Air-and water-stable catalysts for hydroamination/cyclization. Synthesis and application of CCC-NHC pincer complexes of RH and Ir

Article abstract of DOI:10.1021/ol8000766

The scope of CCC-NHC pincer complex synthetic methodology by metalation/transmetalation has been extended to Ir. Structural characterization revealed that it is isomorphous with the Rh complex. Both Rh and Ir complexes are efficient catalysts for the hydr

Full text of DOI:10.1021/ol8000766

ORGANIC
LETTERS
2008
Vol. 10, No. 6
1175-1178
Air- and Water-Stable Catalysts for
Hydroamination/Cyclization. Synthesis
and Application of CCC−NHC Pincer
Complexes of Rh and Ir
|
Eike B. Bauer,‡,§ G. T. Senthil Andavan,‡, T. Keith Hollis,†,‡,* Ramel J. Rubio,‡,
Joon Cho,†,‡ Glenn R. Kuchenbeiser,‡ Theodore R. Helgert,†
Christopher S. Letko,‡ and Fook S. Tham‡
Department of Chemistry and Biochemistry, The UniVersity of Mississippi,
UniVersity, Mississippi, 38677, and Department of Chemistry, UniVersity of California,
RiVerside, California 92521
hollis@olemiss.edu
Received January 11, 2008
ABSTRACT
The scope of CCC−NHC pincer complex synthetic methodology by metalation/transmetalation has been extended to Ir. Structural characterization
revealed that it is isomorphous with the Rh complex. Both Rh and Ir complexes are efficient catalysts for the hydroamination/cyclization of
secondary amines in the presence of air and/or water.
The ability to functionalize alkenes with nitrogen is still in
its infancy, despite examples of efficient and asymmetric
C-N bond formation.1 Recently, the Overman group has
developed highly efficient catalysts for the allylic imidate
rearrangement to afford C-N bonds2 and has found ever-
broadening applicability of their chiral variants.3 C-N bond
formation through asymmetric aminohydroxylation has seen
advances.4 Aryl amination is another area of C-N bond
formation that has seen breakthroughs recently.5 A most
atom-economical method of C-N bond formation is the
direct addition of N-H to unactivated C-C double bonds,
hydroamination/ cyclization. Mark’s seminal report of lan-
thanide catalysts for hydroamination has sparked a flurry of
activity in the field.6-8 Recent reports include hydroamina-
tion/cyclization employing a Pt catalyst that was not sensitive
† The University of Mississippi.
‡ University of California, Riverside.
§ Current address: Department of Chemistry and Bioshemistry, Univer-
sity of Missouri, St. Louis, One University Boulevard, St. Louis, MO 63121.
| Current address: Department of Chemistry, Northwestern University,
Evanston, Illinois 60208.
Current address: Joint Sciences Department, The Claremont Colleges,
W. M. Keck Science Center, 925 N. Mills Avenue, Claremont, CA 91711.
(1) Li, G. G.; Chang, H. T.; Sharpless, K. B. Angew. Chem., Int. Ed.
1996, 35, 451-454. Konsler, R. G.; Karl, J.; Jacobsen, E. N. J. Am. Chem.
Soc. 1998, 120, 10780-10781. DuBois, J.; Tomooka, C. S.; Hong, J.;
Carreira, E. M. Acc. Chem. Res. 1997, 30, 364-372. Evans, D.; Faul, M.;
Bilodeau, M.; Anderson, B.; Barnes, D. J. Am. Chem. Soc. 1993, 115, 5328-
5329. Li, Z.; Conser, K.; Jacobsen, E. J. Am. Chem. Soc. 1993, 115, 5326-
5327.
(3) For a recent report see: Anderson, C. E.; Donde, Y.; Douglas, C. J.;
Overman, L. E. J. Org. Chem. 2005, 70, 648-657. Kirsch, S. F.; Overman,
L. E.; Watson, M. P. J. Org. Chem. 2004, 69, 8101-8104.
(4) Li, G. G.; Chang, H. T.; Sharpless, K. B. Angew. Chem., Int. Ed.
1996, 35, 451-454.
(5) For a recent review see: Hartwig, J. F. in Handbook of Organopal-
ladium Chemistry for Organic Synthesis; Negishi, E.-I., de Meijere, A.,
Eds.; Wiley: New York, 2002; Vol. 1, pp 1051-1096.
(2) Calter, M.; Hollis, T. K.; Overman, L. E.; Ziller, J.; Zipp, G. G. J.
Org. Chem. 1997, 62, 1449-1456. Hollis, T. K.; Overman, L. E.
Tetrahedron Lett. 1997, 38, 8837-8840.
(6) a) Gagne, M. R.; Marks, T. J. J. Am. Chem. Soc. 1989, 111, 4108-
4109. b) Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673-686.
10.1021/ol8000766 CCC: $40.75
© 2008 American Chemical Society
Published on Web 02/23/2008

to the addition of water,9 Rh,10 and numerous other ex-
amples.6b,11,12 Several groups have recently reported asym-
metric variants.13
precursor and an effficient metalation strategy.14,20 Pincer
complexes, in general, have shown a great variety of
chemistries.21 A notable recent example is in the area of N-H
bond activation.22
We recently reported a general methodology for the
synthesis of CCC-NHC pincer complexes that exploited the
basicity and electrophilicity of Zr(NMe2)4 to activate three
C-H bonds simultaneously coupled with transmetalation
from Zr to prepare late transition metal CCC-NHC com-
plexes of Rh (Scheme 1, 2b).14,20 We have extended that
methodology to include Ir 2a.
We report the extension of the metalation/transmetalation
methodology for the synthesis of CCC-NHC pincer com-
plexes to Ir14 and the first examples of Rh and Ir NHC pincer
complexes for the catalysis of intramolecular hydroamination/
cyclization of unactivated alkenes. These systems are highly
active catalysts giving near quantitative yields with low
catalyst loadings for secondary amine substrates. They
function in the presence of air and with water as solvent.
The new CCC-NHC pincer catalysts have been prepared
in high yield by a general synthetic methodology and have
been structurally characterized.
Synthesis of NHC pincer complexes has been an area of
intense research activity lately.15 Numerous groups have
contributed to the development of pyridyl bridged,16 xylyl
bridged,17 and 2,6-lutidinyl bridged systems.17a,18 We have
been focused on developing phenylene bridged systems19 and
have developed a methodology for the synthesis of the ligand
Scheme 1. Synthesis of Pincer Complexes 2a and 2b
(7) For recent examples see: Takaya, J.; Hartwig, J. F. J. Am. Chem.
Soc. 2005, 127, 5756-5757. Hoover, J. M.; Petersen, J. R.; Pikul, J. H.;
Johnson, A. R. Organometallics 2004, 23, 4614-4620.
(8) For asymmetric examples see: Dorta, R.; Egli, P.; Zurcher, F.; Togni,
A. J. Am. Chem. Soc. 1997, 119, 10857-10858. Hultzsch, K. C. AdV. Synth.
Catal. 2005, 347, 367-391. Kim, J. Y.; Livinghouse, T. Org. Lett. 2005,
7, 1737-1739.
(9) Bender, C. F.; Widenhoefer, R. A. J. Am. Chem. Soc. 2005, 127,
1070-1071.
While evaluating several routes to late transition metal
CCC-NHC pincer complexes, it was found that metalation
with Zr followed by transmetalation to Rh or Ir was a high-
yielding process providing Ir 2a in 68% and Rh 2b in 66%
(see Supporting Information). The bis imidazolium salt 1 was
treated in situ with 2.5 equiv of Zr(NMe2)4. It was then stirred
with [IrCl(COD)]2 for 8 h. The resulting iodo-bridged dimer
was isolated in 68% yield. An X-ray quality crystal was
grown by slow evaporation of a CH2Cl2 solution.
A single-crystal X-ray analysis of 2a revealed a structure
that is isomorphous with the Rh analogue (Figure 1). The
iodo-bridges between the Ir centers complete the octahedral
environment. The molecular structure contains a center of
symmetry that relates the two halves of the molecular
structure. Unlike the Rh analogue, no Ir ammine adduct was
noted spectroscopically, but it is anticipated that in solution
this dimer is readily split by coordination to the amine
functinal group of the substrate. Select metric data are
included in Figure 1. Other than the geometric constrains of
the tridentate ligand, the geometry of the complex is within
the normal ranges. Due to the chelating rings the C6-Ir-
C2 angle is only 78°, a significant deviation from the
idealized 90°. Likewise the C2-Ir1-C2′ angle is 156°,
compared to the idealized angle of 180°.
(10) Takemiya, A.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 6042-
6043.
(11) For leading references see: Molander, G. A.; Hasegawa, H.
Heterocycles 2004, 64, 467-474. Field, L. D.; Messerle, B. A.; Vuong, K.
Q.; Turner, P. Organometallics 2005, 24, 4241-4250. Lai, R. Y.; Surekha,
K.; Hayashi, A.; Ozawa, F.; Liu, Y. H.; Peng, S. M.; Liu, S. T.
Organometallics 2007, 26, 1062-1068. Field, L. D.; Messerle, B. A.;
Vuong, K. Q.; Turner, P.; Failes, T. Organometallics 2007, 26, 2058-
2069. Burling, S.; Field, L. D.; Messerle, B. A.; Rumble, S. L. Organo-
metallics 2007, 26, 4335-4343.
(12) For reviews see: Bytschkov, I.; Doye, S. Eur. J. Org. Chem 2003,
935-946. Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673-686.
Molander, G. A.; Romero, J. A. C. Chem. ReV. 2002, 102, 2161-2185.
Muller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675-703.
(13) Martinez, P. H.; Hultzsch, K. C.; Hampel, F. Chem. Commun. 2006,
2221-2223. Horrillo-Martinez, P.; Hultzsch, K. C.; Gil, A.; Branchadell,
V. Eur. J. Org. Chem. 2007, 3311-3325. Gribkov, D. V.; Hultzsch, K. C.;
Hampel, F. J. Am. Chem. Soc. 2006, 128, 3748-3759. Watson, D. A.; Chiu,
M.; Bergman, R. G. Organometallics 2006, 25, 4731-4733. Wood, M. C.;
Leitch, D. C.; Yeung, C. S.; Kozak, J. A.; Schafer, L. L. Angew. Chem.,
Int. Ed. 2007, 46, 354-358. Kim, H.; Kim, Y. K.; Shim, J. H.; Kim, M.;
Han, M. J.; Livinghouse, T.; Lee, P. H. AdV. Synth. Catal. 2006, 348, 2609-
2618.
(14) Rubio, R. J.; Andavan, G. T. S.; Bauer, E. B.; Hollis, T. K.; Cho,
J.; Tham, F. S.; Donnadieu, B. J. Organomet. Chem. 2005, 690, 5353-
5364.
(15) For a recent review see: Peris, E.; Crabtree, R. H. Coord. Chem.
ReV. 2004, 248, 2239-2246.
(16) For a leading reference see: Wright, J. A.; Danopoulos, A. A.;
Motherwell, W. B.; Carroll, R. J.; Ellwood, S.; Sassmannshausen, J. Eur.
J. Inorg. Chem. 2006, 4857-4865.
(17) (a) Grundemann, S.; Albrecht, M.; Loch, J. A.; Faller, J. W.;
Crabtree, R. H. Organometallics 2001, 20, 5485-5488. (b) Nielsen, D. J.;
Cavell, K. J.; Skelton, B. W.; White, A. H. Inorg. Chim. Acta 2002, 327,
116-125. (c) Danopoulos, A. A.; Tulloch, A. A. D.; Winston, S.; Eastham,
G.; Hursthouse, M. B. Dalton Trans. 2003, 1009-1015. (d) Magill, A. M.;
McGuinness, D. S.; Cavell, K. J.; Britovsek, G. J. P.; Gibson, V. C.; White,
A. J. P.; Williams, D. J.; White, A. H.; Skelton, B. W. J. Organomet. Chem.
2001, 617, 546-560.
(18) Tulloch, A. A. D.; Danopoulos, A. A.; Tizzard, G. J.; Coles, S. J.;
Hursthouse, M. B.; Hay-Motherwell, R. S.; Motherwell, W. B. Chem.
Commun. 2001, 1270-1271.
(19) Vargas, V. C.; Rubio, R. J.; Hollis, T. K.; Salcido, M. E. Org. Lett.
2003, 5, 4847-4849.
Our initial evaluation of these complexes as catalysts for
the intramolecular hydroamination/cyclization focused on
(20) Andavan, G. T. S.; Bauer, E. B.; Letko, C. S.; Hollis, T. K.; Tham,
F. S. J. Organomet. Chem. 2005, 690, 5938-5947.
(21) For recent reviews see: The Chemistry of Pincer Compounds;
Morales-Morales, D.; Jensen, C., Eds.; Elsevier: New York, 2007.
(22) Kanzelberger, M.; Zhang, X.; Emge, T. J.; Goldman, A. S.; Zhao,
J.; Incarvito, C.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 13644-13645
and references therein.
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Org. Lett., Vol. 10, No. 6, 2008

Table 1. Comparison of Benzene and Water as Solvent for
Hydroamination/Cyclization of Unactivated Alkenes with 2.5
mol % 2b
a Percent alkene isomerization.
results were obtained when THF, benzene, or toluene was
employed as solvent.
Control experiments were performed without adding
catalyst by heating the substrate neat, in benzene, or in water.
In each of these cases no reaction occurred, and only starting
Figure 1. ORTEP representation of the molecular structure of
CCC-NHC Ir pincer complex 2a. Selected geometric data:
Ir1-C6, 1.965(3) Å; Ir1-C2, 2.059(4) Å, Ir1-I1, 2.6720(3) Å;
Ir1-I2, 2.6803(3) Å; Ir1-I2′, 2.8175(3) Å; C6-Ir1-C2,
78.36(14)°; C2-Ir1-C2′, 156.47(13)°; C6-Ir1-I1, 92.38(10)°;
C2-Ir1-I1, 89.07(10)°; I1-Ir1-I2, 177.705(9)°; C6-Ir1-I2′,
174.89(10)°.
Table 2. Intramolecular Hydroamination/Cyclization of
Unactivated Alkenes Yielding Pyrrolidines and Piperidines
Catalyzed by 2.5 mol % 2a or 2ba
alkenylamine 3. The crude product from the preparation of
3 was employed in the evaluations without further purifica-
tion. No purification of solvents or attempt to exclude air
was performed in the assay of the catalysts. Initial results
indicated the formation of pyrrolidine 4 with no evidence
for the formation of piperidine 5. In some experiments new
1
resonances appeared in the olefin region of the H NMR
spectrum consistent with trace formation of internal alkene
isomers 6. The use of environmentally friendly solvents such
Scheme 2. Initial Hydroamination Results with 2a and 2b
as water for the synthesis of organic compounds serves as a
cornerstone of green chemistry.23 Since no special purifica-
tion or exclusion of water was required in the initial
experiments, the catalysts were evaluated with water as the
solvent. The results are presented in Table 1. Evaluation of
pincer complexes 2a and 2b in water showed no appreciable
loss of catalytic activity. In all cases there was no detectable
formation of isomerization products. The only cyclized
1
product observed by H NMR was pyrrolidine 4. Similar
a Reaction conditions: C6D6, 110 °C, 16 h. Conversion determined by
1H NMR. b (% conversion to heterocycle/% alkene isomerization). c Isomer-
ization not detected. d Isolated yield: 77%. e Isolated yield: 80%. f Isolated
yield: 80%. g 22 h.
(23) Anastas, P. T.; Williamson, T. C. Green Chemistry: Designing
Chemistry for the EnVironment; American Chemical Society: Washington,
DC, 1996. Nelson, W. M. Green SolVents for Chemistry: perspectiVes and
practice; Oxford University Press: Oxford, New York, 2003.
Org. Lett., Vol. 10, No. 6, 2008
1177

material was recovered. A control experiment that excluded
air and used purifed solvent showed no loss of activity.
Additional control experiments were run adding catalytic
quantities of I2 in place of 2a and 2b to check for iodine- or
acid-catalyzed hydroamination as reported by Bergman.24
Under these conditions the product formed was a cyclized
metal complexes.25-27 It is consistent with M-N bond
formation, olefin coordination, and migratory insertion
followed by reductive elimination, or π-coordination with
amine attack.9,10,28
In summary, we have reported the efficient synthesis of a
CCC-NHC Ir pincer complex with applications of the Rh
and Ir pincer complexes as air and water-stable hydroami-
nation/cyclization catalysts for the formation of five- and
six-membered nitrogen-containing rings. Further work on the
scope, limitations, functional-group tolerance and mechanism
of this reaction and applications of these catalysts are
ongoing. Extension of the synthetic methodology is also
underway.
1
iodine addition product based on H NMR and MS data.
An examination of the scope of these catalysts is presented
in Table 2. Secondary aminoalkene substrates gave good
yields of the desired hydroamination/ cyclization products.
Excellent isolated yields were obtained for selected examples
(entries 1, 3, 9; see footnotes), and exo-trig cyclization
products were obtained exclusively (entries 1, 10). Lack of
substitution on the â-position (R ) H) led to a dramatic
decrease in the rate of cyclization and an increase in the
isomerization product as the only product (entry 11). Primary
amines did not yield cyclization products (entry 4). Aryl
amines were cyclized successfully also (entries 3, 9). The
presence of an aryl bromide was tolerated by the catalysts
(entry 5). The Ir catalyst 2a was found to give superior results
for the diphenyl derivatives and was employed in the
evaluation of the dimethyl derivatives in entries 6-9. Pincer
complexes 2a or 2b typically had produced near 90%
conversion at 6 h in examples that were checked. Attempts
at intermolecular cyclization did not yield hydroamination
products, and 6-exo-trig cyclization was found exclusively
in the formation of the piperidinyl derivative (entry 10).
Finally, spirocyclic compounds could be formed in excellent
yields efficiently (entries 12 and 13). Analysis of these data
suggest that the chelate effect along with the Thorpe-Ingold
effect are required of the substrate to achieve efficient
cyclization.
Acknowledgment. The authors gratefully acknowledge
support from the National Science Foundation (CHE-
0317089) and The University of Mississippi. R.J.R. thanks
the Department of Education for a G.A.A.N.N. fellowship.
C.S.L. gratefully acknowledges a CNAS Dean’s Summer
Fellowship. We thank Professor John M. Rimoldi (UM) and
Dr. Paulo Carvalho (UM) for assistance with collecting mass
spectral data for the substrates and cyclized products, and
Mr. Ron New (UCR) and Dr. Rich Kondrat (UCR) for
assistance with the mass spectral data of Ir complex 2a and
organic compounds.
Supporting Information Available: Experimental details
for the preparation and molecular structure determination of
2a, characterization data for the amines and heterocyclic
products, and a typical catalysis procedure. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL8000766
The lack of hydroamination with primary amines is not
consistent with the formation of imido complexes as part of
the catalytic mechanism, which is seen in early transition
(25) Straub, B. F.; Bergman, R. G. Angew. Chem., Int. Ed. 2001, 40,
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Organometallics 2006, 25, 3394-3406.
(28) Hartwig, J. F. Pure. Appl. Chem. 2004, 76, 507-516.
(24) Anderson, L. L.; Arnold, J.; Bergman, R. G. J. Am. Chem. Soc.
2005, 127, 14542-14543.
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