Bifunctionalized allenes. Part XV. Synthesis of 2,5-dihydro-1,2- oxaphospholes by electrophilic cyclization reaction of phosphorylated α-hydroxyallenes

Article abstract of DOI:10.3390/molecules190811056

This paper discusses a reaction of phosphorylated α-hydroxyallenes with protected or unprotected hydroxy groups involving 5-endo-trig cyclizations. Various electrophilic reagents such as sulfuryl chloride, bromine, benzenesulfenyl and benzeneselenenyl chlorides have been applied. The paper describes the reaction of 1-hydroxyalkyl-1,2-dienephosphonates with electrophiles that produces 2-methoxy-2-oxo-2,5-dihydro-1,2-oxaphospholes due to the participation of the phosphonate neighbouring group in the cyclization. On the other hand, (1E)-alk-1-en-1-yl phosphine oxides were prepared as mixtures with 2,5-dihydro-1,2-oxaphosphol-2-ium halides in a ratio of about 1:2 by chemo-, regio, and stereoselective electrophilic addition to the C ²-C³-double bond in the allene moiety and subsequent concurrent attack of the external (halide anion) and internal (phosphine oxide group) nucleophiles. The paper proposes a possible mechanism that involves cyclization and additional reactions of the phosphorylated α- hydroxyallenes.

Full text of DOI:10.3390/molecules190811056

Molecules 2014, 19, 11056-11076; doi:10.3390/molecules190811056
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Bifunctionalized Allenes. Part XV. Synthesis of 2,5-dihydro-1,2-
oxaphospholes by Electrophilic Cyclization Reaction of
Phosphorylated α-Hydroxyallenes
†
†
†,
Ismail E. Ismailov , Ivaylo K. Ivanov and Valerij Ch. Christov *
Department of Organic Chemistry & Technology, Faculty of Natural Sciences, Konstantin Preslavsky
University of Shumen, 115, Universitetska str., BG-9712 Shumen, Bulgaria;
E-Mails: ismail78@mail.bg (I.E.I.); iivanov@shu-bg.net (I.K.I.)
†
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed; E-Mail: vchristo@shu-bg.net;
Tel.: +359-54-830-495; Fax: +359-54-830-371.
Received: 2 July 2014; in revised form: 21 July 2014 / Accepted: 23 July 2014 /
Published: 29 July 2014
Abstract: This paper discusses a reaction of phosphorylated α-hydroxyallenes with
protected or unprotected hydroxy groups involving 5-endo-trig cyclizations. Various
electrophilic reagents such as sulfuryl chloride, bromine, benzenesulfenyl and
benzeneselenenyl chlorides have been applied. The paper describes the reaction of
1
2
-hydroxyalkyl-1,2-dienephosphonates with electrophiles that produces 2-methoxy-2-oxo-
,5-dihydro-1,2-oxaphospholes due to the participation of the phosphonate neighbouring
group in the cyclization. On the other hand, (1E)-alk-1-en-1-yl phosphine oxides were
prepared as mixtures with 2,5-dihydro-1,2-oxaphosphol-2-ium halides in a ratio of about
2
3
1
:2 by chemo-, regio, and stereoselective electrophilic addition to the C -C -double bond in
the allene moiety and subsequent concurrent attack of the external (halide anion) and
internal (phosphine oxide group) nucleophiles. The paper proposes a possible mechanism
that involves cyclization and additional reactions of the phosphorylated α-hydroxyallenes.
Keywords: phosphorylated α-hydroxyallenes; electrophilic cyclization; neighbouring
group participation; 2,5-dihydro-1,2-oxaphospholes; (1E)-2,3-adducts

Molecules 2014, 19
. Introduction
Functionalized allenes are considered to be versatile building blocks for organic synthesis and that
11057
1
fact has attracted growing attention during the past four decades [1–8]. The synthetic potential of
functionalized allenes has led to the development of new and unique methods applied in the process of
constructing various functionalized heterocyclic and carbocyclic systems [9–12].
The reactivity of allenes is mainly characterized by electrophilic addition reactions where the
addition products of the reagent in one and/or other double bond of the allenic system are usually
obtained [13–18]. Functionalized allenes are also very interesting substrates as a material of choice to
study the electrophilic addition reactions on the carbon-carbon double bonds [19–23]. Functional
groups linked to the allenic system change considerably the course of the reactions with electrophilic
reagents and this is the significant differrence from allenic hydrocarbons. One can see [19–23] that in
most cases the reactions proceed with cyclization of the allenic system bearing a functional group
leading to heterocyclic compounds. This makes the investigation of functionalized allenes, more
specifically the study of their reactions with electrophilic reagents, quite an interesting and topical task.
It is known that the 2,5-dihydrofurans and derivatives thereof represent pivotal structural elements
in a wide variety of different biologically active molecules. For instance, they can be found in
mycotoxins such as verrucosidine [24] and the structurally related citreoviridine [25] as well as
vitamin A metabolites [26], polyether antibiotics [27,28], spiroketals [29], and even amino acids [30].
Thus, the efficient synthesis of suitably functionalized 2,5-dihydrofurans by electrophilic cyclization of
α-hydroxyallenes [31–44] is highly attractive.
On the contrary, the literature data on the reactions of phosphorylated allenes (phosphonates,
phosphinates and phosphine oxides) with electrophilic reagents reveal that the reactions proceed with
cyclization of the allenic system bearing the phosphoryl group (O=P-C=C=C) to give heterocyclic
compounds in most cases and the outcome depends on the structure of the starting allenic compound as
well as the type of electrophile used [19–23]. The reaction of electrophilic reagents with
allenephosphonates [19–23] or allenyl phosphine oxides [45–47] leads to 2,5-dihydro-1,2-
oxaphospholes or/and 2,1- or/and 2,3-adducts or a mixture of these compounds, depending on the
1
3
degree of substitution at the C - and C -atoms of the allenic system, as well as on the nature of these
substituents, and on the type of the reagents. Ma and coworkers [48–50] recently observed that the
electrophilic iodohydroxylation [48], fluorohydroxylation [49] and selenohydroxylation [50] reactions
of allenyl phosphine oxides with iodine, Selectfluor and benzeneselenenyl chloride lead to 2-iodo-
(
respectively 2-fluoro- or 2-phenylselenenyl-)3-hydroxy-1(E)-alkenyl phosphine oxides with high
regio- and stereoselectivities. In [48–50] the respective authors comment that this fact is due to the
neighbouring group participation effect of the diphenyl phosphine oxide functionality. In recent papers
we have reported the reactions of 1-vinyl- [51] and 3-vinylallenyl [52] phosphine oxides with
electrophiles leading to formation of various heterocyclic or highly unsaturated compounds.
Our long-standing research program focuses on the development of efficient electrophilic
cyclization reactions of 1,3-bifunctionalized allenes [53,54]. More specifically, our attention is drawn
to 1,1-bifunctionalized allenes such as 1–4 that comprise a phosphoryl and a hydroxyalkyl group
(
Scheme 1). The applications of these groups as temporary transformers of chemical reactivity of the
allenic system in the synthesis of eventually heterocyclic compounds are of particular interest. These

Molecules 2014, 19
11058
molecules can be considered a combination of an allenephosphonate or allenyl phosphine oxide and a
hydroxyallene and they are supposed to have different reactivity profiles in electrophilic reactions. Our
recent research has led to a significant result, whereby we have developed a convenient and efficient
method for the regioselective synthesis of phosphorylated α-hydroxyallenes using an atom economical
[2,3]-sigmatropic rearrangement of intermediate propargyl phosphites or phosphinites, which can be
readily prepared via reactions of protected alkynols with dimethyl chlorophosphite or chlorodiphenyl
phosphine, respectively, in the presence of a base [55].
2
. Results and Discussion
2
.1. Electrophilic Cyclization Reaction of Phosphorylated α-Hydroxyallenes with Protected and
Unprotected Hydroxy Groups
It is necessary to draw attention to the fact that conceptually two distinct modes of cyclization of the
phosphorylated α-hydroxyallenes are possible. They depend on the electrophilic atom that forms a new
bond with the central carbon of the allenic system, which seems likely [19–23]. It is evident that these
pathways are closely connected with the intramolecular neighbouring group participation of the
phosphoryl and/or the hydroxyalkyl groups as internal nucleophile(s) in the final step of the
cyclization. Besides the 5-endo-trig cyclizations [56] to the 2,5-dihydro-1,2-oxaphospholes I or to the
2
3
,5-dihydrofurans II, electrophilic addition might afford the 2,3-adducts III and/or the
,2-adducts IV (Scheme 1).
Scheme 1. Probable products of the electrophilic reaction of the phosphorylated
α-hydroxyallenes 1–4.
O
Z
•
R
R1
1
, Z = THP, Y=MeO
R2
R3
2, Z = OH, Y=MeO
3
4
, Z = THP, Y=Ph
, Z = OH, Y=Ph
Y2P
O
1-4
E-Nu
R2
R3
O
Z
R
R1
O
O
O
Z
O Z
R
R1
R
R1
R
R1
(O)P
E
E
E
R2
R3
Y
R2
R3
Y
2
R2
Y2P
Y2P
E
Nu
P
Y
O
O
R3
Nu
I
II
III
IV
The present paper is a part of our long-term objective to investigate both the advantages and the
limitations of the electrophilic cyclization reactions of 1,1-bifunctionalized allenes.

Molecules 2014, 19
.1.1. Electrophilic Cyclization Reaction of the 1-Hydroxyalkyl-allenephosphonates 1 and 2
We started the present study with the electrophilic cyclization reaction of dimethyl 3-methyl-1-
11059
2
(
tetrahydro-2H-pyran-2-yloxymethyl)-penta-1,2-dienephosphonate (1a) with bromine (Scheme 2).
Scheme 2. Synthesis of the 2-[(4-bromo-5-ethyl-2-methoxy-5-methyl-2-oxo-2,5-dihydro-
1
,2-oxaphosphol-3-yl)methoxy]-tetrahydro-2H-pyran 5a.
OTHP
OTHP
Me
Et
Br2
Br
Me
Et
•
solvent
O
(
MeO)2P
P
O
MeO
O
1a
5a
The reaction occurred with cyclization by neighbouring group participation of the
phosphonate group with formation of the 2-[(4-bromo-5-ethyl-2-methoxy-5-methyl-2-oxo-2,5-
dihydro-1,2-oxaphosphol-3-yl)methoxy]-tetrahydro-2H-pyran (5a). The cyclization of compound 1a
was already reported by Brel [57], although the range of electrophiles used in that case were limited.
We decided to optimize the reaction conditions by studying the electrophile equivalents, reaction
temperature, time and solvent effect under an argon atmosphere (Table 1).
Table 1. Screening of the reaction conditions for the electrophilic cyclization reaction of
the dimethyl 3-methyl-1-(tetrahydro-2H-pyran-2-yloxymethyl)-penta-1,2-dienephosphonate
1
a with bromine.
a
b
Entry Bromine (equiv.)
Solvent
CCl
benzene
CHCl3
Reaction Temp. (°C) Reaction Time (h) Yield (%)
1
2
3
4
5
6
7
8
9
1.0
1.0
1.0
1.0
1.0
1.2
1.5
2.0
1.2
1.2
1.2
1.2
1.2
4
rt
rt
6
8
45
34
58
62
57
81
76
73
77
78
75
68
72
rt
rt
5.5
5
CH
2
Cl
2
CH Cl2
reflux
−20
−20
−20
−78
−20
−30
−20
−20
4
3
2.5
2.5
5
2
CH Cl2
2
CH
2
Cl
2
CH Cl2
2
CH
ClCH
2
Cl
CH
2
1
0
1
2
3
2
2
Cl
4
1
1
1
ClCH CH Cl
4
2
2
MeCN
4.5
4
MeNO2
a
b
1
31
Reaction was carried out in the appropriate solvent (10 mL + 10 mL); Yields determined by H and
P
NMR analysis.
4
It should be noted that when the reaction was conducted in nonpolar solvents like CCl and benzene
at room temperature, thin-layer chromatography showed that the two reactants still interacted and the
reaction was completed within 6 and 8 h with the formation of the desired product albeit with low
yields (45% and 34%, entries 1 and 2). When the reaction was carried out in polar solvent
(entries 3–13), it was completed within 2.5–5 h and the yields were considerably higher (57%–81%).

Molecules 2014, 19
11060
Lower yields were obtained at room temperature and reflux (entries 1–5). Fortunately, when sub-zero
temperatures were used for 2.5–6 h (entries 6–13), the yield improved to 81% (−20 °C for 3 h,
entry 6). Solvents such as 1,2-dichloroethane, acetonitrile, and nitromethane (entries 10–13) gave
lower yields, even after longer reaction times (4–4.5 h). When 1.2 equivalents of electrophilic reagent
were used, the reaction yields were higher (entries 6, and 9–13). Reactions at −78 and −30 °C for 5 and
4
h gave lower yields (77% and 75%, entries 9 and 11). We therefore, conducted the remainder of the
reactions in CH Cl at −20 °C using 1.0 equivalent of the allenephosphonate with protected hydroxy
2
2
group 1a and 1.2 equiv. of the electrophile bromine.
When we used the α-hydroxy-allenephosphonate with unprotected hydroxy group 2a corresponding
to 1a as a starting material, the reaction with bromine under the optimized reaction conditions for 3 h
results in the formation of (4-bromo-5-ethyl-2-methoxy-5-methyl-2-oxo-2,5-dihydro-1,2-oxaphosphol-
1
13
31
3
-yl)-methanol (6a) in 80% yield. We used NMR ( H-, C-, and P-) and IR spectroscopy to reveal
the characteristics of the cyclic products 5a and 6a. Once we determined the optimized reaction
conditions, we focused on the scope of the electrophilic cyclization reaction of the α-hydroxy-
allenephosphonates 1a–e and 2a–e with protected and unprotected hydroxy groups (Scheme 3) and the
results obtained are summarized in Table 2. We have to say that the reaction under this very set of
standard reaction conditions in the favour of 5-endo-trig mode affords the 2-methoxy-2-oxo-2,5-
dihydro-1,2-oxaphospholes 5a–e and 6a–e to have very good to excellent yields and it does not depend
on the nature of the substituents on the allenic system and the hydroxy group, as a result of the
neighbouring group participation of phosphonate group in the cyclization. The reaction scope is the
1
2
3
following: R and R can be H or methyl, R and R can be methyl, ethyl, butyl, or -(CH ) -, E can be
2
5
Cl, Br, PhS, or PhSe, and Nu-Cl or Br.
Scheme 3. Synthesis of the 2-methoxy-2-oxo-2,5-dihydro-1,2-oxaphospholes 5 and 6.
O
O
Z
•
O
Z
R
R1
R
R1
R2
R3
E
E-Nu
O
R2
R3
(
MeO) P
2
P
MeO
O
1
2
, Z = THP
, Z = OH
5, Z = THP
6, Z = OH
Table 2. Synthesis of the 2-methoxy-2-oxo-2,5-dihydro-1,2-oxaphospholes 5 and 6.
1
2
3
a
Entry Allene
R
H
H
H
H
H
R
R
R
E
Nu Product Time (h) Yield (%)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1c
1d
1e
2a
2b
2c
H
H
H
H
Me Et
Me Bu
-(CH ) -
Br
Br
Cl
Br
Br
Br
Cl
Br
5a
5b
5c
5d
5e
5f
3
3
81
80
83
84
74
73
80
75
74
2
5
3
-(CH ) -
3.5
4
2
5
Me -(CH ) - PhSe Cl
2
5
Me Me Me Bu PhSe Cl
4.5
3
H
H
H
H
H
H
Me Et
Br
Br
6a
6b
6c
Me Bu PhS Cl
-(CH ) - PhSe Cl
6
2
5
4.5

Molecules 2014, 19
11061
Table 2. Cont.
1
2
3
a
Entry
Allene
2d
R
R
R
R
E
Nu Product Time (h) Yield (%)
1
1
0
1
H
Me -(CH
2
)
5
-
Cl
Br
Cl
Br
6d
6e
3.5
4
82
81
2e
Me Me Me Bu
a
Isolated yields by chromatographic purification.
2
.1.2. Concurrent Electrophilic Cyclization and Addition Reactions of 1-Hydroxyalkyl-allenyl
Phosphine Oxides 3 and 4
In order to outline the general terms of this methodology, the reaction of the 1-hydroxyalkyl-allenyl
phosphine oxides with protected and unprotected hydroxyl group 3 and 4 with different electrophilic
reagents such as sulfuryl chloride, bromine, benzenesulfenyl chloride and benzeneselenenyl chloride
was thorougly investigated. Surprisingly, once we applied the current standard conditions to the
1
,1-bifunctionalized allenes comprising a phosphine oxide and a hydroxyalkyl groups such as 3 and 4
(
Scheme 4), the interaction affords mixtures of the 2,2-diphenyl-2,5-dihydro-1,2-oxaphosphol-2-ium
halides 7a–g and 9a–g and the (1E)-alk-1-en-1-yl diphenyl phosphine oxides 8a–e and 10a–e in the
ratio about 2:1 in 70%–80% total yield after stirring for several h at −20 °C and for one hour to rt.
Scheme 4. Synthesis of the 2,2-diphenyl-2,5-dihydro-1,2-oxaphosphol-2-ium halides 7 and
8
and the (1E)-alk-1-en-1-yl diphenyl phosphine oxides 9 and 10.
O
Z
•
O
Z
O
Z
R
R1
R
R1
R
R1
R2
R3
E
E
E-Nu
+
R2
R3
R2
R3
Ph
Ph P
Ph
P
2
2
P
O
O
Nu Ph
O
Nu
3
4
, Z = THP
, Z = OH
7, Z = THP
8, Z = OH
9, Z = THP
10, Z = OH
Table 3. Synthesis of the 2,2-diphenyl-2,5-dihydro-1,2-oxaphosphol-2-ium halides 7 and 8
and the (1E)-alk-1-en-1-yl diphenyl phosphine oxides 9 and 10.
Products
1
2
3
Entry Allene
R
R
R
R
E
Nu Time, h
Ratio
a
(
Yield %)
1
2
3
4
5
6
7
8
9
3a
3b
3c
3c
3d
3d
3e
4a
4b
4c
4d
4e
H
H
H
H
H
H
H
H
H
H
Me Et
Me Bu
Br
Br
Br
Br
3
4
7a (50) 9a (23) 2.17:1
7b (48) 9b (22) 2.18:1
7c (50) 9c (24) 2.08:1
7d (49) 9d (24) 2.04:1
7e (49) 9e (25) 1.96:1
7f (48) 9f (24) 2.00:1
7g (54) 9g (25) 2.16:1
8a (52) 10a (23) 2.20:1
8b (46) 10b (26) 1.78:1
8c (54) 10c (26) 2.11:1
8d (45) 10d (25) 1.84:1
8e (46) 10e (24) 1.90:1
-(CH ) - PhSe Cl
5.5
3.5
4
2
5
-(CH ) -
Br
Br
Br
Br
2
5
Me -(CH ) -
2
5
Me -(CH ) - PhSe Cl
5
2
5
Me Me Me Bu
Cl
Br
Cl
Br
4
H
H
H
H
H
H
H
Me Et
2.5
5
Me Bu PhSe Cl
-(CH ) - Cl Cl
1
0
1
2
3
2
5
1
1
Me -(CH ) - PhS Cl
2
5
8
Me Me Me Bu PhSe Cl
6.5
a
Isolated yields by chromatographic purification.

Molecules 2014, 19
11062
The results are summarized in Table 3. These reaction pathways may be interpreted as a result of
the concurrent neighbouring group participation of the phosphonate group as an internal nucleophile to
give cyclic products 7a–g and 9a–g and the highly regio- and stereoselective association of the
external nucleophile, indicating a highly chemoselectively addition reaction of the electrophilic
2
3
reagents to the C -C -double bond of the allenic system with formation of the 1E-2,3-adducts 8a–e and
0a–e.
Thus, the reaction of phosphorylated α-hydroxyallenes with protected or unprotected hydroxy
groups with different electrophilic reagents occurs via 5-endo-trig cyclization. Treatment of the
1
1
1
-hydroxyalkyl-allenephosphonates 1 and 2 with electrophiles gives the 2-methoxy-2-oxo-2,5-dihydro-
,2-oxaphospholes 5 and 6 as a result of the neighbouring group participation of the phosphonate
group in the cyclization, while the (1E)-alk-1-en-1-yl phosphine oxides 9 and 10 were prepared as
mixtures with the 2,5-dihydro-1,2-oxaphosphol-2-ium halides 7 and 8 in a ratio of about 1:2 by chemo,
2
3
regio, and stereoselective electrophilic addition to the C -C -double bond in the allene moiety and
subsequent concurrent attack of the external (halide anion) and internal (phosphine oxide group)
nucleophiles.
2.2. A Rationale for the Reaction of the Phosphorylated α-Hydroxyallenes 1–4 with Electrophilic Reagents
A rationale for this reaction based on available literature data [13–23] and on our recent results [51–54]
is depicted in Scheme 5.
Scheme 5. A rationale for the reaction of the phosphorylated α-hydroxyallenes 1–4 with
electrophilic reagents.
O
Z
R
R
1
E
Y = OMe
Me
O
R2
R3
5, 6
MeNu
P
path a)
MeO
Nu
O
O
O
Z
R
R
1
E
B
E-Nu
R2
R3
Y = Ph
1
-4
Y2P
7, 9
1E)-8, (1E)-10
a)
path b)
b)
(
Y = Ph
Nu
A
+
+
+
+
The starting point is the attack of the electrophile (Cl , Br , S or Se ) on the most nucleophilic
3
atom of the allenic system of π-bonds (C ) with formation of the cyclic onium (chloronium,
2
3
bromonium, thiiranium or seleniranium) ions A after attack on the relatively more electron-rich C -C -
double bond. Then the ions A are easily transformed into the more stable five-membered cyclic ions B
via the attachment of the oxygen atom of the phosphonate functionality (path a). Further, the
intermediates B undergo nucleophilic attack on the MeO group and elimination of methyl halide
(
MeNu) affording the final cyclic products 5 and 6 (when Y is OMe). On the other hand, in the case
where the 1-hydroxyalkyl-allenyl phosphine oxides 3 and 4 are used as starting materials (Y is Ph), the
formation of the final 2,2-diphenyl-2,5-dihydro-1,2-oxaphosphol-2-ium halides 7 and 9 takes place
since the elimination of an methyl halide (second stage of an Arbuzov type rearrangement) and
formation of products with tetracoordinated phosphorus is impossible. The preparation of the

Molecules 2014, 19
11063
(
1E)-alk-1-en-1-yl phosphine oxides 8 and 10 as mixtures with the cyclic phosphonium halides 7 and 9
in a ratio of about 1:2 can be considered in terms of the assumption of a concurrent attack of the
external nucleophile on the cyclic three-membered onium ion A (path b). The stereoselectivity could
be explained by the favorable trans arrangement of the electrophile and the phosphine oxide group and
anti-attack of the external nucleophile Nu on the onium ion A. This is supposed to arise from attack on
2
3
the allenic C -C double bond anti to the phosphoryl group which assists in the cyclization by
neighbouring group participation as an internal nucleophile.
The abovementioned explanation should account for the results on the study of the reactions of
other bifunctionalized allenes with electrophilic reagents and, more specifically, their stereochemistry.
Further work in this area shall focus on exploiting and extending the synthetic utility of the
1
,1-bifunctionalized allenes for the preparation of different heterocyclic systems by application of the
electrophilic cyclization methodology.
3. Experimental Section
3.1. General Information
All new synthesized compounds were purified by column chromatography and characterized on the
basis of NMR, IR, and microanalytical data. NMR spectra were recorded on DRX Bruker Avance-250
1
13
31
(
H at 250.1 MHz, C at 62.9 MHz, P at 101.2 MHz) and Bruker Avance II + 600 (Bruker
1
13
31
BioSpinGmbH, Karlsruhe, Germany) ( H at 600.1 MHz, C at 150.9 MHz, P at 242.9 MHz)
1
13
spectrometers for solutions in CDCl
3
. All H-and C-NMR experiments were measured referring to
the signal of internal TMS and P-NMR experiments were measured referring to the signal of external
5% H PO . J values are given in hertz. IR spectra were recorded with an FT-IR_Afinity-1 Shimadzu
3
1
8
3
4
spectrophotometer (Shimadzu, Tokyo, Japan). Elemental analyses were carried out by the Microanalytical
Service Laboratory of Faculty of Chemistry and Pharmacy, University of Sofia, Bulgaria, using Vario
EL3 CHNS(O) (Elementar Analysensysteme, Hanau, Germany). Column chromatography was performed
on Kieselgel F254 60 (70–230 mesh ASTM, 0.063–0.200 nm, Merck, Darmstadt, Germany). CH
2 2
Cl
was distilled over CaH and other commercially available chemicals were used without additional
2
purification unless otherwise noted. Reactions were carried out in oven dried glassware under an argon
atmosphere and exclusion of moisture. All compounds were checked for purity on Kieselgel F254 60
TLC plates (Merck).
3.2. Starting Materials
Diphenyl disulfide and sulfuryl chloride in dichloromethane and distilled in vacuo
(
bp 80–81 °C/20 mm Hg) [58] were used to prepare benzenesulfanyl chloride. Diphenyl disulfide,
sulfuryl chloride, and benzeneselenenyl chloride were commercially available and used without
purification. The starting phosphorylated α-hydroxyallenes 1–4 were prepared according to the
established procedure [55].

Molecules 2014, 19
11064
3
.3. General Procedure for the Reactions of the Dimethyl 1-(Tetrahydro-2H-pyran-2-yloxy)methyl-1,2-
dienephosphonates 1 with Electrophilic Reagents
To a solution of the dimethyl 1-(tetrahydro-2H-pyran-2-yloxy)methyl-1,2-dienephosphonates 1
3.0 mmol) in dry dichloromethane (10 mL) at −20 °C was added dropwise with stirring a solution of
(
electrophilic reagent (sulfuryl chloride, bromine or benzeneselenenyl chloride) (3.6 mmol) in the same
solvent (10 mL). The reaction mixture was stirred at the same temperature for several h
(
see Table 1) and an hour at room temperature. After evaporation of the solvent, the residue was
chromatographed on a silica gel column (ethyl acetate and hexane 4:1) as eluent to give the pure
products 5 as oils, which had the following properties:
2
-[(4-Bromo-5-ethyl-2-methoxy-5-methyl-2-oxo-2,5-dihydro-1,2-oxaphosphol-3-yl)methoxy]-tetra-hydro-
−1
2
H-pyran (5a). Yellow oil, yield: 81%. R 0.49; IR (neat, cm ): 1015 (C-O-P), 1120 (C-O-C), 1268
f
1
(
P=O), 1583 (C=C). H-NMR (250.1 MHz): δ 0.89 (t, J = 7.2 Hz, 3H, Me-CH
2
), 1.53 (s, 3H, Me-C),
1
3
1
.54–1.89, 3.55–3.68, 4.53–4.63 (overlapping multiplets, 9H, OTHP), 1.77–1.88 (m, 2H, Me-CH ),
2
1
3
2
.83 (d, J = 9.3 Hz, 3H, MeO), 3.91–4.07 (m, 2H, CH O). C-NMR (62.9 MHz) δ = 9.3 (J = 4.7 Hz),
9.6, 24.6 (J = 7.7 Hz), 31.2, 31.5 (J = 7.9 Hz), 32.5 (J = 7.8 Hz), 53.4 (J = 13.9 Hz), 63.7, 65.8
31
(J = 5.7 Hz), 89.6 (J = 9.8 Hz), 97.1 (J = 5.0 Hz), 130.5 (J = 156.4 Hz), 140.7 (J = 51.4 Hz). P-NMR
101.2 MHz): δ 31.8. Anal. Calcd for C13 P (369.19): C 42.29, H 6.01. Found: C 42.35, H 5.93.
(
H22BrO
5
2
2
1
1
-[(4-Bromo-5-butyl-2-methoxy-5-methyl-2-oxo-2,5-dihydro-1,2-oxaphosphol-3-yl)methoxy]-tetra-hydro-
−1
H-pyran (5b). Dark orange oil, yield: 80%. R
f
0.53; IR (neat, cm ): 1012 (C-O-P), 1123 (C-O-C),
), 1.28–1.36,
-Me), 1.51–1.58, 3.56–3.60, 4.54–4.63
1
263 (P=O), 1587 (C=C). H-NMR (600.1 MHz): δ 0.91 (t, J = 7.3 Hz, 3H, Me-CH
2
2 3
.49–1.60, 1.77–1.85 (overlapping multiplets, 6H, (CH )
(
(
overlapping multiplets, 9H, OTHP), 1.56 (s, 3H, Me-C), 3.85 (d, J = 9.4 Hz, 3H, MeO), 3.89–3.99
1
3
m, 2H, CH
2
O). C-NMR (150.9 MHz) δ = 14.1, 19.9, 22.6, 23.4 (J = 4.6 Hz), 25.1 (J = 7.9 Hz),
2
6.7, 32.5, 40.5 (J = 7.9 Hz), 53.2 (J = 14.2 Hz), 62.8, 64.9 (J = 5.6 Hz), 88.7 (J = 10.0 Hz), 96.5
3
1
(
J = 5.1 Hz), 129.9 (J = 155.6 Hz), 141.5 (J = 52.1 Hz). P-NMR (242.9 MHz): δ 31.9. Anal. Calcd
P (397.24): C 45.35, H 6.60. Found: C 45.29, H 6.56.
for C15H26 BrO
5
4
2
-Chloro-2-methoxy-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-oxa-2-phosphaspiro[4.5]dec-3-ene
−1
-oxide (5c). Yellow oil, yield: 83%. R
f
0.47; IR (neat, cm ): 1019 (C-O-P), 1117 (C-O-C), 1261
1
(
P=O), 1584 (C=C). H-NMR (250.1 MHz): δ 1.32–1.92, 2.14–2.23, 3.61–3.77, 4.53–4.59
(
overlapping multiplets, 19H, (CH
2
)
5
, OTHP), 3.69 (d, J = 9.4 Hz, 3H, MeO), 3.95–4.07 (m, 2H,
1
3
CH
2
O). C-NMR (62.9 MHz) δ = 19.5, 22.6 (J = 5.0 Hz), 24.1, 25.7, 31.7, 35.4 (J = 7.8 Hz), 36.5
(
(
(
J = 7.7 Hz), 52.4 (J = 14.5 Hz), 62.4, 64.6 (J = 5.7 Hz), 87.2 (J = 9.5 Hz), 96.5 (J = 4.9 Hz), 129.5
31
5
J = 156.4 Hz), 140.7 (J = 52.5 Hz). P-NMR (101.2 MHz): δ 32.4. Anal. Calcd for C15H24ClO P
350.77): C 51.36, H 6.90. Found: C 51.43, H 6.96.
4
-Bromo-2-methoxy-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-oxa-2-phosphaspiro[4.5]dec-3-ene 2-
−1
oxide (5d). Dark orange oil, yield: 84%. R
f
0.51; IR (neat, cm ): 1013 (C-O-P), 1117 (C-O-C), 1269
1
(P=O), 1581 (C=C). H-NMR (600.1 MHz): δ 1.29–1.68, 1.95–2.05, 2.28–2.36, 3.60–3.76, 4.52–4.57
(
overlapping multiplets, 19H, (CH ) , OTHP), 3.78 (d, J = 9.3 Hz, 3H, MeO), 3.93–4.06 (m, 2H,
2
5

Molecules 2014, 19
11065
1
3
CH
2
O). C-NMR (150.9 MHz) δ = 19.3, 22.0 (J = 4.8 Hz), 23.9, 25.4, 31.5, 34.6 (J = 7.9 Hz), 37.1
(
(
(
J = 7.9 Hz), 52.5 (J = 14.4 Hz), 62.2, 64.8 (J = 5.9 Hz), 87.1 (J = 9.7 Hz), 96.3 (J = 5.0 Hz), 129.2
3
1
J = 156.0 Hz), 139.6 (J = 51.6 Hz). P-NMR (242.9 MHz): δ 33.0. Anal. Calcd for C H BrO P
1
5
24
5
395.23): C 45.58, H 6.12. Found: C 45.63, H 6.19.
2
3
1
-Methoxy-4-phenylselenenyl-3-[1-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1-oxa-2-phosphaspiro[4.5]dec-
−1
-ene 2-oxide (5e). Orange oil, yield: 74%. R
f
0.48; IR (neat, cm ): 1011 (C-O-P), 1122 (C-O-C),
1
259 (P=O), 1589 (C=C). H-NMR (600.1 MHz): δ 1.13–1.74, 2.01–2.09, 3.59–3.69, 4.63–4.68
(
2 5
overlapping multiplets, 19H, (CH ) , OTHP), 1.38 (dd, J = 10.6 Hz, J = 6.5 Hz, 3H, Me-CH), 3.72 (d,
13
J = 9.2 Hz, 3H, MeO), 4.21-4.29 (m, 1H, Me-CH), 7.39–7.44 (m, 5H, Ph). C-NMR (150.9 MHz)
δ = 19.4, 21.0 (J = 5.0 Hz), 21.3 (J = 7.8 Hz), 23.7, 25.6, 31.4, 34.1 (J = 7.8 Hz), 36.3 (J = 7.9 Hz), 51.9
(
(
(
J = 14.7 Hz), 62.5, 76.2 (J = 6.1 Hz), 89.4 (J = 9.8 Hz), 95.2 (J = 4.9 Hz), 129.4–139.0, 131.4
3
1
J = 105.4 Hz), 174.2 (J = 81.4 Hz). P-NMR (242.9 MHz): δ 34.5. Anal. Calcd for C H O PSe
2
2
31
5
485.41): C 54.44, H 6.44. Found: C 54.40, H 6.52.
2
[1-(5-Butyl-2-methoxy-5-methyl-2-oxo-4-phenylselenenyl-2,5-dihydro-1,2-oxaphosphol-3-yl)methyl-
−1
ethoxy]-tetrahydro-2H-pyran (5f). Yellow oil, yield: 73%. R 0.47; IR (neat, cm ): 1014
f
1
(
C-O-P), 1121 (C-O-C), 1266 (P=O), 1586 (C=C). H-NMR (600.1 MHz): δ 0.81 (t, J = 7.4 Hz, 3H,
Me-CH
2
2 3
), 1.26–1.33, 1.39–1.46, 1.81–1.93 (overlapping multiplets, 6H, (CH ) -Me), 1.52–1.70,
3
3
2
.72–3.86, 4.71–4.76 (overlapping multiplets, 9H, OTHP), 1.56 (s, 3H, Me-C), 3.84 (d, J = 9.6 Hz,
1
3
H, MeO), 1.48, 1.53 (ss, 6H, Me
2
C), 7.49–7.58 (m, 5H, Ph). C-NMR (150.9 MHz) δ = 14.2, 20.4,
3.1, 23.6 (J = 4.7 Hz), 24.7 (J = 8.0 Hz), 25.2, 29.9 (J = 7.9 Hz), 32.4, 39.7 (J = 8.1 Hz), 52.4
(
(
(
J = 15.0 Hz), 63.7, 84.2 (J = 6.0 Hz), 91.7 (J = 10.0 Hz), 94.4 (J = 4.8 Hz), 128.7–138.7, 132.7
3
1
35 5
J = 106.9 Hz), 175.4 (J = 82.8 Hz). P-NMR (242.9 MHz): δ 33.5. Anal. Calcd for C23H O PSe
501.45): C 55.09, H 7.04. Found: C 55.02, H 6.99.
3
.4. General Procedure for the Reactions of the 1-Hydroxyalkyl-1,2-dienephosphonates 2 with
Electrophilic Reagents
We got a solution of the 1-hydroxyalkyl-1,2-dienephosphonates 2 (3.0 mmol) where in dry
dichloromethane (10 mL) at −20 °C was added dropwise with stirring a solution of electrophilic
reagent (sulfuryl chloride, bromine, benzenesulfenyl chloride or benzeneselenenyl chloride)
(
(
3.6 mmol) in the same solvent (10 mL). The mixture was stirred at the same temperature for several h
see Table 1) and an hour at room temperature. After evaporation of the solvent, the residue was
chromatographed on a silica gel column (ethyl acetate and hexane 2:1) as eluent to give the pure
products 6 as oils, which had the following properties:
(
4-Bromo-5-ethyl-2-methoxy-5-methyl-2-oxo-2,5-dihydro-1,2-oxaphosphol-3-yl)-methanol
(6a).
0.56; IR (neat, cm ): 1018 (C-O-P), 1263 (P=O), 1587 (C=C), 3413 (OH).
), 1.59 (s, 3H, Me-C), 1.78–1.99 (m, 2H,
−1
Yellow oil, yield: 80%. R
1
f
H-NMR (600.1 MHz): δ 0.89 (t, J = 7.1 Hz, 3H, Me-CH
), 3.11 (s, 1H, OH), 3.79 (d, J = 9.6 Hz, 3H, MeO), 4.51–4.56 (m, 2H, CH
150.9 MHz) δ = 9.4 (J = 4.8 Hz), 24.3 (J = 7.8 Hz), 31.1 (J = 7.8 Hz), 52.7 (J = 14.3 Hz), 61.4
2
1
3
Me-CH
2
2
O). C-NMR
(

Molecules 2014, 19
11066
3
1
(
J = 5.9 Hz), 91.4 (J = 9.9 Hz), 129.7 (J = 155.0 Hz), 140.4 (J = 50.7 Hz). P-NMR (242.9 MHz):
δ 35.7. Anal. Calcd for C P (285.07): C 33.71, H 4.95. Found: C 33.65, H 5.02.
8 4
H14BrO
(
(
(
(
5-Butyl-2-methoxy-5-methyl-2-oxo-4-phenylsulfenyl-2,5-dihydro-1,2-oxaphosphol-3-yl)-methanol
−1
6b). Orange oil, yield: 75%. R 0.49; IR (neat, cm ): 1010 (C-O-P), 1260 (P=O), 1584 (C=C), 3409
f
1
OH). H-NMR (600.1 MHz): δ 0.91 (t, J = 7.2 Hz, 3H, Me-CH
2
), 1.26–1.35, 1.60–1.64, 1.86–2.05
overlapping multiplets, 6H, (CH
2
)
3
-Me), 1.47 (s, 3H, Me-C), 3.69 (s, 1H, OH), 3.75 (d, J = 9.5 Hz,
1
3
3
2
H, MeO), 4.68–4.71 (m, 2H, CH O), 7.16–7.44 (m, 5H, Ph). C-NMR (150.9 MHz) δ = 14.1, 23.2,
2
4.4 (J = 4.7 Hz), 27.8 (J = 7.9 Hz), 40.4 (J = 7.8 Hz), 51.9 (J = 14.6 Hz), 61.6 (J = 6.0 Hz), 88.9
31
(
J = 9.8 Hz), 126.7–135.8, 128.6 (J = 102.0 Hz), 158.1 (J = 51.2 Hz). P-NMR (242.9 MHz): δ 33.1.
Anal. Calcd for C H O PS (342.39): C 56.13, H 6.77. Found: C 56.19, H 6.84.
1
6
23
4
(
2-Methoxy-2-oxo-4-phenylselenenyl-1-oxa-phospha-spiro[4.5]dec-3-en-3-yl)-methanol (6c). Orange
−1
oil, yield: 74%. R
1
f
0.48; IR (neat, cm ): 1018 (C-O-P), 1268 (P=O), 1580 (C=C), 3418 (OH).
), 3.75
O), 7.28–7.37 (m, 5H, Ph).
2 5
H-NMR (250.1 MHz): δ 1.16–1.39, 1.60–1.79, 1.84–2.07 (overlapping multiplets, 10H, (CH )
(
s, 1H, OH), 3.78 (d, J = 9.8 Hz, 3H, MeO), 4.66–4.69 (m, 2H, CH
2
1
3
C-NMR (62.9 MHz) δ = 21.4 (J = 4.9 Hz), 23.9, 33.9 (J = 7.8 Hz), 36.2 (J = 7.9 Hz), 52.4 (J = 14.7 Hz),
0.9 (J = 6.0 Hz), 89.4 (J = 9.8 Hz), 127.4 (J = 106.0 Hz), 127.6–137.9, 174.2 (J = 82.4 Hz).
6
3
1
21 4
P-NMR (101.2 MHz): δ 36.3. Anal. Calcd for C16H O PSe (387.27): C 49.62, H 5.47. Found: C
49.56, H 5.51.
1
-(4-Chloro-2-methoxy-2-oxo-1-oxa-phospha-spiro[4.5]dec-3-en-3-yl)-ethanol (6d). Yellow oil, yield:
−1
1
8
2%. R
f
0.54; IR (neat, cm ): 1011 (C-O-P), 1259 (P=O), 1583 (C=C), 3424 (OH). H-NMR (250.1
), 1.48 (dd, J = 10.5 Hz,
J = 6.4 Hz, 3H, Me-CH), 3.67 (d, J = 9.4 Hz, 3H, MeO), 3.90 (s, 1H, OH), 4.69–4.78 (m, 1H,
2 5
MHz): δ 1.33–1.48, 1.64–1.85, 1.94–2.14 (overlapping multiplets, 10H, (CH )
1
3
Me-CH). C-NMR (62.9 MHz) δ = 22.4 (J = 5.0 Hz), 24.1, 24.5 (J = 7.9 Hz), 34.4 (J = 7.9 Hz), 36.8
(
(
J = 7.9 Hz), 51.9 (J = 15.1 Hz), 72.6 (J = 5.8 Hz), 90.5 (J = 10.1 Hz), 129.3 (J = 101.6 Hz), 160.6
31
4
J = 40.7 Hz). P-NMR (101.2 MHz): δ 35.7. Anal. Calcd for C11H18ClO P (280.68): C 47.07, H 6.46.
Found: C 46.99, H 6.40.
2
-(4-Bromo-5-butyl-2-methoxy-5-methyl-2-oxo-2,5-dihydro-1,2-oxaphosphol-3-yl)-propan-2-ol (6e).
−1
Dark orange oil, yield: 81%. R
f
0.51; IR (neat, cm ): 1009 (C-O-P), 1268 (P=O), 1589 (C=C), 3410
), 1.27–1.34, 1.50–1.57, 1.76–1.92
-Me), 1.48 (s, 3H, Me-C), 1.56, 1.58 (ss, 6H, Me C), 3.48 (s, 1H,
1
(OH). H-NMR (600.1 MHz): δ 0.91 (t, J = 7.3 Hz, 3H, Me-CH
2
(
overlapping multiplets, 6H, (CH
2
)
3
2
1
3
OH), 3.65 (d, J = 9.5 Hz, 3H, MeO). C-NMR (150.9 MHz) δ = 14.2, 23.1, 23.5 (J = 4.6 Hz), 25.4
(
J = 7.9 Hz), 31.4 (J = 8.1 Hz), 39.4 (J = 7.9 Hz), 52.3 (J = 15.0 Hz), 71.4 (J = 6.0 Hz), 92.4 (J = 9.8 Hz),
3
1
1
33.1 (J = 154.3 Hz), 142.8 (J = 51.4 Hz). P-NMR (242.9 MHz): δ 34.1. Anal. Calcd for
C H BrO P (341.18): C 42.24, H 6.50. Found: C 42.31, H 6.56.
1
2
22
4

Molecules 2014, 19
11067
3
.5. General Procedure for the Reactions of the 2-[2-(Diphenylphosphinoyl)-2,3-dienyloxy]methyl-
tetrahydro-2H-pyrans 3 with Electrophilic Reagents
To a solution of the 2-[2-(diphenylphosphinoyl)-2,3-dienyloxy]methyl-tetrahydro-2H-pyrans 3
3.0 mmol) in dry dichloromethane (10 mL) at −20 °C was added dropwise with stirring a solution of
(
electrophilic reagent (sulfuryl chloride, bromine or benzeneselenenyl chloride) (3.6 mmol) in the same
solvent (10 mL). The reaction mixture was stirred at the same temperature for several h (see Table 2)
and an hour at room temperature. The solvent was removed using a rotatory evaporator and the residue
was purified by column chromatography (silica gel, ethyl acetate and hexane 4:1). The pure products 7
and 9 had the following properties:
4
-Bromo-5-ethyl-5-methyl-2,2-diphenyl-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2,5-dihydro-1,2-
−1
oxaphosphol-2-ium bromide (7a). Orange oil, yield: 50%. R 0.38; IR (neat, cm ): 1119 (C-O-C),
f
1
1
3
439, 1484 (Ph), 1583 (C=C). H-NMR (600.1 MHz): δ 1.07 (t, J = 7.1 Hz, 3H, Me-CH
2
), 1.44–1.69,
.61–3.75, 4.80–4.85 (overlapping multiplets, 9H, OTHP), 1.78 (s, 3H, Me-C), 2.28–2.37 (m, 2H,
1
3
Me-CH ), 4.31–4.51 (m, 2H, CH O), 7.75–8.46 (m, 10H, 2Ph). C-NMR (150.9 MHz) δ = 7.9
2
2
(
(
(
J = 4.5 Hz), 19.4, 25.4, 27.1 (J = 7.9 Hz), 31.2, 31.6 (J = 8.0 Hz), 62.6 (J = 7.8 Hz), 63.0, 92.4
3
1
J = 10.1 Hz), 98.4 (J = 4.6 Hz), 111.4–135.2, 134.7 (J = 51.2 Hz), 158.7 (J = 50.9 Hz). P-NMR
242.9 MHz): δ 86.5. Anal. Calcd for C24 P (556.27): C 51.82, H 5.25. Found: C 51.74, H 5.20.
2 3
H29Br O
(
1E)-2,3-Dibromo-3-methyl-1-[(tetrahydro-2H-pyran-2-yloxy)methyl]pent-1-en-1-yl diphenyl phosphine
−1
oxide (9a). Colourless oil, yield: 23%. R
f
0.62; IR (neat, cm ): 1121 (C-O-C), 1153 (P=O), 1435,
), 1.46–1.71,
), 2.16 (s, 3H,
2
O), 7.53–8.12 (m, 10H, 2Ph). C-NMR (150.9 MHz) δ = 9.4, 19.6,
1
1
488 (Ph), 1618 (C=C). H-NMR (600.1 MHz): δ 1.12 (t, J = 7.3 Hz, 3H, Me-CH
2
3
.62–3.77, 4.51–4.57 (overlapping multiplets, 9H, OTHP), 1.98–2.20 (m, 2H, Me-CH
2
1
3
Me-C), 3.91–4.07 (m, 2H, CH
2
5.3, 30.8, 35.4 (J = 4.6 Hz), 36.4 (J = 5.0 Hz), 62.4, 62.6 (J = 7.9 Hz), 68.4 (J = 5.8 Hz), 96.3
31
(
J = 5.0 Hz), 129.3–133.3, 132.4 (J = 154.7 Hz), 141.7 (J = 50.4 Hz). P-NMR (242.9 MHz): δ 39.7.
Anal. Calcd for C H Br O P (556.27): C 51.82, H 5.25. Found: C 51.87, H 5.17.
2
4
29
2
3
4
-Bromo-5-butyl-5-methyl-2,2-diphenyl-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2,5-dihydro-1,2-
−1
oxaphosphol-2-ium bromide (7b). Orange oil, yield: 48%. R
f
0.37; IR (neat, cm ): 1120 (C-O-C),
1
1
1
434, 1489 (Ph), 1588 (C=C). H-NMR (600.1 MHz): δ 0.91 (t, J = 6.3 Hz, 3H, Me-CH ), 1.08–1.15,
2
.28–1.38, 2.26–2.44 (overlapping multiplets, 6H, (CH
2
)
3
-Me), 1.46–1.70, 3.58–3.72, 4.77–4.81
O), 7.73–8.50
m, 10H, 2Ph). C-NMR (150.9 MHz) δ = 14.4, 19.5, 23.0, 23.4 (J = 4.5 Hz), 25.2, 27.3 (J = 8.0 Hz),
(
(
overlapping multiplets, 9H, OTHP), 1.77 (s, 3H, Me-C), 4.35-4.49 (m, 2H, CH
2
1
3
3
1.4, 39.7 (J = 7.7 Hz), 62.3, 62.8 (J = 7.5 Hz), 92.2 (J = 9.8 Hz), 98.3 (J = 4.7 Hz), 110.2–134.8,
3
1
1
33.6 (J = 49.5 Hz), 159.8 (J = 51.2 Hz). P-NMR (242.9 MHz): δ 86.6. Anal. Calcd for
C H Br O P (584.32): C 53.44, H 5.69. Found: C 53.37, H 5.73.
2
6
33
2
3
(
1E)-2,3-Dibromo-3-methyl-1-[(tetrahydro-2H-pyran-2-yloxy)methyl]hept-1-en-1-yl diphenyl phosphine
−1
oxide (9b). Yellow oil, yield: 22%. R
f
0.64; IR (neat, cm ): 1119 (C-O-C), 1163 (P=O), 1439, 1484
1
(Ph), 1612 (C=C). H-NMR (600.1 MHz): δ 0.85 (t, J = 6.3 Hz, 3H, Me-CH ), 1.30–1.43, 1.47–1.72
2
(
overlapping multiplets, 6H, (CH ) -Me), 2.01–2.21, 3.36–3.74, 4.52–4.58 (overlapping multiplets, 9H,
2
3

Molecules 2014, 19
11068
13
OTHP), 2.14 (s, 3H, Me-C), 3.92–4.06 (m, 2H, CH
2
O), 7.51–8.13 (m, 10H, 2Ph). C-NMR (150.9 MHz)
δ = 14.4, 19.4, 22.3, 25.4, 27.3, 31.2, 35.2 (J = 4.7 Hz), 43.2 (J = 5.1 Hz), 58.9 (J = 7.8 Hz), 62.4,
6
7.8 (J = 5.9 Hz), 96.4 (J = 5.1 Hz), 129.7–134.0, 132.5 (J = 155.3 Hz), 142.1 (J = 50.9 Hz).
3
1
2 3
P-NMR (242.9 MHz): δ 39.7. Anal. Calcd for C26H33Br O P (584.32): C 53.44, H 5.69. Found: C
53.50, H 5.76.
5
1
1
1
-Butyl-5-methyl-2,2-diphenyl-4-phenylselenenyl-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2,5-dihydro-
−1
,2-oxaphosphol-2-ium chloride (7c). Orange oil, yield: 50%. R 0.35; IR (neat, cm ): 1120 (C-O-C),
f
1
444, 1487 (Ph), 1585 (C=C). H-NMR (600.1 MHz): δ 0.88 (t, J = 6.4 Hz, 3H, Me-CH
2
), 1.02–1.11,
.24–1.36, 2.35–2.53 (overlapping multiplets, 6H, (CH
2
)
3
-Me), 1.41–1.68, 3.60–3.73, 4.79–4.84
(
overlapping multiplets, 9H, OTHP), 1.67 (s, 3H, Me-C), 4.46–4.61 (m, 2H, CH O), 7.03–8.24 (m,
2
1
3
1
3
1
5H, 3Ph). C-NMR (150.9 MHz) δ = 14.2, 19.4, 23.2, 23.5 (J = 4.7 Hz), 25.4, 26.0 (J = 7.8 Hz),
1.1, 38.8 (J = 7.9 Hz), 62.4, 62.9 (J = 9.7 Hz), 95.7 (J = 10.0 Hz), 98.1 (J = 4.5 Hz), 111.2–138.5,
3
1
26.2 (J = 54.3 Hz), 189.4 (J = 74.3 Hz). P-NMR (242.9 MHz): δ 85.7. Anal. Calcd for
PSe (616.03): C 62.39, H 6.22. Found: C 62.33, H 6.15.
32 3
C H38ClO
(
1E)-3-Chloro-3-methyl-2-phenylselenenyl-1-[(tetrahydro-2H-pyran-2-yloxy)methyl]hept-1-en-1-yl
−1
diphenyl phosphine oxide (9c). Yellow oil, yield: 24%. R
f
0.61; IR (neat, cm ): 1120 (C-O-C), 1149
),
-Me),
O), 7.37–7.77 (m, 15H, 3Ph). C-NMR (150.9 MHz)
δ = 14.1, 19.3, 22.7, 25.4, 26.8, 28.8 (J = 4.8 Hz), 31.0, 42.6 (J = 4.9 Hz), 62.4, 68.7 (J = 6.0 Hz), 80.5
1
(
P=O), 1440, 1493 (Ph), 1614 (C=C). H-NMR (600.1 MHz): δ 0.86 (t, J = 6.2 Hz, 3H, Me-CH
2
1
2 3
.30–1.40, 1.44–1.69, 2.01–2.21, 3.36–3.74, 4.52–4.58 (overlapping multiplets, 15H, (CH )
13
OTHP), 2.17 (s, 3H, Me-C), 4.07–4.21 (m, 2H, CH
2
(
3
J = 7.9 Hz), 96.3 (J = 5.1 Hz), 128.4 (J = 105.3 Hz), 128.5–139.2, 154.2 (J = 85.2 Hz).
1
3
P-NMR (242.9 MHz): δ 38.7. Anal. Calcd for C32H38ClO PSe (616.03): C 62.39, H 6.22. Found: C
62.46, H 6.26.
4
-Bromo-2,2-diphenyl-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-oxa-2-phosphoniaspiro[4.5]dec-3-
−1
ene bromide (7d). Orange oil, yield: 49%. R
f
0.35; IR (neat, cm ): 1123 (C-O-C), 1435, 1490 (Ph),
1
1
582 (C=C). H-NMR (600.1 MHz): δ 1.27–1.70, 1.99–2.05, 2.30–2.35, 3.60–3.77, 4.77–4.82
(
overlapping multiplets, 15H, (CH
2
)
5
2
, OTHP), 4.38–4.50 (m, 2H, CH O), 7.28–7.93 (m, 10H, 2Ph).
6
2.8, 88.6 (J = 9.9 Hz), 98.2 (J = 4.8 Hz), 110.8–133.8, 133.9 (J = 50.8 Hz), 157.7 (J = 49.0 Hz).
3
1
2 3
P-NMR (242.9 MHz): δ 85.4. Anal. Calcd for C26H31Br O P (582.30): C 53.63, H 5.37. Found: C
53.70, H 5.32.
(
E)-2-bromo-2-(1-bromocyclohexyl)-1-[(tetrahydro-2H-pyran-2-yloxy)methyl]vinyl diphenyl phosphine
−1
oxide (9d). Yellow oil, yield: 24%. R 0.62; IR (neat, cm ): 1123 (C-O-C), 1173 (P=O), 1437, 1496
f
1
(Ph), 1620 (C=C). H-NMR (600.1 MHz): δ 1.26–1.37, 1.46–1.71, 2.00–2.19, 3.60–3.77, 4.54–4.59
(
overlapping multiplets, 15H, (CH ) , OTHP), 3.92–4.07 (m, 2H, CH O), 7.51–8.10 (m, 15H, 3Ph).
2
5
2
1
3
C-NMR (150.9 MHz) δ = 19.6, 22.1, 25.1, 25.5, 31.2, 39.6 (J = 5.0 Hz), 62.5, 68.2 (J = 5.8 Hz), 74.5
3
1
(J = 7.9 Hz), 96.1 (J = 5.0 Hz), 129.1–133.9, 132.2 (J = 154.7 Hz), 141.7 (J = 51.4 Hz). P-NMR
242.9 MHz): δ 37.2.Anal. Calcd for C H Br O P (582.30): C 53.63, H 5.37. Found: C 53.58, H 5.45.
(
26
31
2
3

Molecules 2014, 19
11069
4
-Bromo-2,2-diphenyl-3-[1-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1-oxa-2-phosphoniaspiro[4.5]dec-3-
−1
ene bromide (7e). Orange oil, yield: 49%. R
f
0.39; IR (neat, cm ): 1118 (C-O-C), 1439, 1491 (Ph),
1
1
591 (C=C). H-NMR (600.1 MHz): δ 1.29–1.73, 1.92–2.02, 2.27–2.33, 3.58–3.73, 4.91–4.95
(
overlapping multiplets, 15H, (CH
2 5
) , OTHP), 1.55 (d, 3H, J = 6.5 Hz, Me-CH), 4.30–4.39 (m, 1H,
1
3
Me-CH), 7.31–7.89 (m, 10H, 2Ph). C-NMR (150.9 MHz) δ = 19.6, 22.1 (J = 4.8 Hz), 23.7, 25.3
(
J = 7.7 Hz), 25.5, 30.9, 35.8 (J = 8.0 Hz), 62.4, 76.2 (J = 5.4 Hz), 89.4 (J = 9.8 Hz), 97.4 (J = 4.8 Hz),
3
1
1
11.2–134.0, 134.6 (J = 51.0 Hz), 156.8 (J = 48.3 Hz). P-NMR (242.9 MHz): δ 83.7. Anal. Calcd
P (596.33): C 54.38, H 5.58. Found: C 54.45, H 5.64.
2 3
for C27H33Br O
(
E)-2-bromo-2-(1-bromocyclohexyl)-1-[1-(tetrahydro-2H-pyran-2-yloxy)ethyl]vinyl diphenyl phosphine
−1
oxide (9e). Dark orange oil, yield: 25%. R 0.64; IR (neat, cm ): 1118 (C-O-C), 1165 (P=O), 1441,
f
1
1
4
489 (Ph), 1621 (C=C). H-NMR (600.1 MHz): δ 1.26–1.37, 1.40–1.71, 1.98–2.16, 3.59–3.75,
2 5
.64–4.69 (overlapping multiplets, 15H, (CH ) , OTHP), 1.44 (dd, 3H, J = 6.5 Hz, J = 3.4 Hz,
1
3
Me-CH), 4.78–4.86 (m, 1H, Me-CH), 7.50–8.04 (m, 10H, 2Ph). C-NMR (150.9 MHz) δ = 19.6, 21.8,
2.5 (J = 7.9 Hz), 25.3, 25.6, 31.3, 40.2 (J = 4.7 Hz), 62.4, 74.3 (J = 7.8 Hz), 81.4 (J = 5.0 Hz), 95.6
2
31
(
J = 5.0 Hz), 129.4–134.5, 131.9 (J = 155.4 Hz), 142.3 (J = 49.7 Hz). P-NMR (242.9 MHz): δ 38.1.
Anal. Calcd for C27 P (596.33): C 54.38, H 5.58. Found: C 54.32, H 5.54.
2 3
H33Br O
2
,2-Diphenyl-4-phenylselenenyl-3-[1-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1-oxa-2-phosphoniaspiro-
−1
[4.5]dec-3-ene chloride (7f). Dark orange oil, yield: 48%. R
f
0.36; IR (neat, cm ): 1118 (C-O-C),
1
1
4
1
436, 1488 (Ph), 1586 (C=C). H-NMR (600.1 MHz): δ 1.30–1.64, 1.67–1.78, 2.04–2.11, 3.58–3.74,
2 5
.91–4.96 (overlapping multiplets, 15H, (CH ) , OTHP), 1.48 (d, 3H, J = 6.4 Hz, Me-CH), 4.18–4.26 (m,
1
3
H, Me-CH), 7.28–-7.91 (m, 15H, 3Ph). C-NMR (150.9 MHz) δ = 19.5, 21.2 (J = 5.1 Hz), 23.5
(
(
J = 7.9 Hz), 23.6, 25.6, 31.4, 34.8 (J = 7.9 Hz), 62.3, 76.8 (J = 5.3 Hz), 92.4 (J = 9.8 Hz), 97.9
3
1
J = 4.9 Hz), 111.1–138.6, 131.4 (J = 50.7 Hz), 176.7 (J = 88.5 Hz). P-NMR (242.9 MHz): δ 86.5.
PSe (628.04): C 63.11, H 6.10. Found: C 63.18, H 6.16.
Anal. Calcd for C33H38ClO
3
(
E)-2-(1-chlorocyclohexyl)-2-phenylselenenyl-1-[1-(tetrahydro-2H-pyran-2-yloxy)ethyl]vinyl diphenyl
−1
phosphine oxide (9f). Light orange oil, yield: 24%. R 0.62; IR (neat, cm ): 1118 (C-O-C), 1167
f
1
(
P=O), 1438, 1490 (Ph), 1621 (C=C). H-NMR (600.1 MHz): δ 1.28–1.77, 1.99–2.18, 3.59–3.76,
4
.63–4.69 (overlapping multiplets, 15H, (CH ) , OTHP), 1.36 (dd, 3H, J = 6.5 Hz, J = 3.6 Hz,
2 5
1
3
Me-CH), 4.38–4.45 (m, 1H, Me-CH), 7.37–7.74 (m, 15H, 3Ph). C-NMR (150.9 MHz) δ = 19.6, 20.7,
1.0 (J = 7.8 Hz), 25.6, 25.7, 31.2, 38.4 (J = 4.6 Hz), 62.3, 71.4 (J = 7.9 Hz), 81.3 (J = 4.8 Hz), 95.7
2
31
(
J = 4.8 Hz), 128.4–139.4, 131.3 (J = 105.4 Hz), 152.3 (J = 71.5 Hz). P-NMR (242.9 MHz): δ 36.0.
Anal. Calcd for C33 PSe (628.04): C 63.11, H 6.10. Found: C 63.07, H 6.05.
H38ClO
3
5
1
1
1
-Butyl-4-chloro-5-methyl-3-[1-methyl-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]-2,2-diphenyl-2,5-dihydro-
−1
,2-oxaphosphol-2-ium chloride (7g). Yellow oil, yield: 54%. R
f
0.38; IR (neat, cm ): 1119 (C-O-C),
), 1.15–1.21,
-Me), 1.42–1.65, 3.69–3.84, 4.97–5.02
1
435, 1484 (Ph), 1582 (C=C). H-NMR (600.1 MHz): δ 0.91 (t, J = 6.4 Hz, 3H, Me-CH
2
.27–1.34, 2.28–2.41 (overlapping multiplets, 6H, (CH
2
)
3
(
overlapping multiplets, 9H, OTHP), 1.68 (s, 3H, Me-C), 1.70 (s, 6H, Me C), 7.63–8.26 (m, 10H,
2
1
3
2
Ph). C-NMR (150.9 MHz) δ = 14.1, 20.5, 23.2, 23.8 (J = 4.5 Hz), 25.3, 26.1 (J = 7.8 Hz), 29.7
(
J = 8.1 Hz), 32.3, 39.1 (J = 7.8 Hz), 63.7, 79.5 (J = 9.8 Hz), 92.7 (J = 9.7 Hz), 95.7 (J = 4.7 Hz),

Molecules 2014, 19
11070
3
1
1
06.5–134.6, 133.4 (J = 50.2 Hz), 164.8 (J = 40.5 Hz). P-NMR (242.9 MHz): δ 82.0. Anal. Calcd
P (523.47): C 64.24, H 7.12. Found: C 64.19, H 7.05.
2 3
for C28H37Cl O
(
1E)-2,3-dichloro-3-methyl-1-[1-methyl-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]hept-1-en-1-yl diphenyl
−1
phosphine oxide (9g). Orange oil, yield: 25%. R 0.63; IR (neat, cm ): 1119 (C-O-C), 1159 (P=O),
f
1
1
1
439, 1485 (Ph), 1617 (C=C). H-NMR (600.1 MHz): δ 0.87 (t, J = 6.3 Hz, 3H, Me-CH
2
), 1.35–1.48,
.54–1.69, 2.27–2.54 (overlapping multiplets, 6H, (CH
2
)
3
-Me), 1.47–1.68, 3.66–3.80, 4.70–4.76
(
overlapping multiplets, 9H, OTHP), 1.58 (s, 3H, Me C), 1.83 (s, 3H, Me-C), 7.53–7.91 (m, 10H,
2
1
3
2
3
1
Ph). C-NMR (150.9 MHz) δ = 14.0, 20.6, 22.9, 25.2, 26.4, 29.5 (J = 4.7 Hz), 30.8 (J = 7.9 Hz),
2.2, 42.9 (J = 4.7 Hz), 63.6, 76.4 (J = 7.8 Hz), 80.3 (J = 9.9 Hz), 93.4 (J = 4.7 Hz), 129.3–134.2,
3
1
33.6 (J = 101.4 Hz), 152.9 (J = 41.2 Hz). P-NMR (242.9 MHz): δ 37.7. Anal. Calcd for
P (523.47): C 64.24, H 7.12. Found: C 64.28, H 7.20.
28 2 3
C H37Cl O
3
3
.6. General Procedure for the Reactions of the 2-Diphenylphosphinoyl-2,3-dien-1-ols 4a–c and
-Diphenylphosphinoyl-3,4-dien-2-ols 4d,e with Electrophilic Reagents
To a solution of the 2-diphenylphosphinoyl-2,3-dien-1-ols 4a–c or the 3-diphenylphosphinoyl-3,4-
dien-2-ols 4d,e (3.0 mmol) in dry dichloromethane(10 mL) at −20 °C was added dropwise with stirring
a solution of electrophilic reagent (sulfuryl chloride, bromine, benzenesulfenyl chloride, benzeneselenenyl
chloride) (3.6 mmol) in the same solvent (10 mL). The reaction mixture was stirred at the same
temperature for several hours (see Table 2) and an hour at room temperature. The solvent was removed
using a rotatory evaporator and the residue was purified by column chromatography (silica gel, ethyl
acetate and hexane 2:1). The pure products 8 and 10 had the following properties:
4
-Bromo-5-ethyl-3-(hydroxymethyl)-5-methyl-2,2-diphenyl-2,5-dihydro-1,2-oxaphosphol-2-ium bromide
−1
(
8a). Pale orange oil, yield: 52%. R
f
0.38; IR (neat, cm ): 1435, 1485 (Ph), 1581 (C=C), 3375 (OH).
H-NMR (600.1 MHz): δ 1.08 (t, J = 7.3 Hz, 3H, Me-CH ), 1.80 (s, 3H, Me-C), 2.31–2.40 (m, 2H,
), 4.57 (s, 1H, OH), 4.95–5.02 (m, 2H, CH O), 7.80–8.45 (m, 10H, 2Ph). C-NMR (150.9 MHz)
δ = 8.1 (J = 4.6 Hz), 27.2 (J = 7.8 Hz), 31.0 (J = 7.7 Hz), 60.2 (J = 5.8 Hz), 92.7 (J = 9.7 Hz),
1
2
13
Me-CH
2
2
3
1
1
11.5–135.1, 133.7 (J = 49.7 Hz), 158.1 (J = 50.3 Hz). P-NMR (242.9 MHz): δ 88.1. Anal. Calcd
P (472.15): C 48.33, H 4.48. Found: C 48.26, H 4.55.
2 2
for C19H21Br O
(
2E)-3,4-Dibromo-2-diphenylphosphinoyl-4-methylhex-2-en-1-ol (10a). Yellow oil, yield: 23%. R 0.64;
f
−1
1
IR (neat, cm ): 1171 (P=O), 1433, 1482 (Ph), 1628 (C=C), 3374 (OH). H-NMR (600.1 MHz): δ 1.14
(
t, J = 7.3 Hz, 3H, Me-CH
2 2
), 1.98–2.18 (m, 2H, Me-CH ), 2.18 (s, 3H, Me-C), 2.98 (s, 1H, OH), 4.53–4.57
1
3
(
m, 2H, CH O), 7.53–8.08 (m, 10H, 2Ph). C-NMR (150.9 MHz) δ = 9.2, 35.2 (J = 5.0 Hz), 36.4
2
(
J = 5.0 Hz), 62.0 (J = 7.9 Hz), 63.6 (J = 5.9 Hz), 129.4–133.7, 131.5 (J = 49.9 Hz), 141.7 (J = 50.8 Hz).
3
1
2 2
P-NMR (242.9 MHz): δ 39.6. Anal. Calcd for C19H21Br O P (472.15): C 48.33, H 4.48. Found: C
48.40, H 4.52.
5
-Butyl-3-(hydroxymethyl)-5-methyl-2,2-diphenyl-4-phenylselenenyl-2,5-dihydro-1,2-oxaphosphol-2-
−1
ium chloride (8b). Yellow oil, yield: 46%. R
f
0.39; IR (neat, cm ): 1438, 1487 (Ph), 1585 (C=C),
1
3380 (OH). H-NMR (600.1 MHz): δ 0.92 (t, J = 7.2 Hz, 3H, Me-CH ), 1.02–1.11, 1.27–1.37, 2.35–2.54
2

Molecules 2014, 19
11071
(
m, 6H, (CH
2
)
3
-Me), 1.67 (s, 3H, Me-C), 5.08–5.13 (m, 2H, CH
2
O), 5.24 (s, 1H, OH), 6.99–8.28
1
3
(
overlapping multiplets, 15H, 3Ph). C-NMR (150.9 MHz) δ = 13.8, 22.1 (J = 5.1 Hz), 23.4, 26.7
(
J = 7.9 Hz), 38.5 (J = 7.9 Hz), 60.5 (J = 5.8 Hz), 95.8 (J = 9.9 Hz), 111.4–138.6, 126.2 (J = 51.3 Hz),
31
1
89.0 (J = 69.4 Hz). P-NMR (242.9 MHz): δ 86.9. Anal. Calcd for C H ClO PSe (531.91): C
27 30 2
60.97, H 5.68. Found: C 60.92, H 5.73.
(
2E)-4-Chloro-2-diphenylphosphinoyl-4-methyl-3-phenylselenenyl-oct-2-en-1-ol (10b). Yellow oil,
−1
1
yield: 26%. R 0.65; IR (neat, cm ): 1175 (P=O), 1437, 1490 (Ph), 1620 (C=C), 3389 (OH). H-NMR
f
(
600.1 MHz): δ 0.88 (t, J = 7.1 Hz, 3H, Me-CH
2
), 1.30–1.46, 2.36–2.63 (m, 6H, (CH
H, Me-C), 3.74 (s, 1H, OH), 4.67–4.72 (m, 2H, CH O), 7.35–7.98 (overlapping multiplets, 15H,
Ph). C-NMR (150.9 MHz) δ = 14.1, 22.9, 25.7, 28.9 (J = 4.8 Hz), 42.4 (J = 4.7 Hz), 64.7 (J = 6.0 Hz),
2 3
) -Me), 1.79 (s,
3
3
8
3
2
13
3
1
0.0 (J = 7.9 Hz), 127.7 (J = 101.4 Hz), 129.0–139.1, 153.6 (J = 57.4 Hz). P-NMR (242.9 MHz): δ
9.9. Anal. Calcd for C27 PSe (531.91): C 60.97, H 5.68. Found: C 61.02, H 5.75.
H30ClO
2
4
-Chloro-3-(hydroxymethyl)-2,2-diphenyl-1-oxa-2-phosphonia-spiro[4.5]dec-3-ene chloride (8c).
−1
1
Yellow oil, yield: 54%. R 0.37; IR (neat, cm ): 1441, 1489 (Ph), 1582 (C=C), 3389 (OH). H-NMR
f
(
600.1 MHz): δ 1.30–1.49, 1.61–1.88, 2.18–2.24 (overlapping multiplets, 10H, (CH
2
)
5
), 4.99–5.04 (m,
O), 5.30 (s, 1H, OH), 7.75–8.31 (m, 10H, 2Ph). C-NMR (150.9 MHz) δ = 22.5 (J = 4.6 Hz),
4.0, 35.6 (J = 7.8 Hz), 60.3 (J = 5.8 Hz), 90.3 (J = 9.8 Hz), 106.3–133.8, 127.1 (J = 49.7 Hz), 171.4
1
3
2
H, CH
2
2
3
1
(
J = 42.6 Hz). P-NMR (242.9 MHz): δ 86.5. Anal. Calcd for C21
.66. Found: C 61.70, H 5.71.
2 2
H23Cl O P (409.29): C 61.63, H
5
(
2E)-3-Chloro-3-(1-chlorocyclohexyl)-2-diphenylphosphinoyl-prop-2-en-1-ol (10c). Pale orange oil,
−1
1
yield: 26%. R
f
0.62; IR (neat, cm ): 1178 (P=O), 1440, 1493 (Ph), 1619 (C=C), 3384 (OH). H-NMR
), 3.77 (s, 1H,
O), 7.43–7.99 (m, 10H, 2Ph). C-NMR (150.9 MHz) δ = 21.8, 25.7, 38.5
J = 5.1 Hz), 63.7 (J = 5.9 Hz), 68.3 (J = 9.9 Hz), 129.1 (J = 100.9 Hz), 129.5–134.4, 148.7 (J = 39.7 Hz).
(
2 5
600.1 MHz): δ 1.28–1.41, 1.55–1.70, 1.76–1.92 (overlapping multiplets, 10H, (CH )
1
3
OH), 4.58–4.63 (m, 2H, CH
2
(
3
1
2 2
P-NMR (242.9 MHz): δ 34.6. Anal. Calcd for C21H23Cl O P (409.29): C 61.63, H 5.66. Found: C
61.69, H 5.60.
3
-(1-Hydroxyethyl)-2,2-diphenyl-4-phenylsulfenyl-1-oxa-2-phosphonia-spiro[4.5]dec-3-ene chloride
−1
(
8d). Yellow oil, yield: 45%. R
f
0.38; IR (neat, cm ): 1435, 1494 (Ph), 1580 (C=C), 3393 (OH).
H-NMR (600.1 MHz): δ 1.31–1.47, 1.71–1.97, 2.07–2.13 (overlapping multiplets, 10H, (CH ), 1.78
dd, J = 16.6 Hz, J = 6.6 Hz, 3H, Me-CH), 4.32 (s, 1H, OH), 4.96–5.07 (m, 1H, Me-CH), 6.91–8.60
1
2 5
)
(
(
13
overlapping multiplets, 15H, 3Ph). C-NMR (150.9 MHz) δ = 22.8 (J = 5.1 Hz), 23.6, 26.2 (J = 7.9 Hz),
5.8 (J = 7.8 Hz), 70.6 (J = 5.1 Hz), 89.9 (J = 9.9 Hz), 125.6–139.1, 133.4 (J = 51.0 Hz), 164.7
3
31
(
J = 15.1 Hz). P-NMR (242.9 MHz): δ 86.0. Anal. Calcd for C28
.08. Found: C 67.71, H 6.12.
2
H30ClO PS (497.03): C 67.66, H
6
(
3E)-4-(1-Chlorocyclohexyl)-3-diphenylphosphinoyl-4-phenylsulfenyl-but-3-en-2-ol (10d). Orange oil,
−1
1
f
yield: 25%. R 0.62; IR (neat, cm ): 1169 (P=O), 1441, 1488 (Ph), 1618 (C=C), 3391 (OH). H-NMR
(
(
600.1 MHz): δ 1.34–1.46, 1.49–1.54, 1.59–1.78 (overlapping multiplets, 10H, (CH ) ), 1.34
2 5
dd, J = 15.3 Hz, J = 6.5 Hz, 3H, Me-CH), 3.88 (s, 1H, OH), 4.63–4.74 (m, 1H, Me-CH), 7.36–7.71

Molecules 2014, 19
11072
1
3
(
overlapping multiplets, 15H, 3Ph). C-NMR (150.9 MHz) δ = 22.7, 23.4 (J = 7.9 Hz), 25.6, 38.9
(
J = 4.6 Hz), 68.1 (J = 7.9 Hz), 76.3 (J = 5.0 Hz), 126.5–137.4, 133.2 (J = 101.0 Hz), 162.4 (J = 15.0 Hz).
3
1
2
P-NMR (242.9 MHz): δ 34.0.Anal. Calcd for C28H30ClO PS (497.03): C 67.66, H 6.08. Found: C
67.59, H 6.13.
5
-Butyl-3-(1-hydroxy-1-methylethyl)-5-methyl-2,2-diphenyl-4-phenylselenenyl-2,5-dihydro-1,2-oxa-
−1
phosphol-2-ium chloride (8e). Yellow oil, yield: 46%. R
f
0.40; IR (neat, cm ): 1438, 1487 (Ph), 1585
1
(C=C), 3393 (OH). H-NMR (600.1 MHz): δ 0.88 (t, J = 7.1 Hz, 3H, Me-CH ), 1.03–1.11, 1.27–1.34,
2
2
2 3 2
.36–2.50 (m, 6H, (CH ) -Me), 1.58 (s, 3H, Me C), 1.64 (s, 3H, Me-C), 5.24 (s, 1H, OH), 6.94–8.14
1
3
(
overlapping multiplets, 15H, 3Ph). C-NMR (150.9 MHz) δ = 14.1, 22.1 (J = 5.1 Hz), 23.4, 26.4
J = 7.8 Hz), 32.7 (J = 8.0 Hz), 38.4 (J = 7.8 Hz), 81.4 (J = 9.7 Hz), 97.4 (J = 9.8 Hz), 112.7–138.4,
(
3
1
135.3 (J = 53.7 Hz), 178.0 (J = 69.4 Hz). P-NMR (242.9 MHz): δ 89.4. Anal. Calcd for C H ClO PSe
29 34 2
(559.97): C 62.20, H 6.12. Found: C 62.26, H 6.05.
(
3E)-5-Chloro-3-diphenylphosphinoyl-2,5-dimethyl-4-phenylselenenyl-non-3-en-2-ol (10e). Yellow
−1
oil, yield: 24%. R 0.65; IR (neat, cm ): 1170 (P=O), 1438, 1486 (Ph), 1625 (C=C), 3396 (OH).
1
f
H-NMR (600.1 MHz): δ 0.89 (t, J = 7.3 Hz, 3H, Me-CH
2
), 1.30–1.44, 2.38–2.61 (m, 6H, (CH
C), 1.77 (s, 3H, Me-C), 4.13 (s, 1H, OH), 7.38–7.69 (overlapping multiplets,
5H, 3Ph). C-NMR (150.9 MHz) δ = 14.1, 22.9, 25.48, 29.3 (J = 5.1 Hz), 29.9 (J = 7.8 Hz), 43.3
2 3
) -Me),
1
.46, 1.48 (ss, 3H, Me
2
1
3
1
(
J = 4.8 Hz), 82.3 (J = 7.8 Hz), 82.8 (J = 9.9 Hz), 128.4–139.1, 135.8 (J = 102.7 Hz), 153.7 (J = 15.1 Hz).
3
1
2
P-NMR (242.9 MHz): δ 36.9. Anal. Calcd for C29H34ClO PSe (559.97): C 62.20, H 6.12. Found: C
62.25, H 6.08.
4
. Conclusions
In conclusion, a simple and convenient protocol for the reaction of the phosphorylated
α-hydroxyallenes with protected or unprotected hydroxy groups with different electrophilic reagents
was developed. It involves a 5-endo-trig cyclization and 2,3-addition reactions depending on the
substituents on the phosphoryl group. Treatment of 1-hydroxyalkyl-1,2-dienephosphonates with
electrophiles gives 2-methoxy-2-oxo-2,5-dihydro-1,2-oxaphospholes as a result of participation of
the phosphonate group in the cyclization. On the other hand, (1E)-alk-1-en-1-yl phosphine oxides
were prepared as mixtures with 2,5-dihydro-1,2-oxaphosphol-2-ium halides in a ratio of about 1:2 by
2
3
chemo-, regio, and stereoselective electrophilic addition to the C -C -double bond in the allene
moiety and subsequent concurrent attack of the external (halide anion) and internal (phosphine oxide
group) nucleophiles.
Thanks to the ready availability of the starting materials, the convenient operation and the
usefulness of the resulting 1,2-oxaphosphole products this reaction show great potential and will be
useful in organic synthesis. Further studies on the synthetic applications of this reaction and the
physiological activity of selected cyclic and acyclic products, and extension of these studies to the
synthesis and electrophilic cyclization and cycloisomerization reactions of other bifunctionalized
allenes is currently in progress in our laboratory.

Molecules 2014, 19
11073
Acknowledgments
Support from the Research Fund of the Konstantin Preslavsky University of Shumen (Project
No. RD-08-208/2014), National Research Fund of Bulgaria (Project No. DRNF-02-13/2009) and
Human Resources Development Operational Programme of the European Union (BG051PO001-
3
.3.06-0003/2012) is acknowledged.
Author Contributions
V.C.C. proposed the subject designed the study and offered necessary guidance to I.E.I. and I.K.I.
V.C.C. and I.K.I. conceived and designed the experiments. I.E.I. and I.K.I. performed the experiments
under the supervision of the lead author V.C.C. who analyzed the spectral data and wrote the manuscript.
Conflicts of Interest
The authors declare no conflict of interest.
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