Enabling bifunctionality and hemilability of N-heteroaryl NHC complexes

Article abstract of DOI:10.1002/chem.201100521

Functionalized carbene ligands: Increasing the steric bulk of R¹ on 1 from H to tBu results in lengthening of the M-N bond (by up to 9 %), lowered activation energy for chelate opening (cf. 2) by 17 kcal mol ^-1, and improved binding

Full text of DOI:10.1002/chem.201100521

DOI: 10.1002/chem.201100521
Enabling Bifunctionality and HemiACTHNUTRGNElUNG ability of N-Heteroaryl NHC Complexes
Zephen G. Specht,[a] Sara A. Cortes-Llamas,[a, d] Hai N. Tran,[a]
Christoffel J. van Niekerk,[a] Khing T. Rancudo,[a] James A. Golen,[b] Curtis E. Moore,[b]
Arnold L. Rheingold,[b] Tammy J. Dwyer,[c] and Douglas B. Grotjahn*[a]
N-Heterocyclic carbene (NHC) complexes have been
shown to be extremely versatile and stable catalysts for re-
actions as diverse as olefin metathesis, transfer hydrogena-
tion, and C-C coupling reactions.[1] NHCs are attractive lig-
ACHTUNGTRENNUNGands due to their strong s-donating ability, poor back bond-
ACHTUNGTRENNUNG
ing,[2a–h] and relative air, moisture, and thermal stability of
their complexes.[2e,g,i]
Electronic and steric optimization of the properties of
NHC-metal complexes is possible through NHC ligand de-
sign.[2g,j,k] Further improvement of catalyst performance
through NHC functionalization[3] has been studied using a
variety of pendant groups, including heterocycle, phosphine,
amine, and imine donor functions. In many cases the added
ligand creates a stable chelate or pincer, whereas in other
cases a hemilabile system and its temporary ligand loss (as
in 2) favor catalysis.[4]
trum of 5a was reported to remain sharp even at 1108C,[5b]
suggesting that decoordination and rotation about the pyri-
ꢀ
midine NHC bond is a process with a high activation barri-
er. Therefore, in order to fully realize the potential of NHC
ligands with pendant heterocyclic bases their ability to che-
late with a metal must be decreased (Scheme 1), and we hy-
pothesized that this could be achieved by introducing a
large substituent R1. Here we report successful strategies
toward achieving this aim, which should be of general appli-
cation to NHC chemistry.
In contrast, this paper introduces a fundamentally differ-
ent approach, where a substituent on an NHC ligand will
act as a hydrogen bond acceptor (3) or base (4), which
could facilitate catalysis (Scheme 1). Some recent studies on
NHC metal complexes have raised the possibility of pendant
nitrogen involvement,[5] though as far as we are aware, no
direct evidence was presented in these studies.
In particular, for 5a,[5b] decoordination of the pyrimidine
(cf. 1!2) would make a basic nitrogen available near the
metal active site (cf. 2!3 or 4). However, the NMR spec-
Scheme 1. Enabling chemistry of a pendant group.
[a] Z. G. Specht, Prof. S. A. Cortes-Llamas, H. N. Tran, C. J. van Niekerk,
K. T. Rancudo, Prof. D. B. Grotjahn
Department of Chemistry and Biochemistry
San Diego State University
5500 Campanile Drive San Diego, CA 92182-1030 (USA)
Fax : (+1)619-594-4634
Although many (pyridyl)-[6] and fewer (pyrimidyl)NHC
complexes are known,[7] we were interested in probing more
basic heterocycles; as far as we are aware, there are no
E-mail: grotjahn@chemistry.sdsu.edu
other reports of imidazolyl
(heteroaryl)NHC ligands start with coupling of sodium im-
idazolate with halogenated heterocycles 7 or 11 (Scheme 2).
(NHC) ligands. Syntheses[8] of
ACHTUNGTRENNUNG
[b] Prof. J. A. Golen, Dr. C. E. Moore, Prof. A. L. Rheingold
Department of Chemistry and Biochemistry
University of California at San Diego
AHCTUNGTRENNUNG
The pyrimidyl cases reacted at considerably lower tempera-
ture (110–1408C)[8] than did 11, reflecting the significant dif-
ferences between the two aromatic systems. Transformation
of 8 or 12 by methylation at the most reactive nitrogen and
ion exchange gave 9c-PF6 or 13-PF6, which was converted to
a silver carbene complex, and transmetalated to give 5c, or
6 in high yields. The rhodium analog of 5c (5c-Rh) was
made for comparison of second- and third-row metals. All
complexes were isolated as rather air-stable solids. For com-
La Jolla, CA 92093-0385 (USA)
[c] Prof. T. J. Dwyer
Department of Chemistry and Biochemistry
University of San Diego
San Diego, CA 92110 (USA)
[d] Prof. S. A. Cortes-Llamas
Fulbright Scholar on leave from Universidad de Guadalajara to
SDSU.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201100521.
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Chem. Eur. J. 2011, 17, 6606 – 6609

COMMUNICATION
Figure 1. Molecular structure of the cation of 5c.
porting Information, Figure S3 of 5b shows a similar interac-
tion involving a phenyl ring.
The lability of the chelate in 5c and 5c-Rh suggested by
1
solid-state data was confirmed by H NMR spectra at 308C
showing a single broadened resonance for the two tert-butyl
groups.
Scheme 2. Synthesis of new N-heteroaryl NHC complexes.
parisons, complex 5a was made according to the litera-
Quantification of ligand dynamics (last column in Table 1)
was obtained by variable-temperature NMR experiments.
The case of 5a required EXSY in the range of 110-1358C,
ACHTUNGTRENNUNG
ture.[5b]
Samples of each new species were analyzed by single-crys-
1
tal X-ray diffraction, with key results shown in Table 1 and
the structure of 5c (Figure 1).[9] All complexes exhibited oc-
tahedral geometry about the metal, with consistent distor-
tion imposed by the chelating (heteroaryl)NHC unit (C-Ir-N
angles ca. 74.6–76.78).
whereas for 5c and 5c-Rh line-shape analyses of H NMR
spectra between ꢀ40 and +308C sufficed. The lowered acti-
vation energies clearly show the dramatic effects of phenyl
or tert-butyl groups on the strength of the metal-nitrogen
bond.
Preliminary results show that weakening the chelation has
significant effects on ligand binding: benzylamine reacted
with either 5c or 6, forming adducts 16c and 17 quantita-
tively (Scheme 3). In contrast, 5a remains completely intact.
Distinctive features of 16c and 17 include a four-spin system
for the -CH2NH2 unit, with the two NH protons resonating
at 6.63 and 4.17 ppm (16c), and 3.95 and 7.67 ppm (17).
NMR spectroscopy was used successfully to examine hydro-
Table 1. Key bond lengths [ꢁ] and angles [8][a] and activation energy of
pyrimidyl ring flip (Ea [kcalmolꢀ1]).
Torsion[b] Ea
ꢀ
Ir C
ꢀ
Ir N
Sum
C-Ir-N
5a
5b
5c
2.044(7) 2.109(6) 4.153 76.7(3)
1.996(3) 2.180(2) 4.176 76.5(1)
1.990(7) 2.266(6) 4.256 75.4(3)
1.8
4.1
7.8
29.6ꢁ0.9
22.0ꢁ0.3
12.5ꢁ0.2
14.3ꢁ0.3
NA[c]
5c-Rh 1.998(2) 2.317(2) 4.315 74.60(9) 7.4
1.947(8) 2.200(6) 4.147 76.3(3) 0.2
6
[a]Literature X-ray data for 5a.[5b] [b]Defined as (for example, looking
at Figure 1) carbene C-N3-C-N1 (coordinating N) angle. [c] NA=not ap-
plicable.
Striking features of data in Table 1 are 1) progressive
ꢀ
lengthening of the Ir N bond as (heteroaryl) substitution
becomes more sterically demanding, with a difference be-
ꢀ
tween 5a and 5c-Rh of 9%, 2) compensation for Ir N
ꢀ
lengthening by Ir C contraction, and 3) shorter metal–che-
late bonds for imidazolyl derivative 6 than pyrimidyl ana-
logues with the same tert-butyl substitution (5c or 5c-Rh).
Moreover, Figure 1 shows how the pyrimidyl ring in 5c is
distorted from planarity by interaction of the tert-butyl
group closest to the metal with the Cp*M fragment; in Sup-
Scheme 3. Intramolecular hydrogen bonding of one benzylamine NH and
pendant base as observed by 15N NMR chemical shifts.
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D. B. Grotjahn et al.
Table 2. NMR yields [%] of 19 and 20 from catalyzed conversion of primary (18a) or secondary (18b) amines
gen bonding. For 17, as deter-
mined by 1H-15N gHMBC cor-
relation on natural abundance
material, an upfield 15N chemi-
cal shift (by ca. 10 ppm) for the
by cyclization or isomerization.[a]
basic
imidazolyl
nitrogen
(ꢀ135.3 ppm) relative to values
seen for 13-PF6 and 15-PF6
(ꢀ125.3 and ꢀ121.2 ppm, re-
spectively) may be considered
useful spectroscopic evidence
for the intramolecular hydrogen
bonding shown.[8,10] For the pyr-
imidyl system of 16c at 308C, a
single set of 1H and 13C NMR
peaks for the two tBu groups
suggest free rotation around the
Catalyst
Substrate Conditions[a]
A
1 h
19 20
24 h
19
72 h
19 20
18
18
20
18
1
2
3
4
5
6
7
8
9
A
72
0
0
0
72
64
26
5
0.4
5c[b]
5c[b]
5c
18a
18a
18b
18a
18a
18a
18a
18b
A
B
B
A
A
A
A
B
4
0
68
75
9
57
29 4.4
2.9 89 2.0
3.4
2.0[c]
82
3.0[c] 89[c]
5c-Rh
5b
5a
6
6
9
87
0
0
3
69
98.5
36
0
94
9
10 18
0
1.5
65
3.8
27
86
0
4.4
55
3
37
62 3.9
[a]Conditions A: 18a (0.25 mmol) and catalyst (5 mol%; 2.5 mol% in the case of entry 1) in toluene (1.0 mL)
at 1008C. Yields shown are based 1H NMR spectroscopy, averaging results from two separate runs, except for
entry 1, using 1,3,5-trimethoxybenzene as an internal standard. No entry means yield not determined at that
time. Conditions B: same quantities as in A, except reaction run in [D8]THF and analyzed directly, and only
one run was used. [b]In entries 2 and 3 yields of 19a may be lower because of a dehydrogenation side re-
ꢀ
heteroaryl NHC bond; more-
over for the pyrimidyl nitrogen
atom in the 1H-15N gHMBC
AHCTUNGTRENNGaUN ction, forming an imine. [c]Data collected after 3 h, after which the reaction did not proceed further.
spectrum
a
single peak at
ꢀ108.5 ppm was seen. In con-
trast, at ꢀ908C, two nitrogen
1H-15N gHMBC crosspeaks were seen at ꢀ100.6 and
ꢀ118.0 ppm, clearly showing an upfield shift of 17.4 ppm
which is strong evidence[10] for hydrogen-bond acceptance
by one pyrimidyl nitrogen.
In conclusion, increasing the steric bulk around the pend-
ꢀ
ant nitrogen atom results in dramatic lengthening of the M
N bond as revealed by X-ray crystallography, dynamic NMR
behavior, improved ligand binding, and catalysis of intramo-
lecular hydroamination, a reaction of significant mechanistic
and synthetic interest. The applications of these findings,
which are expected to be applicable to a wide variety of
NHC systems, are a subject of ongoing in work in these lab-
oratories.
Catalyzed cyclization of aminoalkenes 18a or 18b to give
19a,b (Table 2) was chosen as a test reaction because of on-
going and intense synthetic and mechanistic interest in
alkene hydroamination.[11] Table 2 shows that 5c is the most
active of (heteroaryl)NHC catalysts examined, with 6 as the
second most active. Looking at results from primary amine
18a, among (pyrimidyl)NHC derivatives, increase in conver-
sion of 18a occurs on going from 5a, which is virtually in-
Acknowledgements
ACHTUNGTRENNUNGactive (entry 7), to 5b, which is about as active as
[(IrCp*Cl2)2] (entries 6 and 1), to 5c, which is much more
active (entries 2 and 3). The effect of changing from toluene
to THF as the solvent was minimal (entries 2 and 3). Intrigu-
ingly, congener 5c-Rh (entry 5) gives isomerization exclu-
sively as quickly as 5c performs selective hydroamination,
showing a dramatic role for the central metal in the course
of the cyclization. Although our preliminary results have not
resulted in a hydroamination catalyst significantly more
active than recent impressive improvements in the state-of-
the-art,[11a–e,q] nonetheless the fact that a completely inactive
NHC-based system (5a) can be turned into a synthetically
useful one constitutes a significant proof of concept. We also
note that the consumption of the secondary amine substrate
18b is at least 20 times faster than that of the primary
amine (entry 4 versus entry 3), affording cyclized product in
higher yield (89%) using 5c, which are differences consis-
tent with results from other known rhodium and iridium
based catalysts.[11b,i] Given the variety of mechanistic possi-
bilities for hydroamination reactions[12] and their synthetic
utility, further work on these reactions is underway.
We thank the San Diego Foundation, SDSU, and NSF for partial support
of this work, including SDSU NMR facilities (MRI CHE-0521698). S.C.-
L. thanks Fulbright for funding her stay at SDSU.
Keywords: cyclization · iridium · N-heterocyclic carbenes ·
NMR spectroscopy · pendant base
[1] Select reviews: a) E. A. B. Kantchev, C. J. OꢂBrien, M. G. Organ,
Angew. Chem. 2007, 119, 2824–2870; Angew. Chem. Int. Ed. 2007,
46, 2768–2813; b) G. C. Vougioukalakis, R. H. Grubbs, Chem. Rev.
2010, 110, 1746–1787; c) S. D. Gonzꢃlez, N. Marion, S. P. Nolan,
Chem. Rev. 2009, 109, 3612–3676.
[2] a) D. Bourissou, O. Guerret, F. P. Gabbaie, G. Bertrand, Chem. Rev.
2000, 100, 39–91; b) T. Weskamp, V. P. W. Bohm, W. A. Herrmann,
J. Organomet. Chem. 2000, 600, 12–22; c) W. A. Herrmann, Angew.
Chem. 2002, 114, 1342–1363; Angew. Chem. Int. Ed. 2002, 41, 1290–
1309; d) N. M. Scott, S. P. Nolan, Eur. J. Inorg. Chem. 2005, 1815–
1828; e) R. H. Crabtree, J. Organomet. Chem. 2005, 690, 5451–5457;
f) F. E. Hahn, Angew. Chem. 2006, 118, 1374–1378; Angew. Chem.
Int. Ed. 2006, 45, 1348–1352; g) S. Diez-Gonzalez, S. P. Nolan,
Coord. Chem. Rev. 2007, 251, 874–883; h) F. E. Hahn, M. C. Jahnke,
Angew. Chem. 2008, 120, 3166–3216; Angew. Chem. Int. Ed. 2008,
6608
www.chemeurj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 6606 – 6609

N-Heterocyclic Carbenes
COMMUNICATION
47, 3122–3172; i) T. Strassner, Top. Organomet. Chem. 2007, 22,
125–148; j) P. L. Arnold, S. Pearson, Coord. Chem. Rev. 2007, 251,
596–609; k) O. Schuster, L. Yang, H. G. Raubenheimer, M. Al-
brecht, Chem. Rev. 2009, 109, 3445–3478; l) T. Drçge, F. Glorius,
Angew. Chem. 2010, 122, 7094–7107; Angew. Chem. Int. Ed. 2010,
49, 6940–6952.
[9] CCDC-806197 (5b), 806200 (5c), 806201 (5c-Rh) and 806198 (6)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/
cif.
[10] For uses of 15N chemical shifts to characterize hydrogen bonding,
see the following leading references: a) D. B. Grotjahn, Dalton
Trans. 2008, 6497–6508; b) D. B. Grotjahn, Pure Appl. Chem. 2010,
82, 635–647.
[3] a) O. Kuehl, Chem. Soc. Rev. 2007, 36, 592–607; b) D. Pugh, A. A.
Danopoulos, Coord. Chem. Rev. 2007, 251, 610–641; c) A. T. Nor-
mand, K. J. Cavell, Eur. J. Inorg. Chem. 2008, 2781–2800; d) M.
Poyatos, J. A. Mata, E. Peris, Chem. Rev. 2009, 109, 3677–3707;
e) H. M. Lee, C. C. Lee, P. Y. Cheng, Curr. Org. Chem. 2007, 11,
1491–1524.
[4] For the effects of hemilability in general, see for example: a) H.
Werner, Dalton Trans. 2003, 3829–3837; b) C. S. Slone, D. A. Wein-
berger, C. A. Mirkin, Prog. Inorg. Chem. 1999, 48, 233–350; c) P.
Braunstein, J. Organomet. Chem. 2004, 689, 3953–3967; d) A.
Bçrner, Eur. J. Inorg. Chem. 2001, 327–337; e) F. Y. Kwong, A. S. C.
Chan, Synlett 2008, 1440–1448.
[5] a) D. Meyer, M. A. Taige, A. Zeller, K. Hohlfeld, S. Ahrens, T.
Strassner, Organometallics 2009, 28, 2142–2149; b) D. Gnanamgari,
E. L. O. Sauer, N. D. Schley, C. Butler, C. D. Incarvito, R. H. Crab-
tree, Organometallics 2009, 28, 321–325; c) C. Chen, H. Qiu, W.
Chen, D. J. Wang, Organomet. Chem. 2008, 37, 3273–3280; d) M. V.
Jimꢄnez, J. J. Pꢄrez-Torrente, M. I. Bartolomꢄ, V. Gierz, F. J. Lahoz,
L. A. Oro, Organometallics 2008, 27, 224–234.
[6] Examples: a) J. J. Concepcion, J. W. Jurss, T. J. Meyer, Inorg. Chem.
2010, 49, 1277–1279; b) Y. Cheng, H. Xu, X. Chen, Z. Xue, Dalton
Trans. 2009, 7132–7140; c) A. A. Danopoulos, N. Tsoureas, S. A.
Macgregor, C. Smith, Organometallics 2007, 26, 253–263; d) D.
Pugh, J. A. Wright, S. Freeman, A. A. Danopoulos, Dalton Trans.
2006, 775–782; e) B. Liu, Y. Zhou, W. Chen, Organometallics 2010,
29, 1457–1464; f) C. Lu, S. Gu, W. Chen, H. Qiu, Dalton Trans.
2010, 39, 4198–4204; g) B. Liu, Q. Xia, W. Chen, Angew. Chem.
2009, 121, 5621–5624; Angew. Chem. Int. Ed. 2009, 48, 5513–5516.
[7] a) J. Ye, W. Chen, D. Wang, Dalton Trans. 2008, 4015–4022; see also
references [6e,f,g].
[11] Leading references: a) L. D. Julian, J. F. Hartwig, J. Am. Chem. Soc.
2010, 132, 13813–13822; b) K. D. Hesp, S. Tobisch, M. Stradiotto, J.
Am. Chem. Soc. 2010, 132, 413–426; c) Y. Kashiwame, S. Kuwata, T.
Ikariya, Chem. Eur. J. 2010, 16, 766–770; d) C. Michon, F. Medina,
F. Capet, P. Roussel, F. Agbossou-Niedercorn, Adv. Synth. Catal.
2010, 352, 3293–3305; e) X. Shen, S. L. Buchwald, Angew. Chem.
2010, 122, 574–577; Angew. Chem. Int. Ed. 2010, 49, 564–567; f) H.
Ohmiya, T. Moriya, M. Sawamura, Org. Lett. 2009, 11, 2145–2147;
g) E. B. Bauer, G. T. S. Andavan, T. K. Hollis, R. J. Rubio, J. Cho,
G. R. Kuchenbeiser, T. R. Helgert, C. S. Letko, F. S. Tham, Org.
Lett. 2008, 10, 1175–1178; h) B. M. Cochran, F. E. Michael, J. Am.
Chem. Soc. 2008, 130, 2786–2792; i) Z. Liu, J. F. Hartwig, J. Am.
Chem. Soc. 2008, 130, 1570–1571; j) G. Kovꢃcs, G. Ujaque, A.
Lledos, J. Am. Chem. Soc. 2008, 130, 853–864; k) C. Munro-Leight-
on, S. A. Delp, E. D. Blue, T. B. Gunnoe, Organometallics 2007, 26,
1483–1493; l) J. Ryu, G. Y. Li, T. J. Marks, J. Am. Chem. Soc. 2003,
125, 12584–12605; selected reviews: m) S. R. Chemler, Org.
Biomol. Chem. 2009, 7, 3009–3019; n) T. E. Mueller, K. C. Hultzsch,
M. Yus, F. Foubelo, M. Tada, Chem. Rev. 2008, 108, 3795–3892;
o) C. Liu, C. F. Bender, X. Han, R. A. Widenhoefer, Chem.
Commun. 2007, 3607–3618; p) R. A. Widenhoefer, X. Han, Eur. J.
Org. Chem. 2006, 4555–4563; q) A. L. Reznichenko, H. N. Nguyen,
K. C. Hultzsch, Angew. Chem. 2010, 122, 9168–9171; Angew. Chem.
Int. Ed. 2010, 49, 8984–8987.
[12] For recent discussions, see references [11a] and [11b].
Received: February 16, 2011
[8] See the Supporting Information for full details.
Published online: April 29, 2011
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