Palladium pincer complex catalyzed cross-coupling of vinyl epoxides and aziridines with organoboronic acids

Article abstract of DOI:10.1002/chem.200500270

Palladium-catalyzed crosscoupling of vinyl epoxides and aziridines with organoboronic acids was performed by using 0.5-2.5 mol % pincer-complex catalyst. The reactions proceed under mild conditions affording allyl alcohols and amines with high regioselectivity and in good to excellent yields. Under the applied reaction conditions aromatic chloro-, bromoand iodo substituents are tolerated. Our results indicate that the mechanism of the pincer complex catalyzed and the corresponding palladium(O) catalyzed process is substantially different. It was concluded that the transformations proceed via transmetalation of the organoboronic acids to the pincercomplex catalyst followed by an S _N2′type opening of the vinyl epoxide or aziridine substrate. In this process the palladium atom is kept in oxidation state +2 under the entire catalytic process, and therefore oxidative side reactions can be avoided.

Full text of DOI:10.1002/chem.200500270

Palladium Pincer Complex Catalyzed Cross-Coupling of Vinyl Epoxides and
Aziridines with Organoboronic Acids
Johan Kjellgren, Juhanes Aydin, Olov A. Wallner, Irina V. Saltanova, and
Kµlmµn J. Szabó*[a]
Abstract: Palladium-catalyzed cross-
coupling of vinyl epoxides and aziri-
dines with organoboronic acids was
performed by using 0.5–2.5 mol%
pincer-complex catalyst. The reactions
proceed under mild conditions afford-
ing allyl alcohols and amines with high
regioselectivity and in good to excel-
lent yields. Under the applied reaction
conditions aromatic chloro-, bromo-
and iodo substituents are tolerated.
Our results indicate that the mecha-
nism of the pincer complex catalyzed
and the corresponding palladium(0)
catalyzed process is substantially differ-
ent. It was concluded that the transfor-
mations proceed via transmetalation of
the organoboronic acids to the pincer-
complex catalyst followed by an SN2’-
type opening of the vinyl epoxide or
aziridine substrate. In this process the
palladium atom is kept in oxidation
state +2 under the entire catalytic pro-
cess, and therefore oxidative side reac-
tions can be avoided.
Keywords: allylic compounds
·
boron · homogeneous catalysis ·
palladium · pincer complexes
Introduction
Palladium catalysis has become one of the most successful
areas of organic synthesis due to its remarkable capacity for
continuous renewal.[1–4] An important current challenge in
palladium chemistry is the development of new redox reac-
tion free catalytic systems.[5–12] In these catalytic reactions
the oxidation state of palladium is usually restricted to +2;
and therefore formation of palladium(0) intermediates can
be avoided. It is well known that palladium(0) complexes
with weakly coordinating ligands easily decompose forming
amorphous palladium metal (palladium black), which is usu-
ally catalytically inactive. Furthermore, palladium(0) com-
plexes readily undergo oxidative addition to aromatic car-
Scheme 1. Pincer-complex catalysts employed in this study.
organo stannanes and silanes. Thus, we have shown that al-
lylic and propargylic substrates undergo substitution reac-
tions with dimetallic reagents (such as distannane and silyl-
stannane reagents) to give allyl and propargyl stannanes and
silanes.[15,16,18] In these reactions, we exploited three impor-
tant features of the palladium-pincer complex catalysts:
i) high redox stability of the palladium(ii) central atom;
ii) very strong terdentate ligand–metal bonding; and
iii) presence of a s-donating aryl ligand. Because of these
features application of pincer-complex catalysts have a great
potential to open new synthetic routes in palladium-cata-
lyzed transformations.
À
bon halogen bonds, which might be undesired limiting the
synthetic scope of the corresponding reaction.[1–4] We have
recently found[13–18] that palladium pincer complexes,[5,6,19–22]
such as 1a–d[23–25] (Scheme 1), are particularly useful species
to catalyze redox free synthesis and transformation of
Recently, our interest turned to the application of pincer-
complex catalysts in organoboron chemistry.[17] We have
shown that potassium(allyl)trifluoroborates undergo pincer
complex catalyzed allylation of sulfonyl imines under mild
reaction conditions.[17] In this study we report our recent re-
sults on the palladium-pincer complex catalyzed ring open-
ing of vinyl epoxides and aziridines (Scheme 2) with organo-
boronic acids. Although, palladium-catalyzed coupling of or-
[a] J. Kjellgren, J. Aydin, O. A. Wallner, I. V. Saltanova,
Prof. Dr. K. J. Szabó
Dept. Organic Chemistry, Stockholm University
10691 Stockholm (Sweden)
Fax : (+46)8-154-908
E-mail: kalman@organ.su.se
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author: 13C NMR spectra
of compounds 4a–n, 7a–p and complex 9.
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FULL PAPER
also important to add that the elegant synthesis of catalyst
1a reported by Yao and co-workers[23] is about as simple as
the preparation of commonly employed palladium catalysts,
such as [Pd(PPh3)4], or [Pd2(dba)3]. Furthermore, in our ex-
perience catalyst 1a is more stable than these classical palla-
dium(0) catalysts, as it can be stored at ambient temperature
and atmosphere without any loss of the catalytic activity.
Because of the mild reaction conditions and the redox sta-
bility of the catalyst (feature i) above) halogenide (Cl and
Br) substituents on the vinyl epoxide substrate (2c) and on
the arylboronic acid component (3c) are tolerated. We did
Scheme 2. Ring opening of a) vinyl epoxides and b) vinyl aziridines with
organoboronic acids in the presence of catalytic amounts (0.5–2.5 mol%)
of pincer complexes.
À
not observe any carbon halogen bond cleavage in the cross-
ganoboronic acids with various unsaturated substrates
(Suzuki–Miyaura cross-coupling) has become one of the
most important processes in synthetic organic chemistry,[26–31]
the literature of palladium-catalyzed cross-coupling reac-
tions of organoboranes with vinyl epoxides and aziridines is
surprisingly scarce. Suzuki and Miyaura reported[32] a suc-
cessful palladium(0)-catalyzed carbon–carbon coupling reac-
tion of vinyl epoxides with alkenylboranes. Interestingly, by
using [Pd(PPh3)4] as catalyst source vinyl epoxides undergo
carbon-oxygen coupling with arylboronic acids via (h3-allyl)-
palladium intermediates.[33] In this reaction the boronic acid
derivatives react as oxygen nucleophiles instead of as
carbon nucleophiles.[33,34] However, palladium-catalyzed
carbon–carbon coupling of vinyl epoxides with aryl-and al-
kenylboronic acids has not been reported in the literature.
Besides, there is a remarkable lack in the literature concern-
ing palladium-catalyzed ring opening reactions of vinyl aziri-
dines with organoboranes. In this study we like to demon-
strate that palladium-pincer complexes 1a–c are efficient
catalysts in cross-coupling of vinyl epoxides and aziridines
with organoboronic acids. In particular, we have studied the
tolerance of the pincer-complex catalysts toward aromatic
halogenide functionalities (chloride, bromide and iodide),
which are often incompatible with palladium(0) catalysts.
Furthermore, we have briefly studied the mechanistic differ-
ences between the palladium(0) and pincer-complex cataly-
sis in ring opening of vinyl aziridines and epoxides with or-
ganoboronic acids.
coupling reactions involving 2c or 3c (entries 9, 11–14 and
18). It was found that the reactivity of the acyclic epoxides
2a–d is lower than that of cyclic epoxide 2e, and that the
parent epoxide 2a reacted faster than its substituted ana-
logues 2b–d. We have briefly studied the substituent effects
on the reactivity of the vinyl epoxide component. These
studies indicate that phenyl-( 2b) and cyclohexyl-( 2d) sub-
stituted epoxides react similarly, while in the presence of an
electron-withdrawing chloro substituent (2c) the reactivity is
increased leading to about 50% faster cross-coupling reac-
tions (compare entries 6 and 11, 8 and 13, or 9 and 14,
Table 1).
The reaction of 2b–d with phenyl boronic acid 3a can
also be carried out under mild conditions by using only
0.5 mol% catalyst 1a (entries 7, 12 and 16). In these proc-
esses somewhat longer reaction times are required than with
2.5 mol% catalyst, nevertheless the high yields can be main-
tained. The reaction rates also depend on the substituents of
the organoboronic acid component. Alkenylboronic acid 3b
reacts much faster than arylboronic acids 3a and 3c–d. Me-
thoxy substitution of the arylboronic acid (3d) has a rela-
tively weak effect on the rate of reaction (compare entries 6
and 10, or 15 and 19 in Table1); however, bromo substitu-
tion of the arylboronic acid component (3c) clearly acceler-
ate the cross-coupling process (see entries 6 and 9, 11 and 14
or 15 and 18).
The regioselectivity of the cross-coupling reactions involv-
ing acyclic vinyl epoxides (2a–d) is excellent. The reaction
of the parent epoxide 2a results in mainly 1,4-coupling prod-
ucts 4a and 4b, and traces of the 1,2-coupling products 5a
and 5b (entries 1 and 3). The catalytic transformation of the
substituted acyclic vinyl epoxides (2b–d) provide exclusively
the 1,4-coupling products, allyl alcohols 4c–m (entries 6–19).
Cyclic epoxide 2e reacts with a poor regioselectivity provid-
ing 4n and 5c in 2:1 ratio even at low temperatures
(entry 20). Interestingly, however, only trans isomers (4n
and 5c) were obtained in this reaction indicating a trans
mechanism for the epoxide opening. The related palladi-
um(0)-catalyzed opening of 2e with phenyltrimethylstan-
nane reported[35] by Echavarren and Stille also proceeds
with trans mechanism and with a relatively poor regioselec-
tivity.
Results and Discussion
Catalytic ring-opening of vinyl epoxides with organoboronic
acids: Our studies have shown that vinyl epoxides 2a–e can
be efficiently coupled with arylboronic acids 3a–d using cat-
alytic amounts of 1a. In these processes we have employed
the typical reaction conditions of the Suzuki–Miyaura cou-
pling reactions including the use of base and water as addi-
tives. Accordingly, in a typical procedure the appropriate ep-
oxide (2a–e), the organoboronic acid derivative 3a–d
(1.2 equiv), Cs2CO3 (2 equiv) and catalyst 1a (2.5 mol%) in
THF/water 10:1 were stirred at 208C for 4–9 h. Subsequent-
ly the solvent was evaporated and the product was purified
by chromatography. This reaction does not require use of inert
gas atmosphere or employment of carefully dried THF. It is
We have also tried other pincer complexes as catalysts in
the cross-coupling reactions. Complex 1b[24] displayed a high
catalytic activity, however it required higher reaction tem-
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K. J. Szabó et al.
Table 1. Pincer complex catalyzed cross-coupling reaction of vinyl epoxides with organoboronic acids.[a]
complex 1d[18,25] does not dis-
play any catalytic activity
under the applied mild reac-
tion conditions. We have also
attempted coupling reactions
of 2a with organoboronic acids
employing commonly used pal-
ladium(0) catalysts. Catalyst
Substrate
Cat.[b]
R-B(OH)2
Cond.[c] Product
[8C]/[h]
Ratio[d] Yield
[%][e]
1
2
1a
0/16
11:1
7:3
94
95
2a
2a
[Pd2(dba)3] 3a
0/16
0/3
4a
5a
3
1a
9:1
95
[Pd2(dba)3] displayed
a high
4
5
2a
2a
1b
3b
20/4
0/3
4b
4b
5b
5b
7:3
3:2
95
94
catalytic activity using 2a with
phenyl and vinyl boronic acid
derivatives 3a and 3b. Howev-
er, the regioselectivity of the
[Pd2(dba)3]-catalyzed reaction
is considerably lower than the
corresponding process with 1a
(compare entries 1 and 2 or en-
tries 3 and 5). Under the same
reaction conditions [Pd(PPh3)4]
proved to be ineffective as the
corresponding cross-coupling
products 4a and 5a could not
be observed in the reaction
mixture.
[Pd2(dba)3] 3b
6
1a
3a
20/9
>20:1
86
7
8
2b
2b
1a (0.5%) 3a
20/17
0/3
4c
>20:1
>20:1
85
95
1a
1a
3b
9
2b
20/6
20/7
>20:1
>20:1
88
86
10 2b
1a
1a
11
3a
20/5
20/17
0/1.5
>20:1
>20:1
>20:1
95
81
95
12 2c
13 2c
1a (0.5%) 3a
4g
1a
3b
Cross-coupling of vinyl aziri-
dines
with
organoboronic
acids: The above successful
studies on pincer complex cat-
alyzed ring-opening of vinyl
epoxides (2a–e) led us to
extend the synthetic scope of
the reaction to vinyl aziridine
based substrates (6a–d) (Sche-
me 2b). Although the reaction
conditions used for ring open-
ing of vinyl epoxides were also
suitable for aziridines, the cata-
lytic process was rather slug-
gish. However, it was found
that application of CsF in place
of Cs2CO3 gave a fast reaction
and high yields at 208C
(Table 2). In these cross-cou-
pling reactions diastereomeric
mixtures of cis-and trans-aziri-
dines (6a–d) were employed,
which were easily prepared by
the method reported by Dai
and co-workers.[36] The cross-
14 2c
1a
1a
3c
3a
20/4
20/9
>20:1
>20:1
76
95
15
16 2d
17 2d
1a (0.5%) 3a
20/17
0/3
4j
>20:1
>20:1
91
90
1a
1a
1a
3b
3c
3d
18 2d
19 2d
20/6
20/6
>20:1
>20:1
75
76
20
1a
3a
À20/2
2:1
88
[a] The reactions were carried out by using 0.5–2.5 mol% catalyst in the presence of Cs2CO3 in THF/H2O
10:1. [b] Typically 2.5 mol% catalyst was employed. The use of 0.5 mol% catalyst is indicated in parentheses.
[c] Reaction temperature/reaction time. [d] Isomer ratio 4:5. The >20:1 ratio indicates that isomer 5 was not
1
detected in the crude or in the isolated product by H NMR spectroscopy. [e] Isolated yield.
perature than 1a (entry 4). Furthermore, the regioselectivity
of the cross-coupling reaction between 2a and 3b is much
lower with 1b than with 1a as catalyst (entries 3 and 4).
Bedford and co-workers[25] successfully employed the tri-
fluoroacetate salt of PCP complex 1d for Suzuki coupling of
aryl boronic acid 3a with various aryl halogenides at elevat-
ed reaction temperature (1308C). However, we found that
coupling reaction of 6a–d with organoboronic acids 3a–h
gave the corresponding trans-products 7a–p together with
trace amounts (typically 5%) of their cis isomers.
Most of the reactions could be carried out using pincer-
complex catalyst 1a under mild conditions with excellent
yields. Similarly to the epoxide opening reactions the func-
tional group tolerance of the reaction is very high, as aro-
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Cross-Coupling
FULL PAPER
Table 2. Catalytic ring opening of vinyl aziridines with organoboronic acids.[a]
matic halogenides (fluoro,
bromo and iodo substituents,
entries 5–7 and 12–16) and
nitro group (entry 17) are tol-
erated. Catalyst 1a reacted
slowly with iodo-derivative 3g,
and therefore the more active
trifluoroacetate complex 1c
Substrate[b]
Cat.
R-B(OH)2
Cond.[c]
Product
trans/cis[d] Yield
[8C]/[h]
[%][e]
1
2
1a
1a
3a
3b
20/18
20/3
19:1
19:1
95
95
6a
6a
6a
6a
was employed to achieve
a
3
4
5
1a
1a
1a
3c
3d
20/15
20/15
20/15
14:1
19:1
14:1
95
95
93
high yield (entry 7). Remarka-
bly, product 7g could be isolat-
ed with an intact iodo func-
tionality. It is well known that
aryliodides are usually incom-
patible with palladium(0) cata-
lysts because of the rapid oxi-
dative addition of the catalyst
to the carbon-iodine bond.[1]
Indeed, the reaction of 6a and
3g with [Pd2(dba)3] as catalyst
(entry 8) proceeds with a con-
siderably lower yield than the
corresponding reaction cata-
lyzed by pincer complex 1c
(entry 7). The pincer complex
catalyzed reactions also toler-
ate ortho substituents in the ar-
omatic substrates (3 f and 3h).
In these processes trifluoroace-
tate complex 1c was employed
as catalyst to provide high
yields (entries 6 and 9). The
cross-coupling reaction of 6a
and 3h was also attempted
with [Pd2(dba)3] as catalyst.
The crude reaction mixture in-
dicated formation of 7h to-
gether with several unidenti-
fied by-products. Unfortunate-
ly, the isolated yield could not
be determined for this reac-
tion, since we were unable to
separate 7h from the by-prod-
ucts even after repeated silica-
gel chromatographies.
6
6a
1c
20/18
17:1
95
7
8
6a
6a
1c[f]
20/16
20/18
8:1
8:1
93
50
[Pd2(dba)3][f] 3g
7g
9
6a
1c
20/18
20/17
25:1
17:1
95
82
10
1a
1a
1a
1a
3a
3e
3a
3b
11 6b
20/17
20/16
20/3
17:1
10:1
19:1
95
86
95
12
13 6c
14 6c
15 6c
16 6c
17
1a
1a
1a
1a
3c
3d
3e
3a
20/17
20/17
20/16
20/16
10:1
14:1
10:1
19:1
95
95
95
95
Mechanistic Aspects
In order to explore the mecha-
nistic differences between the
pincer complex (1a or 1c) cat-
alyzed and [Pd2(dba)3]-cata-
lyzed reactions we carried out
stoichiometric reactions with
arylboronic acid 3 f and epox-
ide substrate 2a, which was fol-
[a] The reactions were carried out by using 2.5 mol% catalyst in the presence of CsF in THF/H2O 10:1.
[b] trans/cis (about 2:1) mixture was used as substrate. Bs=benzenesulfonyl; Ts=toluenesulfonyl. [c] Reaction
temperature/reaction time. [d] trans/cis ratio of the double bond geometry in the products. [e] Isolated yield.
[f] 5 mol% catalyst was employed.
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K. J. Szabó et al.
1
lowed by 19F and H NMR spectroscopy. It was found that
tion of 3 f with the pincer complex 1c to give 10, which un-
dergo hydrolysis providing 8 (Scheme 5). Unfortunately, in
the presence of water direct observation or isolation of 10 is
prevented by this hydrolysis process. Intermediary formation
1c reacted readily with 3 f in the presence of CsF and water
in THF (Scheme 3). Monitoring the reaction at 208C with
19F NMR spectroscopy revealed formation of fluorobenzene
Scheme 3. Stoichiometric reactions with fluoro boronic acid 3 f.
8 after 20 min. Under the same reaction conditions using
[Pd2(dba)3] instead of 1c the fluoroboronic acid 3 f remained
unchanged and formation of 8 was not observed even after
several hours of reaction time. The same result was obtained
without employment of any palladium sources.
Scheme 5. Rationalization of the formation of fluorobenzene 8 in the sto-
ichiometric reactions.
of complex 10 is also in line with our previous mechanistic
results[15] on the trimethyltin transfer reactions catalyzed by
1b. In this reaction the active catalyst is formed by transme-
talation of hexamethylditin with the pincer-complex catalyst.
Considering the above, we assume that the initial step of
the catalytic cycle (Scheme 6) is transmetalation of 1a or 1c
with the corresponding organoboronic acid derivative 3.
Prior to this step the B(OH)2 group is converted to a better
leaving group by application of Cs2CO3/CsF and water.[26,29]
Transmetalation of 1 with 3 results in complex 11, from
which the aryl or vinyl functionality (R) is subsequently
transferred to the vinyl epoxide substrate in an SN2’ (or SN2)
type of reaction. A fast SN2’ process requires a high elec-
tron-density on the organic functionality ensured by the
electron-donating SeCSe and NCN ligands, when 1a–c are
employed as catalysts. On the other hand the low catalytic
activity of 1d can be explained by the presence of p-accept-
or phosphorous ligands, which decrease the electron density
on the organic group. The reaction rate also depends on the
electronic properties of the epoxide substrate 2. An elec-
tron-withdrawing group on the epoxide substrate, such as a
chloro functionality in 2c, increases the electrophilicity of
this substrate leading to a fast transfer of the organic group.
We have also carried out stoichiometric experiments with
the palladium catalyst and epoxide 2a in the absence of or-
ganoboronic acids (Scheme 4). When [Pd2(dba)3] was mixed
with 2a in [D8]THF in the presence of LiCl the color of the
solution rapidly turned from purple to yellow and the
1H NMR spectrum showed formation of (h3-allyl)palladium
complex 9, which could also be isolated. This reaction was
also carried out with CsF in the presence of water. Although
this reaction mixture also showed the above described color
change, analogues of complex 9 could not be observed, only
unidentified decomposition products of 2a. This observation
indicated that the application of chloride salts is necessary
to form a stable complex, such as 9, otherwise the (h3-allyl)-
palladium complex formed from 2a and [Pd2(dba)3] easily
decomposes. Pincer complexes with chloride and triflouroa-
cetate counterions (1a and 1c) do not react with epoxide 2a
at all. This reaction mixture remained unchanged after sev-
eral days.
Scheme 4. Stoichiometric reaction with epoxide 2a.
According to the above stoichiometric studies there are
important mechanistic differences between the pincer com-
plex catalyzed cross-coupling reaction and the correspond-
ing [Pd2(dba)3]-catalyzed process. Vinyl epoxides (such as
2a) and a palladium(0) complex readily form an (h3-allyl)-
palladium(ii) complex by opening of the epoxide ring
(Scheme 4).[32–34] However, in 1a and 1c there is only a
single free coordination site available on the metal atom;
and the oxidation state of palladium is restricted to +2 (fea-
tures i) and ii) above), and therefore formation of an (h3-al-
lyl)palladium complex with a vinyl epoxide is unlikely. On
the other hand 1c reacts directly with boronic acid 3 f
(Scheme 3). The relatively fast appearance of fluorobenzene
8 in this reaction mixture can be explained by transmetala-
Scheme 6. Proposed catalytic cycle for the pincer complex (1a, 1c) cata-
lyzed reaction.
Concluding Remarks
We have shown that palladium-pincer complexes catalyze
the carbon–carbon cross-coupling reaction of vinyl epoxides
and aziridines with organoboronic acids. These catalytic
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Cross-Coupling
FULL PAPER
tional hour at 258C in a dark reaction vessel. The AgBr precipitation was
separated by centrifugation and the solvent was evaporated to yield com-
plex 1c, which was used without further purification. According to
1H NMR, complex 1c was formed in a diastereomeric ratio of 3:1.
1H NMR: d = 4.20 (d, 3J(H,H)=16.0 Hz, 2H, major diastereomer), 4.54
(d, 3J(H,H)=14.1 Hz, 2H, minor diastereomer), 4.66 (d, 3J(H,H)=
14.1 Hz, 2H, minor diastereomer), 4.92 (d, 3J(H,H)=16.0 Hz, 2H, major
diastereomer), 7.07 (d, 3J(H,H)=7.5 Hz, 2H), 7.18 (m, 1H), 7.30 (m,
3H), 7.41 (m, 3H), 7.56 (d, 3J(H,H)=7.9 Hz, 3H), 7.80 (d, 3J(H,H)=
7.0 Hz, 1H); 19F NMR: d = À73.55 (brs).
transformations proceed with high regioselectivity affording
allyl alcohols and amines in good to excellent yields. Be-
cause of the high redox stability of the palladium(ii)-pincer
complex catalyst aromatic chloro-, bromo- and iodo sub-
stituents are tolerated. The applied catalysts 1a and 1c are
easily available and the catalytic reaction does not require
the use of inert gas atmosphere or application of dry sol-
vents. It was found that [Pd2(dba)3] also show a high catalyt-
ic activity in the presented cross-coupling reactions. Howev-
er, the pincer complex catalyzed reactions proceed with
higher regio-and chemoselectivity than the corresponding
[Pd2(dba)3]-catalyzed processes. Our mechanistic studies in-
dicate that the pincer complex catalyst does not undergo
redox reactions; and that the oxidation state of the palladi-
um atom is +2 under the catalytic process. It was concluded
that the initial step of the reaction is transmetalation of the
organoboronic acid to the pincer complex followed by an
SN2’ type transfer process. The presented pincer complex
catalyzed process allows cross-coupling reactions of easily
accessible organoboronic acids[26–28,30] with vinyl epoxides
and aziridines broadening the synthetic scope of selective
palladium catalysis.
(E)-4-Phenyl-2-buten-1-ol (4a): The reaction mixture was stirred at 08C
for 16 h. For column chromatography pentane/Et2O 3:2 was used, yield-
ing 4a (22 mg, 94%). The obtained NMR data were in agreement with
the published literature values.[35]
(2E,5E)-6-Phenyl-2,5-hexadien-1-ol (4b): The reaction mixture was stir-
red at 08C for 3 h. For column chromatography pentane/Et2O 3:2 were
used, yielding 4b (27 mg, 95%). The obtained NMR data were in agree-
ment with the published literature values.[35]
(E)-1,4-Diphenyl-2-buten-1-ol (4c): The reaction mixture was stirred at
208C for 9 h. For column chromatography pentane/Et2O 3:2 was used,
yielding 4c (33 mg, 86%). This reaction was also performed with
0.5 mol% of 1a. In this case the reaction mixture was stirred at 208C for
17 h yielding 4c (32 mg, 85%). The obtained NMR data were in agree-
ment with the published literature values.[35]
(2E,5E)-1,6-Diphenyl-2,5-hexadien-1-ol (4d): The reaction mixture was
stirred at 08C for 3 h. For column chromatography pentane/Et2O 2:1 was
used, yielding 4d (37 mg, 92%). The obtained NMR data were in agree-
ment with the published literature values.[35]
(E)-4-(4-Bromophenyl)-1-phenyl-2-buten-1-ol (4e): The reaction mixture
was stirred at 208C for 6 h. For column chromatography pentane/EtOAc
3:1 was used, yielding 4e (45 mg, 88%). 1H NMR: d = 1.99 (brs, OH),
3.35 (d, 3J(H,H)=6.5 Hz, 2H), 5.2 (d, 3J(H,H)=6.5 Hz, 1H), 5.74 (ddt,
3J(H,H)=6.6, 15.3 Hz, 4J(H,H)=1.3 Hz, 1H), 5.88 (dt, 3J(H,H)=6.6,
15.2 Hz, 1H), 7.05 (d, 3J(H,H)=8.4 Hz, 2H), 7.25–7.43 (m, 7H);
13C NMR: d = 37.88, 74.84, 117.19, 119.94, 126.16, 127.69, 128.55, 130.14,
130.31, 131.49, 132.35, 134.01, 138.81, 142.92.
Experimental Section
The NMR spectra were recorded on Varian spectrometers. 1H NMR
spectra were recorded at either 300 or 400 MHz, 13C NMR spectra were
recorded at either 75.4 or 100.5 MHz. In these measurements CHCl3 was
used as internal standard (d[1H]=7.26 ppm), d[13C]=77.0 ppm).
19F NMR spectra were recorded at either 282.2 or 376.3 MHz, by using
a,a,a-trifluorotoluene as standard. For column chromatography silica gel
(230–400 mesh) was used. MALDI-TOF spectra were recorded on a
Bruker Biflex III instrument by using 2’,4’,6’-trihydroxy acetophenone
(THAP) as matrix. Complex 1a was prepared according to Yao and co-
workers[23] except that the complex was purified by column chromatogra-
phy by using CH2Cl2/Et2O 20:1. Complex 1b was prepared according to
the procedure published by van Koten and co-workers[24] except that the
final product was purified by column chromatography with CH2Cl2/Et2O
20:1. Preparation of the trifluoroacetate salt of complex 1d was first re-
ported by Bedford and co-workers;[25] however we prepared complex 1d
by a modified procedure.[18] The vinyl epoxides and aziridines were pre-
pared according to literature procedures.[36, 37] The boronic acids are com-
mercially available and were used as received.
(E)-4-(4-Methoxyphenyl)-1-phenyl-2-buten-1-ol (4 f): The reaction mix-
ture was stirred at 208C for 7 h. For column chromatography pentane/
Et2O 2:1 was used, yielding 4 f (36 mg, 86%). 1H NMR: d = 2.0 (brs,
1H), 3.35 (d, 3J(H,H)=6.5 Hz, 2H), 3.79 (s, 3H), 5.2 (d, 3J(H,H)=
3
4
6.6 Hz, 1H), 5.74 (ddt, J(H,H)=6.6, 15.3 Hz, J(H,H)=1.3 Hz, 1H), 5.91
(dt, 3J(H,H)=6.6, 15.3 Hz, 1H), 6.84 (d, 3J(H,H)=8.5 Hz, 2H), 7.10 (d,
3J(H,H)=8.5 Hz, 2H), 7.25–7.40 (m, 5H); 13C NMR: d = 37.66, 55.23,
74.92, 113.86, 126.17, 127.54, 128.47, 129.47, 131.38, 131.91, 133.30, 143.13,
158.00.
(E)-1-(4-Chlorophenyl)-4-phenyl-2-buten-1-ol (4g): The reaction mixture
was stirred at 208C for 5 h. For column chromatography pentane/EtOAc
4:1 was used, yielding 4g (41 mg, 95%). This reaction was also per-
formed by using 0.5 mol% of 1a. In this case the reaction mixture was
General procedure for palladium-pincer complex catalyzed coupling of
organoboronic acids with vinyl epoxides: Palladium-pincer complex 1a
(0.004 mmol, 2.5 mol%), vinyl epoxide (0.16 mmol), organoboronic acid
(0.192 mmol, 1.2 equiv), and Cs2CO3 (0.32 mmol, 2 equiv) were dissolved
in THF/water (10:1, 0.33 mL). This reaction mixture was stirred for the
allotted reaction times and temperatures given below (see also Table 1).
After completion of the reaction, the crude reaction mixture was purified
by column chromatography.
1
stirred at 208C for 17 h yielding 4g (34 mg, 81%). H NMR: d = 1.96 (s,
1H), 3.40 (d, 3J(H,H)=6.7 Hz, 2H), 5.18 (d, J=6.8, 1H), 5.70 (dd, 3J
(H,H)=6.6, 15.1 Hz, 1H), 5.86–5.98 (m, 1H), 7.14–7.36 (m, 9H);
13C NMR: d = 38.53, 74.25, 126.21, 127.55, 128.49, 128.53, 128.58, 131.50,
133.26, 139.66, 141.47.
(2E,5E)-1-(4-Chlorophenyl)-6-phenyl-2,5-hexadien-1-ol (4h): The reac-
tion mixture was stirred at 08C for 1.5 h. For column chromatography
pentane/EtOAc 5:1 was used, yielding 4h (44 mg, 95%). 1H NMR: d =
1.97 (brs, 1H), 2.98 (t, 3J(H,H)=6.5 Hz, 2H), 5.19 (d, 3J(H,H)=6.5 Hz,
1H), 5.73 (dd, 3J(H,H)=6.8, 14.9 Hz, 1H), 5.79–5.90 (m, 1H), 6.14–6.25
(m, 1H), 6.41 (d, 3J(H,H)=16.0 Hz, 1H), 7.17–7.39 (m, 9H); 13C NMR:
d = 35.39, 74,37, 126.03, 127.15, 127.35, 127.55, 127.59, 128.50 128.59,
130.50 131.20, 133.19, 133.25, 137.36, 141.51.
General procedure for palladium-pincer complex catalyzed coupling of
organoboronic acids with vinyl aziridines: Palladium-pincer complex 1a
(0.004 mmol, 2.5 mol%), vinyl aziridine (0.16 mmol), organoboronic acid
(0.192 mmol, 1.2 equiv), and CsF (0.32 mmol, 2 equiv) were dissolved in
THF/water (10:1, 0.33 mL). This reaction mixture was stirred for the al-
lotted reaction times and temperatures given below (see also Table 2).
After completion of the reaction, the crude reaction mixture was purified
by column chromatography.
(E)-4-(3-Bromophenyl)-1-(4-chlorophenyl)-2-buten-1-ol (4i): The reac-
tion mixture was stirred at 208C for 4 h. For column chromatography
pentane/EtOAc 5:1 was used, yielding 4I (42 mg, 76%). 1H NMR: d =
Exchange of the counterion in complex 1a to obtain TFA-complex 1c:
Chloro-complex 1a was added to AgOCOCF3 (2 equiv) suspended in
CHCl3 at 08C. This mixture was stirred for 1 h at 08C and then an addi-
3
3
1.95 (apps, 1H), 3.34 (d, J(H,H)=6.6 Hz, 2H), 5.17 (d, J(H,H)=6.6 Hz,
1H), 5.67 (dt, 3J(H,H)=6.5, 15.2 Hz, 1H), 5.81–5.93 (m, 1H), 6.98–7.46
Chem. Eur. J. 2005, 11, 5260 – 5268
www.chemeurj.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5265

K. J. Szabó et al.
(m, 8H); 13C NMR: d
130.67, 131.55, 133.35, 133.70, 138.61, 141.36.
=
37.87, 74.15, 120.04, 127.53, 128.65, 130.30,
138.32, 139.61, 140.63; MS (MALDI-TOF): m/z: 465.09/467.08 [M+Na]+,
481.09/483.08 [M+K]+.
N1-[(E)-4-(4-Methoxyphenyl)-1-phenyl-2-butenyl]-1-benzenesulfonamide
(7d): The reaction mixture was stirred at 208C for 15 h. For column chro-
matography pentane/EtOAc 4:1 was used, yielding 7d (58 mg, 95%).
1H NMR: d = 3.17 (d, 3J(H,H)=6.5 Hz, 2H), 3.78 (s, 3H), 4.97 (t, 3J
(H,H)=6.8 Hz, 1H), 5.35 (d, 3J(H,H)=7.3 Hz, 1H), 5.48 (dd, 3J(H,H)=
6.4, 15.2 Hz, 1H), 5.61 (dt, 3J(H,H)=6.6, 15.3 Hz, 1H), 6.8 (d, 3J(H,H)=
1-[(E)-3-Phenyl-1-propenyl]-1-cyclohexanol (4j): The reaction mixture
was stirred at 208C for 9 h. For column chromatography pentane/Et2O
2:1 was used, yielding 4j (33 mg, 95%). This reaction was also performed
by using 0.5 mol% of 1a. In this case the reaction mixture was stirred at
208C for 17 h also yielding 4j (32 mg, 91%). The obtained NMR data
were in agreement with the literature values.[38]
3
3
8.5 Hz, 2H), 6.95 (d, J(H,H)=8.5 Hz, 2H), 7.11–7.23 (m, 5H), 7.34 (t, J
(H,H)=7.9 Hz, 2H), 7.46 (t, 3J(H,H)=7.5 Hz, 1H), 7.74 (d, 3J(H,H)=
7.9 Hz, 2H); 13C NMR: d = 37.39, 55.17, 59.38, 113.78, 126.9, 127.04,
127.53, 128.47, 128.66, 129.38, 129.81, 131.36, 132.21, 132.57, 139.81,
140.65, 157.92; MS (MALDI-TOF): m/z: 416.18 [M+Na]+, 432.17
[M+K]+.
1-[(1E,4E)-5-Phenyl-1,4-pentadienyl]-1-cyclohexanol (4k): The reaction
mixture was stirred at 08C for 3 h. For column chromatography pentane/
Et2O 2:1 was used, yielding 4k (35 mg, 95%). 1H NMR: d = 1.37 (m,
11H), 2.96 (d, 3J(H,H)=6.2 Hz, 2H), 5.62–5.82 (m, 2H), 6.22 (dt, 3J
(H,H)=7.0, 15.9 Hz, 1H), 6.41 (d, 3J(H,H)=15.9 Hz, 1H), 7.17–7.38 (m,
5H); 13C NMR: d
= 22.15, 25.53, 35.60, 37.99, 71.31, 125.55, 125.99,
126.97, 128.45, 128.58, 130.62, 137.56, 139.10.
N1-[(E)-4-(4-Fluorophenyl)-1-phenyl-2-butenyl]-1-benzenesulfonamide
(7e): The reaction mixture was stirred at 208C for 15 h. For column chro-
matography pentane/EtOAc 4:1 was used, yielding 7e (57 mg, 93%).
1H NMR: d = 3.21 (d, 3J(H,H)=6.45 Hz, 2H), 4.96 (t, 3J(H,H)=6.9 Hz,
1-[(E)-3-(4-Bromophenyl)-1-propenyl]-1-cyclohexanol (4l): The reaction
mixture was stirred at 208C for 6 h. For column chromatography pen-
1
tane/EtOAc 2:1 was used, yielding 4l (37 mg, 75%). H NMR: d = 1.23–
3
1H), 5.1 (d, 3J(H,H)=7.3 Hz, 1H), 5.49 (dd, J(H,H)=6.3, 15.2 Hz, 1H),
1.68 (m, 11H), 3.31 (d, 3J(H,H)=7.1 Hz, 2H), 5.68 (dt, 3J(H,H)=1.3,
3
3
5.63 (dt, J(H,H)=6.6, 15.4 Hz, 1H), 6.9–7.24 (m, 9H), 7.35 (t, J(H,H)=
3
3
15.7, 1H), 5.78 (dt, J(H,H)=6.6, 15.6 Hz, 1H), 7.04 (d, J(H,H)=8.8 Hz,
2H), 7.40 (d, 3J(H,H)=8.8 Hz, 2H); 13C NMR: d = 22.10, 25.48, 37.96,
38.05, 71.30, 119.78, 126.00, 130.25, 131.41, 139.39, 139.71.
7.5 Hz, 2H), 7.47 (t, 3J(H,H)=7.4 Hz, 1H), 7.72 (d, 3J(H,H)=7.5 Hz,
2H); 13C NMR: d
= 37.5, 59.38, 115.28, 115.06, 127.0 (d, J(C,F)=
16.4 Hz), 127.74, 128.68 (d, J(C,F)=12.7 Hz), 129.88 (d, J(C,F)=8.4 Hz),
130.4, 132.04, 132.35, 134.97 (d, J(C,F)=3.8 Hz), 139.7, 140.67, 160.21,
162.63; MS (MALDI-TOF): m/z: 404.13 [M+Na]+, 420.12 [M+K]+.
1-[(E)-3-(4-Methoxyphenyl)-1-propenyl]-1-cyclohexanol (4m): The reac-
tion mixture was stirred at 208C for 6 h. For column chromatography
pentane/Et2O 3:2 was used, yielding 4m (30 mg, 76%). 1H NMR: d =
N1-[(E)-4-(2-Fluorophenyl)-1-phenyl-2-butenyl]-1-benzenesulfonamide
(7 f): In this reaction 2.5 mol% of complex 1c was used as catalyst. The
reaction mixture was stirred at 08C for 1 h and an additional 15 h at
208C. For column chromatography pentane/EtOAc 5:1 was used, yielding
7 f (58 mg, 95%). 1H NMR: d = 3.25 (d, 3J(H,H)=6.1 Hz, 2H), 4.97 (t,
3J(H,H)=7.0 Hz, 1H), 5.13 (d, 3J(H,H)=7.5 Hz, 1H), 5.50 (dd, 3J
3
1.22–1.72 (m, 11H), 3.31 (d, J(H,H)=6.9 Hz, 2H), 3.79 (s, 3H), 5.63 (dt,
3
3J(H,H)=1.4, 15.7 Hz, 1H), 5.80 (dt, J(H,H)=6.8, 15.5 Hz, 1H), 6.84 (d,
3J(H,H)=9.1 Hz, 2H), 7.09 (d, 3J(H,H)=9.1 Hz, 2H); 13C NMR: d =
22.18, 25.54, 37.82, 38.00, 55.24, 71.30, 113.81, 127.08, 129.40, 132.49,
138.91, 157.92.
3
(H,H)=6.3, 15.5 Hz, 1H), 5.60 (dt, J(H,H)=6.3, 15.2 Hz, 1H), 6.95–7.06
Reaction of 2e with 3a to obtain 4n and 5c: The reaction mixture was
stirred at À208C for 2 h. For column chromatography pentane/EtOAc
2:1 were used to separate the regioisomers 4n and 5c to yield 4-phenyl-
2-cyclohexen-1-ol (4n; 39 mg, 78%) and 2-phenyl-3-cyclohexen-1-ol (5c;
8.4 mg, 10%). The NMR data obtained were in agreement with the liter-
ature values.[35]
N1-[(E)-1,4-Diphenyl-2-butenyl]-1-benzenesulfonamide (7a): The reac-
tion mixture was stirred at 208C for 15 h. For column chromatography
pentane/EtOAc 4:1 was used, yielding 7a (56 mg, 95%). 1H NMR: d =
3.25 (d, 3J(H,H)=6.6 Hz, 2H), 4.97 (t, 3J(H,H)=7.1 Hz, 1H), 5.03 (d, 3J
(H,H)=7.3 Hz, 1H), 5.51 (dd, 3J(H,H)=6.3, 15.1 Hz, 1H), 5.63 (dt, 3J
(H,H)=6.5, 15.2 Hz, 1H), 7.04 (d, 3J(H,H)=7.0 Hz, 2H), 7.1–7.3 (m,
8H), 7.34 (t, 3J(H,H)=7.8 Hz, 2H), 7.46 (t, 3J(H,H)=7.5 Hz, 1H), 7.72
(d, 3J(H,H)=7.4 Hz, 2H); 13C NMR: d = 38.36, 59.41, 126.16, 126.94,
127.1, 127.68, 128.42, 128.49, 128.58, 128.73, 130.15, 132.29, 132.32, 139.35,
139.77, 140.66; MS (MALDI-TOF): m/z: 386.1 [M+Na]+, 402.08
[M+K]+.
(m, 3H), 7.10–7.24 (m, 6H), 7.33 (t, 3J(H,H)=7.7 Hz, 2H), 7.45 (t, 3J
(H,H)=7.3 Hz, 1H), 7.72 (d, 3J(H,H)=7.6 Hz, 2H); 13C NMR: d
=
31.38 (d, J(C,F)=3.1 Hz), 59.25, 115.20 (d, J(C,F)=21.8 Hz), 124.03 (d, J
(C,F)=3.8 Hz), 126.27 (d, J(C,F)=16 Hz), 126.76, 127.01 (d, J(C,F)=
11.8 Hz), 127.14, 127.67, 127.95 (d, J(C,F)=7.9 Hz), 128.63 (d, J(C,F)=
14.4 Hz), 130.39, 130.53 (d, J(C,F)=4.7 Hz), 130.64, 132.31, 139.7, 140.62,
159.58, 162.02; MS (MALDI-TOF): m/z: 404.1 [M+Na]+, 420.08
[M+K]+.
1-[(E)-4-(4-Iodophenyl)-1-phenyl-2-butenyl]-1-benzenesulfonamide (7g):
In this reaction three equivalents of 4-iodo phenyl boronic acid (3g) and
CsF was employed in the presence of 5 mol% of complex 1c. The reac-
tion mixture was stirred at 208C for 16 h. For column chromatography
pentane/EtOAc 5:1 was used, yielding 7g (75 mg, 93%). 1H NMR: d =
3.17 (d, 3J(H,H)=6.5 Hz, 2H), 4.96 (t, 3J(H,H)=7.0 Hz, 1H), 5.27 (d, 3J
(H,H)=7.0 Hz, 1H), 5.49 (dd, 3J(H,H)=6.3, 15.6 Hz, 1H), 5.60 (dt, 3J
(H,H)=6.3, 15.6 Hz, 1H), 6.75–7.82 (m, 14H); 13C NMR: d = 37.77,
59.32, 91.29, 126.89, 127.03, 127.07, 127.70, 128.59, 128.73, 128.78, 130.59,
130.69, 131.38, 132.33, 137.41, 139.00, 139.60, 140.60; MS (MALDI-TOF):
m/z: 512.33 [M+Na]+, 528.32 [M+K]+.
N1-[(2E,5E)-1,6-Diphenyl-2,5-hexadienyl]-1-benzenesulfonamide
(7b):
The reaction mixture was stirred at 208C for 3 h. For column chromatog-
1
raphy pentane/EtOAc 5:1 was used, yielding 7b (59 mg, 95%). H NMR:
N1-[(E)-4-(2,6-Dimethylphenyl)-1-phenyl-2-butenyl]-1-benzenesulfon-
amide (7h): In this reaction 2.5 mol% of complex 1c was used as cata-
lyst. The reaction mixture was stirred at 08C for 1 h and an additional
17 h at 208C. For column chromatography pentane/CH2Cl2 1:1 was used,
d = 2.81 (t, J=6.0 Hz, 2H), 5.00 (brt, J=6.6 Hz, 1H), 5.27 (brd, J=
7.4 Hz, 1H), 5.54 (m, 2H), 6.01 (dt, J=15.9 Hz, 6.8 Hz, 1H), 6.30 (dt, J=
15.9 Hz, 1.3 Hz, 1H), 7.13–7.39 (m, 12H), 7.41–7.47 (m, 1H), 7.75–7.78
(m, 2H); 13C NMR: d
= 35.2, 59.5, 126.0, 126.9, 127.1, 127.1, 127.3,
1
3
yielding 7h (59 mg, 95%). H NMR: d = 2.17 (s, 6H), 3.24 (d, J(H,H)=
5.7 Hz, 2H), 4.93 (t, 3J(H,H)=7 Hz, 1H), 5.11 (d, J(H,H)=7.7 Hz, 1H),
3
127.6, 128.4, 128.5, 128.7, 130.0, 131.1, 131.3, 132.3, 137.3, 139.8, 140.7;
MS (MALDI-TOF): m/z: 389.07 [M+H]+, 413.25 [M+Na]+, 428.23
[M+K]+.
5.30 (dd, 3J(H,H)=6.3, 15.4 Hz, 1H), 5.53 (dt, 3J(H,H)=5.7, 15.3 Hz,
3
3
1H), 6.95–7.24 (m, 8H), 7.31 (t, J(H,H)=7.2 Hz, 2H), 7.44 (t, J(H,H)=
7.5 Hz, 1H), 7.71 (d, 3J(H,H)=7.4 Hz, 2H); 13C NMR: d = 19.78, 32.01,
59.24, 126.10, 126.88, 126.97, 127.54, 128.01, 128.47, 128.65, 129.01, 130.17,
132.26, 135.54, 136.42, 139.90, 140.61; MS (MALDI-TOF): m/z: 414.13
[M+Na]+, 430.11 [M+K]+.
N1-[(E)-4-(4-Bromophenyl)-1-phenyl-2-butenyl]-1-benzenesulfonamide
(7c): The reaction mixture was stirred at 208C for 15 h. For column chro-
matography pentane/EtOAc 4:1 was used, yielding 7c (67 mg, 95%).
1H NMR: d = 3.18 (d, 3J(H,H)=6.3 Hz, 2H), 4.96 (t, 3J(H,H)=6.7 Hz,
1H), 5.18 (d, 3J(H,H)=7.3 Hz, 1H), 5.49 (dd, 3J(H,H)=6.0, 15.1 Hz,
1H), 5.6 (dt, 3J(H,H)=6.3, 15.4 Hz, 1H), 6.9 (d, 3J(H,H)=8.3 Hz, 2H),
N1-[(E)-1-(4-Methylphenyl)-4-phenyl-2-butenyl]-4-methyl-1-benzenesul-
fonamide (7i): The reaction mixture was stirred at 208C for 17 h. For
column chromatography pentane/EtOAc 5:1 was used, yielding 7i
3
7.07–7.24 (m, 5H), 7.31–7.38 (m, 4H), 7.47 (t, J(H,H)=7.4 Hz, 1H), 7.72
(d, 3J(H,H)=7.5 Hz, 2H); 13C NMR: d = 37.68, 59.34, 119.95, 126.91,
(51 mg, 82%). 1H NMR: d
=
2.29 (s, 3H), 2.39 (s, 3H), 3.25 (d, 3J
127.05, 127.74, 128.61, 128.74, 130.25, 130.69, 131.45, 131.47, 132.35,
(H,H)=6.3 Hz, 2H), 4.90 (t, 3J(H,H)=6.8 Hz, 1H), 4.99 (d, 3J(H,H)=
5266
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 5260 – 5268

Cross-Coupling
FULL PAPER
3
3
6.8 Hz, 1H), 5.50 (dd, J(H,H)=6.2, 15.4 Hz, 1H), 5.64 (dt, J(H,H)=6.1,
15.1 Hz, 1H), 7.00–7.32 (m, 11H), 7.62 (d, 3J(H,H)=8.3 Hz, 2H);
13C NMR: d = 20.97, 21.44, 38.35, 59.14, 126.08, 126.86, 127.20, 128.36,
128.48, 129.19, 129.28, 129.35, 130.46, 131.80, 137.02, 137.32, 137.75,
139.47, 142.96; MS (MALDI-TOF): m/z: 414.35 [M+Na]+, 430.36
[M+K]+.
8.4 Hz, 2H), 7.56 (d, 3J(H,H)=8.3 Hz, 2H); 13C NMR: d = 21.45, 37.47,
58.76, 115.16 (d, J(C,F)=22.2 Hz), 121.54, 127.11, 128.75, 129.37, 129.91,
131.56, 132.51, 134.77 (d, J(C,F)=3.2 Hz), 137.47, 138.82, 143.34, 159.79,
163.03; 19F NMR: d = À117.43 (m); MS (MALDI-TOF): m/z: 496.34/
498.34 [M+Na]+, 512.35/514.36 [M+K]+.
N1-[(E)-1-(4-Nitrophenyl)-4-phenyl-2-butenyl]-4-methyl-1-benzenesulfon-
amide (7p): The reaction mixture was stirred at 208C for 16 h. For
column chromatography pentane/EtOAc 4:1 was used, yielding 7p
(64 mg, 95%). 1H NMR: d = 2.37 (s, 3H), 3.23 (d, 3J(H,H)=6.6 Hz,
2H), 5.0 (t, 3J(H,H)=6.8 Hz, 1H), 5.44 (dd, 3J(H,H)=6.8, 13.7 Hz, 2H),
5.6 (dt, 3J(H,H)=7.3, 15.7 Hz, 1H), 7.01 (d, 3J(H,H)=7 Hz, 2H), 7.10–
7.36 (m, 7H), 7.59 (d, 3J(H,H)=8.4 Hz, 2H), 8.03 (d, 3J(H,H)=8.5 Hz,
2H); 13C NMR: d = 21.43, 38.34, 58.80, 123.63, 126.34, 127.11, 127.93,
128.42, 128.49, 128.75, 129.49, 133.95, 137.16, 138.77, 143.69, 147.12,
147.19; MS (MALDI-TOF): m/z: 445.07 [M+Na]+, 461.06 [M+K]+.
N1-[(E)-4-(4-Fluorophenyl)-1-(4-methylphenyl)-2-butenyl]-4-methyl-1-
benzenesulfonamide (7j): The reaction mixture was stirred at 208C for
17 h. For column chromatography pentane/EtOAc 5:1 was used, yielding
7j (65 mg, 95%). 1H NMR: d = 2.29 (s, 3H), 2.38 (s, 3H), 3.21 (d, 3J
(H,H)=6.3 Hz, 2H), 4.88 (t, 3J(H,H)=6.4 Hz, 1H), 5.09 (d, 3J(H,H)=
3
3
6.4 Hz, 1H), 5.49 (dd, J(H,H)=5.7, 15.6 Hz, 1H), 5.62 (dt, J(H,H)=6.2,
15.6 Hz, 1H), 6.87–7.06 (m, 8H), 7.14 (d, 3J(H,H)=8.0 Hz, 2H), 7.61 (d,
3J(H,H)=7.7 Hz, 2H); 13C NMR: d = 20.97, 21.42, 37.45, 59.11, 115.07
(d, J(C,F)=21.5 Hz), 126.84, 127.18, 129.22, 129.28, 129.92, 130.71,
131.59, 135.09 (d, J(C,F)=3.2 Hz), 136.94, 137.74, 143.01, 159.75, 162.99;
19F NMR: d = À117.59 (m); MS (MALDI-TOF): m/z: 432.36 [M+Na]+,
448.36 [M+K]+.
Stoichiometric reaction of complex 1c and boronic acid 3 f: Complex 1c
(prepared from 2.2 mg chloro complex 1a, 0.004 mmol) was mixed with
2-fluorophenyl boronic acid 3 f (0.008 mmol, 1.1 mg, 2 equiv) in [D8]THF
(0.5 mL) and water (0.05 mL). To this mixture was added CsF
(0.02 mmol, 3.0 mg, 5 equiv). The progress of the reaction was monitored
N1-[(E)-1-(4-Bromophenyl)-4-phenyl-2-butenyl]-4-methyl-1-benzenesul-
fonamide (7k): The reaction mixture was stirred at 208C for 15 h. For
column chromatography pentane/EtOAc 4:1 was used, yielding 7k
(68 mg, 93%). 1H NMR: d = 2.39 (s, 3H), 3.23 (d, 3J(H,H)=6.5 Hz,
2H), 4.89 (t, 3J(H,H)=6.6 Hz, 1H), 5.34 (d, 3J(H,H)=7.9 Hz, 1H), 5.45
(dd, 3J(H,H)=6.1, 16.0 Hz, 1H), 5.60 (dt, 3J(H,H)=6.6, 15.1 Hz, 1H),
6.97–7.61 (m, 13H); 13C NMR: d = 21.46, 38.32, 58.74, 121.46, 126.18,
127.11, 128.41, 128.44, 128.77, 129.35, 129.56, 131.50, 132.71, 137.46,
138.92, 139.15, 143.26; MS (MALDI-TOF): m/z: 478.30/480.30 [M+Na]+,
494.30/496.29 [M+K]+.
1
by an array experiment using H NMR spectroscopy.
Stoichiometric reaction of [Pd2dba3] and boronic acid 3 f: [Pd2(dba)3]
(3.7 mg, 0.004 mmol) was mixed with 2-fluorophenyl boronic acid 3 f
(0.008 mmol, 1.1 mg, 2 equiv) in [D8]THF (0.5 mL) and water (0.05 mL).
To this mixture was added CsF (0.020 mmol, 3.0 mg, 5 equiv). The prog-
ress of the reaction was monitored by an array experiment using
1H NMR spectroscopy.
Stoichiometric reaction of [Pd2(dba)3] and vinyl epoxide 2a affording
complex 9: [Pd2dba3] (3.8 mg, 0.004 mmol) was mixed with vinyl epoxide
2a (0.008 mmol, 0.56 mg, 2 equiv) and LiCl (0.020 mmol, 0.56 mg,
5 equiv) in THF (0.5 mL). The progress of the reaction was followed by
1H NMR spectroscopy. After 60 min the product was purified by column
chromatography by using CH2Cl2 until all dibenzylidene acetone was
eluted and then CH2Cl2/Et2O 1:1 to get pure complex 9. 1H NMR: d =
3.00 (d, 3J(H,H)=12 Hz, 1H), 3.57 (ddd, J(H,H)=4.31 Hz, 7.0 Hz,
14.75 Hz, 1H), 3.81 (ddd, J(H,H)=3.4, 6.4, 14.8 Hz, 1H), 3.96 (dt, 3J
(H,H)=4.2, 10.9 Hz, 1H), 4.06 (d, 3J(H,H)=6.7 Hz, 1H), 5.59 (dt, 3J
(H,H)=6.7, 11.6 Hz, 1H); 13C NMR: d = 60.54, 61.79, 85.99, 107.67.
N1-[(2E,5E)-1-(4-Bromophenyl)-6-phenyl-2,5-hexadienyl]-4-methyl-1-
benzenesulfonamide (7l): The reaction mixture was stirred at 208C for
3 h. For column chromatography pentane/EtOAc 5:1 was used, yielding
7l (73 mg, 95%). 1H NMR: d = 2.35 (s, 3H), 2.81 (t, J=6.2 Hz, 2H),
4.91 (brt, J=6.8 Hz, 1H), 5.18 (brd, J=7.1 Hz, 1H), 5.42–5.59 (m, 2H),
6.01 (dt, J=15.7 Hz, 6.7 Hz, 1H), 6.29 (d, J=15.7 Hz, 1H), 7.01 (d, J=
8.2 Hz, 2H), 7.16 (d, J=8.2 Hz, 2H), 7.19–7.35 (m, 7H), 7.59 (d, J=
8.2 Hz, 2H); 13C NMR: d = 21.4, 35.2, 58.9, 121.5, 126.0, 127.1, 127.2,
128.5, 128.8, 129.4, 129.6, 131.3, 131.6, 131.9, 137.3, 137.6, 138.9, 143.3;
MS (MALDI-TOF): m/z: 504.05/506.04 [M+Na]+, 520.06/522.05 [M+K]+.
N1-[(E)-1,4-di(4-Bromophenyl)-2-butenyl]-4-methyl-1-benzenesulfon-
amide (7m): The reaction mixture was stirred at 208C for 15 h. For
column chromatography pentane/EtOAc 4:1 was used, yielding 7m
(82 mg, 95%). 1H NMR: d = 2.39 (s, 3H), 3.18 (d, 3J(H,H)=6.2 Hz,
2H), 4.88 (t, 3J(H,H)=6.8 Hz, 1H), 5.22 (d, 3J(H,H)=7.3 Hz, 1H), 5.44
(dd, 3J(H,H)=6.2, 15.6 Hz, 1H), 5.57 (dt, 3J(H,H)=6.7, 15.3 Hz, 1H),
6.89 (d, 3J(H,H)=8.1 Hz, 2H), 6.97 (d, 3J(H,H)=8.7 Hz, 2H), 7.13 (d, 3J
(H,H)=8.7 Hz, 2H), 7.30 (d, 3J(H,H)=8.4 Hz, 2H), 7.35 (d, 3J(H,H)=
8.4 Hz, 2H), 7.55 (d, 3J(H,H)=8.2 Hz, 2H); 13C NMR: d = 21.45, 37.47,
58.76, 115.03, 115.11, 115.31, 121.54, 127.11. 128.53, 128.75, 129.37, 129.44,
129.59, 129.80, 129.91, 131.56, 131.68, 132.51, 134.75, 134.79, 137.48,
138.82, 143.34, 159.79, 163.03; MS (MALDI-TOF): m/z: 556.40, 558.40,
560.38 [M+Na]+, 572.39, 574.40, 576.38 [M+K]+.
Acknowledgements
The authors thank the Swedish Research Council (VR) for the financial
support.
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Received: March 10, 2005
Published online: June 30, 2005
5268
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