Sila-morita-baylis-hillman reaction of Arylvinyl ketones: Overcoming the dimerization problem

Article abstract of DOI:10.1021/ol8026522

Arylvinyl ketones, under Morita-Baylis-Hillman (MBH) reaction conditions, produce a mixture of dimerization products. We propose a solution to this problem: a sila-MBH reaction. This cascade reaction involves addition of phosphine catalyst to arylvinyl ke

Full text of DOI:10.1021/ol8026522

ORGANIC
LETTERS
2009
Vol. 11, No. 1
253-255
Sila-Morita-Baylis-Hillman Reaction of
Arylvinyl Ketones: Overcoming the
Dimerization Problem
Alexander Trofimov and Vladimir Gevorgyan*
Department of Chemistry, UniVersity of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
Vlad@uic.edu
Received November 17, 2008
ABSTRACT
Arylvinyl ketones, under Morita-Baylis-Hillman (MBH) reaction conditions, produce a mixture of dimerization products. We propose a solution
to this problem: a sila-MBH reaction. This cascade reaction involves addition of phosphine catalyst to arylvinyl ketones, trapping of the
forming ꢀ-silylenolate with aldehyde, followed by a 1,3-Brook rearrangement to give the Si-MBH adducts in good to excellent yields.
The Morita-Baylis-Hillman (MBH) reaction is one of the
mildest yet most powerful and general methods for C-C
bond formation.1 This reaction was shown to be highly
efficient with a variety of Michael acceptors such as ketones,
esters, cyanides, etc. to produce allylic alcohols A (Scheme
1). Unfortunately, because of high reactivity, the MBH
reaction is not efficient with arylvinyl ketones. In this case,
the formation of a 1:2 adduct B is the major reaction path
together with simple dimerization of the substrate to give
C.2 Most importantly, this approach completely fails to
produce the normal MBH reaction adduct A. Herein we wish
to report a sila-MBH reaction of R-silylated vinyl aryl
ketones 1 with aldehydes 2 in the presence of catalytic
Scheme 1
amounts of TTMPP (tris(2,4,6-trimethoxyphenyl)phosphine)
(1) For recent reviews, see: (a) Masson, G.; Housseman, C.; Zhu, J.
Angew. Chem., Int. Ed. 2007, 46, 4614. (b) Shi, Y.-L.; Shi, M. Eur. J. Org.
Chem. 2007, 18, 2905. (c) Basavaiah, D.; Rao, A. J.; Satyanarayana, T.
Chem. ReV. 2003, 103, 811. For recent advances, see: (d) Jellerichs, B. G.;
Kong, J.-R.; Krische, M. J. J. Am. Chem. Soc. 2003, 125, 7758. (e) Wang,
L.-C.; Luis, A. L.; Agapiou, K.; Jang, H.-Y.; Krische, M. J. J. Am. Chem.
Soc. 2002, 124, 2402. (f) Frank, S. A.; Mergott, D. J.; Roush, W. R. J. Am.
Chem. Soc. 2002, 124, 2404. (g) Thalji, R. K.; Roush, W. R. J. Am. Chem.
Soc. 2005, 127, 16778. (h) Krafft, M. E.; Haxell, T. F. N. J. Am. Chem.
Soc. 2005, 127, 10168.
to produce 3 in good to excellent yields (eq 1).
Previously, we reported the TTMPP-catalyzed sila-MBH
reaction of cyclopropenes. In that case, unusually high reactivity
(2) (a) Shi, M.; Li, C.-Q.; Jaing, J.-K. Molecules 2002, 7, 721. (b) Shi,
M.; Li, C.-Q.; Jaing, J.-K. HelV. Chim. Acta 2002, 85, 1051.
10.1021/ol8026522 CCC: $40.75
Published on Web 12/04/2008
2009 American Chemical Society

of a non-Michael acceptor-type double bond was attributed to
the strain of a cyclopropene ring.3 We intended to test this
tandem transformation on acyclic silylated arylvinyl ketones.4
It was anticipated that zwiterionic enolate i,5 produced upon
addition of nucleophilic catalyst to enone 1, would undergo an
addition to the carbonyl group of aldehyde 26 to generate
alkoxide ii. The latter is perfectly set for the subsequent 1,3-
Brook rearrangement7/elimination cascade to furnish siloxym-
ethylene enone 3 and release the catalyst (Scheme 2).
Table 2. Sila-Morita-Baylis-Hillman Reaction
Scheme 2
We were pleased to find that employment of 5 mol % of
TTMPP8 in dioxane was effective for the reaction of silylated
vinylphenyl ketone 1a and benzaldehyde 2a to produce the
corresponding adduct 3aa in 56% yield (eq 2).
Next, the optimization of the reaction conditions was
performed (Table 1). Screening other N- or P-based nucleo-
Table 1. Optimization of the Reaction Conditionsa
yield,
%
c
entry
Nub
mol %
solvent
Si
time, h
1
2
3
4
5
6
7
8
TTMPP
TDMPP
DABCO
DMAP
5
5
5
5
5
5
5
5
5
5
5
5
10
1
5
5
5
1,4-dioxane Me3Si
1,4-dioxane Me3Si
1,4-dioxane Me3Si
1,4-dioxane Me3Si
1,4-dioxane Me3Si
1,4-dioxane Me3Si
12
12
12
12
12
12
12
12
12
12
12
12
5
56
51
0
5
0
PPh3
Pt-Bu3
0
TTMPP
TTMPP
TTMPP
TTMPP
TTMPP
TTMPP
TTMPP
TTMPP
TTMPP
TTMPP
DMF
Me3Si
52
46
66
48
42
73
71
0
pyridine
toluene
DMSO
Me3Si
Me3Si
Me3Si
9
a Isolated yield. b Reaction was performed at room temperature with
1.5 equiv of benzaldehyde 2a and 1 equiv of enone 1b (1 M).
10
11
12
13
14
15
16
diglyme
C3H7CN
C3H7CN
C3H7CN
C3H7CN
C3H7CN
C3H7CN
Me3Si
Me3Si
Me3Si
Me3Si
PhMe2Si
t-BuMe2Si
Me3Si
philes revealed TTMPP as superior catalysts for this trans-
formation (entries 1-6). Switching solvent from dioxane to
butyronitrile allowed for the substantial increase of the yield,
producing 3aa in 73% yield (entry 12). Changing the catalyst
loading (entries 13 and 14) or nature of the silyl group9
(entries 15 and 16) did not lead to the more efficient reaction.
Notable improvement of the yield (81%) was obtained when
2 equiv of enone 1a was used (entry 17).
12
12
12
12
32d
0
81d e
,
17 TTMPP
a 0.1 mmol scale; 1 M concentration; room temperature; 1.5 equiv of
benzaldehyde. b TDMPP ) tris(2,6-dimethoxyphenyl)phosphine; DABCO
) 1,4-diazabicyclo[2.2.2]octane; DMAP ) 4-(dimethylamino)pyridine. c GC
yield. d Isolated yield. e Slow addition of 2.0 equiv of phenylvinylketone 1a.
254
Org. Lett., Vol. 11, No. 1, 2009

With optimized conditions in hand, the scope of this
transformation was examined (Table 2). Remarkably, the
reaction was found to be quite general with respect to the
alkene component. Electronically different arylvinyl ketones
1a-d reacted smoothly with benzaldehyde 2a, producing
the corresponding silylated MBH adducts 3aa-da in good
yields (entries 1-4). Next, a series of differently substituted
aryl adlehydes 2b-j10 in the reaction with phenylvinyl
ketone 2a were tested (entries 5-13). Both electron-rich and
-deficient aryl aldehydes reacted well under the reaction
conditions. Methoxy, siloxy, and halogen substituents were
well tolerated in this transformation.
In summary, we have developed
a sila-Morita–
Baylis–Hillman reaction of readily available and stable11
R-silylvinylaryl ketones12 with aryl aldehydes. This protocol
proceeds via a 1,3-Brook rearrangement/elimination cas-
cade13 and allows for the mild and efficient synthesis of
syloxymethylene aryl enones, structural units unavailable via
a traditional MBH reaction.
(3) Chuprakov, S.; Malyshev, D.; Trofimov, A.; Gevorgyan, V. J. Am.
Chem. Soc. 2007, 129, 14868.
(4) For the Michael addition/Peterson olefination tandem of R-silyle-
nones, see: (a) Tanaka, J.; Kobayashi, H.; Kanemasa, S.; Tsuge, O. Bull.
Chem. Soc. Jpn. 1989, 62, 1193. (b) Iqbal, M.; Evans, P. Tetrahedron Lett.
2003, 44, 5741.
(5) For spectroscopic characterization of analogous phosphonium in-
termediates, see: Zhu, X.-F.; Henry, C. E.; Kwon, O. J. Am. Chem. Soc.
2007, 129, 6722.
Acknowledgment. The support of the National Science
Foundation (CHE-0710749) is gratefully acknowledged.
(6) For reactions of R-silylenolates with alkyl and carbonyl electrophiles,
see: (a) Demuth, M. HelV. Chim. Acta 1978, 61, 3136. (b) Inoue, T.; Sato,
T.; Kuwajima, I. J. Org. Chem. 1984, 49, 4671. (c) Tsuge, O.; Kanemasa,
S.; Suzuki, T.; Matsuda, K. Bull. Chem. Soc. Jpn. 1986, 59, 2851. (d) Tsuge,
O.; Kanemasa, S.; Otsuka, T.; Suzuki, T. Bull. Chem. Soc. Jpn. 1986, 61,
2851.
Supporting Information Available: Preparative proce-
dures and analytical and spectral data. This material is
available free of charge via the Internet at http://pubs.acs.org.
(7) For a review on Brook rearrangement, see: (a) Moser, W. H.
Tetrahedron 2001, 57, 2065. For recent advances, see: (b) Takeda, K.;
Sawada, Y.; Sumi, K. Org. Lett. 2002, 4, 1031. (c) Xin, L.; Nicewicz, D. A.;
Johnson, J. S. Org. Lett. 2002, 4, 2957. (d) Fleming, I.; Lawrence, A. J.;
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OL8026522
(10) Employment of aliphatic aldehydes under these reaction conditions
was not efficient.
(11) R-Silylated aryl vinyl ketones are stable compounds in contrast to
their nonsilylated counterparts.
(12) Sato, S.; Matsuda, I.; Izumi, Y. Tetrahedron Lett. 1983, 24, 3855.
(13) This reaction appeared to be quite sensitive to the substitution at
the ꢀ-position of the alkene moiety, thus ruling out possible involvement
of an alternative mechanism proceeding via TTMPP activation of a silyl
group14 followed by trapping of the forming allenolate with aldehyde. See
Supporting Information for details.
(14) For TTMPP activation of a silyl group, see: (a) Matsukawa, S.;
Saijo, M. Tetrahedron Lett. 2008, 49, 4655. (b) Matsukawa, S.; Okano,
N.; Imamoto, T. Tetrahedron Lett. 2000, 41, 103. (c) Matsukawa, S.; Obu,
K. Chem. Lett. 2004, 33, 1626. (d) Matsukawa, S.; Kitazaki, E. Tetrahedron
Lett. 2008, 49, 2982. (e) Kobayashi, S.; Tsuchiya, Y.; Mukaiyama, T. Chem.
Lett. 1991, 4, 537.
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H.; Nakamichi, N.; Hayashi, M. Chem. Lett. 2001, 934. (b) Kawabata, H.;
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Chisholm, J. D. Tetrahedron Lett. 2006, 47, 9313.
(9) For Brook rearrangement of different silyl groups, see for example:
Bra¨uer, N.; Michel, T.; Schaumann, E. Tetrahedron 1998, 54, 11481.
Org. Lett., Vol. 11, No. 1, 2009
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