Tin-mediated CH activation and cross-coupling in a single flask

Article abstract of DOI:10.1021/om060388s

Tin-mediated CH activation and cross-coupling in a single flask has been achieved by employing a mixed stannylene/phenyl iodide reagent followed by Stille cross-coupling. The reagent has been successfully employed for alkanes and ethers and shows radical-like regioselectivity.

Full text of DOI:10.1021/om060388s

4738
Organometallics 2006, 25, 4738-4740
Tin-Mediated CH Activation and Cross-Coupling in a Single Flask
Jeffrey M. Bartolin, Ajdin Kavara, Jeff Kampf, and Mark M. Banaszak Holl*
Chemistry Department, 930 North UniVersity AVenue, Ann Arbor, Michigan 48109-1055
ReceiVed May 5, 2006
Summary: Tin-mediated CH actiVation and cross-coupling in
a single flask has been achieVed by employing a mixed
stannylene/phenyl iodide reagent followed by Stille cross-
coupling. The reagent has been successfully employed for
alkanes and ethers and shows radical-like regioselectiVity.
form C-C bonds using Ge-C reagents are extremely limited.17-20
To improve the utility of this method for the direct formation
of main-group-metal to carbon bonds, we explored the extension
of this chemistry to stannylenes. We now report that the
stannylene Sn[N(SiMe3)2]2 (1)21-23 can be employed in con-
junction with an aryl halide for C-H activation of alkanes and
ethers and that the products derived from these reactions can
be used in subsequent Stille-type C(sp3)-C(sp2) cross-coupling
reactions24-26 to form new carbon-carbon bonds.
Carbon-hydrogen (C-H) bond activation has been the focus
of many academic and industrial studies.1-3 The vast majority
of these studies have involved transition-metal-mediated C-H
activation reactions. Significant progress has been made in recent
years applying this transition-metal-based approach to practical
problems in organic synthesis.4-8 Considerably less progress
has been made in the discovery and development of CH
activation reactions that generate an E-C bond, where E is a
main-group element. In principle, such reactions are highly
desirable, since they generate a product containing an E-C bond
which could be directly employed in carbon-carbon bond
forming reactions. A notable success in this area is the work of
Crabtree et al. using Hg to both activate CH bonds and
subsequently form new carbon-carbon bonds by cross-
coupling.9-11 Electrophilic arene activations are well-prece-
dented for Hg, Tl, Pb, and Sn.12 In addition, substantial progress
has been made in CH activation to form B-C bonds.13,14
C-H activation is observed when equimolar amounts of 1
and phenyl iodide (0.060 mmol, 0.03 M) are mixed in
hydrocarbon solvent (eq 1). Activation of C-H bonds in
cyclohexane, cyclopentane, pentane, tetrahydrofuran (THF), and
tert-butyl methyl ether were observed (Scheme 1). A new Sn-C
bond is formed, and 1 equiv of benzene is formed. The
cyclohexane case was also run using C6D12 and m-iodotoluene.
Mass spectroscopy indicated the formation of monodeuterio-
toluene. When the reactants are simply mixed, a substantial
amount of the oxidative addition product 3 is also formed.
Similar to the results previously observed for R2Ge/PhI,15 CH
activation preferentially occurs R to the oxygen in THF and
the secondary sites are preferred over the primary sites for
pentane (∼6.2:1, secondary to primary).
Recently, we reported the C-H activation of ethers and
alkanes by a mixed germylene/aryl halide reagent as well as
the salt-catalyzed insertion of germylenes into nitrile C-H
bonds, ketones, and phenones.15,16 Unfortunately, methods to
* To whom correspondence should be addressed. E-mail: mbanasza@
umich.edu.
(1) Arndtsen, B. A.; Bergman, R. G.; Mobley, T. A.; Peterson, T. H.
Acc. Chem. Res. 1995, 28, 154-162.
(2) Shilov, A. E.; Shul’pin, G. B. Chem. ReV. 1997, 97, 2879-2932.
(3) Labinger, J. A.; Bercaw, J. E. Nature 2002, 417, 507-514.
(4) Kakiuchi, F.; Chatani, N. AdV. Synth. Catal. 2003, 345, 1077-1101.
(5) Davies, H. M. L.; Venkataramani, C.; Hansen, T.; Hopper, D. W. J.
Am. Chem. Soc. 2003, 125, 6462-6468.
The amount of CH activation product (2a-g) could be
maximized and the amount of oxidative-addition product (3)
minimized by performing the reaction under highly dilute
conditions. In a typical reaction, 25 mL of a 0.018 M solution
(6) Thalji, R. K.; Ahrendt, K. A.; Bergman, R. G.; Ellman, J. A. J. Am.
Chem. Soc. 2001, 123, 9692-9693.
(7) Dick, A. R.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004,
126, 2300-2301.
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2049.
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2002, 4, 3165-3167.
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R. R. AdV. Chem. Ser. 1992, 230, 197-210.
(20) Kosugi, M.; Tanji, T.; Tanaka, Y.; Yoshida, A.; Fugami, K.;
Kameyama, K.; Migita, T. J. Organomet. Chem. 1996, 508, 255-257.
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7160-7162.
(15) Miller, K. A.; Bartolin, J. M.; O’Neill, R. M.; Sweeder, R. D.;
Owens, T. M.; Kampf, J. W.; Banaszak Holl, M. M.; Wells, N. J. J. Am.
Chem. Soc. 2003, 125, 8986-8987.
(16) Miller, K. A.; Watson, T. W.; Bender, J. E.; Banaszak Holl, M.
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10.1021/om060388s CCC: $33.50 © 2006 American Chemical Society
Publication on Web 08/23/2006

Communications
Organometallics, Vol. 25, No. 20, 2006 4739
Scheme 1. Activation of Alkanes and Ethers by a Stable
Stannylene and Phenyl Iodide
Figure 1. ORTEP diagram of [(Me3Si)2N]2SnI(C5H9) (2g). Selected
bond lengths (Å) and angles (deg): Sn-C1, 2.169(2); Sn-N1,
2.049(2); Sn-N2, 2.055(2); Sn-I, 2.727(5); C1-Sn-N1, 118.19(7);
C1-Sn-N2, 108.82(7); C1-Sn-I, 103.67(5); N2-Sn-I, 110.32(4);
N1-Sn-I, 102.23(5); N1-Sn-N2, 112.84(6).
of stannylene in the solvent of choice was added slowly via a
syringe pump (0.07 mL/min) to a stirred 25 mL solution of 0.02
M PhI. Reactions in which the yellow color of the stannylene
instantly disappears (cyclopentane and cyclohexane) yield no
detectable 3. However, reactions in which the yellow color of
the stannylene builds up (pentane, THF, tert-butyl methyl ether,
diethyl ether) still yield appreciable amounts of 3 (11, 36, 32,
and 63%, respectively). The rates of addition used for this
chemistry are ∼4-6 times slower than were required for the
analogous germylene chemistry.15
Slow addition techniques effectively eliminated the side
product 3 and made it possible to isolate pure [(Me3Si)2N]2SnIR
for R ) cyclohexyl, cyclopentyl. The cyclopentyl product was
also characterized by X-ray crystallography (Figure 1).27
Although the mixture of primary and secondary CH activation
products and 3 that resulted from the reaction with n-pentane
did not prove amenable to separation, pure [(Me3Si)2N]2SnI-
(CH2)4CH3 (2c) was obtained by the oxidative addition of
1-iodopentane with 1. The NMR assignments from this material
were then used to positively identify the presence of the primary
pentyl product in the CH activation reaction mixture. For THF
and tert-butyl methyl ether, neither reducing the concentration
of the solutions further (as low as 0.01 M) nor further slowing
the rate of addition (as low as 0.023 mL/min) was effective at
lowering the amount of 3 below 36 and 32%, respectively. The
solubilities of 2a and 3 are virtually identical, and we were
unable to separate these materials by recrystallization from
hydrocarbon, aromatic, or ethereal solvents or using mixtures
such as diethyl ether/acetonitrile. Attempts to separate 2a from
3 using sublimation also failed as a purification method, as the
materials cosublimed. Fortunately, the presence of 3 does not
prevent the cross-coupling reaction.
PhI > PhBr >>> PhCl are consistent with the trend in both
strengths with respect to homolytic C-X bond cleavage.
Fouquet et al. have previously demonstrated that this class
of tin reagents provides excellent substrates for the Stille cross-
coupling reaction.28-31 Products obtained from the CH activation
reaction can be directly applied to the cross-coupling reactions.
The Fouquet conditions are restricted to primary C-Sn bonds;
thus, 2a,c are the only CH activation products with the
appropriate structure. These compounds were smoothly con-
verted into benzyl tert-butyl ether and amylbenzene, respec-
tively. The reaction conditions employed differ in terms of an
increase in catalyst load (3% vs 1% for Fouquet) and a greater
degree of dilution.
Ideally, the CH activation and cross-coupling could both be
performed in the same reaction flask without an isolation step.
Indeed, this proved to be the best way to run these reactions. In
a typical one-pot reaction, 25 mL of a 0.018 M solution of 1 in
tert-butyl methyl ether was dripped into an equimolar 25 mL
stirred 0.02 M solution of phenyl iodide over a period of 5 h
(Scheme 2). After 12 h of stirring to ensure completion of the
reaction, the volatiles (excess tert-butyl methyl ether and
benzene) were removed, leaving a yellow powder. The cross-
coupling reagents were then added to the same flask in order:
phenyl iodide (0.440 mmol, 1 equiv), tetrabutylammonium
fluoride (TBAF, dissolved in THF; 1.32 mmol, 3 equiv),
tetrakis(triphenylphosphine)palladium as a catalyst (15 mg, 3%
catalyst load), and 10 mL of dioxane as solvent. The solution
was refluxed for 12 h and then cooled to room temperature
(20 °C).
The use of phenyl bromide and phenyl chloride was also
tested. Similar to the previously reported case for germylenes,
CH activation could be achieved using phenyl bromide but was
dramatically slower. For example, refluxing 1, phenyl bromide,
and cyclohexane for 24 h resulted in 15% and 25% conversion
to CH activation and oxidative addition products, respectively.
The remaining 60% of 1 did not react. Neither CH activation
nor oxidative addition was observed for reaction of phenyl
chloride, even under refluxing conditions. The relative rates of
The resulting dark yellow solution, also containing black
sediment, was filtered through 1 in. of Celite in a glass pipet,
resulting in a light yellow solution. Milliliter aliquots were used
for GC/MS experiments. A 67% yield (by GC/MS) of cross-
coupled product was obtained for tert-butyl methyl ether (overall
26% yield from 1), and a yield of 65% was obtained for pentane
(overall 5% from 1).
(28) Rodriguez, A. L.; Peron, G.; Duprat, C.; Vallier, M.; Fouquet, E.;
Fages, F. Tetrahedron Lett. 1998, 39, 1179-1182.
(29) Fouquet, E.; Pereyre, M.; Rodriguez, A. L. J. Org. Chem. 1997,
62, 5242-5243.
(27) Crystal data for 2g: C17H45N2Si4ISn, Mr ) 635.50, orthorhombic,
Pbca, colorless block, a ) 13.481(2) Å, b ) 17.536(3) Å, c ) 23.734(4)
Å, V ) 5610.8(2) Å3, T ) 123(2) K, Z ) 8, R(F, observed data) ) 0.0202,
GOF ) 1.104. Data were collected on a Bruker SMART CCD-based
X-ray diffractometer. The structure was solved and refined using Bruker
SHELXTL software. Hydrogen atoms were placed in idealized positions
and refined isotropically; non-hydrogen atoms were refined anisotropically.
(30) Fouquet, E.; Pereyre, M.; Roulet, T. J. Chem. Soc., Chem. Commun.
1995, 2387-2388.
(31) Herve, A.; Rodriguez, A. L.; Fouquet, E. J. Org. Chem. 2005, 70,
1953-1956.

4740 Organometallics, Vol. 25, No. 20, 2006
Scheme 2. One-Pot C-H Activation and Cross-Coupling
Communications
In summary, a new method for CH activation of alkanes and
ethers is reported that leads directly to the formation of a Sn-C
bond. The products derived from the activation of primary
carbons can be carried forward directly for C-C bond formation
reactions using Stille cross-coupling methodology without need
of further isolation. Additional studies are underway to explore
the mechanism of this reaction and develop synthetically useful
applications.
Acknowledgment. This work was supported by the National
Science Foundation (Grant No. CHE-0453849).
Supporting Information Available: Text giving complete
experimental preparation details and a CIF file giving crystal-
lographic data. This material is available free of charge via the
Internet at http://pubs.acs.org.
OM060388S