Frustrated Lewis pair-mediated C-O or C-H bond activation of ethers

Article abstract of DOI:10.1039/c4cc01922a

Protocols for the FLP-mediated transformation of ethers are presented. Distinct reaction pathways involving either C-O or C-H bond activation occur depending on the application of oxophilic B(C₆F₅) ₃ or hydridophilic trity

Full text of DOI:10.1039/c4cc01922a

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Frustrated Lewis pair-mediated C–O or C–H bond
activation of ethers†
Cite this: Chem. Commun., 2014,
50, 10038
Michael H. Holthausen,a Tayseer Mahdi,a Christoph Schlepphorst,b
Lindsay J. Hounjet,a Jan J. Weigand*b and Douglas W. Stephan*ac
Received 14th March 2014,
Accepted 15th July 2014
DOI: 10.1039/c4cc01922a
www.rsc.org/chemcomm
Protocols for the FLP-mediated transformation of ethers are pre- ring-opening reactions, using the Lewis acid B(C6F5)3 in the
sented. Distinct reaction pathways involving either C–O or C–H presence of silanes, to catalytically deoxygenate carbohydrates.8
bond activation occur depending on the application of oxophilic
B(C6F5)3 or hydridophilic tritylium ions as the Lewis acid.
Reactions of a variety of FLPs with cyclic ethers, THF in
particular, are well documented.6,7 The ring-opening of THF
was first described by Wittig and Ru¨ckert in 1950,9 who showed
The recent renaissance of main-group chemistry has been driven C–O bond scission by combination of the anion [Ph3C]ꢀ and
by the discovery that main-group compounds can be used in THF(BPh3) affording [Ph3C(CH2)4OBPh3]ꢀ. Subsequent reports
transformations that are typically the purview of transition metal have shown similar THF ring-opening reactions by phosphine/
complexes.1 In this context, frustrated Lewis pairs (FLPs), which ZrCl4(THF)4,10 and other transition metal Lewis acids based
are sterically encumbered Lewis acids and bases, have garnered on U,11 Sm,12 Ti13 Zr14 and Mn,15 as well as other main group
considerable interest due to their propensity to bind and activate systems, like Al Lewis acids16 and Te nucleophiles.17 Nonetheless,
a plethora of small molecules.2
A variety of O-based substrates including CO2, CO, alde- bases have drawn less attention.
reactions of acyclic ethers with combinations of Lewis acids and
hydes, ketones, isocyanates, enones and ynones have been
In the present manuscript, we describe the stoichiometric
shown to react stoichiometrically with intermolecular P/B FLPs reactions of differing FLPs with ethers. We demonstrate that
resulting in cooperative addition to the C–O multiple bonds.2 judicious choice of the components of the FLP altered the
Similarly, intramolecular P/B FLPs have been shown to bind chemistry observed. Selective routes to C–O bond activation
carbonyl fragments of ketones and aldehydes.2 The reactions of and unprecedented avenues to a-C–H bond activation in these
endiones with intermolecular P/B systems were shown to result substrates are described.
in a 1,4 addition product while the corresponding reaction
The intermolecular FLP, t-Bu3P and B(C6F5)3 reacts with an
of intramolecular FLPs results in cyclization to give an acetal equivalent of dibenzyl ether, (PhCH2)2O to effect heterolytic
derivative.3 Furthermore, such FLP combinations have also C–O bond cleavage yielding the salt (1) isolated in 86% yield
been shown to deprotonate alcohols yielding phosphonium- (Scheme 1). The 1H NMR spectrum reveals two distinct methylene
alkoxyborates.4 While the (Et2O)B(C6F5)3 adduct has been resonances, a singlet at 4.30 ppm assignable to a benzyloxy-
shown to act as an FLP activating H2,5 P/B FLPs react with borate anion and a doublet at 3.71 ppm with two-bond PH
THF to effect C–O bond cleavage resulting in its ring-opening.6 coupling of 13 Hz attributable to the benzyl-phosphonium
Such FLP ring-openings have also been applied to a number of moiety. Collectively, the heteronuclear NMR spectroscopy,
7
´
other ethers including dioxane, thioxane, and lactides. Gagne elemental analysis and X-ray crystallography are consistent
and co-workers have exploited related C–O bond cleavage and with the formulation of 1 as [t-Bu3PCH2Ph][PhCH2OB(C6F5)3].
The new B–O and P–C bond distances of 1.457(4) and 1.896(3) Å
in 1 are typical (Fig. 1).
a Department of Chemistry, University of Toronto, 80 St. George Street, Toronto,
The corresponding reaction of cyclohexyl-vinyl ether with the
P/B FLP gives the salt (2) which was isolated in 80% yield. The
formation of the phosphonium cation [t-Bu3PH]+ was confirmed
by the diagnostic doublet in the 1H NMR spectrum at 5.05 ppm
(1JPH = 427 Hz). Furthermore, the 11B NMR spectrum showed a
sharp singlet at ꢀ3.45 ppm. These data, together with the
resonances in the 19F NMR spectrum, support the presence of
Ontario, Canada M5S 3H6. E-mail: dstephan@chem.utoronto.ca
b
¨
Institut fur Anorganische Koordinationschemie, TU Dresden, 01062 Dresden,
Germany. E-mail: jan.weigand@tu-dresden.de; Fax: +49-351-83-33126
c Chemistry Department, Faculty of Science, King Abdulaziz University (KAU),
Jeddah 21589, Saudi Arabia
† Electronic supplementary information (ESI) available: Synthetic and spectro-
scopic details. CCDC 991775–991782. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c4cc01922a
10038 | Chem. Commun., 2014, 50, 10038--10040
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Fig. 2 POV-ray depiction of the cation of 4. C: black, P: orange, hydrogen
atoms on phenyl and t-Bu groups are omitted for clarity.
Scheme 1 Reaction of ethers with the FLP t-Bu3P/B(C6F5)3.
short C6–C7 and C4–C3 bond distances of 1.332(3) Å and
1.329(3) Å, the C1–C2 bond length of 1.364(3) Å and the sum of
angles at C1 of 359.9(6)1. The P–C5 bond distance of 1.837(2) Å is
shorter than the P–Ctrityl bond length in phosphonium ions of the
type [R3PCPh3]+ (av. 1.876(4) Å, see ESI†),18 consistent with the
diminished steric crowding in 4. It is noteworthy that the corre-
sponding reactions of R2PH (R = Ph, Cy) led to the formation of
cations of type R2PHCPh3+ (see ESI†), illustrating the impact of steric
demand of the phosphine. These latter species are unreactive with
ethers. Analogues of 4 have been spectroscopically observed, how-
ever, to the best of our knowledge, compound 4 represents the first
structurally characterized cyclohexadienyl-phosphonium cation.19
Despite the formation of this phosphonium-cyclohexadienyl
cation in 4, this species behaves as an FLP which reacts with a
range of ethers (Scheme 2).
Fig. 1 POV-ray depiction of 1. C: black, P: orange, O: red, F: pink, B: yellow-
green, hydrogen atoms have been omitted for clarity.
Reacting 4 with THF or THF-d8 yielded the 2-tetrahydrofuranyl-
substituted phosphonium ions 5 or 5-d7 in quantitative yield. An
additional competition reaction containing THF and THF-d8
the [C6H11OB(C6F5)3]ꢀ anion and thus the formulation of 2 as indicates that the dissociation of FLP 4 to [Ph3C]+ and t-Bu2PH is
[t-Bu3PH][C6H11OB(C6F5)3] with the concurrent loss of acetylene the rate determining step in the reaction sequence with ethers
(Scheme 1). The analogous product [t-Bu3PH] [( p-C6H4F)OB(C6F5)3] (see ESI† for additional information). Subsequently, abstraction of
(3) was obtained in 88% isolated yield from the reaction of hydride by [Ph3C]+ from the a-carbon atom of the respective ether
4-fluorophenyl tert-butyl ether with t-Bu3P and B(C6F5)3 (Scheme 1). generates a transient oxonium ion which is intercepted by t-Bu2PH.
In this case, the reaction proceeds with the liberation of isobutylene The FLP 4 slowly isomerizes in solution to compound 40 (see ESI†
(see ESI†).
for details on the mechanism of the isomerization and full char-
The formation of compounds 1–3 is thought to proceed by acterization of 40). Reacting 4 with varying amounts of Et2O showed
initial coordination of the ether to the oxophilic Lewis acid that large ether concentrations favour the C–H bond activation
B(C6F5)3. This is followed by subsequent nucleophilic attack of pathway. The respective phosphonium ion salt 6 was obtained
the Lewis base at the a-carbon leading to alkylation of P or almost quantitatively when 20 equivalents of Et2O were employed.
alternatively deprotonation of the b-carbon atom (Scheme 1). Although Bn2O and tetrahydropyran derivatives were successfully
In either case this is accompanied by the heterolytic cleavage of converted to compounds 7–9, these reactions were accompanied by
a C–O bond.
the formation of considerable amounts of 40. Finally, tetrahydro-
We were interested in probing the impact of less oxophilic thiophene, diethyl sulfide and N-methyldiphenylamine are con-
Lewis acids on the reactivity of FLPs with ethers. To that end, verted to phosphonium ion salts 10–12 in moderate yields
we first considered the combination of the Lewis acid [Ph3C][X] showing that the scope of this synthetic protocol also includes
(X = OSO2CF3 or B(C6F5)4) and the Lewis base t-Bu2PH. Initial thioethers and amines.
combination of these reagents gave the salt [t-Bu2PH-(C6H5)CPh2][X]
4 which was isolated in almost quantitative yield (96% for the preparation of functionalized phosphines. Thus mixtures
X = OSO2CF3). containing the OSO2CF3-salts of 5–7 were prepared and treated
It was of interest to investigate if this method is suitable for
While the NMR data for 4 is consistent with the formulation with t-BuOK (Scheme 3). This resulted in deprotonation of the
of a phosphonium ion featuring a cyclohexadienyl-substituent phosphonium ions and afforded the respective phosphines
(see ESI†), this was further confirmed by X-ray crystallography 13–15 which could be isolated by distillation in satisfying yields
(Fig. 2). The cyclohexadienyl-moiety of 4 is evidenced by the on a multi-gram scale.
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reacts with ethers via hydride abstraction and instalment of a
phosphoniumyl-substituent on an a-carbon atom. This reaction
constitutes a rare example of FLP-mediated C–H bond activation.20
While previous studies have illustrated the ability of FLPs to effect
both ether C–O and aromatic20b or allylic20a C–H activations, the
present results are the first to demonstrate that judicious selection
of the Lewis acid/base composition of an FLP provides an avenue for
selective reactivity of one class of substrates. We are currently
exploring the impact of varying the Lewis acid in the reactivity of
FLPs with other substrates and on catalysis.
NSERC of Canada, the German Science Foundation (DFG,
WE 4621/2-1) and the ERC (SynPhos 307616) is thanked for
financial support. DWS is grateful for the award of a Canada
Research Chair. TM is grateful for an NSERC CGS-D. MHH
is grateful for a scholarship by the Fonds der Chemischen
Industrie.
Notes and references
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Scheme 2 Isomerization of FLP 4 to 40; equilibrium dissociation of 4 to
[Ph3C][X] and t-Bu2PH and compounds 5–12 obtained in the reaction of
FLP 4 with (thio)ethers. X = OSO2CF3 or B(C6F5)4. a Yield determined by
integration of all resonances in the 1H and 31P NMR spectra of the reaction
mixture. b Isolated yield. c Obtained as the free phosphine.
´
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In conclusion, we have uncovered distinct reaction pathways
for the FLP-mediated transformation of ethers. Oxophilic B(C6F5)3
reacts via coordination to the oxygen donor and initiates reaction
sequences which involve heterolytic C–O bond cleavage. In contrast,
the FLP system 4, which is based on a hydridophilic tritylium ion,
10040 | Chem. Commun., 2014, 50, 10038--10040
This journal is ©The Royal Society of Chemistry 2014