A microporous lanthanide-organic framework
The total yield of the NAD adducts A ± E based on
 D. A. Rozwarski, G. A. Grant, D. H. R. Barton, W. R. Jacobs, Jr., J. C.
consumed isoniazid is roughly 50% under the conditions
Sacchettini, Science 1998, 279,98 ± 102.
shown in Figure 1 (micromolar concentrations of both iso-
 F. Minisci, E. Vismara, F. Fontana, Heterocycles 1989, 28, 489 ± 519.
 Recombinant InhA was purified by using a N-terminal His-tag. For
niazid and NAD). The efficient formation of the inhibitor 2
the incubation experiments, InhA (5.4mm) was incubated with horse-
in the absence of InhA is, in our opinion, of great importance
radish peroxidase (44 mm), isoniazid (250mm), MnCl2 (7.5mm) and
for an understanding of the mechanism of action of isoniazid.
either NAD or NADH (each 47mm) at pH 7.5 (50mm Na2HPO4) and
As the concentration of NAD inside M. tuberculosis is also in
258C. The InhA activity was monitored by using a NADH-based
assay. After the activity dropped below 10% of the value at t
the micromolar range, we propose that inside the bacterium
sample was dialyzed for 12 h at 4 8C in a microdialysis system
2 is formed by the fast addition of acyl radical 3 to electron-
(GibcoBRL; Cut-off of the dialysis membrane: 12 ± 14 kD) against
deficient heterocycles such as NAD and outside the active
100 mm triethylammonium acetate, pH 7. MALDI-TOF spectra were
site of InhA. Considering the low binding affinity of InhA for
recorded by using a RP Biospectrometry Voyager DE; sinapinic acid,
2,5-dihydroxybenzoic acid, or 2-amino-5-nitropyridine were used as a
I 4mm) and the resulting low concentration of
InhA-bound NAD, the also conceivable addition of 3 to
 M. Wilming, Diploma thesis, Universität Bochum, 1998.
NAD within the active site of InhA appears rather unlikely.
 HPLC analysis was performed on a Merck LiChroCART 250 ± 4
Furthermore, the catalase-peroxidase KatG does not play an
Purospher RP-18e (5 mm) using a linear gradient from NH4OAc
active role in the addition of 3 to NAD (although it is
(75 mm) to acetonitrile. UV spectra of the peaks were recorded using a
required for oxidation of isoniazid), as the yield of isonico-
tinoyl-NAD adducts as well as the product composition is
I value of product B/E was determined by using 2-trans-
octenoyl-CoA and NADH as substrates at pH 7.5 (100 mm Na2HPO4)
about the same after oxidation of isoniazid by KatG or Mn3.
and 25 8C. At fixed concentrations of NADH and 2-trans-octenoyl-
The mechanism of action of isoniazid therefore relies on
CoA the concentration of B/E was varied.
the efficient formation of the isonicotinoyl ± NAD adducts
 Y. Pocker, J. E. Meany, J. Am. Chem. Soc. 1967, 89, 631 ± 636.
 (4 ± 2H)-NAD was synthesized according to the procedure of
by a Minisci reaction as well as the inhibitory potential of
Charlton et al.: P. A. Charlton, D. W. Young, B. Birdsall, J. Feeny,
2 (B/E), whose KI value is about 100nm (see above) and
G. C. K. Roberts, J. Chem. Soc. Perkin Trans. 1 1985, 1349 ± 1353.
therefore about a factor of 100 below the K
 K. P. Gopinathan, M. Sirsi, T. Ramakrishnan, Biochem. J. 1963, 87,
 a) L. Miesel, T. R. Weisbrod, J. A. Marcinkeviciene, R. Bittman, W. R.
The proposed reaction mechanism also allows one to
Jacobs Jr., J. Bacteriol. 1998, 180, 2459 ± 2467; b) P. Chen, W. R. Bishai,
reinterpret the observations that a number of isoniazid-
Infect. Immun. 1998, 66, 5099 ± 5106.
resistant mycobacteria appear to possess a higher ratio of
NADH/NAD as the result of defects in NADH-dehydrogen-
ases,[16a] and that overexpression of NAD-binding proteins
might contribute to isoniazid-resistance.[16b] A lower intra-
cellular concentration of NAD should, according to our
mechanism, directly lead to a diminished rate of formation of
2 and therefore to an increased resistance towards isoniazid.
In summary, the demonstrated spontaneous formation of
the bioactive form of isoniazid significantly simplifies the
proposed mechanism of action of the drug and should be
helpful in obtaining a better understanding of the molecular
The recent upsurge of reports on open metal ± organic
events leading to isoniazid-resistance.
frameworks has provided compelling evidence for the ability
to design and produce structures with unusual pore shape,
size, composition, and function. To realize the potential of
these materials in host ± guest recognition, separation, and
German version: Angew. Chem. 1999, 111, 2724 ± 2727
catalysis, it is essential that their frameworks exhibit perma-
Keywords: bioorganic chemistry ´ cofactors ´ enzyme catal-
[*] Prof. O. M. Yaghi, T. M. Reineke, Dr. M. Eddaoudi,
 B. R. Bloom, C. J. L. Murray, Science 1992, 257, 1055 ± 1064.
 a) Y. Zhang, B. Heym, B. Allen, D. Young, S. Cole, Nature 1992, 258,
Arizona State University, Box 871604, Tempe, AZ 85287 (USA)
591 ± 593; b) K. Johnsson, P. G. Schultz, J. Am. Chem. Soc. 1994, 116,
 F. G. Winder, P. B. Collins, J. Gen. Microbiol. 1970, 63, 41 ± 48.
 a) A. Banerjee, E. Dubnau, A. Quemard, V. Balasubramanian, K.
Sun Um, T. Wilson, D. Collins, G. de Lisle, W. R. Jacobs, Jr., Science
1994, 263, 227 ± 230; b) K. Mdluli, R. A. Slayedn, Y. Zhu, S.
Ramaswamy, X. Pan, D. Mead, D. D. Crane, J. M. Musser, C. E.
[**] The financial support of this work by the National Science Foundation
Barry III, Science 1998, 280, 1607 ± 1610.
(Grant CHE-9522303) and Department of Energy (Division of
 A. Quemard, J. C. Sacchettini, A. Dessen, C. Vilcheze, R. Bittman,
Chemical Sciences, Office of Basic Energy Sciences, Grant DE-
W. R. Jacobs Jr., J. S. Blanchard, Biochemistry 1995, 34, 8235 ± 8241.
FG03-98ER14903), and the crystallographic work provided by Dr.
 K. Johnsson, D. S. King, P. G. Schultz, J. Am. Chem. Soc. 1995, 117,
Fred Hollander (University of California-Berkeley) are gratefully
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
nent microporosity even in the absence of guests, an aspect
that is routinely considered for zeolites but has remained
largely unexplored for the analogous metal ± organic materi-
als. In attempting to address this issue, we aimed at coupling
our interest in designing new frameworks with the desire to
achieve stable microporous structures. Here we report the
synthesis and structure of Tb(bdc)NO3 ´ 2DMF (bdc 1,4-
benzenedicarboxylate; DMF N,N-dimethylformamide) and
show that its desolvated derivative Tb(bdc)NO3 has a stable
zeolite-like framework that is capable of reversible molecular
sorption and of maintaining microporosity in the absence of
Previous studies on the copolymerization of ZnII with BDC
have shown that stable frameworks can be produced.[3d, 4] This
was attributed to the bis-bidentate functionality of BDC and
its tendency to form large, tightly bound metal carboxylate
cluster aggregates that ultimately act as building blocks in the
crystal structure. We sought to extend this strategy to the
pursuit of lanthanide ± organic open frameworks, which
remain virtually unknown, despite the established role of
lanthanide compounds sensor technology.
Deprotonation of the acid form of BDC (H2BDC) with
pyridine followed by its copolymerization with TbIII in
methanol/DMF at room temperature gave a crystalline color-
less solid, which was formulated as Tb(bdc)NO3 ´ 2DMF on
the basis of elemental analysis and single-crystal X-ray
diffraction.[6, 7] Complete deprotonation of BDC was con-
firmed by the absence of any strong absorption bands due to
protonated carboxyl groups (1715 ± 1680 cmÀ1) in the FT-IR
Figure 2. a) Tb ± BDC chains shown perpendicular to the c axis. b) A
spectrum. This material is stable in air and is insoluble in
projection along the c axis with DMF shown in space-filling (C, shaded; N,
common organic solvents such as methanol, ethanol, acetoni-
cross-hatched; O, open) and the Tb ± BDC ± NO3 framework as ball-and-
stick (Tb, filled; N, cross-hatched; C and O, open) representations.
Hydrogen atoms are omitted for clarity.
The single-crystal structure analysis revealed an extended
Tb ± BDC framework with two crystallographically distinct
Tb atoms, BDC units, nitrate ions, and four DMF ligands. The
BDC to form a three-dimensional network (Figure 2b) in
two Tb atoms are each coordinated by eight oxygen atoms:
which the nitrate anions and DMF molecules point into the
One each from four carboxylate groups of different BDC
channels. The topology of the structure is best described in
ligands, two from a nitrate anion, and one from each of two
terms of a simple (3,4)-connected net derived from the
DMF molecules (Figure 1). The framework is composed only
4-connected net of the PtS structure (Figure 3a and b). In this
of Tb and BDC, whereby each carboxylate moiety bridges two
case, each of the planar 4-connected vertices (filled circles)
terbium atoms in a bis-monodentate fashion to form chains
are split into pairs of 3-connected vertices that share a
along the c axis (Figure 2a). These chains are cross-linked by
common link. As shown in Figure 3c, the 4-connected
Figure 1. The asymmetric unit of crystalline Tb(bdc)NO3 ´ 2DMF; atoms labeled by the letter A are related by symmetry to those
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
195 K. When no further weight change was observed, a single
isotherm point was recorded. A plot of weight sorbed per
gram of Tb(bdc)NO3 versus p/p0 (p0 saturation pressure;
780 Torr for CO2) revealed a reversible type I isotherm
(Figure 4), characteristic of a microporous material with
Figure 3. a) The 4-connected net of PtS (S, open; Pt, filled). b) The (3,4)-
connected net of Tb(bdc)NO3 ´ 2DMF that is derived from (a) by
converting the planar 4-connected vertices (filled) to pairs of 3-connected
vertices. c) Schematic identification of the atoms in the crystal structure of
Tb(bdc)NO3 ´ 2DMF with net vertices; open circles are Tb atoms [4-
connected vertices in (b)] and filled circles are carboxylate C atoms of
BDC [3-connected vertices in (b)]; the benzene ring of BDC is super-
imposed on the link between 3-connected vertices.
Figure 4. CO2 sorption (dark circles) and desorption (open circles)
vertices are the Tb atoms which are connected through ÀOÀ
isotherm for Tb(bdc)NO3 plotted with sorbed amount w versus relative
links to the carboxylate C atoms of BDC (the 3-connected
pressure p/p0 (p0 saturation pressure).
vertices); these are in turn joined in pairs by ÀC
its highest symmetry form the network is tetragonal, space
zeolite-like sorption behavior. The pore volume was estimat-
group P42/mmc, but the symmetry is lower (P21/c) in the
ed from this data by using the Dubinin ± Raduskhvich
equation to be 0.032 cm3gÀ1, which is comparable to that of
To create an open framework with accessible voids, we
common zeolites.[2a] Applying the same technique at room
examined the possibility of removing the DMF ligands by
temperature for the vapor sorption, we found that dichloro-
means of a thermogravimetric (TG) study. A sample of the as-
methane (4 kinetic diameter) is readily sorbed into the
synthesized material (46.87 mg) showed an onset of weight
pores of Tb(bdc)NO3 with a type I isotherm. However,
loss at 1208C that terminated at 2238C with 27.1% total weight
sorption of cyclohexane was not observed due to its larger
loss, which is equivalent to the removal of 1.97 DMF
molecules per formula unit (calculated: 27.5%). The FT-IR
The dissociation and removal of DMF from the channels
spectrum of the remaining solid Tb(bdc)NO 
means that terbium becomes coordinatively unsaturated in
absorption bands to those of the original solid, albeit with
the resulting porous solid. Exploring the chemistry of such
minor differences due to the removal of DMF. Its X-ray
Lewis acid sites may reveal their potential use in sensors or as
powder diffraction pattern was significantly broadened with
catalysts for organic transformations. On studying the solution
only two discernible diffraction lines; this indicates a degra-
stability of the porous framework, we observed that immer-
dation of long-range order. However, the fact that
sion of the evacuated solid in water results in its quantitative
Tb(bdc)NO3 did not show any weight loss up to 3208C
and irreversible conversion to another recently reported
suggested the presence of a stable framework material. Re-
porous solid, namely, Tb2(bdc)3 ´ 4H2O.[5a] Nevertheless,
sorption of DMF into the solvent-free material resulted in
Tb(bdc)NO3 appears to be unaffected by organic solvents,
regeneration of the most prominent diffraction lines of the as-
and this allowed allowed the study of its inclusion chemistry.
The solution sorption isotherms for methanol, ethanol, and
To determine the microporosity of Tb(bdc)NO3, the gas
isopropyl alcohol are shown in Figure 5. A known amount of
sorption isotherm was measured. Initially, we confirmed the
the evacuated solid (30 ± 40 mg) was immersed in a solution in
loss of DMF from the original solid by placing a sample of
toluene containing a specific amount of a potential guest
Tb(bdc)NO3 ´ 2DMF (151.50 mg) in an electromicrogravimet-
(0.10 ± 0.90m). The change in guest concentration was then
ric balance (CAHN 1000) setup at room temperature under
measured by gas chromatography with a thermal conductivity
vacuum (5 Â 10À5 Torr). Then the loss of DMF was monitored
detector. Each equilibrium point was obtained by monitoring
by heating to 135 and 1858C at 0.15 KminÀ1. The total weight
the change in guest concentration with time until no further
losses of 18.68 (1.35DMF) and 26.97% (1.97DMF), respec-
change was observed. The sorption process was successfully
tively, confirm the TG results. At this point, carbon dioxide
modeled with a 1:1 complex as suggested by the Langmuir
(UHP grade) was introduced into the sample chamber
isotherm equation (assuming equivalent available sites), and
containing the completely evacuated sample, and the weight
all compounds showed good agreement to the model with
changes were monitored at different pressure intervals at
high nonlinear regression parameters (typically 0.99). The
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
Hoskins, J. Liu in Supramolecular Architecture: Synthetic Control in
Thin Films and Solids (Ed.: T. Bein), American Chemical Society,
Washington, DC, 1992, chap. 19; k) T. Iwamoto in Inclusion Com-
pounds, Vol. 5 (Eds.: J. L. Atwood, J. Davies, D. D. MacNicol), Oxford
University Press, New York, 1991, p.177.
 a) D. W. Breck in Zeolite Molecular Sieves, Structure, Chemistry, and
Use, Wiley, New York, 1974; b) S. J. Gregg, K. S. W. Sing, Adsorption,
Surface Area, Porosity, 2nd ed., Academic Press, London, 1982.
 a) S. A. Allison, R. M. Barrer, J. Chem. Soc. A 1969, 1717; b) D.
Ramprasad, G. P. Pez, B. H. Toby, T. J. Markley, R. M. Pearlstein, J.
Am. Chem. Soc. 1995, 117, 10 694; c) M. Kondo, T. Yoshitomi, K. Seki,
H. Matsuzaka, S. Kitagawa, Angew. Chem. 1997, 109, 1844; Angew.
Chem. Int. Ed. Engl. 1997, 36, 1725; d) H. Li, M. Eddaoudi, T. L. Groy,
O. M. Yaghi, J. Am. Chem. Soc. 1998, 120, 8571.
 H. Li, C. E. Davis, T. L. Groy, D. G. Kelley, O. M. Yaghi, J. Am. Chem.
 a) T. M. Reineke, M. Eddaoudi, M. Fehr, D. Kelley, O. M. Yaghi, J.
Figure 5. Room-temperature isotherms for the sorption of liquid alcohols
Am. Chem. Soc. 1998, 121, 1999; b) Lanthanide Probes in Life,
Chemical and Earth Sciences (Eds.: J.-C. G. Bünzli, G. R. Choppin),
3 . Molar ratio of guest to Tb(BDC)NO3 (y) versus
equilibrium concentration of guest (x).
 Elemental analysis (%) calcd for C14H18O9N3Tb: Tb(bdc)(NO3) ´
2DMF: C 31.65, H 3.42, N 7.91; found: C 31.33, H 3.35, N 7.90. FT-
results show that the number of molecules sorbed per formula
IR (KBr, 2000 ± 500 cmÀ1): nÄ 1702 (m), 1663 (vs), 1630 (s), 1591 (vs),
unit decreases as the size of the guest increases, and a similar
1512 (w), 1440 (s), 1400 (vs), 1314 (s), 1255 (w), 1110 (m), 1064 (w),
trend is observed for the association equilibrium constant K
1031 (w), 900 (w), 821 (m), 761 (s), 682 (m), 544 (m), 511 cmÀ1 (s). The
europium analogue of this compound was also prepared by an
(Figure 5). Both of these parameters indicate a size- and
identical procedure and found to have the same composition and
structure as the terbium compound. Elemental analysis (%) calcd for
This study demonstrates that lanthanide carboxylate open
C14H18O9N3Eu: Eu(bdc)(NO3) ´ 2DMF: C 32.07, H 3.46, N 8.01;
frameworks can have sufficient stability to support zeolite-
like microporosity. Current studies are focused on exploring
 An X-ray single-crystal analysis was performed on a colorless
the accessibility of the Lewis acid metal sites within the
sions of 0.07 Â 0.16 Â 0.19 mm at À 115 Æ 18C: monoclinic, space group
channels and the design of analogous frameworks with larger
P21/c, a 17.5986(1), b 19.9964(3), c 10.5454(2) , b 91.283(1)8,
V 3710.09(7) 3, Z 8, 1calcd 1.90 gcmÀ3; m(MoKa) 38.57 mmÀ1.
All measurements were made on a SMART CCD area detector with
graphite-monochromated MoKa radiation. Frames corresponding to
an arbitrary hemisphere of data were collected by w scans of 0.308
counted for a total 10.0 s per frame. Cell constants and an orientation
matrix, obtained from a least-square refinement of the measured
positions of 7766 reflections in the range 3.00 ` 2q ` 45.008 corre-
3 ´ 2 DMF : 1,4-benzenedicarboxylic acid (H2BDC) (0.050 g,
0.30 mmol) and terbium(iii) nitrate pentahydrate (0.131 g, 0.30 mmol)
sponded to a primitive monoclinic cell. Data were integrated by the
were placed in a small vial and dissolved in a mixture of methanol (3 mL)
program SAINT to a maximum 2q value of 49.58 and corrected for
and DMF (3 mL) with mild heating. The vial was then placed in a larger vial
Lorentzian and polarization effects by using XPREP. The data
containing pyridine (4 mL), which was sealed and left undisturbed for 5 d at
were corrected for absorption by comparison of redundant and
room temperature. The resulting colorless block-shaped crystals were
equivalent reflections by using SADABS (Tmax 0.74, Tmin 0.47).
collected by filtration, washed with methanol (3 Â 10 mL), and air dried to
The structure was solved by direct methods. Terbium and oxygen
atoms were refined with anisotropic displacement parameters, and
3 ´ 2 DMF (0.12 g, 73 % yield). The isostructural europium
analogue was prepared by a similar procedure from europium(iii) nitrate
carbon atoms with isotropic parameters. Hydrogen atoms of the
organic ligands were included but not refined. The final cycle of full-
matrix least-squares refinement was based on 3156 observed reflec-
tions (I b 3.00s(I)) and 227 variables and refined to convergence R1
German version: Angew. Chem. 1999, 111, 2712 ± 2716
0.058 (unweighted, based on F)and Rw 0.065. The maximum and
minimum peaks on the final difference Fourier map corresponded to
Keywords: host ± guest chemistry ´ lanthanides ´ micro-
5.19 and À1.87 eÀ À3, respectively. Crystallographic data (excluding
structure factors) for the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC-119758. Copies of the data
can be obtained free of charge on application to CCDC, 12 Union
 a) D. M. L. Goodgame, D. A. Grachvogel, D. J. Williams, Angew.
Road, Cambridge CB21EZ, UK (fax: (44)1223-336-033; e-mail:
Chem. 1999, 111, 217; Angew. Chem. Int. Ed. 1999, 38, 153; b) O. M.
Yaghi, H. Li, C. Davis, D. Richardson, T. L. Groy, Acc. Chem. Res.
 Generation of 3- and (3,4)-connected nets from 4-connected nets: M.
1998, 31, 874; c) J. Lu, T. Paliwala, S. C. Lim, C. Yu, T. Niu, A. J.
OKeeffe, B. G. Hyde, Crystal Structures I: Patterns and Symmetry,
Jacobson, Inorg. Chem. 1997, 36, 923; d) C. Janiak, Angew. Chem. 1997,
Mineralogical Society of America, Washington, DC, 1996, p. 359.
109, 1499; Angew. Chem. Int. Ed. Engl. 1997, 36, 1431; e) P. Losier,
 Elemental analysis (%) calcd for C8H4O7NTb: Tb(bdc)(NO3) C 24.95,
M. J. Zaworotko, Angew. Chem. 1996, 108, 2957; Angew. Chem. Int.
H 1.05, N 3.64; found: C 25.37, H 1.31, N 3.95. FT-IR (KBr, 2000 ±
Ed. Engl. 1996, 35, 2779; f) G. B. Gardner, D. Venkataraman, J. S.
500 cmÀ1): nÄ 1630 (m), 1564 (s), 1512 (m), 1387 (vs), 1320 (w), 1163
Moore, S. Lee, Nature 1995, 374, 792; g) O. Yaghi, G. Li, H. Li, Nature
(w), 1117 (w), 1025 (w), 893 (w), 847 (w), 814 (w), 761 (m), 518 cmÀ1
1995, 378, 703; h) M. Fujita, Y. J. Kwon, O. Sasaki, K. Yamaguchi, K.
(m). When this material is exposed to DMF vapor for 1 d, the original
Ogura, J. Am. Chem. Soc. 1995, 117, 7287; i) L. Carlucci, G. Ciani,
product is regenerated. Elemental analysis (%) calcd for the
D. M. Proserpio, A. Sironi, J. Chem. Soc. Chem. Commun. 1994, 2755;
regenerated product C14H18O9N3Tb: Tb(bdc)(NO3) ´ 2DMF: C 31.65,
j) R. Robson, B. F. Abrahams, S. R. Batteen, R. W. Gable, B. F.
H 3.42, N 7.91; found: C 31.40, H 3.44, N 7.88.
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
 A standard solution containing the same guest concentration was
cally behaves like iodine azide (3b). Since the pioneering
periodically checked with the same techniques employed for each
work of Hassner et al. azido-iodination of alkene double
experiment. To further show that the alcohol guests were included
bonds has become a very useful procedure for introducing a
within the pores rather than on the crystal surface, the GC sample was
filtered, washed with toluene, air dried, and then elemental micro-
nitrogen functionality into a carbon skeleton. Iodine azide
analysis was performed to confirm the presence of alcohol.
(3b) has commonly been generated in situ from sodium azide
 SAX Area-Detector Integration Program (SAINT), V4.024, Siemens
and iodine chloride in polar solvents.[12, 13] However, its
Industrial Automation, Inc., Madison, WI, 1995.
explosive character is regarded to be a major disadvantage.
 XPREP, V 5.03, is part of the program SHELXTL Crystal Structure
Our approach to iodine azide (3b) is based on the reaction
Determination, Siemens Industrial Automation, Inc., Madison, WI,
of (diacetoxyiodo)benzene with polystyrene-bound iodide
 Siemens Area Detector ABSorption correction program (SADABS),
1 in dichloromethane at room temperature, which presum-
G. Sheldrick, personal communication, 1996.
ably afforded polymer-bound di(acetyloxy)iodate(i) (2)
(Scheme 1).[14, 15] Treatment of 2 with trimethylsilylazide
furnished a resin which synthetically acts like immobilized
iodine azide (3b). However, extensive washing of the resin
does not result in deactivation thus we propose that polymer-
bound bis(azido)iodate(i) (3a) is the active species. Reagent
Stable Polymer-Bound Iodine Azide**Andreas Kirschning,* Holger Monenschein, and
In addition to numerous methods for the syntheses of
organic molecules on polymeric supports, there has been a
recent upsurge in the interest in the use of polymer-bound
reagents in organic chemistry. The intrinsic advantage of this
hybrid solid-/solution-phase technique lies in the simple work-
up and isolation of the reaction products combined with the
Scheme 1. Preperation of novel polymer-bound iodine azide.
flexibility of solution-phase chemistry. Furthermore, these
reagents may be used in excess in order to drive the reaction
to completion without making the isolation of the products
3a may also be generated by direct azido transfer after
more difficult. Although stoichometric polymer-supported
treatment of iodide 1 with (diazidoiodo)benzene. However, as
reagents have been employed in organic synthesis for many
PhI(N3)2 has to be prepared in situ from (diacetoxyiodo)ben-
years, their application to the construction of small molecule
zene and trimethylsilylazide efficient azido transfer to 1 is
libraries is a relative recent phenomenon. This can be ascribed
hampered by the presence of trimethylsilyl acetate in solution.
to the fact that the number of readily available reagents of this
The IR spectrum of the new polymer 3a shows a pair of strong
type is still small. Important developments in this field are
bands at nÄ 2010 and 1943 cmÀ1, which confirm the presence
polymer-supported reductants, oxidants, solution-phase
of an azido group. It smoothly promotes azido-iodination of
scavengers, chelating proton donors, carbodimide equiv-
alkenes 4 ± 18 to give the anti addition product (Table 1).
alents, or reagents that are capable of promoting CÀC bond-
Except for electron-defficient alkenes 5 and 11 and for
forming reactions. However, polymer-bound reagents for
methylenecyclopropane 17 (Table 1), sensitive b-iodo azides
1,2-cohalogentions[8, 9] of alkenes have not been described so
19, 21 ± 25, and 27 ± 33 are generated in good to excellent
yield. They are conveniently purified by filtration and
As an extension of our earlier work on ligand-transfer
removal of the solvent. The regioselectivity of the 1,2-
reactions from hypervalent iodine(iii) reagents to halides in
addition is governed by the more stable intermediate carben-
solution, we initiated a study on the development of the
ium ion formed after electrophilic attack. Only when alkyl-
first stable electrophilic polymer-bound reagent that syntheti-
substituted alkenes 15 and 16 were subjected to the azido-
iodination conditions, were small amounts of the anti-
Markovnikov 1,2-adducts formed. Remarkably, free hydroxy
groups in allyl or homoallyl position, such as in alkenes 7, 13,
Institut für Organische Chemie der Technische Universität Clausthal
Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld (Germany)
and 14, are tolerated under the conditions employed. Addi-
tion to methylenecyclopropane 17 proceeded in a highly
regioselective and stereoselective manner to furnish 32.
Rearrangement products which may have originated from
Bayer AG, Business Group Pharma PH-R-CR, D-42096 Wuppertal
the very stable intermediate cyclopropylmethyl cation were
not isolated. The relative configuration of 32 was uneqivocally
[**] This work was supported by the Fonds der Chemischen Industrie. We
thank Bayer AG and particularly Dr. D. Häbich (Wuppertal) for
assigned by nuclear Overhauser effect (NOE) experiments
(Table 2). Finally, also 1,2-functionalization of carbohydrate-
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
Learning To Read without a Teacher: A Case Study* This chapter is the story of John, middle child in a black family of five, son of a trucker and a hospital maid, living in subsidized housing in a crowded southern city. According to most predictions, John should have reading problems all through his school career. But John is one of the thousands of children who somehow learn to read in mu
Tips für das Club 41 International AGM in Lusaka /Sambia Herewith a few titbits about Lusaka, where this year's AGM will be held. Favour us with your fellowship through registration now. 41er Steve MwansaREGISTRATION CONVENOR 41 CLUBS ZAMBIA 2010 AGM LUSAKA Lusaka, the capital city of Zambia, is located on a limestone plateau 4,198 feet (1,280 meters) above sea level. It lies at the juncti