Lewis acid catalyzed carbon-carbon bond cleavage of aryl oxiranyl diketones: Synthesis of cis-2,5-disubstituted 1,3-dioxolanes

Article abstract of DOI:10.1021/ol2000292

Carbonyl ylide is one of the most important intermediates which can undergo a series of 1,3-dipolar cycloaddition reactions. The C-C heterolysis of oxirane is believed to be the most atom-economic and straightforward way to generate carbonyl ylide. Howeve

Full text of DOI:10.1021/ol2000292

ORGANIC
LETTERS
2
011
Vol. 13, No. 5
170–1173
Lewis Acid Catalyzed Carbon-Carbon
Bond Cleavage of Aryl Oxiranyl
Diketones: Synthesis of cis-2,5-
Disubstituted 1,3-Dioxolanes
1
†
Zuliang Chen, Lai Wei, and Junliang Zhang*
†
,†,‡
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of
Chemistry, East China Normal University, 3663 North Zhongshan Road, Shanghai
2
00062, P.R. China, and State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road,
Shanghai 200032, P.R. China
jlzhang@chem.ecnu.edu.cn
Received January 5, 2011
ABSTRACT
Carbonyl ylide is one of the most important intermediates which can undergo a series of 1,3-dipolar cycloaddition reactions. The C-C heterolysis
of oxirane is believed to be the most atom-economic and straightforward way to generate carbonyl ylide. However, this chemistry was only
achieved under photochemical and thermal conditions in past years. In this work, the one-step diastereoselective synthesis of cis-2,5-
disubstituted 1,3-dioxolanes via [3 þ 2] cycloadditions of aldehydes and carbonyl ylide, which is obtained from Lewis acid catalyzed C-C bond
heterolysis of aryl oxiranyl diketones at ambient temperature, is described.
1
,3-Dipolar cycloaddition reactions are known to be one
this dipole have been developed involving photochemical
2
of the most powerful tools for the synthesis of complex
skeletons possessing five-membered heterocycles, since
many 1,3-dipolar species are readily available and react
with a wide range of dipolarophiles such as aldehydes,
imines, electron-deficientalkenes, and alkynes. The chem-
istry of carbonyl ylide as a reactive 1,3-dipole has been
extensively reported; several methods for the generation of
or thermal C-C bond heterolysis of oxiranes, thermal
decomposition of oxadiazolines, 1,3-elimination reac-
3
4
tions of trimethylsilyl substituted chloromethyl ethers,
SmI -mediated generation of nonstabilized carbonyl ylides
2
1
5
from iodomethyl trialkylsilyl ethers, thermal decomposi-
6
tion of organomercury compounds, and a transition
(
2) (a) Huisgen, R. Angew. Chem., Int. Ed. Engl. 1977, 16, 572 and
references cited therein. (b) Bemaus, C.; Font, J.; de March, P. Tetra-
hedron 1991, 47, 7713. (c) Wang, G.-W.; Yang, H.-T.; Wu, P.; Miao,
C. B.; Xu., Y. J. Org. Chem. 2006, 71, 4346.
†
East China Normal University.
Chinese Academy of Sciences.
‡
(
1) (a) 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley:
(3) (a) Shimizu, N.; Bartlett, P. D. J. Am. Chem. Soc. 1978, 100, 4260.
(
b) B ꢀe khazi, M.; Warkentin, J. J. Am. Chem. Soc. 1983, 105, 1289. (c)
B
New York, 1984; Vol. 1. (b) 1,3-Dipolar Cycloaddition Chemistry; Padwa,
A., Ed.; Wiley: New York, 1984; Vol. 2. (c) Huisgen, R. In Advances in
Cycloaddition; Curran, D. P., Ed.; JAI Press Inc.: Greenwich, 1988; Vol. 1,
pp 1-32. (d) Deshong, P.; Lander, S. W.; Leginus, J. M., Jr.; Dicken,
C. M. In Advances in Cycloaddition; Curran, D. P., Ed.; JAI Press Inc.:
Greenwich, 1988; Vol. 1, pp 87-128. (e) Gothelf, K. V.; Jorgensen., K. A.
Chem. Rev. 1998, 98, 863. (f) Kanemasa, S. Synlett 2002, 1371. (g) The
Chemistry of Heterocyclic Compounds: Synthetic Applications of 1,3-
Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural
Products; Padwa, A., Pearson, W. H., Eds.; Wiley and Sons: New York,
ꢀ
ekhazi, M.; Risbood, P. A.; Warkentin, J. J. Am. Chem. Soc. 1983, 105,
5675. (d) Couture, P.; Terlouw, J. K.; Warkentin, J. J. Am. Chem. Soc.
996, 118, 4214. (e) Warkentin, J. J. Chem. Soc., Perkin Trans. 1 2000,
2161.
(4) (a) Hojo, M.; Ohkuma, M.; Ishibashi, N.; Hosomi, A. Tetrahe-
1
dron Lett. 1993, 34, 5943. (b) Hojo, M.; Aihara, H.; Suginohara, Y.;
Sakata, K.; Nakamura, S.-Y.; Murakami, C.; Hosomi, A. J. Org. Chem.
1997, 62, 8610.
(5) Hojo, M.; Aihara, H.; Hosomi, A. J. Am. Chem. Soc. 1996, 118,
3533.
2
002; Vol. 59. (h) Topics in Heterocyclic Chemistry: Synthesis of
Heterocycles via Cycloadditions I; Hassner, A., Ed; Springer-Verlag: Berlin,
Heidelberg, 2008; Vol. 12.
(6) (a) Gill, H. S.; Landgrebe, J. A. Tetrahedron Lett. 1982, 23, 5099.
(b) Gill, H. S.; Landgrebe, J. A. J. Org. Chem. 1983, 48, 1051.
1
0.1021/ol2000292 r 2011 American Chemical Society
Published on Web 02/10/2011

7
metal catalyzed diazo compound decomposition in the
and easy to make substrates, oxiranyl diketones, may bind
with certain Lewis acid and result in the C-C bond
heterolysis.
presence of carbonyl compounds. Among these methods
of generation of carbonyl ylide, it is obvious that the C-C
bond heterolysis of the easily made oxiranes is the most
atom-economical and straightforward one; however, the
major drawback of this method is the harsh reaction
conditions. On the other hand, the chemistry of oxiranes
We tested our hypothesis by using (3-phenyloxirane-2,2-
diyl)bis(phenylmethanone) 1a and benzaldehyde 2a as
model substrates. Initially, 1a and 2a were subjected to a
solution of 5 mol % Cu(OTf) in CH Cl at room tem-
2
2
2
8
is dominated by the C-O bond heterolysis. In this com-
perature. The reaction yielded the cis-1,3-dioxolane 3aa in
30% yield with excellent diastereoselectivity, and 69% of
starting material 1a was recovered after running the reac-
tion overnight (Table 1, entry 1). To improve the yield, a
representative selection of Lewis acids including Sn(OTf)2,
Bi(OTf)3, Fe(OTf) , Mg(OTf) , In(OTf) , Ni(ClO )
munication, we report a mild and efficient approach to
carbonyl ylides by Lewis acid catalyzed C-C bond hetero-
lysis of oxiranes. To the best of our knowledge, this is the
first example of Lewis acid promoted C-C heterolysis of
9
,10
oxiranes.
3
2
3
4 2
3
6
H O, Sc(OTf) , Y(OTf) , and Yb(OTf) in various sol-
2 3 3 3
vents were tested (Table 1). Catalysts such as Sn(OTf)2,
Bi(OTf)3, Fe(OTf) , and Mg(OTf) result in either low
3
2
efficiency or no catalytic activity (Table 1, entries 2-5). To
our delight, the reaction works very well in CH Cl , DCE,
or toluene at room temperature by using 1.5 equiv of 2a
under the catalysis of 5 mol % of Yb(OTf) to give the
2
2
3
1
cycloadducts 3aa in 98% H NMR yield as a single
diastereomer (Table 1, entries 10-12).
Figure 1. Novel strategies for cutting C-C bond of oxirane (a)
from previous work and (b) this work.
Table 1. Screening Reaction Conditions of Benzaldehyde 2a and
Oxirane 1a
a
Very recently, we developed a novel strategy to achieve
the selective C-C bond cleavage of an oxirane motif by
introduction of one alkyne moiety; the reaction is triggered
by gold(I) activation of the alkyne moiety (Figure 1a).
During this study, we envisaged that the more common
1
1
b
entry
catalyst
solvent
yield (%)
dr
(
7) For selected examples, see: (a) De March, P.; Huisgen, R. J. Am.
Chem. Soc. 1982, 104, 4952. (b) Huisgen, R.; De March, P. J. Am. Chem.
Soc. 1982, 104, 4953. (c) Doyle, M. P.; Forbes, D. C.; Protopopova,
M. N.; Stanley, S. A.; Vasbinder, M. M.; Xavier, K. R. J. Org. Chem.
1
2
3
4
5
6
7
8
9
Cu(OTf)
2
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
2
2
2
2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
2
2
2
2
2
2
2
2
2
2
30 (69)
13 (81)
9 (5)
22
100:0
100:0
100:0
3.5:1
-
3.4:1
6.8:1
16:1
Sn(OTf)
2
1997, 62, 7210. (d) Jiang, B.; Zhang, X.-B.; Luo, Z.-H. Org. Lett. 2002, 4,
Bi(OTf)
Fe(OTf)
3
2453. (e) Mehta, G.; Muthusamy, S. Tetrahedron 2002, 58, 9477. (f) Lu,
3
C.-Y.; Chen, Z.-Y.; Liu, H.; Hu, W. H.; Mi, A.-Q. J. Org. Chem. 2004,
9, 4856. (g) Russell, A. E.; Brekan, J.; Gronenberg, L.; Doyle, M. P. J.
Mg(OTf)
In(OTf)
Ni(ClO
Sc(OTf)
Y(OTf)
2
0 (96)
66
6
Org. Chem. 2004, 69, 5269. (h) Suga, H.; Ebiura, Y.; Fukushima, K.;
Kakehi, A.; Baba, T. J. Org. Chem. 2005, 70, 10782. (i) Padwa, A. Helv.
Chim. Acta 2005, 88, 1357. (j) Torssell, S.; Somfai, P. Adv. Synth. Catal.
3
4
)
2
3 6H2O
96
3
89
2
(
1
006, 348, 2421. (k) Son, S.; Fu, G. C. J. Am. Chem. Soc. 2007, 129, 1046.
l) DeAngelis, A.; Talor, M.; Fox, J. M. J. Am. Chem. Soc. 2009, 131,
101.
8) For selected examples, see: (a) Parker, R. E.; Isaacs, N. S. Chem.
3
97
100:0
100:0
100:0
100:0
1
0
Yb(OTf)
Yb(OTf)
Yb(OTf)
3
98
(
11
12
3
3
DCE
toluene
98
Rev. 1959, 59, 737. (b) Jacobsen, E. N. Acc. Chem. Res. 2000, 33, 421. (c)
Molinaro, C.; Jamison, T. F. J. Am. Chem. Soc. 2003, 125, 8076. (d)
Zheng, X.-L.; Jones, C. W.; Weck, M. J. Am. Chem. Soc. 2007, 129, 1105.
98
a
Reaction conditions: 1a (0.3 mmol), 2a (0.45 mmol), 5 mol %
˚
catalyst, and 60 mg of activated 4 A MS in 3 mL of solvent at room
temperature. Determined by H NMR (CH Br as a standard), and the
2 2
(
9) For metal-promoted carbon-carbon bond cleavage of N-aryl
aziridines, please see: (a) Vaultier, M.; Carrie, R. Tetrahedron Lett. 1978,
9, 1195. (b) Pohlhaus, P. D.; Bowman, R. K.; Johnson, J. S. J. Am.
Chem. Soc. 2004, 126, 2294.
10) For reviews on Lewis acid catalyzed cycloaddition of do-
b
1
1
number in parentheses refers to the recovered starting material 1a.
(
nor-acceptor cyclopropanes, see: (a) Reissig, H.-U.; Zimmer, R. Chem.
With the optimal reaction conditions in hand, the scope
of this Lewis acid catalyzed cycloaddition reaction was
explored with a variety of oxiranes 1 and 2a, and the results
are summarized in Table 2. The cycloaddtion reaction of
Rev. 2003, 103, 1151. (b) Yu, M.; Pagenkopf, B. L. Tetrahedron 2005, 61,
321. (c) Xiao,Y.; Zhang, J. In Handbook of Cyclization Reactions; Ma, S.,
Ed.; Willey-VCH: Weinheim, 2010; Vol. 2, p 733. For selected examples,
see: (d) Young, I. S.; Kerr, M. A. Angew. Chem., Int. Ed. 2003, 42, 3023.
(
(
e) Sibi, M. P.; Ma, Z.; Jasperse, C. P. J. Am. Chem. Soc. 2005, 127, 5764.
f) Young, I. S.; Kerr, M. A. J. Am. Chem. Soc. 2007, 129, 1465. (g)
2a with oxiranes 1b could give the corresponding 1,3-
Kang, Y.-B.; Sun, X.-L.; Tang, Y. Angew. Chem., Int. Ed. 2007, 46, 3918.
h) Jackson, S. K.; Karadeolian, A.; Driega, A. B.; Kerr, M. A. J. Am.
dioxolanes 3ba in 88% yield (Table 2, entry 2). Do-
nor-acceptor oxiranes bearing a 4-methoxy-phenyl sub-
stituent as the R worked well to give the corresponding
(
Chem. Soc. 2008, 130, 4196. (i) Pohlhaus, P. D.; Sanders, S. D.; Parsons,
A. T.; Li, W.; Johnson, J. S. J. Am. Chem. Soc. 2008, 130, 8642. (j)
Parsons, A. T.; Johnson, J. S. J. Am. Chem. Soc. 2009, 131, 3122. (k)
Parsons, A. T.; Smith, A. G.; Neel, A. J.; Johnson, J. S. J. Am. Chem.
Soc. 2010, 132, 9688.
2
highly substituted 1,3-dioxolanes 3ca in 94% yield
(Table 2, entry 3). There was a significant drop in the rate
of the reaction as the R substituents became more electron
2
(11) Wang, T.; Zhang, J. Chem.;Eur. J. 2011, 17, 86.
Org. Lett., Vol. 13, No. 5, 2011
1171

Table 2. Variation of Oxiranyl Diketone and Aldehyde
Component
Table 3. Reaction of 1a with Various Aldehydes
1
2
3
a
3
a
entry
R /R (1)
R (2)
t (h) yield (%)
entry
R (2)
t (h)
yield (%)
b
1
2
Ph/Ph (1a)
Ph/1-naphthyl (1b)
Ph/4-MeOC (1c)
(1d)
Ph (2a)
2
3aa (90)
1
4-MeOPh (2b)
4-MePh (2c)
4-BrPh (2d)
4-ClPh (2e)
1
2
3ab (97)
3ac (90)
3ad (94)
3ae (91)
3af (80)
3ag (85)
3ah (90)
3ai (90)
3aj (91)
3ak (93)
3al (96)
Ph (2a)
Ph (2a)
10 3ba (88)
10 3ca (94)
26 3da (89)
2
b
3
6
H
4
3
2
c
4
Ph/4-BrC
6
H
4
Ph (2a)
4
2
d
5
1d
4-MeOC
6
H
4
4
(2b)
(2b)
2
3db (93)
5
4-MeO CPh (2f)
16
10
4
2
e
6
Ph/4-MeO
CC H
2 6 4
(1e) Ph (2a)
Ph (2a)
30 3ea (89)
6
3,4,5-(MeO)C H (2g)
6
2
7
Me/Ph (1f)
2
1
2
1
3fa (87)
3fb (88)
3fc (96)
3fd (82)
7
2-furyl (2h)
d
8
1f
1f
1f
4-MeOC
6
H
8
(E)-CHdCHPh (2i)
Ethyl (2j)
2
9
4-MeC
4-BrC
6
H
4
(2c)
(2d)
9
10
12
12
1
0
6
H
4
10
(Me) CHCH (2k)
2
2
11
Ph(CH )
2 2
(2l)
a
b
Isolated yield and no any detectable other isomer. The reaction
c
was carried out at 0 °C. 10 mol % Yb(OTf)
used. 1.5 equiv of oxirane and 1.0 equiv of 2b were used. 20 mol %
Yb(OTf) and 3.0 equiv of 2a were used.
3
and 3.0 equiv of 2a were
a
b
Isolated yield and no other stereoismer is detectable. Since the
product 3ab and aldehyde 2b cannot be separable by TLC, 1.5 equiv of
a and 1.0 equiv of 2b were used in order to achieve complete conversion
d
e
3
1
of 2b.
withdrawing as in entries 4 and 6 of Table 2. Higher
catalyst loadings as well as longer reaction times were
needed in these cases; however, under the optimized con-
ditions these heterocycles could be obtained in excellent
yields. Whenthe acceptor group was switchedtoacetyl, the
desired products 3fa-3fd were also obtained in 82-96%
yields regardless of the electronics of the aldehyde (Table 2,
entries 7-10). The structure and the relative stereochem-
istry of the products were established by X-ray crystal-
desired product3ahin90% yield (Table3, entry 7). Finally,
3
introduction of alkenyl or alkyl substituents on the R
position were well tolerated, affording the corresponding
cycloadducts 3ai-3aj in 90-96% yields (Table 3, entries
8-11). It is also noteworthy that no other stereoisomer in all
the reactions we carried out is detectable.
Competition experiments were performed using substi-
tuted benzaldehydes versus benzaldehyde to gain insight
into this cycloaddition reaction. The treatment of oxirane
1
2
lography analysis of 3ba and 3fb (Figure 2).
1a with 3.0 equiv of benzaldehyde 2a and 3.0 equiv of
methyl 4-formylbenzoate 2f under 5 mol % Yb(OTf) gave
3
1
the products 3aa and 3af in 84% and 15% H NMR yield,
respectively (eq 1). The control reaction of 1a with benzal-
dehyde and electron-rich anisaldehyde 2b gave a similar
result (eq 2). These results indicate that the aldehyde
component is involved in the rate-determining step.
Figure 2. X-ray crystal structures of 3ba (left) and 3fb (right).
The hydrogen atoms on the aryl ring are deleted for clarity.
We next turned to study the scope of this reaction by
variation of the aldehyde component (Table 3). The data in
Table 3 showed that the reactions of aldehydes 2 bearing
an electron-donating or electron-withdrawing group at the
para position of the phenyl ring proceeded smoothly to
provide the corresponding cycloadducts 3ab-3ag in
8
0-97% yields (Table 3, entries 1-6). Furthermore, the
furfural was also compatible with the reaction, giving the
According to these experimental results and previous
1
0
reports for donor-acceptor cyclopropane and oxiranyl
1
1
(12) The CCDC contains the supplementary crystallographic data
3ba and 3fb) for this paper. These data can be obtained free of charge
ketone, a plausible mechanism that accounts for these
results is proposed in Scheme 1. Initially, the Lewis acid
Yb(OTf)3 binds to a bisketone moiety to give the
(
from The Cambridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/datarequest/cif.
1
172
Org. Lett., Vol. 13, No. 5, 2011

aldehyde acts as a nucleophile, causing inversion of the
2
stereochemistry at the activated R substituted carbon
center of oxirane, which has been explored by Johnson in
Scheme 1. Plausible Mechanism
1
0i
donor-acceptor cyclopropanes. Thus, the reaction of
enantioenriched oxiranyl diketone would give an enan-
tioenriched cycloadduct. In order to know which reaction
pathway is the real one, enantioenriched 1a was prepared
1
3
according to Lattanzi’s developed method. After run-
ning for 3 h under standard conditions, the reaction
afforded a racemic cycloadduct 3ad (eq 3), indicating
reaction path a may be the more possible reaction pathway
and the rate-determining step of this reaction is the step of
converting IB into IC wherein the nucleophilicity of the
aldehyde plays a significant role.
In summary, we have established for the first time an
efficient approach to carbonyl ylides by Lewis acid cata-
lyzed chemoselective C-C bond heterolysis of readily
available aryl oxiranyl diketones under mild conditions.
Synthetically useful cis-1,3-disubstituted 1,3-dioxolanes
with excellent diastereoselectivity can be afforded in ex-
cellent yields via the 1,3-dipolar cycloaddition of the
resulting carbonyl ylides and various aldehydes. Further
studies including asymmetric catalysis and expansion of
the scope of dipolarophiles are ongoing in this laboratory
and will be reported in due course.
intermediate IA. This binding would allow IA to easily
undergo C-C bond cleavage via two possible reaction
pathways (path a/b). The direct C-C heterolysis of IA
would yield metal-coordinated carbonyl ylide IB (path a),
which would readily react with aldehyde to give a zwitter-
ionic intermediate IC. Subsquent ring closure via the
favored conformation TS would afford the 1,3-dipolar
cycloadducts and regenerate the catalyst. The alternative
reaction pathway (path b) to generate IC from IA is via an
unusual stereospecific intimate ion pair process wherein
Acknowledgment. Financial support from 973 Program
(2009CB825300) is greatly appreciated.
Supporting Information Available. Experimental de-
tails, characterization data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(
13) Lattanzi, A. Adv. Synth. Catal. 2006, 348, 339.
Org. Lett., Vol. 13, No. 5, 2011
1173