A highly chemoselective, Zr-Catalyzed C-O Bond functionalization of benzofuran

Article abstract of DOI:10.1021/om4008295

The chemoselective C-O bond functionalization of benzofuran with an aluminum dihydride may be catalyzed by zirconocene dichlorides. The reaction proceeds with the formal addition of a C-O bond to, and elimination of dihydrogen from, aluminum. The product of C-O bond alumination reacts with benzaldehyde via insertion of the carbonyl into the newly formed Al-C bond.

Full text of DOI:10.1021/om4008295

Communication
pubs.acs.org/Organometallics
A Highly Chemoselective, Zr-Catalyzed C−O Bond Functionalization
of Benzofuran
Shuhui Yow,† Adi E. Nako,† Leonard Neveu, Andrew J. P. White, and Mark R. Crimmin*
́
Department of Chemistry, Imperial College London, London SW7 2AZ, United Kingdom
S
* Supporting Information
ABSTRACT: The chemoselective C−O bond functionalization of benzofuran with
an aluminum dihydride may be catalyzed by zirconocene dichlorides. The reaction
proceeds with the formal addition of a C−O bond to, and elimination of dihydrogen
from, aluminum. The product of C−O bond alumination reacts with benzaldehyde
via insertion of the carbonyl into the newly formed Al−C bond.
n the face of the changing natural resource balance, the field
of synthetic chemistry will need to adapt. In the coming
(Me)}2CH). We have recently reported BDIAlH2 (1)10 as a
terminal reductant in the hydrodefluorination of sp2C−F
bonds11 and speculated upon the use of this main-group
hydride as a reagent for C−O bond cleavage.
The reaction in Eq 3 can be considered as a net elimination
of H2 from, and addition of the C−O bond to, aluminum.
While the dearth of accurate data on Al−H and Al−C bond
enthalpies currently precludes an assessment of the Gibbs free
energy of this process, removal of the dihydrogen is expected to
drive the equilibrium toward the products. Herein we report
our initial findings upon the catalytic, chemoselective C−O
bond functionalization of benzofuran.
Reaction of 1 with benzofuran in the presence of 5 mol % of
Cp2ZrCl2 in C6D6 for 1h at 80 °C yielded 75% of a 1.1:1
mixture of the C−O bond functionalization products 2 and 2-
H2 (Table 1). There is precedent for this mode of reactivity.
Activation of the carbon−oxygen bond in benzofuran by
precoordination of the arene to manganese tricarbonyl followed
by reaction with [(Ph3P)3Pt(η2-C2H4)] has been reported
previously.12 Furthermore, excess lithium powder along with a
catalytic quantity of 4,4′-di-tert-butyldiphenyl is known to effect
the C−O bond cleavage of benzofuran.13 The former reaction
is stoichiometric in two transition metals, whereas the latter
requires strongly reducing conditions and offers limited
possibilities in terms of catalyst control over selectivity.
Following investigation of a series of catalysts and additives,
conditions were discovered for the selective formation of 2
(Table 1; for full experimental details see the Supporting
Information). Hence, employing 5 mol % of (indenyl)2ZrCl2 as
a precatalyst in the presence of 7.5 equiv of the known H2 trap
3,3-dimethylbut-1-ene after 15 h at 80 °C yielded 60% (47%
isolated crystalline yield) of a >50:1 mixture of 2:2-H2.14
Attempts to bias the selectivity toward 2-H2 were less
successful, and performing the reaction with 5 mol % of
I
years, dwindling petroleum resources will be replaced by
alternative raw materials that will contain a higher amount of
elemental oxygen by mass.1 For example, saturated and
unsaturated ethers are available from lignocellulosic biomass,1,2
while benzofuran and dibenzofuran are minor byproducts of
coal gasification.3 Hence, methods for the activation and
functionalization of chemically inert C−O bonds have the
potential to underpin future chemical enterprise using renew-
able resources.
In the past few years, a number of catalysts have been
reported for the hydrodeoxygenation and cross-coupling of C−
O bonds.4,5 Despite these advances, to our knowledge, a
catalytic and selective C−O bond functionalization that
generates an isolable product that is more reactive than the
organic starting materials has yet to be reported. This
observation is in direct contrast to studies in the related field
of C−H functionalization.6 For example, unreactive C−H
bonds in alkanes or arenes may be catalytically transformed into
reactive C−B bonds using boranes as stoichiometric reagents
(Eqs 1 and 2; Bpin = pinacolborane). The reaction products of
C−H borylation, boronic esters, provide an important point for
synthetic diversification.7
Inspired by this work, along with the precedent for
stoichiometric C−O bond cleavage with early transition
metals,8,9 we envisioned the possibility of the C−O bond
alumination of nonreactive ethers (Eq 3, BDI = κ2-{MesNC-
Received: August 16, 2013
Published: September 25, 2013
© 2013 American Chemical Society
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Organometallics
Communication
Table 1. Catalytic C−O Bond Functionalization of
Benzofuran
a
1
Concentration of 1 0.2 M in C6D6,; yields calculated by H NMR
spectroscopy by comparison against ferrocene as an internal standard.
b
c
1
Ratio calculated by H NMR spectroscopy. An unidentified minor
byproduct was present. Ind = indenyl, BDI = {MesNC(Me)C}2H.
Cp2ZrCl2 under 1 atm of H2 or varying the temperature of the
reaction had little effect on the ratio of products (see the
Supporting Information for details).
The organometallic products of C−O bond cleavage were
fully characterized by multinuclear NMR spectroscopy and
single-crystal X-ray diffraction (Figure 1). A comparison of the
solid-state structures reveals a slight shortening of the Al−C
bond in 2 in comparison to its saturated analogue 2-H2, while
the Al−O bonds are comparable between the two. Exposing a
crystalline sample of 2 in C6D6 to hydrogen in the presence of 5
mol % of (indenyl)2ZrCl2 and 5 mol % of 1 for 24 h at 80 °C
did not yield 2-H2. Similarly heating an isolated sample of a 3:1
mixture of 2-H2 and 2 in C6D6 either in the absence of a
catalyst or in the presence of 5 mol % of (indenyl)2ZrCl2 and
7.5 equiv of 3,3-dimethylbut-2-ene for 40 h at 80 °C did not
change the ratio. These data suggest that the reaction products
cannot be interconverted by hydrogenation or dehydrogenation
under the conditions we have examined.
To demonstrate the selectivity of C−O bond functionaliza-
tion, an excess of benzofuran, 2,3-dihydro-2H-pyran, and
tetrahydrofuran along with 3,3-dimethylbut-1-ene was reacted
with 1 in the presence of (indenyl)2ZrCl2.15 After 48 h,
complex 2 was observed in 50% yield and excellent selectivity
(Scheme 1). Despite five different types of carbon−oxygen
bonds being present, 2 was formed in a yield comparable to
that presented in Table 1. A similar competition experiment
with a mixture of benzofuran and dibenzofuran, but run in only
a slight excess of the substrates, was again selective for the
formation of 2 (Scheme 2).
Figure 1. (top) Crystal structure of 2(A), one of the two independent
molecules in the unit cell of 2. Selected bond angles (deg) and bond
lengths (Å): 2A, Al−O = 1.7455(13), Al−C = 1.9260(19), CC =
1.338(3), O−Al−C = 101.55(7); 2(B), Al−O = 1.7544(14), Al−C =
1.9328(18), CC = 1.338(3), O−Al−C = 102.65(8). (bottom)
Crystal structure of 2-H2(A), one of the two independent molecules in
the unit cell of a cocrystallized mixture of 2 and 2-H2. The second
molecule in the unit cell of 2/2-H2 is a disordered mixture of 2 and 2-
H2; 2-H2 is the dominant species. Selected bond angles (o) and bond
lengths (Å): Al−O = 1.7507(13), Al−C = 1.9498(17), C−C =
1.519(3), O−Al−C = 102.46(7).
Scheme 1. Catalytic C−O Bond Functionalization of
Benzofuran in the Presence of Saturated and Unsaturated
Ethers
Despite the sterically crowded metal center in 2, the
aluminum vinyl moiety reacts selectively with an external
electrophile. Hence, the reaction of 2 with 3 equiv of
benzaldehyde in C6D6 solution after 5 days at 80 °C gave
clean insertion of the carbonyl into the metal−carbon bond of
2. While the corresponding aluminum alkoxide 3-Al formed in
61% yield (by NMR spectroscopy, internal standard), it was not
isolated from the crude mixture; following hydrolysis with citric
acid, the known diol 3 was isolated in 33% unoptimized yield
(Scheme 3).
In summary, we have reported the C−O bond cleavage of
benzofuran by a β-diketiminate-supported aluminum dihydride
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Scheme 2. Catalytic C−O Bond Functionalization of
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Scheme 3. Ring Expansion of 2 with Benzaldehyde
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formal two-electron redox process at a main-group element
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metal catalyst. The reaction is highly chemoselective, and
benzofuran reacts preferentially in the presence of dibenzofuran
or saturated/unsaturated cyclic ethers. We are continuing to
study the mechanism and scope of this new C−O bond
transformation and expand the reactivity of the C−O bond
cleavage products reported herein.
ASSOCIATED CONTENT
* Supporting Information
■
S
Text, figures, tables, and CIF files giving full experimental
details and crystallographic data for 2 and 2/2-H2. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail for M.R.C.: m.crimmin@imperial.ac.uk.
■
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Author Contributions
†These authors contributed equally.
́
ac, N.;
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
We are grateful to Imperial College for funding a Ph.D.
studentship (A.E.N.) and the Royal Society for provision of a
University Research Fellowship (M.R.C.).
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