An unexpected Lewis acids-catalyzed tandem ring-opening rearrangement of vinylcyclopropane ketone with aryl aldehyde

Article abstract of DOI:10.1016/j.tetlet.2014.03.035

A novel tandem reaction of vinylcyclopropane ketone with benzaldehyde has been successfully developed. This provides a new method for the preparation of γ-oxo-hexenone derivatives from easily accessible starting materials.

Full text of DOI:10.1016/j.tetlet.2014.03.035

Tetrahedron Letters 55 (2014) 2545–2547
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An unexpected Lewis acids-catalyzed tandem ring-opening
rearrangement of vinylcyclopropane ketone with aryl aldehyde
⇑
Jun Ren, Yu Bai, Weijie Tao, Zhongwen Wang
State Key Laboratory and Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University,
94# Weijin Road, Tianjin 300071, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A
novel tandem reaction of vinylcyclopropane ketone with benzaldehyde has been successfully
Received 13 January 2014
Revised 27 February 2014
Accepted 6 March 2014
Available online 14 March 2014
developed. This provides a new method for the preparation of
accessible starting materials.
c
-oxo-hexenone derivatives from easily
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Cyclopropane
Tandem reactions
Rearrangement
Ring opening
Vinyl cyclopropanes (VCPs) are useful C5 synthons in organic
synthesis. Typical reactions of VCPs being applied in organic
synthesis include rearrangements to cyclopentenes and transition
metal-catalyzed cycloadditions.1,2 During our exploration for
development of novel acid-catalyzed polar formal cycloadditions
of activated cyclopropanes for the construction of cyclic skeletons,
we observed an unexpected tandem process of VCP ketone 1a with
Table 1
Screening of Lewis acids for optimal conditiona
O
O
O
OTBS
O
Lewis acid
O
+
Ph
H
Ph
+
CH2Cl2, -78 °C-r.t.
Ph
O
TBSO
Ph
O
1a
2a
3a
4a
benzaldehyde, which led to
c
c-oxo-hexenone 4a (Table 1). Because
-oxo-hexenones are useful intermediates in organic synthesis,3,4
Entry
Cat.a
Time
Yield
3a 66%
3a 17%, 4a 26%
3a 31%
3a 34%
4a 59%
3a 5%, 4a 33%
3a 16%
4a 26%
3a 7%
—
we started to explore this novel reaction.
Under catalysis of Sc(OTf)3, reaction of 1a with benzaldehyde 2a
was carried out from À70 °C to room temperature. The reaction
was sluggish but finally gave 4a after 5 days (Table 1, entry 1).
The structure of 4a was confirmed by X-ray crystallographic anal-
ysis (Fig. 1).5,6 Various Lewis acids were screened and the results
are listed in Table 1. In some cases, a Mukaiyama–Aldol product
3a was obtained. We found that when it was first carried out at
À70 °C for 2 h under catalysis of Sc(OTf)3 and was then carried
out at rt for additional 54 h under catalysis of TMSOTf, the reaction
was accelerated with a better yield (entry 11). This reaction condi-
tion was selected for further investigation.
1
2
3
4
5
6
7
8
9
Sc(OTf)3
Yb(OTf)3
BF.3Et2O
SnCl4
TiCl4
ZnCl2
5 d
9 d
2 d
10 d
15 d
13 d
3 d
13 d
2 d
Sn(OTf)2
Zn(OTf)2
Cu(OTf)2
TMSOTf
10
11
15 h
56 h
Sc(OTf)3 + TMSOTfb
3a 75%
a
General condition: 1a (0.66 mmol), 2a (0.55 mmol), Lewis acids (0.2 equiv), and
CH2Cl2 (10 mL) were mixed and stirred from À70 °C to rt.
The scope of substrates 2 was then explored (Table 2). We found
that both electron-rich and electron-deficient benzaldehydes
worked well with moderate to excellent yields (entries 2–9).
b
The reaction was first carried out at À70 °C for 2 h under catalysis of Sc(OTf)3
(0.2 equiv), and then at rt for 54 h under catalysis of TMSOTf (0.2 equiv).
Benzaldehyde substituted with NO2, 2-furaldehyde and aliphatic
butyraldehyde did not give the corresponding products.
⇑
Corresponding author. Tel.: +86 010 022 23498191.
E-mail address: wzwrj@nankai.edu.cn (Z. Wang).
http://dx.doi.org/10.1016/j.tetlet.2014.03.035
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

2546
J. Ren et al. / Tetrahedron Letters 55 (2014) 2545–2547
O
O
O
O
O
O
OTBS
Ph
O
Sc(OTf)3
Ph
via Ph
Ph
+
H
CH2Cl2, -78-0 o
C
Ph
Ph
4 A MS
67 %
Ph
1b
2a
5
Scheme 2.
of A gave 2,3-dihydrofuran C.8 Probably due to the contaminating
water in the reaction mixture, C was then transferred to 3a through
a hetero-Michael reaction and C–C bond cleavage process.
When substrate 1b was employed in the reaction with 2a,
Figure 1. X-ray crystal structure of 3a.
instead of the
c-oxo-hexenone product, tetrahydrofuran 5 was
obtained (Scheme 2). This was probably due to the hydrolysis of
enol silyl ether to cyclopropane 1,1-diketone, with the donor-acti-
vation of a phenyl group which underwent a subsequent [3+2]
cycloaddition with 2a.9
Table 2
Reactions of vinylcyclopropane ketone 1a with benzaldehydes 2a
In summary, we have developed a novel tandem reaction of
vinylcyclopropane ketone with benzaldehyde. This method
O
R
O
OTBS
1. Sc(OTf)3, -70 oC, 2 h, CH2Cl2
2. TMSOTf, r. t.
O
H
+
Ph
O
provides a new strategy for the preparation of
c-oxo-hexenone
R
O
derivatives from the easily accessible starting materials.
3a-i
1a
2a-i
Acknowledgments
Entry
R
Time (h)
Yieldb
We thank NSFC (Nos 21172109, 21121002) and MOST (Nos
2010CB126106, 2011BAE06B05) for financial support.
1
2
3
4
5
6
7
8
9
2a H
56
53
56
62
48
67
60
51
51
3a 75%
3b 84%
3c 42%
3d 63%
3e 93%
3f 38%
3g 61%
3h 61%
3i 47%
2b p-Cl
2c p-Br
2d p-F
2e p-Me
2f o-Cl
2g p-tBu
2h p-MeO
2i m-MeO
Supplementary data
Supplementary data (experimental procedures and spectral
data for all new products) associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.03.
035.
a
General addition: 1a (0.66 mmol), 2a (0.55 mmol), Lewis acids (0.2 equiv), and
CH2Cl2 (10 mL). The reaction was first carried out at À70 °C for 2 h under catalysis
References and notes
of Sc(OTf)3 (0.2 equiv), and then at rt for 54 h under catalysis of TMSOTf (0.2 equiv).
b
Isolated yields.
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Ph
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Scheme 1. Proposed mechanism.
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give cyclopropane 1,1-diketone A.7 A ring-opening rearrangement

J. Ren et al. / Tetrahedron Letters 55 (2014) 2545–2547
2547
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5. Structure of 3a was confirmed by the single-crystal X-ray diffraction analysis.
CCDC 800958 contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge Crystallographic
DataCentre via www.ccdc.cam.ac.uk/data_request/cif.
6. Physical data for compound 3a: 1H NMR (400 MHz, CDCl3) d 8.04 (d, J = 7.3 Hz,
2H), 7.62–7.35 (m, 10H), 6.76 (d, J = 16.2 Hz, 1H), 4.41 (t, J = 6.3 Hz, 2H), 2.86 (t,
J = 7.2 Hz, 2H), 2.19 (p, J = 6.7 Hz, 2H). 13C NMR (101 MHz,) d 199.06, 166.54,
142.73, 134.36, 132.94, 130.52, 129.55, 128.93, 128.35, 128.27, 125.98, 64.24,
37.19, 23.31.IR (neat): m = 2964, 2897, 1709, 1689, 1612, 1450, 1314, 1283, 1127,
1041, 977, 762, 713, 684 cmÀ1; HRMS (ESI) Calcd For C19H18O3Na (M+Na)+:
317.1148; found: 317.1148.
9. Pohlhaus, P. D.; Johnson, J. S. J. Org. Chem. 2005, 70, 1057.
7. Unfortunately, a try to isolate the intermediates A, C and D failed.