RhII-catalyzed cycloadditions of carbomethoxy iodonium ylides

Article abstract of DOI:10.1016/S0040-4039(02)01260-1

Carbomethoxy iodonium ylides, generated from methyl acetoacetate and methyl malonate, respectively, are exploited in synthesis of cyclopropanes, cyclopropenes as well as various heterocycles.

Full text of DOI:10.1016/S0040-4039(02)01260-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5997–6000
RhII-catalyzed cycloadditions of carbomethoxy iodonium ylides†
Christina Batsila, George Kostakis and Lazaros P. Hadjiarapoglou*
Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
Received 15 April 2002; revised 4 June 2002; accepted 27 June 2002
Abstract—Carbomethoxy iodonium ylides, generated from methyl acetoacetate and methyl malonate, respectively, are exploited
in synthesis of cyclopropanes, cyclopropenes as well as various heterocycles. © 2002 Elsevier Science Ltd. All rights reserved.
Despite the fact that a significant number of iodonium
ylides,1 a class of hypervalent iodine compounds, are
known in the literature, their chemistry still remains
unexplored, especially when compared to the corre-
sponding diazo compounds.2 Generally speaking, the
easily isolable3 phenyliodonium ylides, formed quanti-
tatively from the reaction of an active methylene com-
pound and a hypervalent iodine precursor, have often
been used as alternatives to diazo precursors in metal-
catalyzed or photochemical cycloadditions and CH
insertion reactions.4 These reactions occur sometimes in
the absence of catalysts, albeit in much lower yields.
Quite generally speaking, phenyliodonium ylides usu-
ally decompose at lower temperatures than the corre-
sponding diazo compounds, thus leading to better
yields of the desired products.
carbenoid) leading finally to alkene 4, a product resem-
bling the decomposition of a bis(carbo-methoxy) iodo-
nium ylide. Upon heating ylide 2a in various solvents,
iodo ether 3a and alkene 4a (cis/trans mixture) were
isolated in varying amounts (Scheme 1). The formation
of iodo ether 3a was suppressed when a catalyst, e.g.
Rh2(OAc)4, Cu(acac)2, or photochemical conditions
were used and alkene 4a was isolated instead. The
structure of iodo ether 3a was elucidated from the fact
that the methyl group of the carbomethoxy substituent
appears at l 3.79, indicating that it is anti to the
phenoxy group. In contrast, alkene 4b was the only
isolable product when ylide 2b was heated or irradiated
under various conditions.
As was anticipated, ylide 2a reacts5 easily with styrene
5a leading to the corresponding cyclopropane 6a6 in
moderate yields (Scheme 2). Although the reaction
works thermally without any catalyst, it was found that
Rh2(OAc)4 gives rise to the best yield (85% yield,
cis/trans 8.1:1.9).
The major drawback of iodonium ylide chemistry, is
the requirement for two similar strong electron-with-
drawing substituents at the carbanionic center. Gener-
ally, such ylides are isolable in pure form, while ylides
with different carbanionic substituents are rather labile
entities with unknown behavior.
Ylides 2, bearing at least one carbomethoxy substituent
were easily prepared from methyl acetoacetate 1a and
methyl malonate 1b, respectively, in moderate yields
(Scheme 1), employing the well-known procedure.3,4b
There are two IꢀC bonds which could, in principle, be
cleaved. Cleavage of the IꢀCaromatic bond could yield an
iodo ether 3, resembling the decomposition product of
a b-dicarbonyl iodonium ylide, while the cleavage of
the IꢀCcarbanionic bond could yield initially a carbene (or
MeO2C
MeO2C
PhI(OAc)2,
IPh
KOH, MeOH,
-10 oC, 3.5 h
RCO
RCO
2
1
1a, 2a: R = Me (58%)
1b, 2b: R = MeO (61%)
∆
MeO2C
Me
I
MeO2C
MeO2C
COR
COR
+
OPh
* Corresponding author. Tel.: +30-651-098380; fax: +30-651-098799;
3a
4
e-mail: lxatziar@cc.uoi.gr
†
Dedicated to Professor Dr. Waldemar Adam, University of
Wu¨rzburg, on the occasion of his 65th birthday.
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01260-1

5998
C. Batsila et al. / Tetrahedron Letters 43 (2002) 5997–6000
R1
R2
RCOMe(8),
Rh2(OAc)4, ∆
MeO2C
COMe
R
C
O
(5)
R1
R2
2-15 min
CO2Me
Me
Rh2(OAc)4, ∆
Me
+
2a
CS2(11),
2-3 min
9
MeCO
EtO
Rh2(OAc)4,
O
7
CO2Me
6
MeO2C
∆, 10 min
MeO2C
S
O
O
2a
R
ca. 100%
S
Me
Scheme 2.
O
12
Me
Me
Ar2C=S(13),
Rh2(OAc)4,
120-125 oC,
10a: R = Me(26%)
10b: R = Et (79%)
There is a pronounced preference for the formation of
the cyclopropane bearing the phenyl and carbomethoxy
substituents cis to one another. When the same reaction
was repeated photochemically (400 W Hg lamp,
medium pressure), the yields were somewhat lower
(CH3CN as solvent; 63% yield; cis/trans 5.5:4.5) while
in the presence of benzophenone the yield was worse
(51% yield; cis/trans 4.3:5.7). The reaction was extended
to other mono- and disubstituted alkenes (Table 1)
yielding the corresponding cyclopropanes 6 in moderate
yields. Surprisingly, when ethyl vinyl ether 5e was
employed, dihydrofuran 7e was isolated instead, quan-
titatively. Similar dihydrofurans were detected (<1%) in
the reaction with styrenes 5a,b, the most were probably
formed during the column chromatography. There is
extended literature concerning the question of the dihy-
drofuran formation, if it arises directly via 1,3-cycload-
dition or via initially formed cyclopropyl ketones with
or without partial loss of the stereochemical identity of
the starting cyclopropane.7
MeO2C
Me
S
Ar
Ar
2 min
65%
O
14
Ar = p-MeOC6H4
Scheme 3.
R1C≡CH(15),
1 MeO2C
R
1
Rh2(OAc)4, ∆
MeO2C
RCO
+
R1
N
3
2
R
O
17
16
2
R1C≡N(18),
MeO2C
RCO
N
Rh2(OAc)4, ∆
+
R1
R1
R
MeO
O
O
20
19
Scheme 4.
lonate in the presence of phenylacetylene results in the
formation of a mixture of a cyclopropene and a furan,
while sensitized photolysis generates10 furans as the
primary products. The rhodium(II) acetate catalyzed
decomposition11 of diazo diketones in the presence of
terminal alkynes, results in cyclopropenes or furans, the
isolation of which depends on the nature of the electron
withdrawing group of the carbenoid. However, the
rhodium(II)-catalyzed reaction of iodonium ylides of
b-diketones with terminal alkynes yields12 furans in
moderate yields, while photochemically,13 a similar car-
boethoxy-iodonium ylide gives ethynylated compounds
in 14% yield (ca. 1:1 mixture with the enolic form) upon
reaction with phenylacetylene. Quite surprisingly, the
thermal rhodium(II)-catalyzed decomposition of ylides
Upon reaction of 2a with methyl ketones 8, dioxolanes
10 were isolated in good yields (Scheme 3). The forma-
tion of 10 implies the initial generation8 of carbonyl
ylides 9, which further rearranged, intramolecularly,
into dioxolanes 10. Attempts to intermolecularly trap
these carbonyl ylides with DMAP failed. Similarly, the
reaction with carbon disulfide yields oxathiole 12 quan-
titatively, while reaction with p,p%-dimethoxythioben-
zophenone results in the isolation of oxathiole 14 in
65% yield (Scheme 3).
Similar cycloadditions were observed upon reaction
with terminal acetylenes. It is known, that copper(II)
sulfate-catalyzed decomposition9 of diethyl diazoma-
Table 1. Reactions of iodonium ylide 2a with alkenes 5
Alkene
Substituents
R1
Conditions
Product
Yield (%)a
R2
H
5a
C6H5
A
B
6a
58
63
C
A
A
A
A
51
65
31
33
5b
5c
5d
5e
p-MeOC6H4
C6H5
C6H5
H
6b
6c
6d
7e
Me
C6H5
H
EtO
ca. 100
a Yield of isolated product after column chromatography. Method A: ylide (0.5g; 1.57 mmol), alkene (1.0 g; 5.55–9.61 mmol), Rh2(OAc)4 (0.02
mol%), 95–100°C, 2–3 min. Method B: ylide (1.0 g; 3.14 mmol), alkene (1.0 g; 9.61 mmol), CH3CN (10 mL), hw (400 W Hg street lamp), 35 min.
Method C: ylide (1.0 g; 3.14 mmol), alkene (1.0 g; 9.61 mmol), Ph2CO (0.57 g; 3.14 mmol), CH3CN (10 mL), hw (400 W Hg street lamp), 45
min.

C. Batsila et al. / Tetrahedron Letters 43 (2002) 5997–6000
Table 2. Reactions of ylides 2 with alkynes 15 and nitriles 18
5999
Ylide
Alkyne/nitrile
Substituent
Reaction temp. (°C)
Conditions time (min)
Product [yield (%)]a
R1
R2
2a
2b
2a
2b
2a
2b
2a
2b
2a
2a
2b
15a
15a
15b
15b
18a
18a
18b
18b
18c
18d
18d
Me
MeO
Me
MeO
Me
Me
Me
MeO
Me
Me
MeO
nPr
nPr
Ph
Ph
Me
Me
ClCH2
ClCH2
PhCH2
Ph
Reflux
Reflux
100
2
2
1
2
5
2
1
2
2
1
2
16a (66)
16b (36)
16c (77)
16d (63), 17d (29)
19a (82)
19b (65)
19c (39), 20c (20)
19d (61)
19e (61)
19f (86)
110
Reflux
Reflux
125
105
115
120
120
Ph
19g (85)
a Yield of isolated product after column chromatography.
2 in the presence of terminal alkynes 15 leads to the
isolation of cyclopropene 16 with good yields (Scheme
4). Only when ylide 2b and phenylacetylene 15b were
employed was furan 17d isolated as the by-product in
29% yield (Table 2) along with cyclopropene 16d (63%
yield). The structure of the cyclopropene was elucidated
from the spectral data. For example, for 16c, the
absence of 13C signals for enolic carbons at 160–170
ppm as well as signals at 205.6, and 171.5 for the ketone
and ester groups, respectively, excluded furan structure
17. The 13C signals at 112.9, 96.2, and 40.3 ppm for the
C-1, C-2, and C-3 cyclopropene carbon atoms, respec-
tively, establish cyclo-propene structure 16.
References
1. (a) Koser, G. F. The Chemistry of Functional Groups,
Supplement D; Wiley: New York, 1983; Chapter 18; (b)
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The rhodium(II)-catalyzed decomposition of ylides 2 in
the presence of nitriles 18, results in oxazoles 19, 20
(Scheme 4) in good to excellent yields (Table 2).
Although in general for ylide 2a, the keto group partic-
ipates in the formation of the oxazole ring, however
there is an exception with chloroacetonitrile, where a
separable mixture of oxazoles 19 and 20 in 39 and 20%
yields, respectively, were isolated. On the other hand,
ylide 2b results in the isolation of oxazole 19 in good to
excellent yields, similar to dimethyl diazomalonate.14
In summary, Rh2(OAc)4 is an effective catalyst for the
syntheses of valuable cyclopropanes, cyclopropenes and
heterocycles from the reaction of carbomethoxy-substi-
tuted iodonium ylides with alkenes, alkynes, methylke-
tones, etc. The examples that are reported here, albeit
with moderate to good yields, demonstrate the synthetic
potential of the iodonium ylide strategy. We are cur-
rently examining the optimization and applications of
this useful synthetic sequence.
5. For reactions of 2b with alkenes and dienes, see: Geor-
gakopoulou, G.; Kalogiros, C.; Hadjiarapoglou, L. P.
Synlett 2001, 1843–1846.
6. Representative experimental procedure. Method A: A sus-
pension of the ylide (0.5 g; 1.57 mmol), styrene (1.0 g;
9.62 mmol), Rh2(OAc)4 (0.02 mol%) was heated at 95–
100°C for 2 min. Purification by flash column chromato-
graphy on silica gel (eluent:methylene chloride) gave
cyclopropane 6a (290 mg; 85% yield; cis/trans 8.1:1.9).
Method B: A suspension of ylide (1.0 g; 3.14 mmol),
Acknowledgements
The general support, kindly-provided by Professor Dr.
W. Adam (University of Wu¨rzburg), Professor Dr. A.
de Meijere (University of Go¨ttingen), and the skillful
NMR measurements of Mr. E. Gogonas are greatly
appreciated.

6000
C. Batsila et al. / Tetrahedron Letters 43 (2002) 5997–6000
styrene (1.0 g; 9.62 mmol) in CH3CN (10 mL) was
3H); 13C NMR (63.5 MHz, CDCl3) l 25.2, 25.5, 51.4,
53.5, 114.9, 161.5. 12: colorless oil; 1H NMR l (250
MHz, CDCl3) 2.50 (s, 3H), 3.75 (s, 3H); 13C NMR (63.5
MHz, CDCl3) l 14.0, 52.5, 11.8, 159.0, 161.7, 200.2. 16c:
irradiated (400 W Hg lamp medium pressure) for 35 min.
The solvent was evaporated under reduced pressure,
purification by flash column chromatography on silica gel
(eluent: methylene chloride) gave cyclopropane 6a (431
mg; 63% yield; cis/trans 5.5:4.5). Method C: A suspension
of ylide (1.0 g; 3.14 mmol), styrene (1.0 g; 9.62 mmol),
benzophenone (0.57 g; 3.14 mmol) in CH3CN (10 mL)
was irradiated (400 W Hg lamp medium pressure) for 35
min. The solvent was evaporated under reduced pressure,
purification by flash column chromatography on silica gel
(eluent: methylene chloride) gave cyclopropane 6a (350
mg; 51% yield; cis/trans 4.3:5.7). All products have been
satisfactorily characterized by 1H NMR, 13C NMR and
IR spectroscopy. Experimental data for 2: colorless crys-
tals; mp 112–114°C; IR (KBr) 3200, 1640, 1580, 1540,
1480, 1450, 1380, 1350, 1280, 1250, 1195, 1090, 1015, 900,
1
colorless oil; H NMR (250 MHz, CDCl3) l 2.11 (s, 3H),
3.58 (s, 3H), 6.87 (s, 1H), 7.28–7.36 (m, 3H), 7.46–7.50
(m, 2H); 13C NMR (63.5 MHz, CDCl3) l 27.7, 40.3, 51.9,
96.2, 112.9, 122.7, 128.1, 128.8, 130.0, 130.5, 171.5, 205.6;
1
17d: colorless oil; H NMR (250 MHz, CDCl3) l 3.82 (s,
3H), 4.19 (s, 3H), 6.85 (s, 1H), 7.23–7.27 (m, 1H), 7.33–
7.40 (m, 2H), 7.52–7.55 (m, 2H); 13C NMR (63.5 MHz,
CDCl3) l 51.3, 58.1, 93.2, 106.3, 122.8, 127.2, 128.7,
129.7, 143.5, 161.6, 163.3. 20c: colorless oil; 1H NMR
(250 MHz, CDCl3) l 2.40 (s, 3H), 4.20 (s, 3H), 4.49 (s,
2H); 13C NMR (63.5 MHz, CDCl3) l 27.4, 35.8, 59.7,
147.3, 190.8.
7. (a) Alonso, M. E.; Morales, A. J. Org. Chem. 1980, 45,
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2000, 41, 9299–9303.
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5041–5044.
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750, 700 cm−1 1H NMR (250 MHz, DMSO-d6) l 2.39
;
(3H, s), 3.52 (3H, s), 7.38–7.50 (3H, m), 7.69–7.73 (2H,
m); 13C NMR (63.5 MHz, DMSO-d6) l 24.4, 49.6, 68.1,
113.1, 128.7, 129.5, 130.2, 164.2, 183.9. 3a: white solid;
1
mp 69–70°C; H NMR (250 MHz, CDCl3) 2.29 (3H, s),
3.79 (3H, s), 6.98 (2H, d, J 2.9 Hz), 7.14–7.20 (1H, m),
7.32–7.38 (2H, m); 13C NMR (63.5 MHz, CDCl3) 18.2,
52.9, 71.21 119.7, 124.8, 129.8,153.6, 165.3, 166.9. cis-6a:
colorless oil; 1H NMR (250 MHz, CDCl3) l 1.72 (1H,
dd, J 4.6, 9.2 Hz), 2.22 (1H, dd, J 4.6, 8.1 Hz), 2.43 (3H,
s), 3.28 (1H, t, J 8.6 Hz), 3.32 (3H, s), 7.09–7.29 (5H, m);
13C NMR (63.5 MHz, CDCl3) l 21.3, 29.3, 35.4, 44.5,
51.7, 127.3, 128.0, 128.6, 134.8, 168.5, 202.0. trans-6a:
colorless oil; 1H NMR (250 MHz, CDCl3) l 1.67–1.73
(1H, m), 1.94 (3H, s), 2.28-2.33 (1H, m), 3.23–3.32 (1H,
m), 3.80 (3H, s), 7.10–7.27 (5H, m); 13C NMR (63.5
MHz, CDCl3) l 19.1, 27.3, 34.5, 44.1, 52.5, 127.3, 128.1,
128.6, 133.7, 170.9, 199.8. 10a: colorless oil; 1H NMR
(250 MHz, CDCl3) l 1.56 (s, 6H), 2.15 (s, 3H), 3.78 (s,