Acyclic diaminocarbenes: Simple, versatile ligands for cross-coupling reactions

Article abstract of DOI:10.1039/b516398f

Acyclic diaminocarbenes are found to be useful ligands for palladium catalyzed Suzuki-Miyaura, Sonogashira and Heck cross-coupling reactions of aryl/alkenyl bromides and chlorides. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b516398f

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Acyclic diaminocarbenes: simple, versatile ligands for cross-coupling
reactions{
Bhartesh Dhudshia and Avinash N. Thadani*
Received (in Bloomington, IN, USA) 17th November 2005, Accepted 3rd January 2006
First published as an Advance Article on the web 19th January 2006
DOI: 10.1039/b516398f
1
4
Acyclic diaminocarbenes are found to be useful ligands for
palladium catalyzed Suzuki–Miyaura, Sonogashira and Heck
cross-coupling reactions of aryl/alkenyl bromides and chlorides.
isolated yield. There was very little difference in efficacy when
isolated carbene 1a (entry 3) was used in place of the in situ
generated variant (entry 2).
The room temperature Suzuki–Miyaura reaction was extended
to a variety of other substrates, the results of which are shown in
Table 2. The coupling was effective for sterically hindered aryl
bromides (entries 5–7), heterocyclic bromides (entries 2,3) and
alkenyl bromides (entries 8,9). The scope of the reaction was also
established with a number of sterically demanding (entries 1–4)
and electron rich boronic acids (entry 9). The nature of the boronic
acid was also expanded to include alkenyl (entries 5,6) and
heterocyclic variants (entry 7).
The major driving force behind the impressive growth in transition
metal catalysis has been the continual development of new
1
ligands. Recently, a new class of ligands—N-heterocyclic carbenes
2
,3
(
NHC)—has been introduced into the field of catalysis. In
particular, the application of NHC in a variety of cross-coupling
4–6
reactions has proved very fruitful. Several of the more widely
used NHC (2–4) are shown below.
7,8
Acyclic diaminocarbenes (ADC) (1), on the other hand, have
not attracted the same degree of attention as NHC despite several
appealing characteristics. These include the simple, straightforward
A significant improvement to the process was to enable the use
of aryl chlorides in the Suzuki–Miyaura reaction. Initial optimiza-
tion studies involving 2-chloro-1,3-dimethylbenzene and 2-methyl-
phenylboronic acid revealed that the coupling reaction, when
conducted under the conditions reported in Table 2, proceeded
rather sluggishly (22% isolated yield of 5a). Fortunately, elevating
the reaction temperature from rt to 45 uC resulted in a much more
facile reaction (80% isolated yield of 5a). A variety of aryl chlorides
and boronic acids were then subjected to the cross-coupling
reaction using ADC ligand 1a (Table 3). As before, the desired
products were obtained in good yields.
9
preparation of the formamidinium salt precursors, and the more
8
i,j
basic nature of the resulting carbenes. We were thus interested in
investigating a series of ADC (vide infra) in a select number of
10
palladium catalyzed cross-coupling reactions.
We next explored the efficacy of 1a in the Sonogashira
1
5
reaction. The optimized copper-free protocol, which turned out
1
6
to be similar to one previously reported by Soheili et al., is as
follows: halide (1 equiv.), alkyne (1.1 equiv.), [Pd(allyl)Cl]2
Table 1 Suzuki–Miyaura coupling of 2-bromo-1,3-dimethylbenzene
with 2-methylphenylboronic acid using ADC 1a–d as ligands
We chose to evaluate the utility of ADC 1a–d as ligands in the
Suzuki–Miyaura reaction between 2-bromo-1,3-dimethylbenzene
1
1
and 2-methylphenylboronic acid (Table 1). Several reaction
parameters were initially varied including the palladium source,
1
2
base, solvent, and other additives. After extensive screening, the
following set of standard reaction conditions were established with
respect to the aryl/alkenyl halide: 0.5 mol% Pd (dba) , 1.25 mol%
2
3
n
13
1
, 1.25 mol% Bu NBr, 1.1 equiv. ArB(OH)
4
2
and 2 equiv.
b
Cs CO in toluene–THF. The requisite ADC were synthesized
2 3
Entry
ADC (1)
Yield (%)
in situ through deprotonation (LDA) of the corresponding
c
1
2
3
4
5
6
a
—
1a
1a
1b
1c
1d
,3%
9
7
formamidinium salts, as originally reported by Alder et al.
Bis(diisopropylamino)carbene (1a) was found to be the ligand of
choice affording the desired tri-ortho-substituted biaryl (5a) in 89%
89
90
88
49
40
d
Department of Chemistry & Biochemistry, University of Windsor,
Windsor, Ontario, Canada N9B 3P4. E-mail: athadani@uwindsor.ca;
Fax: +1 519 973 7098; Tel: +1 519 253 3000 ext. 3556
Prepared in situ via deprotonation (LDA) of the corresponding
Isolated yield (average of two runs).
1 d
Estimated yield based on crude H NMR spectra. Isolated 1a was
used.
b
formamidinium salt.
c
{
Electronic Supplementary Information (ESI) available: Optimization
studies and characterization data. See DOI: 10.1039/b516398f
6
68 | Chem. Commun., 2006, 668–670
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Table 2 Room temperature Suzuki–Miyaura coupling of aryl/alkenyl
bromides using ADC ligand 1a
Table 3 Suzuki–Miyaura coupling of aryl/alkenyl chlorides using
ADC ligand 1a
1
Entry R –Br
2
R –B(OH)
b
1
R –Cl
2
R –B(OH)
b
2
Yield (%)
Entry
1
Yield (%)
2
1
2
3
4
5
6
7
8
86 (5a)
81 (5a)
85 (5b)
89 (5c)
79 (5d)
93 (5e)
89 (5f)
91 (5b)
88 (5g)
2
3
4
5
89 (5j)
80 (5a)
86 (5k)
88 (5l)
6
7
85 (5m)
92 (5n)
89 (5i)
8
9
93 (5h)
95 (5i)
a
Prepared in situ via deprotonation (LDA) of the corresponding
formamidinium salt. Isolated yield (average of two runs).
b
1
0
Finally, we also briefly examined the applicability of ADC 1a in
17
intermolecular Heck reactions. Aryl bromides were readily
coupled to an electron deficient alkene in good yields under a
12
modified set of conditions (eqn (1)). The corresponding aryl
chlorides, however, were poor substrates for the Heck reaction
a
Prepared in situ via deprotonation (LDA) of the corresponding
formamidinium salt. Isolated yield (average of two runs).
b
(
35% and 29% isolated yields of 7a and 7b respectively) under the
12
conditions shown in eqn (1).
(1.5 mol%), 1a (4 mol%), Cs CO (2 equiv.), PhCH –THF, rt, 16 h.
2 3 3
A variety of aryl halides were subjected to the conditions reported
above, the results of which are shown in Table 4. The room
temperature Sonogashira reaction worked well with both aromatic
(entries 1,2,4–6) and aliphatic alkynes (entries 3,7). A range of
sterically hindered- (entry 1), electron rich- (entries 2–4) and
heterocyclic aryl bromides (entries 6,7) were employed as coupling
partners. The resulting products were consistently obtained in
good isolated yields.
(1)
Chem. Commun., 2006, 668–670 | 669
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using ADC ligand 1a
1
R –Br
b
Entry
1
Yield (%)
2005, 7, 1829.
80 (6a)
5
For selected recent application of NHC as ligands in Sonogashira
couplings, see: (a) M. S. Viciu, R. F. Germaneau, O. Navarro-
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2
3
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87 (6b)
80 (6c)
91 (6d)
89 (6e)
1
M. B. Andrus, Org. Lett., 2003, 5, 3317; (e) E. Mas-Marza,
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W. A. Herrmann, Organometallics, 2005, 24, 4416.
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see: (a) W. A. Herrmann, G. P. Reisinger and M. J. Spiegler,
J. Organomet. Chem., 1998, 55, 93; (b) D. S. McGuinness and
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Soc., 2004, 126, 5046; (g) M. Shi and H.-X. Qian, Tetrahedron, 2005, 61,
6
4949.
7
8
R. W. Alder, P. R. Allen, M. Murray and A. G. Orpen, Angew. Chem.,
Int. Ed. Engl., 1996, 35, 1121.
For other reports on ADC, see: (a) R. W. Alder and M. E. Blake,
Chem. Commun., 1997, 1513; (b) R. W. Alder, M. E. Blake and
J. M. Olivia, J. Phys. Chem. A, 1999, 103, 11200; (c) K. Denk, P. Sirsch
and W. A. Herrmann, J. Organomet. Chem., 2002, 649, 219; (d)
6
7
a
90 (6f)
81 (6g)
¨
M. Tafipolsky, W. Scherer, K. Ofele, G. Artus, B. Pedersen,
W. A. Herrmann and G. S. McGrady, J. Am. Chem. Soc., 2002, 124,
¨
5
865; (e) W. A. Herrmann, K. Ofele, D. Preysing and E. Herdtweck,
J. Organomet. Chem., 2003, 684, 235; (f) R. W. Alder, M. E. Blake,
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R. W. Alder, M. E. Blake, L. Chaker, J. N. Harvey, F. Paolini and
J. Sch u¨ tz, Angew. Chem., Int. Ed., 2004, 43, 5896; (h) M. Otto,
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and B. F. Yates, J. Am. Chem. Soc., 2004, 126, 8717.
Prepared in situ via deprotonation (LDA) of the corresponding
b
formamidinium salt. Isolated yield (average of two runs).
In summary, we have demonstrated that ADC are useful
ligands for the Suzuki, Sonogashira and Heck reactions, affording
the desired products in good to excellent yields.
9
R. W. Alder, M. E. Blake, S. Bufali, C. P. Butts, A. G. Orpen, J. Sch u¨ tz
and S. J. Williams, J. Chem. Soc., Perkin Trans. 1, 2001, 1586.
0 F u¨ rstner et al. have reported the synthesis and characterization of a
This work was supported by NSERC, ORDCF and the
University of Windsor.
1
series of ADC–metal complexes, and applied some of these catalysts in
Heck cross-coupling reactions: D. Kremzow, G. Seidel, C. W. Lehmann
and A. F u¨ rstner, Chem. Eur. J., 2005, 11, 1833.
Notes and references
1
1 For a review on the Suzuki–Miyaura reaction, see N. Miyaura, in Metal
Catalyzed Cross-Coupling Reactions, ed. A. de Meijere, A. Diederich and
F. Diederich, Wiley-VCH, New York, 2nd edn, 2004, ch. 2.
1
For recent monographs on the subject, see: (a) Transition metals for
organic synthesis, ed. M. Beller and C. Bolm, Wiley-VCH, New York,
nd edn, 2005; (b) J. Tsuji, in Transition metal reagents and catalysts:
innovations in organic synthesis, John Wiley & Sons, New York, 2000.
For recent reviews on NHC, see: (a) D. Kremzow, G. Seidel,
C. Lehmann and A. F u¨ rstner, Chem. Eur. J., 2005, 11, 1833; (b)
C. M. Crudden and D. P. Allen, Coord. Chem. Rev., 2004, 248, 2247; (c)
N. M. Scott and S. P. Nolan, Eur. J. Inorg. Chem., 2005, 10, 1815; (d)
12 For optimization studies, the possible roles of the additives and further
2
discussion, please see the electronic supporting information{.
3 K. Arentsen, S. Caddick, F. G. N. Cloke, A. P. Herring and
1
2
P. B. Hitchcock, Tetrahedron Lett., 2004, 45, 3511.
4 Pending further studies, we believe that 1a and 1b are more efficacious
ligands due to their increased steric sizes.
1
¨
15 K. Sonogashira, in Metal-Catalyzed Cross-Coupling Reactions,
ed. F. Diederich and P. J. Stang, Wiley-VCH, New York, 1998,
ch. 5.
16 A. Soheili, J. Albaneze-Walker, J. A. Murry, P. G. Dormer and
D. L. Hughes, Org. Lett., 2003, 5, 4191.
W. A. Herrmann, K. Ofele, D. Preysing and S. K. Schneider,
J. Organomet. Chem., 2003, 687, 229; (e) K. Burgess and M. C. Perry,
Tetrahedron: Asymmetry, 2003, 14, 951; (f) W. A. Hermann, Angew.
Chem., Int. Ed., 2002, 41, 1290.
3
4
A. J. Arduengo, III, R. L. Harlow and M. Kline, J. Am. Chem. Soc.,
1991, 113, 361.
For selected recent application of NHC as ligands in Suzuki couplings,
see: (a) A. F u¨ rstner and A. Leitner, Synlett, 2001, 290; (b) G. A. Grasa,
17 For a review on the Heck reaction, see: S. Br a¨ se and A. de Meijere, in
Metal Catalyzed Cross-Coupling Reactions, ed. A. de Meijere and
F. Diederich, Wiley-VCH, New York, 2nd edn, 2004, ch. 5.
6
70 | Chem. Commun., 2006, 668–670
This journal is ß The Royal Society of Chemistry 2006