Palladium-catalyzed desulfitative mizoroki-heck couplings of sulfonyl chlorides with mono-and disubstituted olefins: Rhodium-catalyzed desulfitative heck-type reactions under phosphine- And base-free conditions

Article abstract of DOI:10.1002/chem.200400838

New conditions have been found for the desulfitative Mizoroki-Heck arylation and trifluoromethylation of mono- and disubustituted olefins with arenesulfonyl and trifluoro-methanesulfonyl chlorides. Thus (E)-1,2- disubstituted alkenes with high ster-eoselectivity and 1,1,2-disubstituted alkenes with 12:1 to 21:1 E/Z steroselectivity can be obtained. Herrmann's palladacycle at 0.1 mol% is sufficient to catalyze these reactions, for which electron-rich or electron-poor sulfonyl chlorides and alkenes are suitable. If phosphine- and base-free conditions are required. 1 mol% [RriCl(C ₂,H₄)₂] catalyzes the desulfitative cross-cou pling reactions. Contrary to results reported for [RuCl₂(PPh ₃)₂]-catalyzed coupling reactions with sulfonyl chlorides, the palladium and rhodium desulfitative Mizoroki-Heck coupling reactions are not inhibited by radical scavenging agents. Possible sulfones arising from the sulfonylation of alkenes at 60°C are not desulfitated at higher temperatures in the presence of the Pd or Rh catalysts.

Full text of DOI:10.1002/chem.200400838

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FULL PAPER
Chem. Eur. J. 2005, 11, 2633 – 2641
DOI: 10.1002/chem.200400838
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2633

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Palladium-Catalyzed Desulfitative Mizoroki–Heck Couplings of Sulfonyl
Chlorides with Mono-and Disubstituted Olefins: Rhodium-Catalyzed
Desulfitative Heck-Type Reactions under Phosphine- and Base-Free
Conditions
Srinivas Reddy Dubbaka and Pierre Vogel*[a]
Abstract: New conditions have been
found for the desulfitative Mizoroki–
Heck arylation and trifluoromethyla-
tion of mono- and disubustituted ole-
fins with arenesulfonyl and trifluoro-
methanesulfonyl chlorides. Thus (E)-
1,2-disubstituted alkenes with high ster-
eoselectivity and 1,1,2-disubstituted al-
kenes with 12:1 to 21:1 E/Z steroselec-
tivity can be obtained. Herrmannꢂs pal-
ladacycle at 0.1 mol% is sufficient to
catalyze these reactions, for which elec-
tron-rich or electron-poor sulfonyl
chlorides and alkenes are suitable. If
phosphine- and base-free conditions
are required, 1 mol% [RhCl(C2H4)2]
catalyzes the desulfitative cross-cou-
pling reactions. Contrary to results re-
ported for [RuCl2(PPh3)2]-catalyzed
coupling reactions with sulfonyl chlor-
ides, the palladium and rhodium desul-
fitative Mizoroki–Heck coupling reac-
tions are not inhibited by radical scav-
enging agents. Possible sulfones arising
from the sulfonylation of alkenes at
608C are not desulfitated at higher
temperatures in the presence of the Pd
or Rh catalysts.
Keywords: alkenes
·
Mizoroki–
Heck reaction · palladium · phase-
transfer catalysis · rhodium
Introduction
undergo desulfitative and carbonylative Stille,[4] Suzuki–
Miyaura,[5] and Sonogashira–Hagihara[6] cross-coupling reac-
tions. The sulfonyl chlorides are generally more reactive
than the corresponding bromides and chlorides.[4,5] The Miz-
oroki–Heck arylation of alkenes is very useful for synthe-
ses.[1,2] Aroyl chlorides and alkenes can be coupled under
decarbonylative conditions.[7] With [{RhCl(alkene)2}2] as cat-
alyst the reactions can be carried out under phosphine- and
base-free conditions.[8] From further exploration of the po-
tential of sulfonyl chlorides as reactants in transition-metal-
catalyzed reactions, we have now extended their application
in the Mizoroki–Heck reaction using Pd and Rh cata-
lysts.[9,10] We have found conditions under which desulfita-
tive Mizoroki–Heck cross-coupling can be carried out with
sulfonyl chlorides under phosphine- and base-free condi-
tions.
ꢀ
Transition-metal-catalyzed C C bond-forming reactions are
among the most powerful methods of organic synthesis.[1,2]
In recent years, new conditions (ligands, additives) have
been developed that permit cross-coupling of a large variety
of reactants (Scheme 1).[2] A search for more economical
procedures has implied reduction or suppression of co-prod-
ucts and side products and the use of inexpensive starting
materials.[3] We have shown that the readily available sulfo-
nyl chlorides (RSO2Cl, R = aryl, alkenyl, methallyl, benzyl)
Scheme 1. Substrates for general Mizoroki–Heck-type reactions.
Results and Discussion
[a] S. R. Dubbaka, Prof. Dr. P. Vogel
Laboratory of Glycochemistry and Asymmetric Synthesis
Ecole Polytechnique Fꢁdꢁerale de Lausanne (EPFL)
BCH, 1015 Lausanne (Switzerland)
Palladium-catalyzed desulfitative Mizoroki–Heck-type cou-
pling with sulfonyl chlorides: In continuation of work by
Kasahara[9a,b] and Miura [9c,d] and their respective co-workers,
we
investigated
whether
catalysts
other
than
Fax : (+41)21-693-9375
E-mail: pierre.vogel@epfl.ch
[PdCl2(PhCN)2], Pd(OAc)2, PdCl2, Pd black, and
2634
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DOI: 10.1002/chem.200400838
Chem. Eur. J. 2005, 11, 2633 – 2641

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Rhodium-Catalyzed Desulfitative Heck-Type Reactions
FULL PAPER
[PdCl2(PPh3)2] would improve the yield of the desulfitative
vinylations. Our exploratory experiments started with the
coupling of 1-naphthalenesulfonyl chloride (1; 2 mmol) and
butyl acrylate (2; 5.5 mmol) in the presence of
[PdCl2(PhCN)2] (3 mol%), Me(oct)3NCl (15 mol%), and
K2CO3 (4 mmol) in m-xylene. After 4 h at 1408C a 53%
chloride (Table 1, entry 1 versus 2). Bulky organic bases
were not suitable in our examples, whereas an inorganic
base such as K2CO3 led to higher yields (Table 1, entry 1
versus 3 and 4). Addition of electron-rich ligands such as
4,[15] 5,[16a] and 6[16b] increased the yields. The best results
were obtained by using the palladacycle 7,[17] developed by
Herrmann et al., as catalyst (Table 1, entries 5, 8–10). When
using low boiling polar solvents, the yields were lower than
in boiling m-xylene (Table 1, entries 6 and 7).
yield of coupling product
3 was obtained (Table 1,
entry 1).[9d] It is known that phase-transfer catalysts can be
beneficial to Mizoroki–Heck-type reactions.[11–14] By screen-
ing various phase-transfer catalysts we have found that the
bulky trioctylmethylammonium chloride leads to better re-
sults than the smaller tetrabutyl- or tetraethylammonium
Table 1. Catalyst, bases, and PTC screening.
Entry
Pd source (Concn. [mol%])
Base
Yield [%][a]
We applied these optimized conditions to the desulfitative
coupling of electron-rich, electron-neutral, and electron-
poor sulfonyl chlorides with a wide variety of olefins. For
good yields of Mizoroki–Heck-type products 10 from the re-
action of sulfonyl chlorides (8) (Table 2) with butyl acrylate,
styrene, 1-hexene, and phenylvinylsulfone (9), the reaction
temperature must be higher than 1208C (Table 2, entry 5).
In most cases the reaction is over after 4–5 h, except when
unreactive olefins such as 1-hexene are used. In the latter
case, the reaction with 4-acetylbenzenesulfonyl chloride
1
2
3
4
5
6
7
8
[PdCl2(PhCN)2] (3)
[PdCl2(PhCN)2] (3)
[PdCl2(PhCN)2] (3)
[PdCl2(PhCN)2]/4 (3/6)
[PdCl2(PhCN)2]/4 (3/6)
[PdCl2(PhCN)2]/4 (3/6)
[Pd2dba3]/4 (1.5/6)
[PdCl2(PhCN)2]/5 (3/6)
[PdCl2(PhCN)2]/6 (3/6)
palladacycle 7 (0.1)
K2CO3
K2CO3
Et3N
Cy2NMe
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
53
15[b,c]
30
<20
78
45[d]
54[d]
80
9
10
78
90[e]
[a] Yields of coupling products determined after flash chromatography.
[b] Bu4NCl was used instead of Me(oct)3NCl. [c] Yield was 5 mol% when
Et4NCl was used instead of Me(oct)3NCl. [d] The mixture was refluxed in
THF instead of m-xylene, starting material and side product were ob-
served after 24 h. [e] Yield was also 90% with 0.4 mol% of palladacycle
7.
Table 2. The palladium-catalyzed desulfitative Mizoroki–Heck type of
reaction of various sulfonyl chlorides with terminal alkenes.
Entry
R
R1
Yield [%][a]
90[b]
83
Abstract in French: De nouvelles conditions sont rapporteꢀs
pour les couplages dꢀsulfitants du type Mizoroki–Heck des
chlorures dꢁarꢂnesulfonyles et trifluoromꢀthanesulfonyle avec
des olꢀfines mono- et disubstitueꢀs. La mꢀthode permet la
synthꢂse de (E)-alcꢂnes 1,2-disubstituꢀs avec haute stꢀrꢀosꢀ-
lectivitꢀ et dꢁalkꢂnes 1,1,2-trisubstituꢀs avec des stꢀrꢀosꢀlecti-
vitꢀs E/Z variant de 12:1 ꢃ 21:1. La palladacycle de Herr-
mann ꢃ 0.1 mol% est suffisant pour catalyser ces reactions
qui peuvent engager des chlorures de sulfonyles et des alcꢂnes
soit riches ou pauvres en ꢀlectron. Si des conditions sans
phosphine et sans base sont requises, 1 mol% de
[RhCl(C2H4)2] est un excellent catalyseur pour ces couplages
dꢀsulfitants. Contrairement ꢃ ce qui est rapportꢀ pour des rꢀ-
actions analogues catalysꢀes par [RuCl2(PPh3)2] et qui impli-
quent des intermꢀdiaires radicalaires, les couplages du type
Mizoroki–Heck dꢀsulfitants catalysꢀs par des complexes de
palladium ou de rhodium ne sont pas inhibꢀs par des piꢂges
ꢃ radicaux. De plus, les sulfones qui peuvent se former par
sulfonylation des alcꢂnes (60oC) ne sont pas dꢀsulfitꢀes ꢃ
plus haute tempꢀrature en prꢀsence des catalyseurs au Pd ou
au Rh.
1
2
3
4
5
6
7
8
1-naphthyl
1-naphthyl
COOnBu
Ph
COOnBu
Ph
COOnBu
nBu
COOnBu
COOnBu
COOnBu
COOnBu
COOnBu
SO2Ph
COOnBu
COOnBu
Ph
4-methylphenyl
4-methylphenyl
4-acetylphenyl
4-acetylphenyl
4-trifluorophenyl
4-fluorophenyl
4-methoxyphenyl
3-cyanophenyl
4-nitrophenyl
4-trifluorophenyl
4-(pyrazol-1-yl)phenyl
2,4,6-trimethylphenyl
trifluoromethyl
trifluoromethyl
76
80[c]
74[d]
51[e,f]
72
70[g]
75
9
10
11
12
13
14
15
16
73[h]
78
49
40
45[i]
50[j]
32[j]
COOnBu
[a] Yields of coupling products determined after flash chromatography.
[b] Yield 53% according to ref. [9d]. [c] Yield 75% with 3%
[PdCl2(PhCN)2], 6% ligand 5 instead of palladacycle 7. [d] Yield 35% in
THF under reflux. [e] In p-xylene under reflux, 21 h and with five equiva-
lents of alkene. [f] Yield 51% in THF under reflux with 3%
[PdCl2(PhCN)2], 6% ligand 5 instead of palladacycle 7. [g] Yield 64%
with 3% [PdCl2(PhCN)2], 6% ligand
[h] Under reflux for 13 h. [i] Under reflux for 24 h. [j] Using a microwave
5 instead of palladacycle 7.
oven at 1508C for 10 h and with five equivalents of alkene.
Chem. Eur. J. 2005, 11, 2633 – 2641
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P. Vogel and S. R. Dubbaka
gave 51% yield of the product
of desulfitative Mizoroki–Heck
coupling after 24 h, and only
one isomer was isolated. The
crude reaction mixture did not
show evidence of the presence
of isomeric products, apart from
polymeric material. The lower
yield might be attributed to the
presence of an excess of alkene.
It is known from previous work
on Heck reactions that an in-
creased concentration of olefin
Scheme 2. The reactions of n-butyl acrylate with disulfonyl dichlorides. a) K2CO3 (5.7 mmol), Me(oct)3NCl
(0.43 mmol), palladacycle 7 (1 mol%) and m-xyxlene (5 mL) under reflux for 4–7 h.
significantly reduces the catalyst efficiency. With phenyl-
vinylsulfone the yield was also moderate (Table 2, entry 12).
Heterocyclic compounds were also applied successfully in
the reaction, but led only to moderate yields (Table 2,
entry 13). Sterically hindered substrates required longer re-
action times (see, for example, Table 2, entry 14). The reac-
tion of trifluoromethanesulfonyl chloride with an excess of
styrene (5 equiv) in a sealed tube or microwave oven at
1508C in m-xylene gave the desired desulfitative Mizoroki–
Heck coupling product ((E)-3,3,3-trifluoro-1-phenylprop-1-
ene) in about 10 h (Table 2, entry 15).[10e] With butyl acry-
late, the same reaction pro-
palladium-catalyzed conditions using electron-rich li-
gands.[15e] We have found that arenesulfonyl chlorides can
react with disubstituted olefins under our conditions, with
high stereoselectivity (Table 3). Both electron-rich and elec-
tron-poor sulfonyl chlorides can be coupled with methyl
crotonate and butyl methacrylate with acceptable yields
(Table 3).
Preparation of a,b-unsaturated sulfones: mechanism of the
palladium-catalyzed desulfitative Mizoroki–Heck coupling:
We have found that the reaction of arenesulfonyl chlorides
duced butyl (E)-4,4,4-trifluoro-
but-2-enoate in 32% yield
(Table 2, entry 16).
Table 3. Palladium-catalyzed synthesis of trisubstituted olefins.
Entry
Sulfonyl chloride
Olefin
Product
(E)/(Z) ratio[a]
Yield [%][b]
Double desulfitative Mizoro-
ki–Heck couplings have also
been realized. The reaction be-
tween butyl acrylate 2 with bi-
phenyl-4,4’-disulfonyl chloride
11 and with 1,3-benzenedisul-
fonyl chloride 13 produced the
important polymer precursors[18]
12 and 14 respectively, in good
yields (Scheme 2).
There are very few reports
on Mizoroki–Heck-type aryla-
tion of disubustituted olefins
with aryl halides. Buchwald and
Gꢃrtler have presented a gener-
al procedure for the Mizoroki–
Heck arylation of disubustitut-
ed olefins with heteroaryl bro-
mides using bulky amines as
bases and a phase-transfer cata-
lyst under phosphine-free con-
ditions.[13] Moreno-MaÇas and
co-workers have reported Heck
arylations of disubstituted ole-
fins that require expensive aryl
iodides.[19] Littke and Fu
showed that cheaper aryl chlor-
ides can react with mono- and
1
20:1
40
2
3
4
14:1
12:1
21:1
40
52
47
5
15:1
60
[a] E/Z isomer ratio of product of the second desulfitative Mizoroki–Heck reaction as determined after flash
chromatography. [b] Yield of all known products. We have verified their structures by NOE 1H NMR experi-
disubustituted olefins under ments.
2636
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Chem. Eur. J. 2005, 11, 2633 – 2641