Metal-Free Catalytic Reductive Cleavage of Enol Ethers

Article abstract of DOI:10.1021/acs.orglett.8b02932

In contrast to the well-known reductive cleavage of the alkyl-O bond, the cleavage of the alkenyl-O bond is much more challenging especially using metal-free approaches. Unexpectedly, alkenyl-O bonds were reductively cleaved when enol ethers were reacted with Et₃SiH and a catalytic amount of B(C₆F₅)₃. Supposedly, this reaction is the result of a B(C₆F₅)₃-catalyzed tandem hydrosilylation reaction and a silicon-assisted β-elimination. A mechanism for this cleavage reaction is proposed based on experiments and density functional theory (DFT) calculations.

Full text of DOI:10.1021/acs.orglett.8b02932

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Metal-Free Catalytic Reductive Cleavage of Enol Ethers
Karina Chulsky and Roman Dobrovetsky*
School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel
S
* Supporting Information
ABSTRACT: In contrast to the well-known reductive cleavage of the alkyl−
O bond, the cleavage of the alkenyl−O bond is much more challenging
especially using metal-free approaches. Unexpectedly, alkenyl−O bonds were
reductively cleaved when enol ethers were reacted with Et3SiH and a
catalytic amount of B(C6F5)3. Supposedly, this reaction is the result of a
B(C6F5)3-catalyzed tandem hydrosilylation reaction and a silicon-assisted β-
elimination. A mechanism for this cleavage reaction is proposed based on experiments and density functional theory (DFT)
calculations.
he activation of alkenyl−O bonds is of great interest in
We first reacted EtOC(H)CH2 (2) with Et3SiH and 1 (1
mol %) in C6H6 at rt. Almost immediately gas formation was
observed. 1H NMR analysis revealed clean formation of
Et3SiOEt and H2CCH2 (3) (Table 1, entry 1). The
formation of these products was rather surprising since it
implied that the reductive cleavage of a more robust vinyl
group had occurred and not the expected cleavage of the ethyl
group.5−8
T
synthetic organic chemistry, where it is often used in
cross-coupling reactions.1 The reductive cleavage of enol
ethers has also garnered attention due to their presence in
crude oil distillates and potential biofuels such as lignin.2 Since
the seminal work of Wenkert in 1979, in which the alkenyl
group was reductively cleaved from enol ethers by i-PrMgBr in
the presence of Ni-based catalysts (Figure 1A),3 few other Ni-
To study this reactivity further, we tried other alkyl enol
ethers in this reaction. Thus, reactions of ROC(H)CH2 (R
= i-Bu (4), Cy (5), Ph (6), Cl(CH2)2 (7), and Me3SiO-
(CH2)2O(CH2)2 (8)) all led to cleavage of the vinyl group
(Table 1, entry 1). In EtOC(Me)CH2 (9) the cleavage of
the propenyl group (10) occurred (Table 1, entry 2). The
cleavage of MeOC(Me)CH2 (11) was not as selective and
yielded CH4, MeOSiEt3, and Et3SiOCH(CH3)CH2SiEt3 (12)
as the major products (eq 1).
Figure 1. Catalytic reductive cleavage of enol ethers.
based catalysts have been found to activate these bonds.1
Remarkably, Johnson very recently reported a Ni hydride
complex, which was capable of dismantling vinyl ethers.4 In
contrast, the catalytic reductive cleavage of an alkenyl group from
enol ethers, using a main group based catalyst, has never been
reported. Alkyl−O bonds, however, are readily cleaved by
catalytic metal-free methods. In 2000, Gevorgyan reported the
B(C6F5)3 (1) catalyzed cleavage of dialkyl ethers by hydro-
silanes.5 Later, this chemistry was used in the deoxygenation of
carbohydrates and polyols6 and in functional group manipu-
lations.7 We recently reported selective chlorination of Si−H
bonds using this reactivity.8
Herein we report the B(C6F5)3-catalyzed reductive cleavage
of an alkenyl group from enol ethers using Et3SiH (Figure 1,
B). A mechanism for this cleavage is proposed based on
experiments and DFT calculations that involves an unprece-
dented B(C6F5)3-catalyzed silicon-assisted β-elimination9 of an
alkoxysilane from the ether adducts with a silyl substituent β to
oxygen.
The formation of these products could be explained by a
number of processes taking place simultaneously, such as
methyl and propenyl group cleavage and hydrosilylation of the
CC double bond in 11. The difference in the reactivity
between 9 and 11 is not surprising since the cleavage of dialkyl
ethers is strongly influenced by sterics.5,6
However, when 11 was reacted with 2 equiv of Et3SiH and 1
(1 mol %) in C6H6, 12 was formed cleanly and, after heating,
gave propylene and (Et3Si)2O (Table 1, entry 2). Interestingly,
the same reaction in CH2Cl2 led to the cleavage products
directly without heating. Silyl enol ethers were also tested in
this reaction. Thus, the reaction with 1-(trimethylsilyloxy)-
cyclopentene (13) led to cleavage of the cyclopentenyl group
Received: September 13, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b02932
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Organic Letters
Letter
The accepted mechanism for ether cleavage by hydrosilanes
in the presence of 1 relies on the formation of a R3Si−H−
B(C6F5)3 intermediate (32).10 The silicon center in 32 is then
attacked by the oxygen of the R′2O leading to [R′2OSiR3]-
[HB(C6F5)3] salt (33).5,6 Afterward, the hydride of the
HB(C6F5)3 in 33 substitutes the R′ group at the oxygen
center via an SN2-type reaction giving the ether cleavage
products.5,6 While this mechanism can explain the alkyl−O
bond cleavage,5,6 it does not, however, explain the cleavages of
the alkenyl groups (Table 1, entries 1−6). An SN2 reaction in
the last step of this mechanism is hardly possible in these cases
due to the development of δ+ at the sp2 carbon, which is
strongly disfavored.
Table 1. B(C6F5)3-Catalyzed Cleavage of the Alkyl/Silyl
Enol Ethers
Therefore, based on the experimental findings, we propose a
different mechanism for the alkenyl group cleavage. We believe
that in our case the nucleophilic CC double bond of 34
attacks the Si center in 32, and dissociation of the Si−H bond
leads to a [Et3SiCH2C(R)O−R′][HB(C6F5)3] salt (35).
Intermediate 35 then reacts further through the delivery of the
hydride from HB(C6F5)3 to the electrophilic CO+−Et
moiety of the cation in 35 giving the hydrosilylation product,
Et3SiCH2CH(R)OR′ (36). This step is supported by the fact
that we see the formation of 12 in the reaction of 11 (see eq
1). Noteworthy, hydrosilylation of silyl enol ethers was
previously reported.11 We believe that the last step is the
silicon-assisted β-elimination, promoted by 1, that leads to the
reaction products, H2CC(R)H and R′OSiEt3 (Scheme 1).
Scheme 1. Proposed Mechanism for B(C6F5)3-Catalyzed
Reductive Cleavage of Enol Ethers by Et3SiH
Overall, our proposed mechanism (Scheme 1) involves a
sequence of addition/elimination reactions, which resembles
the nucleophilic vinylic substitution (SNV) type reaction,12
where the EtO− is the nucleofuge and H− is the nucleophile.
However, unlike typical SNV reactions that work on electron-
poor CC double bonds,12 in our case the electron-rich C
C double bond reacts to give the substitution products. To
support this hypothesis, Et3SiD, 2, and 1 (1 mol %) were
reacted and led to H2CC(D)H and Et3SiOEt (eq 2). This
supports our suggestion that the EtO− group is replaced by
H−/D− originating from Et3SiH/D.
a
b
c
Reaction works better in CH2Cl2. NMR yields. 2 equiv of Et3SiH
d
was used. Works better with 5% of 1.
(14) (Table 1, entry 3). Alkenyl groups in silyl enol ethers
bearing bulky alkyl groups (R = Cy (15), Oc (16)) were also
cleaved, but much less efficiently (Table 1, entry 4). The
terminal CC double bond in the cleavage product of 16
partially isomerized to an internal position. Interestingly, the
cleavage of silyl enol ethers substituted by aryls led not only to
olefins but also to vinylsilanes (Table 1, entries 5 and 6). In the
case of 20a, 20b, and 20c (Table 1, entry 5), polymerization of
the obtained olefins occurred. Noteworthy, in large-scale
experiments, the polymerization process was even more
pronounced, and the formation of vinylsilanes was diminished.
EtOC(H)C(H)Me (28) and EtOC(H)C(H)Et (29)
reacted with Et3SiH and 1 (1 mol %) differently than 2−9,
giving solely the cleavage of the Et−O bond (Table 1, entry 7).
The difference in the reactivity between 28, 29, and 2−11
means that the substitution at the terminal position of the C
C double bond plays a crucial role in the outcome of the
reaction (alkenyl vs alkyl cleavage).
To support the last step of the proposed mechanism, the
silicon-assisted β-elimination, we independently synthesized
Me3SiCH2CH2OR (R = Et (37),13 Me3Si (38)14) which are
the analogs of 36 and 12, respectively. Heating both 37 and 38
did not result in any reactivity. However, when 37 and 38 were
mixed with 1 equiv of 1 in C6H6 the olefination reaction took
place immediately leading to Me3SiOR (R = Et or SiMe3,
B
DOI: 10.1021/acs.orglett.8b02932
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Organic Letters
Letter
respectively) and ethylene (3) (eq 3), supporting our
suggestion regarding the last step of the proposed mechanism
(Scheme 1). The same reaction with a catalytic amount of 1
also works but requires heating to 80 °C.
To understand this silicon-assisted β-elimination we
performed a DFT calculation at the BP86(D3)/def2-SVP15
level of theory of the reaction shown in eq 3 in C6H6 using a
polarizable continuum model (PCM).16 Based on these
calculations, we believe that this elimination proceeds in a
two-step mechanism. The first step is the cleavage of the C−O
bond in 37−B(C6F5)3, which leads to salt 39 (Scheme 2) with
Scheme 2. Calculated Mechanism for the B(C6F5)3-
Catalyzed Silicon-Assisted β-Elimination in C6H6 Using
a
PCM16
Figure 2. DFT calculation of the two possible reaction profiles for
ethyl vinyl ether cleavage (ethyl group cleavage (blue) and vinyl
group cleavage (red)) in C6H6 using PCM.16 Gibbs free energies are
given in kcal mol−1 relative to the starting materials.
a
ΔG is presented on the arrows in kcal mol−1.
Scheme 3. Possible Two Mechanistic Paths for the Cleavage
of 14 by Et3SiH
the ΔG = +12.8 kcal mol−1. Notably, β-silyl-substituted
carbocations (analogous to 39) were synthesized previously.17
In addition, the fact that the cleavage of 9 (Table 1, entry 8) in
CH2Cl2 proceeds directly without heating also supports the
assumption that an intermediate ion pair of type 39 is formed
in this reaction. Noteworthy, a similar reactivity is obtained for
38, which in CH2Cl2 undergoes olefination at rt in the
presence of 1 (10 mol %). The calculated energy barrier for the
cleavage of [EtOB(C6F5)3]− anion from 37−B(C6F5)3 (TS5)
is +21.0 kcal mol−1 (Figure 2). The last step of the proposed
mechanism is the release of ethylene, formation of Me3SiOEt,
and regeneration of 1 and is an irreversible and strongly
exergonic step (ΔG = −32.3 kcal mol−1).
Accordingly, the formation of an intermediate of type 39′
also explains the formation of vinylsilanes in the reactions of
aryl-substituted silyl enol ethers (Table 1, entries 5 and 6). For
example, the formation of 22a in the reaction of 20a (Table 1,
entry 5) could be explained by the reaction of the anion
[Me3SiOB(C6F5)3]− in 39′, which could act either as a
nucleophile leading to styrene and Et3SiOSiMe3 via
desilylation reaction (Scheme 3, path a) or as a base,
abstracting the proton from the carbon α to the carbocation
leading to 22a (Scheme 3, path b).
Finally, to compare the cleavages of the alkyl group vs
alkenyl group in alkyl enol ethers, we performed a DFT
calculation using the same level of theory on both possible
reactions of ethyl vinyl ether (2) with Me3SiH and 1 in C6H6
using PCM.16 According to these calculations, the formation of
adduct 32 is exergonic (ΔG = −3.1 kcal mol−1). The first
pathway (Figure 2, blue), the attack of the nucleophilic oxygen
atom of 2 at the silicon center in 32 producing [Et(CH2CH)-
OSiMe3][HB(C6F5)3] (33′), is endergonic (ΔG = +14.0 kcal
mol−1) with an energy barrier of +20.6 kcal mol−1 (TS1). The
reaction of the hydride in [HB(C6F5)3]− with [Et(CH2CH)-
OSiMe3]+ in 33′ leading to the formation of ethane, vinyl silyl
ether, and regeneration of 1 is exergonic with ΔG of −34.0 kcal
mol−1, and the ΔG⧧ for this step is 18.5 kcal mol−1 (TS2). In
the second pathway (Figure 2, red), the nucleophilic attack of
the silicon center in 32 by CC double bond of 2 leading to
[EtOCHCH2SiMe3][HB(C6F5)3] (35′) is endergonic with
ΔG = 9.1 kcal mol−1, and ΔG⧧ for this step is 14.5 kcal mol−1
(TS3). The delivery of hydride from [HB(C6F5)3]− to [EtO
CHCH2SiMe3]+ in 35’ leading to a hydrosilylation product
37−B(C6F5)3 is exergonic (ΔG = −6.7 kcal mol−1) with no
activation barrier (TS4). The olefination, from 37−B(C6F5)3,
occurs in a two-step reaction via intermediate 39, as was shown
previously (Scheme 2), with ΔG = −26.2 kcal mol−1.
Overall, the cleavage of the vinyl group (Figure 2, red) is less
exergonic than the cleavage of the ethyl group (Figure 2, blue)
(−26.2 vs −34.0 kcal mol−1, respectively). However, the rate-
determining state (RDS)18 TS3 (Figure 2, red) is 6.1 kcal
mol−1 lower than TS1 (Figure 2, blue). We, therefore, believe
that the cleavage of the vinyl group is a kinetically driven
process. This also explains the reactivity of 28 and 29 (Table 1,
entry 7) where the thermodynamic process took over the
kinetic one, i.e., Et−O bond cleavage (Figure 2, blue), due to
C
DOI: 10.1021/acs.orglett.8b02932
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Letter
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reductively cleaved from alkyl/silyl enol ethers catalytically by
hydrosilanes and catalytic amounts of B(C6F5)3. We suggest
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silicon-assisted β-elimination of the ROSiEt3. This reactivity
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b02932.
Full experimental data, including synthetic procedures,
characterization data, and NMR spectra (PDF)
̈
A. Y.; Hurmalainen, J.; Mansikkamaki, A.; Piers, W. E.; Tuononen, H.
M. Nat. Chem. 2014, 6, 983−988.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: rdobrove@tau.ac.il.
ORCID
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Roman Dobrovetsky: 0000-0002-6036-4709
Notes
The authors declare no competing financial interest.
́
993−1003. (f) Fernandez, I.; Bickelhaupt, F. M.; Uggerud, E. J. Org.
ACKNOWLEDGMENTS
We are thankful to the Tel Aviv University for supporting this
research.
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DEDICATION
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Dedicated to Prof. Doug Stephan on the occasion of his 65th
birthday.
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