Molybdenum-Catalyzed Stereospecific Deoxygenation of Epoxides to Alkenes

Article abstract of DOI:10.1002/adsc.201600840

Mild and simple catalytic systems consisting of molybdenum(VI) dichloride dioxide [MoO₂Cl₂] as a catalyst and a phosphine as reductant have been developed for the stereospecific deoxygenation of epoxides to alkenes. The reactions using 1,2-bis(diphenylphosphino)ethane (dppe) and triphenylphosphine (PPh₃) proceed with retention and inversion of stereochemistry, respectively. The mild reaction tolerates the presence of various functional groups and affords stereodefined substituted olefins in good yields. (Figure presented.).

Full text of DOI:10.1002/adsc.201600840

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DOI: 10.1002/adsc.201600840
Very Important Publication
Molybdenum-Catalyzed Stereospecific Deoxygenation of
Epoxides to Alkenes
Sobi Asako,a,* Takahisa Sakae,a Masahito Murai,a and Kazuhiko Takaia,*
a
Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University,
3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan
E-mail: asako@cc.okayama-u.ac.jp or ktakai@cc.okayama-u.ac.jp
Received: July 29, 2016; Revised: October 11, 2016; Published online: && &&, 0000
Supporting information for this article can be found under: http://dx.doi.org/10.1002/adsc.201600840.
Abstract: Mild and simple catalytic systems consist-
ing of molybdenum(VI) dichloride dioxide
[MoO2Cl2] as a catalyst and a phosphine as reduc-
tant have been developed for the stereospecific de-
oxygenation of epoxides to alkenes. The reactions
using 1,2-bis(diphenylphosphino)ethane (dppe) and
triphenylphosphine (PPh3) proceed with retention
and inversion of stereochemistry, respectively. The
mild reaction tolerates the presence of various func-
tional groups and affords stereodefined substituted
olefins in good yields.
systems for the stereospecific deoxygenation of epox-
ides, including unactivated aliphatic epoxides, that
proceed under mild conditions to afford stereodefined
substituted olefins. Attractive features include the use
of an abundant and inexpensive molybdenum com-
plex as a catalyst,[8] good functional group compatibil-
ity, and the control of stereochemistry by the appro-
priate choice of reaction conditions.
We commenced our investigation with the deoxyge-
nation of cis-1,6-diphenyl-3-hexene oxide (1a) in the
presence of MoO2Cl2 as a catalyst and various phos-
phine reductants, because similar catalytic systems
were known to be effective for the deoxygenation of
sulfoxides, N-oxides, and nitro compounds.[4a,9] After
extensive experimentation, we established two com-
plementary reaction conditions that stereospecifically
afford (Z)- and (E)-1,6-diphenyl-3-hexene (2) with re-
tention and inversion of stereochemistry, respectively.
Keywords: molybdenum; deoxygenation; epoxides;
alkenes; stereospecific process
While the epoxidation of olefins has been extensively Thus, the deoxygenation of cis-epoxide 1a proceeded
studied and has found many applications in organic with stereoretention to afford Z-olefin 2a using 1,2-
synthesis,[1] the reverse reaction, deoxygenation of ep- bis(diphenylphosphino)ethane (dppe) as a reductant
oxides, has not received much attention despite its po- [Eq. (1)], while 1a was converted to E-olefin 2b with
tential utility for the stereoselective synthesis of mul- stereoinversion using PPh3 as a reductant [Eq. (2)].
tisubstituted olefins.[2] Preceded by the extensive de-
We found that the yield and stereochemical out-
velopment of a variety of stoichiometric reducing come of the reaction depend strongly on the structure
agents since the early 1950s,[3] significant advances
have recently been made in the catalytic deoxygena-
tion of epoxides, among which the reactions in the
presence of a catalytic amount of oxorhenium com-
plexes and various reductants are particularly note-
worthy.[4,5,6] However, the reactions have several draw-
backs such as limited substrate scope (e.g., only effec-
tive for styrene oxides and cycloalkene oxides) or
poor chemo- and stereoselectivity. On the other hand,
we recently reported a general and practical method
for the stereoretentive deoxygenation of epoxides
under rhenium catalysis.[7] Nevertheless, the low avail-
ability of rhenium still remains a major issue to be ad-
dressed with the growing demand for sustainability.
Herein we report simple molybdenum-based catalytic
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of the phosphines, but in a rather unpredictable fash- could not improve the product yield with tris(2-furyl)-
ion (Table 1). Thus, while dppe stereoretentively af- phosphine as a reductant, the inversion ratio with
forded the Z-olefin 2a from the cis-epoxide 1a PPh3 was improved by increasing the reaction concen-
(entry 2), the reactions using related bidentate phos- tration,[10] which was instead accompanied by a de-
phines with different backbones resulted in the forma- crease in the product yield because of the formation
tion of a mixture of the stereoisomers (entries 1, 3–5). of 1,6-diphenylhexan-3-one via Lewis acid-promoted
The deoxygenation reactions with monodentate phos- ring-opening rearrangement (entries 7 and 8).[11] The
phines with various electronic and steric properties side reaction could be suppressed by performing the
took place with low yield and stereoselectivity in reaction with 3 equiv. of PPh3 in concentrated 1,4-di-
most cases, but the reactions with PPh3 and tri(2-fur- oxane, and thus we achieved the smooth deoxygena-
yl)phosphine were worth further investigation be- tion with stereoinversion that affords E-olefin 2b
cause they showed either good yield or high stereoin- from cis-epoxide 1a (entry 10).
version efficiency (entries 6 and 14). Although we
With the above results, in the following scope and
limitation studies, the reactions were conducted either
with dppe as a reductant in toluene (0.1M) for the
stereoretentive deoxygenation (conditions A), or with
PPh3 in 1,4-dioxane (1M) for the deoxygenation with
stereoinversion (conditions B), respectively. Careful
monitoring of the reaction revealed that the E/Z ratio
remained constant throughout the reaction. More-
over, when 2a and 2b were subjected to the reaction
conditions described in Eqs. (1) and (2), no olefin iso-
merization was observed. These results indicate that
the stereochemical outcome is due not to stereocon-
vergent isomerization of olefin product but to the ste-
reospecific deoxygenation itself.
Table 1. Molybdenum-catalyzed deoxygenation of epoxides
with phosphine reductants.[a]
The scope of the stereoretentive deoxygenation re-
action under conditions A is summarized in Table 2.
The reactions with cis-epoxides bearing a linear alkyl,
a branched alkyl, an ethoxycarbonyl, and a phenyl
group and cis-cyclododecene oxide proceeded
smoothly with retention of stereochemistry to afford
the corresponding Z-olefins (entries 1, 3, 4, 6, and 9),
while cis-stilbene oxide showed moderate stereoselec-
tivity (entry 7). trans-Epoxides also took part in the
reaction and were converted to E-olefins with good
yield and selectivity (entries 2, 5, 8, and 10). While tri-
substituted epoxides including the one derived from
geraniol were also deoxygenated to the corresponding
olefins (entries 11 and 12), the monosubstituted epox-
ide gave the olefin product in low yield (entry 13).
Under conditions A, we did not find any carbonyl
products formed via the Lewis acid-promoted rear-
rangement.
[a]
Reactions were performed on a 0.3 mmol scale with
MoO2Cl2 (10 mol%) and phosphine (1.2 equiv. P) in tolu-
The scope of the deoxygenation reaction under
conditions B is illustrated in Table 3. The reactions
ene (0.1M) at 1208C for 18 h.
[b]
1
The yields were determined by H NMR. Yields in pa- with cis-epoxides bearing a linear alkyl and a phenyl
rentheses refer to isolated yields.
Determined by GLC.
For 12 h [conditions in Eq. (1)].
0.3 M.
group took place with inversion of stereochemistry to
afford the corresponding E-olefins (entries 1, 2, and
4), while a cis-epoxide bearing a bulky alkyl group
showed low inversion efficiency (entry 3). trans-Epox-
ides were also poor substrates under standard condi-
tions B (entry 5). However, we could improve the in-
version efficiency by performing the reaction with
tris(2-furyl)phosphine in MeCN solvent, albeit in
moderate yield (entry 7).[12] The last reaction, which
transforms a trans-epoxide to a thermodynamically
[c]
[d]
[e]
[f]
1 M.
[g]
[h]
1,4-Dioxane as a solvent.
The reaction was performed with PPh3 (3.0 equiv,) in 1,4-
dioxane (1M) for 12 h [conditions in Eq. (2)].
dppm=Ph2PCH2PPh2, dppe=Ph2P(CH2)2PPh2, dppp=
Ph2P(CH2)3PPh2, dppb=Ph2P(CH2)4PPh2, dpppent=
Ph2P(CH2)5PPh2.
[i]
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Table 2. Molybdenum-catalyzed deoxygenation of epoxides
Table 3. Molybdenum-catalyzed deoxygenation of epoxides
with stereoretention.[a]
with stereoinversion.[a]
[a]
Reactions were performed on a 0.2 mmol scale with
MoO2Cl2 (10 mol%) and PPh3 (3.0 equiv.) in 1,4-dioxane
(1M) at 1208C for 12 h (conditions B).
Isolated yield.
[b]
[c]
Determined by GLC.
Yield determined by 1H NMR.
[d]
[e]
The reaction was performed with
(1.2 equiv.) in MeCN (1M) for 18 h.
a
phosphine
less stable Z-olefin, is the most challenging and will
be our next research project, as it requires further op-
timization.[13]
The mild and neutral reaction conditions allowed
us to explore the functional group compatibility of
the deoxygenation reaction further (Supporting Infor-
mation, Table S6). Thus, the stereoretentive deoxyge-
nation reactions of 1a were performed in the presence
of compounds bearing various functional groups.[14]
The reactions proceeded smoothly in the presence of
ester, ketone, nitrile, alcohol, aryl bromide, aryl
methyl ether, internal alkyne, and terminal alkyne
without much affecting the yield and stereoselectivity
of the reaction, while carboxylic acid, aldehyde, and
phenol negatively affected the product/recovery
yields and/or stereoselectivity. It should be noted that
alcohol, internal alkyne, and terminal alkyne re-
mained intact and did not significantly affect the de-
oxygenation reaction in the present molybdenum-
based system, whereas these functional groups de-
composed or shut down the deoxygenation reaction
under the rhenium catalysis, that we developed previ-
ously.[7]
[a]
Reactions were performed on a 0.2–0.3 mmol scale with
MoO2Cl2 (10 mol%) and dppe (0.6 equiv.) in toluene
(0.1M) at 1208C for 18 h (conditions A).
Isolated yield.
Determined by GLC.
For 12 h.
At 1008C.
For 2 h.
[b]
[c]
[d]
[e]
[f]
[g]
At 1508C.
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Figure 1. A possible mechanism.
While the origin of the stereoselectivity is not fully Experimental Section
understood at this stage, we propose that the stereo-
specific reactions proceed through the mechanisms Typical Procedure
shown in Figure 1. First, the well-known reduction of
cis-1,6-Diphenyl-3-hexene oxide (75.8 mg, 0.30 mmol) was
Mo(VI)O2Cl2 by a phosphine generates the Mo(I-
V)OCl2 active species,[5,9,15,16] which reacts with an ep-
oxide to form a molybdena-2,5-dioxolane intermedi-
ate.[17] Similar intermediates have been proposed in
the related molybdenum-catalyzed deoxydehydration
of vicinal diols.[18] Under conditions A, stereoretentive
olefin extrusion takes place to form a dioxomolybde-
num(VI) complex, which is subsequently reduced by
a phosphine to regenerate the active species.[19] Con-
sidering that the reaction reaches completion with
0.6 equiv. of dppe, the dppe monoxide that is formed
after the initial deoxygenation also functions as an
oxygen atom acceptor.[20] Under conditions B, the in-
termolecular nucleophilic attack of PPh3 takes place
from the backside of one of the C–O bonds with in-
version of stereochemistry and forms the oxaphosphe-
added to a stirred mixture of MoO2Cl2 (6.0 mg, 30 mmol)
and dppe (71.7 mg, 0.18 mmol) in toluene (2.7 mL) in an
oven-dried test tube under argon, and the resulting mixture
was stirred at 1208C for 12 h. The reaction mixture was then
filtered through a pad of silica gel with Et2O and concen-
trated under reduced pressure. The crude product was puri-
fied by column chromatography on silica gel (hexane/
AcOEt=50/1) to afford 1,6-diphenyl-3-hexene as a colorless
oil; yield: 66.0 mg (93%). The E/Z ratio was determined to
be 5/95 by GLC analysis. The spectral data were in accord
with those reported in the literature.[7]
Acknowledgements
We thank MEXT for financial support, and KAKENHI
tane intermediate, which subsequently gives an E- Grant-in-Aid for Scientific Research (A) No. 26248030.
olefin and regenerates the active species. The effect
of the concentration may be explained by the general
trend that intramolecular processes are preferred over
intermolecular processes under dilute conditions.
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[20] The reaction with dppe monoxide (1.2 equiv.) under
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cies should be formed in the presence of dppe.
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6 Molybdenum-Catalyzed Stereospecific Deoxygenation of
Epoxides to Alkenes
Adv. Synth. Catal. 2016, 358, 1 – 6
Sobi Asako,* Takahisa Sakae, Masahito Murai,
Kazuhiko Takai*
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