Reduction of Tertiary Phosphine Oxides by BH 3 Assisted by Neighboring Activating Groups

Article abstract of DOI:10.1055/s-0036-1591546

Tertiary sulfanylphosphine and aminoalkylphosphine oxides can be easily converted into the corresponding tertiary sulfanylphosphine- and aminoalkylphosphine-boranes, respectively, through the facile P=O bond reduction by borane complexes. The easy reduction of the strong P=O bond by BH ₃, a mild reducing agent, has been achieved through an intramolecular P=O - B complexation directed by proximal SH or NH activating groups located at the α- or β-position to the P=O bond. A generalized reduction mechanism has been proposed.

Full text of DOI:10.1055/s-0036-1591546

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–M
paper
A
en
S. Sowa et al.
Paper
Synthesis
Reduction of Tertiary Phosphine Oxides by BH3 Assisted by
Neighboring Activating Groups
Sylwia Sowa
BH3
O
P
R2
H3B·SMe2
Marek Stankevič
Anna Flis
P
SH
n
SH
n
R1
R2
R1
THF or toluene, 60 °C
K. Michał Pietrusiewicz*
4 examples
up to 71% yield
n = 1,2
Department of Organic Chemistry, Faculty of Chemistry, Maria
Curie Skłodowska University, Gliniana St. 33, Lublin 20-614,
Poland
BH3
H
O
H3B·SMe2
H
P
N
kazimierz.pietrusiewicz@poczta.umcs.lublin.pl
P
N
R1
R3
R1
R2
R3
THF, r.t. or 60 °C
R2
n
n
6 examples
up to 77% yield
n = 1,2
Received: 12.12.2017
Accepted after revision: 25.01.2018
Published online: 21.02.2018
during purification.8 Therefore new, milder, simpler, and
more selective methods for the reduction of strong P=O
bond are in constant demand.
DOI: 10.1055/s-0036-1591546; Art ID: ss-2017-z0812-op
A rational approach to avoid dissipative phosphine iso-
lation process would be a direct transformation of phos-
phine oxides into easily handled and storable phosphine-
boranes. The development of new protocols for this type of
transformations is one of the most attractive research top-
ics in current organophosphorus chemistry.9 Protocols,
which can use BH3 or its complexes as reducing agents are
getting growing attention due to the mild reducing charac-
ter of BH3.10
Previously, we have shown that H3B·SMe2 could be used
for P=O bond reduction in secondary phosphine oxides di-
rectly providing the corresponding secondary phosphine-
boranes. This reaction proceeded under mild reaction con-
ditions and the addition of a small amount of water to the
reaction mixture remarkably increased the yield of the
products (Scheme 1A).11 Recently, our group demonstrated
that the same effect could be achieved for tertiary phos-
phine oxides possessing hydroxyl group in the carbon skel-
eton at the α- or β-carbon atom (Scheme 1B). The role of
the hydroxyl group is to bind BH3 and to facilitate its intra-
molecular coordination with phosphoryl oxygen, which in
turn enables reduction of the P=O bond by another mole-
cule of BH3. Moreover, phosphine oxides possessing
hydroxyalkyl group undergo the reduction of P=O bond in a
highly stereoselective way.12 Therefore, this approach could
be recognized as a useful tool for the synthesis of new P-
stereogenic phosphine-boranes as elegantly demonstrated
by Buono and co-workers.13
Abstract Tertiary sulfanylphosphine and aminoalkylphosphine oxides
can be easily converted into the corresponding tertiary sulfanylphos-
phine- and aminoalkylphosphine-boranes, respectively, through the
facile P=O bond reduction by borane complexes. The easy reduction of
the strong P=O bond by BH3, a mild reducing agent, has been achieved
through an intramolecular P=O -- B complexation directed by proximal
SH or NH activating groups located at the α- or β-position to the P=O
bond. A generalized reduction mechanism has been proposed.
Key words phosphine-boranes, phosphine oxides, P=O bond reduc-
tion, reduction by borane, aminophosphines, sulfanylphosphines,
neighboring group effects
The reduction of phosphine oxides to phosphines is one
of the most useful and explored synthetic routes in organo-
phosphorus chemistry.1 Many different reducing agents
have been employed but none of them resolve all problems.
Metal hydrides, the reagents of first choice, are often used
as reducing agents but they are incompatible with com-
pounds possessing other reactive functionalities or chirality
centers at the phosphorus atom.2 To date, silanes are reduc-
ing agents of the greatest importance in organophosphorus
chemistry. Among them HSiCl3,3 PhSiH3,4 and Si2Cl65 appear
to be the most efficient and tolerant towards other func-
tional groups. The reduction reactions usually occur in high
yields and with high stereoselectivity. A range of modifica-
tions have also been developed, which include the addition
of various additives to both silane5a,6 and metal hydride re-
agents7 for improving their activity or selectivity. The re-
duction of phosphine oxide is very often the limiting step in
the synthetic sequence leading sometimes to the failure of
the synthesis due to the huge loss of target phosphine
Herein, we wish to present our results concerning the
use of BH3 for reduction of P=O bond in phosphine oxides
possessing neighboring SH or NH activating groups
(Scheme 1C). The success of this type of reductions opens a
new route to the precursors of P,N-14–16 and P,S-type17
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

B
S. Sowa et al.
Paper
Synthesis
Table 1 Reactivity of α-Sulfanylphosphine Oxides Towards H3B·SMe2
Our previous work
BH3
O
P
A11
O
P
BH3
P
H3B·SMe2/H2O
BH3
P
H3B·SMe2
conditions
P
H
R1
H
R2
SH
S
OH
SH
+
R2
R1
R
R
R
4
R
R
R
H3B·SMe2
or H3B·THF
BH3
1a R = Ph
1b R = Cy
O
P
3a R = Ph
3b R = Cy
2a R = Ph
2b R = Cy
B12
OH
P
OH
R1
R2
R2
n
R1
n
n = 1, 2
Entry Com- Conditions
pound
Product Yield (%)a
This work
H3B·SMe2
or H3B·THF
BH3
O
P
XH
n
P
XH
29 (37)b
31 (63)b
R1
R2
1
2
3
4
1a
1a
1a
1be
H3B·SMe2 (3 equiv), THF, 60 °C, 3 h
H3B·SMe2 (10 equiv), THF, 60 °C, 24 h
2a
3a
R1
R2
C
n
X = S, NR
n = 1, 2
2b
3b
14 (25)b
27 (75)b
Scheme 1 Reduction of functionalized tertiary phosphine oxides with
H3B·SMe2 (6 equiv), toluene, 60 °C, 16 h 2a
H3B·SMe2 (10 equiv), toluene, 60 °C, 24 h 2b
51
(60)b,c,d
BH3
72
(77)b,c,d
ligands or reagents for Staudinger ligation.18 Some prece-
dents for NH-assisted reductions of phosphine oxides by
BH3 already exist13a,14 but, to the best of our knowledge,
there has been no evidence in the literature for the reduc-
tion of P=O bond in organophosphorus compounds pos-
sessing SH moiety as an activating group.
a Isolated yields.
b Numbers in parentheses indicate yields according to 31P NMR analysis.
c Isolated yield after additional boronation of the free phosphine formed
under the reaction conditions (see Experimental Section).
d Partial oxidation took place before boranation.
e Compound 1b has undergone partial dimerization forming bis-(di-c-hex-
ylphosphorylmethyl) disulfide (4) while standing in CHCl3 overnight (see
Experimental Section).
To probe the effect of an α-sulfanyl group on the facility
of reduction of the P=O bond by BH3, diphenyl(α-sulfanyl-
methyl)phosphine oxide (1a) and di-c-hexyl(α-sulfanyl-
methyl)phosphine oxide (1b) were chosen as substrates. In
the preliminary experiment, phosphine oxide 1a was treat-
ed with 3 equivalents of H3B·SMe2 under conditions analo-
gous to those developed by us for the reduction of α-
hydroxyphosphine oxides.12 It turned out that the activat-
ing effect of sulfur has been lower than oxygen still, howev-
er, this protocol enabled the complete conversion of phos-
phine oxide 1a. We observed the formation of two phos-
phine-borane products 2a and 3a in a ratio of 0.56:1
(according to 31P NMR spectrum) isolated in 29% and 31%
yield, respectively (Table 1, entry 1). The phosphine oxide
1b showed lower reactivity than 1a. To complete the con-
version of 1b an increase in the amount of H3B·SMe2 to 10
equivalents and prolongation of the reaction time to 24
hours were needed. That resulted in the formation of 3b as
the main product (according to 31P NMR spectrum) isolated
in 27% yield (entry 2).
cases a mixture of phosphine-borane 2 and the correspond-
ing free phosphine in a ratio of 1:1.14 (for the reaction of
1a) and 1:1 (for the reaction of 1b) were observed in the
crude reaction mixtures by 31P NMR spectroscopy. Howev-
er, evaporation of toluene, dissolution of the residue in ethyl
acetate, and addition of extra H3B·SMe2 (3 equiv) enabled
the isolation of 2a and 2b as the only products in 51% and
72% yield, respectively (entries 3 and 4).
To confirm the activating effect of the α-sulfanyl group
in the studied reductions, tert-butyl(phenylthiometh-
yl)phenylphosphine oxide (5) possessing protected sulfanyl
group was submitted to the reaction under the studied con-
ditions. As indicated in Scheme 2, no reaction was ob-
served. This observation underscores the key role of the
free SH group in the studied reduction process.
O
H3B·SMe2 (5 equiv)
S
no reaction
P
t-Bu
Ph
Ph
THF, 60 °C, 48 h
5
The observed formation of phosphine-boranes 3 could
be explained by the nucleophilic attack of an α-sulfanyl-
phosphine-borane 2 on a BH3-activated THF molecule re-
sulting in the ring opening. To avoid this side reaction, THF
was replaced with toluene. In this solvent, the complete
conversion of an α-sulphanylphosphine oxide required the
use of 6 equivalents of H3B·SMe2and 16 hours reaction time
in the case of 1a, and 10 equivalents of H3B·SMe2 and 24
hours reaction time in the case of 1b (Table 1, entry 3 and 4,
respectively). Quite surprisingly, despite the applied excess
of borane a complete in situ complexation of the formed
phosphines by BH3 in toluene could not be achieved. In both
Scheme 2 Attempted reduction tert-butylphenyl(phenylthiomethyl)-
phosphine oxide (5)
Next, we decided to check the reduction of diphenyl(2-
sulfanylethyl)phosphine oxide (6) as a model for β-sulfanyl-
phosphine oxides. Not unexpectedly, it turned out that
placing the SH group in the β-position to phosphorus atom
drastically decreased its activating effect. When the reac-
tion was carried out at 60 °C, no conversion of the starting
material was observed even after prolonged reaction time.
Raising the reaction temperature to 110 °C for 18 hours led
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

C
S. Sowa et al.
Paper
Synthesis
to the formation of the desired diphenyl(2-sulfanyl-
ethyl)phosphine-borane (7) albeit only in 25% yield
(Scheme 3). However, under these conditions, starting
phosphine oxide 6 appeared to be unstable, which might
partially account for the observed low yield of 7.
BH3
P
BH3
P
BH3
N
O
P
H3B·THF (5 equiv)
THF, r.t., 24 h
H
H
N
N
or
Ph
Ph
R
Ph
Ph
R
Ph
Ph
H
R
9a R = H
9c R = p-BrC6H4
9d R = p-MeC6H4
8a R = H
8b R = CH2Ph
8c R = p-BrC6H4
8d R = p-MeC6H4
10 R = CH2Ph
BH3
O
H3B·SMe2 (10 equiv)
BH3
H
BH3 BH3
BH3
P
Ph
Ph
P
BH3
SH
Ph
Ph
P
N
P
N
Ph
SH
H
P
NH2
toluene, 110 °C, 18 h
25% (40%)*
Ph
Ph
Ph
Ph
H
P
N
6
Ph
Ph
7
Ph
Ph
Me
* according to 31P NMR spectrum of the crude reaction mixture
Br
9a 0% (83%)b
9c 71% (72%)b,c,d
9d 77% (85%)b,e
10 63% (66%)b,f
Scheme 3 Reduction of diphenyl(2-sulfanylethyl)phosphine oxide (6)
a Isolated yields of products are shown; b Numbers in parentheses indicate yields according to
31P NMR analysis; c Reaction was carried out for 1 h; d Additionally 9% of diphenylphosphine-
borane (11) and 20% of starting material 8d were isolated; e Formation of diphenylphosphine-
borane (11) was also observed; f Reaction was carried out with 10 equiv of H3B·SMe2.
In extension of our study on BH3 reduction of α-amino-
phosphine oxides, a short series of phosphine oxides 8 with
varied substitution patterns were tested (Scheme 4). The
activating effect of the α-amino group in these reactions
was found to be higher than the one observed for α-sulfan-
ylphosphine oxides. In nearly all cases the reactions pro-
ceeded to completion within 24 hours and at room tem-
perature. It was also found that substituents at nitrogen
atom remarkably improved stability of phosphine-boranes
during their isolation. The formation of phosphine-borane
9a with a primary amino group was observed only by 31P
NMR spectroscopy as this compound underwent decompo-
sition during attempted purification. Interestingly, intro-
duction of an aryl electron-withdrawing group at the nitro-
gen atom, like in 8c, remarkably facilitated the reduction
process. In this case, the formation of the desired amino-
phosphine-borane 9c in 71% yield [along with 9% of second-
ary diphenylphosphine-borane (11) as the by-product] was
observed already after 1 hour. By comparison, the analo-
gous oxide 8b possessing an electron-donating substituent
was converted to the corresponding tertiary phosphine-
borane with similar effectiveness but only after 24 hours
and after using 10 equivalents of BH3. In this case, however,
the reaction afforded diborane 10, apparently as a conse-
quence of the higher electron density on alkyl-substituted
nitrogen atom coinciding with a larger excess of used BH3
enabling additional complexation at nitrogen atom.
Scheme 4 Reactivity of α-aminophosphine oxides 8 towards BH3
complexes.a
borane (16,11a 4%) (Scheme 5). The latter three products were
most probably formed in a retro-Kabachnik–Fields process
reverting phosphine oxide 12 to a secondary phosphine ox-
ide and an imine, which both were further reacted with BH3
under the reaction conditions to give the observed 16,11a
15,11b and amine 14. It is worth noting that α-Ph-substitut-
ed (aminomethyl)phosphine oxide 12 was found to be ther-
mally stable when heated without BH3 at 60 °C for 24 hours.
Most probably, in the studied reduction, BH3 acted also as a
Lewis acid facilitating the observed retro-Kabachnik–Fields
reaction. The same explanation could be applied to the for-
mation of secondary diphenylphosphine-borane (11)
during the reduction of 8c and 8d.21
In accordance with the literature precedent,14b oxide 17
was found reactive enough to undergo reduction by
H3B·SMe2 and afforded the desired phosphine-borane prod-
uct 18 in 60% yield. In this case, however, it was necessary
to increase the reaction temperature to 60 °C to achieve the
complete conversion of phosphine oxide 17.
Finally, a singular β-aminophosphine oxide 17 was sub-
jected to reduction with H3B·SMe2 (Scheme 6).
In turn, reduction of an α-Ph-substituted (amino-
methyl)phosphine oxide 1219 provided the desired phos-
phine-borane 1320 in 37% yield along with a secondary
amine 14 (32%), secondary o-anisylphenylphosphinous
acid-borane (15,11b 26%), and o-anisylphenylphosphine-
In light of this and the previous work,12,13a we would like
to propose a generalized reduction mechanism as depicted
in Scheme 7. Initially, a reaction of BH3 with an XH group of
I affords intermediate II along with liberation of hydrogen
gas. The formation of an intermediate of type II seems to be
BH3
O
BH3
P
BH3
P
H
N
H
H
H3B·SMe2 (3 equiv)
THF, 60 °C, 24 h
Ph
P
N
P
N
+
+
Ph
o-An
+
Ph
o-An
Ph
OH
Ph
H
o-An
o-An
Ph
13 37%
Ph
Br
Br
Br
16 4%
12
14 32%
15 26%
Scheme 5 Reduction of α-Ph-substituted (aminomethyl)phosphine oxide 12 with H3B·SMe2
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

D
S. Sowa et al.
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Synthesis
BH3
P
O
O
P
BH2
O
P
BH3
– H2
H3B·SMe2 (5 equiv)
P
X
XH
R1
R2
Ph
N
Ph
Ph
Ph
N
Ph
R1
R2
THF, 60 °C, 48 h
60% (100%)*
H
H
n
Ph
n
18
17
II
I
* according to 31P NMR spectrum of the crude mixture
X = S, NR, O12
n = 1, 2
Scheme 6 Reduction of β-aminophosphine oxide (17)
H
B
H
O
P
H
X
B
H
O
P
R1
R2
R1
R2
prerequisite for the reduction process to occur. This would
explain the observed lack of reactivity of S-protected thiolo
phosphine oxide 6 towards BH3, in analogy to inertness of
an O-protected hydroxy phosphine oxide studied previous-
ly.13a In the next step, the intramolecular coordination of
the resulting proximal boron functionality to phosphoryl
oxygen leads to the formation of a cyclic zwitterionic inter-
mediate III. Such intramolecular coordination process is ef-
fective only for phosphine oxides possessing an activating
group at the α- or the β-position to phosphorus atom for
which generation of the readily formed 5- or 6-membered
ring intermediate III is possible.12 In the next step, hydride
transfer from external borane to phosphorus atom causes
cleavage of the activated P–O bond in an SN2-type process.
In this step, the occurrence of a 5-membered ring in the
trigonal bipyramidal transition state TS IV (n = 1) leads to
lowering of its energy and facilitates the reduction process
under mild conditions. As the experiments have confirmed,
less effective stabilization of TS IV (n = 2) by a 6-memberd
ring in the case of β-positioned activating groups necessi-
tates typically elevation of reaction temperatures and appli-
cation of longer reaction times.
n
X
III
n
H
BH2
O
H
BH2
O
TS IV
R1
R2
R1
R2
O
O
n
n
B
P
H
P
B
X
X
H
H
– H2
H
VI
V
1. BH3
2. hydrolysis
BH3
P
XH
R2
R1
n
VII
Scheme 7 Plausible generalized mechanism of P=O bond reduction
with BH3
Finally, the protonated phosphine V liberates another
hydrogen molecule to give a free phosphine VI, which even-
tually undergoes complexation with BH3 followed by hy-
drolytic deprotection of the activating group to give the fi-
nal phosphine-borane VII.
The proposed mechanism seems to be general regard-
less of the type of activating group present in the phos-
phine oxide structure. It also implies that the inversion of
configuration at phosphorus has to take place in the reduc-
tion step in each case. Reported observations that P-stereo-
genic hydroxymethylphosphinates, hydroxymethylphos-
phine oxides and β-aminophosphine oxides are reduced by
BH3 with inversion of configuration10f,12,13a,14b corroborate
this statement fully.
In conclusion, a general and efficient method for the re-
duction of the P=O bond in tertiary phosphine oxides pos-
sessing activating group in proximity to phosphorus atom
by commercially available BH3 complexes has been further
expanded. The key role of neighboring α or β activating
group in the reduction process of phosphine oxide as well
as the effect of the distance between the interacting centers
were demonstrated. New convenient synthetic routes lead-
ing directly to aminophosphine-boranes and sulfanylphos-
phine-boranes have been developed.
All reactions were performed under an argon atmosphere using
Schlenk techniques. Only anhydrous solvents were used and all glass-
ware were heated under vacuum prior to use. All chemicals were
used as received, unless noted otherwise. Solvents for chromatogra-
phy and crystallization were distilled once before use and the sol-
vents for extraction were used as received. THF and toluene were dis-
tilled from sodium/benzophenone ketyl under argon. 1H NMR, 31P
NMR, and 13C NMR spectra were recorded on a Bruker Avance-500
spectrometer at ambient temperature in CDCl3, unless otherwise not-
ed. Chemical shifts (δ) are reported in ppm relative to residual solvent
peak (7.26 ppm for 1H and 77 ppm for 13C). Mass spectra were record-
ed on Shimazu GC-MS QP2010S in electron ionization (EI) or fast
atom bombardment (FAB) mode. IR spectra were recorded on Thermo
Scientific Nicolet iS50 FT-IR ATR mode with diamond prism (4000–
400 cm–1 window) as solids or thin films. In the IR spectra, only the
strongest/structurally most important peaks (cm–1) are listed. Melting
points were determined on Büchi Melting Point M-560 in a capillary
tube and are uncorrected. HPLC-HRMS analyses were performed on
Shimazu HRMS ESI-IT-TOF using reverse phase stationary phase with
H2O/MeOH (80:20) as eluent, electrospray ionization (ESI), and IT-TOF
detector. Optical rotations were measured on PerkinElmer 341LC
spectrometer using a 1 mL cell with a 10 mm path length and are re-
25
ported as follows: [α]D (c g/100 mL, solvent). Elementary analyses
were performed on a PerkinElmer CHN 2400 analyzer. TLC analyses
were performed with precoated silica gel plates and visualized by UV
light or KMnO4 solution or I2 on silica gel. The reaction mixtures were
purified by column chromatography over silica gel (60–240 mesh).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

E
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Synthesis
The starting compounds: tert-butylphenylphosphine oxide,22 o-ani-
sylphenylphosphine oxide,23 diphenylphosphine oxide,2c di-c-hexyl-
phosphine oxide24 were prepared according to reported methods. Op-
tically active 2-[N-(1-methylbenzylamino)]ethyl(diphenyl)phosphine
oxide16 and diphenylvinylphosphine oxide25 were available from an-
other studies. The syntheses of starting sulfanylalkylphosphine ox-
ides 1a,b, 5, 6 and aminoalkylphosphine oxides 8a–d and 12 are de-
tailed below.
Di-c-hexyl(hydroxymethyl)phosphine Oxide12
Di-c-hexylphosphine oxide (0.428 g, 2.0 mmol) was reacted according
to the general procedure to afford the title compound (0.366 g, 1.5
mmol, 75%) as a yellowish solid; mp 154.1–155 °C; Rf = 0.21 (CHCl3/
EtOAc/MeOH 30:5:1).
IR (solid, ATR): 3231, 2931, 2917, 2851, 1739, 1446, 1141, 1116, 1042,
899, 857, 780, 657, 529, 491, 448, 426 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 4.47 (br s, 1 H), 3.95 (s, 2 H), 1.92–1.99
(m, 2 H), 1.79–1.91 (m, 8 H), 1.69–1.74 (m, 2 H), 1.40–1.54 (m, 4 H),
1.20–1.31 (m, 6 H).
α-Hydroxyphosphine Oxides; General Procedure
To a solution of respective secondary phosphine oxide (2.0 mmol) in
anhyd THF was added DBU (29 μL, 0.2 mmol) followed by paraformal-
dehyde (180 mg, 6 mmol). The reaction mixture was heated at 60 °C
for 24 h. The mixture was then evaporated to dryness and the residue
was dissolved in CH2Cl2 (10 mL) and quenched with sat. aq NH4Cl (5
mL). The resulting mixture was extracted with CH2Cl2 (5 × 30 mL), the
combined organic phases were dried (anhyd Na2SO4), and evaporated.
The residue was purified by column chromatography on silica gel us-
ing CHCl3/EtOAc/MeOH (30:5:1, v/v/v) as eluent.
13C NMR (125 MHz, CDCl3): δ = 56.02 (d, JP,C = 72.66 Hz), 34.15 (d, JP,C
61.67 Hz), 26.48 (d, JP,C = 11.81 Hz), 26.46 (d, JP,C = 11.81 Hz), 25.84,
25.33, 24.99.
31P NMR (202 MHz, CDCl3): δ = 50.41 (s).
HRMS (ESI-TOF): m/z [2 M + H]+ calcd for C13H25O2P: 489.3257; found:
489.3244.
=
Anal. Calcd for C13H25O2P: C, 63.91; H, 10.31. Found: C, 63.76; H,
10.63.
tert-Butyl(hydroxymethyl)phenylphosphine Oxide12
α-Chlorophosphine Oxides; General Procedure
tert-Butylphenylphosphine oxide (0.364 g, 2.0 mmol) was reacted ac-
cording to the general procedure to afford the title compound (0.33 g,
1.56 mmol, 78%) as a beige solid; mp 153.7–154.7 °C; Rf = 0.47
(EtOAc–MeOH 10:1).
In a two-necked round-bottom flask (50 mL) equipped with a mag-
netic stirrer and an argon inlet were placed the respective α-hydroxy-
phosphine oxide12 (1.4 mmol) and PCl5 (0.295 g, 1.41 mmol) in anhyd
toluene/CHCl3 mixture(5 mL/2 mL). The reaction mixture was heated
at 60 °C for 24 h. Then, the solvent and POCl3 were removed under
reduced pressure. The residue was purified by column chromatogra-
phy on silica gel using CHCl3/EtOAc/MeOH (30:5:1 v/v/v) as eluent.
IR (film, ATR): 3161, 2948, 2868, 1475, 1436, 1361, 1218, 1140, 1105,
1049, 839, 816, 753, 742, 694, 631, 507, 471, 439 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.66–7.69 (m, 2 H), 7.40–7.44 (m, 2 H),
7.48–7.50 (m, 1 H), 5.47 (br s, 1 H), 4.44 (dd, JP,H = 14.5 Hz, JH,H = 6.94
(Chloromethyl)diphenylphenylphosphine Oxide27
Hz, 1 H), 4.24 (dd, JP,H = 14.19 Hz, JH,H = 6.31 Hz, 1 H), 1.18 (d, JH,P
14.19 Hz, 9 H).
13C NMR (125 MHz, CDCl3): δ = 131.6 (d, JP,C = 2.73 Hz), 131.5 (d, JP,C
7.3 Hz), 128.7 (d, JP,C = 85.4 Hz), 128.2 (d, JP,C = 10.9 Hz), 57.4 (d, JP,C
71.8 Hz), 32.5 (d, JP,C = 64.5 Hz), 24.6.
=
Diphenyl(hydroxymethyl)phosphine oxide (0.325 g, 1.4 mmol) was
reacted according to the general procedure to afford the title com-
pound (0.295 g, 1.18 mmol, 84%) as a white solid; mp 134.8–135.3 °C;
Rf = 0.44 (CHCl3/EtOAc/MeOH 30:5:1).
=
=
31P NMR (202 MHz, CDCl3): δ = 46.39 (s).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C11H17O2P: 213.1039; found:
IR (solid, ATR): 2974, 2924, 1441, 1404, 1194, 1127, 1106, 814, 756,
693, 671, 534, 491, 449, 417 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.79–7.84 (m, 4 H), 7.58–7.62 (m, 2 H),
7.50–7.54 (m, 4 H), 4.05 (d, JH-P = 6.62 Hz, 2 H).
213.1039.
Anal. Calcd for C11H17O2P: C, 62.25; H, 8.07. Found: C, 62.40; H, 8.11.
13C NMR (125 MHz, CDCl3): δ = 132.63 (d, JP,C = 3.63 Hz), 131.52 (d,
JC,P = 9.08 Hz), 129.61 (d, JC,P = 130.54 Hz), 128.73 (d, JC,P = 12.72 Hz),
37.66 (d, JC,P = 71.75 Hz).
Diphenyl(hydroxymethyl)phosphine Oxide26
Diphenylphosphine oxide (0.404 g, 2 mmol) was reacted according to
the general procedure to afford the title compound (0.371 g, 1.43
mmol, 73%) as a white solid; mp 135.4–135.9 °C; Rf = 0.27 (CHCl3/
MeOH 30:1).
31P NMR (202 MHz, CDCl3): δ = 28.32 (s).
MS (EI, 70 eV): m/z (%) = 251 (0.2), 250 (0.6, [M]), 249 (0.4), 201 (13),
201 (100), 183 (5), 152 (5), 108 (4), 91 (9), 77 (28), 51 (22).
IR (solid, ATR): 3201, 1436, 1214, 1151, 1122, 1097, 1052, 852, 740,
HRMS (ESI-TOF): m/z [2 M + H]+ calcd for C13H12ClOP: 501.0701;
found: 501.0715.
718, 691, 543, 489, 460, 435 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.78–7.75 (m, 3 H), 7.55–7.52 (m, 2 H),
7.48–7.45 (m, 3 H), 5.2 (br s, 1 H), 4.43 (s, 2 H).
Anal. Calcd for C13H12ClOP: C, 62.29; H, 4.83. Found: C, 61.99; H, 4.58.
13C NMR (125 MHz, CDCl3): δ = 132.14 (s), 131.36 (d, JP,C = 9.08 Hz),
Chloromethyl(di-c-hexyl)phosphine Oxide
130.60 (d, JP,C = 86.29 Hz), 128.67 (d, JP,C = 10.90 Hz), 61.38 (d, JP,C
=
Hydroxymethyl(di-c-hexyl)phosphine oxide (0.342 g, 1.4 mmol) was
reacted according to the general procedure to afford the title com-
pound (0.324 g, 1.23 mmol, 88%) as a white solid; mp 84.2–84.6 °C;
Rf = 0.44 (CHCl3/EtOAc/MeOH 30:5:1).
81.74 Hz).
31P NMR (202 MHz, CDCl3): δ = 30.90 (s).
HRMS (ESI-TOF): m/z [2 M + H]+ calcd for C13H13O2P: 465.1379; found:
465.1388.
IR (solid, ATR): 2972, 2917, 2846, 1739, 1445, 1215, 1169, 1143, 1003,
888.47, 856, 671, 533, 478, 420 cm–1
.
Anal. Calcd for C13H13O2P: C, 67.24; H, 5.64. Found: C, 67.09; H, 5.34.
1H NMR (500 MHz, CDCl3): δ = 3.58 (d, JH,P = 7.57 Hz, 2 H), 1.97–2.05
(m, 4 H), 1.81–1.90 (m, 6 H), 1.70–1.76 (m, 2 H), 1.46–1.64 (m, 4 H),
1.21–1.36 (m, 6 H).
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13C NMR (125 MHz, CDCl3): δ = 34.21 (d, JC,P = 58.1 Hz), 31.76 (d, JC,P
57.22 Hz), 26.45 (d, JC,P = 12.73 Hz), 26.50 (d, JC,P = 11.81 Hz), 25.74,
25.39 (d, JC,P = 3.63 Hz), 24.90 (d, JC,P = 2.72 Hz).
=
MS (EI, 70 eV): m/z (%) = 261 (5), 260 (29, [M]), 259 (16), 251 (11), 250
(8), 219 (6), 218 (6), 213 (8), 179 (22), 178 (100), 177 (7), 163 (5), 162
(14), 113 (12), 97 (29), 95 (14), 94 (13), 83 (27), 82 (8), 81 (33), 80 (5),
79 (14), 67 (10), 60 (25), 55 (71), 47 (6), 46 (7), 45 (39).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H27O2PS: 303.1542; found:
303.1531.
31P NMR (202 MHz, CDCl3): δ = 50.43 (s).
MS (EI, 70 eV): m/z (%) = 264 (1), 262 (3, [M]), 213 (9), 207 (6), 183 (7),
182 (12), 180 (32), 125 (12), 113 (12), 99 (23), 83 (66), 82 (31), 81(21),
79 (14), 67 (22), 55 (100), 54 (14), 53 (12).
Anal. Calcd for C15H27O2PS: C, 59.57; H, 9.00. Found: C, 59.27; H, 8.69.
HRMS (ESI-TOF): m/z [2 M + H]+ calcd for C13H24ClOP: 525.2579;
found: 525.2573.
α-Sulfanylphosphine Oxides 1; General Procedure
Aq 3 M NaOH (0.7 mL, 2.1 mmol) was added to a solution of acetylth-
iomethylphosphine oxide (0.7 mmol) in anhyd MeOH (5 mL). The
mixture was stirred at r.t. for 30 min. Then, the reaction mixture was
acidified with aq 1 M HCl and extracted with CHCl3 (5 × 20 mL). The
combined organic phases were dried (anhyd Na2SO4), filtered, and
evaporated. The residue was purified by column chromatography us-
ing CHCl3/EtOAc/MeOH (30:5:1, v/v/v) or CHCl3/MeOH (100:1, v/v) as
eluent.
Anal. Calcd for C13H24ClOP: C, 59.42; H, 9.21. Found: C, 59.05; H, 8.95.
α-Acetylthiophosphine Oxides; General Procedure
In a two-necked round-bottom flask (25 mL) equipped with a mag-
netic stirrer and an argon inlet containing a solution of the respective
α-chlorophosphine oxide (1 mmol) in anhyd DMF (2 mL) was added
KSAc (2.5 mmol, 0.286 g). Then, the reaction mixture was stirred for
18 h at r.t. (25 °C) and evaporated to dryness. The residue was dis-
solved in CH2Cl2 (10 mL) and sat. aq NH4Cl (5 mL) was added. The re-
sulting mixture was extracted with CH2Cl2 (5 × 30 mL). The combined
organic phases were dried (anhyd Na2SO4) and evaporated. The resi-
due was purified by column chromatography on silica gel using
CHCl3/EtOAc/MeOH (30:5:1, v/v/v) or CHCl3/MeOH (100:1, v/v) as
eluent.
Diphenyl(sulfanylmethyl)phosphine Oxide (1a)18b
Acetylthiomethyl(diphenyl)phosphine oxide (0.203 g, 0.7 mmol) was
reacted according to the general procedure to afford 1a as a white sol-
id (0.132 g, 0.532 mmol, 76%); mp 121.4–122.1 °C; Rf = 0.29 (CHCl3/
MeOH 50:1).
IR (solid, ATR): 2944, 2898, 2360, 1435, 1182, 1120, 936, 776, 741,
720, 690, 529,506, 451, 416 cm–1
.
Acetylthiomethyl(diphenyl)phosphine Oxide27
Chloromethyl(diphenyl)phosphine oxide was reacted according to the
general procedure (0.251 g, 1 mmol) to afford the title compound
(0.232 g, 0.8 mmol, 80%) as a white solid; mp 94.7–96.3 °C; Rf = 0.40
(CHCl3/EtOAc/MeOH 30:5:1).
1H NMR (500 MHz, CDCl3): δ = 7.75–7.79 (m, 4 H), 7.56–7.74 (m, 6 H),
3.18–3.21 (m, 2 H), 1.99 (q, J = 7.88 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 132.20 (d, JP,C = 2.72 Hz), 131.16 (d,
JP,C = 9.99 Hz), 131.10 (d, JP,C = 100.82 Hz), 128.72 (d, JP,C = 11.82 Hz),
22.42 (d, JP,C = 68.12 Hz).
IR (solid, ATR): 3053, 2948, 2896, 1694, 1438, 1188, 1123, 1102, 956,
752, 722, 692, 623, 533, 500, 418 cm–1
.
31P NMR (202 MHz, CDCl3): δ = 29.47 (s).
1H NMR (500 MHz, CDCl3): δ = 7.74–7.78 (m, 4 H), 7.52–7.56 (m, 2 H),
7.45–7.49 (m, 4 H), 3.76 (d, JH,P = 8.20 Hz, 2 H), 2.35 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 193.07 (d, JP,C = 4.54 Hz), 132.28 (d,
JP,C = 2.72 Hz), 131.14 (d, JP,C = 103.54 Hz), 131.02 (d, JP,C = 9.99 Hz),
128.61 (d, JP,C = 11.81 Hz), 29.98, 27.23 (d, JP,C = 69.94 Hz).
MS (EI, 70 eV): m/z (%) = 250 (3), 248 (16, [M]), 202 (45), 201 (71), 183
(10), 155 (24), 152 (11), 125 (15), 124 (17), 123 (18), 91 (13), 79 (6),
77 (100), 69 (6), 65 (9), 60 (37), 52 (11), 51 (76), 50 (21), 48 (55), 47
(78), 46 (72), 45 (87).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H13OPS: 249.0497; found:
249.0488.
31P NMR (202 MHz, CDCl3): δ = 29.01 (s).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H15O2PS: 291.0595; found:
Anal. Calcd for C13H13OPS: C, 62.89; H, 5.28. Found: C, 62.66; H, 5.33.
291.0603.
Di-c-hexyl(sulfanylmethyl)phosphine Oxide (1b)
Anal. Calcd for C15H15O2PS: C, 62.06; H, 5.21. Found: C, 61.91; H, 5.00.
Prepared according to the general procedure from acetylthiometh-
yl(di-c-hexyl)phosphine oxide (0.212 g, 0.7 mmol). The crude product
was purified by column chromatography to give 1b as an orange oil
(0.129 g, 0.497 mmol, 71%); Rf = 0.45 (CHCl3/EtOAc/MeOH 30:5:1).
Acetylthiomethyl(di-c-hexyl)phosphine Oxide
According to the general procedure, chloromethyl(di-c-hexyl)phos-
phine oxide (0.262 g, 1 mmol) was heated at 60 °C for 24 h to afford
the title compound (0.299 g, 0.99 mmol, 99%) as a beige waxy solid;
mp 94.7–96.3 °C; Rf = 0.40 (CHCl3/EtOAc/MeOH 30:5:1).
IR (solid, ATR): 3420, 2922, 2850, 1640, 1447, 1158, 1116, 1005, 889,
854, 825, 770, 657, 531, 484, 420 cm–1
.
IR (solid, ATR): 2926, 2849, 1693, 1445, 1165, 1112, 956, 852, 825,
1H NMR (500 MHz, CDCl3): δ = 2.69 (m, 2 H), 1.86–2.07 (m, 12 H),
1.70–1.77. (m, 2 H), 1.45–1.47 (m, 4 H), 1.20–1.33 (m, 5 H).
789, 626, 534, 453, 415 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 3.21 (d, JH,P = 8.20 Hz, 2 H), 2.38 (s, 3
H), 1.95–1.98 (m, 2 H), 1.78–1.89 (m, 8 H), 1.69–1.74 (m, 2 H), 1.37–
1.49 (m, 4 H), 1.19–1.21 (m, 6 H).
13C NMR (125 MHz, CDCl3): δ = 193.64 (d, JP,C= 3.63 Hz, C), 35.98 (d,
JP,C= 65.39 Hz, CH), 30.19 (CH3), 26.45 (d, JC,P = 12.73 Hz, CH2), 26.38 (d,
JC,P = 12.73 Hz, CH2), 25.77 (CH2), 25.65 (d, JC,P = 2.72 Hz, CH2), 25.23
(d, JC,P = 3.63 Hz, CH2).
13C NMR (125 MHz, CDCl3): δ = 35.56 (d, JP,C = 61.76 Hz, CH), 26.56 (d,
JP,C = 12.72 Hz, CH2), 26.52 (d, JP,C = 11.81 Hz, CH2), 25.92 (d, JP,C = 1.82
Hz, CH2), 25.86, 27.74 (d, JP,C = 1.82 Hz, CH2), 15.93 (d, JP,C = 54.50 Hz,
CH2).
31P NMR (202 MHz, CDCl3): δ = 49.29 (s).
MS (EI, 70 eV): m/z (%) = 261 (1), 260 (3, [M]), 179 (9), 133 (11), 132
(7), 97 (51), 96 (25), 95 (10), 83 (41), 82 (22), 81 (28), 79 (18), 77 (13),
67 (32), 64 (26), 63 (7), 60 (14), 55 (100), 54 (21), 53 (15), 48 (22), 47
(13), 46 (40), 45 (50).
31P NMR (202 MHz, CDCl3): δ = 49.26 (s).
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HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H25OPS: 261.1436; found:
261.1426.
15 mL). The combined organic phases were dried (anhyd Na2SO4), and
concentrated. Column chromatography of the residue on silica gel us-
ing CHCl3/EtOAc/MeOH (30:5:1, v/v/v) as eluent gave 5 as a yellowish
solid (0.276 g, 0.906 mmol, 87%); mp 127.2–127.4 °C; Rf = 0.45
(CHCl3/EtOAc/MeOH 30:5:1).
Anal. Calcd for C13H25OPS: C, 59.97; H, 9.68. Found: C, 59.67; H, 9.60.
Bis(di-c-hexylphosphorylmethyl) Disulfide (4)
IR (solid, ATR): 2949, 2905, 1576, 1473, 1437, 1404, 1171, 1113, 1026,
It was observed by the way that compound 1b underwent partial oxi-
dative dimerization to bis-(di-c-hexylphosphorylmethyl) disulfide (4)
while left in CHCl3 at r.t. overnight. In order to complete oxidation of
1b, the solution was left at r.t. for another 48 h. The resulting disulfide
4 was analyzed without further purification; brownish oil; Rf = 0.28
(CHCl3/EtOAc/MeOH 30:5:1).
818, 740, 731, 693, 624, 506, 480, 472, 462 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.75–7.71 (m, 2 H), 7.40–7.57 (m, 5 H),
7.17–7.29 (m, 3 H), 3.57 (m, 2 H), 1.20 (d, JP,H = 15.0 Hz, 9 H).
13C NMR (125 MHz, CDCl3): δ =136.28 (d, JP,C= 5.45 Hz, C), 131.9 (d,
JP,C= 8.17 Hz, CH), 131.81 (d, JP,C= 2.73 Hz, CH), 130.14 (CH), 129.11 (d,
JP,C= 90.83 Hz, C), 128.98 (CH), 128.2 (d, JP,C= 10.90 Hz, CH), 126.82
(CH), 33.68 (d, JP,C= 68.12 Hz, C), 28.76 (d, JP,C= 58.13 Hz, CH2), 24.69
(CH3).
IR (film, ATR): 2925, 2851, 2205, 1447, 1161, 1116, 890, 854, 770, 725,
641, 531, 484, 420 cm–1
.
1H NMR (500 MHz, CDCl3): δ =3.32 (d, J = 6.94 Hz, 1 H), 1.69–2.03 (m,
24 H), 1.17–1.56 (m, 20 H).
31P NMR (202 MHz, CDCl3): δ = 45.68 (s).
13C NMR (125 MHz, CDCl3): δ = 35.97 (d, JP,C= 65.40 Hz, CH), 33.71 (d,
JP,C = 46.32 Hz, CH2), 26.48 (d, JP,C = 11.81 Hz, CH2), 26.46 (CH2), 26.40
(d, JP,C = 12.72 Hz, CH2), 25.78 (d, JP,C = 3.76 Hz, CH2), 25.36 (d, JP,C = 1.82
Hz, CH2).
MS (EI, 70 eV): m/z (%) = 305 (4), 304 (21, [M]), 259 (11), 248 (21), 247
(20), 202 (51), 201 (12), 182 (9), 157 (8), 155 (6), 154 (13), 139 (13),
126 (19), 125 (76), 124 (17), 123 (100), 121 (18), 109 (15), 92 (13), 91
(36), 79 (13), 77 (32), 65 (16), 57 (62), 47 (43), 45 (80).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C17H21OPSNa: 327.0943;
31P NMR (202 MHz, CDCl3): δ = 49.02 (s).
found: 327.0935.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H48O2P2S2: 519.2644;
Anal. Calcd for C17H21OPS: C, 67.08; H, 6.95. Found: C, 66.88; H, 6.80.
found: 519.2646.
Diphenylvinylphoshine Oxide25
[tert-Butyl(phenyl)phosphoryl]methyl Mesylate
This compound was available from our earlier studies.25
In a two-necked round-bottom flask (25 mL) equipped with a mag-
netic stirrer and an argon inlet, t-butylphenyl(hydroxymethyl)phos-
phine oxide12 (0.331 g, 1.56 mmol) was dissolved in anhyd CH2Cl2(10
mL). Then, Et3N (0.22 mL, 1.56 mmol) was added and the reaction
mixture was cooled to 0 °C. MsCl (0.12 mL, 2.25 mmol) was added
and the mixture was allowed to warm to r.t. and stirred overnight.
The reaction mixture was acidified with aq 1 M HCl (5 mL) and ex-
tracted with CH2Cl2 (3 × 30 mL). The combined organic phases were
dried (anhyd Na2SO4), filtered, and evaporated. The residue was puri-
fied by column chromatography using EtOAc as eluent affording [tert-
butyl(phenyl)phosphoryl]methyl mesylate as a white solid (0.425 g,
1.47 mmol, 94%); mp 121.5–122.5 °C; Rf = 0.24 (EtOAc).
White solid; mp 115.0–115.8 °C; Rf = 0.64 (CHCl3/EtOAc/MeOH
30:5:1).
IR (solid, ATR): 2996, 1437, 1174, 1119, 1105, 971, 763, 734, 722, 693,
611, 532, 503, 471, 452 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.74–7.68, 7.56–7.53 (m, 2 H), 7.51–
7.46 (m, 4 H), 6.74–6.63 (m, 1 H), 6.39–6.24 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 134.82, 132.20 (dd, J = 2.72 Hz, JC,P
148.72 Hz), 131.90 (d, JP,C = 2.72 Hz), 131.35 (d, JP,C = 9.99 Hz). 131.07
(dd, J = 2.72 Hz, JP,C = 432.31 Hz), 128.58 (d, JP.C = 11.88 Hz).
=
31P NMR (202 MHz, CDCl3): δ = 23.93 (s).
IR (solid, ATR): 3303, 2971, 2929, 1436, 1365, 1352, 1339, 1167, 1114,
MS (EI, 70 eV): m/z (%) = 229 (12), 228 (80, [M]), 227 (78), 202 (9), 201
(38), 200 (6), 199 (10), 185 (23), 183 (38), 152 (16), 149 (16), 134 (5),
133 (22), 121 (7), 10 (7), 107 (9), 105 (11), 104 (100), 95 (9), 91 (7), 78
(21), 77 (82), 76 (5), 51 (66), 50 (13), 47 (58).
1004, 973, 819, 761, 736, 670, 632, 532, 501, 485, 466, 448 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.73–7.77 (m, 2 H), 7.56–7.62 (m, 1 H),
7.49–7.52 (m, 2 H), 4.83 (d, JP,H = 3.15 Hz, 2 H), 3.09 (s, 3 H), 1.20 (d,
JP,H = 15.45 Hz, 9 H).
Anal. Calcd for C14H13OP: C, 73.68; H, 5.74. Found: C, 73.63; H, 5.64.
13C NMR (125 MHz, CDCl3): δ = 132.47 (d, JP,C= 2.73 Hz), 131.63 (d, JP,C
=
8.17 Hz), 128.58 (d, JP,C= 11.81 Hz), 127.36 (d, JP,C= 90.83 Hz), 62.71 (d,
JP,C= 69.03 Hz), 37.83, 33.25 (d, JP,C= 69.03 Hz), 24.41.
31P NMR (202 MHz, CDCl3): δ = 41.44 (s).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C12H19O4PS: 291.0814; found:
291.0819.
Diphenyl(2-sulfanylethyl)phosphine Oxide (6)
In a two-necked round-bottom flask (100 mL) equipped with a mag-
netic stirrer and an argon inlet, diphenylvinylphosphine oxide22
(0.228 g, 1 mmol) was dissolved in anhyd DMF (2 mL) and KSAc
(0.343 g, 3 mmol) was added. The reaction mixture was stirred at
80 °C for 3 d, then evaporated to dryness, and the residue was parti-
tioned between CH2Cl2 (20 mL) and H2O (30 mL). The resulting mix-
ture was extracted with CH2Cl2 (5 × 30 mL). The combined organic
phases were dried (anhyd Na2SO4) and concentrated. The residue was
purified by crystallization from EtOAc affording 6 as a beige solid
(0.152 g, 0.58 mmol, 58%); mp 122.3–123.7 °C (EtOAc); Rf = 0.38
(CHCl3/MeOH 15:1).
Anal. Calcd for C12H19O4PS: C, 49.65; H, 6.60. Found: C, 49.70; H, 6.70.
tert-Butylphenyl(phenylthiomethyl)phosphine Oxide (5)
In a two-necked round-bottom flask (50 mL) equipped with a mag-
netic stirrer and an argon inlet, thiophenol (0.107 mL, 1.04 mmol)
was dissolved in anhyd THF (10 mL). The resulting mixture was
cooled to –78 °C and n-BuLi (1.83 mL, 1.14 mmol, 1.6 M in hexanes)
was added followed by [tert-butyl(phenyl)phosphoryl]methyl
mesylate (0.3 g, 1.04 mmol). The resulting reaction mixture was al-
lowed to warm to r.t. and stirred for 48 h. After that time, the residue
was quenched with sat. aq NH4Cl (5 mL) and extracted with CHCl3 (3 ×
IR (solid, ATR): 3051, 1436, 1282, 1177, 1120, 1104, 1071, 784, 733,
690, 533, 505, 456, 420 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.68–7.78 (m, 4 H), 7.43–7.52 (m, 6 H),
2.71–2.76 (m, 2 H), 2.45–2.50 (m, 2 H).
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13C NMR (125 MHz, CDCl3): δ = 132.12 (d, JP,C = 99.9 Hz), 131.94 (d,
JP,C = 2.73 Hz), 130.63 (d, JP,C = 9.99 Hz), 128.74 (d, JP,C = 11.81 Hz),
30.17 (d, JP,C = 67.21 Hz), 23.70 (d, JP,C = 1.82 Hz).
31P NMR (202 MHz, CDCl3): δ = 30.27 (s).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H15OPS: 263.0654; found:
31P NMR (202 MHz, CDCl3): δ = 29.14 (s).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H17BrNOP: 386.0304;
found: 386.0300.
Anal. Calcd for C19H17BrNOP: C, 59.09; H, 4.44; N, 3.63. Found: C,
58.82; H, 4.30; N, 3.43.
263.0644.
Diphenyl(N-p-tolylaminomethyl)phosphine Oxide (8d)29
Anal. Calcd for C14H15OPS: C, 64.10; H, 5.76. Found: C, 64.41; H, 5.60.
Diphenylphosphine oxide (0.61 g, 3 mmol), paraformaldehyde (3
mmol, 0.09 g), and p-tolylamine (0.321 g, 3 mmol) were reacted ac-
cording to the general procedure to afford the title compound as a yel-
low solid (0.299 g, 0.93 mmol, 31%); mp 156.4–157.4 °C; Rf = 0.57
(CHCl3/EtOAc/MeOH 30:5:1).
α-Aminophosphine Oxides 8 and 9; General Procedure
In a two-necked round-bottom flask (100 mL) equipped with a mag-
netic stirrer and an argon inlet were placed the respective secondary
phosphine oxide (3 mmol), aldehyde (3 mmol), primary amine (3
mmol), and anhyd Na2SO4 (10 g) in anhyd toluene (20 mL). The reac-
tion mixture was heated at 110 °C for 24 h. After completion, the reac-
tion was allowed to cool to r.t., the solution was filtered, and evapo-
rated. The residue was dissolved in CHCl3(10 mL), then H2O (10 mL)
was added, and the mixture was extracted with CHCl3 (3 × 30 mL).
The combined organic phases were dried (anhyd Na2SO4), filtered,
and toluene was evaporated. The residue was purified by column
chromatography using CHCl3/EtOAc/MeOH (30:5:1, v/v/v) as eluent.
IR (solid, ATR): 3377, 3014, 1611, 1521, 1486, 1436, 1298, 1174, 1123,
1107, 806, 791, 741, 690, 555, 503, 414 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.77–7.82 (m, 4 H), 7.55–7.58 (m, 2 H),
7.47–7.51 (m, 4 H), 6.98–7.00 (m, 2 H), 6.59–6.61 (m, 2 H), 3.92 (d,
JP,H = 8.83 Hz), 2.24 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 145.31 (d, JP,C = 11.81 Hz), 132.29 (d,
JP,C = 2.73 Hz), 131.14 (d, JP,C = 99.91 Hz), 131.12 (d, JP,C = 9.08 Hz),
129.70, 128.77 (d, JP,C = 11.81 Hz), 127.95, 113.56, 44.21 (d, JP,C = 79.93
Hz), 20.35.
N-Benzylaminomethyldiphenylphosphine Oxide (8b)28
31P NMR (202 MHz, CDCl3): δ = 29.61 (s).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H20NOP: 322.1355; found:
Diphenylphosphine oxide (0.61 g, 3 mmol), paraformaldehyde (0.09 g,
3 mmol), and benzylamine (0.327 mL, 3 mmol) were reacted accord-
ing to the general procedure to afford the title compound as a yellow
solid (0.597 g, 1.86 mmol, 62%); mp 87.1–88.1 °C; Rf = 0.51 (CH-
Cl3/EtOAc/MeOH 30:5:1).
322.1360.
Anal. Calcd for C20H20NOP: C, 74.75; H, 6.27; N 4.36. Found: C, 74.55;
H, 6.22; N, 4.43.
IR (solid, ATR): 3023, 2811, 1493, 1456, 1438, 1174, 1122, 1100, 1071,
1026, 805, 782, 753, 718, 691, 541, 509, 455, 448 cm–1
.
o-Anisylphenyl{1-phenyl-[N-(p-bromophenyl)amino]methyl}-
phosphine Oxide (12)
1H NMR (500 MHz, CDCl3): δ = 7.74–7.78 (m, 4 H), 7.45–7.48 (m, 4 H),
7.52–7.55 (m, 2 H), 7.24–7.32 (m, 5 H), 3.88 (s, 2 H), 3.43 (d, JP,H = 7.88
Hz, 2 H), 2.16 (s, 1 H).
13C NMR (125 MHz, CDCl3): δ = 138.94 (d, JP,C = 0.91 Hz), 131.92 (d,
JP,C = 2.73 Hz), 131.81 (d, JP,C = 98.08 Hz), 131.12 (d, JP,C= 9.08 Hz),
128.56 (d, JP,C= 11.81 Hz), 128.36, 128.24, 127.18, 54.99 (d, JP,C= 14.53
Hz), 48.02 (d, JP,C= 81,47 Hz).
o-Anisylphenylphosphine oxide (0.696 g, 3 mmol), benzaldehyde
(0.305 mL, 3 mmol,) and p-bromophenylamine (0.516 g, 3 mmol)
were reacted according to the general procedure to afford 12 as two
diastereomers (dr = 1:0.9) isolated as a mixture (1.18 g, 2.4 mmol,
80%); Rf = 0.58 (CHCl3/MeOH 30:1).
IR (solid, ATR): 3261, 3062, 1588, 1514, 1488, 1463, 1430, 1318, 1273,
1242, 1175, 1112, 1109, 1075, 1012, 828, 799, 765, 714, 690, 559,
31P NMR (202 MHz, CDCl3): δ = 29.45 (s).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H20NOP: 322.1355; found:
522, 504, 478, 428 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.03–8.08 (m, 1 H, major), 7.82–7.86
(m, 2 H, minor), 7.72–7.77 (m, 1 H, minor), 7.52–7.56 (m, 1 H, major),
7.47–7.51 (m, 1 H, minor), 7.36–7.47 (m, 6 H), 7.19–7.31 (m, 7 H),
7.17–7.19 (m, 2 H, minor), 7.12–7.17 (m, 4 H), 7.11–7.12 (m, 2 H, ma-
jor), 7.07–7.10 (m, 1 H), 7.05–7.07 (m, 1 H, major), 6.94–6.97 (m, 1 H,
major), 6.91–6.94 (m, 1 H, minor), 6.76–6.78 (m, 1 H, minor), 6.55–
6.58 (m, 2 H, minor), 6.44–6.49 (m, 2 H, major), 5.46–5.56 (m, 3 H),
5.25–5.31 (m, 1 H, major), 3.83 (s, 3 H, major), 3.77 (s, 3 H, minor).
322.1343.
Anal. Calcd for C20H20NOP: C, 74.75; H, 6.27, N, 4.35. Found: C, 74.72;
H 6.44, N, 4.30.
(N-p-Bromophenylaminomethyl)diphenylphosphine Oxide (8c)
Diphenylphosphine oxide (0.61 g, 3 mmol), paraformaldehyde (0.09 g,
3 mmol), and p-bromophenylamine (0.516 g, 3 mmol) were reacted
according to the general procedure to afford the title compound as a
yellow solid (0.846 g, 2.19 mmol, 73%); mp 168.1–169.1 °C; Rf = 0.53
(CHCl3/EtOAc/MeOH 30:5:1).
13C NMR (125 MHz, CDCl3): δ = 159.6 (d, JP,C= 4.5 Hz, C), 158.9 (d, JP,C
=
4.5 Hz, C), 145.9 (d, JP,C,N,C = 11.8 Hz, C), 145.4 (d, JP,C,N,C = 12.7 Hz, C),
135.8 (CH), 135.5 (d, JP,C = 5.45 Hz, CH), 134.5 (d, JP,C = 4.5 Hz, CH),
134.2 (d, JP,C = 14.5 Hz, CH), 132.8 (d, JP,C = 100.0 Hz, C), 131.8 (CH),
131.7 (CH), 131.6 (d, JP,C = 2.7 Hz), 131.3 (d, JP,C = 10.0 Hz, CH), 130.9 (d,
JP,C = 9.08 Hz, CH), 130.8 (d, JP,C = 103.5 Hz, C), 128.5 (d, JP,C = 4.5 Hz,
IR (solid, ATR): 3396, 3056, 1593, 1501, 1435, 1160, 1116, 1092, 1069,
998, 811, 748, 732, 691, 600, 567, 504, 482, 448, 406 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.75–7.79 (m, 4 H), 7.56–7.60 (m, 2 H),
7.23–7.25 (m, 2 H), 7.48–7.52 (m, 4 H), 6.54–6.56 (m, 2 H), 4.44 (br s,
1 H), 3.90 (d, JH,P= 8.51 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 146.60 (d, JP,C = 9.99 Hz), 132.55 (d,
JP,C = 2.73 Hz), 131.88, 131.55 (d, JP,C = 81.74 Hz), 131.06 (d, JP,C = 9.08
CH), 128.2 (d, JP,C = 11.8 Hz, CH), 128.1 (CH), 128.0 (CH), 127.9 (d, JP,C
=
5.5 Hz, CH), 127.8 (CH), 127.6 (d, JP,C= 1.8 Hz, CH), 121.6 (d, JP,C = 10.9
Hz, CH), 121.1 (d, JP,C = 10.9 Hz, CH), 118.5 (d, JP,C = 95.4 Hz, C), 118.0
(d, JP,C = 101.7 Hz, C), 115.4 (CH), 115.2 (CH), 111.1 (d, JP,C= 6.36 Hz,
CH), 110.3 (d, JP,C= 7.27 Hz, CH), 109.5 (d, JP,C= 33.6 Hz, C), 58.0 (d, JP,C
74.5 Hz, CH), 55.52 (CH3), 55.50 (d, JP,C = 77.2 Hz, CH), 55.2 (CH3).
=
Hz), 128.89 (d, JP,C = 11.81 Hz), 121.45, 114.99, 110.33, 43.90 (d, JP,C
=
78.11 Hz).
31P NMR (202 MHz, CDCl3): δ = 32.90 (s, minor), 33.20 (s, major).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

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Anal. Calcd for C26H23BrNO2P: C, 63.43; H, 4.71; N, 2.84. Found: C,
63.77; H, 4.74; N, 2.65.
the mixture was evaporated to dryness and the residue was purified
by column chromatography using hexane/EtOAc (6:1, v/v) and hex-
ane/EtOAc (2:1, v/v) as eluent.
Aminomethyl(diphenyl)phosphine Oxide (8a)30
Diphenyl(sulfanylmethyl)phosphine-Borane (2a)18b
N-Benzylaminomethyl(diphenyl)phosphine oxide (8b; 0.307 g, 0.956
mmol) and Pd/C (61 mg) were placed in a freshly distilled MeOH (1
mL) in a Schlenk tube (25 mL), which was attached to a source of H2 at
atmospheric pressure (balloon). The mixture was carefully degassed
by three freeze-pump-thaw cycles, refilled with H2, and then warmed
to r.t. The mixture was heated at 70 °C for 4 d. After completion of the
reaction, the resulting mixture was filtered through a Celite pad,
washed with MeOH (3 × 10 mL), and then MeOH was evaporated. The
residue was purified by column chromatography using basic Al2O3
and CHCl3/EtOAc/MeOH (30:5:1, v/v/v) as eluent affording 8a as a col-
orless waxy solid; Rf = 0.38 (CHCl3/EtOAc/MeOH 30:5:1).
Phosphine oxide 1a (0.062 g, 0.25 mmol) was reacted according to the
general procedure to afford 2a18b (0.0178 g, 0.0725 mmol, 29%) and
[S-(4-hydroxybutyl)thiomethyl]diphenylphosphine-borane
(0.0247 g, 0.078 mmol, 31%).
2a18b
(3a)
Colorless oil; Rf = 0.57 (hexane/EtOAc 2:1).
IR (thin film, ATR): 3192, 3056, 2917, 2378, 2254, 1483, 1435, 1130,
1106, 1058, 999, 935, 778, 739, 692, 585, 493, 471, 436 cm–1
1H NMR (500 MHz, CDCl3): δ = 7.70–7.73 (m, 4 H), 7.47–7.56 (m, 6 H),
3.20 (dd, J = 6.31, 8.20 Hz, 2 H), 1.90 (q, J = 8.20 Hz, 1 H), 0.7–1.31 (br
m, 3 H).
.
IR (solid, ATR): 3392, 3053, 1671, 1543, 1436, 1160, 1120, 1036, 1014,
996, 889, 818, 717, 691, 544, 502 cm–1
.
13C NMR (125 MHz, CDCl3): δ = 132.51 (d, JP,C= 9.09 Hz), 131.67 (d, JP,C
2.73 Hz), 128.93 (d, JP,C= 9.99 Hz), 127.76 (d, JP,C= 54.50 Hz), 19.69 (d,
JP,C= 32.70 Hz).
31P NMR (202 MHz, CDCl3): δ = 21.99 (br m).
11B NMR (160.5 MHz, CDCl3): δ = –39.39 (br m).
HRMS (ESI-TOF): m/z [M]+ calcd for C13H16BPS: 245.0717; found:
=
1H NMR (500 MHz, CDCl3): δ = 7.73–7.78 (m, 4 H), 7.52–7.55 (m, 2 H),
7.46–7.50 (m, 4 H), 3.51 (d, JP,H = 4.10 Hz, 2 H), 1.67 (br s, 2 H).
13C NMR (125 MHz, CDCl3): δ = 132.06 (d, JP,C = 2.73 Hz), 128.75 (d,
JP,C = 10.90 Hz), 131.01 (d, JP,C = 95.37 Hz), 131.04 (d, JP,C = 9.08 Hz),
41.90 (d, JP,C = 72.66 Hz).
31P NMR (202 Hz, CDCl3): δ = 30.41 (s).
HRMS (ESI-TOF): m/z calcld for C13H14NOP [M + H]+: 232.0886; found:
245.0708.
232.0872.
Anal. Calcd for C13H16BPS: C, 63.44; H, 6.55. Found: C, 63.12; H, 6.30.
Anal. Calcd for C13H14NOP: C, 67.53; H, 6.10; N, 6.06. Found: C, 67.55;
H, 6.00; N, 6.00.
3a
Colorless oil; Rf = 0.13 (hexane/EtOAc 2:1).
2-[N-(1-Methylbenzylamino)]ethyl(diphenyl)phosphine Oxide
IR (thin film, ATR): 3372, 3056, 2933, 2379, 1435, 1106, 1056, 1027,
(17)16
999, 807, 739, 691, 608, 492, 470, 433 cm–1
.
This compound was available from our earlier studies.16
1H NMR (500 MHz, CDCl3): δ = 7.70–7.74 (m, 4 H), 7.45–7.54 (m, 6 H),
3.62 (t, J = 6.31 Hz, 2 H), 3.26 (d, J = 6.94 Hz, 2 H), 2.60 (t, J = 6.94 Hz, 2
H), 1.56–1.67 (m, 4 H), 1.56 (br s, 1 H), 0.70–1.36 (br m, 3 H).
White solid; mp 228.2–229.5 °C; Rf = 0.57 (CHCl3/EtOAc/MeOH
30:5:1), [α]D25 –26.33 (c 1, CHCl3).
13C NMR (125 MHz, CDCl3): δ = 132.51 (d, JP,C= 9.09 Hz), 131.48 (d, JP,C
2.72 Hz), 128.77 (d, JP,C= 9.99 Hz), 127.43 (d, JP,C= 54.49 Hz), 62.22,
34.58 (d, JP,C= 2.72 Hz), 31.48, 27.56 (d, JP,C= 32.70 Hz), 25.26.
=
IR (solid, ATR): 2983, 2840, 2775, 2544, 2440, 1598, 1465, 1437, 1379,
1192, 1159, 1120, 1097, 1070, 924, 793, 752, 729, 704, 694, 566, 544,
511, 499, 467, 419 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.58–7.66 (m, 4 H), 7.47–7.51 (m, 4 H),
7.31–7.43 (m, 7 H), 4.17 (q, J = 6.62 Hz, 1 H), 3.08–3.21 (m, 2 H), 2.84–
2.95 (m, 2 H), 2.05 (br s, 1 H), 1.70 (d, J = 6.94 Hz, 3 H).
31P NMR (202 MHz, CDCl3): δ = 18.46 (br m).
11B NMR (160.5 MHz, CDCl3): δ = –39.01 (br m).
HRMS (ESI-TOF): m/z [M]+ calcd for C17H24BOPS: 317.1292; found:
13C NMR (125 MHz, CDCl3): δ = 135.53, 132.53 (d, JP,C = 2.73 Hz),
317.1282.
132.45 (d, JP,C = 2.73 Hz), 130.71 (d, JP,C = 83.56 Hz), 130.57 (d, JP,C
=
Anal. Calcd for C17H24BOPS: C, 64.16; H, 7.60. Found: C, 64.36; H. 7.80.
9.99 Hz), 130.53 (d, JP,C = 9.99 Hz), 130.07 (d, JP,C = 81.74 Hz), 129.39,
129.37, 128.97 (d, JP,C = 11.81 Hz), 128.94 (d, JP,C = 11.81 Hz), 127.68,
59.02, 40.46, 25.95 (d, JP,C = 69.09 Hz), 20.43.
Di-c-hexyl(sulfanylmethyl)phosphine-borane (2b)
31P NMR (202 MHz, CDCl3): δ = 33.68 (s).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C22H24NOP: 350.1668; found:
Di-c-hexyl(sulfanylmethyl)phosphine oxide (1b; 0.0651 g, 0.25
mmol) was reacted according to the general procedure to afford di-c-
hexyl(sulfanylmethyl)phosphine-borane (2b) (0.009 g, 0.035 mmol,
14%) and di-c-hexyl[S-(4-hydroxybutyl)thiomethyl]phosphine-bo-
rane (3b) (0.022 g, 0.068 mmol, 27%).
350.1668.
Anal. Calcd for C22H24NOP: C, 75.62; H, 6.92; N, 4.01. Found: C, 75.43;
H, 6.61; N, 3.81.
2b
Reduction of α-Sulfanylmethylphosphine Oxides 1 in THF; Gener-
White solid; mp 73.5–74.5 °C; Rf = 0.66 (hexane/EtOAc 6:1).
al Procedure
IR (solid, ATR): 2928, 2848, 2549, 2381, 2271, 1739, 1453, 1446, 1261,
1134, 1063, 1048, 1003, 932, 888, 852, 794, 777, 752, 693, 670, 583,
In a two-necked round-bottom flask (25 mL) equipped with a mag-
netic stirrer and an argon inlet, α-sulfanylmethylphosphine oxide 1
(0.25 mmol) was dissolved in anhyd THF (2 mL). Then, H3B·SMe2 (71
μL, 0.75 mmol or 237 μL, 2.5 mmol) was added via syringe over a pe-
riod of 2 min to avoid uncontrolled bubbling. After the addition of BH3
complex, the reaction mixture was heated at 60 °C for 3 or 24 h. Then,
516, 504, 450 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 2.69 (dd, J = 5.67, 7.57 Hz, 2 H), 1.81–
1.98 (m, 11 H), 1.71–1.77 (m, 2 H), 1.39–1.52 (m, 4 H), 1.23–32 (m, 6
H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

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13C NMR (125 MHz, CDCl3): δ = 31.05 (d, JP,C = 30.88 Hz, CH), 26.99 (d,
JP,C = 0.69 Hz, CH2), 26.88 (d, JP,C = 0.72 Hz, CH2), 26.82 (d, JP,C = 1.82 Hz,
CH2), 26.77 (d, JP,C = 8.17 Hz, CH2), 25.87 (CH2), 13.52 (d, JP,C = 25.43 Hz,
CH2).
31P NMR (202 MHz, CDCl3): δ = 30.90 (br m).
11B NMR (160.5 MHz, CDCl3) δ = –43.47 (br m).
Attempted Reduction of tert-Butylphenyl(phenylthiometh-
yl)phosphine Oxide (5)
In a two-necked round-bottom flask (25 mL) equipped with a mag-
netic stirrer and an argon inlet, tert-butylphenyl(phenylthiometh-
yl)phosphine oxide (5; 0.1 g, 0.328 mmol) was dissolved in anhyd THF
(2 mL). Then, H3B·SMe2 (156 μL, 1.64 mmol) was added via syringe
over a period of 2 min to avoid uncontrolled bubbling. After the addi-
tion of BH3 complex, the reaction mixture was stirred for 48 h at
60 °C. Then, the reaction mixture was evaporated to dryness. The
NMR analysis showed the presence of only the starting material.
HRMS (ESI-TOF): m/z [(M – BH3) + O + H]+ calcd for C13H28BPS:
261.1436; found: 216.1443.
Anal. Calcd for C13H28BPS: C, 60.47; H, 10.93. Found: C, 60.17; H,
10.65.
Reduction of Diphenyl(2-sulfanylethyl)phosphine Oxide (6) to Di-
phenyl(2-sulfanylethyl)phosphine-Borane (7)
3b
Colorless oil; Rf = 0.40 (hexane/EtOAc 2:1).
In a two-necked round-bottom flask (25 mL) equipped with a mag-
netic stirrer and an argon inlet, diphenyl(2-sulfanylethyl)phosphine
oxide (6; 0.0786 g, 0.3 mmol) was dissolved in anhyd toluene (2 mL).
Then, H3B·SMe2 (285 μL, 3 mmol) was added via syringe over a period
of 2 min to avoid uncontrolled bubbling. After the addition of BH3
complex, the reaction mixture was stirred for 18 h at 110 °C. Then,
the mixture was evaporated to dryness and the residue was purified
by column chromatography using hexane/acetone (4:1, v/v) as eluent
affording 7 as a white solid (0.0195 g, 0.075 mmol, 25%); mp 153–
154 °C (dec.); Rf = 0.38 (hexane/acetone 4:1).
IR (thin film, ATR): 3366, 2927, 2852, 2378, 1448, 1060, 1004, 889,
854, 826, 792, 753, 600, 449, cm–1
.
1H NMR (500 MHz, CDCl3): δ = 3.68 (t, J = 5.67 Hz, 2 H), 2.72 (d, J =
7.25 Hz, 2 H), 2.64 (t, J = 6.94 Hz, 2 H), 2.54 (t, J = 6.94 Hz, 1 H), 2.11 (s,
1 H), 1.89–1.98 (m, 2 H), 1.77–1.89 (m, 6 H), 1.63–1.77 (m, 6 H), 1.37–
1.58 (m, 5 H), 1.20–1.35 (m, 5 H), 0.01–0.66 (br m, 3 H).
13C NMR (125 MHz, CDCl3): δ = 62.36 (d, JP,C = 24.52 Hz, CH2), 35.20 (d,
JP,C = 3.63 Hz, CH2), 34.01 (CH2), 31.67 (d, JP,C = 22.71 Hz, CH2), 30.78 (d,
JP,C = 31.79 Hz, CH), 26.83 (d, JP,C = 11.81 Hz, CH2), 26.71 (d, JP,C = 10.90
Hz, CH2), 25.90 (CH2), 25.34 (d, JP,C = 9.99 Hz, CH2), 22.04 (d, JP,C = 25.43
Hz, CH2).
IR (solid, ATR): 2922, 2852, 2378, 2250, 1435, 1109, 1061, 732, 690,
594, 492, 468, 444 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.68–7.78 (m, 4 H), 7.43–7.52 (m, 6 H),
2.71–2.76 (m, 2 H), 2.45–2.50 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 132.12 (d, JP,C = 99.9 Hz), 131.94 (d,
JP,C = 2.73 Hz), 130.63 (d, JP,C = 9.99 Hz), 128.74 (d, JP,C = 11.81 Hz),
30.17 (d, JP,C = 67.21 Hz), 23.70 (d, JP,C = 1.82 Hz).
31P NMR (202 MHz, CDCl3): δ = 28.30 (br m).
11B NMR (160.5 MHz, CDCl3): δ = –42.38 (br m).
HRMS (ESI-TOF): m/z [M]+ calcd for C17H36BOPS: 329.2231; found:
329.2238.
31P NMR (202 MHz, CDCl3): δ = 15.03 (br m).
Anal. Calcd for C17H36BOPS: C, 61.81, H, 10.99. Found: C, 62.11; H,
10.80.
Anal. Calcd for C14H18BPS: C, 64.64; H, 6.97. Found: C, 64.70 H 7.01.
Reduction of α-Sulfanylmethylphosphine Oxides 1 in Toluene;
General Procedure
Reduction of α-Aminophosphine Oxides 8 and 12; General Proce-
dure
In a two-necked round-bottom flask (25 mL) equipped with a mag-
netic stirrer and an argon inlet, α-sulfanylmethylphosphine oxide 1
(0.25 mmol) was dissolved in anhyd toluene (2 mL). Then, H3B·SMe2
(142 μL, 1.5 mmol or 237 μL, 2.5 mmol) was added via syringe over a
period of 2 min to avoid uncontrolled bubbling. After the addition of
BH3 complex, the reaction mixture was heated at 60 °C for 24 h. Then,
the mixture was evaporated to dryness and controlled by NMR analy-
sis. The residue was dissolved in anhyd EtOAc and H3B·SMe2 (71 μL,
0.75 mmol) was added. When complexation of the phosphine was ob-
served (10 min), the residue was quenched with sat. aq NH4Cl (5 mL)
and extracted with CHCl3 (5 × 15 mL). The combined organic phases
were dried (anhyd Na2SO4) and concentrated. The residue was puri-
fied by column chromatography on silica gel using hexane/EtOAc (6:1,
v/v) as eluent.
In a two-necked round-bottom flask (25 mL) equipped with a mag-
netic stirrer and an argon inlet, aminomethylphosphine oxide (0.3
mmol) was dissolved in anhyd THF (2 mL). Then, H3B·THF (1.5 mL, 1.5
mmol, 1 M) was added via syringe over a period of 2 min to avoid un-
controlled bubbling. After the addition of BH3 complex, the reaction
mixture was stirred at r.t. for 24 h. Then, the mixture was evaporated
to dryness and the residue was purified by column chromatography
using hexane/EtOAc (4:1, v/v) or hexane/acetone (4:1, v/v) as eluent.
Aminomethyldiphenylphosphine-Borane (9a)
Aminomethyldiphenylphosphine oxide (8a; 0.0693 g, 0.3 mmol) was
reacted according to the general procedure to afford the title com-
pound with 83% yield according to 31P NMR spectroscopy; Rf = 0.53
(hexane/EtOAc 4:1).
31P NMR (202 MHz, CDCl3): δ = 14.42 (br m).
Diphenyl(sulfanylmethyl)phosphine-Borane (2a)18b
Diphenyl(sulfanylmethyl)phosphine oxide (1a; 0.0621 g, 0.25 mmol)
was reacted according to the general procedure to afford 2a as a color-
less oil (0.032 g, 0.128 mmol, 51%).
[N-(p-Bromophenyl)aminomethyl]diphenylphosphine-Borane
(9c)
According to the general procedure, 8c (0.116 g, 0.3 mmol) was react-
ed at r.t. for 1 h affording 9c together with a small amount of diphen-
ylphosphine-borane (11) as side-product.
Di-c-hexyl(sulfanylmethyl)phosphine-Borane (2b)
Di-c-hexyl(sulfanylmethyl)phosphine oxide (1b; 0.0651 g, 0.25
mmol) was reacted according to the general procedure to afford 2b as
aa white solid (0.0465 g, 0.18 mmol, 72%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

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S. Sowa et al.
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9c
IR (solid, ATR): 3219, 3060, 2930, 2381, 2317, 2277, 1483, 1435, 1407,
1172, 1161, 1103, 1069, 1059, 1015, 844, 746, 735, 688, 597, 497,
White solid (0.0817 g, 0.213 mmol, 71%); mp 99.7–100.7 °C; Rf = 0.41
(hexane/EtOAc 6:1).
467, 417 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.73–7.84 (m, 2 H), 4.55 (br s, 1 H),
7.27–7.60 (m, 13 H), 3.98–4.02 (m, 1 H), 3.88–3.92 (m, 1 H), 3.80–3.84
(m, 1 H), 3.50–3.55 (m, 1 H), 0.68–1.84 (br m, 6 H).
13C NMR (125 MHz, CDCl3): δ = 133.05, 132.62 (d, JP,C = 9.99 Hz),
129.26 (d, JP,C = 9.99 Hz), 130.06, 131.90 (d, JP,C = 9.99 Hz), 132.23 (d,
JP,C = 2.72 Hz), 132.51, 129.22 (d, JP,C = 10.90 Hz), 129.02, 128.86,
IR (solid, ATR): 3406, 2393, 1591, 1497, 1435, 1312, 1236, 1108, 1073,
998, 899, 807, 749, 733, 688, 605, 493, 460, 427, 418 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.68–7.72 (m, 4 H), 7.52–7.55 (m, 2 H),
7.45–7.48 (m, 4 H), 7.22–7.25 (m, 2 H), 6.50–6.53 (m, 2 H), 4.10 (br s,
1 H), 3.91 (d, JP,H= 5.67 Hz, 2 H), 0.69–1.41 (br m, 3 H).
13C NMR (125 MHz, CDCl3): δ = 146.39 (d, JP,C,N,C = 9.08 Hz), 134.34,
132.32, 131.91, 131.83 (d, JP,C = 2.72 Hz), 129.08 (d, JP,C = 9.99 Hz),
127.05 (d, JP,C = 55.40 Hz), 115.04, 110.47, 41.49 (d, JP,C = 42.69 Hz).
127.72 (d, JP,C = 58.13 Hz), 125.68 (d, JP,C = 59.04 Hz), 61.36 (d, JP,C
=
3.63 Hz), 50.80 (d, 1JP,C = 36.33 Hz).
31P NMR (202 MHz, CDCl3): δ = 15.57 (br m).
11B NMR (160.5 MHz, CDCl3): δ = –13.03 (br m), –41.08 (br m).
31P NMR (202 MHz, CDCl3): δ = 16.13 (br m).
HRMS: m/z [M – H]+ calcd for C19H20BBrNP: 382.0523; found:
MS (FAB): m/z (%) = 333 (2, [M]), 198 (11), 183 (18), 129 (11), 120
(17), 108 (20), 91 (100), 77 (12), 65 (26), 50 (13).
382.0520.
Anal. Calcd for C19H20BBrNP: C, 59.42; H, 5.25; N, 3.65. Found: C,
59.28; H, 4.98; N 3.74.
Anal. Calcd for C20H26B2NP: C, 72.13; H, 7.87; N, 4.21. Found: 71.77; H,
7.72; N, 4.35.
1131
o-Anisyl-{1-[N-(p-bromophenyl)amino]-1-phenylmethyl}phenyl-
phosphine-Borane (13)
Colorless oil (0.0054 g, 0.027 mmol, 9%); Rf = 0.54 (hexane/EtOAc 6:1).
IR (thin film, ATR): 2384, 1437, 1056, 901, 699 cm–1
1H NMR (500 MHz, CDCl3): δ = 7.65–7.70 (m, 4 H), 7.44–7.54 (m, 6 H),
6.33 (dq, JP,H = 179.80 Hz, JH,H = 6.94 Hz, 1 H), 0.77–1.51 (br m, 3 H).
31P NMR (202 MHz, CDCl3): δ = 1.51 (br m).
.
According to the general procedure, 12 (0.246 g, 0.5 mmol) was react-
ed with H3B·SMe2 (142 μL, 1.5 mmol) at 60 °C for 24 h to afford 13;
benzyl-p-bromophenylamine (14)32; o-anisylphenylphosphinous acid
borane (15)11b; and o-anisylphenylphosphine-borane (16).11a
13C NMR (125 MHz, CDCl3): δ = 132.92 (d, JP,C = 9.99 Hz), 131.62 (d,
JP,C = 1.82 Hz), 129.04 (d, JP,C = 10.90 Hz), 126.11 (d, JP,C = 57.22 Hz).
13
White solid, two diastereomers (dr = 1:0.4, 31P NMR) isolated as a
mixture (0.091 g, 0.185 mmol, 37%); dr = 1:0.55; Rf = 0.38 (hex-
ane/EtOAc 6:1).
MS (EI, 70 eV): m/z (%) = 186 (26, [M – BH3]), 152 (4), 109 (9), 108
(100), 107 (44), 92 (5), 81 (5), 57 (5), 51 (10).
HRMS (ESI-TOF): m/z [M – BH3 + H]+ calcd for C12H14BP: 187.0671;
found: 187.0667.
IR (thin film, ATR): 3384, 3027, 2940, 2377, 1735, 1590, 1493, 1475,
1461, 1428, 1309, 1276, 1247, 1175, 1065, 1017, 802, 759, 740, 699,
Anal. Calcd for C12H14BP: C, 72.06; H, 7.05. Found: C, 71.80; H, 6.99.
689, 600, 591, 550, 496, 459, 436 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.92–7.97 (m, 1 H, minor), 7.64–7.67
(m, 3 H), 7.54–7.57 (m, 1 H, minor), 7.33–7.46 (m, 5 H), 7.20–7.32 (m,
8 H), 7.07–7.20 (m, 7 H), 6.97–6.99 (m, 1 H, minor), 6.86–6.81 (m, 1 H,
major), 6.82–6.85 (m, 1 H, major), 6.56–6.57 (m, 2 H, major), 6.38–
[N-(p-Tolyl)aminomethyl]diphenylphosphine-Borane (9d)
[N-(p-Tolyl)aminomethyl]diphenylphosphine oxide (8d; 0.096 g, 0.3
mmol) was reacted according to the general procedure to afford 9d as
a solid (0.0737 g, 0.231 mmol, 77%); mp 93.0–94.0 °C; Rf = 0.51 (hex-
ane/EtOAc 4:1).
6.40 (m, 2 H, minor), 5.85 (d, JH,P = 17.65 Hz, major), 5.82 (d, JH,P
=
16.08 Hz, minor), 5.34 (br s, 2 H), 3.78 (s, 3 H, minor), 3.69 (s, 3 H,
major), 0.73–1.24 (br m, 6 H).
13C NMR (125 MHz, CDCl3): δ = 161.2 (d, JP,C= 1.5 Hz, minor, C), 160.8
(d, JP,C= 1.82 Hz, major, C), 145.7 (d, JP,C,N,C = 9.1 Hz, minor, C), 145.1 (d,
JP,C,N,C = 11.8 Hz, major, C), 137.1 (d, JP,C= 13.63 Hz, minor, CH), 137.0 (d,
IR (solid, ATR): 3379, 3211, 3055, 2386, 1612, 1519, 1436, 1175, 1122,
1108, 1070, 944.53, 805, 739, 718, 689, 642, 550, 553, 495, 417 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.71–7.77 (m, 4 H), 7.51–7.53 (m, 2 H),
7.44–7.49 (m, 4 H), 6.98–7.01 (m, 2 H), 6.57–6.61 (m, 2 H), 3.94 (d,
JP,H= 5.99 Hz), 2.24 (s, 3 H), 0.71–1.43 (br m, 3 H).
JP,C= 14.5 Hz, major, CH), 135.7 (d, JP,C= 3.6 Hz, major, C), 135.6 (d, JP,C
=
3.6 Hz, minor, C), 134.3 (d, JP,C = 1.8 Hz, major, CH), 134.1 (d, JP,C= 1.8
Hz, minor, CH), 132.7 (d, JP,C = 8.2 Hz, minor, CH), 131.9 (s, major, CH),
13C NMR (125 MHz, CDCl3): δ = 145.16 (d, JP,C,N,C = 9.99 Hz), 132.46 (d,
JP,C = 9.09 Hz), 131.64 (d, JP,C = 2.73 Hz), 129.70, 128.97 (d, JP,C = 9.99
Hz), 128.07, 127.39 (d, JP,C = 55.40 Hz), 113.63, 41.78 (d, JP,C = 42.69
Hz), 20.36.
131.8 (s, minor, CH), 131.3 (d, JP,C = 9.1 Hz, major, CH), 130.97 (d, JP,C
2.72 Hz, minor, CH), 130.4 (d, JP,C = 2.7 Hz, major, CH), 129.8 (d, JP,C
=
=
57.2 Hz, C), 128.5 (d, JP,C = 3.6 Hz, CH), 128.3 (d, JP,C = 10.0 Hz, major,
CH), 128.0 (d, JP,C = 10.0 Hz, minor, CH), 127.8 (d, JP,C = 1.9 Hz, major,
CH), 128.71, 127.9 (d, JP,C = 3.6 Hz, minor), 127.2 (d, JP,C = 57.2 Hz, C),
121.7 (d, JP,C = 11.8 Hz, minor, CH), 121.3 (d, JP,C = 12.7 Hz, major, CH),
115.4 (s, major, CH), 115.2 (s, minor, CH), 114.5 (d, JP,C = 57.2 Hz, ma-
jor, C), 114.5 (d, JP,C = 51.8 Hz, minor, C), 111.5 (d, JP,C = 4.5 Hz, minor,
CH), 111.1 (d, JP,C = 3.6 Hz, major, CH), 109.9 (s, major, CH), 109.6 (s,
minor, CH), 55.6 (s, minor, CH3), 55.4 (s, major, CH3), 54.8 (d, JP,C = 38.2
Hz, minor, CH), 51.8 (d, JP,C = 43.6 Hz, major, CH).
31P NMR (202 MHz, CDCl3): δ = 16.11 (br m).
HRMS (ESI-TOF): m/z [M]+ calcd for C20H23BNP: 318.1575; found:
318.1570
Anal. Calcd for C20H23BNP: C, 75.26; H, 7.26; N, 4.39. Found: C, 75.40;
H, 7.35; N, 4.50.
N-Benzylaminomethyldiphenylphosphine Bisborane (10)
N-Benzylaminomethyldiphenylphosphine oxide (8b; 0.0963 g, 0.3
mmol) was reacted with H3B·SMe2 (285 μL, 3 mmol) according to the
general procedure to afford 10 as a white solid (0.0629 g, 0.189 mmol,
63%); mp 121–122 °C (dec.); Rf = 0.64 (hexane/EtOAc 2:1).
31P NMR (202 MHz, CDCl3): δ = 27.64 (br m, minor), 25.19 (br m, ma-
jor).
11B NMR (160.5 MHz, CDCl3): δ = –41.47 (br m).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M

L
S. Sowa et al.
Paper
Synthesis
HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H26BBrNOP: 490.1098;
found: 490.1101.
MS (EI, 70 eV): m/z (%) = 218 (8), 216 (58) [M], 183 (24), 138 (55), 137
(62), 123 (7), 109 (21), 108 (66), 107 (45), 95 (8), 94 (12), 92 (11), 91
(100), 81 (6), 78 (16), 77 (16), 68 (10), 65 (13), 63 (7), 57 (6), 51 (19).
HRMS (ESI-TOF): m/z [M]+ calcd for C13H16BOP: 229.0945; found:
Anal. Calcd for C26H26BBrNOP: C, 63.71; H, 5.35; N, 2.86. Found: C,
63.34; H, 5.30; N, 2.70.
229.0944.
1432
Anal. Calcd for C13H16BOP: C, 67.87; H, 7.01. Found: C, 67.58, H, 6.70.
White solid (0.0419 g, 0.16 mmol, 32%); Rf = 0.63 (hexane/EtOAc 6:1).
Reduction of β-Aminophosphine Oxide 17 by H3B·SMe2 to 2-[N-(1-
Methylbenzylamino)]ethyl(diphenyl)phosphine-Borane (18)
IR (solid, ATR): 3192, 2259, 1593, 1492, 1451, 1398, 1321, 1294, 1262,
1190, 1178, 1068, 883, 809, 730, 696, 641, 546, 502, 456 cm–1
.
In a two-necked round-bottom flask (25 mL) equipped with a mag-
netic stirrer and an argon inlet β-aminophosphine oxide 17 (0.105 g,
0.3 mmol) was dissolved in anhyd THF (5 mL). Then, H3B·SMe2(142
μL, 1.5 mmol) was added via syringe over a period of 2 min to avoid
uncontrolled bubbling. After the addition of BH3 complex, the reac-
tion mixture was heated at 60 °C for 48 h. Then, the mixture was
evaporated to dryness and the residue was purified by column chro-
matography using basic Al2O3 and hexane/EtOAc (4:1, v/v) as eluent
affording 18 as a colorless oil (0.0625 g, 0.18 mmol, 60%); Rf = 0.57
(hexane/EtOAc 4:1); [α]D25 –35 (c 0.70, CHCl3).
1H NMR (500 MHz, CDCl3): δ = 7.34–7.36 (m, 4 H), 7.30–7.32 (m, 1 H),
7.24–7.25 (m, 2 H), 6.51–6.52 (m, 2 H), 4.31 (s, 2 H).
13C NMR (125 MHz, CDCl3): δ = 147.01, 109.09, 114.39, 127.36,
128.67, 131.90, 138.82, 41.28.
MS (EI, 70 eV): m/z (%) = 263 (13, [M + 1]), 261 (13), 91 (100), 65 (13).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H12BrN: 262.0226; found:
262.0227.
Anal. Calcd for C13H12BrN: C, 59.56; H, 4.61; N, 5.34. Found: C, 59.62;
H, 4.65; N, 5.37.
IR (thin film, ATR): 3056, 2961, 2916, 2849, 2379, 1436, 1107, 1060,
1027, 734, 692, 592, 544, 472, 428 cm–1
.
1511b
1H NMR (500 MHz, CDCl3): δ = 7.59–7.63 (m, 4 H), 7.38–7.47 (m, 6 H),
7.19–7.18 (m, 5 H), 3.71 (q, J = 6.31 Hz, 1 H), 2.70–2.78 (m, 2 H), 2.37–
2.42 (m, 2 H), 1.60 (br s, 1 H), 1.27 (d, J = 6.62 Hz, 3 H), 0.53–1.19 (br
m, 3 H).
White solid (0.0312 g, 0.13 mmol, 26%); mp 94.0–94.2 °C; Rf = 0.25
(hexane/EtOAc 2:1).
IR (solid, ATR): 3406, 2386, 2292, 1591, 1573, 1470, 1458, 1433, 1277,
1249, 1163, 1155, 1138, 1114, 1089, 1071, 1014, 888, 799, 759, 706,
13C NMR (125 MHz, CDCl3): δ = 145.08, 132.01 (d, JP,C = 9.99 Hz),
689, 628, 489, 471, 434 cm–1
.
131.99 (d, JP,C = 9.09 Hz), 131.12 (d, JP,C = 2.73 Hz), 129.35 (d, JP,C
=
1H NMR (500 MHz, CDCl3): δ =7.86–7.90 (m, 1 H), 7.62–7.66 (m, 2 H),
7.54–7.58 (m, 1 H), 7.40–7.49 (m, 3 H), 7.13–7.18 (m, 1 H), 6.96–6.98
(m, 1 H), 5.29 (br s, 1 H), 3.79 (s, 3 H), 0.67–1.39 (br m, 3 H).
13C NMR (125 MHz, CDCl3): δ = 160.62, 134.31 (d, JP,C = 16.35 Hz),
133.85 (d, JP,C = 61.76 Hz), 131.24, 130.18 (d, JP,C = 11.81 Hz), 128.34 (d,
JP,C = 10.90 Hz), 121.74 (d, JP,C = 12.72 Hz), 119.81 (d, JP,C = 57.22 Hz),
111.38, 56.0.
55.40 Hz), 128.76 (d, JP,C = 9.99 Hz), 128.38, 126.92, 126.49, 57.78,
41.63 (d, JP,C = 2.73 Hz), 26.32 (d, JP,C = 36.33 Hz), 24.10.
31P NMR (202 MHz, CDCl3): δ = 13.80 (br m).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C22H27BNP: 348.2044; found:
348.2040.
Anal. Calcd for C22H27BNP: C, 76.10, H, 7.84, N, 4.03. Found: C, 76.20,
H, 7.90, N, 4.00.
31P NMR (202 MHz, CDCl3): δ = 97.13 (br m).
11B NMR (160.5 MHz, CDCl3): δ = –38.17 (br m).
HRMS (ESI-TOF): m/z [M]+ calcd for C13H16BO2P: 245.0894; found:
245.0887.
Funding Information
This work was financially supported by the Polish Ministry of Science
Anal. Calcd for C13H16BO2P: C, 63.46; H, 6.55. Found: C, 63.70; H, 6.88.
and Higher Education through the grant (N N204 111 035).
)(
1611a
White solid (0.0046 g, 0.02 mmol, 4%); mp 92.0–92.6 °C; Rf = 0.45
(hexane/EtOAc 6:1).
Acknowledgment
We acknowledge the synthetic assistance of M. Sc. Anna Szmigielska
(Department of Organic Chemistry, Faculty of Chemistry, Maria Curie
Sklodowska University).
IR (solid, ATR): 2380, 2256, 1587, 1576, 1477, 1455, 1432, 1295, 1247,
1133, 1060, 1023, 912, 898, 767, 739, 694, 591, 486, 442, 419 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.73–7.78 (m, 1 H), 7.60–7.72 (m, 2 H),
7.49–7.54 (m, 1 H), 7.44–7.49 (m, 1 H), 7.38–7.43 (m, 2 H), 7.05–7.10
(m, 1 H), 6.91–6.96 (m, 1 H), 6.58 (dq, JP,H= 392.36 Hz, 1 H), 3.85 (s, 3
H), 0,67–1.34 (br m, 3 H).
References
13C NMR (125 MHz, CDCl3): δ = 160.51, 134.90 (d, JP,C = 13.62 Hz),
133.81 (d, JP,C = 1.82 Hz), 132.78 (d, JP,C = 9.08 Hz), 131.04 (d, JP,C = 1.81
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11.81 Hz), 110.72 (d, JP,C = 3.63 Hz), 55.72.
31P NMR (202 MHz, CDCl3): δ = –16.44 (br m).
11B NMR (160.5 MHz, CDCl3): δ = –40.38 (br m).
=
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meric mixture while the crude reaction mixture indicated dr =
1:0.55.
(21) The product of retro-Kabachnik–Fields reaction of 8c and 8d in
the presence of BH3 was diphenylphosphine oxide, which
underwent reduction with BH3 leading to the formation of
diphenylphosphine-borane (11), similar to the reaction of 12
with H3B·SMe2 where phosphinous acid-borane 15 and second-
ary phosphine-borane 16 were present as products of complex-
ation and reduction, respectively. For more details, see refer-
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–M