RhII-catalyzed thermal cyclopropanations of a phenyliodonium bis(carbomethoxy)methylide with alkenes and dienes

Article abstract of DOI:10.1055/s-2001-18750

Iodonium ylide 2, derived front dimethyl malonate, undergoes facile thermal cycloaddition with alkenes and dienes catalyzed with Rh₂(OAc)₄ to form the corresponding cyclopropanedicarboxylates and vinylcyclopropanedicarboxylates, resp

Full text of DOI:10.1055/s-2001-18750

LETTER
1843
RhII-Catalyzed Thermal Cyclopropanations of a Phenyliodonium
Bis(carbomethoxy)methylide with Alkenes and Dienes
II
R
h
-Catalyzed
T
he
e
rma
l
Cyclo
o
propanation
r
s
gia Georgakopoulou,1 Christos Kalogiros,2 Lazaros P. Hadjiarapoglou*
Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece
Fax +30(651)98799; E-mail: lxatziar@hotmail.com
Received 23 July 2001
isolation6b of iodonium ylide 2 in moderate yields
(Scheme 1). Heating or irradiating a suspension of iodoni-
um ylide 2 in an appropriate solvent yields tetracar-
bomethoxyethylene (3) quantitatively. This alkene is a
side product of all attempted cycloadditions of iodonium
ylide 2, possibly produced by attack of a „carbene inter-
mediate“ on 2.
Abstract: Iodonium ylide 2, derived from dimethyl malonate, un-
dergoes facile thermal cycloaddition with alkenes and dienes cata-
lyzed with Rh2(OAc)4 to form the corresponding
cyclopropanedicarboxylates and vinylcyclopropanedicarboxylates,
respectively, in excellent yields.
Key words: hypervalent iodine, ylide, Rh-catalysis, alkene, 1,3-di-
ene, cyclopropane
PhI(OAc)2,
Iodonium ylides,3 a class of hypervalent iodine-com-
pounds,4 have been used quite often as rather reactive al-
ternatives to diazo compounds without major drawbacks
such as explosive and health hazards. Quite generally
speaking, an iodonium ylide can be easily prepared5 from
the corresponding active methylene compound and a hy-
pervalent iodine precursor, i.e. PhI(OAc)2. Its reactivity
pattern3 consists of its decomposition in various solvents,
C-H insertion reactions, oxidation reactions, and/or cy-
cloaddition reactions leading to a variety of products, usu-
ally new heterocyclic compounds. A major question
arising from the literature6 is whether or not a carbene (or
a carbenoid) is involved in this rich reactivity pattern. A
singlet or triplet carbene (or a carbenoid) could easily ex-
plain the observed results but this could not be always the
case.
KOH, MeOH,
-10 oC, 3-4 h
MeO2C
MeO2C
MeO2C
IPh
MeO2C
2
1
∆ or hν
CO2Me
CO2Me
MeO2C
MeO2C
3
Scheme 1
Nevertheless, this formal carbene dimer was produced in
minor amounts, when an excess of an alkene is present.
The reaction9 with styrene 4a and indene 4h were used as
a probe to examine the overall yield of the desired reac-
tion. Heating a mixture of 2 and styrene 4a in the presence
of catalytic amounts of Rh2(OAc)4 or Cu(acac)2 led to the
isolation of cyclopropanedicarboxylate 5a (Scheme 2) in
80% and 57% yield, respectively. On the other hand, irra-
diating a suspension of 2 and 4a in CH3CN led to the iso-
lation of 5a in 51% yield. Although the photochemical
reaction yields cyclopropane 5a in moderate yield, the
Rh-catalyzed process is superior. Similarly, heating a
mixture of 2 and indene 4h, with no catalyst or with cata-
lytic amounts of Rh2(OAc)4 or Cu(acac)2 led to the isola-
tion of the corresponding cyclopropanedicarboxylate 5h
in 58%, 88%, and 80% yield, respectively. Albeit, the
non-catalyzed reaction yields cyclopropane 5h in moder-
ate yields, again the thermal-catalyzed (RhII or CuII) con-
ditions are superior. Other catalysts, such as RhCl3, PdCl2,
etc., failed to accelerate this cycloaddition.
We were more fascinated with the synthetic applications
than the mechanistic aspects of the reactivity of iodonium
ylides. Within our studies, we had seen rich reactivity of a
-dicarbonyl7a,b iodonium ylide with various substrates,
improvement7 of the reaction yield by shifting from the
cheap Cu-catalyst into the expensive Rh-catalyst, while
we were observing the loss of stereochemistry.7c,d This
fact had been explained as the result of a two step polar re-
action although there is no strong evidence that an initial-
ly-formed cyclopropane rearranged into dihydrofuran. On
the other hand, recently it was reported8 that a phenyliodo-
nium ylide is a precursor for dicarboethoxycarbene. So,
with the aim to develop and define the scope and limita-
tion of this synthetic methodology, we extended our study
to the reactivity of phenyliodonium bis(car-
bomethoxy)methylide towards alkenes and dienes.
R1
R4
R2
R3
The reaction of methyl malonate (1) with diacetoxyiodo-
benzene in basic methanol at –10 °C leads to the
R1
R2
R4
R3
MeO2C
MeO2C
4
2
Rh2(OAc)4, ∆ or hν
Synlett 2001, No. 12, 30 11 2001. Article Identifier:
1437-2096,E;2001,0,12,1843,1846,ftx,en;G15401ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214
5
Scheme 2

1844
G. Georgakopoulou et al.
LETTER
Table 1 Reactiona of Iodonium Ylide 2 with Alkenes 4
Entry Alkene
Substituents
R1
Reaction conditions
Product
Yield (%)b
R2
H
R3
H
R4
H
Catalyst
Temp (°C)
Time (min)
1
4a
Ph
Rh2(OAc)4
Cu(acac)2
120
80
1
10
100
1
5a
80
57
51
99
81
67
81
12
91
88
h
c, CH3CN
2
3
4
5
6
7
8
4b
4c
4d
4e
4f
PhCH2
Ph
H
H
H
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
120
5b
5c
5d
5e
5f
H
H
Me
Ph
H
120
5
Ph
H
H
120
1
Me
i-Pr
H
H
reflux
reflux
reflux
120
30
20
20
20
Me
i-Pr
H
H
4g
4h
(CH2)3
H
5g
5h
H
H
CH2
Cu(acac)2
100
30
40
3
80
58
63
100
9
4i
(CH2)4
H
H
Rh2(OAc)4
reflux
5i
a All reactions were performed by heating a mixture of iodonium ylide (1.50 mmol), alkene (excess) and catalytic amount of Rh2(OAc)4 at the
given temperature (°C) for the required time (min).
b Isolated yield after column chromatography.
c Hg street lamp 400W, medium pressure.
The reaction was extended to a variety of alkenes 4b–g,4i, could lead eventually to cyclopentenes, or with minor al-
which underwent facile cycloadditions, affording the cor- terations to cycloheptadienes.11 Indeed, heating a suspen-
responding cyclopropanedicarboxylates 5 in excellent sion of iodonium ylide 2 with the appropriate diene 6 in
yields (Table 1). It is noteworthy that the reaction pro- the presence of catalytic amounts of Rh2(OAc)4 led to the
ceeds without the use of an inert atmosphere. Acyclic 4a– isolation of vinylcyclopropanes 7 in excellent yields. Acy-
f, with various degrees of substitution, as well as cyclic clic 6a,b, as well as cyclic dienes 6c–j were found to un-
alkenes 4g–i were found to undergo cycloaddition. The dergo cycloadditions (Table 2) while non-conjugated
reactions with 2-methyl-3-pentene (entries 5, 6 Table 1) dienes 6e–h or conjugated dienes 6a–e,i,j led to the corre-
were used to examine the spin state of a possible interme- sponding cyclopropanes 7. Again, the data presented in
diate carbene (or carbenoid); cis-alkene 4e led to the for- Table 2 indicate that the addition of iodonium ylide 2 to
mation of cis-cyclopropane 5e in 81% yield, while trans- dienes is rather more sensitive to steric effects than elec-
alkene 4f led to a complex reaction mixture, from which tronic (cf. entries 4, 7 ,8 of Table 2).
trans-cyclopropane 5f was isolated in only 12% yield.
The very high degree of stereospecificity indicates
R1
cyclopropanation8 of the double bond by a singlet car-
( )n
bene, but the data presented in Table 1 indicate also that
the addition of iodonium ylide 2 into alkenes is rather
more sensitive to steric effects than electronic, a similar
observation to that of dimethyl diazomalonate.10 The ad-
dition seems to be electrophilic in nature, but steric factors
are dominant.
R2
R4
MeO2C R1
MeO2C
R3
6
( )n
2
R2
Rh2(OAc)4, ∆
R4
7
R3
Having this in mind, we turned our attention into cycload-
Scheme 3
ditions with dienes 6 (Scheme 3). Reaction with a diene
Synlett 2001, No. 12, 1843–1846 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
RhII-Catalyzed Thermal Cyclopropanations
1845
Table 2 Reactiona of Iodonium Ylide 2 with Dienes 6
Entry
Diene
Reaction conditions
Product
Yield (%)b
Temp (°C)
reflux
Time (min)
CO2Me
CO2Me
1
2
30
95
88
7a
6a
6b
reflux
120
5
CO2Me
CO2Me
7b
3
4
1
5
ca 100
H
CO2Me
CO2Me
H
7c
80–85
71
H
CO2Me
CO2Me
H
H
7d
7e
7f
5
6
7
120
1
1
5
ca 100
CO2Me
CO2Me
6e
6f
H
H
120
44
CO2Me
CO2Me
H
95–97
61 (dr 52:48)
CO2Me
CO2Me
7g
7h
6g
8
9
125
2
5
55 (dr 50:50)
CO2Me
CO2Me
6h
6i
reflux
81
H
CO2Me
CO2Me
H
7i
10
120
2
58
H
CO2Me
CO2Me
H
6j
7i
a A suspension of iodonium ylide (1.5 mmol), diene (excess), and catalytic amount of Rh2(OAc)4 was heated at the above mentioned tempera-
ture for the given time.
b Isolated yield after column chromatography.
In summary, Rh2(OAc)4 is an effective catalyst for the that are reported here demonstrate the synthetic potential
syntheses of cyclopropane derivatives of predictable ste- of the iodonium ylide strategy for the construction of cy-
reochemistry, from the reaction of iodonium ylide of dim- clopropanes. We are currently examining the optimization
ethyl malonate with alkenes and dienes. The examples and applications of this useful synthetic sequence.
Synlett 2001, No. 12, 1843–1846 ISSN 0936-5214 © Thieme Stuttgart · New York

1846
G. Georgakopoulou et al.
LETTER
(8) Camacho, M. B.; Clark, A. E.; Liebrecht, T. A.; DeLuca, J.
P. J. Am. Chem. Soc. 2000, 122, 5210.
References and Notes
(1) Undergraduate Research Participant, Spring 1997.
(2) Undergraduate Research Participant, Spring 2001.
(3) Koser, G. F. In The Chemistry of Functional Groups,
Supplement D; Wiley: New York, 1983, Chap. 18.
(4) (a) Varvoglis, A. The Organic Chemistry of
(9) Representative Experimental Procedure. Synthesisof 5a:
A mixture of iodonium ylide 2 (0.5 g, 1.50 mmol), styrene
4a (1.0 g, 9.62 mmol) and catalytic amounts (0.1 mol%) of
Rh2(OAc)4 was heated at 120 °C for 1 min. The reaction
mixture was subjected to column chromatography (silica
gel, CH2Cl2) to afford 5a6b (0.28 g, 80%) as colorless oil. IR
(neat): = 3010, 2940, 1720, 1430, 1328, 1270, 1210, 1190,
1175, 1125cm–1; 1H NMR (250 MHz, CDCl3): = 1.68–1.75
(m, 1 H), 2.15–2.20 (m, 1 H), 3.18–3.23 (m, 1 H), 3.34 (s, 3
H), 3.77 (s, 3 H), 7.16–7.25 (m, 5 H); 13C NMR (63 MHz,
CDCl3): = 19.0, 32.4, 37.2, 52.0, 52.7, 127.3, 127.5, 128.4,
134.6, 166.9, 170.1. Synthesis of 7a: A mixture of iodonium
ylide 2 (0.5 g, 1.50 mmol), 6,6-dimethylfulvene 6d (1.0 g,
9.43 mmol) and catalytic amounts (0.1 mol%) of Rh2(OAc)4
was heated at 80–85 °C for 5 min. The reaction mixture was
subjected to column chromatography (silica gel, CH2Cl2) to
afford 7d (0.25 g, 71%) as yellow oil. 1H NMR (250 MHz,
CDCl3). = 1.80 (s, 3 H), 1.89 (s, 3 H), 2.94 (dd, J = 2.2, 6.1
Hz, 1 H), 3.02 (d, J = 6.1 Hz, 1 H), 3.56 (s, 3 H), 3.70 (s, 3
H), 5.90–5.94 (m, 1 H), 6.13 (d, J = 5.4 Hz, 1 H); 13C NMR
(63 MHz, CDCl3): = 21.2, 22.0, 34.4, 38.6, 43.3, 52.0,
52.6, 130.2, 130.5, 132.7, 135.9, 166.0.
Polycoordinated Iodine; VCH Publishers: New York, 1992.
(b) Varvoglis, A. Hypervalent Iodine in Organic Synthesis;
Academic Press: London, 1997. (c) Moriarty, R. M.; Vaid,
R. K. Synthesis 1990, 431.
(5) For a general synthesis of -dicarbonyl iodonium ylides, see:
Schank, K.; Lick, C. Synthesis 1983, 393.
(6) (a) Müller, P.; Fernandez, D.; Nury, D.; Rossier, J.-C. J.
Phys. Org. Chem. 1998, 11, 321. (b) Müller, P.; Fernandez,
D. Helv. Chim. Acta 1995, 78, 947. (c) Müller, P.; Bolea, C.
Synlett 2000, 826. (d) Müller, P.; Bolea, C. Helv. Chim. Acta
2001, 84, 1093. (e) Moriarty, R. M.; May, E. J.; Prakash, O.
Tetrahedron Lett. 1997, 38, 4333. (f) Moriarty, R. M.;
Prakash, O.; Vaid, R. K.; Zhao, L. J. Am. Chem. Soc. 1989,
111, 6443. (g) Moriarty, R. M.; Kim, J.; Guo, L.
Tetrahedron Lett. 1993, 34, 4129. (h) Moriarty, R. M.;May,
E. J.; Guo, L.; Prakash, O. Tetrahedron Lett. 1998, 39, 765.
(i) Spyroudis, S.; Tarantili, P. J. Org. Chem. 1993, 58, 4885.
(j) Gallos, J. K.; Koftis, T. V.; Koumbis, A. E. J. Chem. Soc.,
Perkin Trans. 1 1994, 611. (k) Hayasi, Y.; Okada, T.;
Kawanisi, M. Bull. Chem. Soc. Jpn. 1970, 43, 2506.
(7) (a) Hadjiarapoglou, L. P. Tetrahedron Lett. 1987, 28, 4449.
(b) Asouti, A.; Hadjiarapoglou, L. P. Tetrahedron Lett.
1998, 39, 9073. (c) Alexiou, I.; Gogonas, E. P.;
(10) Jones, M. Jr.; Kulczycki, A. Jr.; Hummel, K. F. Tetrahedron
Lett. 1966, 183.
(11) Davies, H. M. L.; Stafford, D. G.; Doun, B. D.; Houser, J. H.
J. Am. Chem. Soc. 1998, 120, 3326.
Hadjiarapoglou, L. P. Synlett 1999, 1925. (d) Gogonas, E.
P.; Hadjiarapoglou, L. P. Tetrahedron Lett. 2000, 41, 9299.
Synlett 2001, No. 12, 1843–1846 ISSN 0936-5214 © Thieme Stuttgart · New York