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

Grubbs, Robert H.

Li, Jean

Stewart, Ian C.

English

Caltech Authors - Main

Synthesis and Structure 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
New procedures for the synthesis of N – heterocyclic carbenes with 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 behavior 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 Free NHCs have also shown great
efficacy as organocatalysts 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
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 dynamics 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 racemic forms. Synthesis of the
racemate could be easily modified to render the enantioenriched mixtures of the trans
species via resolution with inexpensive L-(+)-tartaric acid.19
Hermann 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.
rhg@caltech.edu.
Supporting Information Available. Crystallographic data for complexes 17 and 18, experimental procedures and NMR data for all new
compounds are available.
NIH Public Access
Author Manuscript
Organometallics. Author manuscript; available in PMC 2011 September 13.
Published in final edited form as:
Organometallics. 2010 September 13; 29(17): 3765–3768. doi:10.1021/om100262x.
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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).
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 decomposition of both diamine and the
ruthenium benzylidene species. In order to cloak the diamino functionality, 8 was condensed
with pentafluorobenzaldehyde to form 9, following a recent report.23 Ring-closing with
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-allylaniline. Condensation with glyoxal yielded the bisimine,
which was further functionalized via Grignard addition and in situ urea formation to give
intermediate 12. Although the pentaflurophenyl adduct could be introduced immediately
succeeding addition of Grignard, the urea provided higher yields in the metathesis reaction,
yielding ring-closed 13.
Hydrogenation 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 condensed
with pentafluorobenzaldehyde to provide the carbene precursor 16.
Recently, we reported the facile decomposition of pentaflurophenyl adducts as NHC-
precursors for ruthenium complexes.23 We chose to isolate the masked carbene as
pentaflurophenyl 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.
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 the dihedral torsion angle between C(12)-
C(2)-C(3)-C(13) at 37.57° confirms a cis-orientation (Table 1). Neither arene is orthogonal
to the plane of the NHC, containing dihedral angles at C(5)-C(4)- N(1)-C(1) of 67.86° and at
C(20)-C(21)-N(2)-C(1) of 31.84°.
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 at 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
at C(5)-C(4)- N(1)-C(1) of 50.98° and at C(20)-C(21)-N(2)-C(1) of 62.57°.
A simplified side view of both cis and trans fused Rh-species with hydrogens omitted for
clarity is shown in Figure 5. It is clear that the cis linkage exists for complex 17, however,
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the arenes are locked in a relative trans conformation, similar to that of complex 18, which
shows a higher degree of overall symmetry.
In summary, we have developed the synthesis of stereochemically defined fused N-
heterocyclic carbene structures which can be obtained in gram quantities either as the meso
form or the racemate. X-ray crystallography data confirmed the covalent linkages.
Supplementary Material
Refer to Web version on PubMed Central for supplementary material.
Acknowledgments
The authors wish to thank the NIH (F32GM078734 and K99GM084302 to I. C. S. and 5RO1GM31332 to R. H. G.)
for generous financial support. 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.
References
1. Arduengo AJ, Harlow RL, Kline M. J Am Chem Soc 1991;113:361.
2. Dixon DA, Arduengo AJ. J Phys Chem 1991;95:4180.
3. Diez-Gonzalez S, Marion N, Nolan SP. Chem Rev 2009;109:3612. [PubMed: 19588961]
4. Corberan R, Mas-Marza E, Peris E. Eur J Inorg Chem 2009:1700.
5. Lee HM, Lee CC, Cheng PY. Curr Org Chem 2007;11:1491.
6. Herrmann WA, Schutz J, Frey GD, Herdtweck E. Organometallics 2006;25:2437.
7. Schwab P, France MB, Ziller JW, Grubbs RH. Angew Chem Int Ed 1995;34:2039.
8. Trnka TM, Grubbs RH. Acc Chem Res 2001;34:18. [PubMed: 11170353]
9. Herrmann WA. Angew Chem Int Ed 2002;41:1290.
10. Crudden CM, Allen DP. Coord Chem Rev 2004;248:2247.
11. Snead DR, Seo H, Hong S. Curr Org Chem 2008;12:1370.
12. de Fremont P, Marion N, Nolan SP. Coord Chem Rev 2009;253:862.
13. Enders D, Balensiefer T. Acc Chem Res 2004;37:534. [PubMed: 15311952]
14. Brown MK, May TL, Baxter CA, Hoveyda AH. Angew Chem Int Ed 2007;46:1097.
15. Berlin JM, Campbell K, Ritter T, Funk TW, Chlenov A, Grubbs RH. Organic Letters 2007;9:1339.
[PubMed: 17343392]
16. Vehlow K, Gessler S, Blechert S. Angew Chem Int Ed 2007;46:8082.
17. Clavier H, Correa A, Cavallo L, Escudero-Adan EC, Benet-Buchholz J, Slawin AMZ, Noaln SP.
Eur J Inorg Chem 2009:1767.
18. Ragone F, Poater A, Cavallo L. J Am Chem Soc 2010;132:4249. [PubMed: 20205432]
19. Schanz HJ, Linseis MA, Gilheany DG. Tetrahedron-Asymmetry 2003;14:2763.
20. Herrmann WA, Baskakov D, Herdtweck E, Hoffmann SD, Bunlaksananusorn T, Rampf F,
Rodefeld L. Organometallics 2006;25:2449.
21. Baskakov D, Herrmann WA, Herdtweck E, Hoffmann SD. Organometallics 2007;26:626.
22. Witiak DT, Rotella DP, Filippi JA, Gallucci J. Journal of Medicinal Chemistry 1987;30:1327.
[PubMed: 3612684]
23. Blum AP, Ritter T, Grubbs RH. Organometallics 2007;26:2122.
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Figure 1.
NHCs utilized in metal-mediated catalysis.
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Figure 2.
Design of Rotationally Locked NHCs
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Figure 3.
ORTEP diagram of 17 with 50% probability ellipsoids.
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Figure 4.
ORTEP diagram of 18 with 50% probability ellipsoids.
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Figure 5.
Side-view of structures 17 and 18.
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Scheme 1.
Synthesis of cis carbene precursor 11.
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Scheme 2.
Synthesis of trans carbene precursor 16.
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Scheme 3.
Synthesis of rhodium complexes.
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Table 1
Selected Bond Lengths [Å] and Angles [°] for 17.
Rh(1)-C(1) 1.992(2) C(1)-N(1)-C(2) 111.93(17)
Rh(1)-C(29) 2.105(2) C(1)-N(2)-C(3) 110.99(17)
Rh(1)-C(22) 2.124(2) N(1)-C(1)-N(2) 106.57(19)
Rh(1)-C(25) 2.207(2) N(1)-C(1)-Rh(1) 124.58(14)
Rh(1)-C(26) 2.247(2) N(2)-C(1)-Rh(1) 128.82(15)
Rh(1)-Cl(1) 2.4075(5) N(1)-C(2)-C(3) 98.93(17)
N(2)-C(3)-C(2) 100.04(18)
C(12)-C(2)-C(3)-C(13) 37.57
C(5)-C(4)-N(1)-C(1) 67.86
C(20)-C(21)-N(2)-C(1) 31.84
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Table 2
Selected Bond Lengths [Å] and Angles [°] for 18.
Rh(1)-C(1) 2.0032(7) C(1)-N(1)-C(2) 113.12(5)
Rh(1)-C(22) 2.0969(7) C(1)-N(2)-C(3) 113.17(5)
Rh(1)-C(29) 2.1263(8) N(1)-C(1)-N(2) 107.40(6)
Rh(1)-C(26) 2.1847(8) N(1)-C(1)-Rh(1) 123.40(5)
Rh(1)-C(25) 2.2169(8) N(2)-C(1)-Rh(1) 129.10(5)
Rh(1)-Cl(1) 2.3896(2) N(1)-C(2)-C(3) 101.40(6)
N(2)-C(3)-C(2) 101.27(5)
C(12)-C(2)-C(3)-C(13) 136.83
C(5)-C(4)-N(1)-C(1) 50.98
C(20)-C(21)-N(2)-C(1) 62.57
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Synthesis and Structures of Fused N-Heterocylic Carbenes and Their Rhodium Complexes

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Synthesis and Structures of Fused N-Heterocylic Carbenes and Their Rhodium Complexes

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