Iridium-assisted, enantiospecific aliphatic C-H activation/iodination

Article abstract of DOI:10.1021/om980801z

The observation of an enantiospecific C-H bond activation followed by iodination at an allylic position of a coordinated 1,5-COD ligand in a chiral Ir-(I) complex upon addition of I₂ in CH₂Cl₂ is reported. The same reaction carried out in THF affords an allylic η³,η²-COD derivative. Both reaction products were characterized by X-ray diffraction.

Full text of DOI:10.1021/om980801z

© Copyright 1998
Volume 17, Number 25, December 7, 1998
American Chemical Society
Communications
Ir id iu m -Assisted , En a n tiosp ecific Alip h a tic C-H
Activa tion /Iod in a tion
Romano Dorta and Antonio Togni*
Laboratory of Inorganic Chemistry, Swiss Federal Institute of Technology, ETH-Zentrum,
CH-8092 Zu¨rich, Switzerland
Received September 24, 1998
Summary: The observation of an enantiospecific C-H
bond activation followed by iodination at an allylic
position of a coordinated 1,5-COD ligand in a chiral Ir-
(I) complex upon addition of I2 in CH2Cl2 is reported.
The same reaction carried out in THF affords an allylic
η3,η2-COD derivative. Both reaction products were
characterized by X-ray diffraction.
zymes5 and artificial analogues thereof.6 Despite its
potential importance, C-H activation followed by ha-
logenation is an extremely rare reaction.7
Whereas there is some precedent in Rh- and Ir-
mediated selective COD (1,5-cyclooctadiene) oxidation
8
by H2O2 and by dioxygen,9 respectively, no metal-
mediated halogenation of a CH2 group in this molecule
has been reported. We describe here the first enan-
tiospecific C-H bond activation/iodination of COD,
formally corresponding to the transformation of eq 1.
This is taking place in the coordination sphere of the
The development of systems capable of selective and
eventually catalytic hydrocarbon activation/functional-
ization, taking place within the coordination sphere of
a transition metal, is still a challenging objective.
Nevertheless, stoichiometric C-H bond activation by
metal complexes is well established,1,2 and reports on
C-C3 and catalytic C-H4 bond activation/functional-
ization are becoming more frequent. High selectivity
in the activation of C-H bonds is observed in, for
example, reactions catalyzed by cytochrome P-450 en-
(4) (a) Lin, M.; Hogan, T.; Sen, A. J . Am. Chem. Soc. 1997, 119,
6048. (b) Periana, R. A.; Taube, D. J .; Evitt, E. R.; Lo¨ffler, D. G.;
Wentrcek, P. R.; Voss, G.; Masuda, T. Science 1993, 259, 340. (c)
Periana, R. A.; Taube, D. J .; Gamble, S.; Taube, H.; Satoh, T.; Fujii,
H. Science 1998, 280, 560. (d) Belli, J .; J ensen, C. M. Organometallics
1996, 15, 1532. (e) Maguire, J . A.; Petrillo, A.; Goldmann, A. S. J . Am.
Chem. Soc. 1992, 114, 9492.
(5) For a review, see: Woggon, W.-D. Cytochrome P-450: Signifi-
cance, Reaction Mechanisms and Active Sites Analogues; Springer:
Berlin, Heidelberg, 1996.
(6) Breslow, R.; Zhang, X.; Huang, Y. J . Am. Chem. Soc. 1997, 119,
4535.
* To whom correspondence should be addressed. E-mail: togni@
inorg.chem.ethz.ch.
(1) For a recent review, see: Shilov, A. E.; Shul’pin, G. B. Chem.
Rev. 1997, 97, 2879, and references therein.
(2) For recent examples, see: (a) Bennett, J . L.; Wolczanski, P. T.
J . Am. Chem. Soc. 1997, 119, 10696. (b) Cook, J . K.; Mayer, J . M. J .
Am. Chem. Soc. 1995, 117, 7139. (c) Wick, D. D.; Goldberg, K. I. J .
Am. Chem. Soc. 1997, 119, 10235. (d) Brown, S. N.; Mayer, J . M. J .
Am. Chem. Soc. 1994, 116, 2219. (e) Cook, G. K.; Mayer, J . M. J . Am.
Chem. Soc. 1994, 116, 1855. (f) Ma, Y.; Bergman, R. G. Organometallics
1994, 13, 2548.
(3) (a) Gozin, M.; Weisman, A.; Ben-David, Y.; Milstein, D. Nature
1993, 364, 699. (b) Gozin, M.; Aizenberg, M.; Liou, S.-Y.; Weisman,
A.; Ben-David, Y.; Milstein, D. Nature 1994, 370, 42. (c) Liou, S.-Y.;
Gozin, M.; Milstein, D. J . Am. Chem. Soc. 1995, 117, 9774.
(7) (a) See, for example: (a) Horva´th, I.; Cook, R. A.; Millar, J . M.;
Kiss, G. Organometallics 1993, 12, 8. For a template-directed radical
relay process, see: (b) Breslow, R.; Mehta, M. P. J . Am. Chem. Soc.
1986, 108, 2485. (c) Breslow, R.; Mehta, M. P. J . Am. Chem. Soc. 1986,
108, 6417.
(8) de Bruin, B.; Boerakker, M. J .; Donners, J . J . J . M.; Christiaans,
B. E. C.; Schlebos, P. P. J .; de Gelder, R.; Smits, J . M. M.; Spek, A. L.;
Gal, A. W. Angew. Chem. 1997, 109, 2154.
(9) (a) Day, V. W.; Klemperer, W. G.; Lockledge, S. P.; Main, D. J .
J . Am. Chem. Soc. 1990, 112, 2031. (b) Day, V. W.; Eberspacher, T.
A.; Klemperer, W. G.; Zhong, B. J . Am. Chem. Soc. 1994, 116, 3119.
10.1021/om980801z CCC: $15.00 © 1998 American Chemical Society
Publication on Web 11/14/1998

5442 Organometallics, Vol. 17, No. 25, 1998
Communications
chiral Ir(I) fragment [Ir((R)-(S)-PPFP(Xyl)2)]+ (serving
also as a scavenger for the produced HI).10
Thus, 1 equiv of I2 cleanly reacted with [Ir((R)-(S)-
PPFP(Xyl)2)(COD)]BF4 (1) in THF at room temperature.
The 31P NMR spectrum showed the presence of a main
product characterized by a new pair of doublets at δ
-24.2 and -0.7 ppm (J PP ) 29 Hz). This cationic
complex 3 could be isolated in pure form in 60-80%
yield as a tetrafluoroborate salt.11 An X-ray crystal-
lographic analysis revealed the presence of an η3,η2-
cyclooctadienyl ligand, as shown in the ORTEP repre-
sention of Figure 1B.12 Compound 3 has the composition
[IrI((R)-(S)-PPFP(Xyl)2)(η3,η2-C8H11)]BF4 (Scheme 1) and
formally derives from the addition of I2 to 1, under
extrusion of HI. The coordination sphere around the
Ir(III) center is pseudooctahedral, with the η3,η2-cy-
clooctadienyl ligand occupying three coordination sites
and the iodine atom being located in an endo position
with respect to the ferrocene core. The bonding dis-
tances between the three carbon atoms C(36), C(37), and
C(38), respectively, and Ir (2.336(10), 2.17(2), and 2.23-
(2) Å, respectively) clearly indicate the π-allyl nature
of this fragment.
When the reaction was followed by NMR in THF-d8,
the transient formation of a major Ir-hydride species 2
(along with two minor Ir-hydrides, accounting for less
F igu r e 1. ORTEP views (30% probability ellipsoids) of the
cations 2 (A) and 3 (B). The same absolute configuration
(R)-(S) of the ferrocenyl ligands is shown for both com-
plexes, although the structure of compound 3 has been
determined using crystals containing the (S)-(R) enanti-
omer. For relevant bond distances and angles, see text.
1
than 15% of the mixture) was observed in the H NMR
spectrum at δ -13.8 ppm (dd, J ) 16.0; 10.6 Hz), to
which corresponded a new pair of doublets in the 31P
NMR spectrum (δ -33.3 and -1.9 ppm, J PP ) 22 Hz).
This species could not be isolated from THF solutions
even at low temperature. However, when the reaction
of 1 with I2 was run in CH2Cl2 at -78 °C, the same
hydride species 2 was obtained in an analytically pure
Sch em e 1
(10) We have previously shown that dinuclear Ir(I) complexes
containing ferrocenyl diphosphines are able to undergo aliphatic C-H,
O-H, and N-H bond activation. See: (a) Dorta, R.; Egli, P.; Zu¨rcher,
F.; Togni, A. J . Am. Chem. Soc. 1997, 119, 10857. (b) Dorta, R.; Togni,
A. Organometallics 1998, 17, 3423.
(11) A THF (2 mL) solution of I2 (61.5 mg, 0.242 mmol) was added
dropwise to a THF (3 mL) solution of [Ir(COD)((S)-(R)-PPF-P(Xyl)2)]-
BF4 (1, 248.7 mg, 0.242 mmol). The resulting dark red solution was
stirred for 60 h, whereupon it gradually turned orange. Addition of
Et2O (14 mL) caused precipitation of a red oil and a yellow solid. The
supernatant mother liquor was syphoned off and the residue dried in
vacuo. Redissolving the residue in THF (2 mL) caused almost immedi-
ate crystallization. The yellow precipitate was filtered off, washed with
Et2O, and dried in vacuo, yielding a yellow powder (192 mg, 69%). Anal.
Calcd for C48H51BF4P2FeIIr: C, 50.06; H, 4.46; I, 11.02. Found: C,
49.84; H, 4.69; I, 11.30. 1H NMR (CD2Cl2): δ 1.59 (m, 3 H), 2.14 (s, 6
H), 2.46 (s, 6 H), 3.94 (s and m, 5 and 1 H, respectively), 4.33 (m, 1 H),
4.88 (m, 1 H), 6.06 (m, 2 H), 6.22 (m, 1 H), 6.87 (m, 2 H), 6.99 (m, 2 H),
7.26 (m, 1 H), 7.61 (m, 2 H), 7.67 (m, 1 H), 8.43 (m, 2 H), 8.44 (m, 2 H),
what follows are the resonances of the -η3,η2-C8H11 ligand (numbering
scheme given in eq 1), 6.22 (m, 1 H-C(1)), 4.10 (m, 1 H-C(2)), 2.26
(m, 1 H-C(3)), 3.37 and 3.45 (m, 2 H-C(4)), 3.62 (m, 1 H-C(5)), 3.81
(m, 1 H-C(6)), 3.28 and 3.54 (m, 2 H-C(7)), 1.75 and 2.74 (m, 2
H-C(8)). 31P NMR (CD2Cl2): δ -24.4 (d, J ) 28.6 Hz), -0.7 (d, J )
28.6 Hz). Single crystals suitable for X-ray diffraction analysis were
obtained by dissolving the complex in boiling THF followed by slow
cooling to room temperature.
form and in excellent isolated yields (90-97%), as a
tetrafluoroborate salt.13 Once dissolved in THF-d8, this
Ir-hydride complex evolved to yield quantitatively 3
(based on NMR) over 1 h at 45 °C,14 whereas it was
stable in CD2Cl2 solution at room temperature. An
(12) Crystal data of 3: IrFeIP2C48H51‚BF4, fw 1151.59, monoclinic,
space group P21 (No. 4), a ) 10.741(1) Å, b ) 15.295(2) Å, c ) 15.968-
(2) Å, â ) 104.99(2)°, V ) 2534.0(5) Å3, Z ) 2, F(000) ) 1132,
2
2
Independent reflections 5949 (R(int) ) 0.0364), R for |F| > 2σ(|F| ) )
2
2
0.0474, wR for |F| > 2σ(|F| ) ) 0.1191. The structure was solved by
direct methods. For full details see the Supporting Information.

Communications
Organometallics, Vol. 17, No. 25, 1998 5443
X-ray structural study confirmed the formulation of 2
shown in Scheme 1,15 in particular the specific incor-
poration of an iodine atom at position 3 of the COD
ligand, and the absolute configuration S of the newly
formed stereogenic center, as shown in the ORTEP view
of Figure 1A. The coordination environment of the Ir-
(III) center is distorted octahedral with the iodo ligand
I(1) in an endo-apical position, as in derivative 3. The
Ir atom is displaced 0.23 Å along the Ir-I(1) vector out
of the best plane defined by P(1), P(2), and the midpoints
of the olefinic bonds C(51)dC(52) and C(55)dC(56). The
hydride ligand could not be localized, but its position is
inferred to be trans to I(1). The C(53)-I(2) distance of
2.212(10) is significantly longer than the typical ex-
pected average value of 2.159 for the C(sp3)-I bond.16
Further, the nonbonding distance between Ir and C(53)
is 3.01 Å, therefore shorter than the corresponding
distances to C(54), C(57), and C(58) (ranging from 3.17
to 3.26 Å). Thus, it seems that this structure anticipates
the Ir-C(53) bond-making and C(53)-I bond-breaking
process that leads to 3.
bering of eq 1).19 An alternative to this interpretation
would be an intramolecular C-H oxidative addition
involving the same C-H fragments, to afford an Ir(V)
species. Although Ir(V) complexes formed by oxidative
addition, mainly onto neutral species, are known,20 it
seems unlikely that the dicationic species A could be
involved in such a reaction. Subsequently, the C-H-
activated intermediate A could either undergo (1) an
SN2-type reaction, with iodide attacking C(3) to form
directly 2, or (2) a deprotonation affording the π-allyl
complex 3 directly. The observation that 2 is both
formed as final product in CH2Cl2 and observed as an
intermediate in THF suggests that pathway 1 is operat-
ing. The formation of 3 from 2 observed in THF can
largely be attributed to the higher basicity of THF, as
compared to CH2Cl2. This favors the deprotonation of
2, affording the pentacoordinated, electron-rich Ir(I)
species B,21 undergoing an SNi-type transformation to
give 3. Indeed, the immediate conversion of 2 to 3 in
CD2Cl2 in the presence of 1 equiv of the strong nonnu-
cleophilic base DBU is observed in an NMR control
experiment. Attempts to reverse the latter reaction
path (i.e., trying to generate 2 from 3) by adding a 5-fold
excess of [Bu4N]I and HBF4‚Me2O together to 3 in CD2-
Cl2 failed, leaving the π-allyl complex unchanged. The
addition of iodide alone gave the same negative result,
whereas the addition of strong acid alone led to slow
decomposition. These experiments probably rule out
proton-transfer reactions involving intermediate A and
indicate that 3 is not readily susceptible to nucleophilic
attack by iodide.
The origin of the stereospecificity in the formation of
2 remains a matter of speculation. Whereas the choice
of the pro-R hydrogen at C(3) undergoing the agostic
interaction is obvious because it is closer to Ir than its
pro-S companion, we cannot provide arguments explain-
ing why no reaction involving the adjacent diaste-
reotopic C(4)H2 group was observed.
We have demonstrated the possibility of enantiospe-
cific aliphatic iodination via C-H bond activation within
the coordination sphere of a chiral Ir complex. We are
currently exploring ways of decoordinating the func-
tionalized 3S-3-iodo-1,5-COD and of extending this new
reaction to further substrates.
In CD2Cl2 no incorporation of deuteride into the Ir-H
position of 2 took place, ruling out hydride formation
by solvent activation. Furthermore, the addition of a
radical-trapping reagent such as 5,5-dimethyl-1-pyrro-
line-N-oxide17 did not influence the course of the reac-
tion. These findings strongly suggest a nonradical
mechanism for the formation of 2 from 1. As shown in
Scheme 1, we assume that the starting complex 1 first
reacts with iodine, giving free iodide and the dicationic
Ir(III) intermediate A.18 We postulate that this highly
electrophilic species might be stabilized by undergoing
an agostic interaction with one of the two accessible CH2
groups of COD, i.e., either C(3)-HR or C(4)-HS (num-
(13) Experimental details for the preparation of 2 are as follows:
To a stirred red CH2Cl2 (60 mL) solution of [Ir(COD)((S)-(R)-PPF-
P(Xyl)2)]BF4 (1, 1.475 g, 1.438 mmol) at 195 K was added dropwise a
CH2Cl2 (60 mL) solution of I2 (365 g, 1.438 mmol). The black-red
solution was stirred and allowed to slowly reach room temperature
overnight. The resulting orange-red solution was evaporated, affording
a red glassy solid, which was slurried and washed with Et2O (60 mL)
and dried in vacuo, yielding a beige powder (1.806 g, 95%). Anal. Calcd
for C48H52BF4P2FeI2Ir‚0.5CH2Cl2: C, 44.06; H, 4.04; I, 19.20. Found:
C, 44.25; H, 4.07; I, 20.38. IR (Nujol) ν(Ir-H) ) 2244 cm-1 1H NMR
.
(CD2Cl2): δ -13.82 (dd, J 1 ) 16.0 Hz, J 2 ) 10.6 Hz, 1 H), 1.69 (m, 3
H), 2.21 (s, 6 H), 2.46 (s, 3 H), 3.91 (m, 1 H), 4.12 (s, 5 H), 4.46 (m, 1
H), 4.96 (m, 1 H), 6.04 (s + m, 3 H + 1 H), 6.44 (m, 2 H), 6.54 (m, 1 H),
6.97 (m, 2 H), 7.07 (m, 2 H), 7.10 (m, 1 H), 7.17 (m, 1 H), 7.35 (m, 1 H),
7.60 (m, 2 H), 7.67 (m, 1 H), 8.21 (m, 1 H), 8.31 (m, 2 H), what follows
are the resonances of the 3S-3-I-1,5-COD ligand (numbering scheme
given in eq 1), 5.62 (m, 1 H-C(1)), 5.15 (m, 1 H-C(2)), 4.55 (m, 1
H-C(3)), 1.94 and 2.82 (m, 2 H-C(4)), 4.41 (m, 1 H-C(5)), 4.11 (m, 1
H-C(6)), 3.54 and 3.65 (m, 2 H-C(7)), 1.94 and 2.94 (m, 2 H-C(8)).
31P NMR (CD2Cl2): δ -33.5 (d, 22 Hz), -2.1 (d, 22 Hz). Single crystals
suitable for X-ray diffraction analysis were grown by vapor diffusion
of Et2O into a CH2Cl2 solution of the complex (0.50 g/4 mL).
(14) Concentrated THF solutions of 1 + I2 tended to become viscous
as the reaction progressed toward 3. This is probably due to HI-induced
polymerization of THF.
Ack n ow led gm en t. We thank Arianna Martelletti
and Fabio Zu¨rcher for the X-ray crystallographic studies
of 2 and 3 and Lukas Hintermann for repeating key
experiments. R.D. thanks Novartis Ltd. for financial
support.
(18) Examples of well-characterized reactive pentacoordinate Ir(III)
complexes have recently been reported. See, for example: (a) Este-
ruelas, M. A.; Lahoz, F. J .; On˜ate, E.; Oro, L. A.; Rodr´ıguez, L.
Organometallics 1996, 15, 823. (b) Gupta, M.; Hagen, C.; Kaska, W.
C.; Cramer, R. E.; J ensen, C. M. J . Am. Chem. Soc. 1997, 119, 840.
(19) An agostic interaction of a C-H group adjacent to a coordinated
olefin has been previously observed. See: Green, M. Polyhedron 1986,
5, 427. For a review, see: Brookhart, M.; Green, M. L. H.; Wong, L.-L.
Prog. Inorg. Chem. 1988, 36, 1.
(20) See, for example: (a) Ricci, J . S., J r.; Koetzle, T. F.; Fernandez,
M.-J .; Maitlis, P. M.; Green, J . C. J . Organomet. Chem. 1986, 299, 383.
(b) Hay-Motherwell, R. S.; Wilkinson, G.; Hussain-Bates, B.; Hurst-
house, M. B. Polyhedron 1993, 12, 2009. For the oxidative C-H
addition of a coordinated propene in an Fe system, see: Barnhart, T.
M.; McMahon, R. J . J . Am. Chem. Soc. 1992, 114, 5434.
(15) Crystal data of 2: IrFeI2P2C48H52‚BF4 + 3‚CH2Cl2, fw 1534.27,
monoclinic, space group P21 (No. 4), a ) 10.4216(5) Å; b ) 17.2104(8)
Å; c ) 15.9880(7) Å, â ) 102.101(1)°, V ) 2803.9(2) Å3, Z ) 2, F(000)
2
) 1492, independent reflections 13386 (R(int) ) 0.0353), R for |F|
>
2
2
2
2σ(|F| ) 0.0510, wR for |F| > 2σ(|F| ) 0.1226. The structure was solved
by direct methods. For full details see the Supporting Information.
(16) (a) Orpen, A. G.; Brammer, L.; Allen, F. H.; Kennard, O.;
Watson, D. G.; Taylor, R. J . Chem. Soc., Dalton Trans. 1989, Supple-
ment S1-S83. (b) Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer,
L.; Orpen, A. G.; Taylor, R. J . Chem. Soc., Perkin Trans. 2 1987,
Supplement S1-S19. See also: (c) Bu¨rgi, H.-B., Dunitz, J . D., Eds.
Structure Correlation; VCH: Weinheim, 1994; Vol. 2, Appendix A.
(21) The analogous complex corresponding to 2 but bearing a
nonfunctionalized COD ligand was prepared and fully characterized,
including a solid-state structure. Reactivity studies confirmed the
relatively high acidity of this hydride: it is converted to 1 upon addition
of, for example, pyridine: Dorta, R.; Togni, A. Unpublished results.
(17) It was verified that
1 did not react with 5,5-dimethyl-1-
pyrroline-N-oxide, before iodine was added.

5444 Organometallics, Vol. 17, No. 25, 1998
Communications
Su p p or tin g In for m a tion Ava ila ble: Preparation and
characterization details for compounds 1-3. Tables of crystal-
lographic parameters, atomic coordinates, complete listing of
bond distances and angles, tables of anisotropic displacement
coefficients, coordinates of hydrogen atoms, and ORTEP
representations with complete atom numbering schemes for
2 and 3 (31 pages). Ordering information is given on any
current masthead page.
OM980801Z