Unprecedented organocatalytic reduction of lignin model compounds to phenols and primary alcohols using hydrosilanes

Article abstract of DOI:10.1039/c3cc47655c

The first metal-free reduction of lignin model compounds is described. Using inexpensive Et₃SiH, PMHS and TMDS hydrosilanes as reductants, α-O-4 and β-O-4 linkages are reduced to primary alcohols and phenols under mild conditions using B(C₆F₅)₃ as an efficient catalyst. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3cc47655c

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Unprecedented organocatalytic reduction of
lignin model compounds to phenols and primary
alcohols using hydrosilanes†
Cite this: Chem. Commun., 2014,
50, 862
Received 5th October 2013,
Accepted 12th November 2013
Elias Feghali and Thibault Cantat*
DOI: 10.1039/c3cc47655c
www.rsc.org/chemcomm
The first metal-free reduction of lignin model compounds is described.
Using inexpensive Et3SiH, PMHS and TMDS hydrosilanes as reductants,
a-O-4 and b-O-4 linkages are reduced to primary alcohols and phenols
under mild conditions using B(C6F5)3 as an efficient catalyst.
While 98% of organic chemicals currently derive from fossil
carbon feedstocks, the utilization of renewable carbon sources
has been identified as one of the major challenges facing the
chemical industry for the next decades.1 In this context, CO2 and
biomass are attractive alternatives to oil and gas, for the produc-
tion of chemicals.2 Yet, these renewable feedstocks have a lower
carbon/oxygen ratio than petrochemicals and their reduction is
therefore required to increase their energy content and promote
their deoxygenation.3 In particular, lignin results from the radical
polymerization of the p-coumaryl, coniferyl and sinapyl alcohols
and the catalytic depolymerization of this complex biopolymer
by reduction of the ether linkages would offer an attractive source
Fig. 1 Representative structure of
models of the a-O-4 and b-O-4 linkages utilized in this study.
a lignin fragment and molecular
of aromatics (Fig. 1).4 The homogeneous catalytic reduction of using stoichiometric amounts of alkoxide salts with Et3SiH.9
biomass-based compounds is therefore attracting increased atten- Herein, we report the first organocatalytic reduction of lignin
tion.5 In this regard, hydrosilylation appears as an attractive model compounds. The methodology utilizes inexpensive hydro-
alternative to hydrogenation strategies to achieve the selective silanes as reductants, with B(C6F5)3 as the organic catalyst.
reduction of the strong C–O ether bond under mild reduction
Although the exact structure of lignin depends on its origin,
conditions. Indeed the slightly polar and weaker Si–H bond it is already recognized that ether functional groups represent about
(bond dissociation energy (BDE) of 92 kcal molꢀ1 in SiH4) is two-thirds of its linkages. Typically, hardwood lignin contains 60%
easier to activate than the strong non-polar H–H bond (BDE of b-O-4 and 5–10% a-O-4 linkages, while 5-50, 4-O-5 and b–b groups
104 kcal molꢀ1).6 In fact, the Lewis acid B(C6F5)3 is a potent represent the remaining linkages (Fig. 1).10 The reduction of benzyl-
catalyst for the reduction of carbonyl derivatives, alcohols and phenylether (1), a model for the a-O-4 linkage, was first undertaken,
ethers.7,8 Nonetheless, the utilization of this methodology is mostly using Et3SiH. Catalyst B(C6F5)3 promotes the complete reduction
limited to synthesis of organic chemicals and its potential has not of 1 within 2 h, at 25 1C, with a low loading of 2 mol% and using
been explored for the reduction of poly-functional substrates such 1 equiv. of Et3SiH (eqn (1)). As expected from the seminal work
as lignin. Recently, the C–O bond cleavage in aryl-ether derivatives of the Piers and Gevorgyan groups, the alkyl–O bond in 1 is
relevant to lignin reductive depolymerization has been explored, selectively reduced while the aryl–O bond is left untouched,
leading to the formation of phenoxysilane 2 and toluene, in
60% yield.7 Interestingly, under these electrophilic conditions,
CEA, IRAMIS, SIS2M, CNRS UMR 3299, CEA/Saclay, 91191 Gif-sur-Yvette, France.
mono- and bis-benzylated phenoxysilanes (3) are formed in 40%
E-mail: thibault.cantat@cea.fr; Fax: +33 1 6908 6640; Tel: +33 1 6908 4338
yield, resulting from Friedel–Crafts like alkylation.11 Noticeably,
† Electronic supplementary information (ESI) available: General experimental
when a model of the b-O-4 linkage (4) is utilized, this methodology
also allows the complete reduction, with a very high selectivity.
details, synthetic procedures, data for novel compounds and computational
details. See DOI: 10.1039/c3cc47655c
862 | Chem. Commun., 2014, 50, 862--865
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In fact, 4a is reduced to phenylethane and 2 in 94% yield and the
formation of Friedel–Crafts products is reduced significantly (6% 6a)
(eqn (2)). 4b, a model for the coniferyl derivative of 4a, is reduced
similarly to phenylethane and silylated catechol 5b in 94% yield, the
additional methoxy group being reduced to methane under the
applied conditions (eqn (2)).
(1)
Scheme 1 Proposed pathways for the reduction of 7a to 2a and 8.
(2)
(3)
(4)
Though 4a is a popular model for the b-O-4 linkage in lignin, it
features a low degree of functionality which may not be fully
representative of the outcome of the reaction. Moreover, the
B(C6F5)3 catalyzed hydrosilylation of ethers has been mostly limited
to molecules with no additional functional groups. The reduction of
model 7, featuring an hydroxyl group at the a position, was therefore
carried out, using Et3SiH (3 equiv.) and 2 mol% B(C6F5)3, at RT.
The reduction of alcohols using the hydrosilane–B(C6F5)3 system is
well documented and occurs under conditions similar to ethers.7
Nonetheless, while the ether linkage is cleaved in 7 to afford the
phenoxysilane derivatives 2 and 5b, the hydroxyl function is main-
tained and 8 is obtained in >94% yield after 2 h at RT. Hydrolysis of 8
affords the corresponding phenol and 2-phenylethanol in 66%
isolated yield (see ESI†). While primary alcohols are generally more
reactive than secondary alcohols, including in hydrosilylation chem-
istry, the selective formation of 8 from the polyfunctional substrate 7
is surprising.7 Two pathways, depicted in Scheme 1, may account for
this reaction chemistry. Both routes share the first dehydrogenative
silylation of the O–H bond in 7a to afford 9a, which was observed
experimentally (see ESI†). Electrophilic activation of Et3SiH by the
Fig. 2 Computed pathways for the conversion of 10a+ to 11a+ and 12a+.
the two pathways, isotopic labeling studies were conducted.
Reduction of 7a with Et3Si-D affords 8-D1 with a deuterium atom
at the a position, therefore ruling out the involvement of 11a+ in
the rearrangement of 10a+ (eqn (5)).
(5)
(6)
borane catalyst, in the presence of 9a, leads to the [10a+, HB(C6F5)3ꢀ
]
ion pair.12 Cation 10a+ may either evolve into a cationic epoxide 11a+
(route A) or undergo a semipinacol rearrangement (via 12a+, route B)
prior to its reduction to 8a. DFT calculations were carried out so as to
examine the kinetics involved in each path (Fig. 2). Interestingly, both
kinetics and thermodynamics favor the semipinacol rearrangement,
(7)
Importantly, complete reduction of 7 to phenylethane and 5
with an activation enthalpy of 14.2 kcal molꢀ1 (vs. 18.2 kcal molꢀ1 is feasible and achieved quantitatively in the presence of
for route A). Given the low activation energy difference between 10 mol% B(C6F5)3 and an excess Et3SiH (4 equiv.), after 16 h
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at RT (eqn (6)). This transformation shows that a protected primary
alcohol accumulates at short reaction times, from the hydrosilylation
of 7, which can be further deoxygenated after prolonged reaction
times. The formation of a primary alcohol was also observed from the
more realistic model molecule 13a. Indeed, hydrosilylation of the a,g-
hydroxylated model 13a with Et3SiH provides the bis-silylated alcohol
14a in quantitative yield after 16 h at RT (eqn (7)). Again, the
formation of 14a results from a semipinacol rearrangement, which
was established through labeling studies (eqn (8) and (9)). The
reduction of 13a-D2, featuring two deuterium atoms at the g position,
to 14a-D2 shows that the phenyl ring migrates (eqn (8)), while the
reduction of 13a to 14a-D1 with Et3SiD confirms that the a position is
the reduction site (eqn (9)). It is noteworthy that 14a exhibits a
low reactivity towards reduction and only small amounts of
1-phenylpropane (E21%) were observed after 32 h at RT, in the
presence of an excess Et3SiH (8 equiv.) and 15 mol% B(C6F5)3.
Polymethylhydrosiloxane (Me3Si(OSiMeH)nOSiMe3, PMHS) and
tetramethyldisiloxane (Me2SiHOSiHMe2, TMDS) are especially attrac-
tive reductants for further development of this methodology. Indeed,
these hydrosilanes are by-products of the silicone industry and are
cost-efficient (2–5 h per mole), non-toxic and moisture stable.13
Additionally, the oxidation of TMDS provides a source of methicones,
which are useful compounds in cosmetics.14 Replacing Et3SiH with
PMHS or TMDS allows the complete reduction of 1, 4a,b, 7a,b and
13a,b (eqn (10)–(12) and Fig. S1–S3 in the ESI†). Importantly, TMDS is
able to completely reduce 13a to 1-phenylpropane (eqn (12)). In
contrast, 14a is obtained as the end-product with Et3SiH (eqn (7)).
This increased reactivity is attributed to the proximity of the two
hydrides in TMDS, which facilitates the reduction of the C–O bonds.
The catalytic activity of B(C6F5)3 is maintained in the presence of
water, as H2O is readily dehydrogenated. In fact, eqn (12) can be
conducted successfully in the presence of water (10 mol%) with 16
equiv. TMDS to obtain 15a in quantitative yield.
(12)
In summary, we have reported the first organo-catalytic
reduction of lignin model compounds. B(C6F5)3 is a potent
catalyst for the selective reduction of a-O-4 and b-O-4 linkages
to phenol derivatives, via hydrosilylation. Active hydrosilanes
include inexpensive and air stable PMHS and TMDS. Depending
on the reductant, primary alcohol derivatives can be obtained
selectively. Their formation is shown to involve a semipinacol
rearrangement, based on DFT calculations and labeling studies.
Further work will focus on extending this methodology to
natural lignin.
For financial support of this work, we acknowledge the
CEA, CNRS and the CHARMMMAT Laboratory of Excellence.
T.C. thanks the Fondation Louis D. – Institut de France for its
formidable support.
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