DABCO and DMAP - Why are they different in organocatalysis?

Article abstract of DOI:10.1002/anie.200701489

(Chemical Equation Presented) What makes a good organocatalyst? DABCO (1,4-diazabicyclo[2.2.2]octane) is a thousandfold better nucleophile (k _→) and at the same time a million times better leaving group (k_←) than DMAP (4-(dimethylamino)pyridine). This apparent contradiction is resolved by consideration of the intrinsic reaction barriers.

Full text of DOI:10.1002/anie.200701489

Communications
DOI: 10.1002/anie.200701489
Organocatalysis
DABCO and DMAP—Why Are They Different in Organocatalysis?**
Mahiuddin Baidya, Shinjiro Kobayashi, Frank Brotzel, Uli Schmidhammer, Eberhard Riedle,
and Herbert Mayr*
Dedicated to Professor Ekkehard Winterfeldt on the occasion of his 75th birthday
Table 1: Benzhydrylium ions Ar2CH+ (4) and their electrophilicity
parameters E (from Ref. [4b]).
1,4-Diazabicyclo[2.2.2]octane (DABCO, 1), quinuclidine (2),
and 4-(dimethylamino)pyridine (DMAP, Steglichꢀs base, 3)
Ar2CH+
X
Y
E
Ph2CH+
H
CH3
OCH3
N(Ph)CH2CF3
N(CH3)CH2CF3
NPh2
H
CH3
OCH3
N(Ph)CH2CF3
N(CH3)CH2CF3
NPh2
5.90
3.63
0.00
ꢀ3.14
ꢀ3.85
ꢀ4.72
(tol)2CH+
(ani)2CH+
(pfa)2CH+
(mfa)2CH+
(dpa)2CH+
are important catalysts for a large variety of organic
reactions.[1] Attempts have been made to correlate the
efficiency of organocatalysts with their Brønsted basicities.[2]
Because the relative reactivities of different nucleophiles
towards electrophiles correlate only poorly with the corre-
sponding pKHa values,[3] we recently employed the benzhy-
drylium ion method[4] to compare the nucleophilicities and
carbon basicities of pyridines[5a] and tertiary phosphanes.[5b]
By studying rates and equilibria of the reactions of these
nucleophiles with a series of benzhydrylium ions 4 we showed
that despite widely differing Brønsted basicities, triarylphos-
phanes and donor-substituted pyridines show similar basic-
ities (K) and nucleophilicities (k) toward carbon electro-
philes. Our attempts to use the same spectrophotometric
method to also determine the nucleophilicities of trialkyl-
amines, for example, the well-known organocatalysts 1 and 2,
were unsuccessful.
(mor)2CH+
ꢀ5.53
(mpa)2CH+
(dma)2CH+
(pyr)2CH+
N(Ph)CH3
N(CH3)2
N(CH2)4
N(Ph)CH3
N(CH3)2
N(CH2)4
ꢀ5.89
ꢀ7.02
ꢀ7.69
(thq)2CH+
ꢀ8.22
(ind)2CH+
ꢀ8.76
When benzhydrylium ions 4 (Table 1) of high reactivity
(E > ꢀ9) were combined with 1 or 2, the reactions were too
(jul)2CH+
(lil)2CH+
ꢀ9.45
[*] MSc. M. Baidya, Prof. Dr. S. Kobayashi, Dipl.-Chem. F. Brotzel,
Prof. Dr. H. Mayr
Department Chemie und Biochemie
Ludwig-Maximilians-Universität München
Butenandtstrasse 5–13 (Haus F), 81377 München (Germany)
Fax: (+49)89-2180-77717
ꢀ10.04
E-mail: herbert.mayr@cup.uni-muenchen.de
Homepage: http://www.cup.uni-muenchen.de/oc/mayr
Dipl.-Phys. U. Schmidhammer, Prof. Dr. E. Riedle
Lehrstuhl für BioMolekulare Optik
Ludwig-Maximilians-Universität München
Oettingenstrasse 67, 80538 München (Germany)
Homepage: www.bmo.physik.uni-muenchen.de
fast (k > 106 mꢀ1 sꢀ1 at 208C) to be followed by conventional
stopped-flow methods. Less electrophilic benzhydrylium ions
(E < ꢀ9), on the other hand, did not react with 1 or 2. Only
when high concentrations of 1 or 2 were added to solutions of
(jul)2CH+ or (lil)2CH+ was a small amount of the carbocations
consumed. In these cases, the quaternary ammonium ions 5
are apparently thermodynamically less favorable than the
corresponding reactants.
[**] We thank the Deutsche Forschungsgemeinschaft (Ma673/21-2) and
the Fonds der Chemischen Industrie for support of this work and Dr.
A. Ofial for assistance in preparation of this manuscript.
DABCO=1,4-diazabicyclo[2.2.2]octane, DMAP=4-(dimethylami-
no)pyridine.
We now report on the use of laser flash techniques[6,7] for
the determination of the nucleophilicities of the tertiary
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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amines 1 and 2. We will then compare the nucleophilicities[3c]
and the corresponding carbon basicities[8] (derived from
equilibrium constants) of 1 and 2 with those of other
organocatalysts and discuss the implications.
Table 2: Second-order rate constants (k) for the reactions of benzhy-
drylium ions Ar2CH+ with the amines 1–3 in acetonitrile at 208C.
Ar2CH+
k [mꢀ1 sꢀ1
]
DABCO (1)
Quinuclidine (2)
DMAP (3)[a]
When the tertiary amines 1 or 2 (1 mm) were added to the
colored solutions of 4-BF4 (ꢀ3 > E > ꢀ9, c0 ꢁ 10ꢀ5 m) in
acetonitrile, immediate decolorization was observed, indicat-
ing the formation of the colorless ammonium salts 5-BF4
(Scheme 1). Irradiation of the resulting solutions ([5]
(lil)2CH+
n.r.[b]
n.r.[b]
2.11”103
5.30”103
1.29”104
3.32”104
(jul)2CH+
(ind)2CH+
(thq)2CH+
(pyr)2CH+
(dma)2CH+
(mpa)2CH+
(mor)2CH+
(dpa)2CH+
(mfa)2CH+
(pfa)2CH+
(ani)2CH+
(tol)2CH+
Ph2CH+
n.r.[b]
n.r.[b]
1.10”107
2.79”107
6.95”107
1.82”108
5.77”108
6.16”108
1.57”109
1.82”109
2.50”109
4.55”109
6.33”109
6.71”109
1.08”107
2.41”107
5.22”107
1.18”108
2.97”108
3.34”108
9.70”108
9.97”108
1.59”109
2.49”109
5.25”109
5.44”109
2.31”105
Scheme 1. Formation of ammonium salts 5-BF4 from benzhydrylium
tetrafluoroborates 4-BF4 and bicyclic amines (1 or 2) and laser-flash-
induced heterolytic cleavage of 5-BF4 to give the starting materials.
[a] Second-order rate constants for DMAP (3) from Ref. [5a]. [b] No
reaction.
ꢁ 10ꢀ5 m) with 7-ns laser pulses (266 nm, 40–60 mJ) resulted
in the heterolytic cleavage of 5 with regeneration of the
benzhydrylium ions 4, which were detected by their UV/Vis
spectra.[7] The benzhydrylium ions Ph2CH+ and (tol)2CH+
were obtained by irradiation of the corresponding diary-
lchloromethanes, and (ani)2CH+ was generated by irradiation
of (p-MeOC6H4)2CHOAc.
Because of the high concentrations of the amines 1 and 2
relative to the benzhydrylium ions, the reactions followed
first-order rate laws (exponential decay of the absorbances of
4). Figure 1 shows that the first-order rate constants kobs
increased linearly with the concentration of amine, and the
second-order rate constants derived from the slopes of such
plots[9] are listed in Table 2. It can be seen that (ind)2CH+, the
least electrophilic benzhydrylium ion that combines with 1
and 2 to give the ammonium ion 5, reacts at almost equal rates
with both amines. Considering the statistical factor, the
reactivity per nitrogen is half as high for DABCO (1), which
can be explained by the electron-withdrawing inductive effect
of the second nitrogen. When reactions with more electro-
philic benzhydrylium ions are considered and diffusion
control[10,11] is approached, DABCO becomes slightly more
reactive than quinuclidine (2; Figure 2).
Figure 2. Plot of lgk versus the electrophilicity parameters E for the
reactions of the bicyclic amines DABCO (1) and quinuclidine (2) and
of DMAP (3) with benzhydrylium ions in acetonitrile at 208C.
the nucleophile-specific reactivity parameters for 1 (N =
18.80, s = 0.70) and 2 (N = 20.54, s = 0.60), as defined by the
correlation equation (1) (k: second-order rate constant
Because the linear sections of the correlations for
DABCO (1) and quinuclidine (2) in Figure 2 are very short,
lg k20 ꢂC ¼ sðN þ EÞ
ð1Þ
(Lmolꢀ1 sꢀ1), N: nucleophilicity parameter, E: electrophilicity
parameter, s: nucleophile-specific slope parameter)[4] are not
very accurate.[12] Figure 2 shows clearly, however, that the
bicyclic amines 1 and 2 are three orders of magnitude more
nucleophilic than DMAP (3).
In contrast, the thermodynamic stabilities of the ammo-
nium ions 5 obtained from 1 and 2 appear to be much smaller
than those of the corresponding DMAP-derived ammonium
ions, because 1 and 2 do not react with (lil)2CH+ and
(jul)2CH+ despite the expected high reaction rates. In order to
quantify the thermodynamic effects, the carbon basicities[8] of
1–3 were determined by measuring the equilibrium constants
for some of the reactions described in Scheme 1.
Figure 1. Plot of the first-order rate constants kobs for the reaction of
(dma)2CH+ with amine 2 versus the amine concentration.
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Communications
Table 3: Equilibrium constants (K) for the reactions of amines 1–3 with
some benzhydrylium cations Ar2CH+ in acetonitrile at 208C.[a]
Table 4: Comparison of equilibrium constants (K) for the reactions of
benzhydrylium ions Ar2CH+ with differently substituted pyridines in
acetonitrile at 208C.
Ar2CH+
K [mꢀ1
]
DABCO (1)
Quinuclidine (2)
DMAP (3)[a]
Ar2CH+
K [mꢀ1
]
(lil)2CH+
(4”101)
(4”102)
2.44”104
2.60”104
5.60”105
(1”106)
(jul)2CH+
(ind)2CH+
(thq)2CH+
(pyr)2CH+
(4”101)
(4”102)
(8.7”102)
1.56”103
4.89”103
(9.3”103)
1.68”104
4.49”104
(ind)2CH+
(thq)2CH+
(pyr)2CH+
7.02”101
1.31”102
3.70”102
4.68”101
8.04”101
(3”106)
3.02”101
9.52”101
[a] For the determination of the equilibrium constants in parentheses,
see text.
While the amines 1–3 react quantitatively with benzhy-
drylium ions of E > ꢀ7, their reactions with less reactive
benzhydrylium ions proceed incompletely. As benzhydrylium
ions are colored and the resulting adducts 5 are colorless, the
equilibrium constants (Table 3) can be determined by UV/Vis
spectroscopy. Assuming a proportionality between the absor-
bances and concentrations of the benzhydrylium ions, the
equilibrium constants for reaction (2) can be expressed by the
absorbances of the benzhydrylium ions before (A0) and after
(A) addition of the amine [Eq. (3)].
The availability of rate and equilibrium constants now
allows us to calculate the intrinsic barriers DG°0 for these
reactions (i.e. the barriers of the corresponding reactions with
DrG0 = 0) by substituting DG° and DrG0 into the Marcus
Equation (4),[13] where the work term has been omitted
2
DG° ¼ DG°0 þ 0:5 DrG0 þ ½ðDrG0Þ =16DG°0 ꢃ
ð4Þ
(Table 5). To avoid ambiguity, data derived from estimated
equilibrium constants are identified by the “ ꢁ ” sign in
Table 5.
K
Ar2CHþ þ NR Ar CHꢀNR
ð2Þ
þ
!
3
2
3
Table 5 shows a significant difference in the intrinsic
barriers for the reactions of DABCO (1) and quinuclidine (2)
on one hand and DMAP (3) on the other. While the DG0°
values for the bicyclic amines are around 40 kJmolꢀ1, those
for DMAP (3) are greater than 60 kJmolꢀ1. Considerably
more reorganization energy appears to be needed for the
reactions with the pyridine 3 than for the reactions with 1 and
2.
From the rate constants given in Table 2 and the
equilibrium constants in Table 3 one can also calculate the
rate constants of the reverse reactions, which are listed in the
last column of Table 5. As a consequence of the similar
nucleophilicities of 1 and 2, but the 10-times higher equilib-
rium constants for quinuclidine (2), the nucleofugality of
DABCO (1) is estimated to be about 10 times higher than that
of quinuclidine (2).
½Ar2CHꢀNR3þꢃ ðA0ꢀAÞ
K ¼
¼
½Ar2CHþꢃ½NR3ꢃ A ½NR3ꢃ
ð3Þ
where ½NR3ꢃ ¼ ½NR3ꢃ0ꢀ½Ar2CHꢀNR3þꢃ
Only the equilibrium constants given without parentheses
in Table 3 could be determined directly by this procedure.
High concentrations of 1 and 2 were required to observe at
least partial consumption of the least electrophilic benzhy-
drylium ions (lil)2CH+ and (jul)2CH+. However, the absor-
bances did not remain constant under such conditions,
indicating a slow consecutive reaction which has not been
identified so far. Also, in the reaction of (ind)2CH+ with 1 and
2, the composition of the rapidly formed equilibrium mixture
[Eq. (2)] was not constant, and (ind)2CH+ was consumed by a
slow, unidentified consecutive reaction. The direct determi-
nation of the equilibrium constants for the reactions of
(thq)2CH+ and (pyr)2CH+ with DMAP (3) failed because of
the high value of K.
For this reason, an indirect method was used for estimat-
ing the equilibrium constants shown in parentheses in Table 3.
Equilibrium constants for the reactions of benzhydrylium ions
with other pyridines which have been determined as de-
scribed above [Eqs. (2) and (3)] are given in Table 4. A
comparison of Tables 3 and 4 shows that the directly
measured equilibrium constants for (pyr)2CH+ are 2.67- to
3.15-times higher than those for (thq)2CH+, almost independ-
ent of the nature of the amine. Because the first two lines of
Table 4 show that the reactions of (ind)2CH+ with pyridines
have K values (1.80 ꢄ 0.08) times lower than the correspond-
ing values for (thq)2CH+, this value was used for estimating
the equilibrium constants for the combinations of (ind)2CH+
with 1 and 2 in Table 3. With the assumption that the same
ratios also hold for DMAP (3), the missing equilibrium
constants in Table 3 have been calculated.
A more profound difference is found for DMAP (3),
however: Its considerably lower nucleophilicity and higher
carbon basicity (compared with that of 1 and 2) implies that
Table 5: Activation energies DG°, reaction free energies DrG0, and
intrinsic barriers DG°0 (in kJmolꢀ1) for the reactions of benzhydrylium
tetrafluoroborates Ar2CH+BF4ꢀ with amines 1–3 as well as rate constants
!
k
for the back reactions (CH3CN, 208C).
ꢀ1
!
k [s ]
Amine
Ar2CH+
DG°
DrG0
DG°0
1
(ind)2CH+
(thq)2CH+
(pyr)2CH+
(ind)2CH+
(thq)2CH+
(pyr)2CH+
(lil)2CH+
ꢁ32.2
30.0
27.7
ꢁꢀ16.2
ꢀ17.9
ꢁ40.3
38.9
38.1
ꢁ1”104
1.79”104
1.42”104
ꢁ1”103
ꢀ20.7
2
3
ꢁ32.3
ꢁꢀ22.0
ꢀ23.9
ꢁ43.3
30.3
42.2
1.43”103
1.16”103ꢀ2
8.65”10
28.4
53.1
50.8
48.7
ꢀ26.1
41.5
ꢀ24.6
65.4[a]
63.2[a]
64.8[a]
ꢁ63.2[a]
(jul)2CH+
(ind)2CH+
(thq)2CH+
ꢀ24.8
2.04”10ꢀ1
2.30”10ꢀ2
ꢁ3”10ꢀ2
ꢀ32.2
ꢁ46.4
ꢁꢀ33.7
[a] DG°0 (in CH2Cl2)=60.4, 59.9, 59.2, 57.1 kJmolꢀ1, respectively; from
Ref. [5a].
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Angewandte
Chemie
the leaving-groupability of 3 is 105 to 106 times lower than
that of the bicyclic amines 1 and 2.
Acc. Chem. Res. 2003, 36, 66 – 77; d) H. Mayr, A. R. Ofial in
Carbocation Chemistry (Eds.: G. A. Olah, G. K. S. Prakash),
Wiley, Hoboken, 2004, chap. 13, pp. 331 – 358; e) H. Mayr, A. R.
Ofial, Pure Appl. Chem. 2005, 77, 1807 – 1821.
In summary, we can conclude that DABCO (1) and
quinuclidine (2) are significantly better nucleophiles than
DMAP (3) (by a factor of 103) but at the same time
significantly better nucleofuges (by a factor of 106 and 105,
respectively). What is the impact of these findings for
organocatalysis? It has been shown previously that the
relative reactivities of nucleophiles towards typical Michael
acceptors closely resemble those toward benzhydrylium
ions.[14] For that reason, the different properties of 1–3
described in Tables 2 and 3 can be expected to reflect their
efficiency in Baylis–Hillman reactions. Because of the higher
carbon basicity of DMAP (3), it will generally be superior to
DABCO (1) and quinuclidine (2), if reactivity is controlled by
the concentration of the intermediate ammonium ions
produced by the reactions of the amines with the electro-
philes.[1,15,16] If, however, reactivity is controlled by the rate of
the nucleophilic attack of the organocatalyst or by the release
of the amine component in the final stage of the reaction,
DABCO (1) and quinuclidine (2) will be superior.[1,15,16]
The fact that Baylis–Hillman reactions with cycloalke-
nones and acrylates are better catalyzed by DMAP (3) than
by the standard catalyst DABCO (1)[17] possibly reflects the
need for higher concentrations of the zwitterionic intermedi-
ates in these cases. The relevance of the kinetic and
thermodynamic data determined in this work for acylation
reactions is not yet known.
[5] a) F. Brotzel, B. Kempf, T. Singer, H. Zipse, H. Mayr, Chem. Eur.
J. 2007, 13, 336 – 345; b) B. Kempf, H. Mayr, Chem. Eur. J. 2005,
11, 917 – 927.
[6] a) S. Kobayashi, Y. Hari, T. Hasako, K. Koga, H. Yamataka, J.
Org. Chem. 1996, 61, 5274 – 5279; b) S. Kobayashi, T. Kitamura,
H. Taniguchi, W. Schnabel, Chem. Lett. 1983, 1117 – 1120; c) U.
Schmidhammer, S. Roth, E. Riedle, A. A. Tishkov, H. Mayr,
Rev. Sci. Instrum. 2005, 76, 093111.
[7] a) R. A. McClelland in Reactive Intermediate Chemistry (Eds.:
R. A. Moss, M. S. Platz, M. Jones, Jr.), Wiley, 2004, chap. 1,
pp. 3 – 40; b) P. K. Das, Chem. Rev. 1993, 93, 119 – 144; c) K.
Peters, Annu. Rev. Phys. Chem. 1987, 38, 253 – 270; d) R. A.
McClelland, V. M. Kanagasabapathy, N. S. Banait, S. Steenken,
J. Am. Chem. Soc. 1989, 111, 3966 – 3972; e) R. A. McClelland,
Tetrahedron 1996, 52, 6823 – 6858; f) R. A. McClelland, F. L.
Cozens, S. Steenken, T. L. Amyes, J. P. Richard, J. Chem. Soc.
Perkin Trans. 2 1993, 1717 – 1722; g) R. A. McClelland, V. M.
Kanagasabapathy, N. S. Banait, S. Steenken, J. Am. Chem. Soc.
1991, 113, 1009 – 1014; h) E. O. Alonso, L. J. Johnston, J. C.
Scaiano, V. G. Toscano, J. Am. Chem. Soc. 1990, 112, 1270 – 1271;
i) E. O. Alonso, L. J. Johnston, J. C. Scaiano, V. G. Toscano, Can.
J. Chem. 1992, 70, 1784 – 1794.
[8] a) J. Hine, R. D. Weimar, J. Am. Chem. Soc. 1965, 87, 3387 –
3396; b) E. M. Arnett, R. Reich, J. Am. Chem. Soc. 1980, 102,
5892 – 5902.
[9] R. Schmid, V. N. Sapunov, Non-formal Kinetics, VCH, Wein-
heim, 1982.
[10] a) M. Montalti, A. Credi, L. Prodi, M. T. Gandolfi, Handbook of
Photochemistry, 3rd ed., CRC Press, New York, 2006, p. 421;
b) W. P. Jencks, Acc. Chem. Res. 1980, 13, 161 – 169.
Received: April 5, 2007
[11] a) J. P. Richard, W. P. Jencks, J. Am. Chem. Soc. 1984, 106, 1383 –
1396; b) J. P. Richard, W. P. Jencks, J. Am. Chem. Soc. 1984, 106,
1373 – 1383; c) J. P. Richard, M. E. Rothenberg, W. P. Jencks, J.
Am. Chem. Soc. 1984, 106, 1361 – 1372; d) J. P. Richard, W. P.
Jencks, J. Am. Chem. Soc. 1982, 104, 4689 – 4691.
[12] Based on the nucleophilicity parameters we would expect the
reactions of 1 and 2 with 2,4-dinitrobenzofuroxan (E = ꢀ5.06,
from Ref. [12a]) to be very fast (perhaps reversible), with k >
109 mꢀ1 sꢀ1 at 208C , in contrast to a literature report (Ref. [12b])
which gives second-order rate constants of 0.78 and 0.21mꢀ1 sꢀ1
(in THF), respectively. We, therefore, agree with Cramptonꢀs
criticism of this work (Ref. [12c]): a) S. Lakhdar, M. West-
ermaier, F. Terrier, R. Goumont, T. Boubaker, A. R. Ofial, H.
Mayr, J. Org. Chem. 2006, 71, 9088 – 9095; b) C. Boga, L. Forlani,
J. Chem. Soc. Perkin Trans. 2 2001, 1408 – 1413; c) B. H. M.
Asghar, M. R. Crampton, Org. Biomol. Chem. 2005, 3, 3971 –
3978.
Published online: July 12, 2007
Keywords: kinetics · linear free energy relationships ·
.
nucleofugality · nucleophilicity · organocatalysis
[1] a) P. I. Dalko, Enantioselective Organocatalysis, Wiley-VCH,
Weinheim, 2007; b) A. Berkessel, H. Gröger, Asymmetric
Organocatalysis, Wiley-VCH, Weinheim, 2005; c) A. C. Spivey,
S. Arseniyadis, Angew. Chem. 2004, 116, 5552 – 5557; Angew.
Chem. Int. Ed. 2004, 43, 5436 – 5441; d) D. Basavaiah, A. J. Rao,
T. Satyanarayana, Chem. Rev. 2003, 103, 811 – 891; e) G. C. Fu,
Acc. Chem. Res. 2000, 33, 412 – 420; f) P. Langer, Angew. Chem.
2000, 112, 3177 – 3180; Angew. Chem. Int. Ed. 2000, 39, 3049 –
3052; g) S. E. Drewes, G. H. P. Roos, Tetrahedron 1988, 44,
4653 – 4670; h) G. Höfle, W. Steglich, H. Vorbrüggen, Angew.
Chem. 1978, 90, 602 – 615; Angew. Chem. Int. Ed. Engl. 1978, 17,
569 – 583.
[2] a) V. K. Aggarwal, I. Emme, S. Y. Fulford, J. Org. Chem. 2003,
68, 692 – 700; b) D. J. Maher, S. J. Connon, Tetrahedron Lett.
2004, 45, 1301 – 1305.
[3] a) J. E. Leffler, E. Grunwald, Rates and Equilibria of Organic
Reactions, Wiley, New York, 1963; b) A. Williams, Free Energy
Relationships in Organic Bio-organic Chemistry, The Royal
Society of Chemistry, Cambridge, 2003; c) J. M. Harris, S. P.
McManus, Nucleophilicity, American Chemical Society, Wash-
ington, 1987.
[13] a) R. A. Marcus, J. Phys. Chem. 1968, 72, 891 – 899; b) W. J.
Albery, Annu. Rev. Phys. Chem. 1980, 31, 227 – 263.
[14] a) T. Lemek, H. Mayr, J. Org. Chem. 2003, 68, 6880 – 6886;
b) A. R. Ofial, H. Mayr, Macromol. Symp. 2004, 215, 353 – 367.
[15] a) M. R. Heinrich, H. S. Klisa, H. Mayr, W. Steglich, H. Zipse,
Angew. Chem. 2003, 115, 4975 – 4977; Angew. Chem. Int. Ed.
2003, 42, 4826 – 4828; b) S. Xu, I. Held, B. Kempf, H. Mayr, W.
Steglich, H. Zipse, Chem. Eur. J. 2005, 11, 4751 – 4757; c) H.
Kasprzyk, S. Kinastowski, React. Kinet. Catal. Lett. 2002, 77, 3 –
12; d) G. C. Fu, Acc. Chem. Res. 2004, 37, 542 – 547.
[16] a) C. Faltin, E. M. Fleming, S. J. Connon, J. Org. Chem. 2004, 69,
6496 – 6499; b) J. Wu, X. Sun, Y. Li, Eur. J. Org. Chem. 2005,
4271 – 4275.
[17] a) F. Rezgui, M. M. El Gaied, Tetrahedron Lett. 1998, 39, 5965 –
5966; b) R. Octavio, M. A. de Souza, M. L. A. A. Vasconcellos,
Synth. Commun. 2003, 33, 1383 – 1399.
[4] a) H. Mayr, M. Patz, Angew. Chem. 1994, 106, 990 – 1010;
Angew. Chem. Int. Ed. Engl. 1994, 33, 938 – 957; b) H. Mayr, T.
Bug, M. F. Gotta, N. Hering, B. Irrgang, B. Janker, B. Kempf, R.
Loos, A. R. Ofial, G. Remennikov, H. Schimmel, J. Am. Chem.
Soc. 2001, 123, 9500 – 9512; c) H. Mayr, B. Kempf, A. R. Ofial,
Angew. Chem. Int. Ed. 2007, 46, 6176 –6179
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
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