The reactivity of arylphosphine oxides under Bouveault-Blanc reaction conditions

Article abstract of DOI:10.1016/j.tet.2017.07.004

Treatment of tertiary arylphosphine oxides with alkali metal/alcohol reagent system lead to the corresponding cyclohexyl-substituted phosphine oxides. This transformation makes use of the inexpensive sodium as the electron donor and an alcohol as the proton source, and provides an attractive alternative to reactions mediated by expensive transition metals. Under optimized conditions numerous mono- and diaryl substituted phosphine oxides were transformed into the corresponding mono- and dicyclohexyl-substituted phosphine oxides in good yields. Furthermore, the formation of 1,2-bis(phosphinoyl)cyclohexanes or unknown 5,10-dialkyltetradecahydrophosphanthrene 5,10-dioxides as side products was observed, which are hardly accessible by other procedures.

Full text of DOI:10.1016/j.tet.2017.07.004

Accepted Manuscript
The reactivity of arylphosphine oxides under Bouveault-Blanc reaction conditions
Ewelina Korzeniowska, Anna E. Kozioł, Elżbieta Łastawiecka, Anna Flis, Marek
Stankevič
PII:
S0040-4020(17)30721-4
10.1016/j.tet.2017.07.004
TET 28836
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 11 May 2017
Revised Date: 22 June 2017
Accepted Date: 3 July 2017
Please cite this article as: Korzeniowska E, Kozioł AE, Łastawiecka Elż, Flis A, Stankevič M, The
reactivity of arylphosphine oxides under Bouveault-Blanc reaction conditions, Tetrahedron (2017), doi:
10.1016/j.tet.2017.07.004.
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Graphical Abstract
The reactivity of arylphosphine oxides under
Bouveault-Blanc reaction conditions
Leave this area blank for abstract info.
Ewelina Korzeniowskaa, Anna E. Koziołb, Elżbieta Łastawiecka a, Anna Flis a, Marek Stankevič a,*
aDepartment of Organic Chemistry, Maria Curie-Sklodowska University, Gliniana 33, 20-614 Lublin, Poland
bDepartment of Crystallography, Maria Curie-Sklodowska University, Maria Curie-Sklodowska sq. 3, 20-031
Lublin, Poland

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
The reactivity of arylphosphine oxides under Bouveault-Blanc reaction conditions
Ewelina Korzeniowskaa, Anna E. Koziołb, Elżbieta Łastawiecka a, Anna Flis a, Marek Stankevič a,
aDepartment of Organic Chemistry, Maria Curie-Sklodowska University, Gliniana 33, 20-614 Lublin, Poland
bDepartment of Crystallography, Maria Curie-Sklodowska University, Maria Curie-Sklodowska sq. 3, 20-031 Lublin, Poland
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Treatment of tertiary arylphosphine oxides with alkali metal/alcohol reagent system lead to the
corresponding cyclohexyl-substituted phosphine oxides. This transformation makes use of the
inexpensive sodium as the electron donor and an alcohol as the proton source, and provides an
attractive alternative to reactions mediated by expensive transition metals. Under optimized
conditions numerous mono- and diaryl substituted phosphine oxides were transformed into the
corresponding mono- and dicyclohexyl-substituted phosphine oxides in good yields.
Furthermore, the formation of 1,2-bis(phosphinoyl)cyclohexanes or unknown 5,10-
dialkyltetradecahydrophosphanthrene 5,10-dioxides as side products was observed, which are
hardly accessible by other procedures.
Available online
Keywords:
Bouveault-Blanc reaction
Arylphosphine oxides
Hydrogenation
2009 Elsevier Ltd. All rights reserved
.
Dearomatization
Cyclohexylphosphine oxides
1. Introduction
of the aryl fragment in arylphosphorus compounds is
relatively underexplored. The first attempted hydrogenation
of arylphosphinic and arylphosphonic acids was performed
by Freedman and coworkers who used Rh/Al2O3 as a
catalyst (Scheme 1).8 Other catalysts used in hydrogenation
of aryl substituents in organophosphorus compounds, such
as Ru/C, Raney-Ni or Nb(p-TolCH2)3(2,6-Ph2-C6H3O)2,
appeared to exhibit good activity and selectivity towards
complete hydrogenation of aromatic groups.9
Molecules with incorporated cyclohexane frameworks are
very popular in organic chemistry and can be found in many
useful substances such as natural products, pharmaceuticals
or fuel.1 One of the possible substrates of these compounds
could be the corresponding aromatic compounds which
upon treatment with a hydrogen source should undergo
saturation of the aromatic ring. Transformation of arenes
into the corresponding cycloalkanes could be achieved by
three different pathways: reduction with metal hydrides,2
Birch reduction3 or catalytic heterogeneous hydrogenation.4
The use of metal hydrides is usually associated with the
formation of large amount of metal salts, while Birch
reduction of arenes lead to 1,4-cyclohexadienes which
should be further hydrogenated using classic catalysts. From
synthetic point of view, catalytic hydrogenation is up to now
the most convenient way for the transformation of arenes
into cycloalkanes.4 However, the catalysts used in these
reactions are usually active only under high pressures and
temperatures, although some progress has been made when
using nanoparticle catalysts5 or water as a solvent.6
Scheme 2. Hydrogenation of phenyl substituents in 1.
Reductive dearomatization of arylphosphorus compounds
using alkali metals in liquid ammonia could also be regarded as a
method for transformation of aryl substituents into their
cycloalkyl analogues.10 Two isolated double bonds in the formed
1,4-cyclohexadiene unit are far more reactive towards
hydrogenation than the parent aryl substituent. Despite the
obvious advantages of this reaction the main drawback is the use
of ammonia due to its irritant odor. Therefore, it would be
desirable to develop alternative reaction conditions for Birch
reduction where ammonia is replaced by a more friendly solvent.
It seems that a good alternative here would be Bouveault-Blanc
reduction, a reaction based on the reduction of carbocylic acid
In the case of functionalized arenes, catalytic
hydrogenation might be a good choice if the corresponding
cycloalkanes are the target molecules. The examples include
hydrogenation of phenols,4d,6b simple alkyl-substituted
arenes,6a phenylalanine and phenylglycine derivatives7 or
monosubstituted benzenes.5b Contrary to this, hydrogenation
———
Corresponding author. Tel.: +48 81 537 77 52; fax: +48 81 524 22 51; e-mail: marek.stankevic@poczta.umcs.lublin.pl

2
Tetrahedron
esters to the corresponding primary alcohols with an alkali
enyl)methylphosphine oxide 7 has been observed which suggests
ACCEPTED MANUSCRIPT
metal in alcohol (Scheme 2).11
that compound 6 undergoes saturation of conjugated double bond
in the presence of an excess of an alkali metal. However, the
most intriguing was the presence of trialkylphosphine oxide 8
where the phenyl group underwent complete saturation under the
reaction conditions. This reaction could be regarded as the first
example of transition metal and hydrogen-free arene
hydrogenation. Here, an alkali metal serves as the electron source
and the alcohol is the proton source.
Scheme 2. Bouveault-Blanc reduction of 3.
To the best of our knowledge, no examples of the reduction of
other classes of organic compounds under these conditions have
been reported.
Contrary to n-BuOH, the use of i-PrOH led to a complete shift
of the selectivity towards monohydrogenation product 6,
although the conversions were usually low. One of the reasons
for the incomplete conversion of 5 might be the loss of an alkali
metal due to its reaction with an excess of an alcohol present in
the reaction. Therefore, a slight modification of the reaction
conditions was proposed. In this case, the reaction was
undertaken in THF as a solvent and 6-fold excess of both alkali
metal and i-PrOH was used (Table 2).
2. Results and discussion
An obvious advantage of Bouveault-Blanc reduction over
Birch reduction is the use of readily available and more
manipulation-friendly alcohols compared to ammonia. Regarding
this, we decided to check the reactivity of a simple tertiary
phosphine oxide under Bouveault-Blanc reduction. For initial
screening, t-butylmethylphenylphosphine oxide (5) was used as a
model compound (Table 1).
Table 2
Optimization of reduction conditions for 5.
Table 1
The reactivity of 5 under Bouveault-Blanc reduction
.
Products
Entry
Na
(equiv.)
ROH
(equiv.)
Time
(h)
7
8
Productsa
Entry
Conditions
1
2
3
4
5
6
7
8
9
6.0
10.0
6.0
6.0
6.0
6.0
6.0
6.0
6.0
i-PrOH (6.0)
i-PrOH (6.0)
i-PrOH (6.0)
i-PrOH (6.0)
i-PrOH (6.0)
i-PrOH (6.0)
s-BuOH (6.0)
t-BuOH (6.0)
t-BuOH (6.0)
48
48
1
37%
40%
34%
33%
30%
30%
28%
30%
28%
57%
60%
66%
67%
70%
70%
72%
70%
72%
6
7
8
1
2
3
4
5
6
7
EtOH, rt, 1 h
22%
30%
23%
16%
26%
22%
12%
-
-
n-BuOH, rt, 0.5 h
i-PrOH, rt, 1 h
i-PrOH, rt, 2 h
i-PrOH, rt, 3 h
i-PrOH, rt, 4 h
i-PrOH, rt, 22 h
11%
4%
2
-
-
-
-
-
-
-
-
-
-
3
4
4
4
24
[a] Yields based on NMR analysis of the reaction mixtures.
[a] Conversions based on NMR analysis.
Addition of sodium into a solution of 5 in ethanol led to a
vigorous evolution of gas which ceased in ca. 5 min (Table 1,
Entry 1). The analysis of the reaction mixture revealed the
presence of phosphine oxide 6 as the only reaction product but
the overall conversion was moderate. This compound is most
probably formed by in situ reduction of phenyl substituent by
metallic sodium followed by double bond migration and
protonation of the carbanion (Scheme 3).
Under these conditions the main product was fully saturated
phosphine oxide along with remarkable amount of
cyclohexenylphosphine oxide 7 which suggests the crucial
influence of the amount of used alcohol on the selectivity of the
reaction.
8
a
It appeared also that the reaction selectivity can be modified
slightly by modification of the reaction conditions. The highest
o
conversion of 5 into 8 was observed after 4 h at 50 C; the
reaction temperature was raised in order to shorten the reaction
time. The use of different alcohols had some influence on the
selectivity of the reaction; the use of s-BuOH or t-BuOH led to
the formation of minor amounts of unidentified by-products. On
the other hand, an increase of the amount of alkali metal had no
influence on the selectivity of the reaction.
To test the utility of the optimized reaction conditions a set of
tertiary phosphine oxides was submitted to the modified
Bouveault-Blanc reduction. First, dialkylphenylphosphine oxides
were used as substrates (Table 3).
Scheme 3. Plausible mechanism for the formation of 6.
Further efforts were put towards the optimization of the
reaction conditions. Replacement of ethanol with n-BuOH led to
a quite striking change in the product composition (Table 1,
Entry 2). Apart from 6, the presence of t-butyl(cyclohex-3-

3
Table 3
Next, alkyldiphenylphosphine oxides were submitted to the
ACCEPTED MANUSCRIPT
Reduction of dialkylphenylphosphine oxides.
reaction under modified Bouveault-Blanc reaction conditions
(Table 4).
O
P
O
P
1. Na (6.0), i-PrOH (6.0)
P(O)R1R2
THF, 50 oC, 24 h
R2
R2
Table 4
R1
R1
2. Pd/C (5 mol %), H2 ( 1 atm)
EtOAc, 25 oC,24 h
P(O)R1R2
Reduction of alkyldiphenylphosphine oxides.
13-23
8, 13a-23a
5b, 13b-23b
O
P
O
P
1. Na (12.0), i-PrOH (12.0)
O
O
R
R
THF, 50 oC, 24 h
P
P
R
R
Entry
Substrate
R1
Me
Et
R2
Me
Products
2. Pd/C (5 mol %), H2 ( 1 atm)
EtOAc, 25 oC,24 h
1
13
14
15
16
17
18
19
20
21
22
23
5
13a (45%)
13b (26%)
26a-29a
26-29
26b-29b
2
Et
14a (38%)
15a (39%)
16a (23%)
17a (78%)
18a (62%)
19a (21%)
20a (23%)
21a (31%)
22a (28%)
23a (49%)
8 (71%)
-
Entry
Substrate
R
Products
3
n-Bu
n-Pr
i-Pr
c-Pen
Bn
n-Bu
n-Pr
i-Pr
c-Pen
Bn
15b (22%)
26b (42%)b (4:3:3:13%)c
27b (40%; 4 isomers)b
28b (30%; 4 isomers)b
29b (33%; 4 isomers)b(5%)c
4
16b (11%)
1
2
3
4
26
27
28
29
Me
26a (17%)
27a (24%)
28a (45%)
29a (23%)
5
-
n-Bu
i-Pr
6
-
7
-
c-Pen
8
Bn
Me
-
[a] Yield of isolated product; [b] Yields based on NMR analysis of the
reaction mixtures; [c] Yield of isolated isomers
9
Bn
n-Bu
i-Pr
t-Bu
t-Bu
-
10
11
12
Bn
-
For these substrates, the 12-fold excess of both sodium and i-
PrOH was used. As can be seen from Table 4, phosphine oxides
26-29 can be directly transformed into dicyclohexylphosphine
oxides 26a-29a but with low to moderate yield. Surprisingly, the
formation of different products as a mixture of four isomers has
been observed under the reaction conditions. NMR and HRMS
analysis of these compounds allowed to ascribe their structure as
5,10-dialkyltetradecahydrophosphanthrene 5,10-dioxides 26b-
29b.
Bn
-
Me
5b (4%)b
[a] Yield of isolated products. [b] A mixture of two isomers.
It was a pleasure to conclude that all reductions took place
smoothly and afforded complete conversion of substrates within
4 h. Unfortunately, small amounts of unsaturated by-products
were observed even after 24 h. To simplify the products isolation
the crude reaction mixtures were submitted to hydrogenation in
the presence of Pd/C. For the symmetrically substituted
substrates 13-19 the reaction afforded the corresponding
saturated products with moderate to good yields (Table 3, entries
1-7). Surprisingly, the reduction of phosphine oxides possessing
Me, n-Bu and n-Pr substituents at phosphorus gave substantial
amounts of 1,2-bis(phosphinoyl)cyclohexanes as byproducts
(Table 3, entries 1, 3 and 4). When unsymmetrically substituted
phosphine oxides were used, the formation of trialkylphosphine
oxides was observed with moderate yields (Table 3, entries 8-
11).
One isomer of 26b, which could be obtained in a crystalline
form, has been subjected to an X-ray structural analysis. The
molecular structure of this isomer is given in Fig. 1.
For a comparison, two cyclic phosphine oxides have been
submitted to the reaction with the Na/i-PrOH system (Scheme 4).
Fig. 1. X-ray structure of one of the isomers of 26b-F3 (CCDC No.
1537702).
(
)
n
(
)
O
n
1. Na (6.0), i-PrOH (6.0)
(
(
)
P
P
n
THF, 50 oC, 24 h
P
P
The X-ray analysis of 26b-F3 confirmed the predicted 5,10-
dialkyltetradecahydrophosphanthrene 5,10-dioxide structure of
the molecule. As it can be seen from the Figure 1, the tricyclic
structure possess trans arrangement of the bridgehead carbon
atoms and also both methyl groups at phosphorus atoms. It could
be assumed that the remaining three isomers should also possess
trans arrangement of bridgehead carbon atoms and methyl
groups could be either in cis or trans mutual correlation.
O
2. Pd/C (5 mol %), H2 ( 1 atm)
EtOAc, 25 oC,24 h
O
O
)
n
24 n = 0
25 n = 1
n = 0;
n = 1;
24a (41%)
25a (38%)
24b (0%)
25b (43%)
Scheme 4. The reactivity of cyclic phosphine oxides 24 and 25
.
Upon treatment with the reagent mixture, phenylphospholane
oxide (24) cleanly yielded the reduction product 24a.On the other
hand, the reduction of 1-phenylphosphorinane-1-oxide (25) took
Next,
a set of reactions has been performed with
place smoothly affording
a mixture of the expected 1-
dialkylarylphosphine oxides possessing different substitution
pattern in aryl fragment (Table 5).
cyclohexylphosphorinane-1-oxide (25a) and the corresponding
diphosphine dioxide 25b with comparable yields.
In this case, the applied reduction protocol for
(methylphenyl)-substituted phosphine oxides afforded the

4
Tetrahedron
ACCEPTED MANUSCRIPT
corresponding methyl-substituted cyclohexylphosphine oxides
noted. Chemical shifts (δ) are given in ppm relative to residual
with good yield as mixtures of isomers (Table 5, entries 3 and 4).
Substrates possessing anisyl substituents at phosphorus (30 and
33) underwent additional C-OMe bond cleavage leading to
overall low yields of desired isomeric products and predominant
formation of 13a and 15a (Table 5, entries 1 and 2).
CHCl3. The following abbreviations are used in reporting NMR
data: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet),
br (broad). Coupling constants (J) are in Hz. High resolution
mass spectrometry analyses were obtained using LCMS IT-TOF
spectrometer. Mass spectra were recorded with GC-MS
spectrometer working in electron ionization (EI) mode. Thin
layer chromatography (TLC) was performed with precoated silica
gel plates and visualized by potassium permanganate (KMnO4)
stain. The reaction mixtures were purified by column
chromatography over silica gel (60–240 mesh). Melting points
were determined in a capillary tube.
Table 5
The reactivity of dialkylarylphosphine oxides 30-33.
O
P
O
P
O
P
R
1. Na (6.0), i-PrOH (6.0)
THF, 50 oC, 24 h
1 R1
R1
R1
R2
R2
R1
R1
+
2. Pd/C (5 mol %), H2 ( 1 atm)
EtOAc, 25 oC,24 h
30-33
30a-33a
13a,15a
4.2. Synthesis of Substrates
Entry
1
Substrate
Aryl
R1
Yielda
4.2.1. Tertiary Dialkylarylphosphine Oxides
30
m-OMe-C6H4
Me
30a (30%) (1:6.2)b
13a (33%)
t-Butylmethylphenylphosphine oxide (5) was prepared
according to literature procedure.12 The symmetrically substituted
substrates 13-18 were prepare according to general procedure
described below.
2
31
p-OMe-C6H4
n-Bu
31a (10%) (1:3.2)b
15a (56%)
3
4
32
33
p-Me-C6H4
n-Bu
n-Bu
32a (74%) (1:1.7)b
Into a flame-dried two-necked flask equipped with magnetic
stirrer and argon inlet was placed Grignard or organolithium
reagent (15 mmol) in dry and degassed THF (30 mL). The
3,5-Me2-C6H3
33a (77%) (1:1.7:2)b
o
o
mixture was cooled to 0 C or -78 C and phenylphosphonic
dichloride (6 mmol) was added dropwise. The reaction mixture
was allowed to warm to room temperature and stirred for
overnight under argon atmosphere. The mixture was cooled to 0
oC and hydrogen peroxide (30% in H2O2; 2.5 equiv.) was added
slowly via syringe, allowed to warm to room temperature and
stirred for 2 h. The reaction was quenched by addition of
saturated NH4Cl solution (20 mL), the mixture was extracted
with DCM (3×50 mL), the organic layers were collected, dried
over MgSO4, filtered, and evaporated. The residue was purified
by flash chromatography using chloroform/methanol 15:1 as
eluent.
[a] Yield of isolated products; [b] isomers ratio was determined by 31P
NMR analysis of crude reaction mixture.
Finally, it was decided to submit phosphine oxides with
naphthyl substituent at phosphorus to the modified Bouveault-
Blanc reduction (Scheme 5).
Analytical data for dimethylphenylphosphine oxide (13),10b di-
Scheme 5. The reduction of naphthylphosphine oxides 34 and 35.
n-propylphenylphosphine
oxide
(16),13
dicyclopentyl-
phenylphosphine oxide (18),14 diethylphenylphosphine oxide
(14), di-n-butylphenylphosphine oxide (15) and di-i-
propylphenylphosphine oxide (17)15 are in accordance with
previously reported.
Here, the formation of partially saturated compounds 34a and
35a has been observed. The aryl fragment bonded directly to the
phosphorus group underwent reduction whereas the non-
conjugated arene ring remained unchanged under the reaction
conditions.
Dibenzylphenylphosphine
oxide
(19),
benzylmethyl-
phenylphosphine oxide (20), benzyl(t-butyl)phenylphosphine
3. Conclusions
oxide (23) were prepared according to the literature procedure.10b
In conclusion, an alternative method for arene saturation in
phosphorus-substituted arenes has been presented. The modified
Bouveault-Blanc reduction of arylphosphine oxides led to the
formation of the corresponding cyclohexylphosphine oxides as the
main products. The developed method practically excludes the use of
expensive transition metals as catalysts and H2 gas as hydrogen
source.
Benzyl(n-butyl)phenylphosphine oxide (21) and benzyl(i-
propyl)phenylphosphine oxide (22) were prepared as follows:
Into a flame-dried two-necked flask equipped with magnetic
stirrer and argon inlet was placed benzylphenylphosphine oxide
(1.080 g, 5 mmol) in dry and degassed THF (15 mL). The
o
mixture was cooled to 0 C and sodium hydride (0.22 g, 5.5
mmol, 60% dispersion in mineral oil) was added in one portion.
After the evolution of hydrogen ceased, the appropriate alkyl
halide (n-bromobutane or i-propyl bromide) (5.5 mmol) was
added in one portion and the reaction was allowed to reach room
temperature and stirr for overnight under argon. The reaction was
quenched by addition of saturated NH4Cl solution (10 mL), the
mixture was extracted with DCM (3 x 30 ml), the organic layers
were collected, dried over MgSO4, filtered and evaporated. The
residue was purified by flash chromatography using
chloroform:methanol 15:1 as eluent. Analytical data for
benzyl(n-butyl)phenylphosphine oxide (21) are in accordance
with those reported earlier.16
4. Experimental section
4.1. General remarks
All reactions were performed under an argon atmosphere
using Schlenk techniques. Only dry solvents were used, and the
glassware was heated under vacuum prior to use. Solvents for
chromatography and extraction were commercially available and
used as received without further purification. Tetrahydrofurane
was dried over sodium/benzophenone ketyl. Sodium (ingot) was
commercially available and used as received.
The NMR spectra was recorded with 500 MHz spectrometer
in CDCl3 as a solvent at room temperature unless otherwise

5
4.2.1.1. Benzyl(i-propyl)phenylphosphine oxide (22).
stirred under hydrogen (1 atm), at room temperature for 24 h.
ACCEPTED MANUSCRIPT
o
Yield: 0.337 g (26%). White solid, mp = 121-122 C, Rf =
After this time, the reaction mixture was then filtered through
Celite, which was washed with DCM (2x20 mL) and solvent was
evaporated under reduced pressure. The product was purified by
silica-gel column chromatography (CHCl3/MeOH 15/1).
0.70 (CHCl3/MeOH = 15:1) 1H NMR 1H NMR (500 MHz,
CDCl3) δ 1.06 (dd, JH-H = 6.9 Hz, JP-H = 16.4 Hz, 3H), 1.29 (dd,
JH-H = 7.3 Hz, JP-H = 15.8 Hz, 3H), 2.09-2.21 (m, 1H), 3.30-3.48
(m, 2H), 7.09-7.15 (m, 2H), 7.15-7.25 (m, 3H), 7.39-7.45 (m,
2H), 7.47-7.53 (m, 1H), 7.54-7.61 (m, 2H). 13C NMR (126 MHz,
CDCl3) δ 15.0 (d, JP-C = 3.6 Hz), 15.8 (d, JP-C = 2.7 Hz), 26.9 (d,
4.3.1. t-Butyl(cyclohex-2-en-1-yl)methylphosphine oxide (7)
This compound was formed during the first step of general
procedure from t-butylmethylphenylphosphine oxide (5). The
two diastereoisomers in a 1:1 ratio were isolated as an
inseparable mixture with 8, yield: 16%. Rf = 0.26 (CHCl3/MeOH
= 15:1) 31P NMR (202 MHz, CDCl3) δ 56.1 and 56.2. GC tR =
7.86 min; GCMS (EI, 70 eV), m/z 57 (100) 120 (59) 121 (39) 65
(35) 79 (31) 78 (28) 116 (28) 64 (28) 81 (14) 80 (14) 91 (13) 77
(12) 115 (11) 146 (11) 63 (11) 55 (11) 129 (11). GC tR = 7.89
min; GCMS (EI, 70 eV), m/z 57(100) 120 (49) 121 (37) 65 (28)
79 (26) 64 (26) 78 (24) 116 (18) 80 (11) 77 (11). HRMS (ESI):
m/z = 201.1393 [C11H21OP+H]+, m/z (calc'd) = 201.1403, diff. =
-4.97 ppm.
JP-C = 69.0 Hz), 35.4 (d, JP-C = 59.0 Hz), 126.7, 128.2 (d, JP-C
=
10.9 Hz), 128.4 (d, JP-C = 2.7 Hz), 129.8 (d, JP-C = 5.5 Hz), 131.2
(d, JP-C = 8.2 Hz), 131.5. 31P NMR (202 MHz, CDCl3) δ 43.78.
GC tR = 13.78 min; GCMS (EI, 70 eV), m/z 258 (M) (24), 257
(39), 167 (53), 125 (100), 109 (10), 105 (13), 92 (10), 91 (85), 77
(13), 65 (24), 47 (49). HRMS (ESI): m/z
= 259.1236
[C16H19OP+H]+, m/z (calc'd) = 259.1246, diff. = -3.86 ppm.
Cyclic 1-phenylphospholane oxide (24)17 and 1-
phenylphosphorinane-1-oxide (25)18 were synthesized according
to reported procedures. Analytical data match previously reported
values.
4.3.2. t-Butylcyclohexylmethylphosphine oxide (8)
4.2.2. Tertiary Alkyldiarylphosphine Oxides
The compound 8 was prepared according to the general
procedure from t-butylmethylphenylphosphine oxide (5) (0.13 g,
0.66 mmol), sodium (0.09g, 3.97 mmol, 6 equiv) and i-PrOH
(0.29 mL, 3.97 mmol, 6 equiv). Yield: 0.095 g (71%). Colorless
oil. Rf = 0.26 (CHCl3/MeOH = 15:1) 1H NMR (500 MHz, CDCl3)
The diphenylphosphine oxides 26-29 were prepared according
to general procedure described below.
Into a flame-dried two-necked flask equipped with magnetic
stirrer and argon inlet was placed chlorodiphenylphosphine (6
mmol) in dry and degassed THF (30 mL). The mixture was
cooled to 0 oC and Grignard or organolithium reagent (7.5 mmol)
was added dropwise. The reaction mixture was allowed to warm
to room temperature and stirred for overnight under argon
atmosphere. The mixture was cooled to 0 oC and hydrogen
peroxide (30% in H2O2; 2.5 equivalents) was added slowly via
syringe and allowed to warm to room temperature and stirred for
2 h. The reaction was quenched by addition of saturated NH4Cl
solution (20 mL), the mixture was extracted with DCM (3×50
mL), the organic layers were collected, dried over MgSO4,
δ 1.18 (d, JP-H = 13.9 Hz, 9H), 1.21-1.30 (m, 3H), 1.30 (d, JP-H
=
11.4 Hz, 3H), 1.34-1.49 (m, 2H), 1.69-1.72 (m, 1H), 1.77-1.91
(m, 4H), 2.05-2.15 (m, 1H). 13C NMR (126 MHz, CDCl3) δ 7.9
(d, JP-C = 60.0 Hz), 25.2, 25.9, 26.5 (d, JP-C = 3.6 Hz), 26.6 (d, JP-
C = 11.8 Hz), 26.8 (d, JP-C = 12.7 Hz), 27.7 (d, JP-C = 2.7 Hz),
32.8 (d, JP-C = 65.4 Hz), 35.9 (d, JP-C = 64.6 Hz). 31P NMR (202
MHz, CDCl3) δ 56.0. GC tR = 7.8 min; GCMS (EI, 70 eV), m/z
65 (100) 91 (88) 146 (85) 57 (81) 120 (59) 55 (56) 64 (36) 147
(29) 83 (27) 78 (25) 105 (21) 104 (20) 121 (20) 81 (18) 63 (18)
92 (16) 131 (15) 117 (12) 67 (11) 79 (10) 118 (10). HRMS (ESI):
m/z = 203.1549 [C11H23OP+H]+, m/z (calc'd) = 203.1559, diff. =
-4.92 ppm.
filtered,
methyldiphenylphosphine
and
evaporated.
Analytical
oxide
data
for
n-
(26),19
4.3.3. Cyclohexyldimethylphosphine oxide (13a)
butyldiphenylphosphine oxide (27), i-propyldiphenylphosphine
oxide (28)20 and cyclopentyldiphenylphosphine oxide (29)21 are
in accordance with previously reported.
The compound 13a was prepared according to the general
procedure from dimethylphenylphosphine oxide (13) (0.15 g, 1
mmol), sodium (0.14 g, 6 mmol, 6 equiv) and i-PrOH (0.45 mL,
6 mmol, 6 equiv). Yield: 0.072 g (45%). Colorless crystals, mp =
The dialkylarylphosphine oxides possessing different
substitution pattern in aryl fragment such as di-n-butyl(3-
o
1
127-128 C Rf = 0.31 (CHCl3/MeOH = 15:1). H NMR (500
MHz, CDCl3) δ 1.19-1.34 (m, 5H), 1.41 (d, JP-H = 12.0 Hz, 6H),
1.55-1.65 (m, 1H), 1.74 (d, JP-H = 9.8 Hz, 1H), 1.82-1.89 (m, 2H),
methoxyphenyl)phosphine
methoxyphenyl)phosphine
methylphenyl)phosphine
oxide
oxide
oxide
(30),
(31),
(32),
di-n-butyl(4-
di-n-butyl(4-
di-n-butyl(3,5-
1.92-1.98 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 13.6 (d, JP-C
=
66.3 Hz), 25.4 (d, JP-C = 2.7 Hz), 25.8 (d, JP-C = 1.2 Hz), 26.3 (d,
JP-C = 13.6 Hz), 39.5 (d, JP-C = 70.8 Hz). 31P NMR (202 MHz,
CDCl3) δ 45.95. GC tR = 7.1 min; GCMS (EI, 70 eV), m/z 78
(100) 79 (42) 105 (31) 63 (16) 55 (15) 77 (10) 81 (6) 92 (5).
HRMS (ESI): m/z = 161.1087 [C8H17OP+H]+, m/z (calc'd) =
161.1090, diff. = -1.86 ppm.
dimethylphenyl)phosphine oxide (33), dimethyl(naphthalen-1-
yl)phosphine oxide (34) and di-n-butyl(naphthalen-1-
yl)phosphine oxide (35) were prepared following the synthetic
procedure developed in our laboratory.
4.3. General experimental procedure for the reduction of
phosphine oxides with Na/i-PrOH system
4.3.4. 1,2-Bis(dimethylphosphinoyl)cyclohexane (13b)
In a flame-dried Schlenk tube (20 mL) equipped with
magnetic stirrer and an inert gas inlet a substrate (0.3-1 mmol)
was dissolved in 3-10 mL of dry THF. To this solution was
added (6 or 12 equiv) of i-PrOH followed by (6 or 12 equiv) of
sodium and the reaction mixture was heated at 50 °C for 24 h.
The reaction was then quenched with sat. NaCl (5 mL) and
extracted with DCM (3×20 mL). The combined organic phases
were dried over MgSO4, filtered, and evaporated under the
reduced pressure. The obtained residue and Pd/C (5 mol%) were
placed in a flame-dried Schlenk tube (20 mL) under argon. Dry
EtOAc was added (5 mL, the reaction vessel was evacuated three
times and filled with hydrogen, and the reaction mixture was
The compound 13b was prepared according to the general
procedure from dimethylphenylphosphine oxide (13) (0.15 g, 1
mmol), sodium (0.14 g, 6 mmol, 6 equiv) and i-PrOH (0.45 mL,
6 mmol, 6 equiv). Yield: 0.031 g (26%). White crystal, mp =
223-226 oC, Rf = 0.05 (CHCl3/MeOH = 15:1). 1H NMR 1H NMR
(500 MHz, CDCl3) δ 1.57 (d, JP-H = 12.0 Hz, 6H), 1.62 (d, JP-H
=
11.7 Hz, 6H), 1.65-1.79 (m, 4H), 1.82-1.93 (m, 2H), 2.18 (m,
2H), 2.27-2.36 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 15.5-16.6
(m, CH3), 22.6, 23.4, 34.18-35.17 (m, CH). 31P NMR (202 MHz,
CDCl3) δ 48.5. GC tR = 10.3 min; GCMS (EI, 70 eV), m/z 159
(100) 81 (37) 79 (34) 77 (25) 78 (13) 139 (12) 63 (10) 160 (10)

6
Tetrahedron
221 (8) 47 (6). HRMS (ESI): m/z
=
495.2077
(ESI): m/z = 217.1709 [C12H25OP+H]+, m/z (calc'd) = 217.1716,
ACCEPTED MANUSCRIPT
[C20H44O2P2+Na]+, m/z (calc'd) = 495.2082 , diff. = -1.01 ppm.
diff. = -3.22 ppm.
4.3.5. Cyclohexyldiethylphosphine oxide (14a)
4.3.9. 1,2-Bis(di(n-propyl)phosphinoyl)cyclohexane (16b)
The compound 14a was prepared according to the general
procedure from diethylphenylphosphine oxide (14) (0.11 g, 0.6
mmol), sodium (83 mg, 6 equiv) and i-PrOH (0.274 mL, 6
equiv). Yield: 0.043 g (38%). Colorless oil. Rf = 0.35
(CH2Cl2/MeOH = 15:1). 1H NMR (500 MHz, CHCl3) δ 1.10-1.18
(m, 6H), 1.21-1.40 (m, 5H), 1.58-1.75 (m, 6H), 1.79-1.93 (m,
4H). 13C NMR (126 MHz, CDCl3) δ 5.7 (d, JP-C = 5.5 Hz), 17.7
(d, JP-C = 64.5 Hz), 25.3 (d, JP-C = 2.7 Hz), 25.9 (d, JP-C = 1.8 Hz),
26.5 (d, JP-C = 11.8 Hz), 36.1 (d, JP-C = 66.3 Hz). 31P NMR (202
MHz, CDCl3) δ 52.9. GC tR = 8.8 min; GCMS (EI, 70 eV), m/z
106 (100) 78 (51) 133 (33) 107 (32) 77 (23) 55 (20) 79 (14) 81
The compound 16b was prepared according to the general
procedure from di-n-propylphenylphosphine oxide (16) (0.063 g,
0.3 mmol), sodium (41 mg, 6 equiv) and i-PrOH (0.14 mL, 6
equiv). Yield: 0.006 g (11%). Colorless oil. Rf = 0.35
(CH2Cl2/MeOH = 15:1). 1H NMR (500 MHz, CDCl3) δ 1.01-1.10
(m, 12H), 1.51-1.77 (m, 18H), 1.77-1.92 (m, 4H), 2.13-2.26 (m,
2H), 2.28-2.36 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 15.8 (d,
JP-C = 20.0 Hz), 15.9-16.1 (m, CH3) 22.7, 23.3, 28.7-30.0 (m),
30.8-31.9 (m). 31P NMR (202 MHz, CDCl3) δ 53.6. GC tR = 20.0
min; GCMS (EI, 70 eV), m/z 215 (100) 133 (22) 2162 (20) 263
(13) 63 (10) 81 (10) 73 (8) 181 (8) 135 (7) 305 (6) 79 (5). HRMS
(12) 49 (11) 105 (9). HRMS (ESI): m/z
=
377.2717
(ESI): m/z = =
349.2409 [C18H38O2P2+H]+, m/z (calc'd)
[C20H42O2P2+H]+, m/z (calc'd) = 377.2733, diff. = -4.24 ppm.
349.2420, diff. = -3.15ppm.
4.3.6. Di-n-butylcyclohexylphosphine oxide (15a)
4.3.10. Cyclohexyldi(i-propyl)phosphine oxide (17a)
The compound 15a was prepared according to the general
procedure from di-n-butylphenylphosphine oxide (15) (0.08 g,
0.33 mmol), sodium (46 mg, 6 equiv) and i-PrOH (0.15 mL, 6
equiv). Yield: 0.031 g (39%). Colorless oil. Rf = 0.43
The compound 17a was prepared according to the general
procedure from di-i-propylphenylphosphine oxide (17) (0.14 g,
0.66 mmol), sodium (0.092g, 6 equiv) and i-PrOH (0.299 mL, 6
equiv). Yield: 0.123 g (78%). Colorless oil. Rf = 0.48
1
1
(CH2Cl2/MeOH = 15:1). H NMR (500 MHz, CDCl3) δ 0.94 (t,
(CHCl3/MeOH = 15:1). H NMR (500 MHz, CDCl3) δ 1.16 (dd,
JH-H = 7.3 Hz, 6H), 1.21-1.37 (m, 5H), 1.43 (dq, JP-H = 14.5 Hz,
JH-H = 7.3 Hz, 4H), 1.51-1.77 (m, 10H), 1.81-1.96 (m, 4H). 13C
NMR (126 MHz, CDCl3) δ 13.7, 23.7 (d, JP-C = 4.5 Hz), 24.5 (d,
JP-C = 14.5 Hz), 25.2 (d, JP-C = 63.4 Hz), 25.4 (d, JP-C = 2.7 Hz),
JP-H = 14.2 Hz, JP-H = 7.3 Hz, 12 H), 1.18-1.24 (m, 3H), 1.37 (d,
JP-H = 12.0 Hz, 2H), 1.64-1.69 (m, 1H), 1.78 (dd, JP-H = 10.3 Hz,
JH-H = 3.0 Hz, 2H), 1.83 (dt, JP-H = 12.0 Hz, JH-H = 3.0 Hz, 1H),
1.88 (d, JP-H = 12.3 Hz, 2H), 2.01-2.12 (m, 2H). 13C NMR (126
MHz, CDCl3) δ 16.42 (d, JP-C = 4,5 Hz), 16.45 (d, JP-C = 2.7 Hz),
24.4 (d, JP-C = 61.0 Hz), 26.0 (d, JP-C = 1.8 Hz), 26.3 (d, JP-C = 2.7
Hz), 26.8 (d, JP-C = 11.8 Hz), 35.53 (d, JP-C = 61.0 Hz). 31P NMR
(202 MHz, CDCl3) δ 56.6. GC tR = 8,18 min; GCMS (EI, 70 eV),
m/z (%) 134 (100), 92 (62), 93 (35), 55 (33), 81 (30), 173 (27),
91 (24), 63 (19), 135 (19), 74 (19), 161 (19), 73 (18), 83 (12),
26.0 (d, JP-C = 1.2 Hz), 26.5 (d, JP-C = 12.7 Hz), 36.9 (d, JP-C
=
66.3 Hz). 31P NMR (202 MHz, CDCl3) δ 50.6. GC tR = 8.9 min;
GCMS (EI, 70 eV), m/z 78 (100) 55 (65) 120 (55) 63 (41) 146
(38) 79 (35) 162 (25) 105 (19) 81 (19) 215 (19) 173 (17) 65 (17)
92 (15) 188 (15) 121 (14) 91 (14) 64 (14) 147 (13) 107 (13) 160
(13) 133 (11) 83 (11) 106 (10). HRMS (ESI): m/z = 511.3798
[C28H58O2P2+Na]+, m/z (calc'd) = 511.3804, diff. = -1.17 ppm.
119 (11), 132 (10). HRMS (ESI): m/z
=
239.1524
[C12H25OP+Na]+, m/z (calc'd) = 239.1535, diff. = -4.60 ppm.
4.3.7. 1,2-Bis(di(n-butyl)phosphinoyl)cyclohexane (15b)
The compound 15b was prepared according to the general
procedure from di-n-butylphenylphosphine oxide (15) (0.08 g,
0.33 mmol), sodium (46 mg, 6 equiv) and i-PrOH (0.15 mL, 6
equiv). Yield: 0.015 g (22%). Colorless oil. Rf = 0.35
4.3.11. Cyclohexyldicyclopentylphosphine oxide (18a)
The compound 18a was prepared according to the general
procedure from dicyclopentylphenylphosphine oxide (18) (0.087
g, 0.33 mmol), sodium (0.046g, 6 equiv) and i-PrOH (0.151 mL,
6 equiv). Yield: 0.055 g (62%). Colorless oil. Rf = 0.38
(CH2Cl2/MeOH = 15:1). 1H NMR (500 MHz, CDCl3) δ 1.21-1.37
(m, 5H), 1.54-1.64 (m, 4H), 1.70-1.78 (m, 5H), 1.81-1.94 (m,
11H), 1.98-2.09 (m, 4H). 13C NMR (126 MHz, CDCl3) δ 26.0 (d,
JP-C = 10.0 Hz), 26.3 (d, JP-C = 1.2 Hz), 26.4 (d, JP-C = 9.1 Hz),
26.6 (d, JP-C = 2.7 Hz), 27.0 (d, JP-C = 13.5 Hz), 27.1, 27.2 (d, JP-C
= 1.8 Hz), 36.0 (d, JP-C = 65.4 Hz), 38.4 (d, JP-C = 64.5 Hz). 31P
NMR (202 MHz, CDCl3) δ 53.3. GC tR = 12.6 min; GCMS (EI,
70 eV), m/z 119 (100) 118 (72) 55 (51) 145 (44) 99 (44) 67 (43)
200 (42) 186 (42) 132 (32) 69 (29) 133 (25) 227 (19) 81 (19) 83
(17) 51 (14) 159 (14) 185 (13) 199 (10) 201 (10). HRMS (ESI):
m/z = 291.1835 [C16H29OP+Na]+, m/z (calc'd) = 291.1848, diff. =
-4.46 ppm.
1
(CH2Cl2/MeOH = 15:1). H NMR (500 MHz, CDCl3) δ 0.95 (q,
JH-H = 6.9 Hz, 12H), 1.38-1.49 (m, 9H), 1.50-1.59 (m, 5H), 1.60-
1.95 (m, 16H), 2.14-2.28 (m, 2H), 2.34 (bs, 2H). 13C NMR (126
MHz, CDCl3) δ 13.7 (d, JP-C = 1.8 Hz), 23.0 (d, JP-C = 74.5 Hz),
24.1 (d, JP-C = 24.5 Hz), 24.4 (d, JP-C = 20.0 Hz), 24.4 (d, JP-C
=
7.3 Hz), 26.2-27.5 (m, CH2), 30.71-31.69 (m, CH). 31P NMR
(202 MHz, CDCl3) δ 54.1. GC tR = 12.9 min; GCMS (EI, 70 eV),
m/z 243 (100) 244 (17) 161 (14) 63 (13) 291 (11) 55 (11) 81 (9)
78 (8) 347 (6). HRMS (ESI): m/z = 405.3053 [C22H46O2P2+H]+,
m/z (calc'd) = 405.3046, diff. = 1.73 ppm.
4.3.8. Cyclohexyldi(n-propyl)phosphine oxide (16a)
The compound 16a was prepared according to the general
procedure from di-n-propylphenylphosphine oxide (16) (0.063 g,
0.3 mmol), sodium (41 mg, 6 equiv) and i-PrOH (0.14 mL, 6
equiv). Yield: 0.015 g (23%). Colorless oil. Rf = 0.45
(CH2Cl2/MeOH = 15:1). 1H NMR (500 MHz, CDCl3) δ 0.99-1.07
(m, 6H), 1.19-1.38 (m, 5H), 1.55-1.76 (m, 10H), 1.81-1.87 (m,
4.3.12. Dibenzylcyclohexylphosphine oxide (19a)
The compound 19a was prepared according to the general
procedure from dibenzylphenylphosphine oxide (19) (0.092 g,
0.3 mmol), sodium (0.041g, 6 equiv) and i-PrOH (0.137 mL, 6
equiv). Yield: 0.020 g (21%). White crystal, mp = 151-153 oC; Rf
2H), 1.90 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 15.3 (d, JP-C
=
1
3.6 Hz), 16.0 (d, JP-C = 14.5 Hz), 25.4 (d, JP-C = 2.7 Hz), 25.9,
= 0.4 (CH2Cl2/MeOH = 15:1). H NMR (500 MHz, CDCl3) δ
26.5 (d, JP-C = 12.7 Hz), 27.7 (d, JP-C = 62.7 Hz), 36.9 (d, JP-C
=
1.10-1.23 (m, 3H), 1.23-1.35 (m, 2H), 1.62-1.73 (m, 2H), 1.82 (s,
66.3 Hz). 31P NMR (202 MHz, CDCl3) δ 50.5. GC tR = 9.3 min;
GCMS (EI, 70 eV), m/z 134 (100) 92 (79) 106 (72) 78 (57) 93
(53) 174 (50) 55 (49) 63 (37) 119 (36) 132 (31) 133 (29) 135 (27)
161 (27) 64 (27) 81 (24) 73 (23) 91 (19) 146 (18) 83 (14) 201
(14) 173 (13) 159 (13) 107 (12) 79 (11) 65 (11) 47 (10). HRMS
2H), 1.95 (s, 2H), 2.97-3.15 (m, 4H), 7.24-7.38 (m, 10H). 13C
NMR (126 MHz, CDCl3) δ 25.7 (d, JP-C = 2.7 Hz), 25.9 (d, JP-C
=
1.8 Hz), 26.4 (d, JP-C = 12.7 Hz), 33.5 (d, JP-C = 58.1 Hz), 36.5 (d,
JP-C = 66.3 Hz), 126.8 (d, JP-C = 2.9 Hz), 128.7 (d, JP-C = 2.7 Hz),
129.8 (d, JP-C = 4.5 Hz), 132.2 (d, JP-C = 7.3 Hz). 31P NMR (202
MHz, CDCl3) δ 45.4. GC tR = 15.2 min; GCMS (EI, 70 eV), m/z

7
91 (100) 139 (62) 230 (24) 55 (23) 312 (18) 65 (14) 121 (13) 81
(12) 221 (10). HRMS (ESI): m/z = 625.3370 [C40H50O2P2+H]+,
m/z (calc'd) = 625.3359, diff. = 1.76 ppm.
(0.082 g, 0.3 mmol), sodium (0.41 g, 6 equiv) and i-PrOH
ACCEPTED MANUSCRIPT
(0.137 mL, 6 equiv). Yield: 0.041 g (49%). White crystal, mp =
o
1
113 C; Rf = 0.35 (CH2Cl2/MeOH = 15:1). H NMR (500 MHz,
CDCl3) δ 1.10-1.29 (m, 4H), 1.19 (d, JP-H = 13.60 Hz, 9H), 1.37-
1.48 (m, 1H), 1.65-1.71 (m, 1H), 1.75-1.83 (m, 2H), 1.83-1.93
(m, 1H), 1.99-2.10 (m, 1H), 3.06-3.19 (m, 1H), 7.22-7.26 (m,
1H), 7.31 (t, JH-H = 7.6 Hz, 2H), 7.42 (d, JH-H = 7.6 Hz, 2H). 13C
NMR (126 MHz, CDCl3) δ 25.8, 26.1 (d, JP-C = 1.2 Hz), 27.0 (d,
JP-C = 1.8 Hz), 27.1 (d, JP-C = 1.8 Hz), 27.3 (d, JP-C = 2.7 Hz), 27.5
(d, JP-C = 2.7 Hz), 30.0 (d, JP-C = 53.6 Hz), 34.1 (d, JP-C = 61.8 Hz)
37.2 (d, JP-C = 60.0 Hz), 126.5 (d, JP-C = 1.8 Hz), 128.5, 130.2 (d,
JP-C = 4.5 Hz), 133.2 (d, J = 6.4 Hz). 31P NMR (202 MHz, CDCl3)
δ 53.1. GC tR = 12.0 min; GCMS (EI, 70 eV), m/z 91 (100) 140
(59) 129 (52) 196 (41) 222 (39) 122 (37) 141 (37) 113 (33) 278
(23) 81 (23) 167 (22) 131 (20) 139 (18) 83 (14) 121 (13) 92 (12)
4.3.13. Benzylcyclohexylmethylphosphine oxide (20a)
The compound 20a was prepared according to the general
procedure from benzylmethylphenylphosphine oxide (20) (0.076
g, 0.33 mmol), sodium (0.046 g, 6 equiv) and i-PrOH (0.153 mL,
o
6 equiv). Yield: 0.018 g (23%). White crystal, mp = 107-109 C;
Rf = 0.43 (CH2Cl2/MeOH = 15:1). 1H NMR (500 MHz, CDCl3) δ
1.22-1.28 (m, 2H), 1.28-1.31 (m, 3H), 1.32-1.49 (m, 3H), 1.61-
1.71 (m, 1H), 1.72-1.96 (m, 4H), 2.05 (d, JP-H = 12.3 Hz, 1H),
3.03-3.25 (m, 2H), 7.26-7.31 (m, 3H), 7.32-7.37 (m, 2H). 13C
NMR (126 MHz, CDCl3) δ 11.1 (d, JP-C = 66.3 Hz), 25.8 (d, JP-C
=
2.7 Hz), 25.6 (d, JP-C = 2.7 Hz), 25.9 (d, JP-C = 1.9 Hz), 26.2 (d, JP-
C = 6.4 Hz), 26.3 (d, JP-C = 6.4 Hz), 35.6 (d, JP-C = 60.0 Hz), 37.5
(d, JP-C = 69.0 Hz), 126.8 (d, JP-C = 2.7 Hz), 128.8 (d, JP-C = 1.8
Hz), 129.6 (d, JP-C = 4.5 Hz), 132.4 (d, JP-C = 7.3 Hz). 31P NMR
(202 MHz, CDCl3) δ 46.8. GC tR = 11.6 min; GCMS (EI, 70 eV),
m/z 91 (100) 154 (89) 81 (32) 181 (26) 155 (24) 236 (23) 92 (21)
83 (11). HRMS (ESI): m/z = 473.2754 [C28H42O2P2+H]+, m/z
(calc'd) = 473.2733, diff. = 4.44 ppm.
187 (11) 223 (10). HRMS (ESI): m/z
=
557.3680
[C34H54O2P+H]+, m/z (calc'd) = 557.3672, diff. = 1.44 ppm.
4.3.17. 1-Cyclohexylphosphinane 1-oxide (24a)
The compound 24a was prepared according to the general
procedure from 1-phenylphospholane oxide (24) (0.108 g, 0.6
mmol), sodium (0.083 g, 6 equiv) and i-PrOH (0.276 mL, 6
equiv). Yield: 0.040 g (36%). Colorless oil. Rf = 0.40
(CH2Cl2/MeOH = 15:1). 1H NMR 1H NMR (500 MHz, CDCl3) δ
1.21-1.33 (m, 3H), 1.33-1.44 (m, 2H), 1.60-1.83 (m, 8H), 1.83-
1.90 (m, 2H), 1.92-1.98 (m, 2H), 1.99-2.07 (m, 2H). 13C NMR
(126 MHz, CDCl3) δ 24.9 (d, JP-C = 62.7 Hz), 24.8 (d, JP-C = 7.3
4.3.14. Benzyl(n-butyl)cyclohexylphosphine oxide (21a)
The compound 21a was prepared according to the general
procedure from benzyl(n-butyl)phenylphosphine oxide (21)
(0.082 g, 0.3 mmol), sodium (0.41 g, 6 equiv) and i-PrOH (0.137
mL, 6 equiv). Yield: 0.026 g (31%). White crystal, mp = 95-97
oC; Rf = 0.45 (CH2Cl2/MeOH = 15:1). 1H NMR (500 MHz,
CDCl3) δ 0.87-0.92 (m, 3H), 1.22-1.28 (m, 3H), 1.33-1.40 (m,
3H), 1.44-1.66 (m, 5H), 1.70 (dt, JP-H = 12.0 Hz, JH-H = 3.0 Hz,
1H), 1.74 (dd, JH-H = 5.4 Hz, JP-H = 5.42.2 Hz, 1H), 1.83-2.01 (m,
4H), 3.02-3.21 (m, 2H), 7.22-7.40 (m, 5H). 13C NMR (126 MHz,
CDCl3) δ 13.6, 23.6 (d, JP-C = 4.5 Hz), 24.3, 24.4 (d, JP-C = 5.5
Hz), 25.0, 25.5 (d, JP-C = 2.7 Hz), 25.5 (d, JP-C = 2.7 Hz), 25.9,
Hz), 25.5 (d, JP-C = 2.7 Hz), 25.8 (d, JP-C = 1.8 Hz), 26.2 (d, JP-C
=
12.7 Hz), 38.8 (d, JP-C = 64.5 Hz). 31P NMR (202 MHz, CDCl3) δ
75.4. GC tR = 9.9 min; GCMS (EI, 70 eV), m/z (%) 104 (100)
105 (51) 131 (43) 55 (19) 103 (19) 76 (17) 47 (11). HRMS (ESI):
m/z = 187.1250 [C10H19OP+H]+, m/z (calc'd) = 187.1246, diff. =
2.14 ppm.
4.3.18. 1-Cyclohexylphosphinane 1-oxide (25a)
26.4 (d, JP-C = 13.6 Hz), 33.8 (d, JP-C = 57.2 Hz), 36.6 (d, JP-C
=
The compound 25a was prepared according to the general
procedure from 1-phenylphosphorinane-1-oxide (25) (0.194 g, 1
mmol), sodium (0.138 g, 6 equiv) and i-PrOH (0.449 mL, 6
66.3 Hz), 126.7 (d, JP-C = 2.7 Hz), 128.8 (d, JP-C = 1.8 Hz), 129.6
(d, JP-C = 5.5 Hz), 132.5 (d, JP-C = 7.3 Hz). 31P NMR (202 MHz,
CDCl3) δ 48.4. GC tR = 12.3 min; GCMS (EI, 70 eV), m/z .91
(100) 154 (86) 81 (31) 196 (30) 187 (21) 222 (17) 155 (16) 92
(16) 249 (16) 278 (15) 223 (10) 83 (10). HRMS (ESI): m/z =
557.3663 [C34H54O2P2+H]+, m/z (calc'd) = 557.3672 , diff. = -
1.61 ppm.
o
equiv). Yield: 0.076 g (38%). White crystal, mp = 164 C. Rf =
0.30 (CHCl3/MeOH = 15:1). 1H NMR (500 MHz, CDCl3) δ 1.24-
1.34 (m, 3H), 1.40-1.54 (m, 3H), 1.60-1.84 (m, 9H), 1.85-1.92
(m, 4H), 1.96-2.08 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 22.0
(d, JP-C = 5.5 Hz), 24.4 (d, JP-C = 2.7 Hz), 24.8 (d, JP-C = 60.9 Hz),
25.8 (d, JP-C = 1.2 Hz), 26.3 (d, JP-C = 12.7 Hz), 26.8 (d, JP-C = 5.5
Hz), 35.9 (d, JP-C = 68.1 Hz). 31P NMR (202 MHz, CDCl3) δ 43.7.
GC tR = 9.2 min; GCMS (EI, 70 eV), m/z (%) 118 (100) 119 (33)
145 (30) 55.05 (16) 90 (16) 117 (14) 78 (10). HRMS (ESI): m/z
= 201.1398 [C11H21OP+H]+, m/z (calc'd) = 201.1403, diff. = -
2.49 ppm.
4.3.15. Benzylcyclohexyl(i-propyl)phosphine oxide (22a)
The compound 22a was prepared according to the general
procedure from benzyl(i-propyl)phenylphosphine oxide (22)
(0.039 g, 0.15 mmol), sodium (0.021 g, 6 equiv) and i-PrOH
(0.069 mL, 6 equiv). Yield: 0.011 g (28%). White crystal, mp =
71-73 oC; Rf = 0.46 (CH2Cl2/MeOH = 15:1). 1H NMR (500 MHz,
CDCl3) δ 1.10-1.23 (m, 6H), 1.20-1.28 (m, 3H), 1.29-1.38 (m,
1H), 1.38-1.47 (m, 1H), 1.65-1.77 (m, 1H), 1.80-1.97 (m, 5H),
1.97-2.04 (m, 1H), 3.12 (dd, JP-H = 12.6, JH-H = 4.1Hz, 2H), 7.23-
7.28 (m, 1H), 7.30-7.37 (m, 4H). 13C NMR (126 MHz, CDCl3) δ
16.0 (d, JP-C = 2.7 Hz), 16.1 (d, JP-C = 2.7 Hz), 25.6 (d, JP-C = 63.3
Hz), 25.7 (d, JP-C = 3.6 Hz), 25.8 (d, JP-C = 2.7 Hz), 26.0, 26.6 (d,
JP-C = 5.5 Hz), 26.7 (d, JP-C = 6.4 Hz), 32.1 (d, JP-C = 56.3 Hz),
4.3.19. 1,2-Bis(phosphorinane 1-oxide)cyclohexane (25b)
The compound 25b was prepared according to the general
procedure from 1-phenylphosphorinane-1-oxide (25) (0.194 g, 1
mmol), sodium (0.138 g, 6 equiv) and i-PrOH (0.449 mL, 6
equiv). Yield: 0.068 g (43%). Colorless oil. Rf = 0.22
(CHCl3/MeOH = 15:1). 1H NMR (500 MHz, CDCl3) δ 1.41-1.51
(m, 2H), 1.60-2.08 (m, 24H), 2.14-2.28 (m, 2H), 2.34 (bs, 2H).
36.2 (d, JP-C = 63.6 Hz), 126.7 (d, JP-C = 2.7 Hz), 128.7 (d, JP-C
=
13C NMR (126 MHz, CDCl3) δ 22.3 (dd, JP-C = 30.8 Hz, JP-C
=
1.8 Hz), 129.8 (d, JP-C = 4.5 Hz), 132.8 (d, JP-C = 7.3 Hz). 31P
NMR (202 MHz, CDCl3) δ 51.4. GC tR = 12.0 min; GCMS (EI,
70 eV), m/z 91 (100) 182 (51) 140 (36) 81 (31) 173 (27) 264 (20)
139 (17) 92 (14) 183 (12) 222 (11) 93 (11) 209 (11) 83 (10).
HRMS (ESI): m/z = 529.3342 [C32H50O2P2+H]+, m/z (calc'd) =
529.3359 , diff. = -3.21 ppm.
2.70 Hz), 22.6 (d, JP-C = 2.7 Hz), 26.6 (dd, JP-C = 2.7 Hz, JP-C = 2.7
Hz), 26.9 (dd, JP-C = 60.8 Hz, JP-C = 3.6 Hz), 26.9–27.0 (m), 30.2-
31.5 (m). 31P NMR (202 MHz, CDCl3) δ 46.3. GC tR = 15,3 min;
GCMS (EI, 70 eV), m/z 199 (100) 119 (15) 117 (14) 81 (13) 200
(13). HRMS (ESI): m/z = 339.1623 [C16H30O2P2+Na]+, m/z
(calc'd) = 339.1613, diff. = 2.95 ppm.
4.3.16. Benzyl(t-butyl)cyclohexylphosphine oxide (23a)
4.3.20. Dicyclohexylmethylphosphine oxide (26a)
The compound 23a was prepared according to the general
procedure from benzyl(t-butyl)phenylphosphine oxide (23)
The compound 26a was prepared according to the general
procedure from methyldiphenylphosphine oxide (26) (0.1 g, 0.46

8
Tetrahedron
ACCEPTED MANUSCRIPT
mmol), sodium (0.128 g, 12 equiv) and i-PrOH (0.415 mL, 12
66.3 Hz). 31P NMR (202 MHz, CDCl3) δ 41.3 (dd, J = 604.6,
o
equiv). Yield: 0.018 g (17%). White crystal, mp = 82-83 C (lit.
10.0 Hz). GC tR = 14.2 min; GCMS (EI, 70 eV), m/z 200 (100)
273 (83) 79 (36) 81 (34) 206 (27) 144 (23) 145 (15) 63 (14) 127
(12) 274 (12) 67 (12) 53 (11) 129 (10) 65 (10). HRMS (ESI): m/z
= 599.2695 [C28H52O4P4+Na]+, m/z (calc'd) = 599.2708, diff. = -
2.17 ppm.
79-81 C)22; Rf = 0.36 (CHCl3/MeOH = 15:1). H NMR (500
MHz, CDCl3) δ 1.22-1.34 (m, 9H), 1.34-1.47 (m, 4H), 1.66-1.77
(m, 4H), 1.77-1.83 (m, 2H), 1.86 (d, JP-H = 7.6 Hz, 4H), 1.96-2.04
(m, 2H). 13C NMR (126 MHz, CDCl3) δ 8.6 (d, JP-C = 61.8 Hz),
24.8 (d, JP-C = 3.1 Hz), 25.7 (d, JP-C = 2.5 Hz), 25.9 (d, JP-C = 1.2
Hz), 26.4 (d, JP-C = 11.8 Hz), 26.5 (d, JP-C = 12.7 Hz), 35.8 (d, JP-C
= 66.3 Hz). 31P NMR (202 MHz, CDCl3) δ 50.8. GC tR = 9.6 min;
GCMS (EI, 70 eV), m/z 146 (100) 65 (58) 55 (45) 91 (42) 147
(29) 173 (25.63) 81 (18) 83 (17) 92 (12) 105 (11) 104 (11) 63
(10) 64 (10). HRMS (ESI): m/z = 457.3378 [C26H50O2P2+H]+,
m/z (calc'd) = 457.3359, diff. = 4.15ppm.
o
1
4.3.22. n-Butyldicyclohexylphosphine oxide (27a)
The compound 27a was prepared according to the general
procedure from n-butyldiphenylphosphine oxide (27) (0.086 g,
0.33 mmol), sodium (0.092 g, 12 equiv) and i-PrOH (0.299 mL,
12 equiv). Yield: 0.021 g (24%). Colorless oil. Rf = 0.39
(CHCl3/MeOH = 15:1). 1H NMR (500 MHz, CDCl3) δ 0.95 (t, JH-
H = 7.4 Hz, 3H), 1.22-1.33 (m, 7H), 1.36-1.47 (m, 5H), 1.56-1.69
(m, 4H), 1.73-1.78 (m, 3H), 1.78-1.82 (m, 1H), 1.83-1.90 (m,
5H), 1.91-2.05 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 13.7 (d,
4.3.21. 5,10-Dimethyltetradecahydrophosphanthrene 5,10-
dioxide (26b)
The four isomers of compounds 26b were formed according
to the general procedure from methyldiphenylphosphine oxide
(26) (0.1 g, 0.46 mmol), sodium (0.128 g, 12 equiv) and i-PrOH
(0.415 mL, 12 equiv). According to 31P NMR spectrum, the total
yield of four isomers is 42%. The isomers of 26b(F1-F4) were
separated by column chromatography in 4%+3%+3%+13%
yield, respectively.
JP-C = 64.5 Hz), 23.3, 23.7, 24.1 (d, JP-C = 4.5 Hz), 24.7 (d, JP-C =
13.6 Hz), 25.6 (d, JP-C = 2.7 Hz), 25.9 (d, JP-C = 2.7 Hz), 26.0 (d,
JP-C = 1.2 Hz), 26.6 (d, JP-C = 3.6 Hz), 26.7 (d, JP-C = 4.5 Hz), 36.2
(d, JP-C = 64.5 Hz). 31P NMR (202 MHz, CDCl3) δ 51.6. GC tR =
9.6 min; GCMS (EI, 70 eV), m/z 146 (100) 65 (60) 55.10 (47.96)
91 (45) 147 (30) 173 (24) 83 (18) 81 (17) 92 (12) 105 (11) 104
(11) 63 (10) 64 (10). HRMS (ESI): m/z
= 541.4312
[C32H62O2P2+H]+, m/z (calc'd) = 541.4298, diff. = 2.59 ppm.
Isomer 26b-F1; Yield: 0.005 g (4%); White solid. Rf = 0.13
(CHCl3/MeOH = 15:1). 1H NMR (500 MHz, CDCl3) δ 1.20-1.32
(m, 1H), 1.37-1.40 (m, 2H), 1.47 (d, JP-H = 12.3 Hz, 3H), 1.50 (d,
JP-H = 11.7 Hz, 3H), 1.61 (m, 1H), 1.64 (m, 1H), 1.70 (bs, 4H),
1.78 (m, 2H), 1.91 (m, 3H), 2.07-2.18 (m, 3H), 2.20-2.26 (m,
1H), 2.29 (dt, JP-H = 13.6, JP-H = 3.8 Hz, 1H), 2.38 (m, 1H). 13C
4.3.23. Dicyclohexyl(i-propyl)phosphine oxide (28a)
The compound 28a was prepared according to the general
procedure from i-propyldiphenylphosphine oxide (28) (0.081 g,
0.33 mmol), sodium (0.092 g, 12 equiv) and i-PrOH (0.298 mL,
o
12 equiv). Yield: 0.038 g (45%). White crystal, mp = 79-81 C;
NMR (126 MHz, CDCl3) δ 10.8 (d, JP-C = 65.4 Hz), 12.1 (d, JP-C
66.3 Hz), 21.9, 23.1-23.2 (m), 23.7, 24.9 (d, JP-C = 12.7 Hz), 26.4
=
Rf = 0.40 (CHCl3/MeOH = 15:1). 1H NMR (500 MHz, CDCl3) δ
1.23 (dd, JP-H = 14.2, JH-H = 7.3 Hz, 6H), 1.22-1.32 (m, 6H), 1.39-
1.50 (m, 4H), 1.75 (dt, JH-H = 2.9, JH-H = 1.5 Hz, 2H), 1.82-1.91
(m, 5H), 1.92-1.99 (m, 4H), 2.07-2.16 (m, 2H). 13C NMR (126
MHz, CDCl3) δ 16.5 (d, JP-C = 2.7 Hz), 24.4 (d, JP-C = 60.9 Hz),
26.1 (d, JP-C = 1.2 Hz), 26.4 (d, JP-C = 2.7 Hz), 26.9 (d, JP-C = 10.9
Hz), 35.5 (d, JP-C = 60.9 Hz). 31P NMR (202 MHz, CDCl3) δ 52.9.
GC tR = 9.9 min; GCMS (EI, 70 eV), m/z 174 (100) 93 (92) 55
(74) 132 (52) 81 (43) 119 (32) 92 (32) 133 (32) 83 (27) 175 (20)
201 (16) 113 (15) 63 (15) 213 (14) 79 (14) 67 (12) 73 (11) 91
(11) 173 (10). HRMS (ESI): m/z = 513.4004 [C30H58O2P2+H]+,
m/z (calc'd) = 513.3985, diff. = 3.70 ppm.
(d, JP-C = 13.6 Hz), 27.1-27.3 (m), 32.0 (dd, JP-C = 64.5 Hz, JP-C
2.7 Hz), 32.8 (dd, JP-C = 62.7 Hz, JP-C = 2.7 Hz), 36.3 (dd, JP-C
=
=
63.6 Hz, JP-C = 3.6 Hz), 40.7 (d, JP-C = 64.5 Hz). 31P NMR (202
MHz, CDCl3) δ 44.9 (dd, JP-P = 266.2, 14.9 Hz). GC tR = 13.1
min; GCMS (EI, 70 eV), m/z 191 (100) 273 (85) 81 (52) 206
(30) 127 (26) 145 (18) 126 (15) 288 (15) 80 (14) 207 (13) 144
(12) 274 (11). HRMS (ESI): m/z = 289.1479 [C14H26O2P2+H]+,
m/z (calc'd) = 289.1481, diff. = -0.69 ppm.
Isomer 26b-F2; Yield: 0.004 g (3%); White solid. Rf = 0.12
(CHCl3/MeOH = 15:1). 31P NMR (202 MHz, CDCl3) δ 42.4. GC
tR = 13.5 min; GCMS (EI, 70 eV), m/z 191 (100) (78) 81 (37)
206 (28) 144 (22) 207 (15) 288 (12) 274 (12) 145 (11) 127 (10).
HRMS (ESI): m/z = 289.1473 [C14H26O2P2+H]+, m/z (calc'd) =
289.1481, diff. = -2.77 ppm.
Isomer 26b-F3; White crystal, mp > 400 oC; Yield: 0.004 g (3%).
Rf = 0.11 (CHCl3/MeOH = 15:1). 1H NMR (500 MHz, CDCl3) δ
1.21-1.37 (m, 8H), 1.47 (d, JP-H = 11.4 Hz, 6H), 1.79-1.86 (m,
4H), 1.92-1.99 (m, 4H), 2.36-2.42 (m, 4H). 13C NMR (126 MHz,
CDCl3) δ 5.3 (d, JP-C = 65.4 Hz), 24.38-24.67 (m), 25.29-25.58
(m), 39.1 (dd, JP-C = 66.3 Hz, JP-C = 2.7 Hz). 31P NMR (202 MHz,
CDCl3) δ 43.0. GC tR = 14.6 min; GCMS (EI, 70 eV), m/z 191
(100) 81 (57) 79 (56) 273 (52) 206 (44) 207 (43) 145 (34) 127
(26) 63 (20) 67 (20) 126 (18) 53 (17) 65 (17) 144 (16) 77 (16)
288 (15) 80 (13) 54 (11). HRMS (ESI): m/z = 599.2695
[C28H52O4P4+Na]+, m/z (calc'd) = 599.2708, diff. = -2.17 ppm.
4.3.24. Dicyclohexylcyclopentylphosphine oxide (29a)
The compound 29a was prepared according to the general
procedure from cyclopentyldiphenylphosphine oxide (29) (0.27
g, 1 mmol), sodium (0.276 g, 12 equiv) and i-PrOH (0.896 mL,
12 equiv). Yield: 0.065 g (23%). Colorless oil. Rf = 0.33
(CHCl3/MeOH = 15:1). 1H NMR (500 MHz, CDCl3) δ 1.20-1.25
(m, 6H), 1.29-1.40 (m, 4H), 1.51-1.60 (m, 3H), 1.72 (bs, 5H),
1.78-1.88 (m, 9H), 1.94 (m, 4H), 2.02-2.08 (m, 1H). 13C NMR
(126 MHz, CDCl3) δ 26.1, 26.3 (d, JP-C = 8.2 Hz), 26.6 (d, JP-C
=
2.7 Hz), 26.7, 26.9 (d, JP-C = 11.8 Hz), 33.9 (d, JP-C = 64.5 Hz),
37.1 (d, JP-C = 62.7 Hz). 31P NMR (202 MHz, CDCl3) δ 53.9. GC
tR = 11.3 min; GCMS (EI, 70 eV), m/z 55 (100) 200 (90) 132
(90) 133 (89) 119 (86) 118 (49) 81 (46) 83 (39) 99 (39) 67 (31)
159 (28) 214 (25) 145 (21) 201 (19) 199 (18) 69 (18) 79 (18) 82
(16) 113 (13) 51 (12) 227 (11) 241 (11) 117 (10). HRMS (ESI):
m/z = 565.4307 [C34H62O2P2+H]+, m/z (calc'd) = 565.4298, diff.
= 1.59 ppm.
o
Isomer 26b-F4; White solid, mp = 257-258 C; Yield: 0.017 g
1
(13%). Rf = 0.10 (CHCl3/MeOH = 15:1). H NMR (500 MHz,
4.3.25. 5,10-Dicyclopentyltetradecahydrophosphanthrene 5,10-
dioxide (29b)
CDCl3) δ 1.18-1.35 (m, 5H), 1.35–1.42 (m, 2H), 1.38 (d, JP-H
=
11.0 Hz, 3H), 1.4 (d, JP-H = 11.7 Hz, 3H), 1.42-1.52 (m, 2H),
The four isomers of compound 29b was formed according to
the general procedure from cyclopentyldiphenylphosphine oxide
(29) (0.27 g, 1 mmol), sodium (0.276 g, 12 equiv) and i-PrOH
(0.896 mL, 12 equiv). According to 31P NMR spectrum, the total
yield of four isomers is 33%. The only one isomer 29b was
1.78-1.86 (m, 2H), 1.86-1.98 (m, 6H), 2.35-2.46 (m, 3H). 13C
NMR (126 MHz, CDCl3) δ 4.9 (d, JP-C = 62.7 Hz), 10.6 (d, JP-C
65.4 Hz), 23.7–24.0 (m), 25.0 (d, JP-C = 11.8 Hz), 25.3 (d, JP-C
11.8 Hz), 36.4 (dd, JP-C = 64.5 Hz, JP-C = 3.6 Hz), 39.1 (d, JP-C
=
=
=

9
isolated in a yield of 5% and characterized. White crystal, mp =
(25) 159 (24) 162 (23) 133 (22) 175 (21) 111 (20) 45 (20) 218
ACCEPTED MANUSCRIPT
o
353-355 C; Yield: 0.020 g (5%). Rf = 0.33 (CHCl3/MeOH =
(18) 245 (17) 58 (12) 71 (11) 64 (10) 77 (10) 53 (10). HRMS
(ESI): m/z = 275.2123 [C15H31O2P+H]+, m/z (calc'd) = 275.2134,
diff. = -4.00 ppm.
1
15:1). H NMR (500 MHz, CDCl3) δ 1.17-1.27 (m, 4H), 1.47-
1.55 (m, 4H), 1.59-1.68 (m, 5H), 1.75-1.84 (m, 5H), 1.87-1.84
(m, 4H), 1.96-2.10 (m, 9H), 2.12-2.24 (m, 5H), 2.33-2.40 (m,
5H), 2.41-2.49 (m, 2H). 13C NMR (126 MHz, CDCl3) δ 25.3-25.6
4.3.28. Di-n-butyl(4-methylcyclohexyl)phosphine oxide (32a)
The compound 32a was prepared according to the following
general procedure from di-n-butyl(4-methylphenyl)phosphine
oxide (32) (0.076 g, 0.3 mmol), sodium (0.041 g, 6 equiv) and i-
PrOH (0.137 mL, 6 equiv). Yield: 0.057 g (74%, as a mixture of
two isomers in a ratio of 1.7:1). Colorless oil. Rf = 0.37
(m), 25.7-26.0 (m), 28.6, 34.5 (d, JP-C = 63.6 Hz), 40.5 (d, JP-C
=
58.1 Hz). 31P NMR (202 MHz, CDCl3) δ 45.5. GC tR = 16.0 min;
GCMS (EI, 70 eV), m/z 327.10 (100.00) 246.05 (36.55) 81.10
(30.46) 67.05 (26.22) 79.05 (22.98) 328.10 (20.52) 245.10
(17.81) 69.05 (16.31) 247.00 (10.48) 113.05 (10.07) 178.05
1
(CH2Cl2/MeOH = 15:1). H NMR (500 MHz, CHLOROFORM-
(10.07) 85.05 (9.88). HRMS (ESI): m/z
=
419.2237
d) δ ppm 0.85-1.02 (m, 10H), 1.32-1.48 (m, 6H), 1.50-1.77 (m,
12H), 1.79-1.99 (m, 3H). 13C NMR (126 MHz, CDCl3) δ (major
isomer) 13.7, 20.0 (d, JP-C = 2.7 Hz), 22.6 (d, JP-C = 1.8 Hz), 23.7
(d, JP-C = 4.5 Hz), 24.4 (d, JP-C = 13.6 Hz), 25.3 (d, JP-C = 63.7
Hz), 32.3 (d, JP-C = 1.2 Hz), 35.0 (d, JP-C = 12.7 Hz), 36.4 (d, JP-C
= 66.3 Hz). 31P NMR (202 MHz, CDCl3) δ 51.6 (major isomer)
and 51.7 (minor isomer) (signals ratio 1.7:1). GC (major isomer)
tR = 10.4 min; GCMS (EI, 70 eV), m/z 78 (100) 120 (71) 55 (61)
160 (34) 162 (31) 63 (29) 95 (24) 229 (23) 187 (21) 79 (20) 202
(19) 174 (17) 121 (17) 92 (16) 133 (16) 105 (15) 91 (14) 107 (14)
163 (12) 161 (12) 147 (12) 67 (11) 64 (10) 106 (10); (minor
isomer) tR = 10.3 min; GCMS (EI, 70 eV), m/z 78 (100) 55 (74)
120 (72) 160 (35) 63 (35) 162 (33) 229 (31) 92 (24) 202 (22) 79
(20) 133 (19) 187 (18) 95 (17) 105 (16) 107 (16) 91 (16) 121 (15)
147 (15) 189 (14) 163 (13) 161 (12) 174 (12) 106 (12) 64 (11) 67
[C22H38O2P2+Na]+, m/z (calc'd) = 419.2239, diff. = -0.48 ppm.
4.3.26. Di-n-butyl(3-methoxycyclohexyl)phosphine oxide (30a)
The compound 30a was prepared according to the following
general procedure from di-n-butyl(3-methoxyphenyl)phosphine
oxide (30) (0.081 g, 0.3 mmol), sodium (0.041 g, 6 equiv) and i-
PrOH (0.137 mL, 6 equiv). Yield: 0.025 g (30%, as a mixture of
two isomers in a ratio of 6.16:1). Colorless oil. Rf = 0.27
1
(CH2Cl2/MeOH = 15:1). H NMR (500 MHz, CDCl3) δ (major
isomer) 0.95 (t, JH-H = 7.25 Hz, 6H), 1.12-1.38 (m, 4H), 1.39-1.47
(m, 4H), 1.54-1.73 (m, 8H), 1.79 (d, JP-H = 13.2 Hz, 1H), 1.88 (d,
JP-H = 12.0 Hz, 1H), 1.89-1.97 (m, 1H), 2.10-2.17 (m, 1H), 2.26-
2.33 (m, 1H), 3.16 (s, 1H), 3.38 (s, 3H). 13C NMR (126 MHz,
CDCl3) δ 13.7, 23.6 (d, JP-C = 3.6 Hz), 23.6 (d, JP-C = 3.6 Hz),
24.4 (d, JP-C = 1.8 Hz), 24.5 (d, JP-C = 1.8 Hz), 24.8 (d, JP-C = 14.5
Hz), 24.9 (d, JP-C = 2.7 Hz), 25.2 (d, JP-C = 4.5 Hz), 25.7 (d, JP-C
=
(11) 145 (11) 97 (10). HRMS (ESI): m/z = 517.4304
5.5 Hz), 30.9 (d, JP-C = 1.8 Hz), 31.8, 35.6 (d, JP-C = 66.3 Hz),
55.8, 79.2 (d, JP-C = 14.5 Hz), signals for the minor isomer are
omitted for clarity. 31P NMR (202 MHz, CDCl3) δ 49.8 (major
isomer) and 51.3 (minor isomer) (signals ratio 6.16: 1). GC
(major isomer) tR = 11.2 min; GCMS (EI, 70 eV), m/z 78 (100)
79 (88) 120 (64) 81 (51) 55 (41) 63 (40) 121 (36) 163 (34) 147
(30) 162 (27) 146 (25) 243 (25) 161 (24) 105 (24) 45 (23) 159
(22) 201 (20) 218 (19) 133 (18) 144 (18) 71 (16) 135 (15) 189
(15) 245 (14) 187 (14) 57 (14) 160 (13) 107 (13) 213 (11) 188
(11) 83 (11) 53 (11) 145 (10) 203 (10) 64 (10) 111 (10) 176 (10)
77 (10). (minor isomer) tR = 11.9 min; GCMS (EI, 70 eV), m/z 78
(100) 147 (99) 111 (86) 163 (73) 79 (70) 189 (69) 121 (63) 133
(63) 81 (62) 55 (57) 120 (56) 63 (52) 105 (45) 97 (44) 45 (43)
259 (40) 217 (33) 71 (26) 162 (25) 161 (24) 243 (24) 218 (22)
107 (22) 175 (17) 203 (16) 245 (16) 201 (15) 77 (15) 91 (15) 92
(15) 53 (15) 159 (14) 64 (14) 187 (12) 86 (11) 146 (10) 213 (10)
112 (10) 57 (10) 49 (10). HRMS (ESI): m/z = 275.2137
[C15H31O2P+H]+, m/z (calc'd) = 275.2134, diff. = 1.09 ppm.
[C30H62O2P2+H]+, m/z (calc'd) = 517.4298, diff. = 1.16 ppm.
4.3.29. Di-n-butyl(3,5-dimethylcyclohexyl)phosphine oxide (33a)
The compound 33a was prepared according to the following
general procedure from di-n-butyl(3,5-dimethylphenyl)phosphine
oxide (33) (0.08 g, 0.3 mmol), sodium (0.041 g, 6 equiv) and i-
PrOH (0.137 mL, 6 equiv). Yield: 0.063 g (77%, as a mixture of
three isomers in a ratio of A:B:C = 1:1.7:2.0). Colorless oil.
1
Isomer A. Colorless oil; RfA = 0.4 (CHCl3/MeOH = 15:1). H
NMR (500 MHz, CDCl3) δ 0.89 (d, JH-H = 6.31 Hz, 6H), 0.96 (t,
JH-H = 7.10 Hz, 6H), 1.14-1.26 (m, 2H), 1.39-1.50 (m, 6H), 1.51-
1.62 (m, 2H), 1.64-1.76 (m, 4H), 1.77-1.90 (m, 3H), 1.97-2.09
(m, 4H). 13C NMR (126 MHz, CDCl3) δ 13.7, 18.4, 22.9, 24.33
(d, JP-C = 6.4 Hz), 24.4 (d, JP-C = 16.4 Hz), 26.7 (d, JP-C = 62.7
Hz), 28.7, 33.0 (d, JP-C = 65.4 Hz), 33.8 (d, JP-C = 2.7 Hz), 43.7.
31P NMR (202 MHz, CDCl3) δ 54.2. GC tR = 8.7 min; GCMS (EI,
70 eV), m/z 189 (100) 120 (64) 92 (45) 109 (40) 162 (39) 216
(36) 174 (36) 243 (34) 147 (26) 163 (22) 134 (21) 133 (19) 107
(17) 201 (13) 121 (12) 106 (11) 161 (11) 190 (10) 217 (10) 160
4.3.27. Di-n-butyl(4-methoxycyclohexyl)phosphine oxide (31a)
The compound 31a was prepared according to the following
general procedure from di-n-butyl(4-methoxyphenyl)phosphine
oxide (31) (0.08 g, 0.3 mmol), sodium (0.041 g, 6 equiv) and i-
PrOH (0.137 mL, 6 equiv). Yield: 0.08 g (10%, as a mixture of
two isomers in a ratio of 1:3.24). Colorless oil. Rf = 0.39
(10) 81 (10) 132 (10). HRMS (ESI): m/z
= 545.4619
[C32H66O2P2+H]+, m/z (calc'd) = 545.4611, diff. = 1.47 ppm.
1
Isomer B. Colorless oil; RfB = 0.36 (CHCl3/MeOH = 15:1). H
NMR (500 MHz, CDCl3) δ 0.91 (d, JH-H = 6.31 Hz, 3H), 0.95 (t,
JH-H = 7.30 Hz, 6H), 1.02 (d, JP-H = 7.25 Hz, 3H), 1.16 (td, JP-H
=
1
(CH2Cl2/MeOH = 15:1). H NMR (500 MHz, CDCl3) δ (major
12.77, 4.73 Hz, 1H), 1.39-1.48 (m, 4H), 1.50-1.74 (m, 13H),
1.80-1.91 (m, 1H), 2.01 (qt, JP-H = 12.85, 3.11 Hz, 1H), 2.14-2.21
(m, 1H). 13C NMR (126 MHz, CDCl3) δ 13.7 17.7-18.4 (m) 22.8,
23.6 (d, JP-C = 3.6 Hz), 23.7 (d, JP-C = 4.5 Hz), 24.4 (d, JP-C = 2.2
isomer) 0.94 (t, JH-H = 7.3 Hz, 6H), 1.37-1.48 (m, 6H), 1.54-1.72
(m, 12H), 2.04-2.13 (m, 3H) 3.31 (s, 3H), 3.49-3.54 (m, 1H). 13
C
=
NMR (126 MHz, CDCl3) δ (major isomer) 13.7, 19.6 (d, JP-C
1.8 Hz), 23.5 (d, JP-C = 3.6 Hz), 24.5 (d, JP-C = 13.5 Hz), 25.2 (d,
JP-C = 63.4 Hz), 29.5 (d, JP-C = 11.8 Hz), 36.7 (d, JP-C = 66.5 Hz),
55.7 73.8. 31P NMR (202 MHz, CDCl3) δ 50.5 (minor isomer)
and 50.6 (major isomer) (signals ratio 1:3.24). GC (major
isomer) tR = 11.2 min; GCMS (EI, 70 eV), m/z 78 (100) 79 (69)
120 (54) 121 (36) 81 (34) 243 (34) 55 (33) 159 (32) 63 (31) 163
(31) 162 (22) 201 (21) 161 (15) 218 (12) 144 (11) 133 (11) 57
(10) 45 (10) 158 (10). (minor isomer) tR = 11.3 min; GCMS (EI,
70 eV), m/z 78 (100) 120 (56) 79 (46) 217 (44) 55 (42) 243 (41)
81 (41) 63 (37) 203 (31) 163 (30) 259 (29) 121 (27) 161 (27) 201
Hz), 24.5 (d, JP-C = 1.8 Hz), 25.0 (d, JP-C = 6.4 Hz), 25.5 (d, JP-C
=
6.4 Hz), 26.4 (d, JP-C = 12.7 Hz), 27.6 (d, JP-C = 12.7 Hz), 30.3 (d,
JP-C = 2.7 Hz), 30.8 (d, JP-C = 67.2 Hz), 33.8 (d, JP-C = 3.6 Hz),
40.1. 31P NMR (202 MHz, CDCl3) δ 51.5. GC tR = 9.1 min;
GCMS (EI, 70 eV), m/z 120 (100) 92 (50) 109 (47) 162 (46) 174
(41) 147 (34) 243 (27) 133 (27) 121 (26) 216 (25) 163 (21) 201
(20) 189 (20) 105 (20) 188.05 (18) 107 (17) 91 (14) 106 (13) 134
(12) 161 (11) 132 (11) 118 (10). HRMS (ESI): m/z = 273.2334
[C16H33OP+H]+, m/z (calc'd) = 273.2342, diff. = -2.93 ppm.

10
Tetrahedron
(b) Lyle RE., Thomas JJ. J. Org. Chem. 1965, 30, 1907-1909;
Isomer C. Colorless oil; RfC = 0.37 (CHCl3/MeOH = 15:1).
ACCEPTED MANUSCRIPT
31P NMR (202 MHz, CDCl3) δ 50.0 .GC tR = 9.0 min; GCMS (EI,
70 eV), m/z 120 (100) 174 (48) 162 (42) 243 (38) 216 (30) 109
(29) 121 (29) 188 (23) 163 (21) 92 (19) 133 (17) 107 (16) 201
(15) 159 (13) 105 (13) 106 (12) 111 (10) 161 (10). HRMS (ESI):
m/z = 273.2335 [C16H33OP+H]+, m/z (calc'd) = 273.2342, diff. =
-2.56 ppm.
(c) Gribble GW, Lord PD, Skotnicki J, Dietz SE, Eaton JT,
Johnson JL. J. Am. Chem. Soc. 1974, 96, 7812-7814.
3. (a) Benseker RA, Robinson R E, Sauve DM, Thomas OH. J. Am.
Chem. Soc. 1955, 77, 3230-3233;
(b) Marcinow Z, Rabideau PW. J. Org. Chem. 1990, 55, 3812-
3816.
4. (a) Nishimura S. Handbook of Heterogenous Catalytic
Hydrogenation for Organic Chemistry, John Wiley & Sons, Inc.,
2001, 414-496;
4.3.30. Dimethyl(1,2,3,4-tetrahydronaphthalen-1-yl)phosphine
oxide (34a)
(b) Muetterties EL, Bleeke JR. Acc. Chem. Rev. 1979, 12, 324-
331;
The compound 34a was prepared according to the following
general procedure from dimethyl(naphthalen-1-yl)phosphine
oxide (34) (0.082 g, 0.4 mmol), sodium (0.041 g, 4 equiv) and i-
PrOH (0.122 mL, 4 equiv). Yield: 0.040 g (48%). White crystal,
mp = 51-52 oC; Rf = 0.33 (CH2Cl2/MeOH = 15:1). 1H NMR (500
MHz, CDCl3) δ 1.54 (d, JP-H = 12.0 Hz, 6H), 1.69-1.81 (m, 1H),
2.08 (m, 1H), 2.23-2.31 (m, 1H), 2.82-3.11 (m, 4H), 7.10-7.18
(m, 4H). 13C NMR (126 MHz, CDCl3) δ 13.5 (d, JP-C = 7.3 Hz),
(c) Rothwell IYP. Chem. Commun. 1997, 1331-1338;
(d) Wang Y, Cui X, Deng Y, Shi F. RSC Adv. 2014, 4, 2729-2732.
5. (a) Takasaki M, Motoyama Y, Higashi K, Yoon SH, Mochida I,
Nagashima H. Chem. Asian J. 2007, 2, 1524-1533;
(b) Gonzalez-Galvez D, Lara P, Rivada-Wheelaghan O, Conejero
S, Chaudret B, Philippot K, van Leeuwen PWNM. Catal. Sci.
Technol. 2013, 3, 99-105.
6. (a) Maegawa T, Akashi A, Sajiki H. Synlett 2006, 1140-1142;
(b) Maegawa T, Akashi A, Yasushi K, Iwasaki Y, Shigetsura M,
Monguchi Y, Sajiki H. Chem. Eur. J. 2009, 15, 6953-6963.
7. (a) Ager DJ, Prakash I. Org. Process Res. Dev. 2003, 7, 164-167;
(b) Schuda PF, Greenlee WJ, Chakravarty PK., Eskola P. J. Org.
Chem. 1988, 53, 873-875.
14.1 (d, JP-C = 7.3 Hz), 22.5 (d, JP-C = 2.7 Hz), 28.4, 29.1 (d, JP-C
=
12.7 Hz), 36.2 (d, JP-C = 71.8 Hz), 126.1, 126.2, 129.0, 134.5 (d,
JP-C = 12.7 Hz, CIV) 135.8. 31P NMR (202 MHz, CDCl3) δ 46.2 .
GC tR = 11.3 min; GCMS (EI, 70 eV), m/z 130 (100) 129 (57)
115 (31) 128 (28) 131 (17) 91 (14) 127 (12) 208 (10). HRMS
8. Freedman LD, Doak GO, Petit EL. J. Am. Chem. Soc. 1955, 77,
4262-4263.
9. (a) Yu JS., Rothwell IP. J. Chem. Soc., Chem. Commun. 1992,
632-633;
(ESI): m/z
= =
417.2118 [C24H34O2P2+H]+, m/z (calc'd)
417.2107, diff. = 2.64 ppm.
(b) Yamamoto K, Ur-Rehman S. Chem. Lett. 1984, 1603-1606;
(c) Chiba M, Takahashi H, Takahashi H, Morimoto T, Achiwa K.
Tetrahedron Lett. 1987, 28, 3675-3678;
(d) Demay S, Volant F, Knochel P. Angew. Chem. Int. Ed. 2001,
40, 1235-1238;
4.3.31. Di-n-butyl(1,2,3,4-tetrahydronaphthalen-1-yl)phosphine
oxide (35a)
The compound 35a was prepared according to the following
general procedure from di-n-butyl(naphthalen-1-yl)phosphine
oxide (35) (0.086 g, 0.3 mmol), sodium (0.028 g, 4 equiv) and i-
PrOH (0.092 mL, 4 equiv). Yield: 0.037 g (42%). Colorless oil;
Rf = 0.45 (CH2Cl2/MeOH = 15:1). 1H NMR (500 MHz, CDCl3) δ
0.89 (dt, JP-H = 14.5, 7.3 Hz, 6H), 1.30-1.42 (m, 4H), 1.46-1.73
(m, 9H), 1.96-2.11 (m, 3H), 2.79 (t, JP-H = 5.4 Hz, 2H), 3.40-3.48
(m, 1H), 7.10-7.13 (m, 1H), 7.14-7.17 (m, 2H), 7.49-7.53 (m,
1H). 13C NMR (126 MHz, CDCl3) δ 13.6 (d, JP-C = 1.8 Hz), 21.5
(d, JP-C = 5.5 Hz), 23.6 (d, JP-C = 4.5 Hz), 23.7 (d, JP-C = 4.5 Hz),
23.9 (d, JP-C = 1.9 Hz), 24.3 (d, JP-C = 2.7 Hz), 24.4 (d, JP-C = 2.7
Hz), 26.0 (d, JP-C = 62.7 Hz), 26.7 (d, JP-C = 63.6 Hz), 29.5 (d, JP-C
= 1.2 Hz), 38.4 (d, JP-C = 60.0 Hz), 125.9 (d, JP-C = 2.7 Hz), 126.5
(d, JP-C = 2.7 Hz), 129.5 (d, JP-C = 1.8 Hz), 129.8 (d, JP-C = 3.6
(e) Gavryushin A, Polborn K, Knochel P. Tetrahedron:
Asymmetry 2004, 15, 2279-2288.
10. (a) Stankevič M, Pietrusiewicz KM. Tetrahedron Lett. 2009, 50,
7093-7097;
(b) Stankevič M, Włodarczyk A, Jaklińska M, Parcheta R,
Pietrusiewicz KM. Tetrahedron 2011, 67, 8671-8678;
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2013, 4351-4371.
11. (a) Haworth RD, Woodcock D. J. Chem. Soc. 1939, 1237-1241;
(b) Wu YH, Feldkamp RF. J. Org. Chem. 1961, 26, 1519-1524;
(c) Bodnar BS, Vogt PF. J. Org. Chem. 2009, 74, 2598-2600.
12. Haynes RK, Au-Yeung TL, Chan WK, Lam WL, Li ZY, Yeung
LL, Chan ASC, Li P, Koen M, Mitchell CR, Vonwiller SC. Eur. J.
Org. Chem. 2000, 3205–3216.
13. Jablonkai E, Balázs LB, Keglevich G. Phosph. Sulf. Sil. Relat.
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17. Cremer SE, Trivedi BC, Weitl FL. J. Org. Chem., 1971, 36, 3226–
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Chem., 2015, 80, 9774–9780.
Hz), 131.9 (d, JP-C = 5.5 Hz, CIV) 138.1 (d, JP-C = 5.5 Hz, CIV). 31
P
NMR (202 MHz, CDCl3) δ 52.4. GC tR = 12.2 min; GCMS (EI,
70 eV), m/z 131 (100) 130 (55) 78 (41) 91 (25) 120 (23) 163 (20)
129 (20) 115 (13) 236 (13) 292 (13) 63 (11) 132 (11) 116 (10).
HRMS (ESI): m/z = 315.1840 [C18H29OP+Na]+, m/z (calc'd) =
315.1848, diff. = -2.54 ppm.
Acknowledgments
19. Baptistella LHB, Aleixo AM. Liebigs Ann. Chem. 1994, 785–790.
20. Stankevič M, Pisklak J, Włodarczyk K. Tetrahedron, 2016, 72,
810–824.
Financial support from Polish Ministry of Science and Higher
Education research subsidy is kindly acknowledged.
21. Nazareno M A, Palacios SM, Rossi RA J. Phys. Org. Chem.,
1993, 6, 421–426.
Supplementary Material
22. Abraham KM, van Wazer JR. J. Organomet. Chem., 1975, 85, 41-
46.
1
Supplementary data include the copies of H, 13C NMR and
31P NMR spectra for all products and a copy of CIF file for 26b-
F3 (Cambridge Crystallographic Data Centre No. 1537702)
described in this article can be found at…
References and notes
1. Rylander PN. Catalytic Hydrogenation in Organic Synthesis,
Academic Press, 1979, 175-212.
2. (a) Yalpani M. Chem. Ber. 1990, 123, 983-987;