Markovnikov-addition of H-phosphonates to terminal alkynes under metal- And solvent-free conditions

Article abstract of DOI:10.1039/d1ra04306d

An addition of H-phosphonates to aryl alkynes was realized under solvent- and metal-free conditions, affording Markovnikov-selective α-vinylphosphonates in moderate to good yields. A wide range of aryl alkynes could be applied for the reaction. A tentative mechanism of addition-substitution was proposed based onin situ³¹P {¹H} NMR studies.

Full text of DOI:10.1039/d1ra04306d

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Markovnikov-addition of H-phosphonates to
terminal alkynes under metal- and solvent-free
Cite this: RSC Adv., 2021, 11, 24991
conditions†
a
*
Nana Xin,
Yongjian Lian,a Yongzheng Lv,a Yongjie Wang,b Xian-Qiang Huanga
a
*
and Chang-Qiu Zhao
Received 3rd June 2021
Accepted 6th July 2021
An addition of H-phosphonates to aryl alkynes was realized under solvent- and metal-free conditions,
affording Markovnikov-selective a-vinylphosphonates in moderate to good yields. A wide range of aryl
alkynes could be applied for the reaction. A tentative mechanism of addition–substitution was proposed
based on in situ 31P {1H} NMR studies.
DOI: 10.1039/d1ra04306d
rsc.li/rsc-advances
Vinyl phosphorus compounds are of high importance because species to C(sp2)–P bonds are quite rare. Miura and coauthors
of their wide application in the elds of biological metabolism,1 have reported a Tf2O promoted activation of secondary phos-
functional materials,2 and as synthetic blocks of organophos- phine oxides, which is applied for phosphination and intra-
phorus compounds.3 Some reviews have documented the molecular cyclization with alkynes.13 However, the scopes are
preparations and applications of the vinyl phosphorus.4 Nor- limited with inner-alkynes. The application of H-phosphonates
mally, the compounds can be acquired from alkynes, via the was not reported for the reaction (Chart 1).
addition with H–P species. Aromatic ketones and aldehydes are
Herein we enclosed a novel Tf2O promoted reaction of
also used as the sources of vinyl phosphorus, via multi-step terminal alkyne with H-phosphonates. Vinyl phosphonates
conversions.1b,5 The recently developed methods to obtain were afforded under metal- and solvent-free conditions, in
vinyl phosphorus involving H–P species include decarboxyl- excellent Markovnikov-regio selectivity.
ation of cinnamic acid,6 dehydrogenation of active alkene,7 and
dehydration of alcohols.8
Phenylacetylene (1a) was initially treated with diethyl phos-
phite (2a) in the presence of Tf2O in a molar ratio of 1 : 1 : 1. To
The addition of H–P species to alkynes is undoubtedly the
most effective and atom economical method. The addition was
usually catalysed by metals.4e,9 One of the authors has reported
palladium and rhodium catalysed additions of H–P species to
alkynes.9a–d Similar additions could be realized by catalysis with
copper, nickel, molybdenum and ytterbium (Chart 1).10 The
metal-catalysed procedures also include Suzuki reaction and
others.11 Although much progress has been made in this area,
problems associated with narrow substrate scope, the need to
use expensive transition metals and a stoichiometric amount of
additives, and poor regio- and stereo-control have encouraged
researchers to search for new and more efficient methods.
Recently, triic anhydride (Tf2O) has been applied for elec-
trophilic activation of amides and P]O species, and the acti-
vated intermediates could be used for the substitutions with
various nucleophilic reagents.7b,12 The conversions of P]O
aInstitution of Functional Organic Molecules and Materials, Shandong Provincial Key
Laboratory of Chemical Energy Storage and Novel Cell Technology, Liaocheng
University, College of Chemistry and Chemical Engineering, Liaocheng, Shandong
252059, China. E-mail: xinnana2008@163.com; literabc@hotmail.com
bLiaocheng Power Supply Company, Liaocheng, Shandong 252059, China
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d1ra04306d
Chart 1 Comparison of the construction of C(sp2)–P bonds to our
current work.
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Table 1 Optimization of reaction conditionsa
Table 3 Scope of alkynesa
Molar ratio
Entry of 1a/2a/Cat Base
Solvent Conversion%
Temp. (1 mL)
(isolated yield%)b
1
2
3
4
5
6
7
8
1 : 2 : 1
1 : 2 : 1
1 : 2 : 1
1 : 2 : 1
1 : 2 : 1
1 : 2 : 0.5
1 : 2 : 0.8
1 : 2 : 1.2
1 : 2 : 1
1 : 2 : 1
1 : 2 : 1
1 : 2 : 1
1 : 2 : 1
1 : 2 : 1
1 : 2 : 1
1 : 2 : 1
1 : 2 : 1
—
—
—
—
—
—
—
—
—
—
—
—
Rt
—
—
—
—
—
—
—
—
12
46
92
98 (53)
98 (56)
79
92
40 ꢀ
60 ꢀ
65 ꢀ
C
C
C
80 ꢀC
65 ꢀ
65 ꢀ
65 ꢀ
65 ꢀ
65 ꢀ
65 ꢀ
C
C
C
C
C
C
86
9
—
CH2Cl2
Toluene
0c
10
11
12
13
14
15
16
17
3
9
0
65 ꢀC THF
—
65 ꢀ
65 ꢀ
C
C
EtOAc
—
—
—
—
22
Na2CO3
Pyridine
0d
65 ꢀC
99 (64)d
99 (54)d
99 (64)d
2,6-Lutidine 65 ꢀC
DBU
65 ꢀC
a
Reaction conditions: 1a (0.2 mmol), 2a (0.40 mmol) and Tf2O (0.2
b
mmol) stirring at different temperatures for 24 h. The conversions
were estimated based on 1H NMR spectrum, and isolated yields were
calculated based on 1a. c TfOH was used. d 1.0 equiv. of base was used.
our delight, diethyl 1-phenyl ethenylphosphonate (3aa), a Mar-
kovnikov addition product, was obtained in high regio-
selectivity but in poor yield (10%). The reaction conditions
were subsequently optimized with 1a and 2a. Considering Tf2O
was moisture sensitive, all experiments were performed under
nitrogen. Two equivalents 2a was used to ensure 1a was
consumed as much as possible. The conversion and isolated
yield were calculated based on 1a (Table 1).
When the mixture of 1a, 2a and Tf2O was stirred at room
temperature, a new signal at 17.1 ppm was observed on 31P
NMR spectrum. The two doublet peaks at 6.35 and 6.17 ppm on
proton NMR spectrum, assigned as 3aa, was detected in 12%
(entry 1 of Table 1). The conversion of 1a was improved to 46%
when the reaction was carried out at 40 ꢀC, and to 92% at 60 ꢀC
(entries 2 and 3). At 65 ꢀC, the conversion was detected in 98%,
and 3aa was isolated, whose structure was conrmed by NMR
a
Isolated yield. b Two equivalents of Tf2O were used. c The alkyne/P–H
regent/Tf2O/pyridine were used in the molar ratio of 1 : 4 : 2 : 2.
spectrum.14 The conversion cannot be further improved at
higher temperature such as 80 C.
ꢀ
When 0.5 equiv. Tf2O was used, the conversion of 1a was
dropped to 79%. The usage of 0.8 equivalent of Tf2O led 92%
conversion (entries 6 and 7). However, excessive Tf2O, such as 1.2
equivalents, resulted in the reduced conversion (86%, entry 8).
Once triic acid was used to replace Tf2O, 3aa was not
detected (entry 9).
To carry the reaction in some solvent such as dichloro-
methane, toluene, THF or ethyl acetate, gave worse result than
neat condition (entries 10–13). In the presence of sodium
carbonate, the reaction cannot take place (entry 14). The pres-
ence of pyridine, 2,6-lutidine or 1,8-diazabicyclo[5.4.0]undec-7-
ene (DBU) slightly increased the conversion (entries 15–17).
Adopting the above optimized condition, the reaction of
alkyne with H-phosphonate was performed (Table 2). Dimethyl
phosphite 2b reacted with phenylacetylene to afford dimethyl 1-
phenylethenyl phosphonate 3ab in 43% yield, which was less
than the reaction of 2a. Perhaps due to the bigger spatial
hindrance, diisopropyl phosphite 2c did not reacted with 1a to
Table 2 Reactivity of phenylacetylene and H-phosphonates
a
Isolated yields based on 1a.
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bromo-substituted alkynes, 3ia and 3ja were afforded in 56%
and 46% yields, respectively. Perhaps due to steric hindrance,
the ortho-chlorophenyl ethyne gave lower yield of 3 than para-
substituted alkyne.
Some ethynyl heterocycles, such as 2- or 3-ethynylthiophene
could be employed for the reaction, affording 3la or 3ma,
respectively. For 1,4-diethynylbenzene (1n), the addition was
realized when 2a and Tf2O were used in double equivalents.
However, the alkynes having strong EWG, such as triuoromethyl
or 3-pyridinyl, cannot react with 2a. Aliphatic terminal alkynes,
such as 1-octyne, also did not afford the product.
The mechanism of the reaction was studied via in situ NMR
experiments, and was proposed in Scheme 1. 2a and Tf2O
formed triate 4 of phosphite via an equilibrium.12b,15 Mean-
while, triic acid was generated (step 1). The addition of triic
acid to 1a formed 1-phenylvinyl triate 5 as an intermediate
(step 2). The subsequent nucleophilic substitution of 5 with 4
Scheme 1 Proposed mechanism.
afford 3ac. The reactions of diphenylphosphine oxide or ethyl formed vinyl phosphonate 3aa (step 3).
phenylphosphinate cannot occur.
The step 1 was conrmed by the observation of the signal of
Various terminal alkynes was then examined (Table 3). acidic proton in TfOH during the mixing of 2a with Tf2O
Besides of 1a, aromatic alkynes possessing electron-donating (Fig. 1A). When 1a was added, 5 was detected, as seen the two
groups smoothly reacted with 2a to afford corresponding 3ba– doublet peaks at 5.61 and 5.38 ppm on 1H NMR spectrum (step
3ha in 17–62% yields. The low yield of 3ha may be ascribed to 2 and Fig. 1B). When the mixture was heated at 60 ꢀC, the
meta-methyl that had variable electronic effect. For chloro and signals of 3aa at 6.16–6.37 ppm emerged. The peaks were
increased with prolonged heating, accompanied with the
decreasing of the signals of 5 (step 3, Fig. 1C and D). Similar
results were observed when Tf2O was initially mixed with 1a
(Fig. 1E–H). Aer heating at 60 ꢀC for 8 h, the signals of 1a,
respected by the peak of terminal alkyne at 3.07 ppm, were
disappeared (Fig. 1H).
The addition of triic acid to 1a probably formed a-carbon
ion as intermediate, which could be stabilized by phenyl and be
converted to Markovnikov-product 5. Although the nucleophilic
substitution on vinyl carbon was difficulty, the strong leaving
activity of triuoromethanesulfonyloxy on 5 enabled step 3
occurred. Miura proposed a cyclic phosphirenium intermediate
for the addition and cyclization,13 which could be probably
stabilized by the alkyl groups of inner-alkynes and secondary
phosphine oxides. In our case, the electron-withdrawing alkoxyl
on phosphorus of 2a was not favorable for the formation of the
phosphirenium, thus the reaction proceeded via a-carbon ion
and addition–substitution occurred.
TfOH was necessary to the formation of 5 from 2a (step 2).
However, triic acid cannot sole promote the reaction, as seen in
entry 9 of Table 1. The results indicated the poor nucleophilic
ability of 2a. Aer 2a was converted to P(III) species 4 by triic
anhydride, the lone electron pair on phosphorus of 4 could attack
5 to form the product. It was not sure the small quartet peak at
4.62 ppm belonged to 4 (Fig. 1F). On 31P NMR spectrum, the peak
of 2a at 17.0 ppm obviously became broad in poor resolution
when mixed with triic anhydride (as seen in ESI†). The results
also supported the equilibrium between 2a and 4 (step 1).
Conclusions
In summary, a mild and convenient method to generate vinyl-
phosphonates was developed. The method employed aryl
Fig. 1 The results of in situ NMR experiments of the reaction of 1a with
2a in the presence of triflic anhydride.
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1
a wide range of aryl alkynes. On the basis of in situ H NMR
studies, an addition–substitution mechanism was proposed,
which was different to the reported phosphirenium
mechanism.
Conflicts of interest
There are no conicts to declare.
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Acknowledgements
This study was nancially supported by NSFC (21502084,
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24994 | RSC Adv., 2021, 11, 24991–24994
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