Scope and limitations of cyclopropanations with sulfur ylides

Article abstract of DOI:10.1021/ja1084749

The rates of the reactions of the stabilized and semistabilized sulfur ylides 1a-g with benzhydrylium ions (2a-e) and Michael acceptors (2f-v) have been determined by UV-vis spectroscopy in DMSO at 20 °C. The second-order rate constants (log k₂

Full text of DOI:10.1021/ja1084749

Published on Web 11/29/2010
Scope and Limitations of Cyclopropanations with Sulfur
Ylides
Roland Appel, Nicolai Hartmann, and Herbert Mayr*
Department Chemie, Ludwig-Maximilians-UniVersita¨t Mu¨nchen, Butenandtstrasse 5-13,
81377 Mu¨nchen, Germany
Received September 20, 2010; E-mail: herbert.mayr@cup.uni-muenchen.de
Abstract: The rates of the reactions of the stabilized and semistabilized sulfur ylides 1a-g with
benzhydrylium ions (2a-e) and Michael acceptors (2f-v) have been determined by UV-vis spectroscopy
in DMSO at 20 °C. The second-order rate constants (log k2) of these reactions correlate linearly with the
electrophilicity parameters E of the electrophiles 2 as required by the correlation log k2 ) s(N + E), which
allowed us to calculate the nucleophile-specific parameters N and s for the sulfur ylides 1a-g. The rate
constants for the cyclopropanation reactions of sulfur ylides with Michael acceptors lie on the same
correlation line as the rate constants for the reactions of sulfur ylides with carbocations. This observation
is in line with a stepwise mechanism for the cyclopropanation reactions in which the first step, nucleophilic
attack of the sulfur ylides at the Michael acceptors, is rate determining. As the few known pKaH values for
sulfur ylides correlate poorly with their nucleophilic reactivities, the data reported in this work provide the
first quantitative approach to sulfur ylide reactivity.
Introduction
displacement to yield an epoxide, an aziridine, or a cyclopro-
pane, respectively (Scheme 1).
Sulfur ylides have emerged to an important class of reagents
in organic synthesis. Though the first report on the isolation of
a sulfur ylide by Ingold and Jessop was already published in
1930,1 a systematic investigation of sulfur ylides started only
in the 1960s when these compounds were recognized as versatile
reagents for the preparation of three-membered carbo- and
heterocycles.2 Eventually, the use of chiral sulfur ylides or chiral
electrophilic substrates gave rise to a variety of stereoselective
sulfur ylide-mediated cyclization reactions.3 Detailed investiga-
tions of epoxidation,4 cyclopropanation,4b,5 and aziridination
reactions6 revealed a common mechanistic course. In all cases,
the sulfur ylide initially attacks at an electrophilic carbon center
(i.e., aldehyde, imine, or Michael acceptor) to form a betaine
intermediate, which undergoes an intramolecular nucleophilic
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Chem. ReV. 1997, 97, 2341–2372. (b) Dai, L.-X.; Hou, X.-L.; Zhou,
Y.-G. Pure Appl. Chem. 1999, 71, 369–376. (c) Clark, J. S. In
Nitrogen, Oxygen and Sulfur Ylide Chemistry; Clark, J. S., Ed.; Oxford
University Press: New York, 2002; pp 1-114. (d) Aggarwal, V. K.;
Richardson, J. In Science of Synthesis; Georg Thieme Verlag: Stuttgart,
2004; Vol. 27, pp 21-104. (e) Aggarwal, V. K.; Winn, C. L. Acc.
Chem. Res. 2004, 37, 611–620. (f) Aggarwal, V. K.; Badine, D. M.;
Moorthie, V. A. In Aziridines and Epoxides in Organic Synthesis;
Yudin, A. K., Ed.; Wiley-VCH: Weinheim, 2006; pp 1-35. (g)
McGarrigle, E. M.; Aggarwal, V. K. In EnantioselectiVe Organoca-
talysis; Dalko, P. I., Ed.; Wiley-VCH: Weinheim, 2007; pp 357-
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J.-F.; Metzner, P. In Organosulfur Chemistry in Asymmetric Synthesis;
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17894 J. AM. CHEM. SOC. 2010, 132, 17894–17900
10.1021/ja1084749  2010 American Chemical Society

Cyclopropanations with Sulfur Ylides
A R T I C L E S
Scheme 1. Mechanism of the Sulfur Ylide-Mediated Epoxidation-,
Aziridination-, and Cyclopropanation Reaction (Corey-Chaykovsky
Reaction)4-6
Table 1. Benzhydrylium Ions 2a-e, Michael Acceptors 2f-v, and
their Electrophilicity Parameters E
Depending on the reactivities of the sulfur ylides, the initial
addition step of the sulfur ylide to an aldehyde or an imine has
been shown to be reversible or irreversible.2k,4b,k-n,6a,c,d Stabi-
lized sulfur ylides, i.e., acetyl-, benzoyl-, and ester-substituted
sulfur ylides, are considerably less reactive than the so-called
semistabilized sulfur ylides, i.e., aryl-substituted sulfur ylides,
and do not undergo epoxidation reactions with aldehydes or
react only under harsh conditions.2k,p,4k Obviously, the nucleo-
philicities of the ylides play an important role for their synthetic
applicability. Previous rationalizations of structure-reactivity
relationships of sulfur ylides focused on their basicities.5d,7
However, due to the small amount of available pKaH values of
sulfur ylides and the poor correlation between basicity and
nucleophilicity of carbon-centered nucleophiles,8 a quantitative
comparison of the nucleophilicities of variably substituted sulfur
ylides as well as a comparison with other classes of nucleophiles
has so far not been possible.
In recent years, we have shown that the rates of the reactions of
carbocations and Michael acceptors (some of them are depicted in
Table 1) with n-, π-, and σ-nucleophiles can be described by eq 1,
where k20 °C is the second-order rate constant in M-1 s-1, s is a
nucleophile-specific sensitivity parameter, N is a nucleophilicity
parameter, and E is an electrophilicity parameter.
log k20 C ) s(N + E)
(1)
o
On the basis of this linear free-energy relationship, we have
developed the most comprehensive nucleophilicity and elec-
trophilicity scale presently available.8,9 We have now em-
ployed this method for characterizing the nucleophilicities
of stabilized and semistabilized sulfur ylides 1a-g (Scheme
2), and we will discuss the impact of these results for
predicting scope and limitations of cyclopropanation reactions
of Michael acceptors with sulfur ylides.
Results
Reactions with Benzhydrylium Ions. In order to establish the
course of the reactions, which were studied kinetically, we have
a Electrophilicity parameters E of 2a-e were taken from ref 9b, of
2f-k from ref 9c, of 2l-n from ref 9g, of 2o-q from ref 9h, of 2r-t
from ref 9i, of 2u from ref 9d, and of 2v from ref 9k.
(5) (a) Midura, W. H.; Krysiak, J. A.; Cypryk, M.; Mikolajczyk, M.;
Wieczorek, M. W.; Filipczak, A. D. Eur. J. Org. Chem. 2005, 653–
662. (b) Aggarwal, V. K.; Grange, E. Chem.sEur. J. 2006, 12, 568–
575. (c) Deng, X.-M.; Cai, P.; Ye, S.; Sun, X.-L.; Liao, W.-W.; Li,
K.; Tang, Y.; Wu, Y.-D.; Dai, L.-X. J. Am. Chem. Soc. 2006, 128,
9730–9740. (d) Janardanan, D.; Sunoj, R. B. J. Org. Chem. 2007, 72,
331–341. (e) Riches, S. L.; Saha, C.; Filgueira, N. F.; Grange, E.;
McGarrigle, E. M.; Aggarwal, V. K. J. Am. Chem. Soc. 2010, 132,
7626–7630.
characterized products of the reactions of the sulfur ylides 1a-g
with the benzhydrylium ion 2a. Owing to their low stability,
the initially formed addition products 3a-f were not isolated
but immediately treated with thiophenolate to afford the neutral
addition products 4a-f, which are fully characterized in the
Supporting Information (Scheme 3).
(6) (a) Aggarwal, V. K.; Charmant, J. P. H.; Ciampi, C.; Hornby, J. M.;
O’Brien, C. J.; Hynd, G.; Parsons, R. J. Chem. Soc., Perkin Trans. 1
2001, 3159–3166. (b) Yang, X.-F.; Zhang, M.-J.; Hou, X.-L.; Dai,
L.-X. J. Org. Chem. 2002, 67, 8097–8103. (c) Robiette, R. J. Org.
Chem. 2006, 71, 2726–2734. (d) Janardanan, D.; Sunoj, R. B.
Chem.sEur. J. 2007, 13, 4805–4815. (e) Janardanan, D.; Sunoj, R. B.
J. Org. Chem. 2008, 73, 8163–8174.
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Liu, B.; Zhang, X.-M. J. Org. Chem. 1998, 63, 7574–7575. (c) Cheng,
J.-P.; Liu, B.; Zhao, Y.; Sun, Y.; Zhang, X.-M.; Lu, Y. J. Org. Chem.
1999, 64, 604–610. (d) Fu, Y.; Wang, H.-J.; Chong, S.-S.; Guo, Q.-
X.; Liu, L. J. Org. Chem. 2009, 74, 810–819.
(8) (a) Lucius, R.; Mayr, H. Angew. Chem., Int. Ed. 2000, 39, 1995–
1997. (b) Berger, S. T. A.; Ofial, A. R.; Mayr, H. J. Am. Chem. Soc.
2007, 129, 9753–9761. (c) Appel, R.; Loos, R.; Mayr, H. J. Am. Chem.
Soc. 2009, 131, 704–714. (d) Kaumanns, O.; Appel, R.; Lemek, T.;
Seeliger, F.; Mayr, H. J. Org. Chem. 2009, 74, 75–81.
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A R T I C L E S
Appel et al.
Scheme 2. Benzoyl-Stabilized Sulfur Ylides 1a-d, Semistabilized
Sulfur Ylides 1e-g, and Ester-Stabilized Sulfur Ylide 1h
Scheme 5. Reactions of the Semistabilized Sulfur Ylides 1e-g and
the Stabilized Sulfur Ylide 1h with Different Michael Acceptors
Scheme 3. Reactions of the Sulfur Ylides 1a-f with Benzhydrylium
Tetrafluoroborate 2a-BF4
Scheme 4. Reaction of the Sulfur Ylide 1g with Benzhydrylium
Tetrafluoroborate 2a-BF4
a Reaction conditions: KOtBu, DMSO, rt. b Reaction conditions: K2CO3
(aq)/CHCl3, rt; only one diastereomer isolated.
semistabilized sulfur ylides 1e-g with the benzylideneindan-
diones 2l,m and the diethyl benzylidenemalonates 2r,s as well
as the reaction of the stabilized sulfur ylide 1h with benzylide-
neindandione 2l yielded the expected cyclopropane derivatives
5 (Scheme 5). Due to the high tendency of dimethylsulfoxonium
ylide 1g for multiple addition (see Scheme 4), complex mixtures
of products were formed in the reactions of 1g with the other
types of Michael acceptors. The treatment of the benzylidenebar-
bituric acids 2o,p with the sulfur ylides 1f and 1h did not yield
cyclopropanes, but the dihydrofuran derivatives 6a,b. As
indicated in Scheme 6, the direct nucleophilic displacement of
dimethylsulfide by a carbonyl oxygen of the initially formed
zwitterion would lead to dihydrofurans 6′, which have a different
substitution pattern than was actually found for the compounds
6a,b (derived by 2D-NMR experiments). These findings suggest
that the dihydrofurans 6a,b are formed via a rearrangement of
an intermediate cyclopropane species 6′′.
Treatment of 2a with the dimethylsulfoxonium ylide 1g and
subsequent addition of thiophenolate yielded the 2:1-product
4g (Scheme 4). Obviously, the initially generated 1:1-addition
product from 2a and 1g is rapidly deprotonated to give another
sulfur ylide which reacts with a second molecule of the
electrophile 2a. Eventually, demethylation by thiophenolate
(according to Scheme 3) yields 4g.
Reactions with Michael Acceptors. As the reactions of sulfur
ylides with Michael acceptors had already been known to yield
cyclopropane derivatives (Scheme 1), product analyses have
only been performed for representative combinations of the
sulfur ylides 1 with Michael acceptors. The reactions of the
In analogy to previous reports,10,11 the reaction of the benzoyl-
stabilized sulfur ylide 1c with trans-4-methoxy-ꢀ-nitrostyrene
(2v) does not give a cyclopropane but a dihydroisoxazole
N-oxide, which has been identified as described in the Sup-
porting Information.
(9) (a) Mayr, H.; Patz, M. Angew. Chem., Int. Ed. Engl. 1994, 33, 938–
957. (b) Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.;
Janker, B.; Kempf, B.; Loos, R.; Ofial, A. R.; Remennikov, G.;
Schimmel, H. J. Am. Chem. Soc. 2001, 123, 9500–9512. (c) Lucius,
R.; Loos, R.; Mayr, H. Angew. Chem., Int. Ed. 2002, 41, 91–95. (d)
Lemek, T.; Mayr, H. J. Org. Chem. 2003, 68, 6880–6886. (e) Mayr,
H.; Kempf, B.; Ofial, A. R. Acc. Chem. Res. 2003, 36, 66–77. (f)
Mayr, H.; Ofial, A. R. Pure Appl. Chem. 2005, 77, 1807–1821. (g)
Berger, S. T. A.; Seeliger, F. H.; Hofbauer, F.; Mayr, H. Org. Biomol.
Chem. 2007, 5, 3020–3026. (h) Seeliger, F.; Berger, S. T. A.;
Remennikov, G. Y.; Polborn, K.; Mayr, H. J. Org. Chem. 2007, 72,
9170–9180. (i) Kaumanns, O.; Lucius, R.; Mayr, H. Chem.sEur. J.
2008, 14, 9675–9682. (j) Mayr, H.; Ofial, A. R. J. Phys. Org. Chem.
2008, 21, 584–595. (k) Zenz, I.; Mayr, H. unpublished results, 2010.
(l) For a comprehensive database of nucleophilicity parameters N and
electrophilicity parameters E, see http://www.cup.lmu.de/oc/mayr/.
Kinetic Investigations have been performed in analogy to
earlier studies.10 However, because of the low stability of the
semistabilized ylides 1e,f, several modifications were needed
as described in detail in the Supporting Information. Table 2
(10) Appel, R.; Mayr, H. Chem.sEur. J. 2010, 16, 8610–8614.
(11) (a) Lu, L.-Q.; Cao, Y.-J.; Liu, X.-P.; An, J.; Yao, C.-J.; Ming, Z.-H.;
Xiao, W.-J. J. Am. Chem. Soc. 2008, 130, 6946–6948. (b) Lu, L.-Q.;
Li, F.; An, J.; Zhang, J.-J.; An, X.-L.; Hua, Q.-L.; Xiao, W.-J. Angew.
Chem., Int. Ed. 2009, 48, 9542–9545.
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Cyclopropanations with Sulfur Ylides
A R T I C L E S
Scheme 6. Reactions of the Sulfur Ylides 1f and 1h with the
Benzylidenebarbituric Acids 2o and 2p
Figure 1. Plots of log k2 for the reactions of the stabilized sulfur ylides
1b,d and the semistabilized sulfur ylides 1e,f with the electrophiles 2 (in
DMSO at 20 °C) versus the electrophilicity parameters E of 2. For the
sake of clarity, the correlation lines for the ylides 1a,c,g are only shown in
the Supporting Information.
a Reaction conditions: 1h, DMSO, rt. b Reaction conditions: (1f-H)-BF4,
K2CO3 (aq)/CHCl3, rt; only one diastereomer isolated.
shows a summary of the second-order rate constants, which have
been determined for the reactions of the sulfur ylides 1a-h with
the benzhydrylium ions 2a-e and the Michael acceptors 2f-v.
Discussion
Correlation Analysis. In order to determine the nucleophile-
specific parameters N and s of the sulfur ylides 1a-g, the
second-order rate constants (log k2) of their reactions with the
electrophiles 2 (see Table 2) were plotted against the electro-
philicity parameters E of 2a-v, which have previously been
derived from the rates of the reactions of 2a-v with electron-
rich ethylenes and carbanions.9b-d,g-i,k In Figure 1 these
correlations are shown exemplarily for the stabilized sulfur
ylides 1b,d and the semistabilized sulfur ylides 1e,f. The
correlations for the other nucleophiles investigated in this work
(1a,c,g) are of similar quality (see Table 2 and Supporting
Information) and allow the calculation of the nucleophile-
specific parameters N and s, which are listed in Table 2. The
small deviations between the calculated and experimental rate
constants in Table 2 (72% less than a factor of 1.5, 87% less
than a factor of 3.0, and 100% less than a factor of 5) confirms
that the rate-determining step of these reactions is analogous to
that from which the electrophilicity parameters E of 2a-v have
been derived. The same electrophilicity parameters E of
carbocations and Michael acceptors, which have previously been
demonstrated to be suitable for predicting the rates of their
reactions with aliphatic and aromatic π-systems, carbanions,
hydride donors, phosphines, and amines8,9 have thus been found
to be also suitable for predicting the rates of their reactions with
stabilized and semistabilized sulfur ylides.
Figure 2. Comparison of the nucleophilicity parameters N (in DMSO at
20 °C) of stabilized sulfur ylides (1a-d,h,i) and semistabilized sulfur ylides
a
b
(1e-g). Taken from ref 10; taken from ref 12.
parameters in Table 2, imply that the relative nucleophilicities
of the dimethylsulfonium ylides 1a-f depend only slightly
on the electrophilicity of the reaction partners. Consequently,
the N parameters can be used to compare the relative
reactivities of these compounds (Figure 2). The considerably
lower s parameter for the dimethylsulfoxonium ylide 1g
indicates that the rates of its reactions are less influenced by
a change of the electrophilicity of the reaction partners than
the corresponding reactions of the dimethylsulfonium ylides
1a-f. As a consequence, the relative reactivities of dimeth-
ylsulfonium ylides 1a-f in comparison to dimethylsulfoxo-
The similarities of the slopes of the correlations for the
dimethylsulfonium ylides 1a-f (Figure 1 and Supporting
Information), which are numerically expressed by the s-
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A R T I C L E S
Appel et al.
Table 2. Experimental and Calculated Second-Order Rate Constants (M-1
Electrophiles 2 in DMSO at 20 °C
s
-1) for the Reactions of the Sulfur Ylides 1 with the
a Nucleophilicity parameters N and s derived by using eq 1, determination see below. b Calculated by using eq 1 and the N and s parameters for the
ylides 1 (column 1 of this Table) as well as the electrophilicity parameters E for the benzhydrylium ions 2a-e and the Michael acceptors 2f-v (see
c
Table 1). Deprotonation of the conjugate CH-acid Me3SO+ I- with 0.482 equiv of KOtBu (for details see Supporting Information). d Taken from ref
10.
nium ylide 1g depend significantly on the electrophilicity of
the reaction partner.
Structure-Reactivity Relationships. As shown in Figure 2,
the nucleophilic reactivities of the sulfur ylides 1a-i in DMSO
cover a range of 7 orders of magnitude.
The reactivities of the benzoyl-stabilized ylides 1a-d, which
are the least reactive species in this series, correlate moderately
(12) Lakhdar, S.; Appel, R.; Mayr, H. Angew. Chem., Int. Ed. 2009, 48,
5034–5037.
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Cyclopropanations with Sulfur Ylides
A R T I C L E S
Scheme 7. Relative Reactivities of the Nucleophiles 1d,e,g
towards the Benzhydrylium Ion 2e and the Quinone Methide 2h
(DMSO, 20 °C)
a Absolute rate constant (k2 ) 0.799 M-1 s-1) calculated by eq 1 using
N ) 15.68 and s ) 0.65 for ylide 1d as well as the electrophilicity
parameters E ) -15.83 for the electrophile 2h.
with Hammett’s σp as shown on p S43 of the Supporting
Information. For s ) 0.7, one derives a Hammett reaction
constant of F ) -1.3 which indicates a moderate increase of
reactivity by electron-donating substituents.
Figure 3. Comparison of the nucleophilicities of different ethoxycarbonyl-
and p-nitro-phenyl-stabilized carbanions and sulfur ylides in DMSO at 20
°C.
The ethoxycarbonyl- and cyano-substituted ylides 1h and 1i
show nucleophilic reactivities, which lie in between those of
benzoyl- and aryl-substituted ylides. The semistabilized ylides
1e,f are the strongest nucleophiles in this series despite the
presence of strongly electron-withdrawing groups at the p-
position of the phenyl ring.
for acceptor-stabilized carbanions8 as well as for amide and
imide anions.16
Conclusion
Though the reactions of sulfur ylides with carbocations
(see Schemes 3 and 4) yield products which differ from those
obtained with Michael acceptors (see Schemes 5 and 6), the
rate constants for both types of reactions lie on the same
correlation lines (Table 2 and Figure 1), which allow us to
include sulfur ylides into the nucleophilicity scale on the basis
of eq 1 (Figure 4).
As the nucleophile-specific slope parameter s of the dimeth-
ylsulfoxonium ylide 1g differs significantly from those of the
dimethylsulfonium ylides 1a-f,h,i, the relative nucleophilic
reactivities of these different types of sulfur ylides have to be
compared with respect to a certain reaction partner. Scheme 7
thus shows that 1g reacts 13 times faster with the benzhydrylium
ion 2e than the most reactive benzoyl-stabilized ylide 1d, but 3
times more slowly than the benzylic ylide 1e. In reactions with
the weaker electrophile 2h, 1g exceeds the reactivity of the
benzoyl-substituted sulfur ylide 1d by more than 102 and is even
more reactive than the aryl-stabilized sulfur ylide 1e (Scheme
7).
As indicated in Figure 2, the sulfur ylide 1a is significantly
more nucleophilic in DMSO (ε ) 46.45)13 than in CH2Cl2 (ε
) 8.93)13 solution.12 Obviously, the formation of a sulfonium
ion from a delocalized benzhydrylium ion and a sulfur ylide is
accompanied by a significant localization of charge; as a result
the rates of the reactions of 1a with benzhydrylium ions increase
with increasing solvent polarity.
Figure 3 compares the nucleophilic reactivities of ethoxy-
carbonyl- and p-nitro-phenyl-stabilized sulfur ylides with those
of analogously substituted carbanions. Both columns show that
Me2S+ substitution reduces the nucleophilicity of a carbanionic
center more than a cyano group. The right column indicates
that a nitro group reduces the reactivity even more than a
dimethylsulfonium group. It should be noted, however, that
relative stabilizing effects of different groups thus derived,
cannot be generalized, because geminal substituent effects are
not strictly additive.
The common correlation lines for carbocations and Michael
acceptors furthermore imply that the rate-determining step of
the investigated sulfur ylide-mediated cyclopropanations is the
same as that for additions of sulfur ylides to carbocations. These
findings are in line with a stepwise or highly asynchronous
mechanism for the cyclopropanation of Michael acceptors with
sulfur ylides, in which the formation of the first C-C bond is
rate-determining.5b,e As a consequence, eq 1 and the derived
nucleophilicity parameters N (and s) of sulfur ylides 1 can
efficiently predict the rates of their reactions with Michael
acceptors of known electrophilicity E. As previous mechanistic
investigations have shown that cyclopropanation reactions with
sulfur ylides usually proceed with rate-determining addition steps,
followed by fast cyclizations (sometimes accompanied by preceding
fast proton-transfer reactions),5b,e the rule of thumb that nucleophile-
electrophile combinations at room temperature only occur when
(14) Bug, T.; Lemek, T.; Mayr, H. J. Org. Chem. 2004, 69, 7565–7576.
(15) (a) Keeffe, J. R.; Morey, J.; Palmer, C. A.; Lee, J. C. J. Am. Chem.
Soc. 1979, 101, 1295–1297. (b) Olmstead, W. N.; Bordwell, F. G. J.
Org. Chem. 1980, 45, 3299–3305. (c) Arnett, E. M.; Harrelson, J. A.
J. Am. Chem. Soc. 1987, 109, 809–812. (d) Bordwell, F. G. Acc. Chem.
Res. 1988, 21, 456–463. (e) Bordwell, F. G.; Branca, J. C.; Bares,
J. E.; Filler, R. J. Org. Chem. 1988, 53, 780–782. (f) Bordwell, F. G.;
Cheng, J.-P.; Bausch, M. J.; Bares, J. E. J. Phys. Org. Chem. 1988, 1,
209–223. (g) Bordwell, F. G.; Harrelson, J. A.; Satish, A. V. J. Org.
Chem. 1989, 54, 3101–3105. (h) Zhang, X.-M.; Bordwell, F. G. J. Am.
Chem. Soc. 1994, 116, 968–972. (i) Bordwell, F. G.; Satish, A. V.
J. Am. Chem. Soc. 1994, 116, 8885–8889. (j) Goumont, R.; Kizilian,
E.; Buncel, E.; Terrier, F. Org. Biomol. Chem. 2003, 1, 1741–1748.
(k) For a comprehensive database of pKa-values in DMSO, see http://
www.chem.wisc.edu/areas/reich/pkatable/.
A rather poor correlation is found between the nucleophilic
reactivities of different classes of carbanions and ylides8,9c,14
and their pKaH values7c,15 (Figure S2 of the Supporting Informa-
tion). Thus Brønsted basicities are also a poor guide for the
prediction of nucleophilicities for ylides, as previously shown
(13) Reichardt, C. SolVents and SolVent Effects in Organic Chemistry;
(16) Breugst, M.; Tokuyasu, T.; Mayr, H. J. Org. Chem. 2010, 75, 5250–
5258.
Wiley-VCH: Weinheim, 2003.
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A R T I C L E S
Appel et al.
Figure 4. Comparison of the nucleophilicity parameters N (in DMSO at 20 °C) of different sulfur ylides with other classes of nucleophiles (data referring
to other solvents are marked).
E + N > -5 can be employed9c to predict whether a certain
Acknowledgment. We gratefully acknowledge financial support
cyclopropanation reaction is likely to take place.
by the Deutsche Forschungsgemeinschaft (SFB 749) and the Fonds
der Chemischen Industrie (Scholarship to R.A.). Furthermore, we
thank Dr. Armin R. Ofial and Dr. Sami Lakhdar for helpful
discussions.
Experimental Section
Product Analysis. Detailed synthetic procedures for the prepara-
tion of the addition products 4, the cyclopropanes 5, the dihydro-
furans 6 as well as those for the reaction of the benzoyl-stabilized
sulfur ylide 1c with trans-4-methoxy-ꢀ-nitrostyrene (2v) are given
in the Supporting Information.
Kinetics. The rates of all reactions were determined photo-
metrically in dry DMSO (H2O content <50 ppm). The temperature
was kept constant (20.0 ( 0.1 °C) by using a circulating bath
thermostat. All reactions have been performed under first-order
conditions, and a detailed description of the procedure is given in
the Supporting Information.
Supporting Information Available: Details of the kinetic
experiments, synthetic procedures, and NMR spectra of all
characterized compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
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