l-Menthol-Assisted Synthesis of P-Stereogenic Phosphinous Acid Amides and Phosphine-Boranes

Article abstract of DOI:10.1002/ejoc.201800065

Diastereomerically pure phenylphosphonous acid-borane l-menthyl ester N,N-diethylamide was obtained through the fractional crystallization of a diastereomeric mixture of compounds synthesized from PhPCl₂, l-menthol, diethylamine, and BH₃·THF. Treatment of racemic or diastereomerically pure phenylphosphonous acid-borane derivatives with sodium in liquid ammonia followed by the addition of an electrophile led to the formation of phosphinous acid-amides. Surprisingly, these compounds undergo preferential P–N bond cleavage under Birch reduction conditions.

Full text of DOI:10.1002/ejoc.201800065

A Journal of
Accepted Article
Title: L-Menthol-assisted synthesis of P-stereogenic phosphinous acid
amides and phosphine-boranes
Authors: Adam Włodarczyk, Anna E Kozioł, and Marek Stankevic
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800065
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800065
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10.1002/ejoc.201800065
European Journal of Organic Chemistry
FULL PAPER
DOI: 10.1002/ejoc.200((will be filled in by the editorial staff))
L-Menthol–assisted synthesis of P-stereogenic phosphinous acid amides and
phosphine-boranes
Adam Włodarczyk,[a] Anna E. Kozioł,[b]and Marek Stankevič*[a]
Keywords:Phosphonous acid-borane derivatives/P-stereogenic/Alkali metal/P-O bond cleavage/P-N bond cleavage
Diastereomerically pure phenylphosphonous acid-borane L-menthyl nous acid-borane derivatives with sodium in liquid ammonia
ester N,N-diethylamide was obtained through the fractional followed by an addition of an electrophile led to the formation
crystallization of
a diastereomeric mixture of compounds of phosphinous acid-amides. These compounds surprisingly
synthesized from PhPCl2, L-menthol, diethylamine and BH3-THF. undergo preferential P-N bond cleavage under Birch reduction
Treatment of racemic or diastereomerically pure phenylphospho-
conditions.
____________
diastereomerically pure phenylphosphinous acid-borane L-menthyl
[a]
Department of Organic Chemistry, Faculty of Chemistry, Maria
Curie-Skłodowska University, Gliniana 33, 20-614 Lublin, Poland
Tel: +48 81 537-77-52
ester was used in palladium-catalyzed coupling with iodoarenes.[7]
E-mail: marek.stankevic@poczta.umcs.lublin.pl
www: orgchem.umcs.lublin.pl
[b] Department of Crystalography, Faculty of Chemistry, Maria Curie-
Skłodowska University, Maria Curie-Skłodowska Square 3
20-031 Lublin, Poland
The use of L-menthol as a chiral alkoxy function for the
synthesis of the corresponding phosphorus acids esters is the most
obvious but not the only possible application of this alcohol in
organophosphorus chemistry. The other includes the use of
L-menthyl chloroacetate, which upon treatment with tertiary
phosphines affords the mixture of diastereomeric phosphonium
salts. The latter can be separated and transformed into the
enantiomerically enriched phosphine oxides by removing the
acetate fragment under hydrolytic conditions (Scheme 2).[8a]
tel: +48 81 537 55 02
Supporting information for this article is available on the WWW
under http://www.eurjoc.org/ or from the author.
Introduction
L-Menthol, applied first by Mislow et al.[1] in late 60’s as an
chiral auxiliary for the synthesis of P-stereogenic
organophosphorus compounds (Scheme 1)[1b] quickly became the
most frequently used source of enantio- or diastereoselective
discrimination in organophosphorus chemistry.
Scheme 2. The use of L-menthyl chloroacetate as removable chiral
auxiliary[8a]
Reaction of secondary phosphine derivatives with L-menthyl
chloroacetate affords the corresponding diastereomeric tertiary
phosphine derivatives which facilitates their further separation.[9]
In this case, acetyl fragment is permanently incorporated into the
structure of the phosphine derivative (Scheme 3).[9a]
Scheme 1. L-Menthol as chiral auxiliary in the synthesis of P-stereogenic
tertiary phosphine oxides[1b]
The main principle of the synthesis of P-stereogenic compounds
using menthol is based on the preparation and resolution of
diastereomeric mixture of two organophosphorus compounds
possessing P-OMenthyl functionality. The lability of the ester
group can be further used for the synthesis of tertiary phosphine
oxides,[2] boranes,[3] and sulfides[4] through either nucleophilic
substitution or reductive cleavage-alkylation.[5] L-Menthyl
phenylphosphinate (PhHP(O)OMenthyl) is one the examples of the
Scheme 3. L-Menthyl chloroacetate in the reaction with >P-H-type
compounds[9a]
Beside all examples where L-menthol is used as removable
chiral auxiliary there are also precedences where L-menthol
becomes the integral part of the molecule. This includes
phosphorus(III) esters which have found applications as ligands in
transition metal-mediated catalytic transformations.[10] On the other
hand, menthyl fragment itself was frequently incorporated into the
diastereomerically
pure
P-stereogenic
organophosphorus
compounds obtained using L-menthol as the chiral auxiliary. This
molecule was frequently used as starting material for the synthesis
of other classes of organophosphorus compounds.[6] The analogous
Submitted to the European Journal of Organic Chemistry
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10.1002/ejoc.201800065
European Journal of Organic Chemistry
structure of phosphines and their derivatives.[11] The presence of
bulky and highly stereodefined cycloalkyl substituent at
phosphorus enables the resolution of the formed chirality center at
phosphorus atom. The use of L-menthol for dynamic kinetic
resolution of tertiary phosphine oxides should be noticed as
well.[12]
Results and Discussion
In the course of our research topic related to the synthesis of
P-stereogenic organophosphorus compounds[13] we attempted the
preparation of enantiomerically pure phenylphosphonous acid-
borane monoester monoamides. The method described by Jugé and
coworkers based on the use of ephedrine as chiral auxiliary,[14]
although very efficient and elegant, has nowadays a serious
drawback due to the highly restricted handling of ephedrine, which
is the consequence of their psychoactive properties. On the other
hand, L-menthol is a very cheap and readily available chiral
molecule with no restrictions in handling, so the question is
whether L-menthol can be used as a chiral auxiliary for the
synthesis of enantiomerically pure P-stereogenic phosphonous
acid-borane derivatives. The analogous diastereomerically pure
phenyl-phosphonic acid L-menthyl ester monoamides could be
Figure 1. Molecular structure of diastereomerically pure (RP)-14
The structural analysis of this compound allowed to ascribe the
absolute configuration at phosphorus atom as RP.
A brief look at the possible transformations of analogous
diastereomerically pure oxazaphospholidine-boranes show that
oxazaphospholidine ring opening with organolithium reagents is
the only reaction used to introduce the carbon substituent at
phosphorus atom.[16] Another method for the modification of the
structure would be the dearomatization of arene fragment which
has been developed in our research group for phosphine-boranes
and oxides.[17] Previously, we have also found that the analogous
arylphosphonic acid monoester monoamides exclusively undergo
the dearomatization of the arene fragment.[18] It was therefore
decided to check first the reactivity of racemic borane analogues of
arylphosphonic acid derivatives under Birch reduction conditions
and then to apply the obtained diastereomerically pure (RP)-14 for
the synthesis of P-stereogenic organophosphorus compounds in a
non-racemic form.
prepared
starting
from
L-menthyl
phenylphosphinate,
[15]
corresponding amines and CCl4 but this method is not suitable
for phosphonous acid-borane derivatives. Therefore, the synthesis
of diastereomerically pure phenylphosphonous acid-borane
derivative using L-menthol as chiral auxiliary has been attempted
at the beginning (Scheme 4).
L-Menthol (1.0 equiv.)
NEt3 (1.0 equiv.)
HNEt2 (2.0 equiv.)
DCM, r.t.
P
P
P
O
O
2
Cl
Cl
DCM, r.t.
Cl
NEt
10
11
12
31P NMR
31P NMR
(174.6 and 176.9 ppm
1:1 ratio of epimers)
(124.7 and 128.1 ppm
1:1 ratio of epimers)
not isolated
not isolated
BH
3
First, a set of experiments with racemic analogue of 14, namely
phenylphosphonous acid-borane ethyl ester N,N-diethylamide 15,
has been performed (Scheme 5, Table 1).
BH
P
3
BH3*THF (1.5 equiv.)
DCM, r.t.
crystalization
P
O
O
cyclohexane/Et2O (1/1)
-78oC
NEt
NEt
2
2
rac-13 (99%)
14 (46%)
(after three steps)
Single diastreomer
31P NMR (106.1 ppm)
D = -33.75 (c 0.945, CHCl3)
31P NMR
(106.1 and 107.8 ppm
1:1 ratio of epimers)

Scheme 4. Synthesis of diastereomerically pure 14
Scheme 5. Reaction of 15 with a solution of sodium in liquid ammonia in
Treatment of dichlorophenylphosphine 10 with equimolar
amounts of L-menthol and triethylamine afforded the compound 11
as a mixture of two diastereomers. This intermediate was not
isolated from the reaction mixture but was subjected to the reaction
with the two-fold excess of diethylamine after removal of
ammonium salt from the mixture. This reaction afforded
phosphonous acid monoester monoamide 12 which, after filtering
off the salt, has been treated in situ with BH3-THF complex. A
product of this three-step synthesis, phenylphosphonous acid-
borane L-menthyl ester N,N-diethylamide rac-13 was obtained in
total 99% yield as a mixture of two diastereomers. Attempted
the presence of an electrophile
Table 1. Reaction of 15 with a solution of sodium in liquid ammonia in the
presence of an electrophile
Nr
Electrophile
Product
R
Yield (%)
1
Methyl iodide
16a
16b
16c
16d
16e
16f
Me
89
76
99
64
83
2
Ethyl bromide
Et
3
Benzyl chloride
Propargyl chloride
Allyl chloride[a]
5-Bromo-1-butene
PhCH2
1-propynyl
CH=CH2CH3
4
5
o
fractional crystallization of rac-13 in cyclohexane:Et2O at -78 C
afforded the desired diastereomerically pure 14 in 46% yield.
6
(CH2)3CH=CH2 99
7
Methyl chloroacetate 16g
CH2COOMe
CH2OH
69
76
72
82
8
p-Formaldehyde
Acetaldehyde
Benzaldehyde
16h
16i
16j
A small portion of this compound has been recrystallized in
order to obtain a crystalline sample suitable for the X-ray single-
crystal structure analysis. The structure of the molecule is
presented below (Figure 1).
9
CH(OH)CH3
CH(OH)Ph
10
[a]- The reaction was performed at -33°C.
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10.1002/ejoc.201800065
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It appeared, that under the reaction conditions the compound 15
underwent exclusively the P-O bond cleavage and no traces of
Birch reduction products have been observed. In this regard
compound 15 behaves analogously to phosphinous acid-borane
esters which upon treatment with one-electron reductants
underwent P-O bond cleavage yielding the corresponding P-anions
and then secondary or tertiary phosphine-boranes.[19] This stands
also in a sharp contrast with the reactivity of the structurally similar
phenyl and arylphosphonic acids monoester monoamides which
under the same conditions underwent Birch reduction of arene
fragment exclusively.[18] Treatment of the intermediate P-anion
with different electrophiles led to a set of phosphinous acid-borane
amides 16a-h in fair to excellent yields. The use of propargyl
chloride as electrophile led to the formation of 1-
propynylphosphinous acid-borane amide 16d. The formation of
this product could be explained by in situ isomerization of the
triple bond under the reaction conditions (Table 1, Entry 4). Even
acetaldehyde and benzaldehyde worked well in this reaction
affording the corresponding -hydroxy-functionalized phosphinous
acid-borane amides 16g and 16h in good yields (Table 1, Entries 7
and 8).
1. Na (2.5 equiv.), 5 min
2. EX (2 equiv.), 15 min
BH3
BH3
P
P
NH3/THF, -78C
O
NEt2
NEt2
R
(RP)-14
19
Scheme 7. Reaction of (RP)-14 with a solution of sodium in liquid ammonia
in the presence of an electrophile
Table 2. Reaction of (RP)-14 with a solution of sodium in liquid ammonia in
the presence of an electrophile
[a]
Nr
Product
Yield
(%)
D
Ee[b]
(%)
1[c] 19a (R = Me)
2[d] 19b (R = Et)
99
78
99
75
75
50
69
79
-40.9 (c 0.75)
-6.6 (c 3.395)
51.6 (c 1.20)
-22.0 (c 0.85)
-25.5 (c 1.8)
-1.8 (c1.09)
-31.4 (c 1.1)
>99
99
3[e] 19c (R = CH2Ph)
4[f] 19d (R = 1-propynyl)
5[g] 19e(R = 1-propenyl)
6[h] 19f(R = (CH2)2CH=CH2)
7[i] 19g (R = CH2COOMe)
8[j] 19h (R = CH2OH)
96
99
>99
99
98
-14.9 (c 1.01)
99
o
[a] All measurements were performed in CHCl3 at 22 C. [b] enantiomeric
excess was measured with chiral stationary phase HPLC [c] MeI was used
as an electrophile. [d] EtBr was used as an electrophile. [e] BnCl was used
as an electrophile. [f] AllylCl was used as an electrophile reaction was
performed at -33°C. [g] Homoallyl bromide was used as an electrophile.[h]
Propargyl chloride was used as an electrophile. [i] ClCH2COOMe was used
as an electrophile. [j] Paraformaldehyde was used as an electrophile.
Once the reactivity of the racemic 15 towards sodium in liquid
ammonia has been established, it was decided to perform an
analogous set of experiments using diastereomerically pure (RP)-14.
First, the transformation of (RP)-14 into a known[20] P-stereogenic
methylphenylphosphinous acid-borane methyl ester 18 has been
attempted (Scheme 6).
Treatment of (RP)-14 with sodium in liquid ammonia followed
by addition of an electrophile led in all cases to the formation of
the corresponding phosphinous acid-borane amides in good yields.
The only exception was allyl chloride where a complex reaction
mixture was formed under the standard conditions. But, the same
reaction performed at slightly higher temperature afforded 19e
selectively (Table 2, Entry 5). This compound was most probably
formed through the double bond isomerization in the parent
allylphosphinous acid-borane amide under the reaction conditions.
Similar observations was made for the reaction of (RP)-14 with
propargyl chloride where the only product isolated from the
reaction mixture was 1-propynylphosphinous acid-borane amide
19d (Table 2, Entry 4). In case of homoallyl-substituted
phosphinous acid-borane amide 19f the isomerization of the double
bond was not observed (Table 2, Entry 6). Electrophiles like
methyl chloroacetate and paraformaldehyde underwent the reaction
in a similar way affording the corresponding products with good
yield and excellent stereoselectivity (Table 2, Entries 7 and 8).
BH3
BH3
P
1. Na (2.5 equiv.)
2. MeI (2 equiv.)
P
O
NEt2
NH3/THF, -78oC, 20 min
Me
NEt2
retention
(RP)-14
(RP)-17 (99%)
BH3
P
H2SO4 (1.1 equiv.), MeOH
rt, 24 h
OMe
Me
inversion
(SP)-18 (60%)
Scheme 6. Absolute configuration of 14 through chemical correlation
Treatment of (RP)-14 with sodium in liquid ammonia followed
by an addition of methyl iodide afforded the corresponding
phosphinous acid-borane amide (RP)-17. Phosphorus-oxygen bond
cleavage is known to proceed with retention of the configuration at
phosphorus in the presence of single electron reductants.[19]
Reaction of the amide (RP)-17 with methanol in the presence of
sulfuric acid afforded methylphenylphosphinous acid-borane
methyl ester (SP)-18. The absolute configuration at phosphorus has
been ascribed based on the literature precedences which show that
methanolysis of phosphinous acid-borane amides in the presence of
a catalytic amount of acid proceed with the inversion of
configuration at phosphorus.[16d] Compound (SP)-18 is a valuable
substrate in the synthesis of P-stereogenic phosphine ligands[20] so
the development of an alternative method of the synthesis of this
molecule should inspire chemists for the search of new phosphine
ligands.
It is known that P-O bond cleavage in the phosphinous acid-
borane esters proceeds with the retention of configuration at the
phosphorus atom when the reaction is carried at low
temperature.[21] Based on this, the absolute configuration at
phosphorus for compounds 19a-g has been assigned as RP and SP
for compound 19h. High stereospecificity of the reaction is
demonstrated by the high enantiomeric excesses of the products as
determined by HPLC analysis using a column with chiral
stationary phase.
Phosphinous acid-borane amides obtained either from (RP)-14 or
from 15 are potentially good substrates for the further modification
of the structure using an alkali metal solution in liquid ammonia.
Up to now, there are only two mentions about the reaction of
N-benzyl t-butylphenylphosphinous acid-borane amides with alkali
metal in liquid ammonia[22] where the authors observed both
dearomatization of phenyl substituent at phosphorus and benzyl
group cleavage in the amide moiety but with preservation of P-N
Then, diastereomerically pure (RP)-14 has been subjected to the
reaction with sodium in liquid ammonia followed by an addition of
different electrophiles (Scheme 7, Table 2).
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10.1002/ejoc.201800065
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bond. Previously, it was found that phosphinous acid-borane
amides can undergo Birch reduction of the arene fragment upon
treatment with sodium in liquid ammonia.[23] But, from the
synthetic point of view, more practical transformation would be the
amide group cleavage leading to the corresponding P-anion which
could be used for the reaction with carbon electrophile. This would
lead directly to the corresponding tertiary phosphine-borane in one
step from the corresponding amides. The proposed methodology is
shorter than the two-step synthesis of the same compounds using
methanolysis-substitution sequence and should proceed in a more
unconjugated (Table 3, Entry 6). In the case, when alkyl halide has
been added instead of NH4Cl, the reaction afforded the
corresponding tertiary phosphine-borane in moderate yield (Table
3, Entry 8). A brief look at the results collected in the Table above
points also on the rather modest yields of the products although the
conversion of the substrates was complete in every case. This can
be attributed to the partial instability of the products during work-
up and purification steps as the products might undergo
deprotection-oxidation leading to the corresponding pgospgine
oxides or phosphinic acids.
o
stereospecific way due to the applied reaction conditions (-78 C).
It was therefore decided to perform a set of reactions between
racemic phosphinous acid-borane amides and sodium in liquid
ammonia (Scheme 8, Table 3).
The data presented in the Table 3 suggest that secondary
phosphine-boranes could be obtained directly from the
corresponding phosphinous acid-borane amides under Birch
reduction conditions. It was therefore decided to check the
formation of P-stereogenic secondary phosphine-borane 20c which
could be a valuable substrate for the synthesis of P-stereogenic
tertiary phosphine-boranes (Scheme 9).
BH3
P
BH3
P
1. Na (2.5 equiv.)
2. NH4Cl (2 equiv.)
NH3/THF, -78oC
[]D = +117,5
(c 0.84 CHCl3)
Scheme 8. Reaction of 16 a-g with sodium in liquid ammonia
Table 3. Reactivity of 16 a-g under Birch reduction conditions
NEt2
H
(RP)-19c
96% ee
40 %
(SP)-20c
Scheme 9. Cleavage of amide functionality under Birch reduction
conditions.
Nr
1
Substrate
Product 20]
Product 21
BH3
BH3
16a
P
P
H
(R = Me)
NEt2
Reduction of P-N bond in (RP)-19c followed by an addition of a
proton source afforded the corresponding secondary phosphine-
borane (SP)-20c with moderate yield and variable ratio of
enantiomers. Unfortunately, it appeared that the product is
configurationally unstable in the solution and undergoes slow
racemization at room temperature (Figure 2).
20a (35 %)
21a (20 %)
BH3
BH3
P
2
3
16b
(R = Et)
P
NEt2
21b (20 %)
H
20b (32 %)
BH3
P
BH3
P
16c
(R = CH2Ph)
Figure 2. Rate of racemization[a] of (SP)-20c
Bn
Bn
NEt2
H
21c (8%)
20c (45 %)
BH3
4
5
6
7
16d
(R = 1-propynyl)
P
H
20d (10 %)
BH3
P
BH3
16e
(R = 1-propenyl)
P
NEt2
21e (15 %)
H
20d (22 %)
BH3
BH3
16f
(R =
(CH2)2CH=CH2)
(R = homoallyl)
16g
P
P
NEt2
H
20f (4 %)
21f (16 %)
No reaction
CH2COOMe
[a]: Ee’s of isolated pure (SP)-20c were measured with Diacel Chiralcel
OD-H column with 1 mL flow of hexane:iPrOH - 98:2 as eluent.
8[a] 16c
(R = CH2Ph)
The first determination of enantiomeric excess of the product
was taken shortly after the completion of the reaction and this
value was different from enantiomeric excess measured after the
purification of the compound using column chromatography. Thus,
the rate of racemization of (SP)-20c was analysed with chiral HPLC
and showed a continuous decrease of the enantiomeric excess of
(SP)-20c as a function of time.
[a] Ethyl bromide was used instead of NH4Cl.
Our previous study on the reactivity of phosphinous acid-borane
amides showed that these compounds undergo rather
dearomatization of the arene substituents.[23] In the studied cases,
however, it appeared that substrates underwent two competitive
reactions: P-N bond cleavage and Birch reduction (Table 3, Entries
1-3). The constitution of the reaction mixture suggested that amide
group cleavage dominates in these examples. Compounds
possessing the conjugated double or triple bond additionally
underwent multiple bond saturation under the reaction conditions
(Table 3, Entries 4 and 5) but not when the double bond was
This observation suggests that the most appropriate
transformation of phosphinous acid-amide into the corresponding
tertiary phosphine-borane would be the one-pot reduction-
alkylation as in this case the configurational stability of the formed
Submitted to the European Journal of Organic Chemistry
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10.1002/ejoc.201800065
European Journal of Organic Chemistry
P-anion should be controlled by the temperature. To prove this,
reduction-alkylation of (RP)-19c has been attempted (Scheme 10).
In summary, a new methodology leading to non-racemic
P-stereogenic organophosphorous compounds with the stereogenic
center located at the phosphorus atom has been developed. The use
of a readily available L-menthol as a chiral auxiliary allow the
preparation of diastereomerically pure phenylphosphonous acid-
borane monoester monoamide. This compound serve as a versatile
substrate for the synthesis of both secondary and tertiary
phosphine-boranes in a non-racemic form. It was found, that the
transformation of phosphinous acid-borane amides into the
BH3
P
BH3
P
[]D = +53,8o
1. Na (2.5 equiv.)
2. EtBr (2 equiv.)
(c 0,57 CHCl3)
NEt2
NH3/THF
-78oC
(RP)-19c
(RP)-22
33 %
96% ee
97% ee
Scheme 10. Stereospecific P-N bond cleavage/alkylation of (RP)-19c.
corresponding
phosphine-boranes
could
be
performed
straightforward using a solution of an alkali metal in liquid
ammonia. Under these conditions, amido group cleavage occurs
leading to the corresponding P-anion which can further react with
the appropriate electrophile. This method exhibit higher level of
stereospecificity compared to alcoholysis-nucleophilic substitution
or alcoholysis-P-O bond cleavage-alkylation sequences.
Cleavage of P-N bond in phosphinous acid-borane amide (RP)-
19c followed by alkylation with ethyl bromide afforded (RP)-22
with moderate yield but with excellent stereoselectivity proving the
high stereospecificity of this transformation. Regarding that
phosphorus-heteroatom bond cleavage with an alkali metal
proceeds with the retention of the configuration, the absolute
configuration at phosphorus in 22 has been ascribed as RP. In
theory, structurally the same product could be obtained using the
method reported by Jugé and co workers[14] which relies on the
methanolysis of P-N bond and the subsequent nucleophilic
substitution or P-O bond cleavage-alkylation. In the former case
the product should be obtained as the same enantiomer due to the
double inversion of configuration during both methanolysis and
reaction with an organometallic reagent. In the latter case the
product should be obtained as an opposite enantiomer as here only
single inversion of configuration will take place. Therefore,
transformation of (RP)-19c into (SP)-22 using methanolysis has
been attempted (Scheme 11).
Experimental Section
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. All chemicals were used as received unless
otherwise noted. Solvents for chromatography and crystallization were
distilled once before the use and the solvents for extraction were used as
received. Tetrahydrofuran and diethyl ether were dried over
sodium/benzophenone ketyl.
NMR spectra were recorded with Bruker Ascend (500 MHz) and Varian
Mercury (400 MHz) spectrometers in CDCl3 as a solvent at room
temperature unless otherwise noted. Chemical shifts (δ) are reported in ppm
relative to residual solvent peak. IR spectra were recorded with Thermo
Scientific Nicolet with ATR adapter with diamond prism (4000 – 300 cm-1).
Mass spectra were recorded on Shimadzu GC-MS QP2010S spectrometer
working in electron ionization (EI) mode using Phenomenex Zebron ZB-
35HT INFERNO column (pressure –65.0 kPa, total flow - 33.9 ml/min,
column flow - 1.0 mL/min, linear velocity –36.8 cm/sec, split - 30,
temperature program (80˚C - hold 1 min, 80-300oC/25oC/min - hold 1 min,
BH3
P
BH3
P
MeOH
H2SO4 cat.
NEt2
OMe
60oC, 16 h
70 %
(RP)-19c
(SP)-23
300-340oC/18 oC/min
- hold 2 min - total 15 min)). Thin-layer
96% ee
chromatography (TLC) was performed with precoated silica gel plates and
visualized by UV light or KMnO4 solution. The reaction mixtures were
purified by column chromatography over silica gel (60-240 mesh). The
intensity of X-ray diffraction reflections for 14 were measured at 120(2) K
on a SuperNova diffractometer equiped with the microfucus X-ray source
(Cu K,  = 1.54184 Å) and CCD detector. The CRYSALIS program
system was used for data collection, cell refinement and data reduction. The
data were corrected for Lorentz and polarization effects. A multi-scan
absorption correction was applied. The structure was solved using direct
methods implemented in the SHELXS-97, and refined with the SHELXL-97
program.
BH3
1. Na (2.5 equiv.)
2. EtBr (2 equiv.)
[]D = -43.2o
(c 0.36 CHCl3)
P
NH3/THF
-78oC
(SP)-22
90% ee
21 %
Scheme 11The synthesis of (SP)-22 from (RP)-19c.
Compound (RP)-19c has been submitted to reaction with
MeOH in the presence of a catalytic amount of acid which afforded
(SP)-23 in good yield. Treatment of this compound with sodium in
NH3/THF followed by an addition of EtBr led to (SP)-22 in
moderate yield. It should be also noted, that this sequence proceeds
with small degree of racemization at phosphorus which is not the
case for one-pot reduction-alkylation of (RP)-19c. Nevertheless, the
combination of two approaches give a powerful tool in the
synthesis of both enantiomers of P-stereogenic tertiary phosphine-
boranes in a non-racemic form.
The synthesis of phenylphosphonous acid-borane L-menthyl ester
N,N-diethylamide (rac-13). In a flame-dried three-necked flask (1 L)
DCM was placed (200 mL), then PhPCl2 (5.000 g, 27.93 mmol, 3.79 mL)
and triethylamine (2.820 g, 27.93 mmol, 3.89 mL) were added. After 5 min,
a solution of L-menthol (4.360 g, 27.93 mmol) in diethyl ether (10 mL) was
added through a syringe using a septum cap. After an addition was finished,
the mixture was left to stir for 3 h at room temperature. Then, a solution of
diethylamine (4.090 g, 55.87 mmol, 5.75 mL) in DCM (10 mL) was added
a through syringe. After an addition was complete, the mixture was left to
stir for 3 h at room temperature. Then, BH3-THF (41.9 mL, 41.9 mmol)
was added and the mixture was left to stir overnight at room temperature.
The reaction was quenched by addition of solid NH4Cl (10 g). The whole
reaction was concentrated under reduced pressure and the obtained slurry
Conclusions
Submitted to the European Journal of Organic Chemistry
5
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800065
European Journal of Organic Chemistry
was placed on sintered glass filter and flushed with diethyl ether (3x60 mL).
The filtrate was again concentrated under reduced pressure and the residual
syrup was purified with column chromatography on silica gel using
hexane:acetone (50:1) yielding 9.66 g (99%) of rac-13 as a mixture of two
= 0.46 (hexane:acetone - 50:1). 1H NMR (500 MHz, CDCl3): δ = 0.36-1.02
(m, 3H), 1.06 (t, JH-H = 7.0 Hz, 6H), 1.39 (t, JH-H = 7.1 Hz, 3H), 3.05-3.21
(m, 4H), 3.95-4.04 (m, 1H), 4.10-4.20 (m, 1H), 7.40-7.51 (m, 3H), 7.66-
7.73 (m, 2H) ppm. 13C NMR (126 MHz, CDCl3): δ = 14.2 (d, JP–C = 1.8 Hz),
16.4 (d, JP–C = 6.4 Hz), 39.8 (d, JP–C = 4.5 Hz), 61.5 (d, JP–C = 2.7 Hz),
128.2 (d, JP–C = 10.9 Hz), 130.9 (d, JP–C = 1.8 Hz), 131.0 (d, JP–C = 10.9 Hz),
133.0 (d, JP–C = 94.5 Hz) ppm. 31P NMR (202 MHz, CDCl3): δ = 109.82
ppm. IR (ATR) : 2972, 2378, 1381, 1176, 1069, 948, 702, 600. GC
(Phenomenex Zebron ZB-35 HT Inferno): RT = 6.15 min. GC-MS (EI, 70
eV): m/z (%) = 225 (52) (M-BH3), 196 (32), 182 (30), 153 (53), 148 (40),
140 (14), 134 (70), 125 (55), 120 (100), 109 (41), 58 (20), 47 (46). HRMS
C12H23NOP [M-BH3+H] meas. 226.1359, pred. 226.1355
1
diastereomers. Colorless oil. RF = 0.61 (hexane:acetone - 50:1). H NMR
(500 MHz, CDCl3): δ = 0.36–1.14 (bm, 3H), 0.83 (d, JH–H = 6.94 Hz, 3H),
0.86–0.93 (m, 1H), 0.94–0.97 (m, 6H), 1.05 (t, JH–H = 7.1 Hz, 6H), 1.08–
1.24 (m, 2H), 1.40–1.47 (m, 1H), 1.47–1.57 (m, 1H), 1.67–1.74 (m, 2H),
2.13–2.19 (m, 1H), 2.23–2.31 (m, 1H), 2.99–3.09 (m, 2H), 3.12–3.22 (m,
2H), 4.25–4.32 (m, 1H), 7.41–7.48 (m, 3H), 7.67–7.73 (m, 2H) ppm. 13C
NMR (126 MHz, CDCl3): δ =14.0 (d, JP–C = 1.8 Hz), 15.8, 21.3, 22.2, 22.7,
25.4, 31.4, 34.1, 40.0 (d, JP–C = 3.6 Hz), 43.6, 49.2 (d, JP–C = 7.3 Hz), 77.8
(d, JP–C = 3.6 Hz), 128.2 (d, JP–C = 10.9 Hz), 130.7 (d, JP–C = 1.8 Hz), 131.0
(d, JP–C = 10.9 Hz), 133.8 (d, JP–C = 97.2 Hz) ppm. 31P NMR (202 MHz,
CDCl3): δ = 106.88, 108.73 ppm. IR (ATR) 2926, 2378, 1436, 1397, 1205,
1178, 1009, 951, 925, 696, 683, 614, 475. GC (Phenomenex Zebron ZB-35
HT Inferno): RT = 8.78 min. GC-MS (EI, 70 eV): m/z (%) = 349 (M) (0.5),
198 (62), 197 (24), 120 (20), 106 (100), 72 (52), 58 (70), 55 (29). HRMS
C20H34NOP [M-BH3+H] meas. 336.2444, pred. 336.2451.
General procedure for the P-O bond cleavage of phosphonous acid-
borane monoester monoamides 14 and 15. Through a flame-dried three-
necked 100 mL round-bottom flask, immensed in acetone-dry ice bath and
equipped with magnetic stirrer, inert gas inlet and coldfinger with dry ice-
acetone mixture gaseous ammonia was passes until 15 mL of it was
condensed. Then, sodium (0.029 g, 1.25 mmol) was added and the mixture
o
Preparation of (RP)-phenylphosphonous acid-borane L-menthyl ester
N,N-diethylamide (RP-14)
was allowed to stir at -78 C for 15 min. Once all sodium was dissolved, a
solution of phosphonous acid-borane monoester monoamide (0.5 mmol) in
THF (5 mL) was added at once and the mixture was allowed to stir at -78
oC for 5 min. Then, an electrophile (1.0 mmol) was added and the reaction
In 100 mL flask 9.660 g (27.65 mmol) of (rac-13) was placed and ca. 30-50
mL of hexane and diethyl ether (1:1 v/v) mixture was added. The obtained
mixture was placed in -78°C. After few days crystals started to appear, and
after 2 weeks crystals were separated from solution and washed with small
amount of cold hexane-diethyl ether (1:1 v/v) affording 4.440 g (12.72
mmol) of (RP-14) as colourless crystals. RF = 0.61 (hexane:acetone - 50:1)
°
was left for 15 min at -78 C. The reaction was quenched by addition of
solid NH4Cl (0.5 g), ammonia was removed from the reaction mixture
under water pump and the residue was filtered, the solids were washed with
DCM (2x10 mL) and the filtrate was concentrated using rotary evaporator.
The residue was purified by flash column chromatography.
1
Mp = 84.4-85.9 °C. []D = -33.75 (c 0.945, CHCl3). H NMR (500 MHz,
CDCl3): δ = 0.35-1.05 (bm, 3H), 0.80-0.85 (m, 3H), 0.84-0.93 (m, 2H),
0.93-0.97 (m, 6H), 1.03-1.07 (m, 6H), 1.08-1.19 (m, 2H), 1.40-1.46 (m,
1H), 1.46-1.55 (m, 1H), 1.67-1.74 (m, 1H), 2.13-2.18 (m, 1H), 2.22-2.30
(m, 1H), 2.99-3.09 (m, 2H), 3.12-3.22 (m, 2H), 4.24-4.32 (m, 1H), 7.41-
7.48 (m, 3H), 7.67-7.72 (m, 2H) ppm. 13C NMR (126 MHz, CDCl3): δ =
14.0, 15.8, 21.3, 22.2, 22.7, 25.4, 31.4, 34.1, 40.0 (d, JP–C = 3.6 Hz), 43.6,
49.2 (d, JP–C = 7.3 Hz), 77.8 (d, JP–C = 3.6 Hz), 128.2 (d, JP–C = 11.8 Hz),
130.7 (d, JP–C = 1.8 Hz), 131.0 (d, JP–C = 11.8 Hz), 133.9 (d, JP–C = 96.3 Hz)
ppm. 31P NMR (202 MHz, CDCl3): δ = 106.88 ppm. GC (Phenomenex
Zebron ZB-35 HT Inferno): RT = 8.78 min. GC-MS (EI, 70 eV): m/z (%) =
349 (M) (0.5), 198 (62), 197 (24), 120 (20), 106 (100), 72 (52), 58 (70), 55
(29). HRMS C20H34NOP [M-BH3+H] meas. 336.2444, pred. 336.2451.
Crystal data for (RP-14) C20H37BNOP, Mw = 349.29, crystal system
monoclinic, space group P21, unit cell dimensions a = 11.813(2) Ǻ, b =
10.208(2) Ǻ, c = 18.457(3) Ǻ,  = 107.67(2)°, V = 2120.7(6) Ǻ3, Z = 4,
D(calcd) = 1.094 g/cm3, m = 1.173 mm-1, F(000) = 768. Final R indices [I >
2(I)] R1 = 0.0295, wR2 = 0.0680. Absolute structure parameter 0.006(15).
No. CCDC 1814511.
Methylphenylphosphinous acid-borane N,N-diethylamide (16a). This
compound was prepared according to General Procedure from 15 (0.120 g,
0.5 mmol), sodium (0.029 g, 1.25 mmol) and methyl iodide (0.062 mL, 1.0
mmol). Yield 0.093 g (89%). Colorless oil. RF = 0.29 (hexane:acetone -
1
50:1). H NMR (400 MHz, CDCl3): δ = 0.31–1.56 (m, 3H), 1.05 (t, JH–H
=
7.0 Hz, 6H), 1.68 (d, JP–H = 9.1 Hz, 3H), 3.02–3.12 (m, 4H), 7.41–7.45 (m,
3H), 7.57–7.62 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 12.7 (d, JP–
C = 44.3 Hz), 14.3 (d, JP–C = 12.4 Hz), 40.3 (JP–C = 3.2 Hz), 128.4 (d, JP–C
9.8 Hz), 130.1 (d, JP–C = 10.1 Hz), 130.5 (d, JP–C = 2.3 Hz), 133.9 (d, JP–C
=
=
62.4 Hz) ppm. 31P NMR (162 MHz, CDCl3): δ = 61.99 ppm. IR (ATR)
2969, 2379, 1397, 1178, 1027, 942, 703, 588. GC (Phenomenex Zebron
ZB-35 HT Inferno): RT = 5.89 min. GC-MS (EI, 70 eV): m/z (%) = 195 (32)
(M), 180 (71), 152 (43), 123 (86), 121 (44), 109 (100), 104 (57), 77 (23), 72
(47), 70 (48), 58 (46). HRMS C11H18NP [M-BH3+H]: meas. 196.1254, pred.
196.1250.
Ethylphenylphosphinous acid-borane N,N-diethylamide (16b). This
compound was prepared according to General Procedure from 15 (0.120 g,
0.5 mmol), sodium (0.029 g, 1.25 mmol) and ethyl bromide (0.075 mL, 1.0
mmol). Yield 0.085 g (76%). Colorless oil. RF = 0.29 (hexane:acetone -
The synthesis of phenylphosphonous acid-borane ethyl ester
N,N-diethylamide (15). In a flame-dried three-necked flask (1 L) DCM
was placed (200 mL), then PhPCl2 (5.000 g, 27.93 mmol, 3.79 mL) and
triethylamine (2.820 g, 27.93 mmol, 3.89 mL) were added. After 5 min, a
solution of ethanol (1.280 g, 27.93 mmol, 1.63 mL) in diethyl ether (10
mL) was added through a syringe using a septum cap. After an addition was
finished, the mixture was left to stir for 3 h at room temperature. Then, a
solution of diethylamine (4.090 g, 55.87 mmol, 5.75 mL) in DCM (10 mL)
was added through a syringe. After an addition was complete, the mixture
was left to stir for 3 h in room temperature. Then, BH3-THF (41.9 mL, 41.9
mmol) was added and the mixture was left to stir overnight at room
temperature. The reaction was quenched by addition of solid NH4Cl. The
whole reaction was concentrated under reduced pressure and the obtained
slurry was placed on sintered glass filter and flushed with diethyl ether
(3x60 mL). The filtrate was again concentrated under reduced pressure and
the residual syrup was purified with column chromatography on silica gel
using hexane:acetone (50:1) yielding 6.340 g (95%) of 15. Colorless oil. RF
50:1). 1H NMR (500 MHz, CDCl3): δ = 0.38–1.02 (bm, 3H), 1.05 (t, JH–H
=
7.1 Hz, 6H), 1.24 (dt, JP–H = 17.3 Hz, JH–H = 7.6 Hz, 3H), 1.93–2.03 (m,
1H), 2.06–2.18 (m, 1H), 3.01–3.16 (m, 4H), 7.40–7.46 (m, 3H), 7.59–7.65
(m, 2H) ppm. 13C NMR (126 MHz, CDCl3): δ = 6.8, 14.3 (d, JP–C = 1.8 Hz),
18.6 (d, JP–C = 45.4 Hz), 40.6 (d, JP–C = 2.7 Hz), 128.4 (d, JP–C = 10.0 Hz),
130.4 (d, JP–C = 6.4 Hz), 130.5 (d, JP–C = 4.5 Hz), 133.6 (d, JP–C = 58.1 Hz)
ppm. 31P NMR (202 MHz, CDCl3): δ = 69.64 ppm. IR(ATR) 2969, 2378,
1378, 1176, 1027, 999, 939, 789, 756, 734, 698, 579. GC (Phenomenex
Zebron ZB-35 HT Inferno): RT = 6.25 min. GC-MS (EI, 70 eV): m/z (%) =
209 (16) (M), 181 (7), 180 (69), 109 (100), 70 (34). HRMS C12H20NP [M-
BH3+H]:meas.210.1412, pred. 210.1406.
Benzylphenylphosphinous acid-borane N,N-diethylamide (16c). This
compound was prepared according to General Procedure from 15 (0.120 g,
0.5 mmol), sodium (0.029 g, 1.25 mmol) and benzyl chloride (0.115 mL,
1.0 mmol). Yield 0.141 g (99%). Colorless oil. RF = 0.31 (hexane:acetone -
50:1). 1H NMR (500 MHz, CDCl3): δ = 0.39-1.12 (bm, 3H), 0.82 (t, JH–H
=
Submitted to the European Journal of Organic Chemistry
6
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800065
European Journal of Organic Chemistry
7.0 Hz, 6H), 3.36 (dd, JH–H = 3.8 Hz, JP–H = 14.1 Hz, 1H), 3.59 (dd, JH–H
=
CDCl3): δ = 0.48-0.92 (m, 3H), 1.07 (t, JH–H = 7.2 Hz, 6H), 3.06-3.20 (m,
5H), 3.21-3.27 (m, 1H), 3.74 (s, 3H), 7.45-7.51 (m, 3H), 7.63-7.71 (m, 2H)
ppm. 13C NMR (126 MHz, CDCl3): δ =14.1, 34.3 (d, JP–C = 26.5 Hz), 40.9
(d, JP–C = 3.3 Hz), 52.3, 128.7 (d, JP–C = 10.0 Hz), 130.5 (d, JP–C = 10.0 Hz),
131.1 (d, JP–C = 2.2 Hz), 132.0 (d, JP–C = 67.4 Hz), 167.9 (d, JP–C = 2.2 Hz)
ppm. 31P NMR (162 MHz, CDCl3): δ = 66.65 ppm. IR (ATR) 2971, 2379,
1733, 1434, 1265, 1023, 944, 699, 566. GC (Phenomenex Zebron ZB-35
HT Inferno): RT = 9.12 min. GC-MS (EI, 70 eV): m/z (%) = (M-BH3) 253
(0.2), 249 (16), 248 (100), 202 (81), 200 (62), 155 (18), 77 (24). HRMS
C13H20NO2P [M-BH3+H]: meas. 254.1297, pred. 254.1304.
1.5 Hz, JP–H = 14.1 Hz, 1H), 7.22–7.28 (m, 1H), 7.29–7.35 (m, 4H), 7.43–
7.50 (m, 3H), 7.67–7.72 (m, 2H) ppm. 13C NMR (126 MHz, CDCl3): δ =
13.9 (d, JP–C = 1.8 Hz), 33.6 (d, JP–C = 36.3 Hz), 40.7 (d, JP–C = 2.7 Hz),
126.7 (d, JP–C = 3.6 Hz), 128.1 (d, JP–C = 2.7 Hz), 128.5 (d, JP–C = 9.1 Hz),
130.5 (d, JP–C = 5.5 Hz), 130.6 (d, JP–C = 9.1 Hz), 130.72, 132.74 (d, JP–C
=
3.6 Hz), 133.8 (d, JP–C = 60.9 Hz) ppm. 31P NMR (202 MHz, CDCl3): δ =
68.09 ppm. IR (ATR) 2971, 2378, 1380, 1179, 1029, 699, 490. GC
(Phenomenex Zebron ZB-35 HT Inferno): RT = 10.25 min. GC-MS (EI, 70
eV): m/z (%) = 271 (2) (M), 180 (100), 109 (72), 70 (29), 65 (9). HRMS
C17H22NP [M-BH3+H]: meas. 272.1573, pred. 272.1563.
(1-Hydroxymethyl)phenylphosphinous acid-borane N,N-diethylamide
(16h). This compound was prepared according to General Procedure from
15 (0.2518 g, 1.05 mmol), sodium (0.060 g, 2.632 mmol) and
paraformaldehyde (0.063 g, 2.1 mmol). Yield 0.181 g (76%). Colorless oil.
Phenyl(1-propynyl)phosphinous acid-borane N,N-diethylamide (16d).
This compound was prepared according to General Procedure from 15
(0.120 g, 0.5 mmol), sodium (0.029 g, 1.25 mmol) and propargyl chloride
1
(0.072 mL, 1.0 mmol). Yield 0.075 g (64%). Light yellow paste. RF = 0.21
RF = 0.21 (hexane:acetone - 10:1). H NMR (500 MHz, CDCl3): δ = 0.38-
1
(hexane:acetone - 50:1). H NMR (500 MHz, CDCl3): δ = 1.06 (t, JH–H
=
0.99 (m, 3H), 1.09 (t, JH-H = 7.1 Hz, 6H), 2.18 (s, 1H), 3.06-3.22 (m, 4H),
4.19-4.29 (m, 2H), 7.43-7.51 (m, 3H), 7.60-7.66 (m, 2H) ppm. 13C NMR
(126 MHz, CDCl3): δ = 14.4, 40.9 (d, JP–C = 2.7 Hz), 59.5 (d, JP–C = 48.1
7.1 Hz, 6H), 2.12 (d, JP–H = 2.84 Hz, 3H) 3.07–3.16 (m, 4H) 7.43–7.51 (m,
3H) 7.78–7.84 (m, 2H) ppm. 13C NMR (126 MHz, CDCl3): δ = 5.1 (d, JP–C
= 1.8 Hz), 13.6 (d, JP–C = 2.7 Hz), 40.8 (d, JP–C = 2.7 Hz), 72.1 (d, JP–C
=
Hz), 128.7 (d, JP–C = 10.0 Hz), 130.5 (d, JP–C = 59.9 Hz), 130.7 (d, JP–C =
101.7 Hz), 105.4 (d, JP–C = 18.2 Hz), 128.4 (d, JP–C = 11.8 Hz), 130.8 (d, JP–
9.2 Hz), 131.1 (d, JP–C = 2.7 Hz) ppm. 31P NMR (202 MHz, CDCl3): δ =
66.6 ppm. IR (ATR) 3471, 2970, 2382, 1436, 1025, 701, 494. HRMS
C11H18NOP [M-BH3+H]: meas. 212.1196, pred. 212.1199.
= 11.8 Hz), 131.0 (d, JP–C = 1.8 Hz), 132.1 (d, JP–C = 84.5 Hz) ppm. 31P
C
NMR (202 MHz, CDCl3): δ = 49.21 ppm. IR (ATR) 3209, 2972, 2375,
2196, 1436, 1166, 1021, 700, 532. GC (Phenomenex Zebron ZB-35 HT
Inferno): RT = 10.82 min. GC-MS (EI, 70 eV): m/z (%) = 233 (M) (0.5), 166
(24), 148 (10), 147 (100), 145 (16). HRMS C13H18NP [M-BH3+H]: meas.
220.1259, pred. 220.1250.
(1-Hydroxyethyl)phenylphosphinous acid-borane N,N-diethylamide
(16i). This compound was prepared according to General Procedure from
15 (0.120 g, 0.5 mmol), sodium (0.029 g, 1.25 mmol) and acetaldehyde
(0.056 mL, 1.0 mmol). The compound was isolated as a mixture of
diastereomers. Yield 0.086 g (72%). Colorless oil.
Phenyl(1-propenyl)phosphinous
N,N-diethylamide
(16e).
This
compound was prepared according to General Procedure from 15 (0.120 g,
Major diastereomer: RF = 0.15 (hexane:acetone - 10:1). 1H NMR (500 MHz,
0.5 mmol), sodium (0.029 g, 1.25 mmol) and allyl chloride (0.081 mL, 1.0
CDCl3): δ = 0.37-0.89 (m, 3H), 1.09 (t, JH-H = 7.1 Hz, 6H), 1.49 (dd, JP-H =
mmol). Yield 0.098 g (83%). Colorless oil. RF = 0.27 (hexane:acetone -
15.4 Hz, JH-H = 6.9 Hz, 3H), 2.16 (bs, 1H), 3.12-3.28 (m, 4H), 4.57-4.68 (m,
1H), 7.42-7.50 (m, 3H), 7.66-7.71 (m, 2H) ppm. 13C NMR (126 MHz,
CDCl3): δ = 14.2, 18.1 (d, JP–C = 6.4 Hz), 41.2 (d, JP–C = 2.7 Hz), 65.6 (d,
JP–C = 47.2 Hz), 128.6 (d, JP–C = 10.0 Hz), 130.5 (d, JP–C = 37.2 Hz), 130.9
(d, JP–C = 1.9 Hz), 131.0 (d, JP–C = 35.4 Hz), 131.2 (d, JP–C = 9.1 Hz) ppm.
31P NMR (202 MHz, CDCl3): δ = 72.02 ppm. IR(ATR) 3488, 2970, 2379,
1378, 1173, 1062, 1024, 942, 697.
1
50:1). H NMR (500 MHz, CDCl3): δ = 0.45-0.95 (m, 3H), 1.05 (t, JH-H
=
6.9 Hz, 6H), 1.94-2.03 (m, 3H), 3.07-3.15 (m, 4H), 6.03-6.11 (m, 1H),
6.59-6.71 (m, 1H), 7.40-7.47 (m, 3H), 7.59-7.64 (m, 2H). 13C NMR (126
MHz, CDCl3): δ = 14.1 (d, JP–C = 2.7 Hz), 20.6 (d, JP–C = 16.3 Hz), 40.6 (d,
JP–C = 3.6 Hz), 122.1 (d, JP–C = 62.7 Hz), 128.3 (d, JP–C = 10.0 Hz), 130.5 (d,
JP–C = 2.7 Hz), 131.0 (d, JP–C = 10.0 Hz), 133.2 (d, JP–C = 67.2 Hz) ppm. 31
P
NMR (202 MHz, CDCl3): δ = 61.6 ppm. IR (ATR) 2969, 2378, 1633, 1436,
1379, 1177, 699, 591. GC (Phenomenex Zebron ZB-35 HT Inferno): RT =
6.67 min. GC-MS (EI, 70 eV): m/z (%) = 221 (1) (M), 181(10), 180 (93),
109 (100), 70 (41), 58 (8), 46 (8). HRMS C13H20NP [M-BH3+H]: meas.
222.1409, pred. 222.1406
Minor diastereomer:RF = 0.21 (hexane:acetone = 10:1). 1H NMR (500 MHz,
CDCl3): δ = 0.33-1.00 (m, 3H), 1.02 (t, JH-H = 6.9 Hz, 6H), 1.55 (dd, JP-H
=
13.9, JH-H = 6.9 Hz, 4H), 2.16 (bs, 1H), 2.98-3.12 (m, 4H), 4.57-4.68 (m,
1H), 7.42-7.50 (m, 3H), 7.78-7.84 (m, 2H) ppm. 13C NMR (126 MHz,
CDCl3): δ = 14.2, 18.3 (d, JP–C = 8.2 Hz), 41.2 (d, JP–C = 2.7 Hz), 63.6 (d,
JP–C = 50.0 Hz), 128.5 (d, JP–C = 10.0 Hz), 130.9 (d, JP–C = 1.8 Hz), 131.3 (d,
JP–C = 9.1 Hz) ppm. 31P NMR (202 MHz, CDCl3): δ = 70.83 ppm. HRMS
C12H20NOP [M-BH3+H]: meas. 226.1363, pred. 226.1355.
(But-1-en-4-yl)phenylphosphinous acid-borane N,N-diethylamide (16f).
This compound was prepared according to General Procedure from 15
(0.120 g, 0.5 mmol), sodium (0.029 g, 1.25 mmol) and homoallyl chloride
(0.091 g, 1.0 mmol). Yield 0.123 g (99%). Colorless oil. RF = 0.45
(hexane:acetone:THF - 50:1:1). 1H NMR (500 MHz, CDCl3): δ = 0.40-1.01
(m, 3H), 1.05 (t, JH-H = 7.1 Hz, 6H), 2.01-2.09 (m, 1H), 2.12-2.22 (m, 1H),
2.32 (br. s., 1H), 2.44-2.54 (m, 1H), 3.02-3.19 (m, 4H), 5.04 (dq, JH-H = 10.5,
1.1 Hz, 1H), 5.12 (dq, JH-H = 17.1, 1.7 Hz, 1H), 5.93 (ddt, JH-H = 17.0, 10.4,
6.3, 6.3Hz, 1H), 7.41-7.48 (m, 3H), 7.61-7.66 (m, 2H) ppm. 13C NMR (126
MHz, CDCl3): δ = 14.4 (d, JP–C = 1.8 Hz), 25.0 (d, JP–C = 42.7 Hz), 26.7 (d,
JP–C = 1.8 Hz), 40.7 (d, JP–C = 2.7 Hz), 114.9, 128.5 (d, JP–C = 9.1 Hz), 130.5
(d, JP–C = 9.1 Hz), 130.6 (d, JP–C = 2.7 Hz), 133.4 (d, JP–C = 59.0 Hz), 137.9
(d, JP–C = 16.3 Hz). 31P NMR (202 MHz, CDCl3): δ = 67.4 ppm. IR(ATR)
2970, 2378, 1640, 1379, 1178, 1023, 759, 582. GC (Phenomenex Zebron
ZB-35 HT Inferno): RT = 7.07 min. GC-MS (EI, 70 eV): m/z (%) = 234 (1)
(M), 180 (33), 164 (71), 163 (16), 109 (100), 70 (34). HRMS C14H22NP [M-
BH3+H]: meas. 236.1562, pred. 236.1563.
(1-Hydroxybenzyl)phenylphosphinous acid-borane N,N-diethylamide
(16j). This compound was prepared according to General Procedure from
15 (0.120 g, 0.5 mmol), sodium (0.029 g, 1.25 mmol) and benzaldehyde
(0.101 mL, 1.0 mmol). The compound was isolated as a mixture of
diastereomers. Yield 0.048 g (32%). Colorless oil.
Major diastereomer: RF = 0.23 (hexane:acetone - 10:1). 1H NMR (500
MHz, CDCl3): δ = 0.24-0.97 (bm, 3H), 1.02 (t, JP–C = 7.1 Hz, 6H), 3.16-
3.26 (m, 6H), 5.49-5.58 (m, 1H), 7.31-7.57 (m, 3H), 7.63-7.72 (m, 2H). 13
C
=
NMR (126 MHz, CDCl3): δ =14.0, 41.6 (d, JP–C = 2.72 Hz), 74.0 (d, JP–C
40.87 Hz), 127.7 (d, JP–C = 3.63 Hz), 127.8 (d, JP–C = 2.73 Hz), 128.4 (d, JP–
C = 9.08 Hz), 130.7 (d, JP–C = 1.82 Hz), 131.1 (d, JP–C = 59.95 Hz), 131.6 (d,
JP–C = 9.08 Hz), 137.1 ppm. 31P NMR (202 MHz, CDCl3): δ = 74.18 ppm.
IR(ATR) 2972, 2385, 1378, 1171, 1024, 942, 701, 486.
Minor diastereomer: RF = 0.13 (hexane:acetone - 10:1). 1H NMR (500
((Methoxycarbonyl)methyl)phenylphosphinous
acid-borane
N,N-
MHz, CDCl3): δ = 0.24-0.97 (bm, 3H), 0.70 (t, J= 6.9 Hz, 6H), 2.81-2.98
diethylamide (16g). This compound was prepared according to General
Procedure from 15 (0.126 g, 0.36 mmol), sodium (0.021 g, 0.901 mmol)
and methyl chloroacetate (0.064 mL, 0.72 mmol). Yield 0.067 g (69%).
Colorless oil. RF = 0.35 (hexane:EtOAc - 6:1). 1H NMR (500 MHz,
(m, 4H), 5.49-5.58 (m, 1H), 7.31-7.57 (m, 3H), 7.87-7.94 (m, 1H) ppm. 13
C
=
NMR (126 MHz, CDCl3): δ = 13.6, 41.3 (d, JP–C = 2.73 Hz), 70.7 (d, JP–C
41.78 Hz), 127.7 (d, JP–C = 3.63 Hz), 128.1, 128.5 (d, JP–C = 9.99 Hz), 129.3
(d, JP–C = 95.37 Hz), 130.7 (d, JP–C = 1.82 Hz), 131.1 (d, JP–C = 1.82 Hz),
Submitted to the European Journal of Organic Chemistry
7
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800065
European Journal of Organic Chemistry
131.1 (d, JP–C = 40.90 Hz), 131.3 (d, JP–C = 9.08 Hz), 137.5 (d, JP–C = 3.63
Hz) ppm. 31P NMR (202 MHz, CDCl3): δ = 73.25 ppm. HRMS C17H22NOP
[M-BH3+H]: meas. 288.1515, pred. 288.1512.
In a flame-dried argon filled Schlenk flask equipped with magnetic stirrer
(SP)-17 (0.075 g, 0.347mmol) was placed, then 5 mL of dry methanol and 3
drops of concentrated sulfuric acid were added. Reaction was left to stir in
oil bath at 60°C for overnight (ca 16 h). Then, solid K2CO3 was added in
amount sufficient to neutralize the acid. Next, solid Na2SO4 was added and
the mixture was filtered from solid. Supernatant was concentrated on the
rotary evaporator and the obtained slurry was purified using column
chromatography with hexane:ethyl acetate 10:1 as eluent yielding 0.035 g
(0.208 mmol) of (RP)-18 (60%).
(SP)-Methylphenylphosphinous acid-borane N,N-diethylamide (17, 19a).
This compound was prepared according to General Procedure from 14
(0.175 g, 0.5 mmol), sodium (0.029 g, 1.25 mmol) and methyl iodide
(0.062 mL, 1.0 mmol). Yield 0.103 g (99%). []D = -40.9 (c 0.75, CHCl3).
HPLC Chiralcel OD-H column, eluent: hexane:iPrOH 99:1, flow 0.25
mL/min, RT = 30.2 min. Other analytical data are in accordance with those
reported for racemic 16a.
(RP)-18-Methylphenylphosphinous acid-borane methyl ester Colorless
oil. []D = -87.47 (c 1.365, CHCl3). RF = 0.57 (hexane:ethyl acetate - 10:1).
1H NMR (500 MHz, CDCl3)  0.46-1.14 (m, 3H), 1.71 (d, JH-H = 9.5 Hz,
3H), 3.58 (d, JH-H = 12.3 Hz, 3H), 7.48-7.53 (m, 2H), 7.54-7.58 (m, 1H),
(SP)-Ethylphenylphosphinous acid-borane N,N-diethylamide (19b).
This compound was prepared according to General Procedure from 14
(0.175 g, 0.5 mmol), sodium (0.029 g, 1.25 mmol) and ethyl bromide
(0.075 mL, 1.0 mmol). Yield 0.087 g (78%). []D = -6.6 (c 3.395, CHCl3).
HPLC Chiralcel OJ-H column, eluent: hexane:iPrOH 95:5, flow 1.0
mL/min, RT = 16.0 min. Other analytical data are in accordance with those
reported for racemic 16b.
7.77-7.82 (m, 2H) ppm. 13C NMR (126 MHz, CDCl3)  16.0 (d, JP–C
47.2 Hz), 53.6 (d, JP–C = 3.6 Hz), 128.7 (d, JP–C = 10.0 Hz), 130.6 (d, JP–C
=
=
10.9 Hz), 131.7 (d, JP–C = 55.4 Hz), 132.1 (d, JP–C = 2.7 Hz) ppm. 31P NMR
(202 MHz, CDCl3) δ =113.00 ppm. HPLC Chiralcel OJ-H column, eluent:
hexane:iPrOH 90:10, flow 0.5 mL/min, RT = 19.6 min.
(SP)-Benzylphenylphosphinous acid-borane N,N-diethylamide (19c).
This compound was prepared according to General Procedure from 14
(0.175 g, 0.5 mmol), sodium (0.029 g, 1.25 mmol) and benzyl chloride
(0.115 mL, 1.0 mmol). Yield 0.141 g (99%). []D = 51.6 (c 1.2, CHCl3).
HPLC Chiralcel OD-H column, eluent: hexane:iPrOH 95:5, flow 1.0
mL/min, RT = 15.0 min. Other analytical data are in accordance with those
reported for racemic 16c.
General procedure for the reaction of phosphinous acid-borane amides
with a solution of sodium in liquid ammonia. Through a flame-dried
three-necked 100 mL round-bottom flask, immensed in acetone-dry ice
bath and equipped with magnetic stirrer, inert gas inlet and coldfinger with
dry ice-acetone mixture gaseous ammonia was passes until 15 mL of it was
condensed. Then, sodium (0.029 g, 1.25 mmol) was added and the mixture
o
(RP)-Phenyl(1-propynyl)phosphinous acid-borane N,N-diethylamide
(19d). This compound was prepared according to General Procedure from
14 (0.175 g, 0.5 mmol), sodium (0.029 g, 1.25 mmol) and propargyl
chloride (0.072 mL, 1.0 mmol). Yield 0.116 g (75%). []D = -22.0 (c 0.85,
CHCl3). HPLC Chiralcel AS-H column, eluent: hexane:iPrOH 98:2, flow
1.0 mL/min, RT = 10.9 min. Other analytical data are in accordance with
those reported for racemic 16d.
was allowed to stir at -78 C for 15 min. Once all sodium was dissolved, a
solution of phosphonous acid-borane monoester monoamide (0.5 mmol) in
THF (5 mL) was added at once and the mixture was allowed to stir at -78
oC for 5 min. The reaction was quenched by addition of solid NH4Cl (0.5 g),
ammonia was removed from the reaction mixture under water pump and the
residue was filtered, the solids were washed with DCM (2x10 mL) and the
filtrate was concentrated using rotary evaporator. The residue was purified
by flash column chromatography.
(SP)-Phenyl(1-propenyl)phosphinous acid-borane N,N-diethylamide
(19e). This compound was prepared according to General Procedure from
14 (0.175 g, 0.5 mmol), sodium (0.029 g, 1.25 mmol) and allyl chloride
(0.081 mL, 1.0 mmol). Yield 0.088 g (75%). []D = -25.5 (c 1.8, CHCl3).
HPLC Chiralcel OJ-H column, eluent: hexane:iPrOH 95:5, flow 1.0
mL/min, RT = 10.8 min. Other analytical data are in accordance with those
reported for racemic 16e.
Phenylmethylphosphine-borane (20a). This compound was prepared
according to General Procedure from 16a (0.068 g, 0.33 mmol), sodium
(0.019 g, 0.82 mmol). Yield 0.016 g (35%). Colorless oil. RF = 0.21
(hexane:MTBE - 25:1) 1H NMR (500 MHz, CDCl3):  0.49-1.16 (m,
3H), 1.63 (dd, JP-H = 11.2 Hz, JH-H = 6.0 Hz, 3H), 5.57 (d, JP-H = 371.1 Hz,
1H), 7.46-7.51 (m, 2H), 7.51-7.56 (m, 1H), 7.69-7.74 (m, 2H) ppm. 13C
NMR (126 MHz, CDCl3):  8.1 (d, JP–C = 39.1 Hz), 126.4 (d, JP–C = 56.3
Hz), 129.0 (d, JP–C = 10.9 Hz), 131.6 (d, JP–C = 2.7 Hz), 132.2 (d, JP–C = 9.1
Hz) ppm. 31P NMR (202 MHz, CDCl3):  -16.58 ppm. GC (Phenomenex
Zebron ZB-35 HT Inferno): RT = 3.43 min. GC-MS (EI, 70 eV): m/z (%) =
124 (100) (M-BH3), 109 (80), 108 (57), 107 (27), 79 (16), 78 (20), 77 (19),
51 (20). HRMS C7H9OP [2M+H] (the compound underwent transformation
into secondary phosphine oxide under the measurement conditions): meas.
281.0848, pred. 281.0855.
(SP)-(But-1-en-4-yl)phenylphosphinous acid-borane N,N-diethylamide
(19f). This compound was prepared according to General Procedure from
14 (0.138 g, 0.3954 mmol), sodium (0.022 g, 1.25 mmol) and homoallyl
bromide (0.106 g, 0.79 mmol). Yield 0.049 g (50%). []D = -1.8 (c 1.09,
CHCl3).HPLC Chiralcel OD-H column, eluent: hexane:iPrOH 98:2, flow
1.0 mL/min, RT = 10.8 min Other analytical data are in accordance with
those reported for racemic compound 16f.
(RP)-((Methoxycarbonyl)methyl)phenylphosphinous acid-borane N,N-
diethylamide (19g). This compound was prepared according to General
Procedure from 15 (0.175 g, 0.5 mmol), sodium (0.029 g, 1.25 mmol) and
methyl chloroacetate (0.072 mL, 1.0 mmol). Yield 0.105 g (79%).Colorless
oil. RF = 0.35 (hexane:EtOAc= 6:1). []D = -31.4 (c1.1, CHCl3). HPLC
Chiralcel OD-H column, eluent: hexane:iPrOH 95:5, flow 1.0 mL/min, RT
= 11.8 min Other analytical data are in accordance with those reported for
racemic 16g.
(Cyclohexa-2,5-dienyl)methylphosphinous acid-borane N,N-diethyl-
amide (21a). This compound was prepared according to General Procedure
from 16a (0.068 g, 0.33 mmol), sodium (0.019 g, 0.82 mmol). Yield 0.013
g (20%). Colorless oil. RF = 0.38 (hexane:MTBE - 0.38). 1H NMR (500
MHz, CDCl3): δ = 0.20-0.90 (m, 3H), 1.05 (t, J = 7.1 Hz, 6H), 1.41 (d, J =
8.7 Hz, 3H), 2.69-2.79 (m, 2H), 2.95-3.07 (m, 2H), 3.08-3.24 (m, 3H),
5.70-5.80 (m, 2H), 5.80-5.93 (m, 2H) ppm. 13C NMR (126 MHz, CDCl3): δ
= 9.5 (d, JP–C = 41.8 Hz), 14.6, 26.4 (d, JP–C = 5.4 Hz), 40.92 (d, JP–C = 1.9
Hz), 40.91 (d, JP–C = 31.8 Hz), 122.0 (d, JP–C = 5.4 Hz), 122.2 (d, JP–C = 5.4
Hz), 126.8 (d, JP–C = 8.2 Hz), 127.0 (d, JP–C = 8.2 Hz) ppm. 31P NMR (202
MHz, CDCl3) δ = 69.5 ppm. GC (Phenomenex Zebron ZB-35 HT Inferno):
RT = 5.91 min. GC-MS (EI, 70 eV): m/z (%) = 211 (1) (M), 78 (100), 77
(25), 56 (15), 52 (22), 51 (23), 50 (18). HRMS C11H20NP [M-BH3+H]:
meas.198.1411, pred. 198.1406.
(RP)-((1-Hydroxymethyl)phenylphosphinous acid-borane N,N-diethyl-
amide (19h).
This compound was prepared according to General Procedure from 14
(0.175 g, 0.5 mmol), sodium (0.029 g, 1.25 mmol) and and
paraformaldehyde (0.063 g, 1.0 mmol). Yield 0.089 g (79%). []D = -14.9°
(c 1.01, CHCl3). HPLC Chiralcel AS-H column, eluent: hexane:iPrOH 95:5,
flow 1.0 mL/min, RT = 25.9 min. Other analytical data are in accordance
with those reported for racemic 16h.
Ethylphenylphosphine-borane (20b) This compound was prepared
according to General Procedure from 16b (0.073 g, 0.33 mmol), sodium
(0.019 g, 0.84 mmol). Yield 0.016 g (32%). Colourless oil. RF = 0.29
Assignment of the absolute configuration of (RP)-14 through the
chemical correlation.
Submitted to the European Journal of Organic Chemistry
8
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800065
European Journal of Organic Chemistry
(hexane:MTBE - 25:1). 1H NMR (500 MHz, CDCl3)  0.45-1.09 (bm,
3H), 1.52-1.67 (m, 2H), 1.87-2.00 (m, 2H), 5.43 (d, JP-H = 367.3 Hz 1H),
7.51-7.58 (m, 2H), 7.68-7.73 (m, 3H) ppm. 13C NMR (126 MHz, CDCl3):
= 15.2 (d, JP–C = 12.7 Hz), 17.9 (d, JP–C = 2.7 Hz), 25.6 (d, JP–C = 35.4
3H), 1.17 (dt, J = 17.7, 7.5 Hz, 3H), 1.93-2.03 (m, 2H), 5.40 (d, JP–H
=
367.9 Hz, 1H), 7.42-7.56 (m, 3H), 7.66-7.73 (m, 2H) ppm. 13C NMR (126
MHz, CDCl3)  8.3 (d, JP–C = 3.6 Hz), 16.7 (d, JP–C = 36.3 Hz), 125.2 (d,
JP–C = 54.5 Hz), 128.8 (d, JP–C = 9.1 Hz), 131.5 (d, JP–C = 2.7 Hz), 132.7 (d,
JP–C = 8.2 Hz) ppm. 31P NMR (202 MHz, CDCl3)  1.08 ppm. GC
(Phenomenex Zebron ZB-35 HT Inferno): RT = 4.12 min. GC-MS (EI, 70
eV): m/z (%) = 138 (100) (M-BH3), 126 (19), 110 (55), 109 (83), 108 (96),
107 (42), 83 (23), 79 (23), 78 (47), 77 (19), 65 (19), 60 (19), 57 (24), 51
(27), 47 (18). HRMS C8H11OP [M+H] (the compound underwent
transformation into secondary phosphine oxide under the measurement
conditions): meas. 155.0622, pred. 155.0620.
Hz), 125.7 (d, JP–C = 55.4 Hz), 128.9 (d, JP–C = 10.0 Hz), 131.4 (d, JP–C
=
3.1 Hz), 131.5 (d, JP–C = 1.8 Hz), 132.5 (d, JP–C = 9.0 Hz), 132.7 (d, JP–C
=
9.1 Hz) ppm.31P NMR (202 MHz, CDCl3)  -3.94 ppm GC (Phenomenex
Zebron ZB-35 HT Inferno): RT = 7.53 min. GC-MS (EI, 70 eV) (compound
transforms into the secondary phosphine oxide under the measurement
conditions): m/z (%) = 168 (24) (M), 140 (70), 126 (29), 125 (100), 79 (66),
77 (26), 51 (20), 47 (51). HRMS C9H13OP [2M+H] (the compound
transforms into the secondary phosphine oxide under the measurement
conditions): meas. 337.1490, pred. 337.1481.
Ethyl(cyclohexa-2,5-dienyl)phosphinous acid-borane N,N-diethylamide
(21b). This compound was prepared according to General Procedure from
16b (0.073 g, 0.33 mmol), sodium (0.019 g, 0.84 mmol). Isolated as
inseparable mixture with substrate 16b. Yield 0.015 g (20%). Colorless oil.
Phenylpropylphosphinous acid-borane N,N-diethylamide (21e). This
compound was prepared according to General Procedure from 16e (0.094 g,
0.398 mmol), sodium (0.023 g, 0.996 mmol). Yield 0.014 g (20%).
Colorless oil. RF = 0.23 (hexane:MTBE - 25:1). 1H NMR (500 MHz,
CDCl3):  0.44-0.94 (m, 3H), 0.98-1.11 (m, 9H), 1.78-1.91 (m, 1H), 1.93-
2.02 (m, 1H), 2.07-2.16 (m, 1H), 2.17-2.26 (m, 1H), 3.03-3.20 (m, 4H),
7.41-7.49 (m, 3H), 7.64-7.73 (m, 2H) ppm. 13C NMR (126 MHz, CDCl3):
1
RF = 0.38 (hexane:MTBE - 25:1). H NMR (500 MHz, CDCl3):  0.17-
0.87 (m, 3H), 1.06 (t, JH-H = 7.1 Hz, 6H), 1.15 (dt, JP-H = 16.7 Hz, JH-H = 7.6
Hz, 3H), 1.59-1.67 (m, 1H), 1.88-1.97 (m, 1H), 2.70-2.78 (m, 2H), 2.99-
3.16 (m, 4H), 3.16-3.24 (m, 1H), 5.74-5.79 (m, 2H), 5.80-5.89 (m, 2H)
ppm. 13C NMR (126 MHz, CDCl3):  6.6, 14.5, 16.2 (d, JP–C = 42.7 Hz),
26.4 (d, JP–C = 4.5 Hz), 39.9 (d, JP–C = 32.7 Hz), 40.6 (d, JP–C = 1.8 Hz),
122.14, 122.18 (d, JP–C = 1.8 Hz), 126.80 (d, JP–C = 5.5 Hz), 126.80 (d, JP–C
= 11.8 Hz) ppm. 31P NMR (202 MHz, CDCl3):  77.97 ppm. GC
(Phenomenex Zebron ZB-35 HT Inferno): RT = 6.22 min. GC-MS (EI, 70
eV): m/z (%) = 211 (2) (M), 180 (58), 153 (47), 125 (18), 109 (100), 79
(28), 78 (85), 77 (40), 74 (15), 73 (21), 72 (97), 70 (42), 58 (72), 56 (52),
52 (20), 51 (30), 50 (19), 47 (34). HRMS C12H22NP [M-BH3+H]: meas.
212.1559, pred. 212.1563.
=14.3, 15.9 (d, JP–C = 2.7 Hz), 31.0 (d, JP–C = 40.9 Hz), 34.3 (d, JP–C
10.9 Hz), 40.6 (d, JP–C = 2.7 Hz), 128.4 (d, JP–C = 10.0 Hz), 130.5 (d, JP–C
=
=
10.7 Hz), 130.6 (d, JP–C = 9.1 Hz), 134.2 (d, JP–C = 57.2 Hz) ppm. 31P NMR
(202 MHz, CDCl3):  66.39 ppm. GC (Phenomenex Zebron ZB-35 HT
Inferno): RT = 11.08 min. GC-MS (EI, 70 eV): m/z (%) = 232 (6) (M), 218
(100), 191 (20), 186 (33), 185 (98), 183 (35), 139 (29), 109 (49), 108 (26),
107 (30), 91 (18), 78 (21), 77 (29). Elemental analysis for C13H25BNP:
Calc.: C 65.85; H 10.63; N 5.91; Meas. C 65.84; H 10.64; N 5.92.
(But-1-en-4-yl)phenylphosphine-borane (20f). This compound was
prepared according to General Procedure from 16f (0.060 g, 0.24 mmol),
sodium (0.014 g, 0.60 mmol). Yield 0.002 g (4%). Colorless oil. RF = 0.64
(hexane:ethyl acetate - 6:1). 1H NMR (500 MHz, CDCl3): = 0.45-1.22 (m,
3H), 1.98-2.11 (m, 2H), 2.23-2.41 (m, 2H), 5.03-5.11 (m, 2H), 5.03-5.11
(m, 1H), 5.48 (dm, JP-H = 369.8 Hz, 1H), 5.74-5.82 (m, 1H), 7.45-7.51 (m,
2H), 7.52-7.57 (m, 1H), 7.66-7.73 (m, 2H) ppm. 13C NMR (126 MHz,
CDCl3): = 22.9 (d, JP–C = 34.5 Hz), 28.1 (d, JP–C = 2.7 Hz), 116.2, 125.4
(d, JP–C = 55.4 Hz), 129.0 (d, JP–C = 10.0 Hz), 131.7 (d, JP–C = 2.7 Hz),
132.8 (d, JP–C = 9.1 Hz), 136.4 (d, JP–C = 11.8 Hz) ppm. 31P NMR (202
MHz, CDCl3): = -4.54 ppm. GC (Phenomenex Zebron ZB-35 HT
Inferno): RT = 6.29 min. GC-MS (EI, 70 eV): m/z (%) = 164 (100) (M-BH3),
163 (48), 136 (86), 123 (26), 109 (21), 108 (56), 106 (61), 91 (23), 78 (38),
57 (23), 51 (25). HRMS C10H13OP [M+H] (the compound tranforms into
the secondary phosphine oxide under the measurement conditions): meas.
181.0821, pred. 181.0777.
Benzylphenylphosphine-borane (20c).This compound was prepared
according to General Procedure from 16c (0.047 g, 0.16 mmol), sodium
(0.010 g, 0.041 mmol). Yield 0.016 g (45%). Colorless oil. RF = 0.38
(hexane:MTBE - 25:1). 1H NMR (500 MHz, CDCl3): δ = 0.51-1.20 (m, 3H),
3.15-3.24 (m, 1H), 3.35-3.42 (m, 1H), 5.49 (d, JP-H = 373.6 Hz, 1H), 6.97-
7.02 (m, 2H), 7.22-7.27 (m, 3H), 7.37-7.42 (m, 2H), 7.44-7.53 (m, 3H) ppm.
13C NMR (126 MHz, CDCl3): δ = 32.2 (d, JP–C = 30.9 Hz), 124.6 (d, JP–C
54.5 Hz), 127.1 (d, JP–C = 3.6 Hz), 128.6 (d, JP–C = 2.7 Hz), 128.7 (d, JP–C
10.0 Hz), 129.2 (d, JP–C = 4.5 Hz), 133.1 (d, JP–C = 8.2 Hz), 131.8 (d, JP–C
=
=
=
2.7 Hz), 133.2 (d, JP–C = 9.1 Hz) ppm.31P NMR (202 MHz, CDCl3): δ =
6.89 ppm. GC (Phenomenex Zebron ZB-35 HT Inferno): RT = 9.91 min.
GC-MS (EI, 70 eV) (compound tranforms into the secondary phosphine
oxide under the measurement conditions): m/z (%) = 216 (22) (M), 215
(21), 125 (58), 92 (29), 91 (100), 65 (19). HRMS C13H13OP [2M+H] (the
compound underwent transformation into secondary phosphine oxide under
the measurement conditions) meas. 433.1491, pred. 433.1481.
(Cyclohexa-2,5-dienyl)(but-1-en-4-yl)phosphinous acid-borane N,N-
diethylamide (21f). This compound was prepared according to General
Procedure from 16f (0.060 g, 0.24 mmol), sodium (0.014 g, 0.60 mmol).
Benzyl(cyclohexa-2,5-dienyl)phosphinous acid-borane N,N-diethyl-
amide (21c). This compound was prepared according to General Procedure
from 16c (0.047 g, 0.16 mmol), sodium (0.01 g, 0.041 mmol). Yield 0.004
g (8 %). Colorless oil. RF = 0.42 (hexane:MTBE - 25:1) 1H NMR (500 MHz,
CDCl3): δ = 0.21-0.75 (m, 3H), 0.85 (t, JH-H = 6.9 Hz, 6H), 2.74-2.83 (m,
2H), 2.96-3.11 (m, 5H), 3.33 (s, 2H), 5.78-5.83 (m, 1H), 5.89 (bs, 3H),
7.20-7.25 (m, 1H), 7.28-7.33 (m, 4H) ppm. 13C NMR (126 MHz; CDCl3 ):
1
Yield 0.010 g (16%). Colorless oil. RF = 0.437 (hexane:MTBE - 25:1). H
NMR (500 MHz, CDCl3): = 0.19-0.86 (m, 3H), 1.02-1.13 (m, 6H), 1.65-
1.75 (m, 1H), 1.93-2.08 (m, 1H), 2.13-2.23 (m, 1H), 2.37-2.48 (m, 1H),
2.68-2.81 (m, 2H), 2.98-3.18 (m, 4H), 3.17-3.26 (m, 1H), 4.98-5.11 (m,
2H), 5.73-5.81 (m, 2H), 5.81-5.92 (m, 3H) ppm.13C NMR (126 MHz,
CDCl3): = 14.5, 22.6 (d, JP–C = 40.0 Hz), 26.4 (d, JP–C = 4.5 Hz), 26.7,
40.2 (d, JP–C = 32.7 Hz), 40.7 (d, JP–C = 1.8 Hz), 114.8, 122.05, 122.06 (d,
JP–C = 10.9 Hz), 126.9 (d, JP–C = 4.5 Hz), 127.0 (d, JP–C = 3.6 Hz), 138.1 (d,
JP–C = 14.5 Hz) ppm. 31P NMR (202 MHz, CDCl3): = 75.51 ppm. GC
(Phenomenex Zebron ZB-35 HT Inferno): RT = 7.03 min. GC-MS (EI, 70
eV): m/z (%) = 237 (1) (M), 104 (42), 78 (100), 77 (29), 58 (21), 52 (20),
51 (22), 50 (18). HRMS C14H24NP [M-BH3+H]: meas. 238.1720,
pred .238.1719.
δ = 13.9, 26.5 (d, JP–C = 4.5 Hz), 31.5 (d, JP–C = 39.1 Hz), 40.1 (d, JP–C
=
31.8 Hz), 40.7, 121.9 (d, JP–C = 4.5 Hz), 122.0 (d, JP–C = 5.4 Hz), 126.6 (d,
JP–C = 2.7 Hz), 127.3 (d, JP–C = 8.2 Hz), 127.5 (d, JP–C = 9.1 Hz), 128.1 (d,
JP–C = 2.7 Hz), 130.3 (d, JP–C = 4.5 Hz), 133.1 (d, JP–C = 4.5 Hz) ppm. 31P
NMR (202 MHz, CDCl3): δ = 77.23 ppm. HRMS C17H24NP [M-BH3+H]:
meas. 274.1723, pred. 274.1719.
Phenyl(n-propyl)phosphine-borane (20d).This compound was prepared
according to General Procedure from 16d (0.069 g, 0.295 mmol), sodium
(0.017 g, 0.738 mmol). Isolated as inseparable mixture with substrate 16d
Yield 0.005 g (10%). Colorless oil. RF = 0.33 (hexane:MTBE - 25:1) 1H
NMR (500 MHz, CDCl3): 0.47-0.82 (m, 3H), 1.02 (t, JH-H = 7.3 Hz,
Benzylethylphenylphosphine-borane (22). This compound was prepared
according to General Procedure from 16c (0.059 g, 0.20 mmol), sodium
(0.012 g, 0.52 mmol). Yield 0.014 g (28%). White solid. Mp = 56.8-58.4 °C.
Submitted to the European Journal of Organic Chemistry
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10.1002/ejoc.201800065
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1
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RF = 0.25 (hexane:MTBE - 25:1). H NMR (500 MHz, CDCl3): = 0.40-
1.04 (m, 3H), 1.06-1.16 (m, 3H), 1.80-2.00 (m, 2H), 3.16-3.30 (m, 2H),
6.90-6.98 (m, 2H), 7.18-7.26 (m, 3H), 7.39-7.46 (m, 2H), 7.47-7.60 (m,
3H) ppm. 13C NMR(126 MHz, CDCl3): = 6.9, 16.5 (d, JP–C = 37.2 Hz),
34.4 (d, JP–C = 30.9 Hz), 126.8 (d, JP–C = 2.7 Hz), 127.1 (d, JP–C = 50.9 Hz),
128.2 (d, JP–C = 2.7 Hz), 128.5 (d, JP–C = 10.0 Hz), 129.8 (d, JP–C = 4.5 Hz),
131.3 (d, JP–C = 1.8 Hz), 132.32 (d, JP–C = 7.3 Hz), 132.38 (d, JP–C = 8.8 Hz)
ppm. 31P NMR (202 MHz, CDCl3): = 18.63 ppm. GC (Phenomenex
Zebron ZB-35 HT Inferno): RT = 8.34 min. GC-MS (EI, 70 eV): m/z (%) =
228 (49) (M), 227 (26), 200 (34), 109 (100), 91 (73), 65 (19). HRMS
C15H20BP [2M-H]: meas.483.2714, pred. 483.2702. HPLC Chiralcel OD-H
column, eluent: hexane:iPrOH 98:2, flow 0.5 mL/min, (R)-enantiomer: RT =
20.5 min. (S)-enantiomer: RT = 21.8 min.
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Benzylphenylphosphinous acid-borane methyl ester (SP)-23. This
compound was prepared according to General Procedure for the assignment
of the absolute configuration of 14 through chemical correlation. Colorless
oil. []D = -107.8 (c 1.85, CHCl3). RF = 0.57 (hexane:ethyl acetate - 6:1). 1H
NMR (500 MHz, CDCl3):  0.46-1.12 (m, 3H), 3.33 (dd, JP-H = 10.2, JH-H
= 1.7 Hz, 2H), 3.62 (d, JP-H = 11.7 Hz, 3H), 6.97-7.02 (m, 2H), 7.19-7.23
(m, 3H), 7.40-7.45 (m, 2H), 7.50-7.55 (m, 1H), 7.55-7.60 (m, 2H) ppm. 13
C
NMR (126 MHz, CDCl3):  38.9 (d, JP–C = 40.0 Hz), 54.2 (d, JP–C = 3.6
Hz), 126.8 (d, JP–C = 2.7 Hz), 128.1 (d, JP–C = 2.7 Hz), 128.4 (d, JP–C = 10.0
Hz), 130.24 (d, JP–C = 54.5 Hz), 130.25 (d, JP–C = 14.5 Hz), 131.05 (d, JP–C
= 10.9 Hz), 131.12 (d, JP–C = 5.7 Hz), 131.9 (d, JP–C = 2.7 Hz) ppm. 31P
NMR(202 MHz, CDCl3): = 114.10 ppm. GC (Phenomenex Zebron ZB-35
HT Inferno): RT = 7.95 min. GC-MS (EI, 70 eV): m/z (%) = 230 (18) (M),
139 (100), 109 (72). HRMS C14H18BOP [2M-H]: meas.487.2282, pred.
487.2287.
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Acknowledgments
Financial support from National Research Centre (research grant N N204
3539 40) is kindly acknowledged.
____________
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Entry for the Table of Contents
Asymmetric synthesis
Double
reductive cleavage/
alkylation
BH
BH
3
BH
P
3
3
crystalization
Adam Włodarczyk, Anna E. Kozioł
and Marek Stankevič*…….... Page No.
– Page No.
P
P
Ph
O
O
NEt
2
NEt
Et
2
1:1
>99% de
97% ee
L-Menthol was efficiently used as a
chiral auxiliary for the efficient and
enriched
phosphinous
acid-borane
L-Menthol–assisted synthesis of P-
stereogenic phosphinous acid amides and
phosphine-boranes
amides and secondary or tertiary
phosphine-boranes. The latter were
obtained through the sequential reductive
cleavage-alkylation process.
simple
synthesis
of
the
diastereomerically pure phosphonous
acid-borane monoester monoamide. This
compound has been used for the
synthesis of various enantiomerically
Keywords: L-Menthol / P-Stereogenic /
Reductive cleavage / Phosphinous acid-
borane amides / Stereospecific
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