A new route to acyclic diaminocarbenes via lithium-halogen exchange

Article abstract of DOI:10.1021/ol9013156

A lithium - halogen exchange route has been developed to generate acyclic diaminocarbenes (ADC) from chloroamidinium salts. Convenient access to various ADC complexes (B, Rh, lr, Pd) stems from a one-pot transmetalation protocol. Formation of a carbenoid species is suggested by 1D and 2D NMR studies with a ¹³C-labeled chloroamidinium precursor and also by X-ray structures of transition metal-carbene complexes. Rh-ADC complex 4 is an effective catalyst for the 1,2-addition of aryl boronic acids to aryl aldehydes.

Full text of DOI:10.1021/ol9013156

ORGANIC
LETTERS
2009
Vol. 11, No. 15
3274-3277
A New Route to Acyclic
Diaminocarbenes via Lithium-Halogen
Exchange
David R. Snead, Ion Ghiviriga, Khalil A. Abboud, and Sukwon Hong*
Department of Chemistry, UniVersity of Florida, P. O. Box 117200,
GainesVille, Florida 32611-7200
sukwon@ufl.edu
Received April 17, 2009
ABSTRACT
A lithium-halogen exchange route has been developed to generate acyclic diaminocarbenes (ADC) from chloroamidinium salts. Convenient
access to various ADC complexes (B, Rh, Ir, Pd) stems from a one-pot transmetalation protocol. Formation of a carbenoid species is suggested
by 1D and 2D NMR studies with a 13C-labeled chloroamidinium precursor and also by X-ray structures of transition metal-carbene complexes.
Rh-ADC complex 4 is an effective catalyst for the 1,2-addition of aryl boronic acids to aryl aldehydes.
N-Heterocyclic carbenes (NHCs) have emerged as important
ancillary ligands1 as well as nucleophilic organocatalysts2
as a result of their highly σ-donating capacity. In contrast,
acyclic diaminocarbenes (ADCs) have received much less at-
tention despite several interesting properties.3-7 ADCs are
more electron-donating than NHCs,4 and furthermore they
impose greater steric demands owing to substantially larger
N-C-N bond angles (121.0° vs 104.7°).3c
(1) (a) Hahn, F. E.; Jahnke, M. C. Angew. Chem., Int. Ed. 2008, 47,
3122–3172. (b) Glorius, F. Top. Organomet. Chem. 2007, 21, 1–20. (c)
Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew. Chem., Int. Ed.
2007, 46, 2768–2813. (d) N-heterocyclic Carbenes in Synthesis; Nolan, S. P.,
Ed.; Wiley-VCH: Weinheim, Germany, 2006. (e) Herrmann, W. A. Angew.
Chem., Int. Ed. 2002, 41, 1290–1309.
The paucity of ADCs may be attributed to the more
challenging preparation of acyclic carbenes and ADC-metal
complexes (Figure 1A).3-6 For example, intermolecular
formamidinium ion formation often gives low yield along
with byproduct,3b and stronger bases such as LDA are
required to deprotonate a less acidic formamidinium pro-
ton.3,4,7 Therefore, new alternative routes have been devel-
oped to prepare ADC-metal complexes. Slaughter reported
formation of bidentate, Chugaev-type ADC-metal complexes
(2) (a) Marion, N.; D´ıez-Gonza´lez, S.; Nolan, S. P. Angew. Chem., Int.
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Chem. ReV. Published ASAP (DOI: 10.1021/cr800549j)
.
10.1021/ol9013156 CCC: $40.75
Published on Web 07/08/2009
 2009 American Chemical Society

lithiation has been speculated to generate carbenoid inter-
13
mediates in reaction with R2CBr2 and in the Fritsch-
Buttenberg-Wiechell rearrangement.14 Nevertheless, to the
best of our knowledge, there have been no examples using
lithium-halogen exchange to form diaminocarbenes from
chloroamidiniums. Recently, our group discovered that ADC-
Cu complexes can be generated in situ from chloroamidinium
1 and Cu(I)-thiophenecarboxylate in the presence of Grignard
reagents.15 Herein, we report a more general lithium-halogen
exchange route to acylic diaminocarbenes and convenient
one-pot transmetalation to various metal-ADC species.
First, access to the carbene intermediate through lithium-
halogen exchange was probed. Intercept of a carbene
intermediate with sulfur to form a thiourea can be taken as
simple proof of carbene generation (Scheme 1).16 We were
Figure 1. Routes to acyclic diaminocarbenes.
by nucleophilic addition of either hydrazines or amines to
metal-bound isocyanides (Figure 1B),5 and Fu¨rstner dem-
onstrated that monodentate ADC-Pd complexes can be
prepared via oxidative addition of (Ph3P)4Pd into the C-Cl
bond of chloroamidinium ion precursors (Figure 1C).6
However, this route to carbenes requires the use and
incorporation of phosphine into metal catalyst, limiting the
applicability.
Scheme 1. Proof of Carbene Intermediacy
We envisioned that, when applied to chloroamidinium
precursors, lithium-halogen exchange might provide a new
and general route to diaminocarbenes (eq 1). Organolithium
reagents have played an important role in organic synthesis,8
and the formation of these reagents proceeds through a
number of routes including reduction with metallic lithium,9
deprotonation with a lithiated base,10 lithium-halogen ex-
change,11 and transmetalation.12 It is important to note that
pleased to isolate thiourea 2 in 68% yield when the
organolithium intermediate was treated with elemental sulfur.
Without lithium-halogen exchange no thiourea was formed.
In addition, the carbene intermediacy is further sup-
ported by low-temperature 13C NMR studies with 13C-
labeled chloroamidinium precursor 1′. After treatment of
chloroamidinium 1′ with n-BuLi at -78 °C in THF-d8, a
characteristic ADC resonance at 233 ppm17 was observed
at -30 °C, suggesting the generation of a carbene
species.18 In the 2D gHMBC spectrum, the carbene carbon
(232.9 ppm) displayed couplings with two protons at 3.47
and 3.66 ppm (Figure 2). The gDQCOSY spectrum
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Org. Lett., Vol. 11, No. 15, 2009
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Scheme 2
.
Synthesis of Diaminocarbene-Metal Complexes via
One-Pot Transmetalation
Figure 2. 2D gHMBC spectrum.
revealed the sequence 3.47-1.89-1.76-3.66. The carbons
carrying these protons were detected in the gHMQC
spectrum at 48.4, 26.5, 24.5, and 55.8 ppm, respectively.19
Therefore, the two proton resonances at 3.47 and 3.66 ppm
can be assigned to the two protons at the C2 position of
pyrrolidine, and this gHMBC spectrum is consistent with
the proposed carbene intermediate structure.
Encouraged by these results, we turned our attention
to a potential transfer of the lithiocarbene to ADC-metal
complexes. To our delight, various metal-carbene com-
plexes were prepared in good yields through lithium-
halogen exchange followed by one-pot transmetalation
(Scheme 2). ADC ligands stemming from pyrrolidine and
piperidine, as well as 2-methylpyrrolidine, were success-
fully introduced to Rh and Ir metal centers. When cyclic
chloroimidazolidinium precursor 8 was used, NHC-Rh 9
and NHC-Ir 10 were isolated in reasonable yields. In
addition, an ADC-Pd complex was prepared in 45% yield
using palladacycle 1120 with t-BuLi. Interestingly, this
carbene intermediate can also be trapped with a main
group electrophile, BF3, to form a highly stable Lewis
acid-base adduct.21 It is important to note that the
lithium-halogen exchange protocol has allowed access
to a variety of transition metal-carbene complexes as well
as a main group adduct and does not necessitate the use
of electron-rich metal precursors or the inclusion of
phosphine ligands.
diaminocarbene-metal complexes. ADC-Rh(COD)Cl 4 ex-
hibits a N-C-N carbene bond angle of 117.90°, whereas
NHC-Ir(COD)Cl 10 has an angle of 108.6°. The pyrrolidine
rings of the ADC exhibit a torsion angle of approximately
26°, which contrasts the flat nature of the heterocyclic ring
in the NHC complex 10. Ir-ADC complex 5 exhibits a longer
carbene-Ir bond length of 2.045(5) Å as compared to a
length of 2.028(7) Å for NHC-Ir 10, which suggests the ADC
is more sterically demanding.
Rh-ADC complex 4 proved effective in the 1,2-addition
of aryl boronic acids to aryl aldehydes (Table 1).22
Notably, ADC complex 4 gave yields higher than those
of both an NHC complex and a diene complex (entries
1-3), indicating the potential of ADCs as an alternative
to phosphine23 or NHC24 ligands. The reaction works well
with various boronic acids (entries 3-7), if ortho-
substituted aldehydes (entries 3-8) or electron-deficient
aldehydes (entries 9 and 10) are used.
X-ray structures of ADC-Rh(COD)Cl 4 (Figure 3), ADC-
Ir(COD)Cl 5,18 and NHC-Ir(COD)Cl 1018 provided unam-
biguous proof of the aforementioned methodology for
(18) See Supporting Information for details.
(19) The non-equivalence of the R positions in the pyrrolidine moiety
indicates restricted rotation about the carbene CsN bond.
(20) Cope, A. C.; Friedrich, E. C. J. Am. Chem. Soc. 1968, 90, 909–
913.
(22) (a) Miyaura, N. Bull. Chem. Soc. Jpn. 2008, 81, 1535–1553. (b)
Darses, S.; Genet, J.-P. Chem. ReV. 2008, 108, 288–325. (c) Schmidt, F.;
Stemmler, R. T.; Rudolph, J.; Bolm, C. Chem. Soc. ReV. 2006, 35, 454–
470.
(21) Arduengo, A. J., III.; Davidson, F.; Krafczyk, R.; Marshall, W. J.;
Schmutzler, R. Monatsh. Chem. 2000, 131, 251–265.
3276
Org. Lett., Vol. 11, No. 15, 2009

Table 1. ADC-Rh Catalyzed 1,2-Addition of Boronic Acidsa
Figure 3. Molecular structure of complex 4. Thermal ellipsoids
are drawn at the 50% probability level. Selected bond lengths (Å)
and angles (deg): Rh1-C9, 2.022(2); Rh1-Cl1, 2.3855(6); Rh1-C1,
2.110(2); Rh1-C2, 2.104(2); Rh1-C5, 2.241(2); Rh1-C6, 2.197(2);
N1-C9-N2,117.90(18);N2-C9-N1-C10,25.68(32);N1-C9-N2-C14,
26.69(30).
In summary, a lithium-halogen exchange route has
been developed to generate acyclic diaminocarbenes from
chloroamidinium salts. The one-pot transmetalation allows
convenient access to various metal-ADC complexes.
Generation of a lithiated carbene intermediate is suggested
by NMR studies. The metal-carbene complexes were
confirmed by X-ray. Rh-ADC complex 4 is an efficient
catalyst for the 1,2-addition of aryl boronic acids to aryl
aldehydes. Currently, further elaboration of this methodol-
ogy to access other transition metal-carbene complexes
as well as development of chiral ADC ligands are in
progress in our laboratory.
a The reaction was conducted with 1.5 mol % of [Rh] (0.0075 mmol),
KOtBu (1 mmol), aldehyde (0.5 mmol), and boronic acid (1 mmol) in 1.95
mL of DME and 0.55 mL of H2O. b Yield was taken as the average of
multiple runs. c Reation time of 7 h. IMes-Rh ) IMesRh(COD)Cl.
Acknowledgment. We thank the James & Esther King
Biomedical Research Program and Florida Department of
Health (08KN-04) for support of this research.
(23) (a) Jagt, R. B. C.; Toullec, P. Y.; de Vries, J. G.; Feringa, B. L.;
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X., J.-H.; Shi, W.-J.; Zhang, Q.; Zhou, Q.-L. Org. Lett. 2006, 8, 1479–
1481. (c) Pucheault, M.; Darses, S.; Genet, J.-P. Chem. Commun. 2005,
4714–4716. (d) Sakai, M.; Ueda, M.; Miyaura, N. Angew. Chem., Int. Ed.
1998, 37, 3279–3281.
Supporting Information Available: Detailed synthetic
procedures, analytical data for new compounds, and X-ray
crystallographic data for 4, 5, and 10 in CIF format. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(24) (a) Trindade, A. F.; Gois, P. M. P.; Veiros, L. F.; Andre´, V.; Duarte,
M. T.; Afonso, C. A. M.; Caddick, S.; Cloke, F. G. N. J. Org. Chem. 2008,
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