In situ generation of novel acyclic diaminocarbene-copper complex

Article abstract of DOI:10.1039/b821169h

A novel acyclic diaminocarbene-copper complex appears to be generated from a chloroamidinium salt and Cu(i)-thiophenecarboxylate in the presence of Grignard reagent based on ¹³C NMR studies and is a highly efficient catalyst for S_N2′

Full text of DOI:10.1039/b821169h

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In situ generation of novel acyclic diaminocarbene–copper complexw
Dimitri Hirsch-Weil, David R. Snead, Sebastien Inagaki, Hwimin Seo, Khalil A. Abboud
and Sukwon Hong*
Received (in Berkeley, CA, USA) 27th November 2008, Accepted 10th March 2009
First published as an Advance Article on the web 3rd April 2009
DOI: 10.1039/b821169h
A novel acyclic diaminocarbene–copper complex appears to be
generated from a chloroamidinium salt and Cu(I)-thiophene-
carboxylate in the presence of Grignard reagent based on 13C
NMR studies and is a highly efficient catalyst for SN20-allylic
alkylation.
crystallography (eqn (1)).w Interestingly, when this complex
was used in the SN20 allylic alkylation reaction,7 it gave a very
similar result compared to BIQ–CuCl (7) (eqn (2)).
N-Heterocyclic carbene ligands (NHC) have drawn much
attention recently due to their highly s-donating capacity, and
most carbene ligands are largely based on imidazoline-derived
cyclic frameworks.1,2 Nevertheless, stable acyclic diamino-
carbenes (ADC) as well as their metal complexes are known.3,4
Crystal structures of acyclic carbenes show substantially
larger N–C–N angles (121.01) than those of their cyclic analogs
(104.71), suggesting greater steric demands are exerted by
acyclic carbenes.3d Furthermore, acyclic diaminocarbenes are
more electron-donating than NHCs,4i but despite these inter-
esting properties, there are not many reported examples of
acyclic carbene ligands mainly because preparation of acyclic
carbenes and metal–ADC complexes are quite challenging.3,4
Intermolecular formamidinium ion formation often gives low
yield along with by-products,3b and the formamidinium proton
is less acidic,5 requiring a much stronger base such as lithium
diisopropylamide for deprotonation to generate the carbene
The possibility that Cu–carbene species might be generated
from chloroimidazolium–CuCl2 salt (3) and EtMgBr under the
allylic alkylation conditions led ꢁus to try commercially
available chloroamidinium 8ꢀBF4 as a potential acyclic
carbene precursor. We were pleased to find that the highly
SN20 selective allylic alkylation reaction was efficiently catalyzed
ꢁ
by the mixture of 8ꢀBF4 and CuCl2 (entry 1, Table 1). Cu(I)
salts such as CuCl (entry 2) or CuTC (entry 3) also gave
identical results to those with CuCl2. Note that acyclic carbene
9 prepared by the reported deprotonation protocol4d also gave a
similar result, which is consistent with the idea of in situ carbene
species.3d As an alternative to the deprotonation route, Furstner
¨
and co-workers reported a novel way to generate ADC–metal
complexes via oxidative addition of Pd into the C–Cl bond of
chloroamidinium salts.4g Recently we reported a concise syn-
thesis of biisoquinoline-based chiral tricyclic diaminocarbene
ligands (BIQ) and their Pd and Cu complexes.6 While we were
screening Cu metal precursors for the allylic alkylation reaction,
we serendipitously discovered a new route to ADC–Cu
complexes. Herein we wish to report our preliminary results
on in situ generation of ADC–Cu complexes from readily
available N,N,N0,N0-tetrasubstituted ureas.
Table 1 SN20 Allylic alkylation catalyzed by Cu–carbene complexes
Entry
Ligand precursor
Cu salt
Yield (%)a
g : ab
In the attempted synthesis of Cu(II)–BIQ complex 2 from
imidazolium precursor 1 and CuCl2, unexpectedly chloro-
imidazolium salt 3 was isolated and characterized by X-ray
ꢁ
1
2
3
4c
5
6
7
8ꢀBF4ꢁ
CuCl2
CuCl
82
81
83
71
57
25
9
93 : 7
93 : 7
94 : 6
90 : 10
92 : 8
94 : 6
13 : 87
8ꢀBF4ꢁ
8ꢀBF4
9
CuTC
CuTC
CuTC
None
CuTC
IMesdꢁ
8ꢀBF4
None
Department of Chemistry, University of Florida, P.O. Box 117200,
Gainesville, FL 32611-7200, USA. E-mail: sukwon@ufl.edu;
Fax: +1-352- 846-0296; Tel: +1-352-392-6787
a
b
c
Isolated yield. Determined by 1H NMR. 10 mol% of ADC 9 and
w Electronic supplementary information (ESI) available: Detailed
synthetic procedures and analytical data for new compounds. CCDC
711449. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/b821169h
d
CuTC were used. Isolated free carbene. TC = thiophene carboxylate,
IMes = 1,3-bis(2,4,6-trimethylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene.
ꢂc
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Table 2 Substrate scopea
to give high g selectivity (g : a = 94 : 6) whereas CuTC without
ꢁ
8ꢀBF4
(entry 7) showed very different selectivity
(g : a = 13 : 87).8
This ADC–Cu catalyst (8ꢀBF4ꢁ with CuTC) shows excellent
g
selectivity for various allylic substrates (Table 2).
Symmetrical dibenzoate substrate 10 can be used owing to
high g selectivity (entry 1), and quaternary centers can be
generated from tri-substituted alkene substrates in high yield
(entries 3–5). The reaction with nitrogen atom containing
substrate 16 was sluggish and 15 mol% of catalyst loading
was required (entry 5). However, this ADC–Cu catalyst
appears to be more reactive than the NHC–Cu catalyst
(IMesCuCl)9 which gave 24% yield of 17 under identical
conditions.
A series of 13C NMR studies were performed to monitor the
reaction of chloroamidinium, CuTC and Grignard reagent.
13C-labeled chloroamidinium precursor (80ꢀClꢁ) was prepared
to quickly detect the weak but characteristic 13C resonance
of the sp2-hybridized carbene carꢁbon (Scheme 1). Then
13C-labeled chloroamidinium (80ꢀCl ), CuCl and Grignard
reagent were mixed in THF-d8 and monitored by 13C NMR
at low temperature (Fig. 1).10
Entry Substrate
1
Product
g : a
Yield (%)
84
Z 98 : 2
2
3
4
Z 98 : 2
Z 98 : 2
Z 98 : 2
Z 98 : 2
97
95
96
93
5b
a
Reaction conditions: 5 mol% 8ꢀBF4ꢁ, 5 mol% CuTC, 1.5 equiv.
b
ꢁ
EtMgBr, Et2O, 0 1C, 1 h. 15 mol% CuTC and 8ꢀBF4 were used.
PMP = p-methoxyphenyl.
Scheme 1 Preparation of 13C-labeled chloroamidinium precursor
80ꢀClꢁ.
generation (entry 4). Isolated NHC (IMes) showed similarly
high g selectivity (g:a = 92 : 8) despite the slightly reduced
yield (entry 5). Both the copper salt and the chloroamidinium
seem to be necꢁessary for good yields (entries 6 and 7).
However, 8ꢀBF4 without CuTC (entry 6) still manages
When a mixture of chloroamidinium 80ꢀClꢁ and CuCl was
treated with PhMgBr, the starting material 80ꢀClꢁ was fully
Fig. 1 Direct 13C NMR monitoring (at ꢁ60 1C) of carbene–metal complex generation using C-labeled chloroamidinium precursor (80ꢀClꢁ).
13
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converted to two species showing typical metal–carbene sp2
carbon resonances at 206 and 217 ppm (Fig. 1a).4 The 161 and
168 ppm resonances are assigned to aryl and alkyl amidinium
compounds, 190 and 200, respectively.11,12 We speculated that
the signals at 206 ppm and 217 ppm might be assigned to
Cu–carbene complex (90–Cu)13 and Mg–carbene complex
(90–Mg),14 respectively. These tentative assignments are
supported by the following observations: when chloroamidinium
80ꢀClꢁ was treated with PhMgBr in the absence of CuCl
(Fig. 1b), the 216 ppm resonance appeared as the only carbene
species (90–Mg). When this mixture was further treated with
CuCl (Fig. 1c), the 216 ppm resonance is completely converteꢁd
to the resonance at 206 ppm (90–Cu). When a mixture of 80ꢀCl
and CuCl was treated with EtMgBr (Fig. 1d), the Cu–carbene
resonance at 207 ppm (90–Cu) was again observed while the
216 ppm resonance was not detected in this case. Importantly,
these assignments are also in accord with the 13C NMR studies
with known acyclic carbene species4d,15 prepared from deproto-
nation of 13C-labeled formamidinium ion 220ꢀPF6ꢁ (Scheme 2).w
Notes and references
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Schemeꢁ
2
Preparation of 13C-labeled formamidinium precursor
220ꢀPF6 and observed 13C resonance values.
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In conclusion, highly SN20-selective allylic alkylation can
be catalyzed by a mixture of chloroamidinium salt and
Cu(I)-thiophenecarboxylate in the presence of Grignard
reagent. 13C NMR study results are in accord with generation
of an acyclic diaminocarbene–copper species. Development of
chiral chloroamidinium precursors for enantioselective
reaction is currently in progress.
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We thank the University of Florida, the Donors of the
American Chemical Society Petroleum Research Fund
(PRF # 46157-G1), and James & Esther King Biomedical
Research Program, Florida Department of Health (08KN-04)
for support of this research. We thank Dr. Ghiviriga for
help with low temperature NMR. S. H. thanks Oak Ridge
Associated Universities for the Ralph E. Powe Junior Faculty
Enhancement Award.
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ꢂc
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Chem. Commun., 2009, 2475–2477 | 2477