Aerobic addition of secondary phosphine oxides to vinyl sulfides: A shortcut to 1-hydroxy-2-(organosulfanyl)ethyl-(diorganyl)phosphine oxides

Article abstract of DOI:10.3762/bjoc.11.214

Secondary phosphine oxides react with vinyl sulfides (both alkyl- and aryl-substituted sulfides) under aerobic and solvent-free conditions (80 °C, air, 7-30 h) to afford 1-hydroxy-2-(organosulfanyl)ethyl(diorganyl)phosphine oxides in 70-93% yields.

Full text of DOI:10.3762/bjoc.11.214

Aerobic addition of secondary phosphine oxides to vinyl
sulfides: a shortcut to 1-hydroxy-2-(organosulfanyl)ethyl-
(diorganyl)phosphine oxides
Svetlana F. Malysheva1, Alexander V. Artem’ev1, Nina K. Gusarova1,
Nataliya A. Belogorlova1, Alexander I. Albanov1, C. W. Liu2 and Boris A. Trofimov*1
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2015, 11, 1985–1990.
1A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch,
Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk,
Russian Federation and 2Department of Chemistry, National Dong
Hwa University, Hualien 97401, Taiwan
doi:10.3762/bjoc.11.214
Received: 20 May 2015
Accepted: 21 September 2015
Published: 23 October 2015
Email:
Boris A. Trofimov* - boris_trofimov@irioch.irk.ru
Associate Editor: P. R. Hanson
* Corresponding author
© 2015 Malysheva et al; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
addition; green method; phosphine oxides; regioselectivity; vinyl
sulfides
Abstract
Secondary phosphine oxides react with vinyl sulfides (both alkyl- and aryl-substituted sulfides) under aerobic and solvent-free
conditions (80 °C, air, 7–30 h) to afford 1-hydroxy-2-(organosulfanyl)ethyl(diorganyl)phosphine oxides in 70–93% yields.
Findings
Tertiary phosphines and phosphine chalcogenides are impor- achieved by using radical initiators [13-15], Brønsted/Lewis
tant organophosphorus compounds that are widely used in acids [16,17] and bases [18-20] as well as transition metal cata-
industry, organic synthesis, polymer science, medicinal and lysts [21-23]. Also, examples of the microwave-assisted [24,25]
coordination chemistry [1-4]. Therefore, the synthesis of these and photoinduced [26] addition are described.
compounds has attracted a great interest and numerous syn-
thetic methods have been developed [5-7]. Among them, the Recently, on example of secondary phosphines [27] as well as
addition of P(X)–H (X = none, O, S or Se) to diverse alkenes is secondary phosphine sulfides [28] and selenides [29], it has
one of the most powerful and 100% atom-economic approaches been disclosed that the addition of P–H species to the C=C
to construct new C–P bonds, that provide straightforward access bonds readily proceeds in the absence of any catalyst or initiator
to tertiary phosphines and their chalcogenides [8-12]. Conven- (Scheme 1). The reactions occur under mild solvent-free condi-
tionally, the activation of the P–H bonds in this reaction is tions (70–80 °C, inert atmosphere, 3–15 h) to chemo- and
1985

Beilstein J. Org. Chem. 2015, 11, 1985–1990.
regioselectively furnish the anti-Markovnikov adducts in excel- In this letter, we report our serendipitous finding that secondary
lent yields (up to 99%). The substrate scope includes both phosphine oxides 1a–f under aerobic conditions (air, 80 °C,
EDG- and EWG-substituted alkenes [27-29].
7–18 h) easily add to vinyl sulfides 2a–c to give unknown
1-hydroxy-2-(organosulfanyl)ethyl(diorganyl)phosphine oxides
3a–h in high yields (Table 1). The 10% excess of 2a–c relative
to 1a–f is found to be optimal since the equimolar ratio of the
reactants leads to incomplete conversion of the secondary phos-
phine oxides.
Importantly, under these conditions, the expected [30] anti-
Markovnikov adducts are not observed in detectable amounts
(31P NMR). The main byproducts are phosphinic acids,
R2P(O)OH, formed by air oxidation of secondary phosphine
oxides 1a–f. As seen from Table 1, the reaction is applicable to
Scheme 1: Non-catalyzed addition of P–H species to alkenes.
Table 1: The substrate scope for the aerobic addition of phosphine oxides 1a–f to vinyl sulfides 2a–c.a
Phosphine
oxide 3a–h (yield, %)b
Entry
Phosphine oxide
Vinyl sulfide
Time, h
1
16
2a
1a
3a (80%)
2
30
2b
1a
3b (78%)
3c (70%)
Ph2P(O)H
3
7
1b
2c
4
11
2c
1a
3d (91%)
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Beilstein J. Org. Chem. 2015, 11, 1985–1990.
Table 1: The substrate scope for the aerobic addition of phosphine oxides 1a–f to vinyl sulfides 2a–c.a (continued)
5
6
7
8
15
15
15
18
2c
2c
2c
2c
1c
3e (93%)
1d
3f (90%)
1e
3g (82%)
1f
3h (89%)
aReaction conditions: secondary phosphine oxide 1a–f (1.0 mmol), vinyl sulfide 2a–c (1.1 mmol) at 80 °C for 7–30 h under air. bIsolated yield based
on 1a–f.
both aryl- (1b) and arylalkyl-substituted (1a,c–e) secondary Phosphine oxide 3d crystallizes in the centrosymmetric P21/c
phosphine oxides. The furyl-containing phosphine oxide 1f can space group. Within its extended structure, strong intermolec-
also be reacted under these reaction conditions. On the other ular H-bonding interactions between the O–H hydrogen and
hand, vinyl sulfides bearing alkyl (2a,b) and aryl (2c) P=O oxygen atom of a second molecule {O(1)–H(1)···O(2),
substituents successfully participate in the reaction to provide 1.80(6) Å; O–H···O angle, 174.9(7)°} leads to the formation of
the corresponding phosphine oxides 3a–h. The latter were 1D polymeric chains along the b-axis (Figure S1, Supporting
isolated as air- and moisture-stable powders (3a–f) or oils Information File 1).
(3g,h), soluble in common organic solvents. Their structures
have been established by X-ray diffraction (for 3d, Figure 1), In FTIR spectra of 3a–h, absorption bands of the P=O
NMR (1H, 13C, 31P, 1H,13C-HSQC) and FTIR techniques.
and O–H bonds appear in the regions of 1100–1150 and
3350–3450 cm−1, respectively.
The presence of an asymmetric carbon atom in the reaction
products leads to non-equivalence of both heminal protons in Interestingly, the reaction disclosed is specific for secondary
the SCH2C* fragment and carbon signals in the arylethyl phosphine oxides. Our experiments have shown that their
moiety. In the 1H NMR spectra of 3a–h, protons of the analogues, secondary phosphine sulfides, under similar condi-
PCHCH2S moiety form an ABMX spin system appearing as tions provide exclusively the anti-Markovnikov adducts
three multiplets.
(Scheme 2). On the other hand, vinyl ethers and vinyl selenides
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Beilstein J. Org. Chem. 2015, 11, 1985–1990.
Figure 1: ORTEP drawing (30% thermal ellipsoid) of phosphine oxide 3d. A CIF file with the crystallographic data is available as Supporting Informa-
tion File 2 and is also available on request from the Cambridge Crystallographic Data Centre as deposition 1046604.
(congeners of vinyl sulfides) were found to react with phosphi- conversion of secondary phosphine oxide 1a as compared to
ne oxide 1a at 80 °C for about 30 and 20 h, respectively, to TEMPO-free conditions (15 vs 11 h). Meanwhile, this observa-
deliver difficult-to-separate mixtures of organophosphorus com- tion does not completely exclude a radical mechanism since the
pounds (31P NMR).
cross-coupling reactions between TEMPO and radical inter-
mediates can be reversible [31]. In future, we intend to check
various radical scavengers (other than TEMPO) in order to
better understand the reaction mechanism.
Taking these data into account, the following mechanism is
suggested (Scheme 3). The first step is assumed to be the gener-
ation of phosphinoyl (A) and hydroperoxyl (HOO•) radicals by
the reaction of O2 with phosphine oxide 1. Earlier, the transfer
of a hydrogen atom from the P(O)H species to molecular
oxygen has been reported for example for Ph2P(O)H [30].
Then, the radical addition of A to vinyl sulfide, proceeding in
Scheme 2: Addition of secondary phosphine sulfide to vinyl sulfide
under aerobic catalyst-free conditions.
To gain a primary insight into the reaction mechanism, several an anti-Markovnikov manner, takes place. Subsequently, a 1,2-
experiments were carried out. On example of phosphine oxide intramolecular transfer of an H atom within the radical adduct B
1a and vinyl sulfide 2c, we have shown that the reaction (from PCH2 group to radical center) leads to the formation of
proceeds in the dark with the same efficiency as in the light. R2P(O)-stabilized radical C. The latter recombines with a
Therefore, the photochemical pathway of the reaction is hardly hydroperoxide radical to afford the metastable hydroperoxide
probable. Also, the reaction was established under an argon D, thermal decomposition of which give rise to the final pro-
atmosphere. Under these conditions (argon, 80 °C for 18 h, duct 3.
exemplified by 1a/2c pair) the formation of products 3a–h does
not take place and the starting phosphine oxide remained almost Although quantum chemical computations [MP2/6-
intact (31P NMR). This indicates that the reaction requires the 311++G(d,p)//B3LYP/6-311++G(d,p)] of the model radicals B
presence of oxygen. In the other experiment, when TEMPO, a and C (with R, R' = Me) reveals that the latter is energetically
widely used radical scavenger, was added (10 mol %) into the less preferred than the former, their energy difference is too
reaction system 1a/2c, the product 3d was also formed, small (4.38 kcal/mol) to completely prohibit the B→C transfor-
however, a longer reaction time was required for complete mation.
1988

Beilstein J. Org. Chem. 2015, 11, 1985–1990.
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