Metal-free visible light photoredox enables generation of carbyne equivalents via phosphonium ylide C-H activation

Article abstract of DOI:10.1039/c8sc04195d

Carbyne, an interesting synthetic intermediate, has recently been generated from hypervalent iodine precursors via photoredox catalysis. Given the underexplored chemistry of carbyne, due to the paucity of carbyne sources, we are intrigued to discover a new source for this reactive species from classical reagents-phosphonium ylides. Our novel strategy employing phosphonium ylides in an olefin hydrocarbonation reaction features a facile approach for constructing carbon-carbon bonds through metal-free and benign reaction conditions. Moreover, the hydrocarbonation products were delivered in a highly regioselective manner.

Full text of DOI:10.1039/c8sc04195d

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Metal-free visible light photoredox enables
generation of carbyne equivalents via
phosphonium ylide C–H activation†
Cite this: DOI: 10.1039/c8sc04195d
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have been paid for by the Royal Society
of Chemistry
*
Mrinmoy Das,‡ Minh Duy Vu,‡ Qi Zhang and Xue-Wei Liu
Carbyne, an interesting synthetic intermediate, has recently been generated from hypervalent iodine
precursors via photoredox catalysis. Given the underexplored chemistry of carbyne, due to the paucity of
carbyne sources, we are intrigued to discover a new source for this reactive species from classical
reagents – phosphonium ylides. Our novel strategy employing phosphonium ylides in an olefin
hydrocarbonation reaction features a facile approach for constructing carbon–carbon bonds through
metal-free and benign reaction conditions. Moreover, the hydrocarbonation products were delivered in
a highly regioselective manner.
Received 20th September 2018
Accepted 23rd November 2018
DOI: 10.1039/c8sc04195d
rsc.li/chemical-science
catalysis has greatly advanced ATRA. Liu’s work on reductive
olen hydrocarbonation via nickel catalysis also offers a highly
Introduction
practical alternative for carbon–carbon bond formation from
olens.13 Additionally, since 2014, independent work done by
Baran and Shenvi has revealed the possibility of radical formation
from electron rich olens via silane reduction with iron, manga-
nese or cobalt catalysts.14–19 Furthermore, the new trend of meth-
odology development using inactivated olens as substrates for
carbon–carbon bond formation has been blooming over the past
few years thanks to great contributions from other groups.20–25
With the rise of visible light photoredox catalysis,26–28 its
application to functionalize alkenes has been demonstrated by
Conventionally, in organic structures, carbon atoms with a lack
of valences are categorized into 4 common classes, namely,
carbocations, radicals, carbenes and carbanions. Since 1967,
the interesting carbyne intermediate, which would belong to
the 5th class, was discovered by Strausz in a decomposition
reaction of diethyl mercurybisdiazoacetate.1–3 This species
contains 3 non-bonding electrons and appears to be so reactive
that its chemistry has not been widely established. Until earlier
this year, Suero and co-workers reported convenient access to
a diazomethyl radical, which is a direct equivalent to the car-
byne species, via the use of hypervalent iodine and photoredox
chemistry (Fig. 1a).4 In line with our interest in utilizing ylides
in single electron transfer processes, we proposed that mono-
substituted stabilized phosphonium ylides could undergo
C–H activation to form ylide radicals, which would be new
synthetic equivalents to carbyne. In this article, we report the
reaction between the ylides and activated olens to form
a hydrocarbonation-like product under this novel mechanism.
In recent years, olens have been employed as valuable
synthons for synthesis due to their ubiquitous occurrence in
nature and the chemical industry. The atom transfer radical
addition (ATRA) reaction is a classical choice to forge new
carbon–carbon bonds from alkenes. Seminal work done by
Stephenson,5 Reiser,6,7 Melchiorre,8 and Martin9 on photoredox
catalysis together with Severin’s work10–12 on ruthenium
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical
Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371.
E-mail: xuewei@ntu.edu.sg
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c8sc04195d
Fig. 1 Overview of reported carbyne chemistry, anti-Markovnikov HX
‡ These authors contributed equally.
addition, ylide chemistry and our strategy.
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several groups. Nicewicz and co-workers have pioneered the nucleophiles,39,40 our initial trials achieved remarkable success.
anti-Markovnikov addition of olens by utilizing acridinium In previous literature, the attack of ylides on electron decient
photosensitizers since 2012 (Fig. 1b).29–32 The catalyst’s high olens was reported to form new elongated ylides through
oxidation potential (>2.0 V vs. SCE) is sufficient for the single trivial Michael type addition (Fig. 1c).41 In our reaction, with the
electron oxidation process of several alkenes, leading to the carbyne radical involvement subsequently disclosed, the nal
attack of various nucleophiles such as alcohols,33 amines,34 product is no longer a phosphorane due to phosphine cleavage
carboxylates35 and halides.36 The work was subsequently via in situ reduction (Fig. 1d). To the best of our knowledge,
extended to olen anti-Markovnikov hydration by Lei and co- there is only one recent example of a reaction between ester-
workers.37 Very recently, Huang et al. also demonstrated [4 + 2] stabilized ylides and olen under photoredox conditions, as
cycloaddition of styrene using similar acridinium reported by Miura and Murakami.42 It was proposed that the
photosensitizers.38
formation of an alkyl radical from the phosphonium salt using
Initially, we questioned whether the cationic radical inter- an iridium photocatalyst is the key step in the mechanistic
mediate resulting from olen single electron oxidation would pathway.
be vulnerable to carbon nucleophiles. In that case, useful
carbon–carbon bond formation could be developed. Our
tremendous efforts turned out unsuccessful while employing
Results and discussion
“hard” nucleophiles such as enolates or other organometallic
reagents, presumably due to the low stability of the organo-
Prime investigations with model substrates 1a and 2a revealed
successful carbon–carbon bond formation when using thiol as
photocatalyst under the reaction conditions. When we turned
a hydrogen atom transfer (HAT) catalyst and the Hantzsch ester
our attention to phosphonium ylides, the classical carbon
as a hydride donor. A wide range of aromatic as well as aliphatic
Fig. 2 Phosphonium ylide and olefin substrate evaluation. All reactions were carried out under an inert atmosphere, with 0.1 mmol of the
phosphonium ylides and 0.3 mmol of the corresponding alkenes in dry DCM (0.025 M). 9-Mesityl-10-methylacridinium tetrafluoroborate
(5 mol%) was used as the photosensitizer in all experiments. Isolated yields were reported. a10 equivalents of alkenes were used instead. The
1
isomeric ratio was determined by analysis of crude H-NMR.
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Table 1 Selected results for condition optimizationa
chlorinated non-polar solvents, such as DCM or DCE, are the
best candidates. The conversion of the phosphonium ylide 1a
substrate was almost complete in the majority of trials and the
frequent side product observed results from the reduction of 1a
to acetophenone.43,44 We were pleased to discover that further
diluted reaction concentrations slightly help to improve the
yield of the desired product (entry 13). Control experiments
(entries 9–12) conrmed the necessity of all parameters in the
optimized conditions.
With the optimized reaction conditions in hand, we pro-
ceeded to evaluate the substrate scope of both olens and
phosphonium ylides (Fig. 2). Generally, in most of the
examples, moderate to excellent yields were observed with
absolute regioselectivity as determined by crude 1H-NMR (the
linear form is predominant). Ester stabilized phosphonium
ylides (4–7) worked slightly better than their ketone coun-
terparts (8–23). This is probably due to slow undesirable
Wittig olenation of the expected product with the ylide
starting materials. Aliphatic (8–10 and 18–20) and aromatic
substituted ketone stabilized ylides (11–17 and 21–23)
worked equally well. The electronic effect of substituents on
the aromatic ring does not signicantly affect the reaction
efficiency (Table 1).
In terms of olen substrates, para-substituted styrenes gave
reasonably good yields despite electronic effect differences (24–
27). Additionally, a- and b-disubstituted styrene showed positive
reactivity, although a low yield was obtained for the b-isomer
presumably due to steric effects (30–33). Cyclic alkenes, such as
indene, could be viable substrates for the reaction as well (28
and 29). Besides styrene derivatives, vinyl ether (34 and 36) and
allylic trimethylsilane (35) could also work to a certain extent.
Interestingly, terminal alkynes such as phenyl acetylene
successfully reacted, furnishing the formation of disubstituted
alkenes in decent yields with a mixture of (Z) and (E) isomers
(37). It is worth noting that the alkene product in this case did
not undergo further addition.
Entry Thiol catalyst (10 mol%) Hydride source (1.2 equiv.) Resultsb
1
2
3
4
5
6
7
8
T1
T2
T3
T4
T1
—
T1
T1
—
T1
T1
T1
T1
H1
H1
H1
H1
H2
H3
H4
H5
H1
—
57%
51%
20%
24%
NR.
49%
ND.
ND.
NR.
NR.
NR.
NR.
63%
9
10
11c
12d
13e
H1
H1
H1
a
All reactions were carried out under an inert atmosphere, with
0.1 mmol of 1a and 0.3 mmol of 2a in dry DCM (0.1 M). 9-Mesityl-10-
methylacridinium tetrauoroborate (5 mol%) was used as the
b
photosensitizer in all experiments. Yields were determined from the
crude reaction mixture by 1H-NMR using 1,3,5-trimethoxy benzene as
c
d
an internal standard. Without photosensitizer.
irradiation. Diluted concentration: 0.025 M of 1a, isolated yield was
Without light
e
reported. NR. no reaction. ND. not determined, complex mixture.
Aer measuring the redox potential, we realized that ylide 1a
actually has a considerably lower oxidation potential (Eox
¼
1.12 V vs. SCE) than its alkene partner 2a (Eox ¼ 1.97 V vs. SCE).45
The results from a uorescence quenching plot (Fig. 3) also
suggest that among all reaction components, ylide 1a is the
most efficient quencher. We therefore propose that 1a might
rst undergo single electron oxidation by the excited photo-
catalyst, forming the cationic radical (A) (Fig. 4). This is in
contrast with the mechanism for anti-Markovnikov addition for
C–X bond formation by Nicewicz. To date, the reactivity of
intermediate (A) has not been reported. We rationalize that it
might undergo 3 different pathways (Fig. 4). Its cationic char-
acter could facilitate nucleophilic addition of an alkene while its
radical character could enable radical addition to an alkene.
Either pathway will result in a new radical cation intermediate
Fig.
component.
3 Stern–Volmer plot for fluorescence quenching of each
thiols was found to catalyse the reaction (entries 1–4). Among with the ylide hydrogen intact. To our surprise, starting from
them, thiophenol was chosen as the best catalyst due to its deuterated ylide 1b, the obtained hydrocarbonation product
simplicity and high efficiency. Subsequently, some other does not contain any deuterium (veried by NMR and MS). We
hydride sources were evaluated in place of the Hantzsch ester. hence postulate that the hydrogen in (A) is acidic and possibly
However, diminished yields were obtained in all of these cases undergoes fast proton exchange with the medium. In other
(entries 5–8). Solvent screening (see ESI†) showed that words, deprotonation of (A) leading to a neutral carbyne radical
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Fig. 4 The fate of radical cation (A) resulting from single electron
oxidation of the phosphonium ylide.
Fig. 6 Our hypothesized mechanism.
unclear. We also tested the probability of photoinduced
reduction between the Hantzsch ester and ylide 1b, and
complete reduction to acetophenone was observed aer 12
hours (Fig. 5b).
With all of the information gathered so far, we have
proposed a mechanism for our hydrocarbonation protocol, as
shown in Fig. 6. The key step that determines regioselectivity in
our protocol is the addition of the carbyne radical (A0) to the
olen. A linear chain isomer was obtained in all cases resulting
from the stability of secondary radical (B).
Fig. 5 Other labelling experiments with deuterated Hantzsch esters
and a photoinduced reduction test on the phosphonium ylide.
Conclusions
could happen. Further conrmation by a trapping reaction with
the radical scavenger TEMPO showed traces of unstable trap-
ping product (C) in the MS analysis of the reaction mixture. In
addition, new peaks corresponding to compound (D) were also
observed in the MS analysis. This explains well the formation of
radical intermediate (B) which may undergo a HAT process with
the TEMPO radical (MS peaks for (D) were not observed in the
normal reaction without TEMPO). Together with recent work
conducted by Suero and coworkers,4 this constitutes one of the
rare examples of the formation and reaction of a carbyne
intermediate equivalent.
In conclusion, a benign method for the addition of phospho-
nium ylides to electron rich alkenes was developed. The reac-
tion conditions are completely metal-free, can be carried out at
room temperature, and utilize only visible light as an activation
source. Our reactions gave absolute predictable regioselectivity
and synthetically useful yields. Preliminary studies suggest
a novel mechanism involving the recently introduced carbyne
radical intermediate. The outlook of this study would be the
employment of phosphonium ylides as carbyne equivalents in
multi-functionalization reactions.
To gain more mechanistic insight, we carried out other
deuterium labelling experiments (Fig. 5a) using different
deuterated Hantzsch esters. The results showed that deute-
rium only ends up at C2 of product 24d, despite its origin in
the Hantzsch ester. This interesting phenomenon could
explain that the source of hydrogen at C4 is from the thiol
catalyst through HAT, and the deuterium could be incorpo-
rated into the nal product via reduction with a Hantzsch
ester, even though a detailed mechanism of the reduction is
Conflicts of interest
There are no conicts to declare.
Acknowledgements
We gratefully acknowledge the National Research Foundation
(NRF2016NRF-NSFC002-005) and the Ministry of Education
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