Photoredox-catalyzed decarboxylative alkylation/cyclization of alkynylphosphine oxides: a metal- and oxidant-free method for accessing benzo[b]phosphole oxides

Article abstract of DOI:10.1039/C8CC08689C

By photoredox-catalysis, alkylation/aryl C-H cyclization of readily available alkynylphosphine oxides towards benzo[b]phospholes has been realized under metal- and oxidant-free conditions at room temperature. This reaction readily incorporates various functionalized alkyl groups into the benzo[b]phosphole skeletons, representing a mild and versatile tool for the preparation of valuable phosphole compounds.

Full text of DOI:10.1039/C8CC08689C

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Photoredox-catalyzed decarboxylative alkylation/
cyclization of alkynylphosphine oxides: a metal-
and oxidant-free method for accessing
benzo[b]phosphole oxides†
Cite this: Chem. Commun., 2019,
55, 233
Received 31st October 2018,
Accepted 29th November 2018
a
c
Lixin Liu,a Jianyu Dong, *b Yani Yan,a Shuang-Feng Yin,
Li-Biao Han
and
DOI: 10.1039/c8cc08689c
a
Yongbo Zhou
*
rsc.li/chemcomm
By photoredox-catalysis, alkylation/aryl C–H cyclization of readily because they can ligate to a variety of metal ions.7 Therefore,
available alkynylphosphine oxides towards benzo[b]phospholes has the development of mild procedures, especially oxidant-free
been realized under metal- and oxidant-free conditions at room conditions, for the general synthesis of benzo[b]phospholes is
temperature. This reaction readily incorporates various functionalized still highly desired.
alkyl groups into the benzo[b]phosphole skeletons, representing a
Visible-light photoredox catalysis provides an attractive tool
mild and versatile tool for the preparation of valuable phosphole for the production of various reactive radicals for initiating
compounds.
radical reactions and assembly of diverse carbocyclic and hetero-
cyclic skeletons.8 In 2016, Lakhdar pioneered a photoredox-catalytic
As an important class of organophosphorus compounds, strategy for the preparation of benzo[b]phosphole oxides by inter-
p-conjugated benzo[b]phospholes have received considerable molecular oxidative annulations (N-ethoxy-2-methylpyridinium tet-
attention due to their inherent unique electronic and photo- rafluoroborate as the oxidant) of internal alkynes and secondary
physical properties and extensive applications as advanced organic phosphine oxides at room temperature.9 Alkyl N-hydroxyphthali-
optoelectronic materials and bioimaging probes.1 Conventional mide (NHPI) esters are redox active and can accept an electron in a
synthetic approaches towards this class of organophosphorus single electron transfer to form the corresponding alkyl radicals
compounds mainly rely on intramolecular cyclizations of ortho- without the need of exotic oxidants under visible-light photoredox
phosphorus-functionalized internal alkynes in the presence of a catalysis.10,11 Inspired by these contributions, we envision that a
stoichiometric strong base2 and/or an expensive transition metal cascade reaction including decarboxylation, alkyl radical addition,
catalyst.3 However, the cyclization precursors require complicated and aryl C–H cyclization could be achieved by mixing readily
multistep syntheses, which make these procedures tedious and available alkynyldiphenylphosphine oxides12 and NHPI esters
can decrease their functional group compatibility. Recently, as under photoredox-catalysis conditions, and that benzo[b]phosphole
good alternatives, protocols based on intermolecular oxidative oxides could be prepared in an attractive manner. Fortunately, we
annulations of aryl secondary phosphine oxides with internal realized this strategy by extensively tuning the reaction parameters,
alkynes4 and intermolecular oxidative addition/cyclization of
alkynylarylphosphine oxides5 have been developed, respectively
(Scheme 1). However, these reactions are carried out under strong
oxidant conditions (stoichiometric chemical oxidants and high
temperature), and thus suffer from low functional group tolerance
and/or a limited substrate scope.6 In addition, transition metals are
required in most of the cases, which are generally not easy to
remove from this class of organophosphorus compounds,
a State Key Laboratory of Chemo/Biosensing and Chemometrics, College of
Chemistry and Chemical Engineering, Hunan University, Changsha 410082,
China. E-mail: zhouyb@hnu.edu.cn
b Department of Educational Science, Hunan First Normal University,
Changsha 410205, China. E-mail: djyustc@hotmail.com
c National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba,
Ibaraki 305-8565, Japan
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c8cc08689c
Scheme 1 Synthetic approaches to benzo[b]phosphole oxides.
Chem. Commun., 2019, 55, 233--236 | 233
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Table 1 Substrate scopea
Scheme 2 Optimized reaction conditions.
such as photocatalysts, bases, solvents, and additives (for details,
see the ESI†). Benzo[b]phosphole oxide 3aa was obtained in 82%
yield by the treatment of diphenyl(phenylethynyl)phosphine
oxide (1a, 10% recovered) and 3-amyl NHPI ester 2a in the presence
of eosin B (2.0 mol%), N,N-diisopropylethylamine (i-Pr2NEt,
1.0 equiv.), and H2O (2.0 equiv.) in dimethylsulfoxide (DMSO)
at room temperature under visible-light irradiation for 10 h
(Scheme 2).
Herein, we report the details of the metal- and oxidant-free
synthesis of alkyl functionalized benzo[b]phosphole oxides. As
shown in Table 1, this decarboxylative alkylation/cyclization
reaction exhibited a wide substrate scope and good functional
group tolerance, producing various benzo[b]phosphole oxides
in moderate to high yields. Primary alkyl NHPI esters derived
from simple primary carboxylic acids bearing phenyl, bromine,
ester, and amide groups were well suited for this reaction,
giving the corresponding products (3ab–af) in synthetically
useful yields (34–60%). Interestingly, long-chain alkyl groups
containing terminal alkenyl and alkynyl groups, which are
reactive radical acceptors, are also tolerated, producing the
desired products in 54% (3ag) and 50% (3ah) yields, respectively.
In addition to the primary alkyl NHPI esters, the scope of
secondary alkyl NHPI esters was also broad. Acyclic secondary
groups (3aa, 3ai, and 3aj; 82, 72, and 74% yields, respectively),
alkyl cyclic groups (4- to 7-membered rings, 3ak–ao, 40–71%
yields), and various N- and O-heterocyclic alkyl groups (3ap–au,
29–64% yields) were all amenable to the alkylation/cyclization
reaction. Sterically bulky alkyl groups lowered the yields of this
transformation, which was probably due to the difficult addition
of the alkyl radical to the CꢀC triple bond (vide infra). NHPI
esters containing 5- and 6-membered rings gave higher yields
than those achieved with those containing 4- and 7-membered
rings, e.g., 3ak (40% yield) vs. 3am (71% yield) and 3ap (29%
yield) vs. 3as (60% yield). When tert-butyl N-(acyloxy)phthalimide
was subjected to the reaction system, the reaction produced tert-
butylated benzo[b]phosphole oxide 3av in 40% yield, whereas the
more sterically hindered N-(acyloxy)phthalimide derived from
1-adamantanecarboxylic acid only gave 8% 31P NMR yield (3aw)
with 85% of 1a recovered.
In addition, aliphatic acids are widely encountered functionalities
in bioactive compounds and biomass. We investigated the reactivity
of N-(acyloxy)phthalimides derived from such sources as radical
precursors. For example, NHPI esters from stearic acid (found in
animal fats) and Boc-protected valine could be used as substrates to
obtain the corresponding products in 58% (3ax) and 32% (3ay)
yields, respectively. In addition, the NHPI ester derived from
gemfibrozil (a drug used to lower lipid levels) was also compatible
with this reaction system, providing the desired product (3az) in
40% yield.
a
b
Isolated yields. The proportion of 1 recovered. c 31P NMR yield using
tributyl phosphate as an internal standard.
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We then evaluated the substrate scope of alkynylphosphine mixture as a radical inhibitor, the reaction was completely sup-
oxides. As shown in Table 1, diphenyl(phenylethynyl)phosphine pressed (Scheme 4, eqn (1)). Furthermore, the radical scavenger,
oxides substituted with alkyl (3ba and 3ca), methoxy (3da), 1,1-diphenylethylene, could also block this reaction, and the
halogen (3ea–3ga), trifluoromethyl (3ha), and cyano (3ia) groups radical adduct was observed (Scheme 4, eqn (2)). When NHPI
worked well to give the corresponding products in satisfactory ester 2za containing a hex-1-ene moiety was subjected to the
yields (65–76%), regardless of the electronic effects of the reaction conditions, product 3aza was obtained in 50% yield,
substituents. Notably, the tolerance for halogens (Br and Cl) allows and this product was formed via an additional alkyl radical
the further functionalization of the products for the preparation of cyclization (Scheme 4, eqn (3)). These results suggested that
more complex targets via stepwise coupling reactions. Heterocyclic radical intermediates were involved in the reaction. Fluorescence
substrates containing a pyridine ring or a thiophene ring were titration experiments with eosin B showed that the emission
compatible with the decarboxylative alkylation/cyclization reaction of EB* was quenched by the addition of the electron donor,
and produced the desired heterocyclic products in moderate yields i-Pr2NEt, which proves that a single-electron transfer (SET) occurs
(3ja, 64% yield; 3ka, 40% yield). In comparison, monophenyl between the two species (see the ESI,† Fig. S2 for details). Finally,
alkynylphosphine oxides proceeded sluggishly under this photo- the quantum yield (F) of the reaction was estimated by chemical
catalytic system, and low yields of the desired products were actinometry, and a low value was observed (F = 1.43, see the ESI†
observed (3la, 18% 31P NMR yield; 3ma, 17% 31P NMR yield). for details), indicating that efficient radical chain processes were
When di-p-tolyl alkynylphosphine oxide was employed as the very unlikely to be involved in this mechanism.13
substrate, in addition to the desired benzo[b]phosphole oxide
On the basis of the experimental results described above,
product (3na, 49% yield), the regioisomeric product (3na0) was also and the literature precedents,4,5,9,11f a plausible mechanism for
observed (19% 31P NMR yield). This result demonstrates that the the reaction is illustrated in Scheme 5. Initially, the photocatalyst
reaction probably proceeds through two pathways (vide infra).
(PC) is photoexcited to its excited state (PC*), which is reductively
It is worth noting that the reaction proceeded with high quenched by the electron donor, i-Pr2NEt, to give the corres-
selectivity. Alkyl radical rearrangement products were not found, ponding radical anion (PCꢁꢀ) with concomitant generation of
+
even in the reactions of the primary alkyl NHPI esters (2b–h) and i-Pr2NEtꢁ . Then, the reduction of NHPI ester 2 by PCꢁꢀaffords
unsymmetrical secondary alkyl NHPI esters (2j and 2q). The the corresponding radical anion (B), regenerating PC. The splitting
relatively low yields observed in some cases were due to the low of the N–O bond of B together with subsequent elimination of CO2
conversion of the alkynylphosphine oxides.
generates alkyl radical C. The selective intermolecular addition
To further extend the practicality of this photocatalytic of alkyl radical C to the a-position of the PQO bond in
radical addition/cyclization reaction, a gram-scale model reaction alkynylphosphoryl compound 1 affords alkenyl radical D rather
(2.5 mmol) was conducted under the standard reaction conditions than D0. Finally, the intramolecular aryl C–H cyclization of
and the desired product was obtained successfully (3aa) in 70% radical D produces intermediates E (5-exo-ring) and H (via
yield (Scheme 3, eqn (1)). In addition, a ‘‘one-pot’’ reaction of 4-exo-ring F and vinyl phosphorus radical G),4,5,9 and subsequent
NHPI and 2-ethylbutyric acid was performed, and desired SET and dehydrogenation generates the desired product (3).
benzo[b]phosphole oxide 3aa was produced in a good yield of
In summary, using photoredox catalysis, we have success-
73% (Scheme 3, eqn (2)). These results demonstrate the synthetic fully developed a radical initiated cascade reaction of alkynyl-
value of the procedure in organic synthesis. In addition, the reaction phosphoryl compounds for preparing functionalized benzo[b]phos-
of diyne 1o with NHPI ester 2a afforded bis(benzophosphole-3- pholes. The reaction proceeds with high selectivity and produces a
yl)benzene skeleton 3oa (50% yield), which has potential appli- broad spectrum of alkyl benzo[b]phospholes in satisfactory yields
cations in organic photoelectric materials (Scheme 3, eqn (3)).
without generating alkyl radical rearrangement products. The key to
To elucidate the reaction mechanism, several control experiments success is the photocatalytic generation of the alkyl radical from
were carried out under the standard conditions. First, when 2,2,6,6- the NHPI ester along with its subsequent addition to the alkyne.
tetramethylpiperidine N-oxide (TEMPO) was added to the reaction
Scheme 3 Synthetic applications.
Scheme 4 Experimental probes of the reaction mechanism.
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Conflicts of interest
There are no conflicts to declare.
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