Selective catalytic hydrodefluorination as a key step for the synthesis of hitherto inaccessible aminopyridine derivatives

Article abstract of DOI:10.1002/anie.201301927

Fluorine makes it possible! The regioselective nucleophilic substitution of (oligo)fluoropyridines with the appropriate amines and the subsequent catalytic hydrodefluorination paves the way to hitherto inaccessible aminopyridine derivatives, which are of interest as new ligands. Up to four fluorine atoms can be removed regioselectively in one step in a reaction employing an inexpensive titanium precatalyst. Copyright

Full text of DOI:10.1002/anie.201301927

Angewandte
Chemie
DOI: 10.1002/anie.201301927
Hydrodefluorination
Selective Catalytic Hydrodefluorination as a Key Step for the Synthesis
of Hitherto Inaccessible Aminopyridine Derivatives**
Gabriel Podolan, Dieter Lentz,* and Hans-Ulrich Reissig*
Dedicated to the Bayer company on the occasion of its 150th anniversary
À
À
The synthesis of specifically substituted pyridines is a perma-
nent challenge since new derivatives of this class of hetero-
cycles are required as building blocks for supramolecular
chemistry, as components of new materials, and also in
quent conversion of C F into C H bonds by catalytic
hydrodefluorination (HDF).[8,9] The strong electron-with-
drawing effect of the fluorine substituents in fluorinated
pyridine derivatives allows the selective substitution of
fluoride by nucleophiles at the 4- or 2-/6-positions of the
heterocyclic ring.[7] Hence 4-aminopyridine derivatives with
additional fluorine substituents on the ring are easily acces-
sible[10] and serve as potential precursors for compounds such
as 2 and 3. The catalytic hydrodefluorination (HDF), that is,
pharmaceutical
science.[1]
4-(Dimethylamino)pyridine
(DMAP) (1) is a frequently used basic catalyst in many
important synthetic transformations,[2] but it also strongly
stabilizes nanoparticles by coordination of the Lewis basic
nitrogen to the metal surface.[3] Due to our interest in
multivalent ligands[4] we set out to synthesize divalent
À
À
the conversion of C F into C H bonds, has been extensively
studied;[8] however, due to the high cost of most reagents and
catalysts as well as limitations in the substrate scope it is
scarcely used for synthetic applications.[9] Our synthetic
strategy to prepare hitherto inaccessible aminopyridine
derivatives used the detour employing the nucleophilic
analogues of 1, in particular, compounds
2 and 3
(Scheme 1).[5] Whereas compound 2 was available in moder-
À
aromatic substitution to create the C N bond followed by
catalytic HDF. For this purpose we used the [Cp2TiF2]/
diphenylsilane system, recently developed for the defluori-
nation of fluoroalkenes.[11,12]
Scheme 1. DMAP 1, divalent BiDMAP 2, and cyclic divalent BiDMAP 3.
To prove the viability of the catalytic HDF of fluorinated
aminopyridines, we used 2,3,5,6-tetrafluoro-4-morpholino-
pyridine (4) as a model substrate in 1,4-dioxane as the solvent
(Scheme 2). Under optimized conditions at temperatures
ate yield by the nucleophilic substitution of 4-chloropyridine
employing the appropriate diamine, the chiral divalent
compound 3 with a more rigid backbone could not be
prepared. Neither were the nucleophilic substitutions of 4-
halopyridines with trans-1,2-diaminocyclohexane in the pres-
ence or absence of palladium catalysts successful,[6] nor were
reactions with 4-(methylamino)pyridine as the nucleophile in
its reactions with difunctionalized cyclohexane derivatives.[5]
The high steric hindrance seems to hamper these substitution
reactions.
Thus we developed a new synthetic strategy for the
preparation of 3 based on two key reactions: nucleophilic
substitution of the (oligo)fluorinated pyridines[7] and subse-
Scheme 2. Regioselective catalytic hydrodefluorination of model sub-
strates 4 and 5.
between 90 to 1108C with 15 mol% of the precatalyst we
obtained the twofold hydrodefluorinated product 6 in 95%
yield. These conditions allow the regioselective substitution of
the more reactive fluorine atoms at C-2 and C-6.[7] Lower
loadings of the precatalyst did not lead to full conversion.
Interestingly, the use of 1,2-dimethoxyethane as a solvent led
to a decrease of the reaction rate; a reaction time of 96 h was
necessary to obtain a similar yield of 92%. Higher catalyst
loadings apparently caused decomposition of precursor 4 or
of the possible intermediates, and the completely hydro-
defluorinated 4-morpholinopyridine (7) could not be
detected. To demonstrate that the “inert” fluorine atoms at
C-3 and C-5 of 4 are not required for a successful HDF, we
also examined 2,6-difluoro-4-morpholinopyridine (5) under
[*] Dr. G. Podolan, Prof. Dr. D. Lentz, Prof. Dr. H.-U. Reissig
Institut fꢀr Chemie und Biochemie
Freie Universitꢁt Berlin
Takustrasse 3, 14195 Berlin (Germany)
E-mail: dieter.lentz@fu-berlin.de
hans.reissig@chemie.fu-berlin.de
[**] Support of this work by the Deutsche Forschungsgemeinschaft
(SFB 765 “Multivalency”, GRK 1582 “Fluorine as Key Element” and
Le 423/17-1) and Bayer HealthCare is most gratefully acknowl-
edged. We also thank Dr. Moritz F. Kꢀhnel for experimental advice
and helpful discussions and V. Rojek for preliminary experiments.
Furthermore, we thank P. Jungk for his help in preparing the starting
materials.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201301927.
Angew. Chem. Int. Ed. 2013, 52, 9491 –9494
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
9491

.
Angewandte
Communications
the optimized reaction conditions. The expected 4-morpho-
linopyridine (7) was isolated in excellent yield, thus demon-
strating the feasibility of the developed method for the
synthesis of entirely defluorinated aminopyridine derivatives.
After establishing efficient conditions for the HDF of
simple aminopyridine derivatives, we extended the method to
other oligofluorinated pyridine derivatives. The bis(amino-
tetrafluoroaminopyridine) derivatives 8 and 10 bearing differ-
ent spacer moieties were readily available by nucleophilic
substitution of pentafluoropyridine with the corresponding
diamines. The substitution occurred with high selectivity at
the 4-position of the pyridine ring. The catalytic HDF was
executed with 30 mol% of the precatalyst since two pyridine
rings were involved. The expected products 9 and 11 were
obtained regioselectively in good yields (Scheme 3).
regioisomers 16, 18, and 20 were easily separable by column
chromatography. Apparently, the regioselectivity of the
nucleophilic substitution is strongly dependent on the steric
hindrance of the attacking nitrogen atom.
We tried to methylate NH groups of 20 by reductive
alkylation with formaldehyde, but surprisingly obtained the
bicyclic compound 21. However, by deprotonation of 20 with
sodium hydride and subsequent reaction with methyl iodide
the desired precursor 19 for the catalytic HDF could be
prepared in good yield (Scheme 5).
Scheme 5. N-Alkylations of aminopyridine 20 to 21 and 19.
With the bis(2,6-difluoropyridyl) compounds 22 (synthesis
described in the Supporting Information), 20, 21, and 19 we
performed the catalytic HDF under standard conditions (i.e.
7.5 mol% of precatalyst per fluorine substituent): the sub-
strates were converted into divalent DMPA analogues 2, 23,
24, and 3 in excellent yields of 85–92% (Scheme 6). The
synthesis of the long-awaited compound 3 in racemic and
enantiomerically pure form (R,R enantiomer) should be
emphasized here.
Scheme 3. Regioselective HDF of divalent pyridine derivatives 8 and 10
(compounds 10 and 11 are racemic mixtures).
Whereas the nucleophilic substitution of pentafluoropyr-
idine occurs regioselectively at C-4, the reaction of 2,4,6-
trifluoropyridine as the electrophile shows a surprising
dependency on the degree of substitution of the nitrogen
atoms of trans-1,2-diaminocyclohexane. The bis(N-methyl)-
substituted compound 12 furnished the desired product 19 in
only 1% yield (as result of a twofold substitution at C-4), but
the two regioisomers 15 and 17 were isolated in yields of 12%
and 7%, respectively (Scheme 4). The C-4/C-4 disubstitution
reaction of the primary diamine 13 (used as a racemic mixture
or as the R,R enantiomer) proceeded more efficiently leading
to the desired compound 20 at least in 30% yield. The three
Scheme 4. Nucleophilic substitutions of trans-1,2-diaminocyclohexane
derivatives 12 and 13 with 2,4,6-trifluoropyridine.
Scheme 6. Catalytic HDF of pyridine derivatives 22, 20, 21, and 19
leading to divalent DMAP analogues 2, 23, 24, and 3.
9492 www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 9491 –9494

Angewandte
Chemie
2008, 3408 – 3410; i) W. Aida, W. Ohtsuki, M. Ishibashi, Tetrahe-
Mechanistic studies of the HDF of fluoroalkenes indicate
that a titanium(III) hydride is the catalytically active species.
On reaction with the substrate, biscyclopentadienylfluorido-
titanium(III) is formed and subsequently retransformed to
the hydride by reaction with the silane.[11b,c] The HDF step has
been suggested to proceed by an insertion/b-fluoride elimi-
nation mechanism or by a s-bond metathesis mechanism.
However, given the considerable differences between pyri-
dine derivatives and alkenes as well as the entirely different
reaction conditions, it is possible that other species and
mechanisms are involved.
dron 2009, 65, 369 – 373; j) T. Lechel, J. Dash, P. Hommes, D.
Lentz, H.-U. Reissig, J. Org. Chem. 2010, 75, 726 – 732; k) M.
Ohashi, I. Takeda, M. Ikawa, S. Ogoshi, J. Am. Chem. Soc. 2011,
133, 18018 – 18021; l) C. Eidamshaus, H.-U. Reissig, Eur. J. Org.
Chem. 2011, 6056 – 6069; m) C. Lau, G. C. Tsui, M. Lautens,
Synthesis 2011, 3908 – 3914; n) S. Yamamoto, K. Okamoto, M.
Murakoso, Y. Kuninobu, K. Takai, Org. Lett. 2012, 14, 3182 –
3185; o) R. M. Martin, R. G. Bergman, J. A. Ellman, J. Org.
Chem. 2012, 77, 2501 – 2507. New reviews: p) M. D. Hill, Chem.
Eur. J. 2010, 16, 12052 – 12062; q) T. Lechel, H.-U. Reissig, Pure
Appl. Chem. 2010, 82, 1835 – 1845.
[2] a) Review: G. Hçfle, W. Steglich, H. Vorbrꢃggen, Angew. Chem.
1978, 90, 602 – 615; Angew. Chem. Int. Ed. Engl. 1978, 17, 569 –
583; New studies to DMAP analogues: b) S. Xu, I. Held, B.
Kempf, H. Mayr, W. Steglich, H. Zipse, Chem. Eur. J. 2005, 11,
4751 – 4757; c) I. Held, S. Xu, H. Zipse, Synthesis 2007, 1185 –
1196; d) F. Brotzel, B. Kempf, T. Singer, H. Zipse, H. Mayr,
Chem. Eur. J. 2007, 13, 336 – 345; e) N. D. Rycke, G. Berionni, F.
Couty, H. Mayr, R. Goumont, O. R. P. David, Org. Lett. 2011, 13,
530 – 533; f) N. De Rycke, F. Couty, O. R. P. David, Chem. Eur. J.
2011, 17, 12852 – 12871; g) C. Lindner, R. Tandon, B. Maryasin,
E. Larionov, H. Zipse, Beilstein J. Org. Chem. 2012, 8, 1406 –
1442.
[3] Reports on gold nanoparticles: a) D. Gittins, F. Caruso, Angew.
Chem. 2001, 113, 3089 – 3092; Angew. Chem. Int. Ed. 2001, 40,
3001 – 3004; b) V. Gandubert, R. Lennox, Langmuir 2005, 21,
6532 – 6539.
[4] a) H. Wang, Y. Koshi, D. Minato, H. Nonaka, S. Kiyonaka, Y.
Mori, S. Tsukiji, I. Hamachi, J. Am. Chem. Soc. 2011, 133,
12220 – 12228; b) C. Fasting, C. A. Schalley, M. Weber, O. Seitz,
S. Hecht, B. Koksch, J. Dernedde, C. Graf, E.-W. Knapp, R.
Haag, Angew. Chem. 2012, 124, 10622 – 10650; Angew. Chem.
Int. Ed. 2012, 51, 10472 – 10498.
In conclusion, we have demonstrated that the combina-
tion of nucleophilic aromatic substitution of (oligo)fluori-
nated pyridines with a catalytic HDF offers excellent
opportunities for the preparation of hitherto inaccessible
aminopyridine derivatives. In the nucleophilic substitution
the fluoro substituents act as activating and as leaving groups,
but in the crucial HDF step they were regioselectively
À
removed despite the strength of the C F bond of approx-
imately 500 kJmolÀ1.[13] This key reaction proceeds without
expensive catalysts. Compounds such as the enantiomerically
pure DMPA analogue 3 should have interesting properties as
Lewis bases or as chiral ligands.[14] Our HDF method should
also allow the preparation of fluoro-substituted pharmaceut-
icals[15] and should be of interest in the context of recently
[16]
À
À
developed methods for C C couplings with C F bonds.
Experimental Section
Typical procedure for the titanium-induced HDF of pyridine deriv-
ative 4: 2,3,5,6-Tetrafluoro-4-morpholinopyridine (4) (50 mg,
0.21 mmol), titanocene difluoride (7 mg, 0.032 mmol, 15 mol%),
diphenylsilane (0.235 mL, 1.27 mmol, 6 equiv, distilled from CaH2),
and anhydrous 1,4-dioxane (2 mL) were placed in a single-necked
Schlenk flask equipped with a Young tap. The resulting mixture was
subsequently degassed by repeated freeze–pump–thaw cycles. The
mixture was briefly heated with a heat gun until the color changed
from yellow to dark-brown and the solution was then stirred for 1 d at
1108C. The reaction was quenched with MeOH (2 mL) and water
(20 mL) was added. Extraction with Et2O (3 ꢀ 30 mL), drying with
Na2SO4, filtration, and concentration furnished the crude product.
Purification by flash column chromatography (ethyl acetate/hexanes
1:4 to 1:1) gave compound 6 as a colorless solid (40 mg, 95%, mp 56–
588C).
[5] M. Taszarek, PhD Dissertation, Freie Universitꢄt Berlin, 2011.
[6] a) J. P. Wolfe, S. Wagaw, J. F. Marcoux, S. L. Buchwald, Acc.
Chem. Res. 1998, 31, 805 – 818; b) J. F. Hartwig, M. Koley, Acc.
Chem. Res. 1998, 31, 852 – 860; c) K. W. Anderson, M. Mendez-
Perez, J. Priego, S. L. Buchwald, J. Org. Chem. 2003, 68, 9563 –
9573.
[7] a) L. Estel, F. Marsais, G. Queguiner, J. Org. Chem. 1988, 53,
2740 – 2744; b) H. Benmansour, R. D. Chambers, P. R. Hoskin,
G. Sandford, J. Fluorine Chem. 2001, 112, 133 – 137; c) R. D.
Chambers, M. A. Hassan, P. R. Hoskin, A. Kenwright, P.
Richmond, G. Sandford, J. Fluorine Chem. 2001, 111, 135 –
146; d) R. D. Chambers, P. R. Hoskin, G. Sandford, D. S. Yufit,
J. A. K. Howard, J. Chem. Soc. Perkin Trans. 1 2001, 2788 – 2795;
e) G. Sandford, R. Slater, D. S. Yufit, J. A. K. Howard, A. Vong,
J. Org. Chem. 2005, 70, 7208 – 7216; f) A. Baron, G. Sandford, R.
Slater, D. S. Yufit, J. A. K. Howard, A. Vong, J. Org. Chem. 2005,
70, 9377 – 9381; g) J. A. Christopher, L. Brophy, S. M. Lynn,
D. D. Miller, L. A. Sloan, G. Sandford, J. Fluorine Chem. 2008,
129, 447 – 454; h) R. Ranjbar-Karimi, M. Mashak-Shoshtari, S.
Hashemi-Uderji, R. Kia, J. Fluorine Chem. 2011, 132, 285 – 290.
[8] Reviews: a) J. L. Kiplinger, T. G. Richmond, C. E. Osterberg,
Chem. Rev. 1994, 94, 373 – 431; b) J. Burdeniuc, B. Jedlicka, R. H.
Crabtree, Chem. Ber. 1997, 130, 145 – 154; c) T. G. Richmond in
Activation of Unreactive Bonds and Organic Synthesis, Vol. 3
(Ed.: S. Murai), Springer, New York, 1999, pp. 243 – 269; d) T.
Braun, R. N. Perutz, Chem. Commun. 2002, 2749 – 2757; e) W. D.
Jones, Dalton Trans. 2003, 3991 – 3995; f) H. Torrens, Coord.
Chem. Rev. 2005, 249, 1957 – 1985; g) R. N. Perutz, T. Braun,
Comprehensive Organometallic Chemistry III (Eds.: R. H.
Crabtree, D. M. P. Mingos), Elsevier, Oxford, 2007, pp. 725 –
758; h) V. D. Shteingarts, J. Fluorine Chem. 2007, 128, 797 –
805; i) H. Amii, K. Uneyama, Chem. Rev. 2009, 109, 2119 –
2183; j) T. Braun, F. Wehmeier, Eur. J. Inorg. Chem. 2011,
Received: March 7, 2013
Published online: May 9, 2013
Keywords: catalysis · fluorine · hydrodefluorination · pyridine ·
.
titanium catalysts
[1] Selected publications: a) M. Altuna-Urquijo, S. P. Stanforth, B.
Tarbit, Tetrahedron Lett. 2005, 46, 6111 – 6113; b) J. Dash, T.
Lechel, H.-U. Reissig, Org. Lett. 2007, 9, 5541 – 5544; c) M.
Movassaghi, M. D. Hill, O. K. Ahmad, J. Am. Chem. Soc. 2007,
129, 10096 – 10097; d) J. Barluenga, A. J. Aquino, M. A. Fernꢁn-
dez, F. Aznar, C. Valdꢂs, Tetrahedron 2008, 64, 778 – 786; e) S.
Cacchi, G. Fabrizi, E. Filisti, Org. Lett. 2008, 10, 2629 – 2632; f) S.
Liu, L. S. Liebeskind, J. Am. Chem. Soc. 2008, 130, 6918 – 6919;
g) J. R. Manning, H. M. L. Davies, J. Am. Chem. Soc. 2008, 130,
8602 – 8603; h) D. Craig, F. Paina, S. C. Smith, Chem. Commun.
Angew. Chem. Int. Ed. 2013, 52, 9491 –9494
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 9493

.
Angewandte
Communications
613 – 625; k) J.-F. Paquin, Synlett 2011, 289 – 293; l) E. Clot, O.
Eisenstein, N. Jasim, S. A. Macgregor, J. E. McGrady, R. N.
Perutz, Acc. Chem. Res. 2011, 44, 333 – 348; m) S. A. Johnson,
J. A. Hatnean, M. E. Doster, Prog. Inorg. Chem., Vol. 57 (Ed.:
K. D. Karlin), Wiley, Hoboken, 2012, pp. 255 – 352; n) A. Nova,
R. Mas-Ballestꢂ, A. Lledꢅs, Organometallics 2012, 31, 1245 –
1256; o) M. Klahn, U. Rosenthal, Organometallics 2012, 31,
1235 – 1244; p) M. F. Kꢃhnel, D. Lentz, T. Braun, Angew. Chem.
2013, 125, 3412 – 3433; Angew. Chem. Int. Ed. 2013, 52, 3328 –
3348.
[10] a) R. Ranjbar-Karimi, M. Mousavi, J. Fluorine Chem. 2010, 131,
587 – 591; b) P. Jungk, Masters Thesis, Freie Universitꢄt Berlin,
2011; c) R. Ranjbar-Karimi, M. Mashak-Shoshtari, A. Dare-
hkordi, Ultrasonics 2011, 18, 258 – 263.
[11] a) M. F. Kꢃhnel, D. Lentz, Angew. Chem. 2010, 122, 2995 – 2998;
Angew. Chem. Int. Ed. 2010, 49, 2933 – 2936; b) M. F. Kꢃhnel,
PhD Dissertation, Freie Universitꢄt Berlin, 2011; c) M. F.
Kꢃhnel, P. Holstein, M. Kliche, J. Krꢃger, S. Matthies, D.
Nitsch, J. Schutt, M. Sparenberg, D. Lentz, Chem. Eur. J. 2012,
18, 10701 – 10714.
[9] Selected original reports: a) M. Aizenberg, D. Milstein, Science
1994, 265, 359 – 361; b) J. L. Kiplinger, T. G. Richmond, Chem.
Commun. 1996, 1115 – 1116; c) B.-H. Kim, H.-G. Woo, W.-G.
Kim, S.-S. Youn, T.-S. Hwang, Bull. Korean Chem. Soc. 2000, 21,
211 – 214; d) J. Vela, J. M. Smith, Y. Yu, N. A. Ketterer, C. J.
Flaschenriem, R. J. Lachicotte, P. L. Holland, J. Am. Chem. Soc.
2005, 127, 7857 – 7870; e) U. J. Fiedler, M. Klahn, P. Arndt, W.
Baumann, A. Spannenberg, V. V. Burlakov, U. Rosenthal, J.
Mol. Catal. A 2007, 261, 184 – 189; f) K. Fuchibe, Y. Ohshima, K.
Mitomi, T. Akiyama, J. Fluorine Chem. 2007, 128, 1158 – 1167;
g) T. Braun, D. Noveski, M. Ahijado, F. Wehmeier, Dalton Trans.
2007, 3820 – 3825; h) C. Douvris, O. V. Ozerov, Science 2008, 321,
1188 – 1190; i) S. P. Reade, M. F. Mahon, M. K. Whittlesey, J.
Am. Chem. Soc. 2009, 131, 1847 – 1861; j) D. Breyer, T. Braun, A.
Penner, Dalton Trans. 2010, 39, 7513 – 7520; k) S. A. Prihodko,
N. Y. Adonin, V. N. Parmon, Tetrahedron Lett. 2010, 51, 2265 –
2268; l) J. A. Panetier, S. A. Macgregor, M. K. Whittlesey,
Angew. Chem. 2011, 123, 2835 – 2838; Angew. Chem. Int. Ed.
2011, 50, 2783 – 2786; m) J. Wu, S. Cao, ChemCatChem 2011, 3,
1582 – 1586; n) C. B. Caputo, D. W. Stephan, Organometallics
2012, 31, 27 – 30 o) W. Zhao, J. Wu, S. Cao, Adv. Synth. Catal.
2012, 354, 574 – 578; p) Y. Sawama, Y. Yabe, M. Shigetsura, T.
Yamada, S. Nagata, Y. Fujiwara, T. Maegawa, Y. Monguchi, H.
Sajiki, Adv. Synth. Catal. 2012, 354, 777 – 782; q) P. Fischer, K.
Gçtz, A. Eichhorn, U. Radius, Organometallics 2012, 31, 1374 –
1383; r) G. A. Selivanova, A. V. Reshetov, I. V. Beregovaya,
[12] Experiments to reduce fluorinated aminopyridine derivatives
with stoichiometric amounts of LiAlH4 were completely unse-
lective (Ref. [10b]), also see: R. D. Chambers, C. W. Hall, J.
Hutchinson, R. W. Millar, J. Chem. Soc. Perkin Trans. 1 1998,
1705 – 1713.
[13] Y.-R. Luo, Comprehensive Handbook of Chemical Bond Ener-
gies, CRC, Boca Raton, 2007.
[14] For chiral DMAP analogues, see: E. Larionov, M. Mahesh, A. C.
Spivey, Y. Wei, H. Zipse, J. Am. Chem. Soc. 2012, 134, 9390 –
9399 and references therein.
[15] Selected reviews: a) T. Hiyama, Organofluorine Compounds,
Springer, Berlin, 2000; b) P. Kirsch, Modern Fluoroorganic
Chemistry: Synthesis Reactivity, Applications, Wiley-VCH,
Weinheim, 2004; c) P. Jeschke, ChemBioChem 2004, 5, 570 –
589; d) V. A. Soloshonok in ACS Symp. Ser., Vol. 911, American
Chemical Society, Washington, DC, 2005; e) K. Uneyama,
Organofluorine Chemistry, Blackwell, Oxford, 2006; f) K.
Mꢃller, C. Faeh, F. Diederich, Science 2007, 317, 1881 – 1886;
g) J.-P. Bꢂguꢂ, D. Bonnet-Delpon, Bioorganic and Medicinal
Chemistry of Fluorine, Wiley, Hoboken, 2007; h) S. Purser, P. R.
Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 2008, 37,
320 – 330; i) W. K. Hagmann, J. Med. Chem. 2008, 51, 4359 –
4369; j) D. OꢆHagan, J. Fluorine Chem. 2010, 131, 1071 – 1081.
[16] Selected new publications: a) T. Schaub, M. Backers, U. Radius,
J. Am. Chem. Soc. 2006, 128, 15964 – 15965; b) A. D. Sun, J. A.
Love, Org. Lett. 2011, 13, 2750 – 2753; c) M. Tobisu, T. Xu, T.
Shimasaki, N. Chatani, J. Am. Chem. Soc. 2011, 133, 19505 –
19511; d) D. Yu, Q. Shen, L. Lu, J. Org. Chem. 2012, 77, 1798 –
1804; e) Y. Nakamura, N. Yoshikai, L. Ilies, E. Nakamura, Org.
Lett. 2012, 14, 3316 – 3319; f) M. D. Breyer, T. Braun, P. Klꢄring,
Organometallics 2012, 31, 1417 – 1424.
ˇ
N. V. Vasileva, I. Y. Bagryanskaya, V. D. Shteingarts, J. Fluorine
Chem. 2012, 137, 64 – 72; s) S. Yow, S. J. Gates, A. J. P. White,
M. R. Crimmin, Angew. Chem. 2012, 124, 12727 – 12731; Angew.
Chem. Int. Ed. 2012, 51, 12559 – 12563; t) H. Lv, V.-B. Cai,
Angew. Chem. 2013, 125, 3285 – 3289; Angew. Chem. Int. Ed.
2013, 52, 3203 – 3207.
9494 www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 9491 –9494