First Examples of the Atherton-Todd-Like Reaction in the Absence of Bases

Article abstract of DOI:10.1002/hc.21299

Oxidative cross-coupling between secondary phosphine chalcogenides and alcohols or phenols proceeds in CCl₄ medium at 80-82C to afford phosphinoCyrillic small letter eshalcogenCyrillic small letter oic O-esters in up to 92% yield. These couplings represent first examples of the Atherton-Todd-like reaction occurring in the absence of bases.

Full text of DOI:10.1002/hc.21299

Heteroatom Chemistry
Volume 27, Number 1, 2016
First Examples of the Atherton–Todd-Like
Reaction in the Absence of Bases
Boris A. Trofimov, Nina K. Gusarova, Pavel А. Volkov,
Nina I. Ivanova, and Kseniya O. Khrapova
E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1
Favorsky Str., 664033, Irkutsk, Russian Federation
Received 16 July 2015; revised 25 August 2015; accepted 25 August 2015
reaction are only realized in the presence of the
ABSTRACT: Oxidative cross-coupling between sec-
oxidative system base/polyhaloalkane (as a rule, in
ondary phosphine chalcogenides and alcohols or phe-
the Et3N/CCl4 system) [1–3]. According to the latest
nols proceeds in CCl4 medium at 80–82°C to af-
data [2c, [5]], the role of this system is in its in-
ford phosphinoсhalcogenоic O-esters in up to 92%
teractions with dialkylphosphites by two pathways
yield. These couplings represent first examples of the
(i and ii) to produce intermediate chlorophosphate A
Atherton–Todd-like reaction occurring in the absence
(Scheme 1).
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of bases.
2015 Wiley Periodicals, Inc. Heteroatom
Chlorophosphates A react further with NH-,
OH-, and SH-compounds to give amides, ethers, and
thioethers of phosphoric acid, respectively [1,2].
In this work, on the example of oxidative phos-
phorylation of alcohols and phenols with the system
secondary phosphine chalcogenides/CCl4, we first re-
port on a new variant of the Atherton–Todd reaction
proceeding in the absence of any bases.
Chem. 27:44–47, 2016; View this article online at wi-
leyonlinelibrary.com. DOI 10.1002/hc.21299
INTRODUCTION
The Atherton–Todd reaction [1] continues to attract
the attention of researchers as a convenient tool
to prepare diverse derivatives of phosphoric and
phosphinic acids [2]. This reaction has been dis-
covered as an example of the synthesis of phos-
phoramidates from dialkylphosphites and primary
or secondary amines. Later, the Atherton–Todd re-
action has been extended to alcohols and thiols as
well as to secondary phosphine oxides [2b-d, [3]].
Recently, secondary phosphine sulfides and phos-
phine selenides were also used in the reactions with
NH-, OH-, and SH-compounds for the synthesis of
amides, ethers, and thioethers of chalcogenophos-
phinic acids [2c, [4]]. To the best of our knowledge,
all hitherto known variants of the Atherton–Todd
The experiments have shown that bis(2-
phenethyl)phosphine sulfide 1 and bis(2-phenethyl)
phosphine selenide 2 react with alcohols 3, 4 or
phenols 5, 6 in CCl4 medium at 80–82°C to form
phosphinoсhalcogenоic O-esters 7 in 85–92% yields,
when selenide 2 in used (Table 1, entries 2–5), and in
26% yield in the case of sulfide 1 (Table 1, entry 1).
The oxidative phosphorylation of alcohols and
phenols with the system secondary phosphine
chalcogenide/CCl4 in the absence of bases can be ra-
tionalized as follows. On the first step, P,X-ambident
secondary phosphine chalcogenides 1, 2 react with
CCl4 as tautomers А to give phosphonium salts В.
The latter are in equilibrium with phosphorane С,
in which the cleavage of the C–P and Х–H bonds
occurs to deliver chlorophosphinechalcogenides D
and chloroform. The former reacts further with
ROH to afford phosphinochalcogenoic O-esters 7a–e
(Scheme 2).
Correspondence to: Boris A. Trofimov; e-mail: boris_trofimov@
irioch.irk.ru.
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2015 Wiley Periodicals, Inc.
44

First Examples of the Atherton–Todd-Like Reaction in the Absence of Bases 45
pathways i
pathways ii
B
B
[BCl]
+ CCl4
O
RO
RO
P
CCl3
O
H
O
RO
P
RO
RO
RO
Cl
P
A
CHCl3
SCHEME 1 Two pathways (i and ii) оf chlorophosphate A formation.
To conclude, the direct phosphorylation of al-
cohols or phenols with the secondary phosphine
chalcogenides/carbon tetrachloride system in the
absence of bases affording phosphinochalcogenoic
O-esters fundamentally contributes to the develop-
ment for the Atherton–Todd reaction.
phosphine chalcogenides 1, 2 were prepared from
styrene and elemental phosphorus as previously re-
ported [7]. NMR spectral data of esters 7d,e are
identical to those of samples described in earlier
publication [4a]. The1H, 13C, 31P, and 77Se NMR
spectra were recorded on a Bruker DPX 400 spec-
trometer (400.13, 100.61, 161.98, and 76.31 MHz,
respectively) in CDCl3 solutions and referenced to
TMS (1H NMR, 13C NMR), H3PO4 (31P NMR) and
Me2Se (77Se NMR). IR spectra were run on a
Bruker Vertex 70 instrument. Melting points (uncor-
rected) were measured on a Kofler micro hot-stage
EXPERIMENTAL
All reactions were carried out under an argon at-
mosphere. Carbon tetrachloride was purified ac-
cording to the standard procedure [6]. Secondary
TABLE 1 Synthesis of Phosphinochalcogenoic O-esters 7a–ea
Entry
[Ph(CH2)2]2P(X)H
X
HOR
3–6
R
Time
(h)
Product
7a–e
Yield
(%)
1, 2
1b
2
3
4
5
1
2
2
2
2
S
4
3
4
5
6
Amyl
Bu
Amyl
Ph
74
22
12
12
22
7a
7b
7c
7d
7e
26
92
86
85
87
Se
Se
Se
Se
1-Napht
aAll experiments were carried out under argon atmosphere at 80–82°C for 74 h (in the case of phosphine sulfide 1) and 12–22 h (when
phosphine selenide 2 was used); phosphine chalcogenides 1, 2 (1 mmol), HOR (1.1 mmol) and CCl4 (4 ml) were used. Under these conditions,
chloroform is also formed.
bIn this experiment, significant amount (yield 58%) of bis(2-phenethylthiophosphoryl)oxide is formed.
Heteroatom Chemistry DOI 10.1002/hc

46 Trofimov et al.
SCHEME 2 A plausible mechanism for the formation of O-esters 7a–e.
2
apparatus. The microanalyses were performed on a
Flash EA 1112 Series elemental analyzer.
68.1 Hz), 64.6 (d, OCH2, JPC 6.9 Hz), 126.0 (Cp),
3
127.8 (Co), 128.2 (Cm), 140.3 (d, Ci, JPC 15.1 Hz).
The reaction was monitored using 31P NMR
spectra by the disappearance of peaks of the ini-
tial bis(2-phenethyl)phosphine sulfide 1 (δP 21.3
ppm) [7a], bis(2-phenethyl)phosphine selenide 2
(δP 2.2 ppm) [7b], and appearance of new peaks
corresponding to O-esters 7a–e. Chlorophos-
phinechalcogenides D (Scheme 2) were identified
using an authentic sample [8] by 31P NMR.
31P NMR (161.98 MHz, CDCl3) δ: 101.1. Anal. Calcd
for C21H29OPS: C, 69.97; H, 8.11; P, 8.59; S, 8.90.
Found: C, 69.69; H, 7.99; P, 8.13; S, 8.78.
Bis(2-phenethyl)phosphinoselenoic O-Buthyl Es-
ter (7b). Waxy product; yield: 361 mg (92%). IR
(neat): 1214 (P–O–C), 581 cm–1 (P=Se). 1H NMR
3
(400.13 MHz, CDCl3) δ: 0.92 (t, 3H, Me, JHH
7.3 Hz), 1.32–1.41 (m, 2H, CH2Me), 1.55–1.63
(m, 2H, CH2Et), 2.25–2.41 (m, 4H, CH2P), 2.83–
Phosphinochalcogenoic O-Esters 7a–e (General
3
3.00 (m, 4H, PhCH2), 3.95 (dt, 2H, OCH2, JHH 6.6
Procedure)
Hz, 3JPH 9.2 Hz), 7.16–7.21, 7.26–7.29 (m, 10H, Ph).
13C NMR (100.61 MHz, CDCl3) δ: 13.2 (Me), 18.4
A mixture of bis(2-phenethyl)phosphine chalco-
genide (1.0 mmol) and alcohol or phenols (1.1
mmol) in 4 ml of CCl4 was stirred at 80–82°C
for 74 h (in the case of phosphine sulfide 1) and
12–22 h (when phosphine selenide 2 was used)
(see also Table 1). The formation of chloroform
in the reaction mixture was detected by 13C NMR.
The solvent was removed under the reduced pres-
sure; the precipitate was purified by column chro-
matography (Al2O3, hexane:Et2O:CHCl3 = 10:2:1)
and dried in vacuum to afford esters 7a–b. Bis(2-
phenethylthiophosphoryl)oxide [3b] (in the case of
phosphine sulfide 1) was isolated in 58% yield.
2
(CH2Me), 28.7 (d, PhCH2, JPC 2.0 Hz), 32.0 (d,
CH2Et, 3JPC 6.9 Hz), 36.9 (d, CH2P,1JPC 58.2 Hz), 65.8
2
(d, OCH2, JPC 6.5 Hz), 126.0 (Cp), 127.8 (Co), 128.2
(Cm), 139.9 (d, Ci,3JPC 15.5 Hz). 31P NMR (161.98
1
MHz, CDCl3) δ: 102.0 (s) (+ d satellite, JPSe 771.5
Hz). Anal. Calcd for C20H27OPSe: C, 61.07; H, 6.92;
P, 7.87; Se, 20.07. Found: C, 60.89; H, 6.83; P, 7.69;
Se, 19.88.
Bis(2-phenethyl)phosphinoselenoic
O-1-Pentyl
Ester (7c). Waxy product; yield: 350 mg (86%). IR
(neat): 1213 (P–O–C), 581 cm–1 (P=Se). 1H NMR
3
(400.13 MHz, CDCl3) δ: 0.93 (t, 3H, Me, JHH 6.7
Bis(2-phenethyl)phosphinothioic
O-1-Pentyl
Hz), 1.34–1.37 (m, 4H, CH2Me, CH2Et), 1.61–1.68
(m, 2H, CH2Pr), 2.29–2.45 (m, 4H, CH2P), 2.87–3.06
Ester (7a). Waxy product; yield: 94 mg (26%). IR
(neat): 1214 (P–O–C), 612 cm–1 (P=S). 1H NMR (400.
(m, 4H, PhCH2), 3.97 (dt, 2H, OCH2, JHH 6.7 Hz,
3
3
13 MHz, CDCl3) δ: 0.89 (t, 3H, Me, JHH 6.5 Hz),
3JPH 9.2 Hz), 7.20–7.25, 7.29–7.33 (m, 10H, Ph).
1.31–1.34 (m, 4H, CH2Me, CH2Et), 1.59–1.63 (m,
2H, CH2Pr), 2.16–2.25 (m, 4H, CH2P), 2.87–3.98
13C NMR (100.61 MHz, CDCl3) δ: 14.0 (Me), 22.3
2
(CH2Me), 24.0 (CH2Et), 29.2 (d, PhCH2, JPC 2.0
3
(m, 4H, PhCH2), 3.94 (dt, 2H, OCH2, JHH 6.8 Hz,
Hz), 30.1 (d, CH2Pr, 3JPC 6.9 Hz), 37.4 (d, CH2P,1JPC
3JPH 8.8 Hz), 7.16–7.21, 7.26–7.29 (m, 10H, Ph).
13C NMR (100.61 MHz, CDCl3) δ: 13.5 (Me), 21.8
57.8 Hz), 66.6 (d, OCH2, JPC 6.5 Hz), 126.5 (Cp),
2
128.3 (Co), 128.7 (Cm), 140.4 (d, Ci, 3JPC 15.5 Hz). 31
P
2
(CH2Me), 27.4 (CH2Et), 28.4 (d, PhCH2, JPC 2.2
NMR (161.98 MHz, CDCl3) δ: 102.6 (s) (+ d satellite,
Hz), 29.8 (d, CH2Pr,3JPC 6.5 Hz), 35.8 (d, CH2P,1JPC
1JPSe 770.5 Hz). Anal. Calcd for C21H29OPSe: C,
Heteroatom Chemistry DOI 10.1002/hc

First Examples of the Atherton–Todd-Like Reaction in the Absence of Bases 47
61.91; H, 7.18; P, 7.60; Se, 19.38. Found: C, 61.79;
H, 7.05; P, 7.43; Se, 19.21.
REFERENCES
[1] (a) Atherton, F. R.; Openshw, H. T.; Todd, A. R. J Chem
Soc 1945, 660–663; (b) Atherton, F. R.; Todd, A. R. J
Chem Soc 1947, 674–678.
Bis(2-phenethyl)phosphinoselenoic O-Phenyl Es-
ter (7d). Waxy product; yield: 351 mg (85%). IR
(neat): 1198 (P–O–C), 583 cm–1 (P=Se). 1H NMR
(400.13 MHz, CDCl3) δ: 2.49–2.58 (m, 4Н, СН2Р),
2.97–3.09 (m, 4Н, РhСН2), 7.18–7.23, 7.28-7.37 (m,
15Н, Ph, OPh). 13C NMR (100.61 MHz, CDCl3) δ:
[2] (a) Hassner, A.; Stumer, C. In Tetrahedron Organic
Chemistry Series; Elsevier, New York, 2002; Vol. 22,
p. 443; (b) Wagner, S.; Rakotomalala, M.; Bykov, Y.;
Walter, O.; Do¨ring, M. Heteroatom Chem 2012, 23,
216–222; (c) Le Corre, S. S.; Berchel, M.; Couthon-
Gourve`s, H.; Haelters, J.-P.; Jaffre`s, P.-A. Beilstein J
Org Chem 2014, 10, 1166–1196; (d) Ilia, G.; Petric, M.;
Ba´lint, E.; Keglevich, G. Heteroatom Chem 2015, 26,
29–34; (e) Xiong, B.; Zhou, Y.; Zhao, C.; Goto, M.; Yin,
S.-F.; Han, L.-B. Tetrahedron 2013, 45, 9373–9380; (f)
Mitova, V.; Koseva, N.; Troev, K. RSC Adv 2014, 4,
64733–64736.
[3] (a) Rauhut, M. M.; Currier, H. A. J Org Chem 1961, 26,
4628; (b) Wang, G.; Shen, R.; Xu, Q.; Goto, M.; Zhao,
Y.; Han, L.-B. J Org Chem 2010, 75, 3890–3892.
[4] (a) Gusarova, N. K.; Volkov, P. A.; Ivanova, N. I.;
Larina, L. I.; Trofimov, B. A. Synthesis 2011, 3723–
3729; (b) Gusarova, N. K.; Volkov, P. A.; Ivanova, N.
I.; Larina, L. I.; Trofimov, B. A. Heteroatom Chem
2012, 23, 322–328; (c) Gusarova, N. K.; Volkov, P. A.;
Ivanova, N. I.; Oparina, L. А.; Kolyvanov, N. А.; Vysot-
skaya, O. V.; Larina, L. I.; Trofimov, B. A. Synthesis
2011, 3723–3729; (d) Gusarova, N. K.; Volkov, P. A.;
Ivanova, N. I.; Gatilov, Y. V.; Trofimov, B. A. Tetrahe-
dron Lett 2013, 54, 3543–3545; (e) Gusarova, N. K.;
Volkov, P. A.; Ivanova, N. I.; Sukhov, B. G.; Khrapova,
K. O.; Zelenkov, L. E.; Smirnov, V. I.; Borodina, T. N.;
Vakul’skaya, T. I.; Khutsishvili, S. S.; Trofimov, B. A.
Heteroatom Chem 2015, 26, 329–334.
[5] Krutikov, V. I.; Erkin, A. V.; Krutikova, V. V. Russ J
Gen Chem 2012, 82, 822–826.
[6] Armarego, W. L. E.; Chai, C. L. L. Purification of Labo-
ratory Chemicals, 5th ed.; Elsevier Science: New York,
2003.
[7] (a) Gusarova, N. K.; Bogdanova, M. V.; Ivanova, N.
I.; Сhernysheva, N. А.; Sukhov, B. G.; Sinegovskaya,
L. M.; Kazheva, O. N.; Alexandrov, G. G.; D’yachenko,
O. A.; Trofimov, B. A. Synthesis 2005, 3103–3106; (b)
Sukhov, B. G.; Gusarova, N. K.; Ivanova, N. I.; Bog-
danova, M. V.; Kazheva, O. N.; Alexandrov, G. G.;
D’yachenko, O. A.; Sinegovskaya, L. M.; Malysheva, S.
F.; Trofimov, B. A. J Struct Chem (Engl Transl) 2005,
46, 1066–1071; (c) Trofimov, B. A.; Gusarova, N. K.
Mendeleev Commun 2009, 19, 295–302.
1
29.1 (PhСН2), 37.4 (d, СН2Р, JPС 56.4 Hz), 121.8
(d, Со, OPh,3JРС 4.1 Hz), 125.2 (Сp, OPh), 126.6 (Сp,
Ph), 128.3 (Сo, Ph), 128.7 (Сm, Ph), 129.5 (Сm, OPh),
140.1 (d, Ci, Ph,3JPС 15.5 Hz), 150.5 (d, Ci, OPh,2JPС
9.6 Hz). 31P NMR (161.98 MHz, CDCl3) δ: 104.3 (s)
(+d satellite, 1JPSe 803.1 Hz). 77Se NMR (76.31 MHz,
1
CDCl3) δ: -246.8 (d, JPSe 803.1 Hz). Anal. Calcd for
С22Н23OPSe: С, 63.93; Н, 5.61; Р, 7.49; Se, 19.10.
Found: С, 63.82; Н, 5.54; Р, 7.37; Se, 18.96.
Bis(2-phenethyl)phosphinoselenoic O-1-Naphthyl
Ester (7e). White solid; yield: 403 mg (87%); mp
95–97°C (hexane). IR (KBr): 1228 ν (P–O–C), 587
cm−1 ν (P=Se). 1H NMR (400.13 MHz, CDCl3) δ:
2.64–2.72 (m, 4Н, СН2Р), 2.97–3.16 (m, 4Н, РhСН2),
7.17–7.20 (m, 4Н, Hp), 7.23–7.33 (m, 6Н, Ho, Hm),
3
7.45 (dd, 1Н, H-3, Napht,3JHH 8.1 Hz, JHH 7.8 Hz),
7.53–7.56 (m, 2Н, Н-5, Н-8, Napht), 7.69–7.72 (m,
2Н, Н-2, Н-4, Napht), 7.87–7.89 (m, 1Н, Н-7, Napht),
8.05–8.08 (m, 1Н, Н-6, Napht). 13C NMR (100.61
MHz, CDCl3) δ: 29.5 (PhСН2), 38.0 (d, СН2Р,1JPС 58.6
3
Hz), 116.3 (d, C-2, Napht, JРС 5.5 Hz), 121.6 (C-6,
Napht), 124.8 (C-4, Napht), 125.2 (C-3, Napht), 126.3
(C-5, C-8, Napht), 126.6 (Cp), 128.0 (C-7, С-10,
Napht), 128.3 (Со), 128.7 (Сm), 134.9 (C-9, Napht),
140.0 (d, Сi,3JРС 15.8 Hz), 147.1 (d, С-1, Napht,3JРС
11.0 Hz). 31P NMR (161.98 MHz, CDCl3) δ: 105.1
1
(s) (+d satellite, JPSe 804.2 Hz). 77Se NMR (76.31
MHz, CDCl3) δ: -236.4 (d, 1JPSe 804.2 Hz). Anal. Calcd
for С26Н25OРSe: С, 67.39; Н, 5.44; Р, 6.68; Se, 17.04.
Found: C, 67.27; Н, 5.36; Р, 6.59; Se, 16.88.
[8] (a) Malysheva, S. F.; Artem’ev, A. V.; Gusarova, N. K.;
Klyba, L. V.; Tatarinova, A. A.; Trofimov, B. A. Russ
J Gen Chem 2010, 80, 1043–1044; (b) Gusarova, N.
K.; Volkov, P. A.; Ivanova, N. I.; Khrapova, K. O.;
Trofimov, B. A. Russ J Gen Chem 2015, 85, 380–
382.
ACKNOWLEDGMENT
This work was supported by leading scientific
schools by the President of the Russian Federation
(grant NSh-156.2014.3).
Heteroatom Chemistry DOI 10.1002/hc