C - H oxidative addition to a (PNP)Ir center and ligand-induced reversal of benzyl/aryl selectivity

Article abstract of DOI:10.1021/om701110y

The (PNP)Ir fragment displays a thermodynamic preference for the oxidative addition of aromatic vs benzylic C - H bonds. However, in the case of the mesitylene activation products, the benzylic isomer is kinetically accessible and can be trapped by an external donor ligand. The preference for the benzylic isomer in the six-coordinate Ir(III) adduct of mesitylene activation is ascribed to steric factors.

Full text of DOI:10.1021/om701110y

Organometallics 2007, 26, 6701–6703
6701
C-H Oxidative Addition to a (PNP)Ir Center and Ligand-Induced
Reversal of Benzyl/Aryl Selectivity
Yanjun Zhu, Lei Fan, Chun-Hsing Chen, Shannon R. Finnell, Bruce M. Foxman, and
Oleg V. Ozerov*
Department of Chemistry, Brandeis UniVersity, MS 015, 415 South Street, Waltham, Massachusetts 02454
ReceiVed NoVember 3, 2007
by addition of an external ligand at an Ir(III) center. We provide
an analysis of the underlying causes of this preference reversal
and report on our investigation of the mechanism of the requisite
transformations through kinetic studies. We have previously
reported on the selectivity (C-H vs C-Cl) of the oxidative
addition of chlorobenzene in this system, where the Ir center is
supported by a rigid PNP pincer ligand.12–15
Summary: The (PNP)Ir fragment displays a thermodynamic
preference for the oxidatiVe addition of aromatic Vs benzylic
C-H bonds. HoweVer, in the case of the mesitylene actiVation
products, the benzylic isomer is kinetically accessible and can
be trapped by an external donor ligand. The preference for the
benzylic isomer in the six-coordinate Ir(III) adduct of mesitylene
actiVation is ascribed to steric factors.
Selective activation of C-H bonds by transition-metal
complexes remains a focal point, in part owing to the potential
benefits of selective functionalization of unreactive C-H
bonds.1–3 Control and discrimination between activation of
aromatic C(sp2)-H bonds on one hand and aliphatic C(sp3)-H
bonds, especially benzylic C-H bonds, on the other hand is an
issue for any substrate containing both. As a rule, transition-
metal systems typically display both the thermodynamic and
kinetic preference for the activation of aromatic C-H bonds.
The thermodynamic preference to activate stronger C-H bonds4
has been traced to the greater differences in M-C bond strengths
compared with the case for C-H bond strengths.5 Selectivity
for a product of benzylic activation may come in cases where
(a) formation of an aryl-metal product is sufficiently sterically
disfavored,5–7 (b) the benzylic product is stabilized by η3
coordination,8,9 or (c) in the sense of kinetic selectivity, the
reaction proceeds via homolysis pathways.10 Eisenberg et al.
reported an aryl-to-benzyl rearrangement induced by coordina-
tion of ethylene to an Ir(I) center in (Me3C6H2)Ir(CO)(dppe),11
but the mechanistic details were not fully elucidated. Here we
report an example where the aryl/benzylic preference is reversed
(PNP)Ir(H)(Mes) (1) served as a synthon for the transient
(PNP)Ir species. Thermolysis of 1 in benzene16 or toluene at
70 °C led to the elimination of mesitylene and formation of 2
or 3,17 respectively (Scheme 1). However, when C6D6 solutions
of 1 were treated with excess pyridine, the anticipated C-H
OA of pyridine did not take place. Instead, an entirely different
product (4a) was isolated after 24 h at ambient temperature
(Scheme 1). Similar products were obtained from the reaction
of 1 with PMe3 (4b) and thiazole (4c). Compounds 4a-c were
fully characterized by NMR spectroscopy. For instance, in 4a,
the Ir-CH2 unit gave rise to characteristic resonances in the
1H (δ 3.67, br t, JHP ) 6 Hz) and 13C{1H} (δ -6.6, t, JCP ) 2
Hz) NMR spectra. The hydride resonance in 4b displayed a
large 2JHP value of 142 Hz for the coupling with the 31P nucleus
in PMe3, indicative of the trans disposition of PMe3 and the
hydride. In the solid-state structure of 4c (Figure 1), the N-bound
thiazole ligand is also trans to the hydride. The pyridine ligand
in 4a is most likely trans to the hydride as well.
The rate of the transformation of 1 to 4a in C6D6 was found
to be independent of the concentration of pyridine in the 0.5-2.2
M range. Notably, 1 does not detectably bind pyridine in solution
at 22 °C. This strongly implies that the rate-determining step is
* To whom correspondence should be addressed. E-mail: ozerov@
brandeis.edu.
(1) (a) Shilov, A. E.; Shul’pin, G. B. Chem. ReV. 1997, 97, 2879. (b)
Labinger, J. A.; Bercaw, J. E. Nature 2002, 417, 507. (c) Lersch, M.; Tilset,
M. Chem. ReV. 2005, 105, 2471.
(8) (a) Driver, T. G.; Day, M. W.; Labinger, J. A.; Bercaw, J. E.
Organometallics 2005, 24, 3644. (b) Heyduk, A. F.; Driver, T. G.; Labinger,
J. A.; Bercaw, J. E. J. Am. Chem. Soc. 2004, 126, 15034.
(9) (a) Lam, W. H.; Lam, K. C.; Lin, Z.; Shimada, S.; Perutz, R. N.;
Marder, T. B. Dalton Trans. 2004, 1556. (b) Shimada, S.; Batsanov, A. S.;
Howard, J. A. K.; Marder, T. B. Angew. Chem., Int. Ed. 2001, 40, 2168.
(10) Collman, J. P.; Boulatov, R. Inorg. Chem. 2001, 40, 2461.
(11) (a) Cleary, B. P.; Eisenberg, R. J. Am. Chem. Soc. 1995, 117, 3510.
(b) Cleary, B. P.; Eisenberg, R. Organometallics 1992, 11, 2335.
(12) Fan, L.; Parkin, S.; Ozerov, O. V. J. Am. Chem. Soc. 2005, 127,
16772.
(2) (a) Campos, K. R. Chem. Soc. ReV. 2007, 36, 1069. (b) Kalyani,
D.; Dick, A. R.; Anani, W. Q.; Sanford, M. S. Tetrahedron 2006, 62, 11483.
(c) Daugulis, O.; Zaitsev, V. G.; Shabashov, D.; Pham, Q.-N.; Lazareva,
A. Synlett 2006, 3382. (d) Godula, K.; Sames, D. Science 2006, 312, 67.
(e) Fiori, K. W.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562. (f) Giri,
R.; Maugel, N.; Li, J.-J.; Wang, D.-H.; Breazzano, S. P.; Saunders, L. B.;
Yu, J.-Q. J. Am. Chem. Soc. 2007, 129, 3510.
(3) (a) Chotana, G. A.; Rak, M. A.; Smith, M. R., III J. Am. Chem.
Soc. 2005, 127, 10539. (b) Boller, T. M.; Murphy, J. M.; Hapke, M.;
Ishiyama, T.; Miyaura, N.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127,
14263.
(13) (a) For reviews on the diarylamido-based PNP complexes, see:
Liang, L.-C. Coord. Chem. ReV. 2006, 250, 1152. (b) Ozerov, O. V. In The
Chemistry of Pincer Compounds; Morales-Morales, D. , Jensen, C., Eds.;
Elsevier: Amsterdam, 2007; pp 287–309.
(4) A thermodynamic preference for the metal-aryl bonds does not
necessarily preclude kinetic access to other C-H bonds in the substrate.
For instance, (PCP)IrH2 catalyzes dehydrogenation of ethylbenzene to
styrene: Gupta, M.; Kaska, W. C.; Jensen, C. M. Chem. Commun. 1997,
461.
(14) (a) For reviews on the pioneering PNP work by Fryzuk on the
disilylamido-based PNP ligands, see: Fryzuk, M. D. Can. J. Chem. 1992,
70, 2839–2845. (b) Fryzuk, M. D.; Berg, D. J.; Haddad, T. S. Coord. Chem.
ReV. 1990, 99, 137.
(5) (a) Clot, E.; Megret, C.; Eisenstein, O.; Perutz, R. N. J. Am. Chem.
Soc. 2006, 128, 8350. (b) Jones, W. D. Inorg. Chem. 2005, 44, 4475. (c)
Wick, D. D.; Jones, W. D. Organometallics s 1999, 18, 495. (d) Bennett,
J. L.; Wolczanski, P. T. J. Am. Chem. Soc. 1997, 119, 10696.
(6) Adams, C. S.; Legzdins, P.; Tran, E. Organometallics 2002, 21, 1474.
(7) Nakamura et al. reported Ir-catalyzed benzylic C-C coupling of
toluene with a bulky fullerene derivative; this selectivity may well be
sterically enforced by the bulky substrate: Matsuo, Y.; Iwashita, A.;
Nakamura, E Chem. Lett. 2006, 35, 858.
(15) (a) For the more recent explorations of the Fryzuk-type PNP ligands
by Caulton et al. see the following (and references within)Ingleson, M. J.;
Pink, M.; Fan, H.; Caulton, K. G. Inorg. Chem. 2007, ASAP Article; DOI:
10.1021/ic701171p. (b) Ozerov, O. V.; Watson, L. A.; Pink, M.; Caulton,
K. G. J. Am. Chem. Soc. 2007, 129, 6003.
(16) The thermolysis of 1 in C6D6 led to (PNP)Ir(D)(C6D5) (2-d6); see
the Supporting Information.
(17) 3 and 6 denote mixtures of the corresponding m- and p-tolyls in a
ca. 2:1 ratio; see the Supporting Information for details.
10.1021/om701110y CCC: $37.00
2007 American Chemical Society
Publication on Web 12/04/2007

6702 Organometallics, Vol. 26, No. 27, 2007
Communications
Scheme 1
the transformation of 1 to its benzylic isomer 9 followed by
fast trapping of the latter by pyridine. An attempt to isolate 9
by treatment of (PNP)IrHCl (7) with 3,5-Me2C6H3CH2MgBr
led to the observation of 1 as the major product (Scheme 1).
Thus, for the five-coordinate system, the aryl isomer (1) is
thermodynamically preferred over the benzylic isomer (9),
although 9 is kinetically accessible. Addition of pyridine,
thiazole, or PMe3, however, causes the preference to reverse
and favor the benzylic products 4a-c.19
We set out to investigate the importance of the steric influence
in the aryl/benzyl isomerization. In contrast to the case for 1,
the less sterically encumbered aryl complexes 2 and 3 readily
coordinated pyridine to give 5 and 6,17 respectively (Scheme
1). Neither 3 nor 6 converted to the corresponding benzyl
isomers (PNP)Ir(H)(CH2Ph) (12) and 8 upon thermolysis (20
h, 95 °C). On the other hand, the reverse reactions did proceed:
(a) 8 converted to 6 upon thermolysis (complete disappearance
of 8 after 70 °C, 18 h; unidentified products also observed),
and (b) an attempted synthesis of 12 from (PNP)Ir(H)(Cl) and
PhCH2MgCl led to 3. Thus, unlike the case for the mesityl/
3,5-dimethylbenzyl pair, in the tolyl/benzyl pair, the thermo-
dynamic preference for the aryl isomer exists not only for the
five-coordinate but also for the six-coordinate case. In a sense,
the coordination of pyridine (possible to 1 but not 3) compen-
sates for the ostensibly unfavorable mesityl-to-3,5-dimethyl-
benzyl isomerization, but the difference in the energies of
binding of pyridine to 3 vs 12 does not override the intrinsic
unfavorability of tolyl-to-benzyl isomerization.
Continued thermolysis of 4a in C6H6 led to the production
of 5 via activation of the solvent (Scheme 1).20 Kinetic studies
carried out at 85 °C revealed the inverse dependence of the
rate of conversion of 4a to 5 on the concentration of pyridine
(Figure 2). This is consistent with the dissociation of pyri-
dine from 4a being necessary for the reaction to proceed
(Scheme 2). Elimination of mesitylene generates transient
(PNP)Ir, which reacts with benzene to give 2, and the latter
is trapped by pyridine to give 5. A dissociative mechanism
for the activation of benzene by 1 is consistent with the
previously demonstrated intermediacy of analogous three-
coordinate Ir fragments (e.g., (PCP)Ir and Milstein’s
Figure 1. ORTEP drawing18 (50% probability ellipsoids) of 4c
showing selected atom labeling. Hydrogen atoms (except Ir-H)
are omitted for clarity. Selected bond distances (Å) and angles (deg):
Ir1-P1, 2.2866(7); Ir1-P2, 2.3026(7); Ir1-N1, 2.137(2); Ir1-N2,
2.213(2); Ir1-C27, 2.135(3); P1-Ir1-P2, 159.33(2); N1-Ir1-N2,
179.12(10).
(18) ORTEP plots were created using Ortep-3 for Windows: Farrugia,
L. J. Appl. Crystallogr. 1997, 30, 565.
(19) Fryzuk observed benzylic C-H activation of toluene via ostensibly
radical pathways (no reaction in the dark) by [(Ph2PCH2SiMe2)2N]Rh(Me)(I)
in the presence of MeI. In our case, the transformation of 1 to 4a proceeds
in the dark (see the Supporting Information); radical pathways are unlikely.
See: Fryzuk, M. D.; MacNeil, P. A.; McManus, N. T. Organometallics
1987, 6, 882.
Figure 2. Rate of disappearance of 4a during thermolysis at 85 °C
in C6D6 as a function of pyridine concentration.
(20) Thermolysis of 4a in C6D6 led to (PNP)Ir(D)(C6D5)(py) (5-d6); see
the Supporting Information.

Communications
Organometallics, Vol. 26, No. 27, 2007 6703
Scheme 2
certain cases depend on the coordination number of the metal
center. A higher coordination number favors a less sterically
demanding benzylic product instead of the preference for the
mesityl isomer for the lower coordination number.
Acknowledgment. We gratefully acknowledge Brandeis
University, the Sloan Foundation, the Research Corporation,
the NSF (Grant No. CHE-0521047 to B.M.F. for diffracto-
meter purchase and Grant No. CHE-5017798 to O.V.O.),
the Petroleum Research Fund, and the Dreyfus Foundation
for support of this research. S.R.F. is a student of the
University of Oregon who is thankful to the NSF for support
through an NSF-REU program at Brandeis University (Grant
No. CHE-0552767) in the summer of 2006. We thank
Claudia M. Fafard for assistance with several experiments.
We are grateful to the reviewers for bringing a few important
references to our attention.
[(PNpyrP)Ir]+)21,22 in C-H oxidative addition reactions. The
lack of direct reductive elimination from the six-coordinate
d6 complex 4a dovetails with the findings of Goldberg et
al.23 of the necessity of the five-coordinate intermediate for
C-X reductive elimination from six-coordinate Pt(IV) d6
complexes and the trapping by Goldman et al.24 of the
reductive-elimination-prone d6 complex (PCP)Ir(H)(Ph) as
a robust six-coordinate adduct with CO.
Supporting Information Available: Crystallographic informa-
tion for 19a and 21 in the form of CIF files, experimental details
on the equilibrium and kinetics experiments, and pictorial NMR
spectra for select compounds. This material is available via the
Internet free of charge at http://pubs.acs.org.
In summary, we have demonstrated that the thermodynamic
preference for aryl or benzylic C-H oxidative addition may in
(21) (a) Goldman, A. S.; Roy, A. H.; Huang, Z.; Ahuja, R.; Schinski,
W.; Brookhart, M. Science 2006, 312, 257. (b) Zhu, K.; Achord, P. D.;
Zhang, X.; Krogh-Jespersen, K.; Goldman, A. S. J. Am. Chem. Soc. 2004,
126, 13044. (c) Krogh-Jespersen, K.; Czerw, M.; Summa, N.; Renkema,
K. B.; Achord, P. D.; Goldman, A. S. J. Am. Chem. Soc. 2002, 124, 11404.
(22) Ben-Ari, E.; Cohen, R.; Gandelman, M.; Shimon, L. J. W.; Martin,
J. M. L.; Milstein, D. Organometallics 2006, 25, 3190.
OM701110Y
(23) Procelewska, J.; Zahl, A.; Liehr, G.; Van Eldik, R.; Smythe, N. A.;
Williams, B. S.; Goldberg, K. I. Inorg. Chem. 2005, 44, 7732.
(24) Kanzelberger, M.; Singh, B.; Czerw, M.; Krogh-Jespersen, K.;
Goldman, A. S. J. Am. Chem. Soc. 2000, 122, 11017.