Nickel-Catalyzed Olefination of Unactivated Aliphatic Dithioacetals

Article abstract of DOI:10.1021/ol035802o

(Equation presented) Olefination of aliphatic dithioacetals with Grignard reagents is catalyzed by Ni(acac)₂ in the presence of an appropriate trialkylphosphine ligand.

Full text of DOI:10.1021/ol035802o

ORGANIC
LETTERS
2003
Vol. 5, No. 23
4489-4491
Nickel-Catalyzed Olefination of
Unactivated Aliphatic Dithioacetals
Li-Fu Huang,†,§ Chih-Hao Huang,† Baldur Stulgies,§, Armin de Meijere, and
,†,‡,§
Tien-Yau Luh*
Department of Chemistry and Institute of Polymer Science and Engineering,
National Taiwan UniVersity, Taipei, Taiwan 106, Institute of Chemistry,
Academia Sinica, Nangang, Taipei, Taiwan 115, and Institut fu¨r Organische Chemie,
Georg-August-UniVersita¨t Go¨ttingen, Tammannstrasse 2, 37077 Go¨ttingen, Germany
tyluh@chem.sinica.edu.tw
Received September 18, 2003
ABSTRACT
Olefination of aliphatic dithioacetals with Grignard reagents is catalyzed by Ni(acac)2 in the presence of an appropriate trialkylphosphine
ligand.
There has been an increasing interest in the transition-metal-
catalyzed cross coupling of aliphatic halides or related elec-
trophiles with nucleophiles.1-4 The use of electron-rich ali-
phatic phosphine ligands, inter alia, has provided a powerful
access to these coupling reactions.2 We have extensively
studied the nickel-catalyzed cross-coupling reactions of ben-
zylic or allylic dithioacetals with Grignard reagents.5,6 In the
absence of an auxiliary chelating group(s)6 or specially de-
signed substrates,7 aliphatic dithioacetals alone do not react
with Grignard reagents, even in the presence of the typical
nickel triarylphosphine catalyst. We envisaged that an in-
crease of the nucleophilicity of the nickel catalyst by incorp-
oration of a trialkylphosphine ligand might enhance the
reactivity of the catalytic center toward the oxidative addition
across the carbon-sulfur bond, and we now wish to docu-
ment the first examples of such a nickel-catalyzed olefination
of unactivated aliphatic dithioacetals with Grignard reagents.
In the beginning of this work, we examined the perfor-
mance of different kinds of trialkylphosphine ligands in the
olefination reaction of 1 with the Grignard reagent. Thus,
treatment of 2-(2′-naphthyl)acetaldehyde dithioacetal 1 with
3 equiv of MeMgI in the presence of 5 mol % of Ni(acac)2
and 12 mol % of trialkylphosphine in refluxing toluene for
20 h afforded a mixture of the naphthyl derivatives 2-4 (eq
1). The results are summarized in Table 1.
† Department of Chemistry, National Taiwan University.
‡ Institute of Polymer Science and Engineering, National Taiwan
University.
§ Institute of Chemistry, Academia Sinica.
Institut fu¨r Organische Chemie, Georg-August-Universita¨t Go¨ttingen.
(1) (a) For reviews, see: Leung, M.-K.; Wong, K.-T.; Luh, T.-Y. Chem.
ReV. 2000, 100, 3187-3204. (b) Cardenas, D. J. Angew. Chem., Int. Ed.
2003, 42, 384-387.
(2) (a) Netherton, M. R.; Dai, C.; Neuschu¨tz, K.; Fu, G. C. J. Am. Chem.
Soc. 2001, 123, 10099-10100. (b) Kirchhoff, J. H.; Netherton, M. R.; Hills,
I. D.; Fu, G. C. J. Am. Chem. Soc. 2002, 124, 13662-13663. (c) Kirchhoff,
J. H.; Dai, C.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 1945-1947. (d)
Netherton, M. R.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 3910-3912.
(e) Frisch, A. C.; Shaikh, N.; Zapf, A.; Beller, M. Angew. Chem., Int. Ed.
2002, 41, 4056-4059. (f) Menzel, K.; Fu, G. C. J. Am. Chem. Soc. 2003,
125, 3718-3719. (g) Lee, J. Y.; Fu, G. C. J. Am. Chem. Soc. 2003, 125,
5616-5617.
The reaction may proceed according to a mechanism
similar to the one proposed for the benzylic substrates.5,6 The
two carbon-sulfur bonds in 1 may be cleaved at different
stages and the overall reaction may involve a coupling
process followed by an elimination step. The organonickel
intermediate 5 would be expected to undergo nonselective
(3) (a) Boudier, A.; Bromm, L. O.; Lotz, M.; Knochel, P. Angew. Chem.,
Int. Ed. 2000, 39, 4414-4435. (b) Dohle, W.; Lindsay, D. M.; Knochel, P.
Org. Lett. 2001, 3, 2871-2873. (c) Jensen, A. E.; Knochel, P. J. Org. Chem.
2002, 67, 79-85. (d) Wolter, M.; Nordmann, G.; Job, G. E.; Buchwald, S.
L. Org. Lett. 2002, 4, 973-976. (e) Lei, A.; Zhang, X. Org. Lett. 2002, 4,
2285-2288. (f) Terao, J.; Watanabe, H.; Ikumi, A.; Kuniyasu, H.; Kambe,
N. J. Am. Chem. Soc. 2002, 124, 4222-4223.
(5) Luh, T.-Y. Acc. Chem. Res. 1991, 24, 257-263.
(6) (a) Wong, K.-T.; Yuan, T.-M.; Wang, M.-C.; Tung, H.-H.; Luh, T.-
Y. J. Am. Chem. Soc. 1994, 116, 8920-8929. (b) Luh, T.-Y. Synlett 1996,
201-208.
(4) Ni, Z.-J.; Mei, N.-W.; Shi X.; Tzeng, Y.-L.; Wang, M.-C.; Luh, T.-
Y. J. Org. Chem. 1991, 56, 4035-4042.
(7) Cheng, W.-L.; Luh, T.-Y. Chem. Commun. 1992, 1392-1393.
10.1021/ol035802o CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/10/2003

of 13 improved to 56% when PtBu2Me was used. Similarly,
the cyclododecanone derivative 15 was transformed into the
corresponding olefination product 16 (E/Z ) 10/1) in 52%
and 67% yields, respectively, under the same conditions with
PtBu3 and PtBu2Me as the ligand. Since ketone dithioacetals
in general are more sterically congested than aldehyde di-
thioacetals, a less bulky ligand may provide a more spacious
environment to lead to the desired coupling product. Thus,
by using PtBu2Me as the ligand, the Ni(acac)2-catalyzed reac-
tions of 12 and 15 with 4-MeC6H4MgBr afforded 14 and 17
in 59% and 63% yields, respectively. Dithioacetals derived
from acyclic ketones behaved similarly. Treatment of 18 with
PhMgBr under the same conditions, with PtBu2Me as the
ligand, gave the corresponding olefination product 19 in 61%
yield. Olefin 20 was isolated in 55% yield from a similar
reaction of 18 with 4-MeC6H4MgBr. Aliphatic Grignard
reagent also reacted smoothly. For example, treatment of 21
with Me3SiCH2MgCl afforded the corresponding vinylsilane
22 in 73% yield by using the same procedure.
Table 1. Ni(acac)2-Catalyzed Olefination of 1 in the Presence
of Trialkylphosphine Ligand
entry
ligand (mol %))
% yield
2/3/4a
1
2
3
4
P(Cy)3 (12)
P(n-Bu)3 (12)
P(t-Bu)3 (12)
P(t-Bu)2Me (12)
1
34
20
78
70
10/1/4
10/1/3
12/1/2.5
10/1/4
a Estimated by H spectrum.
In summary, we have demonstrated the first example of
the nickel-catalyzed cross-coupling reaction of the aliphatic
dithioacetals derived from aldehydes and ketones with
Grignard reagents. Our results document an additional
application of trialkylphosphines to assist the activation of
otherwise unactivated aliphatic carbon-sulfur bonds in the
nickel-catalyzed cross-coupling reaction. The reaction may
provide a useful procedure for a direct conversion of a
dithioacetal-protected carbonyl group into the corresponding
olefins. In particular, vinylsilanes are conveniently obtained
by this route. Further investigation to improve the regios-
lectivity in the formation of the new double bond is in
progress in our laboratory.
â-hydride elimination giving a mixture of 2-4. Although
the product distributions were not much affected by the
nature of the trialkylphosphine ligands, phosphines with a
large cone angle may cause higher reactivity in these
olefination reactions, and indeed, the best yield was obtained
when PtBu3 was used.
When 1 was treated with TMSCH2MgCl in the presence
of 5 mol % of Ni(acac)2 and 12 mol % of PtBu3 under the
same conditions as just described, allylsilane 6 was obtained
in 57% yield. Interestingly, only a trace amount of vinylsilane
7 was detected, which was easily removed from 6 by
recrystallization. Vinylsilane 9 was obtained in 91% yield
from the nickel-catalyzed reaction of 8 with PhMe2SiCH2-
MgCl under the same conditions. In a similar manner,
reaction of 10 with PhMgBr afforded 11 (containing a trace
amount of the cis isomer) in 50% yield. Apparently, the ring
size of the dithioacetal moiety does not have any influence
on the reactivity under these olefination conditions.
Ketone dithioacetals also reacted smoothly under similar
conditions. Again, the nature of the ligand does influence
the yield of the reaction. Thus, nickel-catalyzed reaction of
cyclohexanone dithioacetal 12 with PhMgBr afforded 13 in
48% yield when PtBu3 was employed as the ligand. The yield
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Org. Lett., Vol. 5, No. 23, 2003

Acknowledgment. We thank the National Science Coun-
cil and the Ministry of Education of the Republic of China
for financial support. We also thank the PPP exchange
program cosponsored by the NSC (Taiwan) and the DAAD
(Germany) to enable B.S. to do part of the experimental work
at the Academia Sinica.
Supporting Information Available: Experimental details
of the nickel-catalyzed reactions of dithioacetals with Grig-
nard reagents. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL035802O
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