Sila Morita-Baylis-Hillman reaction of cyclopropenes

Article abstract of DOI:10.1021/ja077437s

The first example of sila-Morita-Bayis-Hillman reaction between 1-silylcyclopropenes and carbonyl compounds has been demonstrated. This novel phosphine-catalyzed transformation features a 1,3-Brook rearrangement/elimination cascade and provides convenient

Full text of DOI:10.1021/ja077437s

Published on Web 11/13/2007
Sila Morita-Baylis-Hillman Reaction of Cyclopropenes
Stepan Chuprakov, Denis A. Malyshev, Alexander Trofimov, and Vladimir Gevorgyan*
Department of Chemistry, UniVersity of Illinois at Chicago, Chicago, Illinois 60607
Received September 26, 2007; E-mail: vlad@uic.edu
Table 1. Optimization of the Reaction Conditionsa
The Morita-Baylis-Hillman (MBH) reaction1 is an attractive
and powerful tool for carbon-carbon bond formation (eq 1). This
protocol involves amine- or phosphine-catalyzed coupling of Michael-
acceptors with carbonyl compounds or their equivalents. Herein,
we report the phosphine-catalyzed sila-MBH reaction of 1-silyl-
cyclopropenes 1 with carbonyl compounds, which produces 1-(si-
lyloxymethyl)cyclopropenes 2 in good to excellent yields (eq 2).
entry
catalystb
mol %
solvent
temp
time, h
yieldc, %
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
DABCO
DBU
DMAP
P(t-Bu)3
PPh3
25
25
25
25
25
25
25
25
25
5
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
rt
rt
rt
rt
rt
rt
rt
0 °C
50 °C
rt
rt
rt
rt
rt
rt
3
3
3
3
3
3
3
3
42
0
28
5
12
5
57
33
42
62
62
64
68
66
79
PCy3
TTMPP
TTMPP
TTMPP
TTMPP
TTMPP
TTMPP
TTMPP
TTMPP
TTMPP
DMF
DMF
DMA
3
4.5
4.5
4.5
4.5
4.5
6
5
5
5
5
Cyclopropenes2 are the smallest unsaturated carbocycles, pos-
sessing a highly strained3 double bond, which readily undergoes a
wide array of addition reactions.4,5 We hypothesized that 1-silyl-
substituted cyclopropenes might be suitable substrates for a sila-
MBH reaction on the basis of the following reasoning. It was
thought that the high reactivity of the cyclopropene double bond,
together with the ability of silyl group to stabilize R-carbanion,6
could allow for the formation of R-silylcyclopropyl anion i7 upon
addition of nucleophilic catalyst4a-d to 1-silylcyclopropene 1 (eq
3). If long-lived, intermediate i may undergo an addition to carbonyl
group to produce alkoxide ii, which was reasoned to be an ideal
substrate for a subsequent 1,3-Brook rearrangement8/elimination
cascade to furnish 1-(silyloxymethyl)cyclopropene 2 (eq 3).
DMSO
1,4-dioxane
THF
1
1,4-dioxaned
a 0.1 mmol scale; 1 M concentration; rt ) room temperature. b DABCO
) 1,4-diazabicyclo[2.2.2]octane; DBU ) 1,8-diazabicyclo[5.4.0]undec-7-
ene; DMAP ) 4-(dimethylamino)pyridine; TTMPP ) tris(2,4,6-trimethox-
yphenyl)phosphine. c GC yield. d Reaction run using 2 M concentration, 0.5
mmol scale.
an activated double bond, reacted with 1a highly chemo- and
regioselectively11 to produce 1,4-diene 2h in good yield (entry 8).
Remarkably, primary, secondary, and tertiary aliphatic aldehydes
were equally efficient in sila-MBH reaction (entries 9-11),
suggesting a low sensitivity of this reaction to steric hindrance at
the R-position of aldehyde.
Next, we tested a series of unsymmetrically substituted 1-silyl-
cyclopropenes 1b-e in the reaction with benzaldehyde (eq 4). Both
3-aryl and 3-silyl substrates, as well as tetrasubstituted cyclopropene,
produced the corresponding sila-MBH products 2l-o in good to
excellent yields, though as nearly equimolar mixtures of diastere-
omers. It was also found that the reaction was limited to cyclo-
propenes possessing electron-withdrawing groups at C-3. Presum-
ably, this was required to decrease the energy of the cyclopropene’s
LUMO12 for a more facile addition of nucleophilic catalyst.
To this end, we examined the reaction of 1-(trimethylsilyl)-
cyclopropene-3,3-dicarboxylate 1a with benzaldehyde in the pres-
ence of various nucleophilic catalysts (Table 1). We were pleased
to find that in the presence of 25 mol % of DABCO 1a, indeed,
underwent the sila-MBH reaction to produce the expected cyclo-
propene 2a in 42% yield (entry 1).9 Next, it was found that electron-
rich tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP) was more
efficient than other N- and P-based catalysts (entries 1-7).
However, the yield of 2a produced in the presence of 25 mol % of
TTMPP in DMF at ambient temperature remained moderate (entry
7). Change of temperature did not improve the reaction yield (entries
8-9). To our delight, it was found that reducing the catalyst loading,
together with the use of 1,4-dioxane as a solvent, allowed for a
dramatic increase in the yield of the sila-MBH reaction, producing
2a in 79% yield (entry 15).10
Naturally, with optimized conditions in hand, we examined the
scope of this novel transformation with respect to the aldehyde
component (Table 2). Gratifyingly, a wide selection of aryl and
heteroaryl aldehydes (entries 1-7) reacted smoothly with 1a to
produce 1-(silyloxymethyl)cyclopropenes 2 in good yields. Ester-,
methoxy-, and halo-substituents were well tolerated in this trans-
formation. Notably, cinnamyl aldehyde, a compound possessing
Encouraged by the successful sila-MBH reaction of 1 with
aldehydes, we then attempted the analogous reaction with activated
ketones (eq 5). To our delight, we found that cyclopropene 1a
9
14868
J. AM. CHEM. SOC. 2007, 129, 14868-14869
10.1021/ja077437s CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Phosphine-Catalyzed Sila-MBH Reaction of
1-silylcyclopropene 1aa
the direct and efficient synthesis of 1-(silyloxymethyl)cycloprope-
nes, which are not easily available through existing methods. Further
studies on expanding the scope9 and elucidation of the precise
mechanism of sila-MBH reaction are underway in our laboratories.
Acknowledgment. The financial support of National Science
Foundation (Grant CHE-0710749) is gratefully acknowledged.
Supporting Information Available: Experimental procedures and
spectral data. This material is available free of charge via the Internet
at http://pubs.acs.org.
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a Reaction conditions: 1a (0.5 mmol), aldehyde (1.0 mmol), TTMPP
(0.005 mmol), dioxane (0.25 mL). b Isolated yield.
reacted smoothly with 1,2-dicarbonyl compound to form R-sily-
loxyketone 2p. Moreover, R,R,R-trifluoroacetophenone underwent
reaction with 1a to produce cyclopropene 2q in reasonable yield
(eq 5).13 It deserves mentioning that, prior to the development of
this protocol, there were no direct approaches toward 1-(silyloxym-
ethyl)cyclopropene-3-carboxylates 2. Indeed, these synthetically
(8) For review, see: Moser, W. H. Tetrahedron 2001, 57, 2065.
(9) Simple vinylsilane, R-silyl acrylate, as well as non-silylated cyclopropenes,
did not undergo this transformation. In contrast, a-silyl enones produced
MBH product in moderate yield. Further studies of this transformation
are underway in our laboratories.
(10) It was found that TTMPP causes notable decomposition of 1a. Thus, lower
catalyst loading allowed for higher material balance. See Supporting
Information for details and full optimization data.
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useful building blocks14 may not be obtained through the direct
Rh(II)-catalyzed addition of diazocompounds to secondary prop-
argyl alcohol derivatives, as this route is known to lead to the
corresponding allenes.15 An alternative dianion approach16 requires
hydrolysis of ester group and reesterification.
In summary, we developed a sila Morita-Baylis-Hillman
reaction of readily available17 1-silylcylopropene-3-carboxylates
with aldehydes and activated ketones, involving a 1,3-Brook
rearrangement/elimination sequence. This novel protocol allows for
(13) Attempts to employ acyl halides as electrophiles in this reaction were
unsuccessful.
(14) (a) Simaan, S.; Masarwa, A.; Bertus, P.; Marek, I. Angew. Chem., Int.
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Lee, G. H. Org. Lett. 2004, 6, 1233.
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