Saturated abnormal NHC-gold(I) complexes: Synthesis and catalytic activity

Article abstract of DOI:10.1021/om4000659

New saturated abnormal N-heterocyclic carbene complexes of gold(I) have been prepared by a 1,3-dipolar cycloaddition of an in situ generated azomethine ylide with an isocyanogold(I) choride. A series of different substituents on the nitrogen atom of the 1

Full text of DOI:10.1021/om4000659

Article
pubs.acs.org/Organometallics
Saturated Abnormal NHC−Gold(I) Complexes: Synthesis and
Catalytic Activity
‡,§
Ruben Manzano,† Frank Rominger,
and A. Stephen K. Hashmi*,†, ‡
́
†CaRLa-Catalysis Research Laboratory, Im Neuenheimer Feld 584, 69120 Heidelberg, Germany
‡Organisch-Chemisches Institut, Ruprecht-Karls-Universitat Heidelberg, Im Neuenheimer Feld 270, 69221 Heidelberg, Germany
̈
S
* Supporting Information
ABSTRACT: New saturated abnormal N-heterocyclic car-
bene complexes of gold(I) have been prepared by a 1,3-dipolar
cycloaddition of an in situ generated azomethine ylide with an
isocyanogold(I) choride. A series of different substituents on
the nitrogen atom of the 1,3-dipole are tolerated without
problem. Substitutents on a carbon atom of the 1,3-dipole are
problematic in the case of the isocyanogold(I) chlorides; only
low yields are obtained. However, the corresponding isocyanogold(I) iodide shows good reactivity, and these abnormal N-
heterocyclic carbenes bear the substituent in a position α to the carbene carbon, as proven by a crystal structure analysis of one of
the products. Some of the new saturated abnormal N-heterocyclic carbene complexes were then tested in the gold-catalyzed
phenol synthesis; moderate turnover numbers of 252−380 could be reached.
analogues.2 Despite the interest in these compounds, the
procedures for the synthesis of unsaturated aNHC metal
complexes usually suffer from regioselectivity issues (normal
INTRODUCTION
■
Interest in the synthesis of N-heterocyclic carbene complexes
(NHCs)1 with reduced heteroatom stabilization2 has increased
versus abnormal binding mode), which are usually circum-
vented by blocking the C2 position of the heterocycle or by
means of bulky substituents neighboring this position.
Otherwise, mixtures of unsaturated aNHC and normal NHC
complexes and low yields were typically obtained.8d,9c,e On the
other hand, after one saturated intermediate was assumed
during the preparation of an unsaturated analogue,4 in a
previous publication12 we communicated the synthesis of
saturated abnormal NHC−gold(I) complexes by [3 + 2]
cycloaddition13 between azomethine ylides and isocyanogold(I)
complexes. In that study only the commercially available N-
(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine was re-
acted with a variety of isocyanogold(I) complexes, giving access
to saturated abnormal NHC−gold(I) complexes with different
substituents on the nitrogen atom at the carbene carbon atom.
This strategy completely avoids the regioselectivity issues, as
the carbon atom which becomes the carbene carbon is already
precoordinated to the metal in the isonitrile precursor, and thus
it for the first time allows the synthesis of aNHCs even without
bulky substituents flanking the carbene atom.
in the last few years. In contrast to normal NHCs (I; Figure 1),
Figure 1. Normal NHC (I), unsaturated abnormal NHC (II),
saturated abnormal NHC (III), and CAAC (IV).
the unsaturated abnormal NHCs (aNHCs, II; Figure 1) bear
the metal at a carbon atom in the two-carbon tether and not at
the carbon atom between the two nitrogen atoms. The
saturated analogues, saturated aNHCs (III; Figure 1), with
regard to the electronic situation very much resemble the very
successful cyclic alkyl amino carbenes (CAACs, IV; Figure 1).3
Both species possess only one nitrogen atom close to the
carbene atom; in addition, the saturated aNHCs have one
nitrogen atom in the backbone of the heterocyclic ring.
The first examples of unsaturated aNHC metal complexes
were reported by the groups of Crabtree,4 Lassaletta,5 and
Nolan.6 Since the report of a free isolable unsaturated aNHC by
Bertrand in 2009,7 several unsaturated aNHCs have been
bound to various elements, including palladium,8 iridium,9 and
other transition metals,10 as well as main-group elements.11
New synthetic and catalytic applications are continuously
appearing for these metal complexes, such as Suzuki−Miyaura
cross-coupling,6,8a,e hydrogen transfer reactions,9a,b,10c and
other transformations, probably due to the fact that the
unsaturated aNHCs are stronger donors than their normal
In the context of providing easy access to a library of NHC−
gold(I) complexes starting from isocyanides,14 we present here
the synthesis of saturated abnormal NHC−Au(I) complexes
bearing a variety of substituents both at the nitrogen next to the
carbene carbon and at the nitrogen atom in the backbone as
well as their evaluation as catalysts.
Received: January 25, 2013
Published: March 19, 2013
© 2013 American Chemical Society
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Scheme 1. Synthesis of the Precursors for Symmetrical Azomethine Ylides
RESULTS AND DISCUSSION
■
Synthesis of the aNHC−Gold(I) Complexes. For the
preparation of saturated aNHC−gold(I) complexes with
Table 1. Synthesis of Saturated aNHCs from Symmetrical
a
1,3-Dipole Precursors
Figure 2. Solid-state molecular structure of 7a.
us to place an allyl group and a chiral substituent at the central
position of the building block 4. Even though the second step
of this short sequence is not highly efficient, the starting
materials are readily accessible and thus overall even larger
amounts of 4 can easily be prepared.
In order to demonstrate a broad applicability of the
methodology, the symmetrical 1,3-dipole precursors 4a−c
were reacted with isocyanogold(I) complexes 5a,b in the
presence of a catalytic amount of trifluoroacetic acid at 0 °C.
These new results are summarized in Table 1. Although the
yields differed, all six combinations were successful; the lowest
yield (52%) was obtained in the case of 6b (entry 2), and the
best value (82%) was achieved with the allyl substituent (entry
4).
X-ray diffraction analysis of single crystals of 7a, obtained by
recrystallization from dichloromethane/hexane, unambiguously
showed the abnormal binding mode (Figure 2).15
Precursors 10a−d for asymmetrical 1,3-dipoles were
synthesized following a strategy similar to that outlined in
Scheme 1. The monoalkylation of benzylamine by means of
commercially available (1-chloroethyl)trimethylsilane (8a) or
readily accessible aromatic analogues 8b−d (obtained by
trimethylsilylation of the corresponding benzyl halides)
afforded the secondary amines 9a−d, which underwent
methoxymethylation to yield the N-(methoxymethyl)-N-
((trimethylsilyl)methyl)amines 10a−d (Scheme 2).
Initial attempts at cycloaddition of (tert-butylisocyano)-
chlorogold(I) 5a with 10a provided only traces of the desired
aNHC−gold(I) complex, independent of the amount of
trifluoroacetic acid employed (5 or 30 mol %). Nevertheless,
the cycloaddition of 5b with the same 1,3-dipole precursor
(10a) afforded the corresponding aNHC−gold(I) complex in a
modest but considerable 23% yield with excellent regioselec-
tivty (assignment of the obtained regioisomer by the crystal
structure analysis of another substrate; see Figure 3).
Encouraged by this result, we postulated that a modification
of the isocyanogold(I) complex might lead to an improvement
of the chemical yieldobviously in the two currently used
fragments, the frontier orbitals did not match properly for an
efficient cycloaddition.16 According to Sustmann’s classifica-
tion,17 azomethine ylides undergo type I cycloadditions. The
dominant FMO interaction is that of the HOMOdipole with the
a
Reaction conditions: 0.2 mmol of isocyanogold(I) complex 5, 0.4
mmol of 4 (2 equiv), 0.01 mmol of trifluoroacetic acid, 2 mL of
CH2Cl2, 1−3 h, 0 °C.
different substituents on the remote nitrogen of the hetero-
cycle, we first needed to establish a reliable and practical route
to the required azomethine ylide precursors. As shown in
Scheme 1, a route proceeding through alkylation of amines 2 by
the silylated building block 1 and subsequent installation of a
methoxymethyl group on the synthetic intermediate 3 allowed
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Scheme 2. Synthesis of the Precursors for Asymmetrical Azomethine Ylides
Scheme 3. Preparation of the Isocyanogold(I) Bromide and
Iodide from the Corresponding Chloride by Metathesis
Table 2. Synthesis of Saturated aNHCs from Asymmetrical
1,3-Dipole Precursors
a
18
LUMOalkene
.
The alkyl donor on the azomethine ylide
increases the HOMOdipole energy, and thus we assumed that
increasing the LUMO energy of the isocyanogold(I) complex
should reinstall reactivity. The two substituents, the aryl group
on the isonitrile and the halide on the gold, were the only two
options to achieve this. Since for a specific abnormal saturated
NHC complex a modification of the aryl group was not
desirable, we switched to bromide and iodide as less
electronegative halides on the gold(I) center. Thus the
analogous isocyanogold(I) bromide and iodide complexes
11b and 12b, prepared by simple ligand exchange from the
chloro counterparts as shown in Scheme 3, were subjected to
cycloaddition with 1,3-dipole precursor 10a in the presence of
catalytic amounts of trifluoroacetic acid. While the bromo
derivative did not have any beneficial effect on the trans-
formation, the analogous gold(I) iodide complex was by far
superior and afforded the aNHC−Au(I) complex in a greatly
improved yield (77%, Scheme 4). Since this halide ligand on
the precatalyst is eliminated with the help of silver salts for the
formation of the active catalyst anyway, there is no disadvantage
in preparing the aNHC−Au(I) iodides instead of the common
chlorides.
In order to show the versatility of the method, several
aNHC−gold(I) complexes bearing different R1 substituents
were prepared (Table 2). It became evident that in the case of
aliphatic substituents there were still problems; with the bulky
tBu substituent on the isonitrile (entry 1) only a 19% yield was
achieved and with Bn also only 21% was isolated (entry 6).
With aromatic substituents the yields were better; 46% of
product was accessible in the case of 12d (entry 4), and the
other three combinations gave good yields between 62% and
77% (entries 2, 3, and 5).
a
Reaction conditions: 0.2 mmol of isocyanogold(I) complex 12, 0.4
mmol of 10a (2 equiv), 0.02 mmol of trifluoroacetic acid, 2 mL of
CH2Cl2, 1−3 h, 0 °C.
Scheme 4. Superiority of the Iodide in 1,3-Dipolar Cycloaddition with 1-Methyl-2-benzylazomethine Ylide
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Scheme 6. Two More Challenging Substrates Chosen for the
Test Reactions
a
Table 3. Catalytic Studies with Abnormal NHCs
Figure 3. Solid-state molecular structure of 15b.
The regioselectivity in this case could be unambiguously
confirmed by an X-ray crystal structure analysis of 15b (Figure
3);15 the methyl group is at the position next to the carbene
carbon. It must be noted that the regioisomeric compound with
the methyl substituent in the position between the two nitrogen
atoms has not been detected.
aNHC−
yield of 18
TON for
yield of 20
TON for
Au(I)
(%)
18
(%)
20
Aryl-substituted compounds 10b−d were also reacted with
the isocyanogold(I) iodide complex 12b in the presence of 10
mol % of TFA. In all cases only a small amount of the
corresponding saturated aNHC−Au(I) complex was observed.
However, the use of a large excess of 1,3-dipole precursor 10b
(10 equiv) and a substoichiometric amount of trifluoroacetic
acid (50 mol %) allowed the isolation of the saturated aNHC−
Au(I) complex 16b in a modest 31% yield (Scheme 5).
Test of the Catalytic Activity in the Furan-yne
Reaction. As model reactions to evaluate the catalytic activity
of the saturated aNHC−Au(I) complexes that were synthe-
sized, gold-catalyzed phenol synthesis was chosen.19 Since for
this reaction for the substrates 17 and 19 already quite
reasonable turnover numbers (TONs) had been achieved,14d,20
we chose a catalyst loading of 0.25 mol % (with higher catalyst
loadings a complete conversion to the product was achieved,
and we wanted to explore the limit for the TON), more
difficult test substrates (Scheme 6), and activation by AgNTf2
according to Gagosz.21 The results are summarized in Table 3.
Clearly all the catalysts are good catalysts; the TONs range
from 252 to 336, which are good but not outstanding numbers
for this type of test reaction, which follows a special
mechanism.22 These best TONs reached so far are 730 for
1723 and 1900 for 19.24
6a
78
63
73
64
69
66
71
78
312
252
292
256
276
264
284
312
92
91
89
88
95
92
95
95
368
364
356
352
380
368
380
380
6b
6c
6d
7a
7b
7c
15b
a
Reaction conditions: 200 μmol of substrate 17 or 19, 0.50 μmol of
aNHC−Au(I) (0.25 mol %), 0.50 μmol of AgNTf2 (0.25 mol %), 8
μmol of tri-tert-butylbenzene as internal standard (TTBB), 600 μL of
CD2Cl2, room temperature, 0.5−8 h. The yield was determined by 1H
NMR.
CONCLUSION
■
Now a broad variation of aNHC−gold(I) complexes are
accessible, and the use of the gold(I) iodide precursor could be
very useful for future access to other new carbene ligands by
1,3-dipolar cycloadditions. With functionalized side chains, such
as the allyl group in this investigation, further modification of
the aNHC complexes and even an attachment to solid
supports25 should be possible and should open new
perspectives.
Scheme 5. Use of Isocyanogold(I) Iodides Does Not Allow an Efficient Synthesis with 1-Aryl-2-benzyl-Substituted Azomethine
Ylide
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Abraham, M. Y.; Gilliard, R. J., Jr.; Wei, P.; Campana, C. F.; Schaefer,
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ASSOCIATED CONTENT
* Supporting Information
Text and figures giving experimental details and character-
ization data and CIF files giving crystallographic data. This
material is available free of charge via the Internet at http://
pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*A.S.K.H.: tel, +49(0)6221-548413; fax, +49(0)6221-544205;
e-mail, hashmi@hashmi.de.
(12) Hashmi, A. S. K.; Riedel, D.; Rudolph, M.; Rominger, F.; Oeser,
T. Chem. Eur. J. 2012, 18, 3827.
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Pure Appl. Chem. 1989, 61, 613.
(14) (a) Hashmi, A. S. K.; Yu, Y.; Rominger, F. Organometallics 2012,
■
Author Contributions
31, 895. (b) Hashmi, A. S. K.; Lothschutz, C.; Graf, K.; Haffner, T.;
̈
̈
§Crystallographic investigation.
Schuster, A.; Rominger, F. Adv. Synth. Catal. 2011, 353, 1407.
(c) Hashmi, A. S. K.; Lothschutz, C.; Bohling, C.; Hengst, T.;
̈
̈
Notes
Hubbert, C.; Rominger, F. Adv. Synth. Catal. 2010, 352, 3001.
The authors declare no competing financial interest.
(d) Hashmi, A. S. K.; Hengst, T.; Lothschutz, C.; Rominger, F. Adv.
̈
Synth. Catal. 2010, 352, 1315.
ACKNOWLEDGMENTS
R.M. works at CaRLa of Heidelberg University, cofinanced by
the University of Heidelberg, the State of Baden-Wurttemberg,
and BASF SE.
■
(15) CCDC 920434 (7a) and CCDC 920435 (15b) contain
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.
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