z: 363 [M(79)+H] ; IR (neat): 2955, 2923, 2855, 1595, 1456,
1
C H Br(79)S: 363.0782 [M(Br79)+H] , Found 363.0756; Anal.
Calcd for C H BrS: C, 62.51; H, 6.44. Found: C, 62.80; H,
ppm; C NMR (100 MHz, CDCl ) 152.1, 142.4, 141.6, 133.7,
3
-
1
217, 855, 694 cm ; HRMS (DART-TOF) calcd for
129.4, 128.7, 128.4, 121.7, 111.3, 110.5, 29.7, 12.8 ppm.
+
1
9
24
4
.3 Synthesis of (E)-2-(1-phenyl-1-(pyren-1-yl)but-1-en-2-
1
9
23
yl)thiophene 4, for Scheme 2. Under an argon atmosphere, to a
solution of 2 (2.05 g, 7.0 mmol) in DMF (35 mL) was added 1-
Pyreneboronic acid (2.58 g, 10.5 mmol), and K CO (1.93 g, 14
6
.38.
4
.2.3.
(E)-2-(1-bromo-1-(4-methoxyphenyl)oct-1-en-2-
2
3
yl)thiophene (7b). 61% yield (116 mg); pale yellow viscous
mmol), and Pd(PPh ) (809 mg, 0.7 mmol). After stirred at 90 ºC
3 4
1
materials; H NMR (400 MHz, CDCl ) 7.18 (d, J = 8.9 Hz, 2H),
for 20 h, the reaction mixture was allowed to cool to ambient
temperature. The mixture was filtered through a pad of celite and
frolisil, and the filtrate was evaporated off. The resultant residue
was dissolved into toluene (100 mL), and washed with water (40
mL). The aqueous phase was extracted with toluene (15 mL x 3),
and the combined organic layers were washed with brine (40
mL), and dried over Na SO , and concentrated in vacuo to give a
3
7
=
1
6
1
3
.09 (dd, J = 5.1 Hz, 1.2 Hz, 1H), 6.79-6.76 (m, 3H), 6.66 (dd, J
3.7 Hz, 1.2 Hz 1H), 3.79 (s, 3H), 2.80 (t, J = 7.8 Hz, 2H), 1.60-
.52 (m, 2H), 1.44-1.37 (m, 2H), 1.33-1.29 (m, 4H), 0.89 (t, J =
1
3
.9 Hz, 3H) ppm; C NMR (100 MHz, CDCl ) 159.6, 142.5,
3
35.5, 134.3, 131.5, 127.4, 126.7, 125.7, 122.1, 114.0, 55.5, 40.3,
1.9, 29.5, 28.0, 23.0, 14.4 ppm; MS (DART-TOF) m/z: 379
2
4
+
[
M(79)+H] ; IR (neat): 2950, 2919, 2856, 1603, 1502, 1450,
crude product as a yellowish brown solid. Purification with silica
gel column chromatography (hexane/toluene=4/1) afforded 2.63
-
1
1
293, 1229, 1172, 1030 cm ; HRMS (DART-TOF) calcd for
+
1
C H Br(79)OS: 379.0731 [M(79)+H] , Found 379.0706.
g of 4 as a yellowish white solid in 91% yield. H NMR (400
1
9
24
MHz, CDCl ) 8.38 (d, J = 9.2 Hz, 1H) 8.21-8.16 (m, 3H), 8.10-
8.08 (m, 3H), 8.00 (dd, J = 7.6 Hz, 7.6 Hz, 1H) 7.94 (d, J = 7.8
3
4
.2.4. (E)-2-(1-(anthracen-9-yl)-1-bromo-oct-1-en-2-yl)thiophene
1
(7c). 25% yield (57 mg); yellow viscous materials; H NMR (400
Hz, 1H), 7.25-7.22 (m, 3H), 7.14-7.08 (m, 3H), 6.93-6.92 (m,
MHz, CDCl ) 8.50 (s, 1H), 8.12 (d, J = 8.5 Hz, 2H), 8.02 (d, J =
13
3
2
H) 2.31 (q, J = 7.4 Hz, 2H), 0.95 (t, J = 7.4 Hz, 3H) ppm;
C
8
3
2
0
1
1
.3 Hz, 2H), 7.39 (m, 4H), 6.75 (d, J = 5.0 Hz, 1H), 6.66 (d, J =
.8 Hz, 1H) 6.53 (dd, J = 5.0, 3.8 Hz, 1H), 3.18 (t, J = 8.0 Hz,
H), 1.91 (tt, J = 8.0, 8.0 Hz, 2H), 1.61 (m, 2H), 1.44 (m, 4H),
NMR (100 MHz, CDCl ) 144.2, 143.1, 138.6, 138.4, 136.9,
3
1
31.7, 131.4, 130.7, 130.2, 129.0, 128.3, 128.0, 127.74, 127.71,
127.60, 127.58, 126.91, 126.90, 126.3, 125.8, 125.48, 125.46
two peaks are overlapped), 125.28, 125.26, 125.21, 30.6, 13.6
1
3
.97 (t, J = 6.8 Hz, 3H) ppm; C NMR (100 MHz, CDCl ) 140.7,
3
(
39.4, 134.6, 132.1, 129.4, 129.0, 128.8, 126.9, 126.7, 126.6,
+
ppm; MS (DART-TOF) m/z: 415 [M+H] . IR (neat): 3036, 1595,
1490, 1441, 1176, 1066, 841, 681 cm . HRMS (DART-TOF)
calcd for C30
Calcd for C30
26.1, 125.9, 125.7, 117.7, 39.1, 32.0, 29.9, 28.8, 14.5 ppm; MS
-1
+
(DART-TOF) m/z: 451 [M(81)+H] ; IR (neat): 2924, 2851,
+
-
1
H
23S: 415.1520 [M+H] , Found 415.1507; Anal.
1
521, 1437, 1255, 1219, 1156, 1006 cm ; HRMS (DART-TOF)
+
H22S: C, 86.92; H, 5.35. Found: C, 86.91; H, 5.36.
calcd for C H Br(81)S: 451.0918 [M(81)+H] , Found 451.0896.
2
6
26
4
.4 Synthesis of (E)-triisopropyl(3-phenyl-4-(thiophen-2-
4
.2.5.
(E)-4-(1-bromo-2-cyclohexyl-2-(thiophen-2-
yl)hex-3-en-1-ynyl)silane 9, for Table 3, entry 6. Under an
argon atmosphere, to a solution of 2 (147 mg, 0.5 mmol) in
toluene (1 mL) and Et N (1 mL) was added
triisopropylsilylacetylene (0.22 mL, 1 mmol) and P(t-Bu) (10
wt% in hexane, 0.15 mL, 0.05 mmol). After Pd[P(t-Bu) ] (13
mg, 0.025 mmol) and CuI (10 mg, 0.05 mmol) was added, the
reaction was heated to 70 ºC and stirred for 4 h. The mixture was
allowed to cool to ambient temperature, and filtered through a
pad of celite with eluent of toluene. The filtrate was transferred
into a separatory funnel, and washed with water (15 mL) and
yl)vinyl)benzonitrile (7d). 60% yield (58 mg); yellowish white
viscous materials; H NMR (400 MHz, CDCl ) 7.41 (d, J = 8.6
Hz, 2H), 7.25 (d, J = 8.6 Hz, 2H), 7.14 (dd, J = 5.2 Hz, 1.2Hz,
1
1
3
3
3
H), 6.79 (dd, J = 5.2 Hz, 3.5 Hz, 1H), 6.53 (dd, J = 3.5 Hz, 1.2
3
2
Hz, 1H), 3.14 (tt, J = 12 Hz, 3.2 Hz, 1H), 1.81-1.78 (m, 4H),
1
1
1
4
.69-1.66 (m, 1H), 1.45-1.35 (m, 2H), 1.29-1.19 (m, 2H), 1.15-
.04 (m, 1H) ppm; C NMR (100 MHz, CDCl ) 146.1, 143.2,
38.0, 131.8, 130.5, 128.5, 126.8, 126.4, 121.0, 118.9, 111.3,
6.3, 30.7, 26.6, 26.0 ppm; MS (DART-TOF) m/z: 391
1
3
3
+
[
M(81)+NH ] ; IR (neat): 2929, 2845, 2227 (CN), 1598, 1432,
4
-
1
brine (15 mL), and dried over Na SO , and concentrated in vacuo
to give a crude of 259 mg as a dark brown oil. Purification with
silica gel column chromatography (hexane) afforded 187 mg of 9
as a yellow oil in 95% yield. H NMR (400 MHz, CDCl ) 7.30-
2 4
1
401, 1213, 845 cm ; HRMS (DART-TOF) calcd for
+
C H Br(81)N S: 391.0667 [M(81)+NH ] , Found 391.0644;
Anal. Calcd for C H Br(79)NS: C, 61.29; H, 4.87; N, 3.76.
Found: C, 61.52; H, 4.79; N, 3.88.
1
9
22
2
4
1
9
18
1
3
7
.22 (m, 5H), 7.14 (d, J = 5.1 Hz, 1H), 6.82 (dd, J = 5.1, 3.7 Hz,

7
ACCEPTED MANUSCRIPT
129.9, 129.3 (two peaks are overlapped), 129.1, 127.3, 119.3,
+
1
=
1
1
H), 6.71 (d, J = 3.7 Hz, 1H), 2.97 (q, J = 7.5 Hz, 2H), 1.19 (t, J
7.5 Hz, 3H), 1.10 (s, 21H) ppm; C NMR (100 MHz, CDCl3)
1
3
109.8, 32.2, 14.1 ppm; MS (DART-TOF) m/z: 240 [M+H] ; IR
-
44.5, 142.7, 139.5, 130.0, 128.5, 128.0, 127.5, 126.9, 126.5,
21.1, 107.8, 97.4, 32.1, 19.0, 13.5, 11.8 ppm; MS (DART-TOF)
(neat): 3100, 2970, 2197 (CN), 1573, 1416, 1244, 1049, 718 cm
1
+
; HRMS (DART-TOF) calcd for C H NS: 240.0847 [M+H] ,
15 14
+
m/z: 395 [M+H] ; IR (neat): 2940, 2863, 2128, 1461, 1232, 994,
Found 240.0834; Anal. Calcd for C H NS: C, 75.28; H, 5.47;
15 13
-
1
6
[
93 cm ; HRMS (DART-TOF) calcd for C H SSi: 395.2229
N, 5.85. Found: C, 75.48; H, 5.72; H, 5.92.
2
5
35
+
M+H] , Found 395.2236; Anal. Calcd for C H SSi: C, 76.08;
25 34
4
.7 Synthesis of (E)-2-(1-phenyl-1-(p-tolyl)but-1-en-2-
H, 8.68. Found: C, 75.95; H, 8.57.
yl)thiophene 12, for Scheme 6(a). Under an argon atmosphere,
to a solution of 2 (293 mg, 1.0 mmol) in toluene (3.5 mL) was
added 4-methylphenylzinc iodide (0.5 M in THF, 3 mL, 1.5
mmol), and P(t-Bu) (10wt% in hexane, 0.3 mL, 0.1 mmol), and
Pd[P(t-Bu) ] (26 mg, 0.05 mmol). After stirred at 85 ºC for 2 h,
4
.5 Synthesis of (E)-(4-(furan-2-yl)-3-phenylhex-3-en-1-
ynyl)triisopropylsilane 10, for Scheme 4. [We observed this
compound partially decayed two weeks after its purification.]
Under an argon atmosphere, to a solution of 1 (337 mg, 1.0
3
3
2
mmol) and PPh (393 mg, 1.5 mmol) in toluene (7 mL) was
the mixture was allowed to cool to ambient temperature (the
3
added tributyl(2-furyl)tin (0.47 mL, 1.5 mmol). After CuTC (286
mg, 1.5 mmol) was added, the reaction was heated to 90 ºC and
stirred for 1 h. The mixture was allowed to cool to ambient
temperature, and filtered through a pad of celite. The filtrate was
transferred into a 50 mL separatory funnel, and washed with
brine (20 mL), and dried over Na SO , and concentrated in vacuo
to give a crude of 1.12 g. Purification of short-plugged silica-gel
column chromatography with eluent of hexane afford 413 mg as
a pale yellow oil that included a desired 7f. Right after the
sample was dried under vacuum at room temperature for 15 min,
the fragile sample was provided into the next step. Under an
argon atmosphere, to a solution of the sample 413 mg including
starting 2 was disappeared on TLC monitoring), and the reaction
was quenched with satd. aq. NH Cl (10 mL) at 0 ºC. The mixture
4
was diluted with toluene (15 mL), and the aqueous phase was
extracted with toluene (10 mL x 3). The combined organic layer
was washed with brine (20 mL), and dried over Na SO , and
2
4
concentrated to give a crude of dark brown oil in 368 mg. The
mixture was filtered through a short-plugged chromatographic
column (silica-gel, hexane eluent), and followed by purification
with silica-gel column chromatography (hexane eluent), which
2
4
1
afforded 219 mg of desired 12 in 72% yield. H NMR (400 MHz,
CDCl ) 7.17-7.05 (m, 10H), 6.81 (dd, J = 5.1, 3.6 Hz, 1H), 6.70
3
(dd, J = 3.6 Hz, 1.2 Hz, 1H), 2.52 (q, J = 7.4 Hz, 2H), 2.36 (s,
1
3
7
f in toluene (1.5 mL) and Et N (1.5 mL) was added
3H), 1.08 (t, J = 7.4 Hz, 3H) ppm; C NMR (100 MHz, CDCl3)
144.9, 143.8, 140.7, 140.4, 136.7, 134.6, 130.6, 129.3, 129.2,
128.2, 127.4, 126.69, 126.68, 125.0, 30.0, 21.5, 14.5 ppm; MS
3
triisopropylsilylacetylene (0.45 mL, 2 mmol) and P(t-Bu) (10
3
wt% in hexane, 0.3 mL, 0.1 mmol). After the Pd[P(t-Bu) ] (26
3
2
+
mg, 0.05 mmol) and CuI (19 mg, 0.1 mmol) was added, the
reaction was conducted at 85 ºC and stirred for 17 h. The mixture
was allowed to cool to room temperature, and filtered through a
pad of celite. The filtrate was transferred into a 100 mL
separatory funnel, and washed with water and brine (each 20
mL), and dried over Na SO , and concentrated in vacuo to give a
(DART-TOF) m/z: 305 [M+H] ; IR (neat): 2960, 1440, 1069,
-
1
814, 692 cm ; HRMS (DART-TOF) calcd for C H S: 305.1364
2
1
21
+
[M+H] , Found 305.1360; Anal. Calcd for C H S: C, 82.85; H,
2
1
20
6.62. Found: C, 82.90 ; H, 6.66.
4
1
.8 Synthesis of (Z)-2-(4-phenylhepta-3,6-dien-3-yl)thiophene
4, for Table 5, entry 3. Under an argon atmosphere, to a
2
4
crude of dark brown oil (705 mg). Purification with silica gel
solution of 2 (293 mg, 1.0 mmol) in toluene (2 mL) and THF
(0.32 mL, 4 mmol) at 0 ºC was added t-BuLi (1.9 M in pentane,
column chromatography (hexane) afforded 299 mg of 10 as a
1
yellow oil in 79% yield. H NMR (400 MHz, CDCl ) 7.29-7.24
3
1
.16 mL, 2.2 mmol) dropwise over 2 min, and the mixture was
(m, 6H), 6.22 (dd, J = 3.4, 1.8 Hz, 1H), 5.76 (d, J = 3.4 Hz, 1H),
stirred at 0 ºC for 15 min. Then, 3-bromoprop-1-ene (0.51 mL, 6
mL) was slowly added over 1 min. Conducted at 0 ºC for 1 h, the
2
.92 (q, J = 7.4 Hz, 2H), 1.19 (t, J = 7.4 Hz, 3H), 1.09 (brs, 2H)
1
3
ppm; C NMR (100 MHz, CDCl ) 153.4, 142.1, 140.20, 140.18,
3
reaction was quenched with saturated aqueous NH Cl (14 mL).
4
1
1
29.4, 128.5, 127.4, 120.3, 111.63, 111.56, 107.9, 97.6, 28.0,
+
The aqueous phase was extracted with toluene (10 mL x 3), and
the combined organic layers were washed with brine (20 mL),
9.0, 13.9, 11.8 ppm; MS (DART-TOF) m/z: 379 [M+H] ; IR
-
1
(neat): 2941, 2864, 2125, 1461, 882, 661 cm ; HRMS (DART-
+
and dried over Na SO , and concentrated in vacuo to give a crude
2 4
TOF) calcd for C H OSi: 379.2457 [M+H] , Found 379.2462;
2
5
35
of 302 mg as a yellow oil. The crude was filtered through a short-
plugged silica-gel (hexane/EtOAc 50/1), and followed by
Anal. Calcd for C H OSi: C, 79.31; H, 9.05. Found: C, 79.35;
2
5
34
H, 8.92.
purification
with
silica-gel
column
chromatography
4
.6 Synthesis of (E)-2-phenyl-3-(thiophen-2-yl)pent-2-
(hexane/EtOAc 200/1), which yielded 127 mg of the title
compound 14 in 50% as colorless oil. H NMR (400 MHz,
1
enenitrile 11, for Scheme 5. Under an argon atmosphere, to a
charged Schlenk tube with 2 (88 mg, 0.3 mmol) in DMF (0.75
mL) was added CuCN (32 mg, 0.36 mmol), and the reaction was
heated to 130 ºC. After stirred for 5 h, the mixture was allowed to
cool to room temperature. To the vessel was added toluene (10
mL), and the mixture was transferred into a 25 mL flask, and 3 M
CDCl ), 7.35 (dd, J = 7.0, 7.0 Hz, 2H), 7.29-7.25 (m, 2H), 7.20
3
(d, J = 7.0 Hz, 2H), 7.03 (dd, J = 5.1, 3.5 Hz, 1H), 6.98 (dd, J =
3.5, 1.2 Hz, 1H), 5.70 (ddt, J = 17.0, 10.3, 6.4 Hz, 1H), 4.92 (dd,
J = 10.3, 1.8 Hz, 1H), 4.90 (dd, J = 17.0, 1.8 Hz, 1H), 3.14 (d, J
= 6.4 Hz, 2H), 2.21 (q, J = 7.4, 2H), 0.89 (t, J = 7.4, 3H) ppm;
1
3
aqueous NH (4 mL) was added. After stirred for 30 min at
C NMR (100 MHz, CDCl ) 143.9, 142.7, 138.7, 136.5, 134.0,
3
3
ambient temperature, the mixture was diluted with toluene (10
mL). The aqueous layer was extracted with toluene (10 mL x 3),
and combined organic phases were washed with brine (15 mL),
and dried over Na SO , and filtered, and concentrated in vacuo to
128.8, 128.4, 127.0, 126.9, 126.3, 124.7, 116.1, 41.0, 30.0, 14.1
+
ppm; MS (DART-TOF) m/z: 255 [M+H] ; IR (neat): 3072, 2968,
-
1
2869, 1945, 1802, 1637, 1431, 1235, 911, 692 cm ; HRMS
+
(DART-TOF) calcd for C H S: 255.1207 [M+H] , Found
2
4
17 19
give a crude as a brown oil of 75 mg. The crude was short-
plugged through a pad of silica-gel (hexane/acetone 9/1).
Purification with silica gel column chromatography
255.1189.
Acknowledgments
(
9
6
hexane/toluene=1/1) afforded 66 mg of 11 as an orange oil in
1
1% yield. H NMR (400 MHz, CDCl ) 7.35-7.28 (m, 6H), 6.93-
JSPS Grant-in-Aid for Scientific Research (C), Grant Number
24550066, supported this work. The authors thank Dr. Toshiyuki
Iwai and Dr. Takatoshi Ito at ORIST for measurement of HRMS
3
.88 (m, 2H), 3.01 (q, J = 7.5 Hz, 2H), 1.29 (t, J = 7.5 Hz, 3H)
13
ppm; C NMR (100 MHz, CDCl ) 153.0, 139.4, 134.5, 130.2,
3

8
Tetrahedron
ACCEPTED MANUSCRIPT
1
8. CuTC is Copper (I) 2-Thiophenecarboxylate (CAS# 68986-76-5).
and IR. Dr. Seiji Watase of ORIST, and Dr. Hiroyasu Sato of
We purchased the copper reagents from Aldrich and TCI, and both
worked well equally.
RIGAKU are gratefully thanked for gentle assistance about
measurement of X-ray diffraction and scattering. Professor
Michael P. Schramm at CSULB is gratefully thanked for helpful
discussion.
1
9. The prolonged reaction time completed the reaction, and gave 2 in
7
0% and 3 in 12%.
20. For select example of palladium-catalyzed cross-couplings to
synthesize stereo-defined tetrasubstituted olefins, see: a:) A. N.
Thadani, V. H. Rawal, Org. Lett. 2002, 4, 4317-4320; b) K. Itami,
T. Kamei, J.-i. Yoshida, J. Am. Chem. Soc. 2003, 125, 14670-
Supplementary data
1
4671; c) M. Suginome, A. Yamamoto, M. Murakami, Angew.
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