Asymmetric Cyclopropanation of Olefins with an in situ Generated Phenyliodonium Ylide

Article abstract of DOI:10.1055/s-2003-41456

A procedure for the in situ generation of the phenyliodonium ylide (2) derived from Meldrum's acid (1) and its Rh(II)-catalyzed decomposition to afford an intermediate metallocarbene is described. In the presence of olefins, cyclopropanes are formed with yields and enantioselectivity comparable to that resulting from cyclopropanation with the isolated ylide 2.

Full text of DOI:10.1055/s-2003-41456

1830
LETTER
Asymmetric Cyclopropanation of Olefins with an in situ Generated
Phenyliodonium Ylide
R
h(II)-Catalyz
a
edCyclopr
u
opanation
w
l
ithMeldrum
’
M
s
a
cid üller,* Ashraf Ghanem
Department of Organic Chemistry, University of Geneva, 30, Quai Ernest Ansermet, 1211 Geneva 4, Switzerland
Fax +41(22)3793215; E-mail: paul.muller@chiorg.unige.ch
Received 9 July 2003
been reported with the [Rh2{(S)-nttl}4], and no evidence
for a secondary reaction was found in the intermolecular
cyclopropanation with 2. Similarily, the Rh(II)-catalyzed
olefin aziridination with the iminoiodinane 3 derived from
Abstract: A procedure for the in situ generation of the phenyliodo-
nium ylide (2) derived from Meldrum’s acid (1) and its Rh(II)-
catalyzed decomposition to afford an intermediate metallocarbene
is described. In the presence of olefins, cyclopropanes are formed
with yields and enantioselectivity comparable to that resulting from p-nitrobenzenesulfonamide, NsN=IPh, is stereospecific,8
cyclopropanation with the isolated ylide 2.
and the intermolecular CH insertion proceeds with
retention of configuration.9 Apparently, there is a
Key words: asymmetric catalysis, alkenes, carbenes, rhodium,
ylides
mechanistic analogy between the carbon derived
phenyliodonium ylides such as 2 and their nitrogen-
derived counterparts 3.
Asymmetric carbene transfer has seen spectacular devel-
opment during the recent 15 years thanks to the
development of highly efficient and selective catalysts.1
The reaction involves the transition metal-catalyzed
decomposition of a diazo precursor2 to afford a
metallocarbene as reactive intermediate, which then
transfers the carbene moiety to an appropriate substrate.
The enantioselectivity of the reaction may be controlled
by chiral ligands surrounding the metal.
One of the most promising recent developments in
catalytic nitrene transfer is the in situ generation and
metal-catalyzed decomposition of imino phenyliodinanes
to afford aziridines. A system using tosylamide (TsNH2)
and iodosylbenzene (PhIO) in conjunction with Cu(I)-
catalysts was proposed by Dauban for calaytic and
asymmetric olefin aziridination. When TsNH2 was
replaced by dimethyl malonate, cyclopropanes were
formed.10 In parallel, and independently, DuBois et al.
optimized a system based on PhI(OAc)2 and Rh(II)-
catalysts for intramolecular nitrene transfer of carbamates
The application of asymmetric carbene transfer reactions
is limited owing to the toxic, carcinogenic and potentially
explosive nature of diazo compounds required for the
generation of metallocarbenes.3 Accordingly, only a few
industrial applications of diazo decompositions are
known.4 The development of carbene transfer reactions
avoiding diazo precursors is therefore of considerable
interest. Over the past years, we have investigated phe-
nyliodonium ylides as potential substitutes for diazo
compounds in transition metal-catalyzed transfer of
carbenes and nitrenes. We have shown that
phenyliodonium ylides derived from 1,3-dicarbonyl
compounds react upon decomposition with Rh(II)-or
Cu(I)-catalysts via the same reactive intermediate as the
corresponding diazo compounds, and exhibit the typical
characteristics of carbene transfer reactions.5 An
exception to this general behavior is found in the
intramolecular cyclopropanation of phenyliodonium
ylides, where a competing unspecific and uncatalyzed
secondary pathway may intervene.6
and
sulfamates
via
in
situ
generated
iminophenyliodinanes.11 This reagent combination has
been applied to asymmetric aziridinations.12 It appeared
that all requirements were met for the development of an
asymmetric cyclopropanation procedure using in situ
generated phenyliodonium ylides.
Accordingly, we have adapted the intermolecular olefin
cyclopropanation of the phenyliodonium ylide 2 in such a
way that the ylide was generated from Meldrum’s acid
and PhI(OAc)2 and decomposed in situ by an appropriate
Rh(II)-catalyst in the presence of an olefin. The
announced report of Charette13 on carbene transfer with
an in situ generated phenyliodonium ylide prompts us to
reveal our own findings in this area.
Recently, we reported the Rh(II)-catalyzed intermolecular
olefin cyclopropanation using the ylide 2, derived from
Meldrum’s acid (1) (Figure 1).7 The reaction is
stereospecific. Enantioselectivities of up to 63% have
Figure 1
SYNLETT 2003, No. 12, pp 1830–1833
2
9
.0
9
.2
0
0
3
Advanced online publication: 19.09.2003
DOI: 10.1055/s-2003-41456; Art ID: G16503ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Rh(II)-Catalyzed Cyclopropanation with Meldrum’s acid
1831
The reaction conditions were optimized with styrene (4a) Table 2 shows a comparison of the in situ procedure
as substrate and with [Rh2(OAc)4] in CH2Cl2 (Scheme 1). (Method A) with the results previously reported for
The amount of catalyst was maintained constant at 5 cyclopropanation of olefins 4 with isolated ylide 2 under
mol%. The effect of olefin concentration and different catalysis with [Rh2(OAc)4] (Method B).7,14 In general, the
additives on the yield of cyclopropane 5a is summarized yields of cyclopropanes under otherwise comparable
in Table 1. As the Table reveals, a basic additive is conditions tend to be somewhat lower with the in situ
required for neutralization of the AcOH, liberated from procedure. The cyclopropanation of pent-2-enes 4e,f was
PhI(OAc)2 during the reaction. While addition of found to be stereospecific with both procedures
molecular sieves alone had only a minor effect on the (Scheme 2).
yield of 5a, the combination of molecular sieves with a
basic additive led to the highest yield of cyclopropane
(5a). In addition, a significant excess of olefin (5–10-fold)
is necessary, since otherwise the intermediate
metallocarbene decomposes. This has already been noted
for Rh(II)-catalyzed olefin cyclopropanations with the
isolated phenyliodoniun ylide 2.7 No satisfactory yields
could be obtained, however, when the reaction was
carried out with Meldrum’s acid in excess.
Scheme 2
Table 2 Comparison of in situ Procedure (Method A)a with Reac-
tion of Isolated Ylide 2 (Method B)b with [Rh2(OAc)4]
Scheme 1
Com-
pound
R1
R2
R3
Method Yield (%)
4a
4a
4b
4b
4c
4c
4d
4d
4e
4e
4f
Ph
H
H
H
H
H
H
H
H
Et
Et
H
H
H
H
H
H
H
H
H
H
H
H
H
Et
Et
H
A
B
A
B
A
B
A
B
A
B
A
B
A
85
81
75
87
35
42
30
45
60
75
56
69
0
Ph
Table 1 Optimization of Reaction Conditions with Styrene (4a)a
n-Pr
Entry
1
Excess 4a
Additiveb
None
Yield of 5a (%)
n-Pr
10
10
10
10
10
10
10
10
8
23
67
69
51
33
80
73
85
73
58
49
24
10
t-Bu
2
MgO
t-Bu
3
K2CO3
c-CH=CHCH3
4
Al2O3
c-CH=CHCH3
5
MS
Me
6
MgO + MS
K2CO3+MS
Al2O3 + MS
Al2O3 + MS
Al2O3 + MS
Al2O3 + MS
Al2O3 + MS
Al2O3 + MS
Me
7
Me
8
4f
Me
9
4g
COOEt
10
11
12
13
6
a 10-Fold excess of olefin, 5 mol% of catalyst, 30 °C.
b Refs.7 5 mol% of catalyst.
4
2
No cyclopropane was isolated with ethyl acrylate (4g),
however.
0.5
a Conditions: In CH2Cl2 (10 mL), at 30 °C, 10 mmol of 1, 1.4 equiv-
alents of PhI(OAc)2, 5 mol% of [Rh2(OAc)4].
A third set of experiments was carried out in order to
optimize conditions for asymmetric cyclopropanation of
styrene (Table 3) with [Rh2{(S)-nttl}4] as catalyst. CH2Cl2
was found to be the most convenient solvent. The yields
b 2.3 Equivalents of addititive; MS = molecular sieves 4 Å, 250 mg.
Synlett 2003, No. 12, 1830–1833 © Thieme Stuttgart · New York

1832
P. Müller, A. Ghanem
LETTER
of cyclopropane 5a depended significantly on the catalyst conditions in CH2Cl2 (Method A),15 MeCN (Method C)
concentration, which was routinely fixed to 5 mol%.
with isolated ylide (Method B). The yields resulting from
the in situ procedure are generally lower than those
resulting from Method B as was the case with
[Rh2(OAc)4] (Table 2). On the other hand, the
enantioselectivity of the in situ method compares well
with those of Method B.
Satisfactory results were also obtained in MeCN with a
catalyst load of only 1 mol% (Table 3). For example, the
yield of 5a increased from 21% in CH2Cl2 with 1 mol% of
catalyst to 81%, and the ee from 43% in CH2Cl2 to 59% in
MeCN. THF was also efficient with 48% yield and 52%
ee in the presence of 1 mol% of catalyst. Solvents such as
benzene and trifluorotoluene were ineffective, however.
Acknowledgment
This work was supported by the Swiss National Science Foundation
(Projects No. 20-52581.97 and 2027-048156) and by the European
Commission for Science, Research and Development (COST Ac-
tion D12).
Table 3 Optimization of Reaction Conditions with Styrene (4a) and
[Rh2[(S)-nttl}4]a
Entry
Solvent
[Catalyst]
(mol%)
Yield of 5a ee (%)
(%)
References
1
2
3
4
5
6
7
8
9
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
C6H5CF3
MeCN
C6H6
5
4
3
2
1
1
1
1
1
90
72
54
32
20
0
43
37
36
35
39
–
(1) (a) Pfaltz, A. In Comprehensive Asymmetric Catalysis;
Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds.; Springer:
Berlin, 1999, 513–538. (b) Lydon, K. M.; McKervey, M. A.
In Comprehensive Asymmetric Catalysis; Jacobsen, E. N.;
Pfaltz, A.; Yamamoto, H., Eds.; Springer: Berlin, 1999,
539–580. (c) Doyle, M. P. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; VCH: Weinheim, 1999, 63–99.
(2) Doyle, M. P.; McKervey, M. A. Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds: From
Cyclopropanes to Ylides; Wiley: New York, 1997.
(3) (a) Eistert, B.; Regitz, M.; Heck, G.; Schwall, H. In Houben–
Weyl, Methoden der organischen Chemie, Vol X/4; Muller,
E., Ed.; Thieme Verlag: Stuttgart, 1973, 473. (b) Sax, N. I.
In Industrial Materials, 5th ed.; Van Nostrand Reinhold:
New York, 1979. (c) Bretherick, L. In Hazards in the
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Burlington House, London, 1986. (d) Bretherick, L. In
Handbook of Reactive Chemical Hazards, 3rd. ed.;
Butterworth: London, 1985. (e) Lelen, M. J. Cat. Notes Doc.
1978, 91, 313.
81
0
59
–
THF
48
52
a ReactionConditions: 10 mL of solvent, at 30 °C, 10 mmol of 1, 1.4
equivalents of PhI(OAc)2, 2.3 equivalents of Al2O3, MS 4 Å (250 mg).
Table 4 Asymmetric Cycloproanation of Olefins with [Rh2{(S)-
nttl}4
a
(4) Aratani, T. Pure Appl. Chem. 1985, 57, 1839.
(5) (a) Müller, P.; Fernandez, D. Helv. Chim. Acta 1995, 78,
947. (b) Müller, P.; Fernandez, D.; Nury, P.; Rossier, J.-C. J.
Phys. Org. Chem. 1998, 11, 321.
(6) (a) Müller, P.; Boléa, C. Helv. Chim. Acta 2001, 84, 1093.
(b) Müller, P.; Boléa, C. Synlett 2000, 826.
(7) Müller, P.; Allenbach, Y.; Robert, E. Tetrahedron:
Asymmetry 2003, 14, 779.
(8) (a) Müller, P.; Baud, C.; Jacquier, Y. Tetrahedron 1996, 52,
1543. (b) Müller, P.; Baud, C.; Jacquier, Y. Can. J. Chem.
1998, 76, 738.
(9) (a) Nägeli, I.; Baud, C.; Bernardinelli, G.; Jacquier, Y.;
Moran, M.; Müller, P. Helv. Chim. Acta 1997, 80, 1087.
(b) Müller, P.; Baud, C.; Nägeli, I. J. Phys. Org. Chem. 1998,
11, 597.
(10) (a) Dauban, P.; Sanière, L.; Tarrade, A.; Dodd, R. H. J. Am.
Chem. Soc. 2001, 123, 7707. (b) Duran, F.; Leman, L.;
Ghini, A.; Burton, G.; Dauban, P.; Dodd, R. Org. Lett. 2002,
4, 2481.
(11) (a) Guthikonda, K.; Du Bois, J. J. Am. Chem. Soc. 2002, 124,
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2028.
Com-
pound
Olefin
Method Yield
(%)
ee
(%)
4a
4a
4a
4b
4b
4b
4d
4d
4e
4e
styrene
A
B
C
A
B
C
A
C
A
C
90
84
79
56
97
55
50
61
47
50
43b
37
57c
70
59
59
33
30
33
54
styrene
styrene
pent-1-ene
pent-1-ene
pent-1-ene
cis-penta-1,3-diene
cis-penta-1,3-diene
cis-pent-2-ene
cis-pent-2-ene
a Method A: In situ procedure, in CH2Cl2, 5 mol% of catalyst.
Method B: With isolated ylide 2.7 Method C: In situ procedure, in
MeCN, 1 mol% of catalyst.
(12) Liang, J.-L.; Yuan, S.-X.; Chan, P. W.; Che, C.-M. Org. Lett.
2002, 4, 863.
(13) Wurz, R. P.; Charette, A. B. Org. Lett. 2003, 5, 2327.
Table 4 compares yields and enantioselectivities for
olefin cyclopropanation of several olefins under the in situ
Synlett 2003, No. 12, 1830–1833 © Thieme Stuttgart · New York

LETTER
Rh(II)-Catalyzed Cyclopropanation with Meldrum’s acid
1833
(14) For characterization of the cyclopropanes 5a–f, see ref.7
(15) Representative procedure (Method A): CH2Cl2 (10 mL) was
added through syringe into a 50 mL round bottom flask
containing a mixture of Meldrum’s acid (1, 10 mmol, 1
equiv), PhI(OAc)2 (1.4 equiv), [Rh2(OAc)4] or [Rh2{(S)-
nttl}4] (5 mol%), Al2O3 (2.3 equiv) and molecular sieves 4 Å
(250 mg), followed by the addition of the olefin (10 equiv).
The reaction mixture was thermostated in an oil bath to 30
°C and stirred under Ar. 100 mL Samples were taken after
several time intervals. The samples were filtered using a
syringe filter holder (0.2 mm pore size) and the organic layer
was diluted with 100 mL of CH2Cl2 and analyzed by GC. The
reaction progress was monitored qualitatively by TLC using
pentane–EtOAc (2:1) as eluent. An aliquot of the
supernatant was used for GC. When maximum conversion
was reached, the reaction was terminated by filtration
through celite. The residue on the celite was washed twice
with CH2Cl2. Evaporation of the combined filtrates under
reduced pressure followed by chromatography on silica gel
column with pentane–EtOAc (2:1) as eluent afforded the
desired cyclopropane derivatives.
Synlett 2003, No. 12, 1830–1833 © Thieme Stuttgart · New York