Synthesis and structures of fused N-heterocylic carbenes and their rhodium complexes

Article abstract of DOI:10.1021/om100262x

New procedures for the synthesis of N-heterocyclic carbenes with multiple fused rings have been developed utilizing a key ring-closing metathesis step. Rhodium complexes were obtained via the pentafluorophenyl carbene adducts. Solid-state structural behav

Full text of DOI:10.1021/om100262x

Organometallics 2010, 29, 3765–3768 3765
DOI: 10.1021/om100262x
Synthesis and Structures of Fused N-Heterocylic Carbenes and
Their Rhodium Complexes
Jean Li, Ian C. Stewart, and Robert H. Grubbs*
The Arnold and Mabel Beckman Laboratories of Chemical Synthesis, Division of Chemistry and
Chemical Engineering, California Institute of Technology, Pasadena, California 91125
Received April 2, 2010
New procedures for the synthesis of N-heterocyclic carbenes with multiple fused rings have been
developed utilizing a key ring-closing metathesis step. Rhodium complexes were obtained via the
pentafluorophenyl carbene adducts. Solid-state structural behaviors of the new carbene ligands were
analyzed via X-ray crystallography.
N-Heterocyclic carbenes (NHCs), first isolated by Arduengo
et al. in 1991, have become a well-studied and well-utilized
class of ligands in the field of transition metal-catalyzed
reactions.1 Their proficiency in catalysis, variable electronic
properties, and ease of translation into complex architectural
structures have allowed for the development of unique
reactivity and targeted selectivity.2-6 In the past 20 years,
NHCs have been applied as ligands in reactions such
as palladium-catalyzed cross-coupling, olefin metathesis,
asymmetric hydrosilylation, and conjugate addition.7-12
Figure 1. NHCs utilized in metal-mediated catalysis.
Free NHCs have also shown great efficacy as organocata-
lysts in a variety of reactions.13,14 Exploration of novel
structural motifs has enabled the development of novel
applications for NHCs. Serving as a positive feedback loop,
as the synthetic and catalytic applications have grown, the
array of structural motifs has grown in parallel (Figure 1),
illustrating the dynamic interchange between structure and
function.1,15,16
*To whom correspondence should be addressed. E-mail: rhg@
caltech.edu.
(1) Arduengo, A. J.; Harlow, R. L.; Kline, M. J. Am. Chem. Soc.
1991, 113, 361.
Figure 2. Design of rotationally locked NHCs.
(2) Dixon, D. A.; Arduengo, A. J. J. Phys. Chem. 1991, 95, 4180.
(3) Diez-Gonzalez, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109,
3612.
(4) Corberan, R.; Mas-Marza, E.; Peris, E. Eur. J. Inorg. Chem. 2009,
1700.
(5) Lee, H. M.; Lee, C. C.; Cheng, P. Y. Curr. Org. Chem. 2007, 11,
1491.
(6) Herrmann, W. A.; Schutz, J.; Frey, G. D.; Herdtweck, E. Orga-
nometallics 2006, 25, 2437.
(7) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2039.
(8) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18.
(9) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290.
(10) Crudden, C. M.; Allen, D. P. Coord. Chem. Rev. 2004, 248, 2247.
(11) Snead, D. R.; Seo, H.; Hong, S. Curr. Org. Chem. 2008, 12, 1370.
(12) de Fremont, P.; Marion, N.; Nolan, S. P. Coord. Chem. Rev.
2009, 253, 862.
In particular, fused NHC structures are of interest, as it
has been shown computationally that the rotational lability
of the carbene can greatly influence the behavior and dyna-
mics of the NHC-bound metal complex.17,18 In this study,
the syntheses of fused carbenes 6 and 7 were designed to
allow for control of stereochemistry at the backbone of the
NHC as well as facile modification of the N-bound arene
fragment. A three-carbon chain from the backbone of the
NHC to the aryl was chosen to form the cis-fused as well as
the trans-fused structures (Figure 2). Independent synthesis
of each carbene precursor allowed for separate cis and trans
routes, bypassing a need to separate the meso from the
(13) Enders, D.; Balensiefer, T. Acc. Chem. Res. 2004, 37, 534.
(14) Brown, M. K.; May, T. L.; Baxter, C. A.; Hoveyda, A. H. Angew.
Chem., Int. Ed. 2007, 46, 1097.
(17) Clavier, H.; Correa, A.; Cavallo, L.; Escudero-Adan, E. C.;
Benet-Buchholz, J.; Slawin, A. M. Z.; Nolan, S. P. Eur. J. Inorg. Chem.
(15) Berlin, J. M.; Campbell, K.; Ritter, T.; Funk, T. W.; Chlenov, A.;
Grubbs, R. H. Org. Lett. 2007, 9, 1339.
(16) Vehlow, K.; Gessler, S.; Blechert, S. Angew. Chem., Int. Ed. 2007,
46, 8082.
2009, 1767.
(18) Ragone, F.; Poater, A.; Cavallo, L. J. Am. Chem. Soc. 2010, 132,
4249.
r
2010 American Chemical Society
Published on Web 08/05/2010
pubs.acs.org/Organometallics

3766 Organometallics, Vol. 29, No. 17, 2010
Li et al.
Scheme 2. Synthesis of Trans Carbene Precursor 16
Scheme 1. Synthesis of Cis Carbene Precursor 11
Scheme 3. Synthesis of Rhodium Complexes
racemic forms. Synthesis of the racemate could be easily
modified to render the enantioenriched mixtures of the trans
species via resolution with inexpensive L-(þ)-tartaric acid.19
Herrmann and Blechert have synthesized similar NHC
structures.16,20,21 Carbene 4 was appended to ruthenium and
shown to have limited metathesis activity.16 Unfortunately,
the synthesis of 4 yielded a 3:1 mixture of the meso and
racemic forms, and only the meso form was isolated for
study.16 The crystal structure of carbene 4, which contains a
C2 linkage, exhibited planarity of the N-bound arene with
the heterocycle, thereby rendering the ruthenium species
noncanonical with standard ruthenium-based catalysts.
In designing both syntheses, we chose to utilize a ring-
closing metathesis as the key step in fusing the seven-
membered ring fragment. Previous syntheses of fused NHC
frameworks began from quinoline-type derivatives and were
thus limited in both ring size and stereocontrol.16 With
intimate knowledge of the olefin metathesis reaction at hand,
we imagined separate syntheses hinging upon retention of
the initially introduced backbone stereochemistry during
ring-closing metathesis (RCM).
condensed with pentafluorobenzaldehyde to form 9, follow-
ing a recent report.23 Ring-closing with a ruthenium catalyst
provided cis-fused adduct 10, and hydrogenation gave the
desired carbene precursor 11.
Entry into the racemic trans-fused carbene began with aza-
Claisen rearrangement of commercially available N-allylani-
line. Condensation with glyoxal yielded the bisimine, which
was further functionalized via Grignard addition and in situ
urea formation to give intermediate 12. Although the penta-
fluorophenyl adduct could be introduced immediately suc-
ceeding addition of Grignard, the urea provided higher yields
in the metathesis reaction, yielding ring-closed 13. Hydro-
genation with Pd/C at 1 atm gave the urea 14, which was
readily cleaved with lithium aluminum hydride to afford
trans-fused diamine 15. The free diamine was then conden-
sed with pentafluorobenzaldehyde to provide carbene pre-
cursor 16.
The cis-cyclohexenyldiamine was synthesized by a known
procedure.22 Palladium-catalyzed cross-coupling of the free
diamine with o-bromostyrene yielded secondary diamine 8.
Attempts at ring-closing metathesis of 8 resulted in decom-
position of both diamine and the ruthenium benzylidene
species. In order to cloak the diamino functionality, 8 was
(19) Schanz, H. J.; Linseis, M. A.; Gilheany, D. G. Tetrahedron:
Asymmetry 2003, 14, 2763.
(20) Herrmann, W. A.; Baskakov, D.; Herdtweck, E.; Hoffmann,
S. D.; Bunlaksananusorn, T.; Rampf, F.; Rodefeld, L. Organometallics
2006, 25, 2449.
Recently, we reported the facile conversion of penta-
fluorophenyl adducts as NHC precursors for ruthenium
(21) Baskakov, D.; Herrmann, W. A.; Herdtweck, E.; Hoffmann,
S. D. Organometallics 2007, 26, 626.
(22) Witiak, D. T.; Rotella, D. P.; Filippi, J. A.; Gallucci, J. J. Med.
Chem. 1987, 30, 1327.
(23) Blum, A. P.; Ritter, T.; Grubbs, R. H. Organometallics 2007, 26,
2122.

Article
Organometallics, Vol. 29, No. 17, 2010 3767
Figure 3. ORTEP diagram of 17 with 50% probability ellipsoids.
˚
Table 1. Selected Bond Lengths [A] and Angles [deg] for 17
Figure 4. ORTEP diagram of 18 with 50% probability ellipsoids.
Rh(1)-C(1)
Rh(1)-C(29)
Rh(1)-C(22)
Rh(1)-C(25)
Rh(1)-C(26)
Rh(1)-Cl(1)
1.992(2)
2.105(2)
2.124(2)
2.207(2)
2.247(2)
2.4075(5)
C(1)-N(1)-C(2)
111.93(17)
110.99(17)
106.57(19)
124.58(14)
128.82(15)
98.93(17)
100.04(18)
37.57
C(1)-N(2)-C(3)
˚
Table 2. Selected Bond Lengths [A] and Angles [deg] for 18
N(1)-C(1)-N(2)
N(1)-C(1)-Rh(1)
N(2)-C(1)-Rh(1)
N(1)-C(2)-C(3)
Rh(1)-C(1)
Rh(1)-C(22)
Rh(1)-C(29)
Rh(1)-C(26)
Rh(1)-C(25)
Rh(1)-Cl(1)
2.0032(7)
2.0969(7)
2.1263(8)
2.1847(8)
2.2169(8)
2.3896(2)
C(1)-N(1)-C(2)
113.12(5)
113.17(5)
107.40(6)
123.40(5)
129.10(5)
101.40(6)
101.27(5)
136.83
C(1)-N(2)-C(3)
N(1)-C(1)-N(2)
N(2)-C(3)-C(2)
N(1)-C(1)-Rh(1)
N(2)-C(1)-Rh(1)
N(1)-C(2)-C(3)
C(12)-C(2)-C(3)-C(13)
C(5)-C(4)- N(1)-C(1)
C(20)-C(21)-N(2)-C(1)
67.86
31.84
N(2)-C(3)-C(2)
C(12)-C(2)-C(3)-C(13)
C(5)-C(4)- N(1)-C(1)
C(20)-C(21)-N(2)-C(1)
complexes.23 We chose to isolate the masked carbene as
pentafluorophenyl adducts rather than the traditional
imidazolinium salts in order to allow ligation onto metal
fragments in the absence of a strong base. Thus, reaction of
11 or 16 with rhodium cyclooctadiene chloride dimer gave
the corresponding rhodium complexes shown (Scheme 3).
Crystals suitable for X-ray diffraction studies were obtained
as bright yellow blocks by vapor diffusion of pentane into a
benzene solution of either 17 or 18.
50.98
62.57
Figure 3 shows the ORTEP diagram of the cis-fused
rhodium complex 17 obtained from X-ray diffraction. We
were surprised to note that, although there exists a cis
orientation at the backbone of the NHC, a distortion in
the carbene allows the two linkers to obtain a relative trans
configuration of the N-bound arenes. Note that the dihedral
torsion angle between C(12)-C(2)-C(3)-C(13) of 37.57°
confirms a cis orientation (Table 1). Neither arene is ortho-
gonal to the plane of the NHC, containing dihedral angles
C(5)-C(4)-N(1)-C(1) of 67.86° and C(20)-C(21)-N(2)-
C(1) of 31.84°.
Figure 5. Side view of structures 17 (left) and 18 (right).
X-ray crystal analysis of trans-fused 18 confirmed the
expected anti-anti relationship. Analogous to previously
reported nonfused ligated NHCs, Figure 4 shows the NHC
to be planar, without the distortion noted in Figure 3.
Table 2 lists selected bond lengths and angles for 18. Here
the dihedral torsion angle at the backbone of the carbene is
greater than 90°, with the angle C(12)-C(2)-C(3)-C(13) of
136.83°. Again, neither arene ring is orthogonal or planar to
the NHC, with dihedral angles C(5)-C(4)-N(1)-C(1) of
50.98° and C(20)-C(21)-N(2)-C(1) of 62.57°.
in Figure 5. It is clear that the cis linkage exists for complex
17; however, the arenes are locked in a relative trans con-
formation, similar to that of complex 18, which shows a
higher degree of overall symmetry.
In summary, we have developed the synthesis of stereo-
chemically defined fused N-heterocyclic carbene structures,
which can be obtained in gram quantities as either the meso
form or the racemate. X-ray crystallography data confirmed
the covalent linkages.
A simplified side view of both cis- and trans-fused
Rh species with hydrogens omitted for clarity is shown
Acknowledgment. The authors wish to thank the
NIH (F32GM078734 and K99GM084302 to I.C.S.

3768 Organometallics, Vol. 29, No. 17, 2010
Li et al.
and 5RO1GM31332 to R.H.G.) for generous financial sup-
port. J.L. thanks the National Science Foundation for a
Graduate Research Fellowship. This research was made with
government support under and awarded by DoD, Air Force
Office of Scientific Research, National Defense Science and
Engineering Graduate (NDSEG) Fellowship, 32 CFR 168a.
Dr. Michael W. Day and Lawrence M. Henling are thanked
for crystallographic work, and Dr. David Vandervelde is
thanked for NMR spectroscopy work.
Supporting Information Available: Crystallographic data for
complexes 17 and 18, experimental procedures, and NMR data
for all new compounds are available. This material is available
free of charge via the Internet at http://pubs.acs.org.