Photoinduced Dearomatizing Three-Component Coupling of Arylphosphines, Alkenes, and Water

Article abstract of DOI:10.1002/anie.202013215

A unique photoinduced reaction that couples a triarylphosphine, an alkene, and water to produce 2-(cyclohexa-2,5-dienyl)ethylphosphine oxide is reported herein. The alkene inserts into a C(aryl)?P bond of the arylphosphine, the aryl ring is dearomatized into the cyclohexadienyl ring, and the phosphorus is oxidized. The three components are all readily available, and their intermolecular coupling significantly increases molecular complexity. The products formed are applicable to the Wittig olefination.

Full text of DOI:10.1002/anie.202013215

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Accepted Article
Title: Photo-induced Dearomatizing Three-component Coupling of
Arylphosphines, Alkenes, and Water
Authors: Yusuke Masuda, Hiromu Tsuda, and Masahiro Murakami
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Photo-induced Dearomatizing Three-component Coupling of
Arylphosphines, Alkenes, and Water
Yusuke Masuda, Hiromu Tsuda, and Masahiro Murakami* [a]
Abstract: Herein reported is a unique photo-induced reaction which
reduce benzene rings into 1,4-cyclohexadiene rings.[3]
Transition-metal catalysis also provides a variety of synthetic
reactions involving dearomatization of aromatic rings, especially
couples a triarylphosphine, an alkene, and water to produce 2-
(cyclohexa-2,5-dienyl)ethylphosphine oxide. An alkene inserts into a
C(aryl)–P bond of the arylphosphine, the aryl ring is dearomatized
into the cyclohexadienyl ring, and the phosphorus is oxidized. The
three components are all readily available, and their intermolecular
coupling significantly increases molecular complexity. The products
are applicable to the Wittig olefination.
π-extended arenes.[4]
Recently, photoredox-catalyzed
dearomatization reactions have been explored.[ For example,
Jui[5e] and Stephenson[5f] demonstrated that the well-designed
arene substrates were dearomatized through intramolecular
carbocyclization. König[5c] and Miyake[5h] reported photoredox-
catalyzed Birch-type reduction of arenes, which necessitated
5]
sacrificial reductants.
The present dearomatizing coupling
Photoredox catalysis has brought about a renaissance in
radical chemistry to renew interests in the use or co-use of water
as the solvent, since a polar environment that water creates is
innocuous for electronically neutral intermediates.[1] We have
recently developed the photo-catalyzed reactions of unprotected
sugars in aqueous media. They follow a radical pathway directly
leading to products without any protection/deprotection
procedure. Water was employed as the solvent or co-solvent
for the sake of solubility of sugars. During our continuing
investigation on related radical-mediated reactions in aqueous
media, we encountered an unexpected reaction which
incorporated a water molecule in a product as an essential
component. Herein reported is a unique three-component
coupling reaction of triarylphosphines, alkenes, and water.
A solution of triphenylphosphine (1, 0.20 mmol) and alkene 2
reaction is unique in that all three components are readily
available compounds of simple structures and couple together in
a highly atom-economical manner with significant increase of
molecular complexities. No sacrificial reductants are required.
Ph
P
blue light (470 nm)
Ir catalyst (1 mol%)
O
P
Et Et
Et
[
2]
+
Ph
Ph
Et
Ph
H2O/MeCN, rt, 20 h
3
2
1
(
2.0 equiv)
70% on 0.2 mmol scale
2% on 4.0 mmol scale
8
CF
3
F
t-Bu
t-Bu
N
Ir
N
N
F
F
PF
6
(2 equiv) in water/acetonitrile (1/2 v/v) was irradiated with blue
light (470 nm) in the presence of [Ir(dFCF ppy) dtbbpy]PF (Ir
3
2
6
N
catalyst, 1 mol%) for 20 h (Scheme 1). It was our true surprise
that 1,4-cyclohexadiene-phosphine oxide 3 was isolated from
the crude reaction mixture by chromatographic purification (70%
yield based on 1). The reaction was marked by dramatic
skeletal changes; the alkene 2 was inserted into a C(phenyl)–P
bond of triphenylphosphine (1), the phenyl ring was
dearomatized into the cyclohexadiene ring, and the phosphorus
atom was oxidized. Water split into an oxygen atom and two
hydrogen atoms, being separately incorporated in the produced
molecule (vide infra). The reaction turned out to be scalable to a
gram scale. When 1.0 g of triphenylphosphine (4.0 mmol) was
subjected to the coupling reaction with lower catalyst loading
F
CF
3
[
Ir(dFCF3ppy)2dtbbpy]PF6
(Ir catalyst)
Scheme 1. Dearomatizing coupling of triphenylphosphine, alkene, and water.
The results of the following experiments provided valuable
insights into the mechanism of the unexpected reaction. First,
fluorescence quenching experiments were carried out. The
obtained results confirmed that the excited Ir catalyst was
quenched by triphenylphosphine.[6] When the reaction was
performed in anhydrous acetonitrile, no reaction occurred and
both the phosphine 1 and the alkene 2 remained intact (Scheme
2a). Therefore, water is likely to participate in the early stage of
(0.25 mol%), the product 3 was obtained in an even better
isolated yield (82%, 1.2 g, 3.3 mmol).
The Birch reaction arguably represents one of the most
authentic examples of a dearomatization reaction. It employs
strongly reductive metallic lithium or sodium in ammonia to
the reaction pathway. Next, D
place of H O. The product 3-d obtained with D
2
O and H
2
O18 were employed in
O incorporated
2
2
two deuterium atoms selectively at the 1- and 3-positions of the
cyclohexadiene ring, as shown in Scheme 2b, with high D/H
[a]
Dr. Y. Masuda, H. Tsuda, Prof. Dr. M. Murakami
Department of Synthetic Chemistry and Biological Chemistry
Kyoto University, Katsura, Kyoto 615-8510 (Japan)
E-mail: murakami@sbchem.kyoto-u.ac.jp
18
ratios. On the other hand, the phosphine oxide 3-O obtained
O18 incorporated an O isotope, which was identified by
18
with H
2
high-resolution mass spectrometry (Figure 2c). When tri(p-
tolyl)phosphine (4) was subjected to the reaction with the alkene
2, the geminally disubstituted sp2 carbon of 2 was bound to the
ortho carbon of the original p-tolyl group (Scheme 2d). Finally, a
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cross-over experiment was conducted (Scheme 2e). A mixture
of triphenylphosphine (1) and tri(p-fluorophenyl)phosphine (6)
was used as the arylphosphine component. No cross-over
product 8 nor 9 was observed, which confirmed that the aryl ring
once detached from phosphorus was still tied up with the parent
phosphorus through an ethylene linker after dearomatization.
phosphoranyl radical B.[8,9] Although the radical center of B is
sterically hindered, it adds to the geminally disubstituted alkene
2 at the less-hindered side, forming thermodynamically stable
tertiary alkyl radical C. It undergoes 5-trig cyclization onto the
phenyl group to generate even more stable cyclohexadienyl
radical D at the expense of aromaticity. The iridium(II) complex
transfers a single electron back to D to regenerate iridium(III).
The resulting anion E is protonated by water with a site-
selectivity which is analogous to that of the Birch reduction to
form hydroxyphosphorane F.[10] Finally, F rearranges to the
product 3 through protonative cleavage of the C(alkenyl)–P bond.
An analogous decomposition of hydroxyphosphoranes had been
observed in hydrolysis of phosphonium salts.[11] The last two
protonation events are in accord with the result of the deuterium
experiment shown in Scheme 2b.
Scheme 3. Proposed reaction pathway.
Various alkenes were examined for the coupling reaction with
triphenylphosphine (1) (Table 1).
Methylenecycloalkanes
ranging from 4- to 6-membered rings furnished the
corresponding products 10-12 in yields ranging from 51% to
87%. Gaseous 2-methylpropene at an atmospheric pressure
successfully participated in the reaction to afford 13 in 55% yield.
Even the alkene having a tertiary butyl group underwent the
coupling reaction to give the product 16 possessing two
quaternary carbons in juxtaposition.
Whereas vicinally
Scheme 2. Mechanistic experiments.
disubstituted alkenes such as cyclohexene hardly coupled with 1
and water, 2-norbornene was reactive enough to afford the
coupling product 17 as a single diastereomer, which was
unambiguously confirmed by an X-ray crystallographic analysis.
This result is consistent with the proposed mechanism involving
a 5-trig cyclization step onto a phenyl ring. On the other hand,
mono-, tri- and tetra-substituted alkenes failed to give the
coupling product, probably due to the instability of the radical
species corresponding to C or steric reasons.
The results mentioned above led us to propose a reaction
pathway shown in Scheme 3 for the present dearomatizing
coupling reaction. An iridium(III) catalyst is initially excited upon
red
photoirradiation (E1/2 [Ir(III)*/Ir(II)]
=
+1.21
ox
V
vs SCE in
[
7]
CH
CH
3
CN).
Triphenylphosphine (1) (E1/2 = +0.98 V vs SCE in
CN)[ transfers a single electron to the excited iridium(III)
8]
3
catalyst to generate triphenylphosphine radical cation A and an
iridium(II) complex. A water molecule adds onto the radical
cation A, and the following deprotonation generates
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Table 1. Scope with respect to alkenes. [a,b]
[a] Reaction conditions: triphenylphosphine (0.20 mmol), alkene (0.40 mmol, 2 equiv), Ir catalyst (0.002 mmol, 1 mol%), H
2
O (1 mL), MeCN (2 mL), blue LEDs
(470 nm), rt, 20 h. [b] Isolated yield. [c] Reaction time of 48 h. [d] 1 atm of 2-methylpropene (balloon). [e] Acetone instead of MeCN.
Next examined were
a
range of geminally disubstituted
Testosterone-derived alkene also underwent the coupling
reaction, and the desired product 30 was obtained in 36%
yield.[12]
We investigated the substrate scope also with respect to
triarylphosphines (Scheme 4). Tri(p-methoxyphenyl)phosphine
gave the product 32 in 32% yield along with tri(p-
methoxyphenyl)phosphine oxide (ca. 42% yield). A fluoro group
was tolerated, and the fluoro-1,4-cyclohexadiene 7 was obtained
in 78% yield. Trialkylphosphines were not suitable substrates
due to a lack of an aryl group.
alkenes possessing various functionalities. Free hydroxy, ester,
amide, and acetal groups were all tolerated under the reaction
conditions (18-21). Notably, the alkene bearing a ketonic
carbonyl group participated in the reaction to furnish the 1,4-
cyclohexadiene 22 in 77% yield keeping the carbonyl group
intact.
substrates. Functional groups such as methoxy (24) and fluoro
25) groups on the phenyl ring were compatible with the reaction
Methallylbenzene derivatives were also suitable
(
conditions.
substituted
The coupling reaction of chloro- and bromo-
methallylbenzenes was accompanied by
polymerization to afford the products 26 and 27 in lower yields of
6% and 38%, respectively. 1-Allylindole afforded the coupling
3
product 28 in 53% yield. Limonene has two alkenyl groups, and
the propenyl moiety selectively reacted with 1 to form the
product 29 in 53% yield as
a mixture of diastereomers.
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aldehydes, an aliphatic aldehyde also participated in the
olefination reaction to afford alkene 35 in 41% yield. Even
tetraene product 36 was successfully obtained when cinnamyl
aldehyde was employed.
We next carried out a reduction reaction of the phosphine
oxide
3
(Scheme 5).[15]
When it was treated with
diisobutylaluminium hydride in cyclopentyl methyl ether (CPME),
alkyldiphenylphosphine 37 was produced in 87% yield. Thus,
the present coupling reaction offers a facile access to a new
class of alkyldiarylphosphine(III) compounds starting from
triarylphosphines.
Scheme 4. Synthesis of disubstituted 1,4-cyclohexadienes.
Table 2. Olefination with phosphine oxide 3. [a,b]
Scheme 5. Reduction of phosphine oxide 3.
In conclusion, we have developed the unique photo-induced
three-component coupling reaction of arylphosphines, alkenes,
and water. As a result of dearomatization, the products acquire
a 1,4-cyclohexadiene moiety. The phosphine oxide moiety is
utilized for olefination of aldehydes. Possibilities such as the
usage of the produced phosphines as a bidentate ligand for
transition metals is under investigation.
Acknowledgements
This work was supported by JSPS KAKENHI Grant Numbers
19K15562 (Y.M.). We thank Dr. T. Fujihara and Dr. D. Shimizu
(Kyoto Univ.) for performing an X-ray analysis.
Keywords: Dearomatization • Photocatalysis • Phosphine •
Alkene • Water
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Entry for the Table of Contents (Please choose one layout)
Layout 2:
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Yusuke Masuda, Hiromu Tsuda, and
Masahiro Murakami* *
Page No. – Page No.
Photo-induced Dearomatizing Three-
component Coupling of
Arylphosphines, Alkenes, and Water
Herein reported is
a
unique photo-induced reaction which couples
a
triarylphosphine, an alkene, and water to produce 2-(cyclohexa-2,5-
dienyl)ethylphosphine oxide. An alkene inserts into a C(aryl)–P bond of the
arylphosphine, the aryl ring is dearomatized into the cyclohexadienyl ring, and the
phosphorus is oxidized. The three components are all readily available, and their
intermolecular coupling significantly increases molecular complexity. The products
are applicable to the Wittig olefination.
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