Alkene homologation: via visible light promoted hydrophosphination using triphenylphosphonium triflate

Article abstract of DOI:10.1039/d0cc07025d

A hydrophosphination reaction of alkenes with triphenylphosphonium triflate under photocatalytic conditions is described. The reaction is promoted by naphthalene-fused N-acylbenzimidazole and is believed to proceed through intermediate formation of a phosphinyl radical cation. The resulting phosphonium salts are directly involved in the Wittig reaction leading to homologated alkenes.

Full text of DOI:10.1039/d0cc07025d

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Alkene homologation via visible light promoted
hydrophosphination using triphenylphosphonium triflate
Vitalij V. Levina and Alexander D. Dilman*a
Received 00th
January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A
hydrophosphination
reaction
of
alkenes
with radical hydrophosphination of unactivated alkenes, and the
triphenylphosphonium triflate under photocatalytic conditions is resulting phosphonium salts were used
described. The reaction is promoted by naphthalene-fused N-
Previous work:
acylbenzimidazole and is believed to proceed through intermediate
formation of phosphinyl radical cation. The resulting phosphonium
salts are directly involved in the Wittig reaction leading to
homologated alkenes.
H
H
R
PR2
R = H, Ph
H
H
P
Alk
Alk
R
metall catalyzed
or
radical chain
+
Alk
X
P
Y
P
Addition of the P-H bond at the double bond of alkenes
constitutes an atom economic way of synthesis of
organophosphorus compounds.1-3 Typically, these processes
are performed starting from disubstituted phosphines, their
oxides, phosphinic acids and alkyl phosphites (Scheme 1). While
particular reaction conditions depend on the type of
phosphorus reagent and alkene, the addition proceeds easily
with electron deficient alkenes.2 In case of unactivated double
bonds, the reaction is more challenging to perform,3 and
uncatalyzed thermal addition was described only in case of free
phosphines R2PH.4 The hydrophosphination of alkenes may be
catalyzed by transition metal complexes,1 but the most widely
used activation methods are based on radical initiation and
proceed via P-centered radicals.5 For this, classic activators such
as AIBN,6 triethylborane,7 oxidizing metal salts,8 oxygen9 and UV
light10 were employed. Development of photocatalysis allowed
hydrophosphination to be promoted by visible light.11,12
Reactions of phosphonium salts with Michael acceptors, that is
when phosphonium salt behaves as a source of free phosphine
acting as nucleophile followed by protonation of carbanion,
have also been described.13 Herein we report that easily
prepared triphenylphosphonium triflate can be involved into
R
R
R
R
X = O, S
R = H, Ph, OEt
H
PPh3
PPh3
Z = EWG
+
+
H
PPh3
Z
Z
Z
This work:
Alk
H
via
PPh3
CH2O
Wittig
H
PPh3
PPh3
Alk
Alk
Scheme 1. Addition of the P-H bond to alkenes.
directly for the Wittig reaction.14,15 Importantly, in this process,
olefins as feedstock reagents are directly converted into
phosphonium salts that saves
transformation of alkene-to-alkyl halide.16
a step by avoiding the
The hydrophosphination is expected to involve the
phosphonium radical cation as a key intermediate capable of
adding at unactivated alkenes. Previously these species have
been considered from a general mechanistic perspective.17
However, recently they have found synthetic applications for
the homolytic abstraction of the hydroxy group from carboxylic
acids and alcohols generating the corresponding radicals.18
A
straightforward way of generating phosphonium radical cations
involves single electron oxidation of phosphines, which may be
achieved by using light activated ruthenium- or iridium-based
catalysts.17c,18,19 In this work, we propose that the radical cation
can be formed via proton coupled electron transfer (PCET)20
using an organic photocatalyst.
a. N. D. Zelinsky Institute of Organic Chemistry, 119991 Moscow, Leninsky prosp. 47,
Russian Federation.
Electronic Supplementary Information (ESI) available: Procedures, compound
characterization, NMR spectra. See DOI: 10.1039/x0xx00000x
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a
b
Determined by GC analysis using tetralin as internal standard. Yield of 7a
Our idea is based on application of organic photocatalysts,
which we applied for the thiol-ene reaction.21 The proposed
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DOI: 10.1039/D0CC07025D
determined by 1H NMR using trichloroethylene as internal standard. 0.33 equiv
of PPh3.
c
the absence of photocatalyst. In the presence of 0.5 mol % of
naphthaloylidenebenzimidazol (NBI)22 moderate conversion of
21% was observed within two hours, which reached 37% after
overnight irradiation (entry 2). This phenomenon suggested
catalyst deactivation as reaction proceeds, and this was the case
with all evaluated catalysts. However, since NBI can be made
from readily available precursors,21,22 it can be used in increased
loadings. Rewardingly, with 3 mol % of the catalyst complete
conversion was achieved within 16 hours (entry 3). 9-
Phenylacridine (PhAcr), which was previously used in a PCET
driven process,23 was slightly less effective in this reaction
(entry 9). We also evaluated a fluorinated iridium photocatalyst
(Ir[dF(CF3)ppy]2(dtbpy)PF6). This highly oxidizing complex was
expected to initiate the chain process shown in Scheme 2 by
oxidation of the phosphine into the radical cation 1. Though the
reaction did work, incomplete conversions were observed even
in the presence of increased amount of the phosphine (entries
N
h, PCET
Ph3P
H
N
Ph3P
+
H
N
Ph3P
R
H
1
2
PPh3
PPh3
H
N
Ph3P
1
Alk
Alk
3
2
H
Ph3P
H
N
4
Scheme 2. Proposed mechanism.
concept is shown in Scheme 2. The interaction of phosphonium
salt with a photocatalyst generates a hydrogen-bonded
complex, which under the action of light transforms into P-
centered radical cation 1 and a nitrogen-stabilized radical 2.
Addition of 1 at the double bond generates alkyl radical 3. The
latter intermediate abstracts hydrogen atom either from
phosphonium cation, thereby regenerating radical cation 1, or
from aminyl species 2 with regeneration of the nitrogen
catalyst.
5
and 6) and unidentified byproducts were observed.
Correspondingly, NBI was used in further experiments. For a
representative hydrophosphination reac-
Table 2 Transformation of alkenes.a
(a) HPPh3 TfO (6, 1.3 equiv)
R2
NBI (3 mol %), PPh3 (5 mol %), blue LED, THF, rt, 4 h
4-Phenylbutene 5a was selected as a model substrate and
R1
R1
R2
(b) HMDS (0.3 equiv), n-BuLi (1.3 equiv), 30 C
its reaction with triphenylphosphonium triflate
6 was
8
5
R2
evaluated. Additional amount (5 mol %) of free phosphine and
a photocatalyst were added, and the reaction was irradiated
with blue light for 16 h (Table 1). Tetrahydrofuran was used as
solvent considering further transformations of the resulting
phosphonium salts (vide infra). The reaction did not proceed in
then
O
-30 C to rt, 16 h
R2
Ph
Ph
Ph
C4H9
Ph
Ph
Ph
C3H7
Ph
8a, 78%b
8b, 77%
8c, 72%
Ph
Ph
Table 1 Optimization studies.
Ph
Ph
Ph
8f, 49%c
Cat., blue LED
PPh3 (5 mol %)
Ph
8d, 67%
Ph
8e, 72%
PPh3
+
HPPh3 TfO
Ph
Ph
THF, rt
Ph
Ph
Ph
TfO
CF3
5a
7a
6 (1.3 equiv)
Me3Si
Ph
Ph
Ph
PhS
Ph
8g, 75%b
8h, 80%
8i, 46%d
F
tBu
Ph
Ph
N
O
O
Ph
N
Ph
TIPSO
N
N
Ph
F
F
MeO
N
Ir
8j, 62%
8l, 58%
8k, 53%
MeO
MeO
OMe
S
Ph
N
Ph
Ph
N
tBu
NBI
PhAcr
Ph
Ph
Ph
F
8m, 71%
8n, 46%e
CF3
Ir[dF(CF3)ppy]2(dtbpy)+
PF6
TIPSO
Ph
Ph
Entry
Cat. (mol %)
Conversion of 5a (%)a
Cl
8o, 77%b
8p (E/Z, 1/3), 67%b
8q, 54%
2 h
16 h
1
2
3
4
5
-
<5%
21
28
26
31
<5%
37
100 (80%b)
83
45 (35%b)
55
O
MeO
Ph
NBI (0.5 %)
NBI (3 %)
PhAcr (3 %)
Ir(III) (0.5 %)
Ir(III) (0.5 %)
Ph
MeO
MeO
8r, 37%
8s, 58%
8t, 54%b
N
O
6c
29
S
8u, 50%b
8v, 54%f
2 | J. Name., 2012, 00, 1-3
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a Isolated yields are shown. b Time for step (a) 16 h. c 1 equiv of HMDS was used. d
For step (a), 5% of NBI, time 24 h. e For step (a), 5% of NBI, time 36 h. f 1.5 equiv of
LiHMDS solution was used for deprotonation.
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Scheme 3. Radical cyclization experiment.
In summary, a one pot method for the homologative
transformation of alkenes is described. The reaction involves
light mediated hydrophosphination and the Wittig reaction of
intermediate phosphonium salts. The generation of the
phosphonium radical cation is a key feature of the process.
This work was supported by the Russian Foundation for
Basic Research (project 18-33-20015).
tion, a quantum yield of 0.05 was determined. This means that
the process does not have the chain character, and the product
is formed by interaction of radical 3 with aminyl species 2.
To get more insights into the nature of the generation of
phosphonium radical cation, a series of UV-vis absorption and
fluorescence experiments for combinations of NBI and
phosphonium triflate (6) were performed. These studies
support the formation of a complex, which is believed to
undergo the light induced PCET (see Supporting Information for
details).
Conflicts of interest
There are no conflicts to declare.
Under the optimized conditions, various alkenes were
subjected to hydrophosphination reaction. We noted that
hydrophosphination of unfunctionalized alkenes such as
pentene, hexene, vinyl- and allylcyclohexane proceeded faster
compared to that of model 4-phenylbutene 5a, and for most of
alkenes complete conversion was achieved within 4 hours. The
resulting phosphonium salts 7 were directly involved into the
Wittig reaction (Table 2). Thus, the mixture containing salts 7
was cooled to –30 C and treated with n-butyl lithium in the
presence of 0.3 equiv of hexamethyldisilazane, which removed
the excess of butyllithium. Subsequent addition of a carbonyl
compound and warming to room temperature furnished
alkenes 8.
Benzophenon was used in combination with light alkenes
allowing for the isolation of non-volatile target products. The
fact that hydrophosphination and Wittig reactions require
different conditions (mildly acidic and strongly basic,
respectively) imposes some limitations on the scope of
functional groups. Alkenes bearing PMP, TIPS of thiocarbamate
protected hydroxy group successfully provided expected
products (compounds 8j,k,v). At the same time, 3-buten-1-ol
and 4-peneten-1-ol protected with the benzyl group remained
unreactive in hydrophosphination reaction, and the reason for
such phenomenon is not clear. TBS and THP protecting groups
on oxygen do not tolerate the acidic conditions of the
hydrophosphination step. As carbonyl compounds,
benzophenone and formaldehyde (as paraform) were typically
used, though aromatic aldehydes were also successful
(products 8o,p). In case of formaldehyde, the overall result of
the two-step process corresponds to the homologation of the
starting alkene by one CH2-fragment.24
Notes and references
1
(a) O. Delacroix and A. C. Gaumont, Curr. Org. Chem., 2005, 9,
1851–1882. (b) Q. Xu and L.-B. Han, J. Organomet. Chem.,
2011, 696, 130–140. (c) V. Koshti, S. Gaikwad and S. H.
Chikkali, Coord. Chem. Rev., 2014, 265, 52–73. (d) L.
Rosenberg, ACS Catal., 2013, 3, 2845–2855. (e) D. S. Glueck, J.
Org. Chem., 2020, 85, 14276–14285. (f) C. A. Bange and R.
Waterman, Chem. Eur. J., 2016, 22, 12598–12605.
D. Enders, A. Saint-Dizier, M.-I. Lannou and A. Lenzen, Eur. J.
Org. Chem., 2006, 29–49.
2
3
4
L. Coudray and J.-L. Montchamp, Eur. J. Org. Chem., 2008,
3601–3613.
(a) Y. Moglie, M. J. Gonzaez-Soria, I. Martin-Garcia, G. Radivoy
and F. Alonso, Green Chem., 2016, 18, 4896–4907. (b) D.
Bissessar, J. Egly, T. Achard, P. Steffanut and S. Bellemin-
Laponnaz, RSC Adv., 2019, 9, 27250–27256. (c) F. Alonso, Y.
Moglie, G. Radivoy and M. Yus, Green Chem., 2012, 14, 2699–
2702.
5
6
D. Leca, L. Fensterbank, E. Lacote and M. Malacria, Chem. Soc.
Rev., 2005, 34, 858–865.
(a) L.-B. Han and C.-Q. Zhao, J. Org. Chem., 2005, 70, 10121–
10123. (b) C. M. Jessop, A. F. Parsons, A. Routledge and D.
Irvine, Tetrahedron Lett., 2003, 44, 479–483.
7
8
P. Rey, J. Taillades, J. C. Rossi and G. Gros, Tetrahedron Lett.,
2003, 44, 6169–6171.
(a) S.-F. Zhou, D.-P. Li, K. Liu, J.-P. Zou and O. T. Asekun, J. Org.
Chem., 2015, 80, 1214–1220. (b) G.-Y. Zhang, C.-K. Li, D.-P. Li,
R.-S. Zeng, A. Shoberu and J.-P. Zou, Tetrahedron, 2016, 72,
2972–2978.
(a) T. Hirai and L.-B. Han, Org. Lett., 2007, 9, 53–55. (b) P.
Troupa, G. Katsiouleri and S. Vassiliou, Synlett, 2015, 26,
2714–2719.
9
10 (a) P.-Y. Geant, B. S. Mohamed, C. Perigaud, S. Peyrottes, J.-P.
Uttaro and C. Mathe, New J. Chem., 2016, 40, 5318–5324. (b)
F. Gelat, M. Roger, C. Penverne, A. Mazzad, C. Rolando and L.
Chausset-Boissarie, RSC Adv., 2018, 8, 8385–8392.
11 (a) G. Fausti, F. Morlet-Savary, J. Lalevee, A.-C. Gaumont and
S. Lakhdar, Chem. Eur. J., 2017, 23, 2144–2148. (b) W.-J. Yoo
and S. Kobayashi, Green Chem., 2013, 15, 1844–1848.
To support the radical character of the hydrophosphination
process, a 1,6-diene was evaluated as a substrate affording
cyclized phosphonium salt 9 as a single product (Scheme 3).
12 For recent photocatalyzed reactions involving phosphorus-
centered radicals, see: (a) V. Quint, F. Morlet-Savary, J.-F. o.
Lohier, J. Lalevee, A.-C. Gaumont and S. Lakhdar, J. Am. Chem.
Soc., 2016, 138, 7436–7441. (b) Q. Fu, Z.-Y. Bo, J.-H. Ye, T. Ju,
H. Huang, L.-L. Liao and D.-G. Yu, Nat. Commun., 2019, 10,
3592. (c) X.-C. Liu, K. Sun, X.-L. Chen, W.-F. Wang, Y. Liu, Q.-L.
Li, Y.-Y. Peng, L.-B. Qu and B. Yu, Adv. Synth. Catal., 2019, 361,
3712–3717. (d) Y. Yin, W.-Z. Weng, J.-G. Sun and B. Zhang,
Org. Biomol. Chem., 2018, 16, 2356–2361.
MeO2C
MeO2C
HPPh3 TfO
MeO2C
MeO2C
Standard condtns.
PPh3
MeO2C
MeO2C
MeO2C
MeO2C
13 H. Hoffmann, Chem. Ber., 1961, 94, 1331–1336.
TfO
PPh3
PPh3 TfO
9
not detected
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14 An example of hydrophosphination using (EtO)2PSH followed
by Horner−Wadsworth−Emmons reaction was described: M.
P. Healy, A. F. Parsons and J. G. T. Rawlinson, Org. Lett., 2005,
7, 1597–1600.
View Article Online
DOI: 10.1039/D0CC07025D
15 For photoredox-mediated radical reactions of phosphorus
ylides, see: (a) T. Miura, Y. Funakoshi, J. Nakahashi, D.
Moriyama and M. Murakami, Angew. Chem. Int. Ed., 2018, 57,
15455–15459. (b) T. Miura, D. Moriyama, Y. Funakoshi and M.
Murakami, Synlett, 2019, 30, 511–514.
16 For a review on the use of feedstock reagents in chemical
synthesis, see: R. S. Doerksen, C. C. Meyer and M. J. Krische,
Angew. Chem. Int. Ed., 2019, 58, 14055–14064.
17 (a) X. Pan, X. Chen, T. Li, Y. Li and X. Wang, J. Am. Chem. Soc,.
2013, 135, 3414–3417. (b) F. Hirakawa, H. Nakagawa, S.
Honda, S. Ishida and T. Iwamoto, J. Org. Chem., 2020, 85,
14634–14642. (c) S. Yasui, M. Tsujimoto, K. Shioji and A. Ohno,
Chem. Ber., 1997, 130, 1699–1707. (d) H. Ohmori, T. Takanami
and M. Masui, Tetrahedron Lett., 1985, 26, 2199–2200.
18 (a) E. E. Stache, A. B. Ertel, T. Rovis and A. G. Doyle, ACS Catal.,
2018, 8, 11134–11139. (b) J. I. Martinez Alvarado, A. B. Ertel,
A. Stegner, E. E. Stache and A. G. Doyle, Org. Lett., 2019, 21,
9940–9944. (c) J. A. Rossi-Ashton, A. K. Clarke, W. P. Unsworth
and R. J. K. Taylor, ACS Catal., 2020, 10, 7250–7261. (d) X.-Q.
Hu, Y.-X. Hou, Z.-K. Liu and Y. Gao, Org. Chem. Front., 2020, 7,
2319–2324.
19 In our previous work, it was noted that addition of
triphenylphosphine may have beneficial effect on photoredox
reactions. The intermediacy of the phosphonium radical
cation was proposed, see: (a) L. I. Panferova, V. O. Smirnov, V.
V. Levin, V. A. Kokorekin, M. I. Struchkova and A. D. Dilman, J.
Org. Chem., 2017, 82, 745–753. (b) S. I. Scherbinina, O. V.
Fedorov, V. V. Levin, V. A. Kokorekin, M. I. Struchkova and A.
D. Dilman, J. Org. Chem., 2017, 82, 12967–12974.
20 J. J. Warren, T. A. Tronic and J. M. Mayer, Chem. Rev., 2010,
110, 6961–7001.
21 V. V. Levin and A. D. Dilman, J. Org. Chem., 2019, 84, 8337–
8343.
22 M. Mamada, C. Perez-Bolivar, D. Kumaki, N. A. Esipenko, S.
Tokito and P. Anzenbacher Jr, Chem. Eur. J., 2014, 20, 11835–
11846.
23 M. O. Zubkov, M. D. Kosobokov, V. V. Levin, V. A. Kokorekin,
A. A. Korlyukov, J. Hu and A. D. Dilman, Chem. Sci., 2020, 11,
737–741.
24 For similar alkene homologation based on Ru-catalyzed
metathesis combined with Pd-catalyzed allylic reduction, see:
D. L. Comins, J. M. Dinsmore and L. R. Marks, Chem. Commun.,
2007, 4170–4171.
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