Palladium-catalyzed direct arylations, alkenylations, and benzylations through C-H bond cleavages with sulfamates or phosphates as electrophiles

Article abstract of DOI:10.1021/ol9028034

(Figure Presented) catalytic system comprised of Pd(OAc)₂ and bldentate ligand dppe enabled first direct arylatlons with moisture-stable aryl sulfamates as electrophlles, and proved applicable to unprecedented C-H bond functlonallzations with e

Full text of DOI:10.1021/ol9028034

ORGANIC
LETTERS
2010
Vol. 12, No. 4
724-726
Palladium-Catalyzed Direct Arylations,
Alkenylations, and Benzylations through
C-H Bond Cleavages with Sulfamates
or Phosphates as Electrophiles
Lutz Ackermann,* Sebastian Barfu¨sser, and Jola Pospech
Institut fuer Organische und Biomolekulare Chemie, Georg-August-UniVersitaet,
Tammannstrasse 2, 37077 Goettingen, Germany
lutz.ackermann@chemie.uni-goettingen.de
Received December 4, 2009
ABSTRACT
A catalytic system comprised of Pd(OAc)2 and bidentate ligand dppe enabled first direct arylations with moisture-stable aryl sulfamates as electrophiles,
and proved applicable to unprecedented C-H bond functionalizations with easily accessible alkenyl phosphates as well as benzyl phosphates.
Transition metal-catalyzed direct C(sp2)-C(sp2) bond forma-
tions through C-H bond cleavages are environmentally and
economically sound alternatives to traditional cross-coupling
reactions between organic electrophiles and stoichiometric
amounts of organometallic nucleophiles.1 Particularly, methods
that enable the use of simple (hetero)arenes as surrogates for
preactivated organometallic reagents enable a reduction of
byproduct formation as well as an overall streamlining of
organic synthesis. Until recently, rather expensive and/or
moisture-sensitive aryl iodides, bromides, and triflates or
iodonium salts were largely employed as arylating reagents for
these C-H bond functionalizations. However, significant recent
progress was achieved through the development of catalytic
systems that proved generally applicable to more convenient
electrophiles, such as aryl chlorides,2 tosylates,3,4 or mesylates,4
as well as to phenols5 as proelectrophiles. Unfortunately,
transformations with these (pseudo)halides continue to be
challenging because of the inherent high strength of their
C-Cl or C-OR bonds.
(1) Select recent reviews: (a) Ackermann, L.; Vicente, R.; Kapdi, A.
Angew. Chem., Int. Ed 2009, 48, 9792–9826. (b) Chen, X.; Engle, K. M.;
Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48, 5094–5115. (c)
Thansandote, P.; Lautens, M. Chem.sEur. J. 2009, 15, 5874–5883. (d)
Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc. Chem. Res. 2009, 42, 1074–
1086. (e) Kakiuchi, F.; Kochi, T. Synthesis 2008, 3013–3039. (f) Li, B.-J.;
Yang, S.-D.; Shi, Z.-J. Synlett 2008, 949–957. (g) Lewis, J. C.; Bergman,
R. G.; Ellman, J. A. Acc. Chem. Res. 2008, 41, 1013–1025. (h) Satoh, T.;
Miura, M. Chem. Lett. 2007, 36, 200–205. (i) Alberico, D.; Scott, M. E.;
Lautens, M. Chem. ReV. 2007, 107, 174–238. (j) Seregin, I. V.; Gevorgyan,
V. Chem. Soc. ReV. 2007, 36, 1173–1193. (k) Pascual, S.; de Mendoza, P.;
Echavarren, A. M. Org. Biomol. Chem. 2007, 5, 2727–2734. (l) Campeau,
L.-C.; Stuart, D. R.; Fagnou, K. Aldrichim. Acta 2007, 40, 35–41. (m)
Ackermann, L. Synlett 2007, 507–526.
(2) For representative examples of intermolecular direct arylations with
aryl chlorides, see: (a) Ackermann, L. Org. Lett. 2005, 7, 3123–3125. (b)
Campeau, L.-C.; Parisien, M.; Jean, A.; Fagnou, K. J. Am. Chem. Soc. 2006,
128, 581–590. (c) Lafrance, M.; Rowley, C. N.; Woo, T. K.; Fagnou, K.
J. Am. Chem. Soc. 2006, 128, 8754–8756. (d) Ackermann, L.; Born, R.;
Spatz, J. H.; Althammer, A.; Gschrei, C. J. Pure Appl. Chem. 2006, 78,
209–214. (e) Chiong, H. A.; Daugulis, O. Org. Lett. 2007, 9, 1449–1451.
´
(f) Ackermann, L.; Born, R.; Alvarez-Bercedo, P. Angew. Chem., Int. Ed.
2007, 46, 6364–6367. (g) Chiong, H. A.; Pham, Q.-N.; Daugulis, O. J. Am.
Chem. Soc. 2007, 129, 9879–9884. (h) Ackermann, L.; Vicente, R.; Born,
R. AdV. Synth. Catal. 2008, 350, 741–748. (i) Ackermann, L.; Born, R.;
Vicente, R. ChemSusChem 2009, 546–549.
10.1021/ol9028034  2010 American Chemical Society
Published on Web 01/15/2010

Recently, Albaneze-Walker and co-workers reported aryl
sulfamates to be viable coupling partners for conventional
Suzuki-Miyaura or Negishi cross-coupling reactions with
stoichiometric amounts of preactivated boron- or zinc-based
nucleophiles, respectively.6 Considering the moisture-stable
nature of the imidazolylsulfonates, along with the self-destruc-
tive, thus nongenotoxic, properties of the cross-coupling byprod-
uct imidazolesulfonic acid, we probed C-H bond functional-
izations with these user-friendly electrophiles. As a result of
these efforts, we wish to report herein on first direct arylations
of heteroarenes1j,7,8 with convenient imidazolylsulfonates as
arylating reagents. Additionally, we found that the optimized
palladium(0) catalyst also allowed for direct C-H bond
functionalizations with easily accessible benzyl and alkenyl
phosphates9 as electrophilic coupling partners.
from an aryl-substituted phosphine displayed a superior
catalytic efficacy (entry 7), which could be further improved
when employing bidentate ligands (entries 8-12). Among
a variety of bidentate phosphine ligands, dppe gave rise to
optimal results, particularly when using Cs2CO3 as base and
NMP as solvent (entry 16).10 It is noteworthy that satisfactory
isolated yields were also obtained with PdCl2 as a less
expensive metal precursor (entry 17).
Subsequently, we explored the scope of the optimized
catalytic system in direct arylations of benzoxazoles 1 with
differently substituted imidazolylsulfonates 2 (Scheme 1).
Scheme 1. Direct Arylation with Imidazolylsulfonates 2
At the outset of our studies, we tested representative
ligands for the palladium-catalyzed direct arylation of
benzoxazole (1a) with imidazolylsulfonate 2a (Table 1).
Table 1. Optimization of Direct Arylation with Sulfamate 2aa
entry
L
base
solvent
yield, %
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
-
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
PhMe
DMSO
NMP
NMP
<5c
<5c
<5c
<5c
<5c
<5c
35
41
54
59
61
HIMesClb
HIPrClb
SHIPrClb
b
PCy3
X-Phosb
b
PPh3
Remarkably, the catalyst turned out to be broadly applicable,
and hence enabled the efficient conversion of electron-
dppf
Xantphos
rac-BINAP
dppp
dppe
dppe
dppe
dppe
dppe
dppe
(6) (a) Albaneze-Walker, J.; Raju, R.; Vance, J. A.; Goodman, A. J.;
Reeder, M. R.; Liao, J.; Maust, M. T.; Irish, P. A.; Espino, P.; Andrews,
D. R. Org. Lett. 2009, 11, 1463–1466. For related recent studies, see: (b)
Luo, Y.; Wu, J. Organometallics 2009, 28, 6823–6826. (c) Goegsig, T. M.;
Lindhardt, A. T.; Skrydstrup, T. Org. Lett. 2009, 11, 4886–4888. (d)
Quasdorf, K. W.; Riener, M.; Petrova, K. V.; Garg, N. K. J. Am. Chem.
Soc. 2009, 131, 17748–17749.
74
13c
20c
84
98
(7) Recent reviews on direct arylations of heteroarenes: (a) Bellina, F.;
Rossi, R. Tetrahedron 2009, 65, 10269–10310. (b) Joucla, L.; Djakovitch,
L. AdV. Synth. Catal. 2009, 351, 673–714.
86d
a Reaction conditions: 1a (0.50 mmol), 2a (0.60 mmol), Pd(OAc)2 (5.0
mol %), L (7.5 mol %), base (1.00 mmol), solvent (2.0 mL), 100 °C, 14 h.
b L (15 mol %). c GC-conversion; HIMes ) N,N′-bis(2,4,6-trimethylphe-
nyl)imidazolium, (S)HIPr ) N,N′-bis(2,6-diisopropylphenyl)imidazol(in)-
ium. d With PdCl2 (5.0 mol %).
(8) For select recent examples of direct arylations employing oxazoles,
see: (a) Canivet, J.; Yamaguchi, J.; Ban, I.; Itami, K. Org. Lett. 2009, 11,
1733–1736. (b) Hachiya, H.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett.
2009, 11, 1737–1740. (c) Flegeau, E. F.; Popkin, M. E.; Greaney, M. F.
Org. Lett. 2008, 10, 2717–2720. (d) Sanchez, R. S.; Zhuravlev, F. A. J. Am.
Chem. Soc. 2007, 129, 5824–5825. (e) Do, H.-Q.; Daugulis, O. J. Am. Chem.
Soc. 2007, 129, 12404–12405, and references cited therein.
(9) For representative recent examples of conVentional cross-coupling
reactions with phosphates as electrophiles, see: (a) Gauthier, D.; Beckendorf,
S.; Gøgsig, T. M.; Lindhardt, A. T.; Skrydstrup, T. J. Org. Chem. 2009,
74, 3536–3539. (b) Yoshikai, N.; Matsuda, H.; Nakamura, E. J. Am. Chem.
Soc. 2009, 131, 9590–9599. (c) Bedford, R. B.; Huwe, M.; Wilkinson, M. C.
Chem. Commun. 2009, 600–602. (d) Hansen, A.; Ebran, J.-P.; Gøgsig, T. M.;
Skrydstrup, T. J. Org. Chem. 2007, 72, 6464–6472. (e) Ebran, J.-P.; Hansen,
A. L.; Gøgsig, T. M.; Skrydstrup, T. J. Am. Chem. Soc. 2007, 129, 6931–
6942. (f) Hansen, A. L.; Ebran, J.-P.; Ahlquist, M.; Norrby, P.-O.;
Skrydstrup, T. Angew. Chem., Int. Ed. 2006, 45, 3349–3353. (g) McLaughlin,
M. Org. Lett. 2005, 7, 4875–4878. A review: (h) Lindhardt, A. T.;
Skrydstrup, T. Chem.sEur. J. 2008, 14, 8756–8766, and references cited
therein.
Unfortunately, electron-rich σ-donor ligands, such as N-
heterocyclic carbenes (entries 2-4) or tertiary alkyl-
substituted phosphines (entries 5 and 6), provided only
unsatisfactory results. Contrarily, a palladium catalyst derived
(3) (a) Ackermann, L.; Althammer, A.; Born, R. Angew. Chem., Int.
Ed. 2006, 45, 2619–2622. (b) Ackermann, L.; Vicente, R.; Althammer, A.
Org. Lett. 2008, 10, 2299–2302.
(4) Ackermann, L.; Althammer, A.; Fenner, S. Angew. Chem., Int. Ed.
2009, 48, 201–204.
(5) Ackermann, L.; Mulzer, M. Org. Lett. 2008, 10, 5043–5045.
Org. Lett., Vol. 12, No. 4, 2010
725

deficient as well as electron-rich sulfamates 2, even when
bearing ortho-substituents. Moreover, substituted benzox-
azoles 1 could be employed, thus allowing for the synthesis
of products 3i-q, displaying valuable functional groups for
further synthetic elaboration.
Scheme 4. Direct Alkenylation with Phosphates 6
Importantly, the protocol was found not to be restricted
to benzoxazoles 1, but could be applied to C-H bond
functionalizations on oxazole 4 as well (Scheme 2).
Scheme 2. Direct Arylation of Heteroarene 4
Finally, the optimized protocol also set the stage for
efficient regioselective benzylation reactions12 under nona-
cidic reaction conditions (Scheme 5).
Scheme 5. Direct Benzylation with Phosphate 8
It is worth noting that a competition experiment between
differently substituted benzoxazoles 1 revealed that more
electron-deficient heteroarene 1b reacted preferentially (Scheme
3a). As to the organic electrophiles, intra- (Scheme 1) and
Scheme 3. Intermolecular Competition Experiments
In conclusion, we have developed a palladium catalyst for
general direct arylations through C-H bond cleavages with
moisture-stable sulfamates as electrophiles. Notably, this
catalytic system derived from ligand dppe also allowed for
direct benzylations and alkenylations with easily accessible
phosphates as convenient coupling partners.
Acknowledgment. Financial support by the DFG is
gratefully acknowledged.
Supporting Information Available: Experimental pro-
cedures, characterization data, and 1H and 13C NMR spectra
for new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
intermolecular (Scheme 3b) competition experiments indi-
cated the following series in order of decreasing reactivity:
ArOSO2Im > ArBr > ArCl.
OL9028034
For direct C-H bond alkenylation reactions11 we became
interested in exploring the use of moisture-stable phosphates9
6 as convenient coupling reagents (Scheme 4). As observed
for direct arylations with sulfamates 2 (vide supra), dppe
was found to be the ligand of choice among different mono-
or bidentate additives. Thereby, various alkenylated products
7a-e could be obtained with good yields and excellent
chemoselectivities.
(11) For recent examples of alkenylations with alkenyl triflates or halides
as electrophiles, see: (a) Ackermann, L.; Althammer, A.; Mayer, P. Synthesis
2009, 3493–3503. (b) Cruz, A. C. F.; Miller, N. D.; Willis, M. C. Org.
Lett. 2007, 9, 4391–4393. (c) Ackermann, L.; Althammer, A. Angew. Chem.,
Int. Ed. 2007, 46, 1627–1629. (d) Hughes, C. C.; Trauner, D. Angew. Chem.,
Int. Ed. 2002, 41, 1569–1572, and references cited therein.
(12) For recent reports on intermolecular transition metal-catalyzed direct
benzylations through C-H bond cleavages under basic reaction conditions,
see: [Ru]: (a) Ackermann, L.; Nova´k, P. Org. Lett. 2009, 11, 4966–4969.
[Pd]: (b) Verrier, C.; Hoarau, C.; Marsais, F. Org. Biomol. Chem. 2009, 7,
647–650. (c) Lapointe, D.; Fagnou, K. Org. Lett. 2009, 11, 4160–4163.
For recent examples of direct C-H bond alkylations, see: [Ru]: (d)
Ackermann, L.; Novak, P.; Vicente, R.; Hofmann, N. Angew. Chem. Int.,
Ed. 2009, 48, 6045–6048. [Pd]: (e) Zhang, Y.-H.; Shi, B.-F.; Yu, J.-Q.
Angew. Chem., Int. Ed. 2009, 48, 6097–6100.
(10) This optimized dppe-based catalytic system proved not applicable
to direct arylations of benzoxazoles with aryl tosylates.
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Org. Lett., Vol. 12, No. 4, 2010