Catalytic C-H bond stannylation: A new regioselective pathway to C-Sn bonds via C-H bond functionalization

Article abstract of DOI:10.1021/ja105588v

The ubiquitous Stille coupling reaction utilizes Sn-C bonds and is of great utility to organic chemists. Unlike the B-C bonds used in the Miyaura-Suzuki coupling reaction, which are readily obtained via direct borylation of C-H bonds, routes to organotin compounds via direct C-H bond functionalization are lacking. Here we report that the nickel-catalyzed reaction of fluorinated arenes and pyridines with vinyl stannanes does not provide the expected vinyl compounds via C-F activation but rather provides new Sn-C bonds via C-H functionalization with the loss of ethylene. This mechanism provides a new unanticipated methodology for the direct conversion of C-H bonds to carbon-heteroatom bonds.

Full text of DOI:10.1021/ja105588v

Published on Web 08/06/2010
Catalytic C-H Bond Stannylation: A New Regioselective Pathway to C-Sn
Bonds via C-H Bond Functionalization
Meghan E. Doster, Jillian A. Hatnean, Tamara Jeftic, Sunjay Modi, and Samuel A. Johnson*
Department of Chemistry & Biochemistry, UniVersity of Windsor, Windsor, ON, Canada N9B 3P4
Received June 25, 2010; E-mail: sjohnson@uwindsor.ca.
syntheses of these organotin reagents typically involve multiple
steps from expensive functional-group-containing precursors.
Abstract: The ubiquitous Stille coupling reaction utilizes Sn-C
bonds and is of great utility to organic chemists. Unlike the B-C
bonds used in the Miyaura-Suzuki coupling reaction, which are
readily obtained via direct borylation of C-H bonds, routes to
organotin compounds via direct C-H bond functionalization are
lacking. Here we report that the nickel-catalyzed reaction of
fluorinated arenes and pyridines with vinyl stannanes does not
provide the expected vinyl compounds via C-F activation but
rather provides new Sn-C bonds via C-H functionalization with
the loss of ethylene. This mechanism provides a new unantici-
pated methodology for the direct conversion of C-H bonds to
carbon-heteroatom bonds.
We have previously shown that stoichiometric amounts of
Ni(COD)2 (COD ) 1.5-cyclooctadiene) and the ancillary ligand
MeNC5H4NiPr react with a variety of partially fluorinated aromatics,
such as C6F5H, via selective C-F activation at room temperature.7
The addition of H2CdCHSnBu3 and a partially fluorinated arene
to catalytic amounts of Ni(COD)2, and MeNC5H4NiPr would be
expected to result in catalytic C-F bond functionalization via the
Stille coupling reaction to produce a partially fluorinated styrene.8
Remarkably, these reactions at room temperature yielded no C-F
activation products and practically quantitative catalytic conversions
to the products of C-H functionalization, C6FnH5-nSnBu3, as shown
in Figure 2. The stoichiometric production of ethylene as a
byproduct was positively identified by 1H and 13C{1H} NMR
In the past few decades, transition-metal C-H bond activation1
spectroscopy when the reaction was performed in C6D6 in a sealed
and catalytic functionalization have gone from an exotic branch of
transition-metal reactivity without practical application to cutting-
edge technology in catalytic organic transformations.2 Reactions
that convert C-H bonds into molecules bearing versatile functional
groups, such as regioselective borylations,3 have been extensively
utilized to generate functionalized organics such as arylboronic
esters directly from hydrocarbons and B-H or B-B bond cleavage,
as depicted in Figure 1; these compounds serve as versatile starting
materials used in reactions such as Miyaura-Suzuki coupling.4
NMR tube. The reaction was found to go to completion with as
little as 1 mol % Ni(COD)2 and MeNC5H4NiPr and provided
practically pure product, as monitored by 19F, 1H, and 119Sn NMR
spectroscopy. The reaction could also be performed without the
addition of solvent.
Figure 2. General reaction scheme for the catalytic stannylation of C-H
bonds.
Figure 1. Examples of aryl C-H bond borylation and a comparison to
the known chemistry of tin.
Unfortunately, extensions of the C-H bond borylation method-
ology are limited in scope. For example, although the oxidative
addition of Sn-H bonds to transition metals has precedent, the
catalytic conversion of trialkyltin hydrides, R3SnH, to R3SnSnR3
and H2 is often instantaneous. The oxidative addition of Sn-Sn
bonds has also been reported; to date, however, this reaction has
been utilized only in catalytic coupling to carbon-halide bonds
and additions to carbon-carbon multiple bonds.5 This pair of
currently unsuccessful approaches to catalytic C-H bond stanny-
lation, which are analogous to those used in borylation chemistry,
are shown at the right in Figure 1. A new method for forming C-Sn
bonds from C-H bonds could have significant impact as a facile
route to reagents for the Stille coupling reaction,6 which is widely
utilized because of the air and moisture stability and functional
group tolerance of the organonotin compounds it employs. The
To investigate the generality of this catalytic functionalization,
we examined the scope of fluorinated aromatics that undergo
this reaction. A summary is shown in Table 1. Aromatic sub-
strates with C-H bonds ortho to two fluorines, such as C6F5H,
1,2,4,5-C6F4H2, 1,2,3,5-C6F4H2, 1,2,4-C6F3H3, 1,3,5-C6F3H3, and
1,3-C6F2H4 proved to be the most reactive. The monostannylated
compounds 1, 2, 4, 7, and 10 were obtained with good selectivity
(>91%) using a modest excess of fluorinated aromatic (∼2
equiv); the only significant impurities were the distannylated
compounds 3, 5, 8, and 11, which were readily separated. The
distannylated compounds could be obtained with good selectivity
themselves by using 2.5 equiv of H2CdCHSnBu3. The distan-
nylated isomer, 1,3-(Bu3Sn)2-2,4,5-C6F3H (9), was also present
as a small impurity in the synthesis of 8. The tristannylated
derivative of 1,3,5-C6F3H3, 12, was also accessible using PiPr3
9
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J. AM. CHEM. SOC. 2010, 132, 11923–11925 11923

C O M M U N I C A T I O N S
Table 1. Catalytic C-H Bond Functionalization of Fluorinated
Arenes with Tributylvinylstannane
reactions were found to occur under milder conditions, produce
higher yields, and be more selective, with no C-F functional-
ization products observed.9
The reactions of substrates where only one fluorine substituent
is disposed ortho to a C-H bond were slower under similar
conditions and were not efficiently catalyzed using MeNC5H4NiPr
as the ancillary ligand. Although replacing MeNC5H4NiPr with
traditional phosphine donors, such as PiPr3, led to lower rates than
using MeNC5H4NiPr for the substrates investigated, the thermal
stability of the catalyst improved, which allowed for efficient
functionalization at higher temperatures. For example, with PiPr3
as the ancillary ligand, the functionalization of 1,2,3,4-C6F4H2
occurred in 4 h at 80 °C and provided selective conversion to the
monostannylated product 6. Similar results were observed when
1,2,3-trifluorobenzene was used as the substrate, providing the
monosubstituted product 13. The distannylated product 14 was also
obtained selectively in the presence of excess CH2dCHSnBu3 and
was present as a slight impurity in the synthesis of 13. The activation
of heterocycles such as 2,3,5,6-tetrafluoropyridine also proved to
be possible when phosphines were used but did not occur with the
ancillary ligand MeNC5H4NiPr.
The monostannylated compounds 15, 16, and 18 were obtained
from 1,3-, 1,2-, and 1,4-difluorobenzene, respectively, in >90% yield
at 80 °C when PiPr3 was employed as the ligand. The only
significant impurities were the distannylated compounds 1,4-
(Bu3Sn)2-2,3-C6F2H2 (17), 1,4-(Bu3Sn)2-2,5-C6F2H2 (19), and 1,3-
(Bu3Sn)2-2,5-C6F2H2 (20). With fluorobenzene, only 15% conver-
sion to the monostannylated complex 1-(Bu3Sn)-2-C6FH3 (21) was
achieved. These di- and monofluorinated aromatics proved to be
poor substrates when MeNC5H4NiPr was used as the ancillary
ligand.
Both an ancillary ligand and Ni(COD)2 are necessary for the
desired catalytic reaction to proceed under the conditions used.
Catalysis was observed even in the presence of added Hg, which
argues against Ni metal particles from the decomposition of
Ni(COD)2 acting as the active catalyst. No direct reaction was
observed between pentafluorobenzene and Bu3Sn(vinyl) even when
a toluene solution was heated to 100 °C. Similarly, no reaction
was observed with the addition of the ligand MeNC5H4NiPr in the
absence of the metal-containing catalyst precursor Ni(COD)2.
The reagents Me3Sn(vinyl), cis-(1-propenyl)SnBu3, and trans-
(1-propenyl)SnBu3 all proved to be successful reagents for C-H
bond functionalization. The replacements of these reagents with
Bu4Sn, Ph4Sn, Me3SnSnMe3, and Bu3SnPh were unsuccessful, as
no conversion to the desired products was observed even at elevated
temperatures. The reaction of Bu3SnH and C6F5H using catalytic
Ni(COD)2 and MeNC5H4NiPr or PiPr3 did not yield 1 but instead
produced Bu6Sn2 instantaneously with the liberation of H2 gas. The
ratio of C-H-functionalized product to C-D-functionalized product
in the reaction of the monodeuterated substrate 1,2,4,5-C6F4HD with
Bu3SnCHdCH2 using catalytic Ni(COD)2 and MeNC5H4NiPr was
found to be 2.1:1 at 298 K by integration of the 19F{1H} NMR
resonances of the products. This kinetic isotope effect is consistent
with the equilibrium isotope effect we previously observed in the
oxidative addition of 1,2,4,5-C6F4HD to a Ni(PEt3)2 synthon;10 it
supports a mechanism where oxidative cleavage of the C-H bond
occurs at the transition metal during the catalytic cycle10,11 and
eliminates the possibility that the mechanism involves simple
deprotonation of the fluoroarene.
a NMR yield from integration of 19F{1H} NMR spectra. b Isolated
yield after chromatography. c Using 2.5 equiv of Bu3Sn(vinyl). d Using
3.5 equiv Bu3Sn(vinyl). e Using a 10-fold excess of fluorinated aromatic.
as the ancillary ligand. A decrease in rate was observed with
substrates with a lesser degree of fluorination; however, it proved
possible to increase the turnover rate by increasing the temper-
ature from 25 to 45 °C using the ancillary ligand MeNC5H4NiPr.
Temperatures higher than 60 °C resulted in rapid decomposition
of Ni(COD)2 to nickel metal, and the yields dropped off
significantly. In the cases where data for the analogous borylation
reactions were available for comparison, these stannylation
Two plausible mechanistic manifolds for the functionalization
of C6F5D with cis-(1-propenyl)SnBu3 that invoke the oxidative
addition product L2NiD(C6F5), where L is the ancillary ligand, are
shown in Figure 3. One possibility is that the reaction occurs by
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C O M M U N I C A T I O N S
Figure 3. Two possible reaction pathways for C-Sn bond formation.
oxidative addition of C-H and Sn-C bonds to Ni centers, pure
σ-bond metathesis, or some combination of these processes.12 An
example of this mechanistic manifold showing oxidative addition
of the C-H bond of the fluoroarene and σ-bond metathesis to form
the new C-Sn bond is shown in Figure 3 as mechanism A. In this
mechanism, the double bond of the propenyl group coordinates to
the metal, which brings the Bu3Sn and C6F5 substituents into close
enough proximity to undergo σ-bond metathesis. Reductive elimi-
nation of (Z)-1-deuteropropene followed by oxidative addition of
C6F5D regenerates L2NiD(C6F5). Mechanism B involves 1,2-
insertion of the vinyl moiety into the Ni-D bond followed by
ꢀ-elimination of the SnBu3 group. Mechanism B would produce
(E)-1-deuteropropene and thus can be differentiated from mecha-
nism A.
to the synthesis of other carbon-heteroatom bonds. Efforts to
identify active catalysts and substrates are underway.
Acknowledgment. The Natural Science and Engineering Re-
search Council (NSERC) of Canada is acknowledged for its
financial support in the form of a Discovery Grant to S.A.J. and
postgraduate scholarships to M.E.D. and J.A.H.
Supporting Information Available: Full experimental details for
the preparation and characterization of 1-22 and details of mechanistic
studies. This material is available free of charge via the Internet at
http://pubs.acs.org.
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