Accelerated arene ligand exchange in the (arene)Cr(CO)2L series

Article abstract of DOI:10.1021/ja042705x

Arene ligand exchange in the (η⁶-arene)Cr(CO)₂L series can be accelerated if the ligand L is an electronically unsymmetrical bidentate ligand. The system evaluated here employs derivatives of tris(pyrrolyl)-phosphine as L. A series of 2-L′-substituted pyrroles was prepared, where the substituents include: L′= -SMe, -CH₂SMe, -SPh, -CH₂SPh, -SCF₃, -S-tBu, -CO₂Me, -CONMe₂, -2-pyridinyl, and -PPh₂. Reaction with CIP(pyrrolyl)₂ gave a new series of phosphines, (2-L′-pyrrolyl) (pyrrolyl)₂P. Each of these phosphines was converted to (arene)Cr(CO)₂[P(2-L′-pyrrolyl)(pyrrolyl)₂P) complexes. The substituents L′ are proposed to provide temporary coordination to the Cr and to lower the barrier to arene exchange. The series was evaluated where the arene in the complex (departing) is benzene, fluorobenzene, toluene, o-oxylene, m-xylene, or p-xylene and the incoming arene is C₆D₆, chlorobenzene-d₅, anisole-d ₈, fluorobenzene-d₅, toluene-d₈, o-oxylene-d₁₀, m-xylene-d₁₀, p-xylene-d₁₀, or mesitylene-d₁₂. Most of the new complexes showed a significant increase in the rate of arene exchange due to the side chain unit L′. The strongest effects were seen with the examples where X = -CO₂Me, -CONMe₂, and -(2-pyridinyl), allowing exchange with a half lifetime as low as 8 h/22 °C.

Full text of DOI:10.1021/ja042705x

Published on Web 05/06/2005
Accelerated Arene Ligand Exchange in the (Arene)Cr(CO)2L
Series
M. F. Semmelhack,* Anatoly Chlenov, and Douglas M. Ho
Contribution from the Department of Chemistry, Princeton UniVersity,
Princeton, New Jersey 08544
Received December 4, 2004; E-mail: mfshack@princeton.edu
Abstract: Arene ligand exchange in the (η6-arene)Cr(CO)2L series can be accelerated if the ligand L is an
electronically unsymmetrical bidentate ligand. The system evaluated here employs derivatives of tris(pyrrolyl)-
phosphine as L. A series of 2-L′-substituted pyrroles was prepared, where the substituents include:
L′ ) -SMe, -CH2SMe, -SPh, -CH2SPh, -SCF3, -S-tBu, -CO2Me, -CONMe2, -2-pyridinyl, and -PPh2.
Reaction with ClP(pyrrolyl)2 gave a new series of phosphines, (2-L′-pyrrolyl)(pyrrolyl)2P. Each of these
phosphines was converted to (arene)Cr(CO)2[P(2-L′-pyrrolyl)(pyrrolyl)2P) complexes. The substituents L′
are proposed to provide temporary coordination to the Cr and to lower the barrier to arene exchange. The
series was evaluated where the arene in the complex (departing) is benzene, fluorobenzene, toluene,
o-xylene, m-xylene, or p-xylene and the incoming arene is C6D6, chlorobenzene-d5, anisole-d8, fluoroben-
zene-d5, toluene-d8, o-xylene-d10, m-xylene-d10, p-xylene-d10, or mesitylene-d12. Most of the new complexes
showed a significant increase in the rate of arene exchange due to the side chain unit L′. The strongest
effects were seen with the examples where X ) -CO2Me, -CONMe2, and -(2-pyridinyl), allowing exchange
with a half lifetime as low as 8 h/22 °C.
Scheme 1. General Conversions with Cr(CO)3 Activation
Introduction
Complexation of an arene with transition metals activates the
arene toward nucleophile addition, deprotonation of the ring,
and formation of the benzylic cations, anions, and radicals.1,2
The arene-Cr(CO)3 series allows particularly general substitu-
tion sequences via nucleophile addition/elimination (SNAr, path
a/b) addition/oxidation (path c/d) and indirect substitution (path
c/e/b; Scheme 1). Each of these reaction pathways has seen
application as synthesis methodology on a research scale.
However, the utility is limited by the need for stoichiometric
amounts of the metal-ligand unit.3,4
Scheme 2. Proposed Catalysis of the SNAr Process
A particularly simple catalytic cycle can be written for the
SNAr process (Scheme 2); the addition/substitution step is
followed by spontaneous exchange of the arene ligands,
(1) Merlic, C. A.; Hietbrink, B. N.; Houk, K. N. J. Org. Chem. 2001, 66, 6738-
6744.
(2) (a) Semmelhack, M. F.; Chlenov, A. Aromatic Nucleophilic Substitution.
In New Aspects of Transition Metal Arene Complexes; Kundig, E. P., Ed.;
Springer-Verlag, Berlin, 2004; p 43. (b) Rose-Munch, F.; Rose, E.
Arenetricarbonylchromium Complexes: Ipso, Cine, Tele Nucleophilic
Aromatic Substitution. In Modern Arene Chemistry; Astruc, D., Ed.; Wiley-
VCH Verlag: 2002; p 368.
(3) A Cp*Rh(III) system allows catalytic substitution of a limited number of
fluoroarenes with alkoxide nucleophiles. See: (a) Goryunov, L. I.; Litvak,
V. V.; Shteingarts, V. D. Zh. Org. Khim. 1988, 24, 401-405. (b) Goryunov,
L. I.; Litvak, V. V.; Shteingarts, V. D. Zh. Org. Khim. 1987, 28, 1230-
1237. (c) Litvak, V. V.; Goryunov, L. I.; Shteingarts, V. D. IzV. SOAN
SSSR. Ser. Khim. Nauk 1985, 132-134. (d) Goryunov, L. I.; Terent’eva,
Y. A.; Litvak, V. V.; Shteingarts, V. D. Zh. Org. Khim. 1990, 26, 1058.
(e) Houghton, R. P.; Voyle, M.; Price, R. J. Chem. Soc., Perkin Trans. 1
1984, 925-931.
regenerating the reactant arene and freeing the product arene
from the metal. Efficient catalysis, however, will require that
the arene exchange step be compatible with the conditions of
the SNAr step and that arene exchange be highly efficient (high
catalyst turnover). Here, we detail our efforts to influence the
rate and efficiency of arene exchange by ligand effects.
(4) In the only example of catalysis in the Cr(CO)3 series, arene π complexation
was used to accelerate Pd(0)-catalyzed coupling reactions with aryl
chlorides: Brase, S. Tetrahedron Lett. 1999, 40, 6757-6759.
9
10.1021/ja042705x CCC: $30.25 © 2005 American Chemical Society
J. AM. CHEM. SOC. 2005, 127, 7759-7773
7759

A R T I C L E S
Semmelhack et al.
Scheme 3. Associative Mechanism of Arene Ligand Exchange
Scheme 4. Three-Phase Test for Exchange
Scheme 5. AreneExchange Assisted by Interaction with a Second
Arene Complex
Background
Mechanism Considerations. Arene exchange in the (arene)-
Cr(CO)3 series has been studied for 40 years.5,6 Typically, high
activation barriers are observed, and side reactions, such as
chromium oligomerization via carbonyl bridging, are often faster
and irreversible. Arene exchange reactions are typically run at
140-180 °C in the presence of a large excess of the incoming
arene. Conversions are good when the incoming arene is more
electron rich than the leaving arene, as in the case of (benzene)-
Cr(CO)3 and aniline to give the aniline complex (eq 1).7
arene is followed by attack on the resulting unsaturated η4
species 2. An alternative mechanism begins with a complete
dissociation of the (arene)Cr(CO)3 complex (to give intermediate
6 in Scheme 4) followed by fast coordination of the incoming
arene. This was probed with a “three-phase test”, where a bead-
to-bead migration of the Cr(CO)3 unit was detected at 170 °C
in the presence of polar additives such as cyclohexanone or THF
but not in their absence (cyclohexane solvent).8
Donor Ligand Effect on Arene Exchange. A key observa-
tion was that added (arene′)Cr(CO)3 complex (9 in Scheme 5)
catalyzes arene exchange of another (arene)Cr(CO)3 complex
(10) without undergoing exchange itself.9,10 This effect was
attributed to coordination of the carbonyl ligand (in 11) to lower
the barrier to the η6 f η4 conversion of the arene ligand.
Other donor molecules such as THF and cyclohexanone also
catalyze arene exchange.12,13 The relative catalytic ability of
donor additives is: cyclohexanone/1400; benzonitrile/600;
1,5-cyclooctadiene/200; triglyme/200; THF/30; and complex
9/30.8 When cyclohexanone was used as an additive, the rate
of arene exchange was proportional to the concentration of the
starting arene complex and cyclohexanone, and independent of
the concentration of the incoming arene.8,13 These observations
are consistent with slow displacement of one of the arene double
bonds by the donor molecule to give 12 followed by a fast
coordination of the incoming arene (eq 2). Arene exchange is
detectable at temperatures as low as 80 °C [for (benzene)-
Cr(CO)3 as a substrate and hexamethylbenzene as an incoming
arene in cyclohexanone], although typical experiments were still
performed at 140 °C to ensure a complete reaction.13
The first proposed mechanism involved complete dissociation
of the Cr(CO)3 unit followed by an SN2-like attack on the arene
ligand of another (arene)Cr(CO)3 complex; the central observa-
tion favoring this picture was the second-order rate dependence
on the (arene)Cr(CO)3 concentration.5,6 Additional experiments
were incompatible with this mechanism, and it was soon
replaced by a stepwise “unzipping” mechanism (Scheme 3).8-10
In the first (rate-determining) step, one of the arene double bonds
detaches from 1 to generate a coordinatively unsaturated η4
intermediate, 2. In a subsequent fast step, the incoming arene
coordinates in η2 fashion (in 3). The leaving arene further
detaches, while the incoming arene fills the liberated coordina-
tion site to give first the η4, η2 intermediate, 4, and finally the
η6 product, 5.
Details of the mechanism in Scheme 3 are still unclear since
intermediates 2, 3, and 4 have not been observed spectroscopi-
cally. On the basis of Huckel molecular orbital (MO) calcula-
tions, direct attack of an arene on the chromium complex is
improbable due to high electron density on the chromium
center.11 It was therefore proposed that predissociation of the
(5) Strohmeier, W.; Mittnacht, H. Z. Phys. Chem. 1961, 29, 339-346.
(6) Strohmeier, W.; Staricco, E. H. Z. Phys. Chem. 1963, 38, 315-325.
(7) Natta, G.; Ercoli, R.; Calderazzo, F.; Santambrogio, E. Chim. Ind. 1958,
40, 1003-1007.
(8) Traylor, T. G.; Stewart, K. J.; Goldberg, M. J. J. Am. Chem. Soc. 1984,
106, 4445-4454.
(9) Traylor, T. G.; Stewart, K. J.; Goldberg, M. J. Organometallics 1986, 5,
2062-2067.
(10) Traylor, T. G.; Stewart, K. Organometallics 1984, 3, 325-327.
(11) Howell, J. A. S.; Ashford, N. F.; Dixon, D. T.; Kola, J. C.; Albright, T.
A.; Kang, S. K. Organometallics 1991, 10, 1852-1864.
Structure/Reactivity Relationship in Arene Exchange.
When the temperature is sufficient for arene exchange to
9
7760 J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005

Accelerated Arene Ligand Exchange
A R T I C L E S
Scheme 6. Fast Exchange with Methyl Acrylate23
Figure 1. Relative stability of (arene)Cr(CO)3 complexes.
the fluorobenzene or benzene complex, with mesitylene as the
incoming arene and no added donor catalyst.17
proceed, the equilibrium constant determines the extent of the
exchange reaction. From a study of the equilibrium constants
for both the forward and reverse reactions,8 the stability order
presented in Figure 1 was determined. This order is consistent
with the arene-chromium bond energies measured by micro-
calorimetry.14-16 An interesting point is the absence of a
destabilizing steric effect of the methyl groups on the thermo-
dynamic stability of the (alkylbenzene)Cr(CO)3 complexes. The
stability order parallels the number of the methyl groups and is
fairly independent of their relative position on the aromatic ring.
Notable is the low position of fluorobenzene in the series.
This data point is important for our goal of designing a viable
catalytic system as it implies that arene exchange must proceed
thermodynamically uphill from a more stable arene-chromium
complex to a less stable one in regenerating the activated
fluoroarene (Scheme 2, step b). A somewhat unfavorable
equilibrium can be tolerated in a catalytic process since the
resulting fluoroarene complex will be consumed irreversibly in
the addition/elimination step. The equilibrium constants for arene
exchange are not very large in absolute magnitude, and the
equilibrium can be shifted in the desired direction if a large
excess of the incoming arene is employed.12 Specifically,
(fluorobenzene)Cr(CO)3 can be obtained in over 70% yield from
(benzene)Cr(CO)3 using a large excess of fluorobenzene after
21 h at 150 °C in THF as a solvent.12
While the examples above of accelerated arene exchange
based on substrate changes show significant effects, a generally
useful SNAr process would require that the catalytic efficiency
be relatively independent of arene structure. An attractive
approach to arene labilization is via modification of one of the
spectator ligands (CO in this case). Replacement of a CO in an
(arene)Cr(CO)3 complex with a phosphine donor ligand (such
as triphenyl- or trialkylphosphine) results in increased arene-
chromium bond strength presumably due to increased back
donation to the arene from the metal.18,19,20,21 The increased
arene-metal bond strength leads to a drastic inhibition of the
arene exchange reaction. In addition to the retarding electronic
effect of the phosphine donor ligand, a steric effect was also
suggested to play a negative role.22
Temporary Coordination of a Ligand Side Chain to
Accelerate Arene Exchange. We proposed19 to replace one of
the CO ligands with a bidentate ligand that would have a side
chain group (L′ in 13) able to coordinate temporarily to the
chromium center (14, eq 3) and serve as the donor catalyst.
The ligand chosen in the initial work (diphos) was not
successful; it retarded the arene exchange, probably due to the
electron donating power of the phosphine which increased the
arene metal bond strength in the complex 13.
Kinetic factors that govern relative rates of arene exchange
are much less studied. The effect of methyl substitution on the
leaving arene was evaluated in the reaction of various (arene)-
Cr(CO)3 complexes with hexamethylbenzene in cyclohexa-
none.13 Exchange rates were consistent with the more thermo-
dynamically stable (mesitylene)Cr(CO)3 complex reacting at a
slower rate than those of p-xylene or benzene. The temperature
dependence of the rates, however, showed that the enthalpy of
activation was lowest for the mesitylene complex, leading to
the conclusion that the rate difference was due to entropic
factors.13 In the case of fluoroarene substrates, ground-state
destabilization of the starting material was invoked.17 Again
consistent with thermodynamic stability, the less stable
(1,4-difluorobenzene)Cr(CO)3 complex exchanges faster than
A spectacular rate enhancement attributed to the same concept
involves methyl methacrylate as the new ligand (Scheme 6).23
Arene exchange with a series of alkylbenzenes was observed
at 25 °C. The carbonyl group of the acrylate is suggested to
provide the temporary “push” and reduce the barrier to
exchange, potentially an example of the principle presented in
(18) Choi, H. W.; Sollberger, M. S. J. Organomet. Chem. 1983, 243, C39-
C41.
(12) Mahaffy, C. A. L.; Pauson, P. L. J. Chem. Res., Synop. 1979, 126-127.
(13) Zimmerman, C. L.; Shaner, S. L.; Roth, S. A.; Willeford, B. R. J. Chem.
Res., Synop. 1980, 108.
(19) Semmelhack, M. F.; Seufert, W.; Keller, L. J. Organomet. Chem. 1982,
226, 183-190.
(14) Mukerjee, S. L.; Lang, R. F.; Ju, T.; Kiss, G.; Hoff, C. D. Inorg. Chem.
1992, 31, 4885-4889.
(20) Dabard, R.; Jaouen, G.; Simonneaux, G.; Cais, M.; Kohn, D. H.; Lapid,
A.; Tatarsky, D. J. Organomet. Chem. 1980, 184, 91-101.
(21) Cais, M.; Kaftory, M.; Kohn, D. H.; Tatarsky, D. J. Organomet. Chem.
1980, 184, 103-112.
(15) Brown, D. L. S.; Connor, J. A.; Demain, C. P.; Leung, M. L.; Martinho-
Simoes, J. A.; Skinner, H. A.; Moattar, M. T. Z. J. Organomet. Chem.
1977, 142, 321-335.
(22) Butler, I. S.; Ismail, A. A. Inorg. Chem. 1986, 25, 3910-3914.
(23) (a) Kundig, E. P.; Kondratenko, M.; Romanens, P. Angew. Chem., Int. Ed.
1998, 37, 3146-3148. (b) Kundig, E. P.; Robvieux, F.; Kondratenko, M.
Synthesis, 2002, 2053-2056.
(16) Adedeji, F. A.; Brown, D. L. S.; Connor, J. A.; Leung, M. L.; Paz-Andrade,
I. M.; Skinner, H. A. J. Organomet. Chem. 1975, 97, 221-228.
(17) Jagirdar, B. R.; Klabunde, K.J. J. Coord. Chem. 1995, 34, 31-43.
9
J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005 7761

A R T I C L E S
Semmelhack et al.
Figure 4. Pyrrolyl-based phosphine with donor side chains.
Figure 2. Possible replacements for CO.
Figure 5. Tris(2-subs)pyrrolylphosphines.
triphenyl phosphite analogue (21c) slows the process by a factor
of ca. 330.29 Tris(pyrrole)phosphine [P(Pyr)3, 20] was recog-
nized by Molloy as having useful properties as a replacement
for CO.25 Unlike simple aminophosphines, P(Pyr)3 is relatively
stable toward cleavage of the N-P bond (recrystallizes from
MeOH), relatively nonnucleophilic (no reaction with MeI), and
is strongly electron withdrawing, comparable to CO.25 It is easily
prepared from pyrrole and PCl3. In a calibration test, the P(Pyr)3
ligand promoted rapid substitution for fluoride (Figure 3, 21b)
with a half lifetime of 91 s, only 1.4 times slower than the parent
fluorobenzene-Cr(CO)3 complex.29
Tris(pyrrole)phosphine as the Basis for Ligand Design in
Accelerated Arene Exchange.30 (a) Preparation of the
Complexes. The role of temporary coordination via a side-chain
donor group was explored using the tris(pyrrole)phosphine
structure 20 as a starting point and positioning a donor group
at the 2-position of the pyrrole (in 22 and 23, Figure 4). The
series with three substituted pyrroles (22) allowed a simple
synthesis from PCl3 and was tested first.
Treatment of N-tBoc pyrrole with LiTMP followed by
quenching the 2-lithio intermediate with dimethyl disulfide and
then deprotection gave 2-thiomethylpyrrole (24)31,32 in about
40% yield on a moderate scale, Figure 5. A mixture of 24, NaH,
and PCl3 produced phosphine 25 in 62% yield as a colorless
solid with mp 76-77 °C. Similarly, the N-Boc-2-lithiopyrrole
was trapped with Me3SnCl to give the 2-stannyl derivative, 26.
Pd(0)-catalyzed cross coupling with allyl bromide followed by
deprotection gave 2-allylpyrrole, 27.33 The tris(2-allyl)pyrrolyl-
phosphine 28 was obtained in 41% yield as a colorless oil.
Following the general protocol34 for replacing one CO from
(arene)Cr(CO)3 complexes with a donor ligand, the (arene)-
Figure 3. Relative reactivity toward the SNAr reaction.
eq 3. An application in the catalysis of cycloaddition reactions
via arene exchange has appeared.23b
Results and Discussion
SNAr Reactivity Considerations in Ligand Design. The
observations summarized above for the Cr(CO)3 series and
related studies with other metals not reviewed here support the
hypothesis represented in eq 3. The ideal chelating ligand, L-L′,
would allow rapid SNAr reactions of fluoro- or chloroarenes
and compatible conditions for arene ligand exchange without
significant irreversible side reactions of the catalyst.
The SNAr reactivity of the arene complexes is quite sensitive
to the nature of the other ligands, with CO being a very strong
activator. Ligands of varying electronic properties were con-
sidered, with an emphasis on electron-withdrawing ability.
Obvious candidates are isonitriles,24 (perfluoroalkyl)phosphines,
(perfluoroaryl)phosphines, and tris(pyrrole)phosphines (Figure
2).25 The isonitrile complex (17) was prepared,26 showed
significant instability under the typical SNAr conditions (pyrro-
lidine nucleophile, DMF solvent), and was not pursued. Tris-
(perfluoroalkyl)phosphine ligands present some interesting
possibilities, and synthesis challenges27 are under study. The
tris(perfluorophenyl)phosphine complex 18 was readily prepared
and characterized, but when exposed to pyrrolidine, a fast
reaction occurred via substitution at the para position of the
perfluorophenyl group (to give 19).28
A simple reaction of (fluorobenzene)Cr(CO)3 with pyrrolidine
in DMF at 23 °C (the parent compound, 21a, Figure 3) shows
a half lifetime of 67 s. Replacement of CO with PPh3 resulted
in a much less reactive complex (Figure 3, 21a vs 21d).29 The
(29) Semmelhack, M. F.; Hilt, G.; Colley, J. H. Tetrahedron Lett. 1998, 39,
7683-7686.
(30) A preliminary account of this work has appeared: Semmelhack, M. F.;
Chlenov, A.; Wu, L.; Ho, D. M. J. Am. Chem. Soc. 2001, 123, 8438-
8439.
(31) Prepared by a different method: Nedolya, N. A.; Brandsma, L.; Verkruijsse,
H. D.; Trofimov, B. A. Tetrahedron Lett. 1997, 38, 7247-7248.
(32) We thank Dr. Lingyun Wu for the initial preparation of this compound,
based on a general method for metalation/trapping/deprotection of N-boc-
pyrrole: Gharpure, M.; Stoller, A.; Bellamy, F.; Firnau, G.; Snieckus, V.
Synthesis 1991, 1079-1082.
(33) Direct allylation of pyrrole is reported, but the yields are low and the product
is a mixture of the 2- and 3-substitution product: Papadopoulos, E. P.;
VanderWerf, C. A. Heterocycles 1982, 19, 343.
(24) For an example of SNAr reactivity of fluorobenzene(arylisonitrile) di-
carbonylchromium, see: Maiorana, S.; Baldoli, C.; Licandro, E.; Casiraghi,
L.; de Magistris, E.; Paio, A.; Provera, S.; Seneci, P. Tetrahedron Lett.
2000, 41, 7271-7275.
(25) Moloy, K. G.; Petersen, J. L. J. Am. Chem. Soc. 1995, 117, 7696-7710.
(26) Unpublished work at Princeton.
(27) For discussion and examples, see: Ernst, M. F.; Roddick, D. M. Inorg.
Chem. 1989, 28, 1624-1632.
(28) It is known that even the free tris(perfluorophenyl)phosphine undergoes
SNAr reactions at the para position with ease: Hannah, H. R.; Miller, J.
M. Can. J. Chem. 1978, 57, 1011-1017.
9
7762 J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005

Accelerated Arene Ligand Exchange
A R T I C L E S
Scheme 7. Preparation of the Complexes 41
Figure 6. Complexes from the tris(2-subs)pyrrolylphosphines.
Figure 7. Chelate complexes and generic target ligand.
Cr(CO)3 was irradiated in the presence of cyclooctene (COE)
to give a reactive intermediate, (arene)Cr(CO)2(COE). Then a
thermal reaction at 23 °C produced the ligand substitution
product, 29 (eq 4).
imagined that, with only one side chain donor ligand as in 37,
any steric inhibition to phosphorus coordination would be less
and the possibility of a stable chelated intermediate such as 35
would be removed.
A series of phosphine ligands with one functionalized pyrrole
group as in 37 would allow systematic evaluation of the effects
of side chain length and the coordinating group Y. Coordination
via the side-chain group Y should be easily reversible so as to
allow the incoming arene to compete successfully for the Cr
and generate the arene-exchanged product. Several parameters
were varied: Y can be soft (e.g., sulfur) or hard (e.g., nitrogen
or oxygen) and isolated or part of an extended π system to allow
back donation from the metal. The side chain (R in 37) can
have a secondary influence by modifying both steric and
electronic properties of L′.
The target ligands, represented by 38, were synthesized
according to the general strategy shown in Scheme 7. Chloro-
dipyrrolylphosphine (39) was obtained in good yield from PCl3
and two equivs of pyrrole with triethylamine as a base. Then,
replacement of the chloride with a substituted pyrrole gave the
general phosphine, 38. Gentle thermal reaction of 38 with the
COE complex 40 produced complex 41.
Sulfur was the first donor atom to be studied, partly because
of the encouraging result with the tris(2-methylthiopyrrolyl)-
phosphine ligand (25). Several varieties of the sulfur-containing
side chains L′, which differed in coordinating ability, were
envisioned (Scheme 7). Steric effects were evaluated in the
series methylthio vs tert-butylthio vs phenylthio. Electronic
effects should manifest themselves when comparing methylthio
with (trifluoromethyl)thio and with phenylthio. The effect of
the size of the chelate ring in an intermediate such as 14 (eq 3)
was studied by comparing methylthio with methylthiomethyl
and phenylthio with phenylthiomethyl. The hardness (polariz-
ability) of the donating atom could also be varied by replacing
sulfur with a phosphorus (L′ ) PPh2), nitrogen (L′ ) 2-pyridyl),
or oxygen (L′ ) CO2Me or C(O)NMe2) group.
With tris(2-allylpyrrolyl)phosphine and (fluorobenzene)Cr-
(CO)3, the product 30 was obtained in 53% yield after
chromatography on silica gel (Figure 6). The 1H NMR spectrum
showed evidence of restricted rotation at 23 °C but simplified
at 70 °C. When heated at 70 °C in C6H6, no change was
observed in the 1H NMR spectrum after several days. At higher
temperatures, slow decomposition occurred with no evidence
of arene exchange.
With tris(2-methylthiopyrrolyl)phosphine and a series of
(arene)Cr(CO)3 precursors, somewhat labile complexes were
obtained under the standard conditions for complexation. The
major component in each case was tentatively characterized as
the S-bound versions, 31-34, Figure 6. The primary evidence
is the dominant peak in the 31P NMR spectrum at δ 21.9 ppm,
characteristic of uncomplexed P (the P-bound complex is
expected to show a peak at δ 170 ppm). In the 13C NMR spectra,
the Me group of the free phosphine ligand appears at
δ 21.9 ppm, while in the complexes, one Me group appears
12 ppm further downfield. While this was not the intended mode
of coordination, it does include a side-chain donor atom and
satisfies the design principle. Heating of the fluorobenzene
analogue (33) in mesitylene at 60 °C led to rapid loss of the
fluorobenzene ligand and formation of the chelated version, 35,
in 23% yield (Figure 7). The extra CO ligand presumably arose
from some decomposition of the complex. If the same reaction
is carried out in the presence of triphenylphosphine, the
analogous complex, 36, was obtained and characterized by X-ray
diffraction studies (Supporting Information). The instability of
this series of complexes and easy loss of the fluorobenzene
ligand was taken as an impetus to refine the ligand design. We
Several methods were available for the synthesis of the
substituted pyrroles (Scheme 8). Electrophilic aromatic substitu-
tion on pyrrole33,35 was used to make the methylthiomethyl-
(35) Torisawa, Y.; Satoh, A.; Ikegami, S. Tetrahedron Lett. 1988, 29, 1729-
(34) Butler, I. S.; English, A. M.; Plowman, K. R. Inorg. Synth. 1982, 21, 1-6.
1732.
9
J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005 7763

A R T I C L E S
Semmelhack et al.
Scheme 8. Preparation of 2-Substituted Pyrroles
Scheme 9. Complications from Side-Chain Coordination
(41a), phenylthiomethyl- (41b),36,37 and trifluoromethylthio-
pyrroles (41c).38 Addition of tBuMgBr and PhMgBr to 2-thio-
cyanatopyrrole gave 2-tert-butylthiopyrrole (41d) and 2-phenyl-
thiopyrrole (41e), respectively.38 The 2-lithiation procedure on
the N-boc-pyrrole followed by reaction with PPh2Cl and
deprotection gave the 2-phosphine derivative 41f in 56% yield
as a colorless oil.39 Two acyl derivatives, methyl pyrrole-2-
carboxylate (41g)40 and the N,N-dimethyl amide (41h) of
pyrrole-2-carboxylic acid, were prepared from the carboxylic
acid following literature procedures.41 Palladium coupling was
chosen to synthesize 2-(2′-pyridino)pyrrole after several attempts
to reproduce literature syntheses were unsuccessful.42-44 N-Boc-
pyrrole was converted to the 2-trimethylstannyl derivative45 in
excellent yield via a lithiation/electrophile trapping sequence.
Iodination then yielded protected 2-iodopyrrole (42),46,47 which
was coupled with 2-trimethylstannylpyridine48 using Pd(0)
catalysis.49 After deprotection, 2-pyridinopyrrole (41i) was
obtained in better than 50% yield overall.
case, although the yields were slightly improved by using NaH
in certain cases (Figure 8).
Benzene complexes of type 44 were all obtained in good
yields from (benzene)tricarbonylchromium(0) by the general
procedure described in eq 4. The structures and yields are given
in Figure 9. Complexes 44a-e and 44g are moderately stable
yellow solids. They were routinely purified by column chro-
matography on silica gel without special precautions. Recrystal-
lization from ether/hexanes gave pure samples. When pure,
complexes 44a-e,g can be stored under Ar for a long time.
Complexes 44f,h-j are orange and relatively less stable.
Column chromatography led to significant decomposition, and
recrystallization had to be performed rigorously under Ar.
Complex 44i was only a minor product in the standard
preparation and was not studied.
Typically, minor products were observed during complex-
ation. In the case of the (2-methylthiomethyl)pyrrole and the
(2-phenylthiomethyl)pyrrole cases (44d, and 44e), two minor
products were assigned to an isomer with the side-chain ligand
instead of the phosphorus attached to Cr (45, 46) and a dimeric
structure, where the bidentate phosphine bridges between two
(benzene)Cr(CO)2 units (47, 48). The composition of the
mixtures changed with time. For example, when the product
mixture from the (2-phenylthiomethyl)pyrrole case was allowed
to stand at 23 °C overnight, the minor products slowly decreased
in abundance, and the major isomer (P-bound) increased. With
the (2-methylthiomethyl)pyrrole phosphine ligand, heating at
60 °C was necessary to initiate equilibration, and, again, the
desired complex became essentially the only product. An
extreme case of “wrong” complexation arose from the
(2-diphenylphosphine)pyrrolylphosphine ligand (43i). In this
case, a 4:1 mixture was obtained where the major product was
isolated and fully characterized as the side-bound isomer, 49.
From NMR spectral data on the mixture, the minor isomer was
assigned as the desired phosphine (44i). The ratio did not change
when the mixture was allowed to stir for 3 h at 70 °C. The
The synthesis of the trispyrrole phosphines 43 was achieved
with DMAP as base at 65 °C in THF with Pyr2PCl in the typical
(36) Barcock, R. A.; Moorcroft, N. A.; Storr, R. C.; Young, J. H.; Fuller, L. S.
Tetrahedron Lett. 1993, 34, 1187-1190.
(37) Campiani, G.; Nacci, V.; Bechelli, S.; Ciani, S. M.; Garofalo, A.; Fiorini,
I.; Wikstrom, H.; de Boer, P.; Liao, Y.; Tepper, P. G.; Cagnotto, A.;
Mennini, T. J. Med. Chem. 1998, 41, 3763-3772.
(38) Haas, A.; Niemann, U. Chem. Ber. 1977, 110, 67-77.
(39) The pyrrole phosphine 41f is known, from a different procedure: Allen,
D. W.; Charlton, J. R.; Hutley, B. G. Phosphorus 1976 6, 191-194.
(40) Fischer, E.; van Slyke, D. D. Chem. Ber. 1911, 44, 3166-3171.
(41) Couch, P. W.; Games, D. E.; Jackson, A. H. J. Chem. Soc., Perkin Trans.
1 1976, 2492-2501.
(42) Seki, K.; Ohkura, K.; Terashima, M.; Kanaoka, Y. Heterocycles 1984, 22,
2347-2350.
(43) Corriu, R. J. P.; Huynh, V.; Iqbal, J.; Moreau, J. J. E.; Vernhet, C.
Tetrahedron 1992, 48, 6231-6244.
(44) Savoia, D.; Concialini, V.; Roffia, S.; Tarsi, L. J. Org. Chem. 1991, 56,
1822-1827.
(45) Martina, S.; Enkelmann, V.; Wegner, G.; Schluter, A.-D. Synthesis 1991,
613-615.
(46) Chen, W.; Cava, M. P. Tetrahedron Lett. 1987, 28, 6025-6026.
(47) Groenendaal, L.; Van Loo, M. E.; Vekemans, J. A. J. M.; Meijer, E. W.
Synth. Comm. 1995, 25, 1589-1600.
(48) Anderson, D. G.; Webster, D. E. J. Chem. Soc. B 1968, 765.
(49) Fan, Y.-H.; Haseltine, J. J. Heterocyclic Chem. 1999, 36, 869-872.
9
7764 J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005

Accelerated Arene Ligand Exchange
A R T I C L E S
Figure 8. Yields of the monosubstituted tris(pyrrolyl)phosphines.
Figure 11. Substituted arene ligands on the 2-(methoxycarbonyl)pyr-
rolylphosphine complexes.
Figure 9. Structures and yields of the benzene complexes.
Figure 10. Variations in ligand binding.
preferential attachment of the chromium to the side chain
phosphorus is consistent with higher electron density at that
site.
Figure 12. X-ray structures of the complexes 44a and 44f.
The apparent kinetic preference for initial side-chain coor-
dination and slow equilibration in the phenylthiomethyl and the
methylthiomethyl examples appeared again in the formation of
the corresponding complexes with fluorobenzene, 50. In this
case, 19F NMR provided additional information. Working with
mixtures whose composition changed slowly with time and
The structures of complexes 44a and 44f were determined
by single-crystal X-ray diffraction (Figure 12). An important
feature in 44a is the position of the sulfur about 4 Å away from
the metal center. It is poised to make the interaction leading to
side chain coordination. In 44f, the corresponding oxygen-
chromium distance is even shorter (3.6 Å). In 44a, the arene
ligand is observed only in the staggered conformation with
respect to the CO ligand, while in 44f, there is evidence for a
low barrier to rotation with the population of both the staggered
(64%) and eclipsed (36%) conformations.
1
monitoring by 19F, 31P, and H NMR, tentative correlations of
the peaks in the 19F NMR spectrum are suggested as shown in
Scheme 9. The P-bound complex 50e was isolated and fully
characterized. The S-bound complex 51 was the major product
at the beginning of the reaction, but it slowly converted to the
P-bound complex 50e. Two small peaks of approximately the
same intensity, one close to the peak for the P-bound complex
50e and the other close to the peak for the S-bound complex
51, were tentatively assigned to the bridged species 52. Another
peak, which appeared between the S-bound and P-bound clusters
of peaks, was assigned to the transient COE intermediate 53.
After 2 h, most of the COE adduct 53 was converted to a
mixture of species 51 (S-bound), 50e (P-bound), and 52
(bridged) in an approximate ratio of 1:2:5. The area of the peaks
corresponding to S-bound (51) and the bridged (52) species
decreased with time, while the area of the P-bound species (50e)
increased. The estimated half lifetimes are about 10 h (51) and
14 h (52) at 23 °C.
(b) Arene Exchange Rates. Effect of the Side Chain. The
ability of the side chain of the ligand to facilitate arene exchange
was determined by measurement of the rate of the arene
exchange reaction in neat perdeuteriobenzene (Table 1). The
1
reaction was continuously monitored by H NMR at elevated
temperature (typically at 70 °C) following the disappearance
of the complexed benzene peak at around δ 4 ppm in 44. Signals
due to the phosphine remained unchanged, consistent with the
formation of the perdeuterated benzene complex 55 with
essentially identical environment compared to the starting
material.
As a reference point, the complex with L′ ) H shows no
arene exchange after many hours at 150 °C. For the trifluoro-
1
A series of complexes was synthesized employing the
2-(methoxycarbonyl)pyrrolylphosphine ligand 43h with differing
arene rings. The standard protocol (eq 4) gave the complexes
54a-d as orange solids in the yields shown in Figure 11. The
fluorobenzene complex 54a was too unstable to obtain com-
methylthio complex 44b, no change in the H spectrum was
observed after 12 h at 70 °C, and for the phenylthiomethyl
complex 44e, no exchange was observed after 60 h at 70 °C.
For 44e, partial decomposition of the starting material led to
1
severe line broadening in the H NMR spectrum and did not
1
pletely pure. It was tentatively characterized by H NMR and
allow an investigation of the reaction for longer time. The
dimethylamide and pyridine complexes 44f and 44j decomposed
31P NMR spectral data.
9
J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005 7765

A R T I C L E S
Semmelhack et al.
Table 1. Ligand Effects on the Rate of Arene Exchange of
(Arene)Cr(CO)2(L-L′) 44 with Benzene-d6
complex
half life at 70.0 °C
8.7 h
<5% conversion/12 h
30.6 h
44a L ) SMe
44b L ) SCF3
44c L ) SPh
44d L ) CH2SMe
44e L ) CH2SPh
44f L ) CONMe2
44g L ) St-Bu
44h L ) CO2Me
44j L ) 2-Py
28.7 h
very slow (decomp)
9 h at 22 °Ca
9.91 h
Figure 13. Eyring plot for the arene-exchange reaction of the complex
44h with C6D6.
0.5 h (∼115 h at 23 °C)
8 h at 22 °Ca
a Too fast to measure at 70 °C.
Among the π-acceptor side chains, pyridine is the fastest. It
not only provides a basic lone pair but also possesses a relatively
low energy π* orbital for back bonding from the chromium.
The ester also possesses a lower energy π* then the amide, but
the amide provides a much more basic lone pair (on the oxygen);
evidently the stronger σ-donating ability of the amide is
responsible for a more stable transition state for arene detach-
ment in this case.
quickly at 70 °C. However, when arene exchange was performed
at 22 °C, clean formation of the corresponding C6D6 complex
was observed. The following reactivity order is evident (from
Table 1)
2-Py > CONMe2 > CO2Me . SMe > S-t-Bu >
CH2SMe > SPh . CH2SPh, SCF3
Preliminary Studies of the Temperature Dependence of
Arene Exchange: Eyring Plot. Because the complex bearing
the carbomethoxy side chain (44h) has a relative low barrier to
exchange and is easy to prepare and purify, it was chosen as
the example for further kinetic studies. By use of the degenerate
exchange (except for the deuterium label), the rate of disap-
pearance of 44h was monitored at 23, 50, and 70 °C and the
standard Eyring plot (Figure 13) gave activation parameters of
∆Hq 22 kcal/mol (from the slope) and ∆Sq -2.8 cal/mol K (from
the intercept).
The small value of ∆Sq is not consistent with an associative
reaction for which a value below -10 eu is expected nor with
a dissociative mechanism for which a value above 10 eu is
expected.50 It is consistent with an interchange mechanism, as
defined by Atwood, although “one must be careful in interpret-
ing the mechanism for reactions that have ∆Sq between -10
and +10 eu because solvent reorganization may also contribute,
especially for polar solvents and charged metal complexes”.50
Summary of the Rate Data. (a) Arene exchange is much
faster when the side chain heteroatom possesses an available
π* orbital (L′ ) 2-Py, C(O)NMe2, CO2Me). Sulfur-based
σ donors, which do not have a low energy π* (L′ ) SR and
CH2SR), were much slower. (b) Exchange in a complex with a
large t-BuS side chain is only slightly slower than that for the
MeS analogue, suggesting that steric effects play only a minor
role. However, the electronic effect is very dramatic. The SCF3
complex is much slower than the SMe analogue. Also, SMe is
faster than SPh and CH2SMe is faster than CH2SPh, consistent
with partial electron delocalization from the sulfur into the
phenyl ring as a negative factor. (c) The formation of a five-
membered vs a six-membered chelate ring does not show an
obvious difference (compare 44a vs 44d and 44c vs 44e.
(d) Among carbonyl donors, the more electron-rich amide is
significantly faster than the ester. Pyridine is faster still, although
the difference between pyridine and amide is relatively small.
Interpretation of the Rate Data. To reconcile these results,
we propose that a chromium side-chain heteroatom bond is
present in the rate-determining transition state for arene
exchange. The strength of this bond determines the energy of
the transition state and therefore the rate of the arene exchange.
Even though sulfur is relatively polarizable and a good σ donor,
it does not allow for effective back bonding from the metal.
Such back bonding is expected to be much more significant in
the corresponding transition states for the ester, amide, and the
pyridine side chains and may be a dominant factor in stabilizing
the transition state in these cases.
The Effect of the Structure of the Departing Arene. The
departing arene has a dramatic effect on the rate of the exchange
reaction (Table 2). Fluorobenzene was replaced much faster than
benzene from (arene)Cr(CO)2L-L′ (L′ ) SMe, CO2Me),
compare 50a vs 44a and 54a vs 44h. The half life of the
fluorobenzene complex with the methylthio side chain (50a)
was 45 min at 60 °C, while for the benzene complex 44a, it
was 2 h at 80 °C. With the fluorobenzene ligand and ester side
chain (54a), much faster exchange rates prevented a precise
determination of exchange kinetics; the half life was estimated
to be less than 1 h at 23 °C, whereas the corresponding benzene
complex 44h has a half life of about 115 h at the same
temperature. Xylene complexes 54b-d exchanged the arene
ligand even more slowly than the corresponding benzene
Among the sulfur donor ligands, the electron-donating ability
of sulfur is of major importance. A substituent which depletes
the electron density at sulfur, such as trifluoromethyl or, to a
smaller extent, phenyl, reduces the stability of the chromium-
sulfur bond and slows the exchange rate.
(50) Atwood, J. D. Inorganic and Organometallic Reaction Mechanisms, 2nd
ed.; VCH Publishers: New York, 1997.
9
7766 J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005

Accelerated Arene Ligand Exchange
A R T I C L E S
Table 2. Effect of the Structure of the Departing Arene
lower activation energy for this step in the intramolecular case.
Step b is highly endothermic; it involves a further dissociation
of the arene to give the η2 intermediate B which is formally a
16-electron complex. Loss of arene coordination may be
compensated by an additional interaction with the side-chain
heteroatom, as is possible with the -CO2Me, -CONMe2, or
2-pyridyl side chains. This interaction can be viewed as a back
bond from the zerovalent chromium metal to LUMO of the
heteroatom group. Step c is proposed to be rate determining
and involves an associative step to generate an η2, η2 intermedi-
ate, C. The kinetic significance of this step is implied by a
dependence on the structures of both the departing and incoming
arenes. The following steps d and e are fast and highly
exothermic overall to give the stable product, E. An alternative
(steps f and g) with complete dissociation of the departing arene
to give F is considered unlikely due to the lack of stabilization
of this intermediate and the less direct relationship to the nature
of the departing and incoming arenes.
entry
50a
44a
54a
44h
44h
54b
54c
54d
L
arene
fluorobenzene
benzene
fluorobenzene
benzene
benzene
o-xylene
m-xylene
p-xylene
half life time
45 min/60 °C
120 min/80 °C
<60 min/23 °C
115 h/23 °C
1.5 h/60 °C
8.6 h/60 °C
16.2 h/60 °C
9.1 h/60 °C
-SMe,
-SMe
-CO2Me
-CO2Me
-CO2Me
-CO2Me
-CO2Me
-CO2Me
Table 3. Effect of the Incoming Arene
Summary. The hypothesis that temporary coordination from
an internal ligand can lower the barrier to detachment of an
arene ligand and facilitate arene exchange in arene-metal
π complexes was explored systematically. A series of
2-L′-pyrroles exhibiting a range of steric and electronic
properties was prepared and converted to (2-L′-pyrrolyl)-
(pyrrolyl)2phosphines (L-L′), which were then used to replace
a CO ligand in (arene)Cr(CO)3 complexes and create a series
of (arene)Cr(CO)2(L-L′) complexes. Significant increases in
the rate of arene exchange were observed with these (arene)-
Cr(CO)2(L-L′) complexes, from a slow reaction at 150 °C for
the parent tris(pyrrolyl)phosphine to reactions which proceeded
measurably at 23 °C. It was further demonstrated that the rate
of arene exchange in the system with L′ ) CO2Me shows a
significant dependence on the structure of both the incoming
arene and the departing arene. A mechanism is proposed which
accounts for this rate dependence on both arenes as well as the
side chain ligand. With arene exchange now operating at close
to room temperature in these systems, useful catalytic SNAr
reactions may be realized.
entrya
incoming arene
chlorobenzene-d5
anisole-d8
fluorobenzene-d5
benzene-d6
t1/2 (h)
1
2
3
4
5
6
7
8
9
0.88
1.35
1.64
2.45
2.64
3.01
3.80
4.64
10.7
toluene-d8
o-xylene-d10
m-xylene-d10
p-xylene-d10
mesitylene-d12
a By use of complex 44h at 50.5 °C.
complex 44h (Table 2). The half lives were measured for
o-xylene, 54b, (8.6 h), m-xylene, 54c, (16.2 h), and p-xylene,
54d (9.1 h) complexes in benzene-d6 at 60 °C (the half life for
the benzene complex at this temperature is about 1.5 h).
Different rates may reflect different stabilities of the starting
complexes as well as different transition state energies.
Experimental Procedures.
The Effect of the Structure of the Incoming Arene. The
structure of the incoming arene was also found to affect the
rate of the arene exchange reaction for 44h. In a typical
experiment, a perdeuterated arene was used as a solvent and
the disappearance of the starting material (44h) was monitored
by 1H NMR at 50.5 ((0.2) °C in the NMR probe (Table 3). In
some cases, the new arene created a sufficiently different
Analytical Data. Proton (1H), carbon (13C), fluorine (19F), and
phosphorus (31P) NMR spectra were recorded on a Varian 500
(500 MHz, 1H), Inova 400 (400 MHz, 1H), or Mercury 300 (300 MHz,
1H) spectrometers. Fluorine resonances were indirectly referenced to
external fluorotrichloromethane. Phosphorus resonances were indirectly
referenced to external phosphoric acid. Infrared (IR) spectra were
recorded on a Nicolet 730 FTIR spectrometer with internal calibration.
Mass-spectral data were obtained using a Kratos MS 80 RFA
spectrometer operating in electron impact (EI) mode at 70 eV or fast
atom bombardment (FAB) mode. High-resolution mass spectra were
obtained at the UCR Mass Spectrometry Facility, Department of
Chemistry, University of California, Riverside CA, 92521. Peaks are
identified by mass/charge (m/z (%)) and relative abundance to base
peak (%). Melting points are uncorrected and were recorded on an
Electrothermal Melting Point Apparatus model #IA6304 using open
capillary tubes.
1
environment in the resulting complex 66 so that the H NMR
peaks of the phosphine in the product 66 could be distinguished.
Note that fluorobenzene serves as an effective incoming arene,
which bodes well for the proposed goal of a catalytic SNAr
process.
Proposed Ligand-Assisted Arene-Exchange Mechanism.
A mechanism consistent with the observations above is pre-
sented in Scheme 10. Step a is endothermic and involves
reversible formation of the η4 intermediate A stabilized by the
side chain of the ligand. This stabilization is analogous to an
intermolecular stabilization of the η4-benzene chromium tri-
carbonyl intermediate by a σ-donor molecule. However, it is
likely that the intramolecular stabilization in A is much more
favorable than intermolecular stabilization, consistent with a
Reagents. Commercial reagents were purchased from Aldrich
Chemical Co., Fluka, or Strem and used without further purification,
unless otherwise noted.
Solvents. Anhydrous diethyl ether and tetrahydrofuran (THF) were
obtained by distillation from sodium benzophenone ketyl. Benzene,
toluene, dichloromethane, methanol, hexanes (hex), and acetonitrile
9
J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005 7767

A R T I C L E S
Semmelhack et al.
Scheme 10. Proposed Mechanism of Ligand-Assisted Arene Exchange
were distilled from calcium hydride under Ar. Fluorobenzene,
N-methylpyrrolidinone (NMP), and dimethylformamide (DMF) were
distilled over calcium hydride and stored under Ar over molecular sieves
(4 Å). Deuterated NMR solvents were stored over activated molecular
sieves (4 Å).
General Procedures. Operations with air-sensitive compounds were
performed under Ar using double manifold techniques. A reaction flask
was placed “under Ar” by sequentially evacuating it with an oil pump
(0.1 Torr) and then filling it with Ar three times. Flash chromatography
was performed using Merck Silica Gel 60 (230-400 mesh). For
photochemical reactions, irradiation was performed with a 450-W low-
pressure Hg lamp held in a water-cooled quartz jacket.
procedure for metalation/trapping/deprotection of N-bocpyrrole.52
A
three-neck flask equipped with a stirring bar and a thermometer was
placed under Ar, and a solution of n-butyllithium (31 mL, 50 mmol,
1.6 M in hexane) was added dropwise via syringe to a stirred solution
of TMP (8.4 mL, 50 mmol) in THF (50 mL) at -78 °C. The mixture
was allowed to stir for 10 min at -78 °C and then 10 min at -10 °C,
whereupon it was cooled to -78 °C. To the resulting yellow solution
was added N-(boc)pyrrole (8.4 mL, 50 mmol) dropwise via syringe.
The solution was stirred for 1 h at -78 °C and then was quenched by
rapid addition (<2 s) of dimethyl disulfide (9.9 mL, 110 mmol) at
-78 °C. If dimethyl disulfide is added slowly, the 2,5-disubstituted
product formed in significant amounts. The mixture was warmed to
23 °C slowly and then stirred for 1 h. The mixture was diluted with
ether (50 mL), washed with water (50 mL) and saturated NaCl solution,
and then dried over anhydrous Na2SO4. The solution was filtered, and
the filtrate was concentrated by rotary evaporation. The residue was
purified by column chromatography on silica gel (50:1 hex:EtOAc) to
give the title compound as a colorless oil (6.1 g, 57% yield),
Preparation of 2-Allylpyrrole (27). (a) Preparation of 2-Allylpyr-
role-1-tert-butylcarboxylate. A 100-mL two-neck flask equipped with
a magnetic stirring bar, a reflux condenser, and a vacuum adapter was
charged with palladium(II) chloride (0.27 g, 1.5 mmol), lithium chloride
(68 mg, 1.6 mmol), and 2-trimethylstannyl-N-boc-pyrrole51 (9.4 g,
30 mmol) under Ar. Toluene (50 mL) was added followed by allyl
bromide (5.2 mL, 60 mmol), and the mixture was heated at reflux for
24 h at which time it acquired a dark color. It was allowed to cool to
23 °C, filtered through a silica gel plug, and concentrated by rotary
evaporation to yield the greenish oil. It was chromatographed on a silica
gel column (hex:EtOAc 50:1) to give a title compound (2.8 g, 50%
1
homogeneous by TLC (silica gel, Rf 0.4, 20:1 hex:EtOAc). H NMR
(300 MHz, CDCl3): δ 1.62 (s, 9H), 2.42 (s, 3H), 5.96 (dd, J ) 3.6 Hz,
J ) 1.8 Hz, 1H), 6.20 (t, J ) 3.3 Hz, 1H), 7.25 (dd, J ) 3.3 Hz,
J ) 1.8 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 17.2, 28.2, 84.5,
110.4, 111.6, 121.7, 129.5, 149.2. MS (+EI): m/z (%) 213 (4), 157
(34), 113 (100), 84 (19). HRMS (+EI): found 213.0832
(calcd 213.0823). IR (KBr): 2981 (s), 2923 (s), 1737 (s), 1333 (s),
1
yield). H NMR (400 MHz, CDCl3): δ 1.60 (s, 9H), 3.62 (dd, J )
8 Hz, J ) 2.4 Hz, 2H), 5.04-5.10 (m, 2H), 5.97-6.11 (m, 3H), 7.22-
7.24 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 28.2, 33.4, 83.5, 110.2,
111.8, 116.1, 121.3, 134.0, 136.0, 149.6.
1158 (s) cm-1
.
(b) Deprotection. This product was previously prepared by a
different method.53 Deprotection of N-Boc-2-(methylthio)pyrrole using
a standard procedure (see above) yielded a yellow oil which was purified
by chromatography on silica gel with hex:EtOAc 50:1 to yield
2-methylthiopyrrole 24 as a colorless oil, 2.3 g (70% yield), homoge-
neous by TLC (Rf 0.33, 10:1 hex:EtOAc).
Preparation of 2-(Methylthiomethyl)pyrrole (41a). This compound
was prepared by analogy to 2-allylpyrrole.54 A 250-mL three-neck flask
equipped with a magnetic stirring bar, an addition funnel, and a vacuum
adapter was placed under Ar and then charged with 3 mol equiv of
pyrrole (16 g, 17 mL, 0.24 mol), aqueous potassium carbonate
(5.6 g in 50 mL of H2O), and toluene (50 mL). To the resulting two-
phase mixture, chloromethyl methyl sulfide (7.7 g, 6.7 mL, 80 mmol)
was added dropwise (via the addition funnel) over 10 min with vigorous
(b) Preparation of 2-Allylpyrrole (27). A Standard Procedure
for Boc-Deprotection. A 250-mL round-bottom flask equipped with
a magnetic stirring bar under Ar was charged with N-Boc-2-allylpyrrole
(6.5 g, 34 mmol) and THF (20 mL). The resulting solution was cooled
to 0 °C, and NaOMe (40 mL of 25% soln in MeOH, 190 mmol) was
added slowly via syringe. The solution was stirred for 10 min at 0 °C
and then allowed to warm to 23 °C over 30 min. The resulting solution
was poured into water (100 mL) and extracted with ether (100 mL).
The organic layer was collected, washed with water (100 mL) and brine
(100 mL), dried over anhydrous Na2SO4, filtered, and concentrated by
rotary evaporation followed by a flash distillation at 24 Torr/50 °C to
1
yield 27 (2.0 g, 56% yield). The H NMR data were consistent with
literature values.33
Preparation of 2-(Methylthio)pyrrole (24). (a) Preparation of
N-Boc-2-(methylthio)pyrrole. This method is based on a general
(52) Gharpure, M.; Stoller, A.; Bellamy, F.; Firnau, G.; Snieckus, V. Synthesis,
1991, 1079.
(53) Nedolya, N. A.; Brandsma, L.; Verkruijsse, H. D.; Trofimov, B. A.
Tetrahedron Lett. 1997, 38, 7247.
(51) Martina, S.; Enkelmann, V.; Wegner, G.; Schluter, A.-D. Synthesis 1991,
613.
(54) Papdopoulos, E. P.; VanderWerf, C. A. Heterocycles 1982, 19, 343.
9
7768 J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005

Accelerated Arene Ligand Exchange
A R T I C L E S
stirring. The resulting mixture was allowed to stir for 4 h at which
time the layers were separated, toluene was partially removed from
the organic layer on a rotary evaporator, and the resulting oil was
fractionally distilled at 1 Torr to yield 2-(methylthiomethyl)pyrrole
(100 mL) and washed with H2O (100 mL). The resulting aqueous layer
was extracted with Et2O (2 × 100 mL). The organic layers were
combined and washed with brine. The resulting organic layer was dried
over Na2SO4, filtered, and concentrated on a rotary evaporator. The
residue was purified by column chromatography (4:1 hex:CH2Cl2) to
give N-Boc-2-(diphenylphosphino)pyrrole as a colorless oil (8.8 g, 52%
yield), homogeneous by TLC (silica gel, Rf 0.5, 20:1 hex:EtOAc).
1H NMR (300 MHz, CDCl3): δ 1.41 (s, 9H), 5.57 (dd, J ) 3.3 Hz,
J ) 1.8 Hz, 1H), 6.17 (td, J ) 3.3 Hz, J ) 0.3 Hz, 1H), 7.26-7.36
(m, 10H), 7.54-7.57 (m, 1H). 13C NMR (75 MHz, CDCl3): δ 27.9,
1
(4.4 g, 43% yield) as a colorless oil (bp 55 °C at 1 Torr). H NMR
(300 MHz, CDCl3): δ 2.00 (s, 3H), 3.73 (s, 2H), 6.07-6.11 (m, 1H),
6.12-6.17 (m, 1H), 6.76-6.81 (m, 1H), 8.37 (br s, 1H). 13C NMR
(100 MHz, CD2Cl2): δ 14.8, 30.7, 108.2, 108.3, 118.1, 127.5. MS
(+EI): m/z (%). 127 (13), 80 (100). HRMS (+EI): m/z found
127.04608 (calcd 127.04557). IR (KBr): 3384 (s, br), 2914 (m),
1254 (m), 1090 (m), 1027 (m), 723 (m) cm-1
.
85.0, 111.8, 123.1, 125.4, 128.4 (d, J3CP ) 7 Hz), 128.8, 130.4 (d, J1
CP
) 14 Hz), 133.7 (d, J2 ) 20 Hz), 138.2 (d, J1 ) 10 Hz), 149.3.
CP
CP
Preparation of 2-(Phenylthiomethyl)pyrrole (41b). This compound
was prepared by analogy to 2-allylpyrrole.54 A 250-mL three-neck flask
equipped with a magnetic stirring bar, an addition funnel, and a vacuum
adapter was placed under Ar and then charged with 3.00 mol equiv of
pyrrole (10.5 mL, 10.2 g, 151 mmol), aqueous potassium carbonate
(6.9 g in 50 mL of H2O), and toluene (50 mL). The resulting mixture
was heated to 80 °C, and chloromethyl phenyl sulfide (6.7 mL, 7.9 g,
50 mmol) was added dropwise (via the addition funnel) over 10 min
with vigorous stirring. The resulting mixture was allowed to stir for
6 h at 80 °C. The mixture was then allowed to cool to 23 °C, the layers
were separated, and the organic layer was collected. The volatiles were
removed in vacuo, and the resulting brownish oil was dissolved in Et2O
and cooled to -5 °C whereupon crystallization occurred to yield 6.0 g
(68% yield) of 2-(phenylthiomethyl)pyrrole as a white solid. The
1H NMR data were consistent with literature values.55
31P NMR (162 MHz, CDCl3): δ -17.0. MS (+EI): m/z (%) 351 (0.5),
295 (2.9), 251 (100), 219 (18), 174 (58), 143 (36). HRMS (+EI):
m/z found 351.13935 (calcd 351.13882). IR (KBr): 3070 (m), 3034
(m), 3003 (m), 2982 (m), 2933 (m), 1736 (s), 1478 (m), 1327 (s) cm-1
.
(b) Preparation of 2-(Diphenylphosphino)pyrrole (41f). Depro-
tection of N-Boc-2-(diphenylphosphino)pyrrole using a standard pro-
cedure (see above) yielded 2-(diphenylphosphino)pyrrole as a colorless
oil in quantitative yield. It can be further purified, if necessary, by
chromatography on silica gel with 4:1 hex:CH2Cl2. The 1H NMR data
were consistent with literature values.58
Preparation of N-Boc-2-iodopyrrole (42). According to a modified
literature procedure,59 a 100-mL three-neck flask equipped with a
magnetic stirring bar and a vacuum adapter under Ar was charged with
2-trimethylstannyl-pyrrole-1-tert-butylcarboxylate60 (1.3 g, 4.3 mmol)
and THF (50 mL). The resulting solution was cooled to -78 °C, and
N-iodosuccinimide (0.97 g, 4.3 mmol) was added in small portions
while an Ar stream was bubbled through the flask. The vacuum adapter
was replaced with a septum, and the resulting yellowish suspension
was allowed to warm in the fridge at -5 °C over 1 day. During this
time, the solution became colorless and a white precipitate formed.
The flask was removed from the cold, anhydrous Na2CO3 (about 1 g)
was added, and the mixture was filtered through a silica gel plug to
yield N-Boc-2-iodopyrrole (1.2 g, 99%) as a colorless oil after rotary
evaporation. The 1H NMR data were consistent with literature values.61
Preparation of 2-t-Butylthiopyrrole (41d). A three-neck flask
equipped with a magnetic stirrer bar and a vacuum adapter under Ar
was charged with excess of 1 M solution of t-BuMgCl in THF
(7.6 mL, 7.6 mmol). The solution was cooled to 0 °C whereupon
2-thiocyano-pyrrole (0.34 g, 2.7 mmol)56,57 was added slowly via syringe
as a solution in THF (15 mL). The resulting solution was allowed to
warm to 23 °C over 4 h at which time it was poured into chilled water
and extracted with EtOAc. The volatiles were removed on a rotary
evaporator and the residue was dissolved in dichloromethane and filtered
through a plug of silica gel. Evaporation of the solvent in vacuo yielded
327 mg (78% yield) of 2-tert-butylthiopyrrole as a colorless oil. It can
be further recrystallized from hexane to yield a white solid, mp
Preparation of 2-(2′-Pyridino)pyrrole (41i). (a) Preparation of
2-(2′-Pyridino)pyrrole-1-tert-butylcarboxylate. A 50-mL two-neck
flask equipped with a magnetic stirring bar, a reflux condenser, and a
vacuum adapter was charged with tetrakis(triphenylphosphine)palladium-
(0) (0.68 g, 0.59 mmol) and placed under Ar. N-Boc-2-iodopyrrole 42
(4.3 g, 15 mmol) was added as a solution in toluene (20 mL) and the
mixture was allowed to stir for 25 min. To the resulting orange solution
2-trimethylstannylpyridine (4.4 g, 18 mmol) was added slowly via
syringe. The mixture was heated at reflux for 22 h during which time
it acquired a dark color. It was allowed to cool to 23 °C, poured into
water, and extracted with Et2O. The organic layer was washed with
H2O and then brine. The organic layer was dried over Na2SO4, filtered
and concentrated by rotary evaporation. The residue was chromato-
graphed on a silica gel column with hex:EtOAc 5:1 as the mobile phase
to give 2-(2′-pyridino)pyrrole-1-tert-butylcarboxylate as a colorless oil
(2.0 g, 59% yield). 1H NMR (300 MHz, CDCl3): δ 1.36 (s, 9H), 6.25
(t, J ) 3.3 Hz, 1H), 6.42 (dd, J ) 3.3 Hz, J ) 1.8 Hz, 1H), 7.20 (ddd,
J ) 12 Hz, J ) 4.8 Hz, J ) 1.2 Hz, 1H), 7.36-7.43 (m, 2H), 7.68
(td, J ) 7.5 Hz, J ) 1.8 Hz, 1H), 8.60-8.64 (m, 1H). 13C NMR
(100 MHz, CDCl3): δ 27.8, 83.8, 110.8, 115.8, 122.0, 123.7, 123.7,
134.3, 136.0, 149.0, 149.5, 153.2. MS (+EI): m/z (%) 244 (1), 171
(1), 144 (100), 117 (14), 89 (7). HRMS (+EI): m/z found 244.1227
(calcd 244.1212). IR (KBr): 2981 (m), 2934 (m), 1741 (s), 1590 (s),
1317 (s), 1153 (s), 783 (s), 731 (s).
1
39-40 °C. H NMR (400 MHz, CDCl3): δ 1.27 (s, 9H), 6.25-6.28
(m, 1H), 6.39-6.42 (m, 1H), 6.87-6.90 (m, 1H), 8.2 (br s, 1H).
13C NMR (100 MHz, CDCl3): δ 30.9, 46.8, 110.0, 118.3, 118.7, 120.8.
MS (+EI): m/z (%) 155 (6), 99 (100), 84 (15). HRMS (+EI): m/z
found 155.07519 (calcd 155.07687). IR (KBr): 3348 (br, m), 2964
(m), 2925 (m), 2898 (m), 2863 (m), 1531 (m), 1363 (m), 738 (m) cm-1
.
Preparation of 2-(Diphenylphosphino)pyrrole (41f). (a) Prepara-
tion of N-Boc-2-(diphenylphosphino)pyrrole. A 500-mL four-neck
flask equipped with a thermometer adapter, magnetic stirrer, and
vacuum adapter, and an addition funnel was placed under Ar and
subsequently charged with TMP (8.9 mL, 5.2 mmol) and THF (50 mL).
The solution was cooled to -78 °C and n-butyllithium (34 mL,
55 mmol, 1.6 M in hex) was added dropwise via an addition funnel.
The reaction temperature was maintained below -65 °C. The mixture
was stirred for 10 min at -78 °C and was then allowed to warm to
0 °C in 30 min. It was then cooled to -78 °C, and a solution of N-(boc)-
pyrrole (8.4 g, 50 mmol in 50 mL THF) was added dropwise via an
addition funnel again maintaining the temperature below -65 °C. The
mixture was then stirred for 20 min at -78 °C and then was transferred
via cannula to a solution of chlorodiphenylphosphine (2.00 mol equiv,
100 mmol, 18 mL) in THF (50 mL) kept at -30 °C. Upon addition,
the mixture was allowed to warm to 23 °C over 21 h. The solvent was
then removed on a rotary evaporator and the residue taken up in Et2O
(58) Allen, D. W.; Charlton, J. R.; Hutley, B. G. Phosphorus 1976, 6, 191.
(59) Groenendaal, L.; Van Loo, M E.; Vekemans, J. A. J. M.; Meijer, E. W.
Synth. Comm. 1995, 25, 1589.
(55) Barcock, R. A.; Moorcroft, N. A.; Nicholas, A.; Storr, R. C.; Young, J.
H.; Fuller, L. S. Tetrahedron Lett. 1993, 34, 1187.
(56) Gronowitz, S.; Hornfeldt, A.-B.; Gestblom, B.; Hoffman, R. A. J. Org.
Chem. 1961, 26, 2615.
(60) Martina, S.; Enkelmann, V.; Wegner, G.; Schluter, A.-D. Synthesis 1991,
613.
(57) Matteson, D. S.; Snyder, H. R. J. Org. Chem. 1957, 22, 1500.
(61) Chen, W.; Cava, M. P. Tetrahedron Lett. 1987, 28, 6025.
9
J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005 7769

A R T I C L E S
Semmelhack et al.
(b) Preparation of 2-(2′-Pyridino)pyrrole (41i). Deprotection of
2-(2′-pyridino)pyrrole-1-tert-butylcarboxylate using a standard proce-
dure (see above) yielded 2-(2′-pyridino)pyrrole as an off-white solid
in 94% yield. It was further purified by filtering through a silica gel
plug using 5:1 hex:EtOAc as a solvent. The 1H NMR data were
consistent with literature values.62,63
to give a residual oil which was chromatographed on silica gel with
hex:EtOAc 50:1 as the mobile phase. The volatiles were removed in
vacuo leaving 1.03 g (75% yield) of the title compound as a colorless
oil. It was recrystallized from hexane to yield white crystals, mp
1
45-46 °C. H NMR (400 MHz, CDCl3): δ 2.01 (s, 3H), 6.24-6.29
(m, 2H), 6.40 (t, J3 ) 2 Hz, 4H), 6.55 (ddd, J3 ) 3.2 Hz, J3
)
HH
PH
HH
2.4 Hz, J4HH ) 1.6 Hz, 1H), 6.82-6.86 (m, 4H). 13C NMR (125 MHz,
CDCl3): δ 21.7 (d, J3CP ) 3 Hz), 113.3 (d, J2CP ) 5 Hz), 121.3, 122.9,
123.0, 124.7 (d, J2 ) 4 Hz), 138.7 (d, J2 ) 24 Hz). 31P NMR
Preparation of Tris(2-methylthiopyrrolyl)phosphine (25). To a
suspension of NaH (790 mg, 19.8 mmol, 60% in mineral oil) in THF
(15 mL) at 0 °C was added 2-methylthiopyrrole (1.50 g, 13.3 mmol)
via syringe. After the reaction mixture had been stirred at 23 °C for
2 h, a solution of PCl3 (2.1 mL, 4.2 mmol, 2 M in dichloromethane)
was added dropwise at 23 °C via syringe. Then the mixture was allowed
to stir for 3 h at 23 °C. The mixture was filtered, the filtrate was
concentrated by rotary evaporation, and the residue was purified by
column chromatography on silica gel (30:1 hex:EtOAc) to give
phosphine 25 as a colorless crystals (956 mg, 62%). Recrystallization
from hex at -78 °C gave colorless needles, mp 76-77 °C, homoge-
neous by TLC (Rf 0.60, 10:1 hex:EtOAc). 1H NMR (270 MHz,
CDCl3): δ 2.28 (s, 9H), 6.18 (m, 3H), 6.29 (m, 3H), 6.52 (m, 3H).
13C NMR (67.5 MHz, CDCl3): δ 128.0 (d, J ) 28 Hz), 126.0 (d, J )
3.5 Hz), 121.8, 142.2, 22.9. IR (neat, KBr): 1048 (s), 1416 (s), 1743
(s), 2919 (s), 2989 (s), 3126 (s) cm-1. MS (+EI): m/z (%) 367 (M+,
10.4), 320 (100), 255 (17.5), 207 (89.1), 161 (47.3), 126 (41.6), 112
(31.6), 68 (62.1). Anal calcd for C15H18N3PS3: C, 49.02; H, 4.94; N,
11.43. Found: C, 48.92; H, 5.09; N, 11.43.
CP
CP
(202 MHz, CDCl3): δ 70.1. MS (+EI): m/z (%) 275 (61.3), 228 (38.0),
163 (100). HRMS (+EI): m/z found 275.06438 (calcd 275.06461).
IR (KBr): 3130 (m), 3102 (m), 2921 (m), 1453 (s), 1418 (m),
736 (s) cm-1
.
Characterization of (2-Trifluoromethylthiopyrrolyl)dipyrrolyl-
phosphine (43b). This was obtained (according to procedure A) from
2-trifluoromethylthiopyrrole 41c as a colorless oil in 46% yield.
1H NMR (400 MHz, CDCl3): δ 6.38-6.42 (m, 5H), 6.53-6.55
(m, 1H), 6.7-6.80 (m, 4H), 6.84-6.86 (m, 1H). 13C NMR (100 MHz,
CDCl3): δ 113.7 (d, J3 ) 5 Hz), 114.0, 122.9 (d, J2 ) 15 Hz),
CP
CP
126.5, 128.1 (q, J1 ) 310 Hz), 128.3 (d, J2 ) 4 Hz). 31P NMR
CF
CP
(162 MHz, CDCl3): δ 74.5 (broad). 19F NMR (376 MHz): δ -45.4
(d, J ) 14 Hz). MS (+EI): m/z (%) 329 (7), 228 (75), 193 (8), 163
(100). HRMS (+EI): m/z found 329.03556 (calcd 329.03634). IR
(KBr): 3131 (m), 1577 (m), 1454 (s), 1416 (s), 731 (s), 615 (s) cm-1
.
Characterization of (2-Phenylthiopyrrolyl)dipyrrolylphosphine
(43c). This was obtained (according to procedure A) from 2-phenyl-
thiopyrrole 41e as a white solid in 63% yield. It was recrystallized
from hexane to yield white crystals of mp 60-61 °C. 1H NMR
(400 MHz, CDCl3): δ 6.31 (t, J ) 1.5 Hz, 4H), 6.39 (td, J ) 2.7 Hz,
J ) 0.6 Hz, 1H), 6.49-6.51 (m, 1H), 6.68-6.71 (m, 4H), 6.72-6.74
(m, 1H), 6.69-6.72 (m, 5H). 13C NMR (125 MHz, CDCl3): δ 113.2
(d, J ) 4 Hz), 113.7, 122.8 (d, J ) 14 Hz), 124.1, 126.0, 126.2
(d, J ) 6 Hz), 126.4, 129.1, 137.9. 31P NMR (162 MHz, CDCl3):
δ 73.1. MS (+EI): m/z (%) 337 (49), 271 (19), 244 (16), 228 (45),
204 (45), 174 (73), 161 (100). HRMS (+EI): m/z found 337.08087
(calcd 337.08025). IR (KBr): 3130 (m), 3101 (m), 3072 (m), 3058
Preparation of Tris(2-allylpyrrole)phosphine (28). A three-neck
flask equipped with a magnetic stirring bar was placed under Ar and
charged with NaH (700 mg, 17.5 mmol, 60% in mineral oil) and THF
(20 mL). The suspension was cooled to 0 °C and 2-allylpyrrole
(1.69 g, 15.8 mmol) was added dropwise via syringe. The reaction
mixture was allowed to warm to 23 °C over 3 h. It was then filtered,
concentrated by rotary evaporation, and purified by chromatography
on silica gel (50:1 hex:EtOAc) to yield tris(2-allylpyrrole)phosphine
as a colorless oil (690 mg, 41%). Homogeneous by TLC Rf 0.73
1
(10:1 hex:EtOAc). H NMR (270 MHz, CDCl3): δ 3.44 (d, 6H, J )
5.9 Hz), 4.99 (d, 3H, J ) 9.9 Hz), 5.29 (d, 3H, J ) 4.6 Hz), 5.74-
5.86 (m, 3H), 6.05 (m, 3H), 6.19 (t, 3H), 6.24 (m, 3H). 13C NMR
(75 MHz, CDCl3): δ 31.7 (d, J ) 16 Hz), 111.3, 112.1, 116.6, 122.0,
135.3, 135.7 (d, J ) 20 Hz). LRMS (+EI): m/z (%) 349 (M+, 4.7),
243 (82), 136 (100), 122 (57), 106 (33), 80 (77).
(m), 1583 (m), 1453 (m), 1178 (s), 1165 (s), 729 (s) cm-1
.
Characterization of (2-Methylthiomethylpyrrolyl)dipyrrolyl-
phosphine (43d). This was obtained (according to procedure A) from
2-methylthiomethylpyrrole 41a as a colorless oil in 37% yield. 1H NMR
(300 MHz, CDCl3): δ 1.88 (s, 3H), 3.72 (s, 2H), 6.15-6.20 (m, 2H),
6.36-6.39 (m, 4H) 6.42-6.45 (m, 1H), 6.81-6.85 (m, 4H). 13C NMR
(100 MHz, CD2Cl2): δ 14.7, 30.1 (d, J ) 13 Hz), 11.7, 113.0 (d, J )
4 Hz), 113.8 (d, J ) 3 Hz), 123.12 (d, 4 Hz), 123.14, 133.4 (d, J )
16 Hz). 31P NMR (162 MHz, CDCl3): δ 73.0. MS (+EI): m/z (%).
289 (3), 242 (9), 223 (22), 175 (100), 144 (20). HRMS (+EI): m/z
found 289.08095 (calcd 289.08025). IR (KBr): 3132 (w), 3100 (w),
Preparation of Chlorodipyrrolylphosphine (39). A 100-mL Schlenk
flask equipped with a stirring bar was placed under argon. It was then
charged with pyrrole (2.1 mL, 31 mmol), and triethylamine (4.7 mL,
33 mmol) and THF (50 mL) were added slowly via syringe. The mixture
was cooled to -78 °C, and phosphorus trichloride (1.00 mL,
11.5 mmol) was added rapidly via syringe. The mixture was stirred
for 15 min and then allowed to warm to 23 °C (over 1 h) and
subsequently heated at 60 °C for 24 h. The mixture was then cooled,
and the white precipitate was filtered (using a Schlenk line) and washed
with THF. The volatiles were removed on a rotary evaporator and the
residue distilled at 70 °C at 1 Torr to yield chlorodipyrrolylphosphine
as a colorless oil. 1H NMR (500 MHz, CDCl3): δ 6.39-6.42 (m, 4H),
7.08-7.12 (m, 4H). 13C NMR (75 MHz, CDCl3) δ 113.9 (d, J )
5 Hz), 122.7 (d, J ) 17 Hz). 31P NMR (202 MHz, CDCl3):
δ 104.3 ppm, consistent with published data.25
Preparation of (2-Methylthiopyrrolyl)dipyrrolylphosphine (43a).
Procedure A. A 100-ml Schlenk flask equipped with a stirring bar
under Ar was charged with DMAP (8.0 mmol, 98 mg), 2-methyl-
thiopyrrole (24, 5.0 mmol, 0.57 g), and THF (20 mL) and cooled to
0 °C. Chlorodipyrrolylphosphine (39, 5.0 mmol, 0.99 g) was added
slowly via syringe, and the solution was allowed to warm to 23 °C
over 15 min. It was then heated at 65 °C for 20 h. The resulting mixture
was filtered under argon and then concentrated on a rotary evaporator
2913 (m), 1454 (s), 1179 (s), 1058 (s), 732 (s) cm-1
.
Characterization of (2-Methylthiophenylpyrrolyl)dipyrrolyl-
phosphine (43e). This was obtained (according to procedure A) from
2-methylthiophenylpyrrole 41b as a colorless oil in 75% yield. 1H NMR
(300 MHz, CDCl3): δ 4.18 (s, 2H), 6.03-6.07 (m, 1H), 6.12 (td, J )
3 Hz, J ) 0.6 Hz, 1H), 6.38-6.40 (m, 4H), 6.45 (td, J ) 3.6 Hz, J )
3.3 Hz, 1H), 6.81-6.85 (m, 4H), 7.16-7.28 (m, 5H). 13C NMR
(100 MHz, CD2Cl2): δ 31.8 (d, J ) 15 Hz), 112.1, 113.2 (d, J )
4 Hz), 113.9 (d, J ) 3 Hz), 123.0, 123.1 (d, 14 Hz), 127.1, 128.9,
131.2, 133.1 (d, J ) 19 Hz), 135.2. 31P NMR (162 MHz, CDCl3):
δ 73.4. MS (+EI): m/z (%) 351 (0.4), 272 (0.8), 242 (26), 206 (4),
175(100). HRMS (+EI): m/z found 351.09789 (calcd 351.09590). IR
(KBr): 3131 (w), 3100 (w), 1454 (s), 1179 (s), 1058 (s), 733 (s) cm-1
.
Characterization of (2-(N,N-Dimethylamido)pyrrolyl)dipyrro-
lylphosphine (43f). This was obtained (according to procedure A) from
pyrrole-2-carboxylic acid N,N-dimethyl-amide 41h as a white solid in
79% yield. It was recrystallized from hexane to yield white crystals
that turned yellow at 76 °C and then melted between 102 and 106 °C.
(62) Seki, K.; Ohkura, K.; Terashima, M. Heterocycles 1984, 22, 2347.
(63) Savoia, D.; Concialini, V.; Roffia, S.; Tarsi, L. J. Org. Chem. 1991, 56,
1822.
1
The solid is easily oxidized in air acquiring a yellow color. H NMR
9
7770 J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005

Accelerated Arene Ligand Exchange
A R T I C L E S
(300 MHz, CDCl3): δ 3.18 (br s, 6H), 6.04 (dt, J ) 3 Hz, J ) 1.5 Hz,
1H), 6.26 (td, J ) 2.4 Hz, J ) 0.6 Hz, 1H), 6.34 (t, J ) 2.4 Hz, 4H),
6.72 (dt, J ) 3.6 Hz, J ) 1.2 Hz, 1H), 6.74-6.78 (m, 4H). 13C NMR
(100 MHz, CDCl3): δ 112.1, 112.2 (d, J ) 4 Hz), 117.4, 122.7
(d, J ) 15 Hz), 126.7, 129.8 (d, J ) 5 Hz), 162.8. 31P NMR
(162 MHz, CDCl3): δ 67.4. MS (+EI): m/z (%) 300 (0.7), 285 (0.9),
256 (4), 250 (6), 234 (100), 189 (43), 180 (84), 141 (70). HRMS
(+EI): m/z found 300.11324 (calcd 300.11400). IR (KBr): 1590 (s),
149.3. 31P NMR (162 MHz, CD2Cl2): δ 63.3. MS (+EI): m/z (%)
306 (3), 240 (100), 174 (88), 147 (63), 120 (75), 96 (49), 70 (63).
HRMS (+EI): m/z found 306.10204 (calcd 306.10343). IR (KBr): 3139
(m), 3103 (w), 1592 (s), 1439 (s), 1154 (s), 1059 (s), 742 (s) cm-1
.
Preparative Example of the Standard Ligand Substitution
Procedure. Preparation of η6-Benzene(2-(methylthiopyrrolyl)dipyr-
rolylphosphine)dicarbonyl Chromium (0) (44a). (a) Preparation of
η2-Cyclooctenedicarbonyl Chromium(0). A 20-ml Schlenk tube,
modified to have a flat bottom and equipped with a magnetic stirring
bar, was charged with (benzene)tricarbonylchromium(0) (100 mg,
0.47 mmol), and the tube was placed under argon. Freshly distilled
benzene (15 mL) was added via syringe followed by cyclooctene
(3.0 mL, 23 mmol), and the resulting solution was irradiated using a
standard 450-W medium-pressure Hanovia Hg lamp for 1 h while an
argon was bubbled through the solution by means of a long needle.
(b) Exchange of the Phosphine for Cyclooctene. Upon completion
of irradiation, (2-methylthiopyrrolyl)dipyrrolylphosphine (43a, 130 mg,
0.47 mmol) was added via syringe as a solution in benzene (5 mL)
and stirred for 30 min. The resulting mixture was filtered through Celite,
the solvent was removed on a rotary evaporator, and the resulting yellow
oil was chromatographed on a silica gel column with hex:EtOAc 20:1.
The yellow fractions were collected and the solvent evaporated in vacuo
to yield 143 mg (66% yield) of a yellow solid (mp 147-148 °C dec).
1425 (s), 1187 (s), 1172 (s), 1153 (s), 1062 (s), 1033 (s), 737 (s) cm-1
.
Preparation of (2-t-Butylthiopyrrolyl)dipyrrolylphosphine (43 g).
Procedure B. To a suspension of NaH (75 mg, 1.9 mmol, 60% in
mineral oil) in THF (15 mL) at 0 °C under Ar was added 2-(tert-
butylthio)pyrrole (41d, 0.26 g, 1.7 mmol) via syringe. After the reaction
mixture was stirred at 23 °C for 2h, it was cooled to 0 °C and
chlorodipyrrolylphosphine (39, 0.33 g, 1.7 mmol) was added slowly
via syringe. Then the system was allowed to warm to 23 °C over 3 h.
It was filtered through a silica gel plug, the filtrate was concentrated
on a rotary evaporator, and the residue was purified by column
chromatography on silica gel (4:1 hex:CH2Cl2) to give 370 mg (69%
1
yield) of the phosphine 43g as a colorless oil. H NMR (300 MHz,
CDCl3): δ 1.27(s, 9H), 6.32 (td, J ) 3 Hz, J ) 0.6 Hz, 1H), 6.35-
6.38 (m, 4H), 6.40-6.43 (m, 1H), 6.53-6.56 (m, 1H), 6.72-6.76
(m, 4H). 13C NMR (100 MHz, CDCl3): δ 30.7 (d, J ) 2 Hz), 48.6,
113.1 (d, J ) 4 Hz), 113.3, 122.9 (d, J ) 15 Hz), 123.7, 124.8 (d, J )
25 Hz), 125.2 (d, J ) 4 Hz). 31P NMR (162 MHz, CDCl3): δ 72.3.
MS (+EI): m/z (%) 317 (14), 261 (31), 194 (100), 161 (61), 132 (24).
HRMS (+EI): m/z found 317.11110 (calcd 317.11155). IR (KBr): 3101
(w), 2961 (m), 2921 (w), 2896 (w), 2861 (w), 1454 (m), 1163 (s),
1H NMR (500 MHz, benzene-d6): δ 1.92 (s, 3H), 4.41 (d, J3
)
PH
2.4 Hz, 6H), 5.73 (td, J1 ) 2.8 Hz, J2 ) 1.6 Hz, 1H), 6.03 (dt, J1 )
3.2 Hz, J2 ) 1.2 Hz,1H), 6.23-6.28 (m, 5H), 6.88-6.92 (m,4H).
13C NMR (125 MHz, benzene-d6): δ 21.7, 111.8 (d, J3 ) 4.5 Hz),
CP
112.7 (d, J3 ) 5.9 Hz), 118.9 (d, J3 ) 3.2 Hz), 124.6 (d, J2
)
CP
CP
CP
729 (s) cm-1
.
6.6 Hz), 130.5 (d, J2 ) 9.8 Hz), 236.2 (d, J2 ) 27 Hz). 31P NMR
CP
CP
(162 MHz, benzene-d6): δ 173.5. MS (+FAB, nitrobenzyl alcohol):
m/z (%) 461 (17), 395 (21), 355 (42), 327 (100), 307 (81), 289 (42).
HRMS (+FAB) m/z found 461.0438 (calc 461.0419). IR (CH2Cl2
soln): 1055 (s), 1181 (s), 1444 (s), 1866 (s), 1925 (s), 2925 (m). X-ray
determination: see Supporting Information.
Characterization of (2-Methylcarboxypyrrolyl)dipyrrolylphosphine
(43h). This was obtained (according to procedure B) from methyl
pyrrole-2-carboxylate 41g as a colorless oil that was taken up in hexane
and cooled to 0 °C to yield white crystals, in 64% yield. Mp 80-
1
81.5 °C. H NMR (300 MHz, CDCl3): δ 3.79 (s, 3H), 6.02 (dt, J3
HH
) 3 Hz, J4HH ) J4PH ) 1.8 Hz, 1H), 6.28 (ddd, J3HH ) 3.9 Hz, J3
)
Characterization of η6-Benzene(2-(trifluoromethylthiopyrrolyl)-
dipyrrolylphosphine) Dicarbonylchromium(0) (44b). Obtained as a
yellow solid in 83% yield. It was recrystallized from CH2Cl2/Et2O to
give yellow crystals with mp 211-213 °C (dec). 1H NMR (400 MHz,
benzene-d6): δ 4.26 (d, J3 ) 2.4 Hz, 6H), 5.87 (td, J3 ) 3.2 Hz,
HH
3.0 Hz, J4 ) 0.3 Hz, 1H), 6.39 (t, J3 ) 2.1 Hz, 4H), 6.78-6.81
PH
HH
(m, 4H), 7.09 (ddd, J3HH ) 4.8 Hz, J3PH ) 2.7 Hz, J4HH ) 1.2 Hz, 1H).
13C NMR (125 MHz, CDCl3): δ 52.1, 112.8, 113.1 (d, J3CP ) 4.6 Hz),
113.3 (d, J3 ) 4.6 Hz), 121.0, 122.9 (d, J3 ) 15 Hz), 123.0.
CP
CP
PH
HH
31P NMR (202 MHz, CDCl3): δ 74.1. MS (+EI): m/z (%) 287
(M+, 3.3), 221 (100), 189 (28), 143 (10), 128 (59). HRMS (+EI):
m/z found 287.08236 (calcd 287.08236). IR (KBr, CH2Cl2): 1698 (s),
1540 (m), 1445 (s), 1432 (m), 1412 (m), 1344 (m), 1275 (s), 1161 (s),
J4PH ) 1.6 Hz, 1H), 5.91 (td, J3HH ) 3.6 Hz, J4PH ) 1.2 Hz, 1H), 6.20-
6.24 (m, 4H), 6.66 (br s, 1H), 6.87-6.91 (m, 4H). 13C NMR (100 MHz,
CD2Cl2): δ 92.9, 112.7 (d, J3CP ) 6 Hz), 124.4 (d, J2CP ) 7 Hz), 125.3,
128.1 (q, J1 ) 145 Hz), 128.3, 130.5, 236.2 (d, J2 ) 27 Hz).
CF
CP
1058 (s) cm-1
.
31P NMR (162 MHz, benzene-d6): δ 174.1. 19F NMR (376 MHz):
δ -43.7. MS (+EI): m/z (%) 515 (1.4), 459 (8), 409 (6), 381 (19),
279 (46), 228 (77), 163 (93). HRMS (+EI): m/z found 515.01058
(calcd 515.01363) IR (KBr): 1921 (s), 1868 (s), 1636 (s), 1175 (s),
Characterization of (2-Diphenylphosphinopyrrollyl)dipyrrolyl-
phosphine (43i). This was obtained (according to procedure B) from
2-diphenylphosphinopyrrole 41f in 50% yield as a colorless oil which
solidified at 0 °C. Mp 86-87 °C. 1H NMR (400 MHz, CDCl3):
δ 6.10-6.12 (m, 1H), 6.31 (t, J ) 2 Hz, 4H), 6.34 (t(br), J ) 3.2 Hz,
1H), 6.64-6.67 (m, 1H), 6.67-6.70 (m, 4H), 7.24-7.34 (m, 10H).
13C NMR (100 MHz, CDCl3): δ 113.4 (d, J ) 4.5 Hz), 114.1, 122.9
(d, J ) 14 Hz), 123.3 (d, 57 Hz), 126.6 (br), 128.9 (d, J ) 29 Hz),
129.4, 133.8 (d, 78 Hz), 136.8 (t, J ) 25 Hz). 31P NMR (162 MHz,
CDCl3): δ -28.2 (d, J ) 340 Hz), 76.0 (d, J ) 340 Hz). MS (+EI):
m/z (%) 413 (5.0), 347 (96), 251 (31), 172 (100). HRMS (+EI):
m/z found 413.12137 (calcd 413.12107). IR (KBr): 3100 (m), 3053
1041 (s) cm-1
.
Characterization of η6-Benzene(2-(phenylthiopyrrolyl)dipyrro-
lylphosphine) Dicarbonylchromium (0) (44c). This was obtained as
a yellow solid in 65% yield. Mp 158-159 °C (dec). 1H NMR
(300 MHz, benzene-d6): δ 4.30 (d, 2.4 Hz, 6H), 5.80 (td, J ) 3.3 Hz,
J ) 1.8 Hz, 1H), 6.04 (td, J ) 3.3 Hz, J ) 1.2 Hz, 1H), 6.11-6.17
(m, 4H), 6.62-6.66 (m, 1H), 6.83-6.94 (m, 7H), 7.27-7.33 (m, 2H).
13C NMR (75 MHz, CD2Cl2): δ 92.6, 112.0 (d, J ) 4 Hz), 112.2
(d, J ) 6 Hz), 123.3 (d, J ) 9 Hz), 124.3 (d, J ) 6 Hz), 125.7, 126.4,
126.7, 127.7, 129.3, 137.3, 236.5 (d, J ) 27 Hz). 31P NMR (162 MHz,
benzene-d6): δ 174.5. MS (+EI): m/z (%) 523(<1), 445(2), 389(15),
337 (45), 271 (15), 204 (32), 161 (63). HRMS (+FAB): m/z found
523.0561 (calcd 523.0575). IR (KBr): 1920 (s), 1859 (s), 1445 (m),
(m), 1585 (m), 1453 (s), 1178 (s), 1057 (s), 735 (s) cm-1
.
Characterization of (2-(2′-Pyridino)pyrollyl)dipyrrolylphosphine
(43j). This was obtained (according to procedure B) in 100% yield as
a white solid that was further recrystallized from Et2O. The solid turned
yellow at 146 °C and turned into liquid between 171 and 178 °C.
1H NMR (300 MHz, CDCl3): δ 5.84 (dt, J ) 3 Hz, J ) 1.8 Hz, 1H),
6.27-6.33 (m, 5H), 6.78-6.82 (m, 4H), 6.87-6.90 (m, 1H), 6.95-
7.00 (m, 1H), 7.52-7.64 (m, 2H), 8.25-8.29 (m, 1H). 13C NMR
(100 MHz, CD2Cl2): δ 112.0 (d, J ) 4 MHz), 112.2, 118.2, 120.6,
122.8 (d, J ) 15 Hz), 126.0 (d, 3 Hz), 136.3, 137.0, 145.9 (d, 2 Hz),
1171 (m), 1039 (m), 735 (s) cm-1
.
Characterization of η6-Benzene(2-(tert-butylthiopyrrolyl)dipyr-
rolylphosphine) Dicarbonylchromium(0) (44g). This was obtained
as a yellow solid in 86% yield. It was recrystallized from Et2O to yield
yellow crystals (decomposed without melting between 150 and
157 °C). 1H NMR (400 MHz, benzene-d6): δ 1.20 (s, 9H), 4.46
9
J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005 7771

A R T I C L E S
Semmelhack et al.
(d, 1.6 Hz, 6H), 5.92 (td, J ) 3.6 Hz, J ) 1.6 Hz, 1H), 6.06 (td, J )
3.2 Hz, J ) 1.2 Hz, 1H), 6.24-6.26 (m, 4H), 6.43-6.46 (m, 1H),
6.95-6.98 (m, 4H). 13C NMR (100 MHz, CD2Cl2): δ 31.7, 92.8, 111.7,
112.0 (d, J ) 9 Hz), 121.1, 124.7 (d, J ) 6 Hz), 125.2, 127.8 (d, J )
10 Hz), 236.9 (d, J ) 27 Hz). 31P NMR (162 MHz, benzene-d6):
δ 173.4. MS (+EI): m/z (%) 503 (1), 481 (8), 425 (7), 397 (39), 369
(64), 317 (72). HRMS (+EI): found 503.08984 (calcd 503.08884). IR
(m, 4H), 6.39-6.43 (m, 1H), 6.70-6.80 (m, 1H), 6.93-6.98 (m, 5H),
7.07-7.10 (m, 1H), 8.53-8.55 (m, 1H). 13C NMR (125 MHz, CD2-
Cl2): δ 92.3, 111.4, 111.7 (d, J ) 5 Hz), 116.0, 120.9, 121.0, 124.6
(d, J ) 5 Hz), 127.1, 136.6, 137.7, 148.2, 151.0, 236.8 (d, J ) 26 Hz).
31P NMR (162 MHz, C6D6): δ 175.9. MS (+FAB): m/z (%) 493 (12),
426 (30), 386 (16), 358 (97), 349 (20), 261 (92), 240 (100). HRMS
(+FAB): (MH+) m/z found 493.0872 (calcd 493.0885). IR (KBr):
1914 (s), 1857 (s), 1586 (m), 1435 (m), 1183 (m), 1038 (m), 734 (m)
(KBr): 2960 (m), 1923 (s), 1864 (s), 1458 (m), 1056 (s), 738 (s) cm-1
.
cm-1
.
Characterization of η6-Benzene(2-(methylthiomethylpyrrolyl)-
dipyrrolylphosphine) Dicarbonylchromium(0) (44d). This was ob-
tained as a yellow solid in 80% yield. It was recrystallized from Et2O
to yield yellow crystals (decomposed without melting at 157-160 °C).
1H NMR (400 MHz, C6D6): δ 1.82 (s, 3H), 3.86 (s, 2H), 4.41 (d, J )
2.4 Hz, 6H), 5.74-5.76 (m, 1H), 6.06-6.09 (m, 1H), 6.21-6.23
(m, 4H) 6.60-6.62 (m, 1H), 6.93-6.96 (m, 4H). 13C NMR (100 MHz,
CD2Cl2): δ 16.8, 32.0, 93.0, 111.1, 112.6 (d, J ) 6 Hz), 114.4, 123.0,
124.3 (d, J ) 7 Hz), 133.9, 237.0 (d, J ) 27 Hz). 31P NMR (162 MHz,
C6D6): δ 177.7. MS (+EI): m/z (%): 475 (0.3), 427 (7), 369 (19),
341 (91), 293 (69), 262 (71), 223 (43). HRMS (+EI): found 475.05873
(calcd 475.05754). IR (KBr): 3118 (w), 2905 (w), 1911 (s), 1854 (s),
Attempted Formation of η6-Benzene((2-diphenylphosphinopyr-
rolyl)dipyrrolylphosphine) Dicarbonylchromium(0) (44i). Charac-
terization of Complex 49. The initial product was obtained as an orange
solid (a mixture of PPh2 and PPyr2 bound ligand in about a 4:1 ratio
by NMR). The PPh2 bound complex 49 was purified by a careful
crystallization from CH2Cl2/Et2O as an orange solid; 46% yield. Mp
1
159-164 (dec). H NMR (400 MHz, C6D6): δ 4.19 (d, J ) 2 Hz,
6H), 6.14 (br s, 1H), 6.20 (t, J ) 2 Hz, 4H), 6.48-6.52 (m, 5H), 6.88-
7.05 (m, 7H), 7.78 (br t, J ) 13 Hz, 4H). 13C NMR (100 MHz,
CD2Cl2): δ 91.0, 113.0, 113.2 (d, J ) 5 Hz), 123.3 (d, J ) 11 Hz),
125.6-126.0 (m), 128.5 (d, 9 Hz), 128.8 (br), 129.7, 132.8 (d, J )
11 Hz), 241.2 (d, 30 Hz). 31P NMR (162 MHz, CD2Cl2): δ 70.6-71.2
(m), 77.7-78.3 (m). MS (+EI): m/z (%) 521 (<1), 465 (10), 398 (8),
347 (20), 269 (5). HRMS (+FAB): m/z found (MH+) 600.1068 (calcd
600.1062). IR (KBr): 1889 (s), 1832 (s), 1453 (m), 1435 (m),
1445 (m), 1179 (m), 1036 (m), 742 (s) cm-1
.
Characterization of η6-Benzene(2-(phenylthiomethylpyrrolyl)-
dipyrrolylphosphine) Dicarbonylchromium(0) (44e). This was ob-
tained as a yellow solid in 55% yield. It was recrystallized from Et2O
1176 (m), 1151 (m), 1057 (m), 733 (m) cm-1
.
1
to yield yellow crystals. Mp 164-165 °C (dec). H NMR (400 MHz,
Characterization of η6-Fluorobenzene((2-phenylthiomethylpyr-
rolyl)dipyrrolylphosphine) Dicarbonylchromium(0) (50e). This was
obtained as a yellow solid in 50% yield. It was recrystallized from
Et2O to yield yellow crystals. Mp 135-136 °C (dec). 1H NMR
(400 MHz, C6D6): δ 3.97-4.02 (m, 1H), 4.24-4.30 (m, 2H), 4.35-
4.37 (br s, 2H), 4.46-4.52 (m, 2H) 5.73-5.76 (m, 1H), 6.02-6.06
(m, 1H), 6.17-6.21 (m, 4H), 6.62-6.65 (m, 1H), 6.84-7.00 (m, 7H),
7.32-7.37 (m, 2H). 13C NMR (100 MHz, CD2Cl2): δ 32.0, 80.1
(d, J ) 20 Hz), 89.0, 92.1 (d, 7 Hz), 111.4 (d, J ) 6 Hz), 113.0
(d, 6 Hz), 115.5 (d, 5 Hz), 123.6 (d, 5 Hz), 124.3 (d, 7 Hz), 127.0,
129.5, 129.9, 133.0, 136.8, 235.7 (d, 34 Hz). 19F NMR (376 MHz,
C6D6): δ -136.6. 31P NMR (162 MHz, C6D6): δ 175.5. MS (+FAB):
m/z (%) 578 (2), 527 (2), 489 (7), 403 (96), 367 (31), 175 (100). HRMS
(+FAB): m/z found (MNa+) 578.0533 (calcd 578.0535). IR (KBr):
3083 (w), 1925 (s), 1871 (s), 1457 (m), 1181 (m), 1053 (m), 737 (m)
C6D6): δ 4.37 (d, J ) 2.4 Hz, 6H), 4.43 (s, 2H), 5.71-5.74 (m, 1H),
6.04-6.07 (m, 1H), 6.20-6.23 (m, 4H) 6.63-6.66 (m, 1H), 6.84-
7.00 (m, 7H), 7.34-7.38 (m, 2H). 13C NMR (75 MHz, CD2Cl2):
δ 32.1 (d, J ) 10 Hz), 92.0, 111.4 (d, J ) 5 Hz), 113.2 (d, J ) 6 Hz),
115.3 (d, J ) 4 Hz), 123.2 (d, J ) 3 Hz), 124.5 (d, J ) 6 Hz), 126.7,
129.5, 129.6, 132.8 (d, J ) 7 Hz), 137.5, 236.6 (d, J ) 27 Hz).
31P NMR (162 MHz, C6D6): δ 175.3. MS (+EI): m/z (%) 537 (0.5),
481 (0.5), 459 (45), 427 (70), 403 (100), 371 (55). HRMS (+FAB):
m/z found 537.0739 (calcd 537.0732). IR (KBr): 3134 (w), 3098 (w),
1913 (s), 1858 (s), 1458 (m), 1174 (m), 1038 (m), 737 (s) cm-1
.
Characterization of η6-Benzene((2-methylcarboxypyrrolyl)dipyr-
rolylphosphine) Dicarbonylchromium(0) (44h). This was obtained
in 69% yield as a yellow solid which was further recrystallized from
ether. Mp 146 °C (dec). 1H NMR (300 MHz, benzene-d6): δ 3.39
(s, 3H), 4.29 (d, J3 ) 2.4 Hz, 6H), 5.54 (ddd, 1H), 5.86 (dt, 1H),
PH
cm-1
.
6.21-6.26 (m, 4H), 6.85-6.91 (m, 4H), 7.20 (dt, 1H). 13C NMR
(126 MHz, CD2Cl2): δ 52.2, 92.1, 111.4, 112.2 (d, 5.3 Hz), 123.6,
124.3 (d, 6.4 Hz), 128.1, 130.0, 160.7, 235.9 (d, 28 Hz). 31P NMR
(202 MHz, CD2Cl2): δ 177.8. MS (+EI): m/z (%) 473 (M+, 1.1), 445
(1.6), 424 (24), 417 (13), 367 (36), 339 (62), 221 (58). HRMS
(+FAB): m/z found 473.0577 (calcd 473.0600). IR (CH2Cl2, KBr):
Characterization of η6-Fluorobenzene((2-methylthiopyrrolyl)-
dipyrrolylphosphine) Dicarbonylchromium(0) (50e). This was ob-
1
tained as a yellow solid in 66% yield. Mp 115 °C (dec). H NMR
(400 MHz, benzene-d6): δ 1.90 (s, 3H), 3.95-4.00 (m, 1H), 4.30-
4.36 (m, 2H), 4.47-4.53 (m, 2H), 5.73 (td, J1 ) 3.2 Hz, J2 ) 2 Hz,
1H), 6.02 (td, J1 ) 3.6 Hz, J2 ) 1.2 Hz, 1H), 6.21-6.27 (m, 5H),
6.86-6.91 (m, 4H). 19F NMR (470 MHz, benzene-d6): δ -137.2.
31P NMR (202 MHz, benzene-d6): δ 74.7. 13C NMR (126 MHz,
CD2Cl2): δ 21.5, 79.8 (d, 20 Hz), 89.0, 92.1, 112.1, 112.6, 118.2, 124.4,
130.6, 235.5 (d, 27 Hz). MS (+FAB) m/z (%) 480 (23), 413 (25), 355
(37), 327 (100), 215 (23). HRMS (+FAB): m/z found (MH+) 480.0394
(calcd 480.0403). IR (KBr): 3054 (m), 2987 (m), 2305 (w), 1937 (s),
1917 (m), 1856 (m), 1708 (m), 1653 (m) cm-1
.
Characterization of η6-Benzene(2-(N,N-Dimethylamidopyrrolyl)-
dipyrrolylphosphine) Dicarbonylchromium(0) (44f). This was ob-
tained in 88% yield as a yellow oil which crystallized from CH2Cl2/
Hex to yield an orange solid. 1H NMR (400 MHz, C6D6): δ 2.42
(s, 6H), 4.35 (d, J ) 2.4 Hz, 6H), 6.02-6.05 (m, 1H), 6.06-6.09
(m, 1H), 6.14-6.18 (m, 4H), 6.90-6.95 (m, 4H), 6.98-7.02 (m, 1H).
13C NMR (125 MHz, CD2Cl2): δ 93.5, 110.9, 111.7 (d, J ) 5 Hz),
114.3, 124.5 (d, J ) 6 Hz), 127.4 (d, J ) 10 Hz), 131.1, 162.9, 237.2
(d, J ) 28 Hz). IR (KBr): 1913 (s), 1855 (s), 1634 (s), 1456 (s), 1173
(s), 1055 (s), 734 (s) cm-1. X-ray determination: see Supporting
Information.
1880 (s), 1458 (s), 1265 (s), 736 (s) cm-1
.
Characterization of η6-(o-Xylene)((2-methylcarboxypyrrolyl)-
dipyrrolylphosphine) Dicarbonylchromium(0) (54b). This was ob-
tained as a yellow solid in 93% yield. It was recrystallized from Et2O
to yield yellow crystals that turned orange at 124 °C and black at 140
1
Characterization of η6-Benzene((2-(2′-pyridino)pyrrolyl)dipyr-
rolyl) Phosphinedicarbonylchromium(0) (44j). This was obtained as
an orange oil which solidified on storage at 0 °C. Rapid chromatography
on a short silica gel column yielded 44i in 59% yield (extended
chromatography time led to significant decomposition of the product).
Careful recrystallization from ether/hexane gave an orange solid that
°C. H NMR (400 MHz, benzene-d6): δ 1.65 (s, 6H), 3.40 (s, 3H),
4.27-4.37 (m, 4H), 5.68-5.72 (m, 1H), 5.89 (t, J ) 2.8 Hz, 1H), 6.23-
6.26 (m, 4H), 6.92-6.95 (m, 4H), 7.28 (dt, J ) 3.6 Hz, J ) 1.6 Hz,
1H). 13C NMR (100 MHz, CD2Cl2): δ 19.06, 52.2, 91.9, 94.7, 105.7,
111.3, 112.0 (d, 5.7 Hz), 123.6, 124.2 (d, 6.1 Hz), 130.0, 160.5, 236.4
(d, 24 Hz). 31P NMR (162 MHz, CD2Cl2): δ 176.5. MS (+EI): m/z
(%) 501 (M+, 0.1), 445 (5), 367 (1), 339 (16), 303 (6), 221 (89). HRMS
(+EI): m/z found 501.09123 (calcd 501.09095). IR (CH2Cl2, KBr):
1
decomposed at 114 °C. H NMR (400 MHz, C6D6): δ 4.22 (d, J )
2.4 Hz, 6H), 5.62-5.66 (m, 1H), 6.07-6.10 (m, 1H), 6.22-6.24
9
7772 J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005

Accelerated Arene Ligand Exchange
A R T I C L E S
3129 (w), 3121 (w), 2953 (w), 1911 (m), 1849 (m), 1712 (m), 1146
phosphine peaks of the product (when distinguishable from the starting
material) were integrated. The logarithms of the arene areas were plotted
vs time to yield a straight line from which half lifetime was calculated.
In one case, the product of the reaction between η6-benzene((2-
methylcarboxypyrrolyl)dipyrrolylphosphine) dicarbonylchromium(0)
(44h) and fluorobenzene-d5 was analyzed by 19F and 31P NMR
spectroscopy. Both spectra (19F, δ -138.3 ppm; 31P, δ 177.8 ppm) were
consistent with the formation of the expected product η6-fluorobenzene-
((2-methylcarboxypyrrolyl)dipyrrolylphosphine) dicarbonylchromium-
(0). From the kinetic plot it was evident that the equilibrium for this
arene exchange reaction has been reached after 14 h at 50 °C. An
estimate of an equilibrium constant (∼0.004) was made based on the
1H NMR integrals of the species involved.
(m), 734 (m) cm-1
.
Characterization of η6-(m-Xylene)((2-methylcarboxypyrrolyl)-
dipyrrolylphosphine) Dicarbonylchromium(0) (54c). This was ob-
tained as a yellow solid in 97% yield. It was further recrystallized from
Et2O to yield yellow crystals that turned orange at 139 °C and then
1
black at 149 °C. H NMR (400 MHz, benzene-d6): δ 1.72 (s, 6H),
3.39 (s, 3H), 4.08-4.14 (m, 3H), 4.37-4.43 (m, 1H), 5.56-5.60
(m, 1H), 5.89 (t, J ) 3.6 Hz, 1H), 6.22-6.26 (m, 4H), 6.91-6.96
(m, 4H), 7.25-7.28 (m, 1H). 13C NMR (100 MHz, CD2Cl2): δ 20.8,
52.1, 90.9, 91.2, 94.2, 109.1, 111.2, 112.0 (d, 5.9 Hz), 123.7, 124.2
(d, 6.4 Hz), 128.0, 130.2, 160.6, 236.5 (d, 26 Hz). 31P NMR (202 MHz,
CD2Cl2): δ 176.7. MS (+EI): m/z (%) 501 (M+, 0.1), 445 (8),
367 (5), 339 (25), 287 (55), 221 (100). HRMS (+EI): m/z found
501.08905 (calcd 501.09095). IR (CH2Cl2, KBr): 1914 (m), 1850 (m),
Preparative Scale Exchange Experiment. In a 100-mL flask
equipped with a magnetic stirring bar was put η6-fluorobenzene((2-
methylthiopyrrolyl)dipyrrolylphosphine) dicarbonylchromiu m(0) (50a,
114 mg, 0.240 mmol), and the flask was placed under argon. Then
20 mL of freshly distilled benzene was added and the solution was
heated to 60 °C for 3 h. The resulting yellow solution was cooled to
room temperature, filtered through Celite, and the filtrate was concen-
trated on a rotary evaporator to yield yellow solid that was chromato-
graphed on silica gel (hex:EtOAc 10:1) to yield η6-benzene(2-
(methylthiopyrrolyl)dipyrrolylphosphine) dicarbonylchromium(0) (44a)
1711 (m), 1147 (m), 732 (m) cm-1
.
Characterization of η6-(p-Xylene)((2-methylcarboxypyrrolyl)-
dipyrrolylphosphine) Dicarbonylchromium(0) (54d). This was ob-
tained as a yellow solid in 99% yield. It was recrystallized from Et2O
to yield yellow crystals that turned orange at 125 °C and then brown
1
at 133 °C followed by complete decomposition. H NMR (400 MHz,
benzene-d6): δ 1.67 (s, 6H), 3.38 (s, 3H), 4.28 (d, J3PH ) 3.2 Hz, 4H),
5.65-5.67 (m, 1H), 5.90 (t, J ) 2.8 Hz, 1H), 6.22-6.25 (m, 4H), 6.94-
6.97 (m, 4H), 7.27-7.30 (m, 1H). 13C NMR (100 MHz, CD2Cl2):
δ 20.1, 52.1, 93.3, 106.5, 111.4, 111.9 (d, 5.7 Hz), 123.6, 124.2 (d, 6.6
Hz), 130.1, 160.5, 237.0 (d, 26 Hz). 31P NMR (162 MHz, CD2Cl2):
δ 176.8. MS (+EI): m/z (%) 501 (M+, 0.1), 473 (3), 445 (20), 424
(40), 387 (12), 339 (40), 221 (100). HRMS (+EI): m/z found 501.08977
(calcd 501.09095). IR (CH2Cl2, KBr): 3126 (w), 2949 (w), 1918 (s),
1
(100 mg, 94% yield, pure by H NMR).
Acknowledgment. We wish to thank Drs. Istvan Pelczer and
Carlos Pacheco for assistance with the NMR studies, Dr.
Dorothy Little for mass spectrometry service, Professor R.
Pascal for helpful discussions, and the Bristol-Myers Squibb
Company for a graduate fellowship to A.C.
1863 (s), 1724 (m), 1146 (m), 734 (m) cm-1
.
General Procedure for Monitoring Arene Exchange. In an NMR
tube were put 1-5 mg of (arene)dicarbonyl((2-L-pyrrolyl)dipyr-
rolylphosphine)chromium(0) and 0.5-1.2 mL of the perdeuterated
arene, and the solution was subjected to three freeze-pump-thaw
cycles after which the tube was flame sealed under vacuum. The NMR
probe was preheated to 40-70 °C, and the tube was inserted (actual
probe temperature was assessed via calibration using an ethylene glycol
standard). A series of 1H NMR spectra were collected. Disappearance
of the arene peak of the starting material and appearance of the new
Supporting Information Available: Reproductions of the
1H NMR and 13C NMR spectra for new compounds studied in
this work. CIF files for the X-ray diffraction structure deter-
mination. This material is available free of charge via the
Internet at http://pubs.acs.org.
JA042705X
9
J. AM. CHEM. SOC. VOL. 127, NO. 21, 2005 7773