Prolinol as a Chiral Auxiliary in Organophosphorus Chemistry

Article abstract of DOI:10.1002/ejoc.202100196

Several strategies for the development of the synthesis of P-chiral organophosphorus compounds with (L)-prolinol as a source of chirality have been examined. A reaction of L-prolinol with a set of different alkyl/arylphosphonous acid diamides led in most of the cases to the quantitative formation of the appropriate bicyclic oxazaphospholidines with complete diastereo and enantioselectivity. The latter were reacted with BH₃ complex and the formed borane analogues were submitted to structural modifications leading to tertiary phosphine-boranes. Additionally, the effectiveness of oxazaphospholidines as ligands in transition metal asymmetric catalysis has been tested in hydrogenation of dehydroaminoacid esters and imine.

Full text of DOI:10.1002/ejoc.202100196

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Prolinol as a Chiral Auxiliary in Organophosphorus
Chemistry
Anna E. Kozioł[a] and Adam Włodarczyk*[b]
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Several strategies for the development of the synthesis of P-
chiral organophosphorus compounds with (L)-prolinol as a
source of chirality have been examined. A reaction of L-prolinol
with a set of different alkyl/arylphosphonous acid diamides led
in most of the cases to the quantitative formation of the
appropriate bicyclic oxazaphospholidines with complete dia-
stereo and enantioselectivity. The latter were reacted with BH3
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complex and the formed borane analogues were submitted to
structural modifications leading to tertiary phosphine-boranes.
Additionally, the effectiveness of oxazaphospholidines as
ligands in transition metal asymmetric catalysis has been tested
in hydrogenation of dehydroaminoacid esters and imine.
Introduction
A constant search for novel and more efficient catalytic systems
(especially for asymmetric catalysis) lead to the development of
more and more sophisticated ligands what takes generally a lot
of time and efforts.[1] Constructing new scaffolds is usually
associated with the development of new strategies and the use
of new building blocks. On the other hand some obsolete
methods and molecules may still hide an interesting synthetic
potential.[2] Among them, numerous naturally occurring com-
pounds being excellent starting materials are still tested in
diastereodivergent processes.
Easy access to P-stereogenic organophosphorus compounds
is a key point in a broad range of chemical transformations.
Although there are several well-known synthetic methodologies
leading to these compounds, there is a constant interest in the
development of a new synthetic methods and new precursors
leading to the target molecules. In the end of 1980’s, Jugé and
co-workers have published a method of the synthesis of P-
stereogenic phosphines using ephedrine as a chiral auxiliary
(Scheme 1).[3]
Scheme 1. Method for the synthesis of chiral phosphine derivatives
developed by Jugé et al.
so the other research groups quickly adopted this methodology
for the synthesis of other structural motifs possessing P-
stereogenic phosphorus atom. One more important improve-
ment was introduced later on followed papers by Jugé and co-
workers: borane as protective group for phosphorous stereo-
center became an integral part of this methodology.[4] Riera and
Verdaguer have recently reported several papers describing
attempted construction of chiral phosphines starting from chiral
aminoalcohol attached via nitrogen atom (Scheme 2).[5]
Richter has reported that (L)-prolinol is an effective chiral
auxiliary able to differentiate P-epimers of organophosphorous
compounds. Despite its great utility,[6] prolinol was scarcely
used for chiral resolution of racemic mixtures of compounds
with stereogenic center located at phosphorous atom.[7] Even
though that the synthesis of P-chiral scaffolds raised on prolinol
More importantly, the process was run under dynamic
thermodynamic epimerization at the phosphorus atom what
allowed to obtain one diastereomer exclusively. The amino-
alcohol scaffold used in this transformation had few advantages
[a] Prof. A. E. Kozioł
Department of General and Coordination Chemistry and Crystalography,
Institute of Chemical Sciences,
Faculty of Chemistry
Maria Curie-Skłodowska University in Lublin
5 Maria Curie-Skłodowska sq.,
20-031 Lublin, Poland
[b] A. Włodarczyk
Department of Organic Chemistry,
Institute of Chemical Sciences,
Faculty of Chemistry
Maria Curie-Skłodowska University in Lublin
33 Gliniana st., 20-614
Lublin, Poland?.p
E-mail: adam.wlodarczyk@poczta.umcs.lublin
Scheme 2. Condensation of (1S,2R)-cis-1-amino-2-indanol with tert-butyl-
phosphine derivatives.
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is easy, only a few more reports form Buono and Jugé research
Reaction of PCl3 with excess of secondary amine should lead
to the appropriate diamidophosphorous acid chloride which
upon treatment with a Grignard reagent afforded the corre-
sponding (aryl/alkyl)phosphonous acid diamide. The latter
should undergo transamidation reaction with L-proline leading
to desired bicyclic oxazaphospholidines. A simple reaction of
PCl3 with organometallic species could be an alternative to the
proposed pathway although it is generally difficult to avoid the
formation of R2PCl species in a reaction between organometallic
reagent and PCl3. Separation of RPCl2 and R2PCl usually is a
complicated process due to high reactivity of products and
similar properties.
According to the scheme discussed above, PCl3 was
subjected to a reaction with 4-fold excess of diethylamine
which led to the formation of bis(N,N-diethylamino)
chlorophosphine 2 in good yield. Compound 2 has been
subjected in the next step to a reaction with a set of different
organometallic compounds (Table 1).
Generally, a reaction of Grignard reagents with 2 proceeded
efficiently affording the appropriate (aryl/alkyl)phosphonous
acid diamides in fair to good yields. The lower yields of 3b, 3e
and 3f may be associated with steric hindrance induced by
incoming nucleophile. Best proof for that hypothesis is
observed with a failed formation of mesityl-substituted 3g.
In the next step, transamidation reaction between (L)-
prolinol and a set of phosphonous diamides was attempted
(Scheme 5, Table 2).
It appeared that in most of cases the formation of desired
product occurred quantitatively, as judged by 31P NMR analysis
of the reaction mixture (Figure 1). Only in a case of mesityl
derivative there was no reaction at all, probably due to a high
steric hindrance caused by two ortho-methyl substituents. A
consistent observation was noted by Mezetti and co-workers,
where the bulky ortho-substituted lithiated arenes were non-
reactive towards the oxazaphospholidine-boranes derived from
ephedrine, modification of synthetic route resulted successful
transformation in their case.[9] Unfortunately in our instance this
procedure was not effective. Once the transamidation reaction
was completed, BH3*SMe2 complex was added in order to fix
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groups were published in past.[8]
Discussed literature records strongly rely on the formation
of rigid oxazaphospholidine scaffold. The conformational
stability of formed 5-membered heterocyclic structure is
beneficial for forecoming ring opening with a nucleophile,
determining the direction of nucleophile attack. The chemo-
selectivity of PÀ O vs PÀ N bond cleavage is also a very useful
advantage of this type compounds comparing them to eg.
chiral diol-based phosponates. An ease access to prolinol,
obtained from cheap and abundant proline, makes this
approach even more attractive because of formation of fused 5-
membered rings. Therefore, we decided to determine the
effectiveness of this chiral auxiliary in the synthesis of P-
stereogenic phosphines and their derivatives.
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Herein, we would like to present our results concerning the
synthesis of P-stereogenic oxazaphospholidines and their
borane derivatives along with their applications in the synthesis
and catalysis.
Results and Discussion
The basic concept of this research topic was the usage of easily
accessible reagents, available in large amounts, allowing to
obtain preparative quantities of P-chiral compounds
(Scheme 3). Here the designed synthetic path starts from PCl3,
and leads through phosphonous acid amide, which in an
exchange reaction with (L)-Prolinol defines a space orientation
of substituents. Intended complexation of electron lone pair
located at phosphorous atom, with borane, prevents the
oxidation as well as locks the stereogenic center in defined
configuration.
Afore mentioned phosphorous trichloride was a precursor
which should undergo double PÀ N bond formation prior to the
reaction with organometallic compound (Scheme 4).
Table 1. Yields of isolated phosphonous diamides.
Compound
R=
Yield
3a
3b
3c
3d
3e
3f
p-Tol
o-An
98
43
83
99
37
67
47
1-Nph
t-Bu
c-Hex
c-Pent
Mesityl
3g
Scheme 3. General concept for possessing P-stereogenic compounds de-
rived from (L)-Prolinol.
Scheme 4. Synthesis of a starting material.
Scheme 5. Synthesis of oxazaphospholidine boranes.
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Table 2. Yields of isolated oxazaphospholidine-boranes (6a–g).
1
2
R=
Yield (conv.)
[α]D =
(c=in CHCl3) [de]
3
100(100) [32%[a]]l
32(100)
14(100)
7(100)
36(100)
51(100)
0(0)
+123,1; (1,0) [100%de]
+87,1; (1,145) [100%de]
+49,5; (1,0) [100%de]
+76,6; (1,325) [100%de]
+66,9; (1,925) [100%de]
+73,9; (0,955) [100%de]
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p-Tol (6a)
o-An (6b)
1-Nph (6c)
t-Bu (6d)
c-Hex (6e)
c-Pent (6f)
Mesityl (6g)
[b]
–
[a] Yield of collected crystal. [b] No new signals in 31P NMR was observed, substrate remained unreacted.
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Figure 1. 31P NMR signals of respective compounds leading to formation of compound 6a.
the configuration at phosphorus but also to prevent the
oxidation of phosphorous atom. Final products were isolated
from the reaction mixtures with moderate yields, probably due
to partial decomposition during chromatographic purification.
Only one of them (6a) formed crystals suitable for an X-ray
structure analysis which allowed to determine the absolute
configuration at phosphorus atom as RP (Figure 2).
Preparation of oxazaphospholidine-borane with confirmed
configuration allowed us to perform a quick look at the PÀ O
bond cleavage with strong carbon nucleophiles.(Scheme 6) This
would allow to obtain the appropriate P-stereogenic phosphi-
nous acid-borane amides in a non-racemic form provided by
the SN2 mechanism. Already published reports are ambiguous
in their claims about obtained optical purity. Most of authors
declare that the phosphorus stereogenic center sustains its
Figure 2. Perspective view of molecular structure of (R)P-6a. Elipsoids are at
50% probability level.
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optical purity during the nucleophilic substitution reaction,
possible only with 6a and other analogues were completely
non-reactive. The same situation was observed with t-butyl-
lithium as nucleophile but, here, the steric crowd created by
alkyl group may play a crucial role.
The optimized conditions for PÀ Me bond formation were
applied for a set of previously obtained oxazaphospholidine-
boranes 6a–g (Scheme 7, Table 4).
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however in few reports partial racemization was noticed.[10] First,
a short screen over different organometallic reagents was run in
order to find the most effective nucleophile for this trans-
formation. León, Riera and Verdaguer reported an opening of
hindered oxazaphospholidine rings by nucleophilic substitution
of PÀ O bond with several organometallic reagents. In most
cases they observed a loss of diastereomeric excess to ca. 92%
de. The ephedrine-derived oxazaphospholidine-borane under-
goes organolithium compounds substitution in a diastereose-
lective manner preserving optical purity, thus we have decided
to try this procedure with our substrates.[8,10] In many literature
reports describing PÀ O bond cleavage via nucleophilic sub-
stitution of chiral oxazaphospholidines boranes only a slight
drop of optical purity was recorded.[8] (Table 3).
It appeared that only
a substrate possessing p-tolyl
substituent (7a) underwent a reaction with methyllithium
stereospecifically and with good yield (Table 4). Other sub-
strates underwent substitution reaction less efficiently or failed
to provide a product at all. This was the case for 6d with bulky
t-butyl substituent at phosphorus. This substituent most
probably create too high steric crowd around the electrophilic
phosphorus center thus the substrate becomes unreactive
under these conditions. For compounds possessing less bulky c-
hexyl and c-pentyl substituents attached to phosphorus (6f and
6g, respectively) the reaction proceeds with modest effective-
ness and the stereospecificity of the reaction is not complete.
Interestingly, a compound possessing smaller c-pentyl substitu-
ent (6g) afforded the product with lower stereospecificity than
the compound with larger c-hexyl group (6f). Compounds with
o-anisyl substituent (6b) afforded product with modest yields
and remarkable erosion of enantiomeric purity at phosphorus
center. Only in case of oxazaphospholidine-boranes possessing
p-tolyl and 1-naphtyl substituents at phosphorus products were
obtained with acceptable yields and with almost complete
retention of configuration at phosphorus.
In situ generated phosphineoxazoline (5a) was selected as
model substrate to perform reactions at tri-coordinated
phosphorus atom. Michaelis-Arbusov was chosed as a test
reaction. Publications form Jugé and co-workers reports that
analogous compounds derived from ephedrine afforded good
yields but with loss of optical purity at phosphorous.[6] Addi-
tional experiments, performed with compound 5a, mostly
afforded complex mixtures of undefined products, which after
isolation and purification were obtained in trace amounts.
Although the Michaelis-Arbusov reaction was described by
Buono and co-worker with similar structures,[7,11] many attempts
performed in our case gave poor results with complex reaction
mixtures or with traces amounts of products
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From a set of tested organometallic reagents organolithium
compounds provided the most satisfying results (Table 3, 7a
and 7aa). With methyllithium, the yield of 7a was found to be
78% and the reaction appeared to proceed with complete
stereospecificity. With phenyllithium the stereospecificity was
preserved albeit with lower yield of the product. Organozinc
compounds failed to give the desired substitution products,
same as Grignard reagents. On the other hand, treatment of 6a
with methylmagnesium bromide in toluene afforded the
corresponding 7a albeit in low yield and with a significant loss
of stereochemical information at phosphorus atom. Further
experiments showed that the reaction with phenyllithium was
Scheme 6. Cleavage of PÀ O bond with various organometallic reagents.
Table 3. Yields of PÀ O bond cleaving products.
Product
R=
Yield
This situation was observed in Michaelis-Arbusov reaction
with methyl iodide. (Scheme 8) Also, reactions of tricoordinated
oxazaphospholidine with organometallic reagent such as meth-
yl lithium and methyl magnesium bromide afforded the same
effects.
7a
7a
Zn(Me)2
Zn(Et)2
0
0
7a
7a
7a
7a
7aa
7ab
i-PrMgCl*LiCl
MeMgBr
MeMgBr[a]
MeLi
PhLi
t-BuLi
0
0
37 (dr 5:2)
78
60
0
°
[a] Reaction was run in toluene in 100 C.
Table 4. Yields of products of PÀ O bond substitution with methyllithium.
Product R=
Yield (de)
[α]D (c, CHCl3)
p-Tol (7a)
o-An (7b)
1-Nph (7c)
t-Bu (7d)
c-Hex (7e)
c-Pent (7f)
78 (100%de)
31 (62%de)
56 (98%de)
0[a]
34 (98%de)
47 (85%de)
À 16,5 (1,075)
À 1,01 (1,05)
À 3,35 (1,105)
–
À 6,15 (1,3)
+1,44 (1,45)
Scheme 7. Cleavage of PÀ O bond with methyllithium in 6.
[a] No product was observed
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Replacement of alkoxy group by an alkyl group can be also
reaction with methanol in the presence of sulfuric acid
(Scheme 10, Table 6).
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2
3
4
5
6
7
8
9
accomplished via a sequence of PÀ O bond cleavage with alkali
metals in liquid ammonia[12] followed by an alkylation with an
alkyl halide. The same set of substrates was therefore submitted
to a reaction with lithium in liquid ammonia followed by a
reaction with methyl iodide as an electrophile (Scheme 9,
Table 5). Products were obtained with poor yields and, even
more sadly, almost complete racemization was detected.
It was surprising to conclude that PÀ O bond cleavage by
methyllithium led to diastereomerically pure compounds in
only two cases. These results are quite interesting as usually a
cleavage of PÀ O bond proceeds with high degree of
stereospecificity.[12,13] It is difficult to conclude now, what is the
reason of such a behavior as the structure of the substrate
seems to lack any special interactions in the molecule.
Attempted synthesis of methyl esters 8 has been performed
as these compounds are convenient precursors for the synthesis
of chiral phosphine-boranes. Some loss of optical purity was
detected for compounds 8a and 8c whereas for 8e and 8f the
determination of enantiomeric excess was impossible by
chromatographic methods. All this caused that only one proved
experiment revealing the effectiveness of complete transforma-
tion from oxazaphosphoborolidine to chiral phosphine-borane
has been successfully completed (Scheme 11).
Albeit prolinol proved high effectiveness in differentiating
P-epimers, utility in further processes was much lower than
expected. A set of in situ prepared single diastereomers of
phoshinooxazolines were applied as ligands for asymmetric
hydrogenation of α-acetamidocinnamic acid methyl ester
(Scheme 12) and imine hydrogenation (Scheme 13).
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Compounds obtained in the above sequence were trans-
formed into phosphinous acid-borane methyl esters by a
Catalytic asymmetric hydrogenation reactions performed
with several ligands (5a–f) showed mostly good selectivity
Table 6. Isolated yields of 8a, 8c, 8e, and 8f.
Product
R=
Yield [%] ee
8a
8c
8e
8f
p-Tol
67 (82% ee)
1-Nph
c-Hex
c-Pent
25 (89% ee)
25 (unknown)[a]
33 (unknown)[a]
Scheme 8. Attempts for P-3 coordinated 5a and methyl reagents.
[a] Compounds do not absorb an UV-Vis spectrum, no signals were
detected on HPLC with UV-Vis detector.
Scheme 9. Sequence of reduction of PÀ O bond with alkaline metal in liquid
ammonia, followed by alkylation.
Table 5. Yields of reduction-alkylation sequence products.
Product
R=
Yield (de)
7a
7b
7c
7d
7e
7f
p-Tol
o-An
1-Nph
t-Bu
c-Hex
c-Pent
46 (26%de)
14 (100%de)
12 (10%de)
13 (12%de)[a]
12 (44%de)
21 (50%de)
[a] O-Methylated product was yielded.
Scheme 11. Synthesis of both enantiomers of methylphenyl(p-tolyl)
phosphine-borane (9).
Scheme 10. Synthesis of methylphosphinite boranes (8a–f).
Scheme 12. Catalytic asymmetric hydrogenation of α,β-unsaturated ester.
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Table 8. Imine catalytic asymmetric hydrogenation with various ligands.
1
2
Ligand
R=
Conversion
ee [%][a]
3
4
5
6
5a
5b
5c
5e
5f
p-Tol
o-An
1-Nph
c-Hex
c-Pent
100
100
100
100
100
100
2 (R)
8 (S)
79 (S)
83 (S)
3 (S)
2(R)
Scheme 13. Imine catalytic asymmetric hydrogenation with various ligands.
7
(R)P-9
p-TolPhPMe
Table 7. α,β-Unsaturated ester catalytic asymmetric hydrogenation with
various ligands.
8
9
[a] Absolute configuration was assigned with chiral stationary phase HPLC.
Ligand
R=
Conversion
ee [%][a]
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5a
5b
5c
5e
5f
p-Tol
o-An
1-Nph
c-Hex
c-Pent
p-TolPhPMe
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100
100
100
100
100
86 (S)
83 (S)
85 (S)
79 (S)
86 (S)
3(R)
and solvents for extraction were used as received. Tetrahydrofuran
and diethyl ether were dried by distillation from sodium/benzophe-
none ketyl.
NMR spectra were recorded with Bruker Ascend (500 MHz)
spectrometer at room temperature using CDCl3 as a solvent.
Chemical shifts (δ) are reported in ppm, and spectra were calibrated
using residual solvent peaks. High Resolution Mass spectra were
recorded with a Shimadzu IT-TOF spectrometer in electrospray
ionization (ESI). Optical rotations were masured with Perkin-Elmer
Polarimeter with sodium lamp (λ=589 nm). Thin-layer chromatog-
raphy (TLC) was carried out with precoated silica gel plates, which
were visualized using UV light or KMnO4 solution. Reaction mixtures
were purified by column chromatography on silica gel (60–
240 mesh). The intensities of X-ray diffraction reflections for 6a
were measured at 120(2) K with a SuperNova diffractometer
equipped with a microfocus X-ray source (Cu-Kα, λ=1.54184 Å)
(R)P-9
[a] Absolute configuration was assigned with chiral stationary phase HPLC
Daicell OJ-H column.
leading to individual enantiomers of hydrogenated products
with moderate to high ee values (Table 7). Considering that the
reaction conditions were adopted strictly from literature with-
out optimization, these results are optimistic towards further
trials. A narrow distribution of ee values suggest that the
asymmetric outcome of the reaction depends in major from the
structure of the ligand. In case of asymmetric hydrogenation of
imine (Scheme 13, Table 8) the enantiomers differentiation was
highly dependent from substituent at phosphorus atom. Bulky
substituents gave higher ee’s of the appropriate amine. We
omitted obvious experiments with ligands cluched with t-butyl
substituent, because after many unsuccessful attempts, we
decided to give up and summarize our efforts without this
representative.
and
a CCD (charge-coupled device) detector. The CRYSALIS
program system was used for data collection, cell refinement, and
data reduction. The data were corrected for Lorentz and polar-
ization effects. A multi-scan absorption correction was applied. The
structure was solved by direct methods implemented in the
SHELXS-97 program, and refined with SHELXL-97.
Chlorophosphonic acid bis(N,N)-diethylamide (2) prepared accord-
ing to Gilson B. H. et al. Canad. J. Chem. 2007, 1045–1052, and Qin
L. et al. Angew. Chem Int. Ed. 2012, 5915–5919. Analytical data were
in accordance with previously reported.
(L)-Prolinol (4) was prepared from (L)-Proline according to patent
WO 2006/025920. Analytical data are in accordance with previously
reported in literature.
Conclusion
General procedure for synthesis of phosphonic acid bis(N,N)-
diethylamides:
We have proved that the L-prolinol is an easily avialable chiral
auxiliary with a great efficiency for diastereoselective differ-
entiation of organophosphorus compounds. Difficult processing
of PÀ O and PÀ N bond cleavage were observed forcing us to
explore a field of catalysis with oxazaphospholidines as chiral
ligands. The results of test reactions were not outstanding but
did not discouraged us from applying those ligands to better
fitted reactions. Also, protection of phosphorous atom with BH3
group is not the best solution in here, thus essential
modifications of presented methodology are necessary and will
be described in further reports.
In a flame dried, argon filled 2 neck 250 mL flask equipped with a
stirring bar, 50 mL of dry THF was placed. Chlorophosphonic acid
bis(N,N)-diethylamide (2) was added to the solvent and flask was
chilled in acetone/CO2 bath. Previously prepared Grignard reagent
(2.0 equivalent) was added via canula to stirred solution in a period
of ca. 5 minutes. After the addition was complete flask was left to
stir in a room temperature overnight. The solution was filtered
under inert atmosphere through glass frit, solvent was evaporated
and the resulting oli was distilled on a short path apparatus under
reduced pressure.
p-Tollylphosphonic acid bis(N,N)-diethylamide (3a). Prepared ac-
cording to general procedure from p-TollylMgBr (30 mmol), and 2
°
(25 mmol) after distillation (120-125 C @ 2mmHg) yielded 6,52 g
(98% 24,5 mmol) as bright yellow oil. 1H NMR (500 MHz, CDCl3) δ=
1.13 (t, J=7.1 Hz, 12 H), 2.37 (s, 3 H), 3.06–3.16 (m, 8 H), 7.15–7.21
(m, 2 H), 7.32–7.37 (m, 2 H) ppm. 31P NMR (202 MHz, CDCl3) δ=
97.24 ppm. 13C NMR (126 MHz, CDCl3) δ=14.57 (d, J=3.6 Hz),
21.14, 42.67 (d, J=17.3 Hz), 128.91 (d, J=3.6 Hz), 130.95 (d, J=
Experimental Section
General Remarks: All reactions were carried out under an argon
atmosphere using Schlenk techniques. Only dry solvents were used,
and glassware was heated under vacuum before use. All chemicals
were used as received unless otherwise noted. Solvents for
chromatography and crystallization were distilled once before use,
Eur. J. Org. Chem. 2021, 1931–1941
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Full Papers
doi.org/10.1002/ejoc.202100196
16.3 Hz), 136.91, 138.44 (d, J=4.5 Hz) ppm. Other data are in
(1R,3aS)-1-(p-tolyl)hexahydropyrrolo[1,–2c][1, 3, 2]oxazaphosphole
borane (6a). Prepared according to general procedure from 3a
(1 mmol), and 4 (1 mmol) after workup yielded 0.2350 g (100%
0.1 mmol) as colourless oil. Resulting oil was dissolved in a mixture
of: 4 mL diethyl ether, 4 mL MTBE, 8 mL hexane. Crystallization
gave 0.075 g (0.32 mmol) of transparent crystals. MP t=95.2–
1
2
3
4
5
6
7
8
9
accordance with reported in literature.[14]
o-Anisylphosphonic acid bis(N,N)-diethylamide (3b). Prepared ac-
cording to general procedure from o-AnisylMgBr (30 mmol), and 2
°
(25 mmol) after distillation (143 C @ 2mmHg) yielded 3.03 g (43%
10.7 mmol) as colourless oil. 1H NMR (500 MHz, CDCl3)=δ 1.07–
1.14 (m, 12 H), 2.99–3.13 (m, 8 H), 3.82 (s, 3 H), 6.79–6.86 (m, 1 H),
6.93–7.00 (m, 1 H), 7.25–7.32 (m, 1 H), 7.35–7.40 (m, 1 H) ppm. 31P
NMR (202 MHz, CDCl3) δ=89.54 ppm. 13C NMR (126 MHz, CDCl3)
δ=14.66 (d, J=2.7 Hz), 43.22 (d, J=18.2 Hz), 54.79, 109.68, 120.17,
129.10 (d, J=1.8 Hz), 129.62 (d, J=9.1 Hz), 131.70 (d, J=5.4 Hz),
160.04 (d, J=16.4 Hz) ppm. Other data are in accordance with
reported in literature.[14]
°
96.7 C. TLC Rf =0.34 (hexane-ethyl acetate 10–1). ORP [α]D = +
1
°
123.1 (c=1.0 in CHCl3) H NMR (500 MHz, CDCl3) δ=0.46–1.13 (m,
3 H), 1.70–1.77 (m, 1 H), 1.91–2.00 (m, 2 H), 2.05–2.13 (m, 1 H), 2.41
(s, 3 H), 3.12–3.20 (m, 1 H), 3.76–3.85 (m, 2 H), 3.88–3.94 (m, 1 H),
4.23–4.29 (m, 1 H), 7.25–7.28 (m, 2 H), 7.63–7.68 (m, 2 H) ppm. 31P
NMR (202 MHz, CDCl3) δ=141.51 ppm. 13C NMR (126 MHz, CDCl3)
δ=21.55, 26.39 (d, J=1.82 Hz), 30.51 (d, J=2.72 Hz), 48.36 (d, J=
6.36 Hz), 62.50 (d, J=1.82 Hz), 72.08 (d, J=5.45 Hz), 129.16 (d, J=
10.90 Hz), 130.29 (d, J=11.81 Hz), 131.21 (d, J=69.94 Hz), 142.31 (d,
J=1.82 Hz) ppm. HRMS [M+MeOH+H] predicted 268.1634 found
268.1629.
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1-Naphtylphosphonic acid bis(N,N)-diethylamide (3c). Prepared
according to general procedure from 1-NphMgBr (30 mmol), and 2
°
(25 mmol) after distillation (157-161 C @ 2mmHg) yielded 6.27 g
1
(83% 20.7 mmol) as colourless oil. H NMR (500 MHz, CDCl3) δ=
Crystal data: crystal system orthorhombic, space group P212121, unit
cell dimensions a=7.6840(2) Å, b=11.0636(3) Å, c=14.9848(3) Å,
V=1273.90(5) Å3, Z=4. Independent reflections 2602 [R(int)=
0.0434], parameters 221, Goodness-of-fit on F2 1.106; final R indices
[I>2σ (I)] R1=0.0290, wR2=0.0721; R indices (all data) R1=0.0341,
wR2=0.0809. Absolute structure parameter À 0.015(12).
(1R,3aS)-1-(o-anisyl)hexahydropyrrolo[1,–2c][1,3,2]oxazaphosphole
borane (6b). Prepared according to general procedure from 3b
(1 mmol), and 4 (1 mmol) after workup yielded 0.0803 g (32%
1.10 (t, J=7.1 Hz, 12 H), 3.10–3.19 (m, 8 H), 7.43–7.50 (m, 3 H), 7.65
(s, 1 H), 7.76–7.80 (m, 1 H), 7.81–7.87 (m, 1 H), 8.37–8.43 (m, 1 H)
ppm. 31P NMR (202 MHz, CDCl3) δ=93.86 ppm. 13C NMR (126 MHz,
CDCl3) δ=14.76 (d, J=2.7 Hz), 43.62 (d, J=17.3 Hz), 125.07, 125.42,
126.42, 126.53, 126.85 (d, J=50.0 Hz), 128.37 (d, J=1.8 Hz), 128.58
(d, J=1.8 Hz), 129.00 (d, J=7.3 Hz), 133.60, 133.77 (d, J=2.7 Hz).
Other data are in accordance with reported in literature.[14]
t-Buthylphosphonic acid bis(N,N)-diethylamide (3d). Prepared ac-
cording to general procedure from t-BuMgCl (30 mmol), and 2
0.32 mmol) as colourless oil. TLC Rf =0.35(hexane-ethyl acetate 10-
°
(25 mmol) after distillation (90-95 C @ 2mmHg) yielded 5.75 g
1
°
1). ORP [α]D = +87.1 (c=1.145 in CHCl3) H NMR (500 MHz, CDCl3)
(99% 24 mmol) as colourless oil. 1H NMR (500 MHz, CDCl3) δ=1.05
(t, J=7.3 Hz, 12 H), 1.08–1.12 (m, 9 H), 3.04–3.12 (m, 8 H) ppm. 31P
NMR (202 MHz, CDCl3) δ=110.56 ppm. 13C NMR (126 MHz, CDCl3)
δ=14.78 (d, J=2.7 Hz), 28.56 (d, J=20.0 Hz), 38.78 (d, J=20.0 Hz),
44.60 (d, J=18.2 Hz) ppm. Other data are in accordance with
reported in literature.[15]
δ=0.45–1.12 (m, 3 H), 1.26 (t, J=7.3 Hz, 2 H), 1.69 (td, J=11.7,
6.0 Hz, 1 H), 1.88–1.97 (m, 2 H), 2.01–2.09 (m, 1 H), 2.78–2.90 (m,
1 H), 3.08–3.18 (m, 1 H), 3.78 (dd, J=14.5, 7.6 Hz, 1 H), 3.85 (td, J=
11.3, 5.4 Hz, 1 H), 3.91 (s, 2 H), 4.30 (dd, J=14.9, 8.7 Hz, 1 H), 6.93
(dd, J=8.2, 4.7 Hz, 1 H), 6.99 (t, J=7.4 Hz, 1 H), 7.46 (t, J=7.9 Hz,
1 H), 7.65 (dd, J=12.3, 7.6 Hz, 1 H) ppm. 31P NMR (202 MHz, CDCl3)
δ=140.22 ppm. 13C NMR (126 MHz, CDCl3) δ=11.81, 26.44 (d, J=
1.8 Hz), 30.50 (d, J=2.7 Hz), 48.03 (d, J=7.3 Hz), 49.09, 55.90, 62.36
(d, J=1.8 Hz), 72.58 (d, J=5.4 Hz), 111.44 (d, J=5.4 Hz), 120.41,
120.50, 122.39 (d, J=65.4 Hz), 132.32 (d, J=10.9 Hz), 133.69 (d, J=
1.8 Hz), 160.85 (d, J=5.4 Hz) ppm. HRMS [M+MeOH+H] predicted
284.1573 found 284.1579.
c-Hexylphosphonic acid bis(N,N)-diethylamide (3e). Prepared ac-
cording to general procedure from c-HexMgBr (30 mmol), and 2
°
(25 mmol) after distillation (120 C @ 2mmHg) yielded 2,39 g (37%
9 mmol) as colourless oil. H NMR (500 MHz, CDCl3) δ=1.03 (t, J=
1
7.1 Hz, 12 H), 1.09–1.18 (m, 2 H), 1.19–1.31 (m, 3 H), 1.62–1.75 (m,
3 H), 1.75–1.88 (m, 3 H), 2.93–3.06 (m, 8 H) ppm. 31P NMR (202 MHz,
CDCl3) δ=98.50 ppm. 13C NMR (126 MHz, CDCl3) δ=14.51 (d, J=
2.7 Hz), 26.22 (d, J=13.6 Hz), 26.93 (d, J=12.7 Hz), 28.58 (d, J=
20.9 Hz), 37.67 (d, J=6.4 Hz), 42.51 (d, J=14.5 Hz) ppm. Other data
are in accordance with reported in literature.[15]
(1R,3aS)-1-(1-naphtyl)hexahydropyrrolo[1,–2c][1,3,2]oxazaphosphole
borane (6c). Prepared according to general procedure from 3c
(1 mmol), and 4 (1 mmol) after workup yielded 0.0352 g (14%
0.13 mmol) as colourless oil. TLC Rf =0.34(hexane-ethyl acetate 10–
1
°
1). ORP [α]D = +49.5 (c=1.0 in CHCl3) H NMR (500 MHz, CDCl3)
c-Pentylphosphonic acid bis(N,N)-diethylamide (3f). Prepared ac-
cording to general procedure from c-PentMgBr (30 mmol), and 2
δ=0.61–1.36 (m, 3 H), 1.69–1.76 (m, 1 H), 1.97–2.04 (m, 2 H), 2.06–
2.14 (m, 1 H), 3.34 (ddt, J=12.5, 10.3, 7.2, 7.2 Hz, 1 H), 3.74–3.81 (m,
1 H), 3.87 (ddd, J=10.4, 8.8, 6.0 Hz, 1 H), 4.00 (ddt, J=12.1, 10.5,
6.0, 6.0 Hz, 1 H), 4.12–4.18 (m, 1 H), 7.47–7.63 (m, 3 H), 7.87–7.98 (m,
3 H), 8.54 (d, J=8.5 Hz, 1 H) ppm. 31P NMR (202 MHz, CDCl3) δ=
141.23 ppm. 13C NMR (126 MHz, CDCl3) δ=26.45 (d, J=2.7 Hz),
30.94 (d, J=2.7 Hz), 48.29 (d, J=6.4 Hz), 61.96, 72.23 (d, J=7.3 Hz),
124.51 (d, J=10.0 Hz), 126.26, 126.51 (d, J=6.4 Hz), 126.72, 128.70,
130.19 (d, J=7.3 Hz), 130.39–131.04 (m), 132.40 (d, J=13.6 Hz),
132.54 (d, J=1.8 Hz), 133.70 (d, J=8.2 Hz) ppm. HRMS [M-BH3 +H]
predicted 258.1041 found 258.1042
°
(25 mmol) after distillation (105 C @ 2mmHg) yielded 2.26 g (37%
9.25 mmol) as colourless oil. H NMR (500 MHz, CDCl3) δ=1.01 (t,
1
J=6.9 Hz, 12 H), 1.39–1.50 (m, 2 H), 1.52–1.60 (m, 2 H), 1.61–1.74
(m, 4 H), 2.36–2.45 (m, 1 H), 2.92–3.06 (m, 8 H) ppm. 31P NMR
(202 MHz, CDCl3) δ=97.26 ppm. 13C NMR (126 MHz, CDCl3) δ=
14.74 (d, J=2.7 Hz), 26.82 (d, J=8.2 Hz), 29.14 (d, J=26.3 Hz), 34.51
(d, J=1.8 Hz), 42.54 (d, J=13.6 Hz) ppm. Other data are in
accordance with reported in literature.[11]
General procedure for preparation of oxazaphosphole boranes. In
flame dried, argon filled, 10 mL screw cap tube, equipped with
stirrer, 1 mmol of various acid bis(N,N)-diethylamide was palced,
1 mmol of (L)-Prolinol and 3–5 mL of toluene were added. After
completion of reaction (monitored on NMR) mixture was chilled to
room temperature and BH3*SMe2 (3 mmol) was slowly added. After
about 5 minutes mixture was transferred to separatory funnel and
was washed with 2% HCl, next with 5% NaHCO3, and twice with
water. Organic phase was separated, dried with MgSO4 and
condensed with rotary evaporator to give viscous oil as a product
(1R,3aS)-1-(t-butyl)hexahydropyrrolo[1,–2c][1,3,2]oxazaphosphole bor-
ane (6d). Prepared according to general procedure from 3d
(1 mmol), and 4 (1 mmol) after workup yielded 0.014 g (7%
0.07 mmol) as colourless oil. TLC Rf =0.375(hexane-ethyl acetate 10-
1
°
1). ORP [α]D = +76.6 (c=1.325 in CHCl3) H NMR (500 MHz, CDCl3)
δ=0.10–0.88 (m, 3 H), 1.10 (d, J=14.8 Hz, 9 H), 1.65–1.71 (m, 1 H),
1.74–1.84 (m, 1 H), 1.88 (s, 1 H), 1.94–2.02 (m, 1 H), 2.91–3.00 (m,
1 H), 3.50 (td, J=8.7, 2.4 Hz, 1 H), 3.61–3.69 (m, 1 H), 3.80–3.86 (m,
Eur. J. Org. Chem. 2021, 1931–1941
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Full Papers
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1 H), 4.33 (ddd, J=15.1, 8.7, 6.5 Hz, 1 H) ppm. 31P NMR (202 MHz,
129.43 (d, J=9.08 Hz) 130.48 (d, J=9.99 Hz) 141.53 (d, J=2.72 Hz)
ppm. HRMS [M-BH3 +O+H] predicted 254.1304 found 254.1302
1
2
3
4
5
6
7
8
9
CDCl3) δ=167.80 ppm. 13C NMR (126 MHz, CDCl3) δ=23.71 (d, J=
3.6 Hz), 26.22, 29.33 (d, J=3.6 Hz), 34.97 (d, J=40.9 Hz), 48.64 (d,
J=5.4 Hz), 62.83 (d, J=1.8 Hz), 73.06 (d, J=4.5 Hz) ppm. HRMS [M-
BH3 +H] predicted 188.1197 found 188.1199
P-(S)-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)quinolin-2-ol-P-(phenyl)-
P-(4-methylphenyl) Phosphine borane(7aa). Prepared according to
general procedure from 6a (0.385 mmol), and Phenyllithium
(0.769 mmol) after workup yielded 0.0715 g (60%) as colourless oil.
TLC Rf =0.41 (chloroform-methanol 50–1). ORP [α]D =À 31.6 (c=
0.99 in CHCl3) 1H NMR (500 MHz, CDCl3) δ=0.69–1.42 (m, 3 H),
1.61–1.75 (m, 1 H), 1.84–2.00 (m, 3 H), 2.38–2.46 (m, 3 H), 2.88–2.98
(m, 1 H), 3.06–3.15 (m, 1 H), 3.52 (dd, J=10.9, 6.5 Hz, 1 H), 3.58–3.64
(m, 1 H), 4.04–4.12 (m, 1 H), 7.21–7.32 (m, 3 H), 7.41–7.55 (m, 5 H),
7.55–7.63 (m, 1 H), 7.64–7.71 (m, 2 H) ppm. 31P NMR (202 MHz,
CDCl3) δ=59.83 ppm. 13C NMR (126 MHz, CDCl3) δ=21.47, 25.31
(d, J=4.5 Hz), 28.91 (d, J=5.4 Hz), 48.45 (d, J=2.7 Hz), 61.27 (d, J=
6.4 Hz), 65.68–65.82 (m), 115.27, 120.39, 127.13 (d, J=62.7 Hz),
128.51 (d, J=10.0 Hz), 128.49 (d, J=10.0 Hz), 129.27 (d, J=10.0 Hz),
130.94 (d, J=2.7 Hz), 131.82 (d, J=10.9 Hz), 131.94 (d, J=10.0 Hz),
132.17 (d, J=10.9 Hz), 132.34 (d, J=10.0 Hz), 141.66 (d, J=2.7 Hz)
ppm. HRMS [M+Na] predicted 336.1656 found 336.1661
(1R,3aS)-1-(c-hexyl)hexahydropyrrolo[1,–2c][1,3,2]oxazaphosphole bor-
ane(6e). Prepared according to general procedure from 3e
(1 mmol), and 4 (1 mmol) after workup yielded 0.0817 g (36%
0.36 mmol) as colourless oil. TLC Rf =0.50(hexane-ethyl acetate 10–
1
°
1). ORP [α]D = +66.9 (c=1.952 in CHCl3) H NMR (500 MHz, CDCl3)
δ=0.11–0.78 (m, 3 H), 1.16–1.33 (m, 5 H), 1.54–1.64 (m, 1 H), 1.65–
1.73 (m, 2 H), 1.74–1.83 (m, 3 H), 1.84–1.95 (m, 3 H), 1.96–2.04 (m,
1 H), 2.97 (dddd, J=13.95, 10.64, 9.14, 5.99 Hz, 1 H), 3.52 (td, J=
8.51, 4.10 Hz, 1 H), 3.62 (tdd, J=11.11, 11.11, 7.41, 3.15 Hz, 1 H),
3.78–3.84 (m, 1 H), 4.28 (ddd, J=13.24, 8.67, 6.46 Hz, 1 H) ppm. 31P
NMR (202 MHz, CDCl3) δ=160.89 ppm. 13C NMR (126 MHz, CDCl3)
δ=25.16 (d, J=12.72 Hz), 25.86 (d, J=1.82 Hz), 26.06, 26.17 (d, J=
2.72 Hz), 29.59 (d, J=2.72 Hz), 41.42 (d, J=43.60 Hz), 48.47 (d, J=
5.45 Hz), 62.44, 72.45 (d, J=4.54 Hz) ppm. HRMS [M+MeOH+H]
predicted 260.1952 found 260.1942
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P-(S)-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)quinolin-2-ol-P-(methyl)-
P-(1-Naphtyl) Phosphine borane(7c). Prepared according to general
procedure from 6c (1.834 mmol), after workup yielded 0.3041 g
(56%) as colourless oil. TLC Rf =0.36(hexane-ethyl acetate 2-1). ORP
[α]D =À 3.35 (c=1.105 in CHCl3) 1H NMR (500 MHz, CDCl3) δ=
0.71–1.34 (m, 3 H), 1.58–1.66 (m, 1 H), 1.76–1.91 (m, 4 H), 1.94 (s,
2 H), 2.68–2.75 (m, 1 H), 3.01–3.06 (m, 1 H), 3.37–3.50 (m, 2 H), 4.01–
4.07 (m, 1 H), 7.48–7.64 (m, 3 H), 7.75 (ddd, J=12.7, 7.2, 1.3 Hz, 1 H),
7.89–7.93 (m, 1 H), 7.97–8.01 (m, 1 H), 8.48 (dd, J=7.4, 0.8 Hz, 1 H)
ppm. 31P NMR (202 MHz, CDCl3) δ=56.25 (major dia), 59.21 (minor
dia) ppm. 13C NMR (126 MHz, CDCl3) δ=14.08 (d, J=46.3 Hz), 24.96
(d, J=5.4 Hz), 28.64 (d, J=5.4 Hz), 47.23, 61.33 (d, J=5.4 Hz), 65.52,
124.71 (d, J=10.9 Hz), 125.82 (d, J=6.4 Hz), 126.46, 126.88, 128.34
(d, J=59.9 Hz), 129.11–129.33 (m), 130.87 (d, J=9.1 Hz), 132.54 (d,
J=1.8 Hz), 133.15 (d, J=9.1 Hz), 133.77 (d, J=7.3 Hz) ppm. HRMS
[M+Na] predicted 310.1500 found 310.1500
(1R,3aS)-1-(c-Pentyl)hexahydropyrrolo[1,–2c][1,3,2]oxazaphosphole
borane(6f). Prepared according to general procedure from 3f
(1 mmol), and 4 (1 mmol) after workup yielded 0.1086 g (51%
0.51 mmol) as colourless oil. TLC Rf =0.34(hexane-ethyl acetate 10-
1
°
1). ORP [α]D = +73.9 (c=1.145 in CHCl3) H NMR (500 MHz, CDCl3)
δ=0.14–0.79 (m, 3 H) 1.53–1.60 (m, 2 H) 1.61–1.72 (m, 5 H) 1.75–
1.91 (m, 4 H) 2.00 (ddt, J=12.45, 9.62, 6.94, 6.94 Hz, 1 H) 2.04–2.12
(m, 1 H) 2.97 (dddd, J=13.95, 10.56, 8.91, 5.99 Hz, 1 H) 3.51–3.57
(m, 1 H) 3.65 (tdd, J=11.11, 11.11, 7.41, 3.15 Hz, 1 H) 3.80–3.88 (m,
1 H) 4.30 (ddd, J=13.08, 8.83, 6.46 Hz, 1 H) ppm. 31P NMR
(202 MHz, CDCl3) δ=162.26 ppm. 13C NMR (126 MHz, CDCl3) δ=
26.07 (d, J=1.82 Hz) 26.26 (d, J=6.36 Hz) 26.33 (d, J=6.36 Hz)
26.57, 26.71 (d, J=2.72 Hz) 29.65 (d, J=2.72 Hz) 41.23 (d, J=
45.41 Hz) 48.51 (d, J=5.45 Hz) 62.48 (d, J=1.82 Hz) 72.38 (d, J=
5.45 Hz) ppm. HRMS [2M+H2O+H] predicted 463.3196 found
463.3186
P-(S)-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)quinolin-2-ol-P-(methyl)-
P-(cyclo-hexyl) Phosphine borane(7e). Prepared according to gen-
eral procedure from 6e (1.725 mmol), after workup yielded
0.1426 g (34% 0.5868 mmol) as colourless oil. TLC Rf =0.32(toluene-
General procedure for Phosphineoxazolodine ring opening with
methyllithium: In a flame dried, argon filled schlenck flask equipped
with a magnetic stirrer, the substrate was placed and the flask was
deaired with triple vaccum/argon flushing sequence. Next, about
5–10 mL of THF was added and flask was left for several minutes to
let the substrate dissolve. Flask was then cooled in dry ice acetone
mixture and when it was cold, appropriate volume of MeLi (2
equivalents) solution was added and left to stir overnight (ca. 16 h)
and let to warm to room temperature. On a next day, a pinch
(about 200 mg) of solid NH4Cl was added to quench the reaction
and was let to stir for about 5 minutes. Solution was then
transferred to funnel with celite plug and was filtered from solid
residues. Supernatant was then condensed with rotary evaporator
and resulted oil was purified with column chromatography with
chloroform:methanol 50:1 (vol.) as eluent.
ethyl acetate 9-1). ORP [α]D =À 6.15 (c=1,3 in CHCl3) 1H NMR
°
(500 MHz, CDCl3) δ=0.16–0.85 (m, 3 H), 1.17–1.30 (m, 3 H), 1.39 (d,
J=9.5 Hz, 3 H), 1.41–1.50 (m, 2 H), 1.59–1.66 (m, 1 H), 1.67–1.75 (m,
2 H), 1.80–1.97 (m, 8 H), 3.04–3.16 (m, 2 H), 3.40–3.45 (m, 1 H), 3.51–
3.56 (m, 1 H), 3.78 (br. s., 1 H) ppm. 31P NMR (202 MHz, CDCl3) δ=
63.28 ppm. 13C NMR (126 MHz, CDCl3) δ=11.07 (d, J=42.7 Hz),
24.93 (d, J=3.6 Hz), 25.92 (d, J=13.6 Hz), 26.58 (d, J=11.9 Hz),
26.63 (d, J=27.2 Hz), 28.82 (d, J=4.5 Hz), 35.69 (d, J=38.1 Hz),
46.04 (d, J=1.8 Hz), 61.58 (d, J=4.5 Hz), 65.58 ppm. HRMS [MÀ H]
predicted 242.1837 found 242.1849
P-(S)-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)quinolin-2-ol-P-(methyl)-
P-(cyclo-pentyl) Phosphine borane(7f). Prepared according to
general procedure from 6f (2.375 mmol), and 4 (1 mmol) after
workup yielded 0.2558 g ( 47% 1.116 mmol) as colourless oil. TLC
P-(S)-((S)-2-(hydroxymethyl)pyrrolidin-1-yl)quinolin-2-ol-P-(methyl)-
P-(4-methylphenyl) Phosphine borane(7a). Prepared according to
general procedure from 6a (0.309 mmol), after workup yielded
0.0605 g (78%) as colourless oil. TLC Rf =0.28 (chloroform-methanol
°
Rf =0.39(hexane-ethyl acetate 2-1). ORP [α]D = +1.44 (c=1.455 in
CHCl3) 1H NMR (500 MHz, CDCl3) δ=0.15–0.80 (m, 3 H), 1.39 (d, J=
9.1 Hz, 3 H) major dia, 1.46 (d, J=9.1 Hz, 3 H) minor dia, 1.53–1.62
(m, 2 H), 1.62–1.68 (m, 1 H), 1.68–1.79 (m, 6 H), 1.79–1.96 (m, 5 H),
2.29–2.43 (m, 1 H), 3.06–3.18 (m, 2 H), 3.41–3.48 (m, 1 H), 3.49–3.54
(m, 1 H), 3.77–3.85 (m, 1 H) ppm. 31P NMR (202 MHz, CDCl3) δ=
65.8 ppm. 13C NMR (126 MHz, CDCl3) δ=12.39 (d, J=42.7 Hz),
24.98 (d, J=3.6 Hz), 26.54 (d, J=7.3 Hz), 26.64, 27.13 (d, J=2.7 Hz),
27.69 (d, J=4.5 Hz), 28.84 (d, J=4.5 Hz), 35.05 (d, J=40.0 Hz),
46.32, 61.36, 65.51 ppm. HRMS [MÀ H] predicted 228.1680 found
228.1684
50–1). ORP [α]D =À 16.5 (c=1.075 in CHCl3) 1H NMR (500 MHz,
°
CDCl3) δ=0.24–0.93 (m, 3 H) 1.39–1.48 (m, 1 H) 1.52 (d, J=9.46 Hz,
3 H) 1.54–1.63 (m, 3 H) 1.68–1.95 (m, 1 H) 2.17 (s, 3 H) 2.63–2.71 (m,
1 H) 2.80–2.86 (m, 1 H) 3.21–3.30 (m, 2 H) 3.62–3.70 (m, 1 H) 7.01–
7.07 (m, 3 H) 7.29–7.35 (m, 2 H) ppm. 31P NMR (202 MHz, CDCl3)
δ=55.15 ppm. 13C NMR (126 MHz, CDCl3) δ=12.04 (d, J=
49.05 Hz) 21.44 (s) 25.06 (d, J=4.54 Hz) 29.01 (d, J=4.54 Hz) 47.33
(d, J=2.72 Hz) 61.13 (d, J=5.45 Hz) 65.54, 128.43 (d, J=59.90 Hz)
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°
General procedure for PÀ O bond cleavage with alkali metals in
liquid ammonia: 50 mL 2-neck flask equipped with a stirrer was
flame dried and argon filled and was left with argon overpressure
(ballon or manifold). Next the dry ice coldfinger condenser was
placed on one neck, and flask was placed in cooling bath with dry
ice CO2 mixture. Coldfinger was loaded with CO2/acetone mixture
and gaseous ammonia hose was attached to condenser. After 5–
10 mL of liquid ammonia was collected, Ammonia source was
disconnected and vessel was sealed. Next alkali metal was put into
a liquid ammonia and was left to stir for 5 minutes to form deep
blue colour of solution. After that time, substrate dissolved in 5 mL
of dry THF was added via syringe and was left to react for
5 minutes. After 5 minutes MeI (ca. 10 equiv.) was added with
syringe and mixture was left for stir for 10 minutes. Addition of a
pinch (ca 0.2 g) of NH4Cl quenched the residual anion and then
solution was transferred on a rotary evaporator to get rid of NH3.
Product was then dissolved in DCM and filtered through a plug of
celite and again condensated in vacuo. The resulting oil was
analysed and if necessary purified on collumn chromatography on
silica gel with hexanes-ethyl acetate 2-1 as an eluent.
in a freezer (À 17 C) for 48 hours. After that time, small amount of
K2CO3 was added to quench the reaction. Supernatant was filtered
through plug of cellite filtrate was concentrated on rotary
evaporator and purified on chromatography column with hexane:
chloroform:methanol 50:50:1 as an eluent.
1
2
3
4
5
6
7
8
9
(S)-p-Tollylmethyl boranephosphinous acid methyl ester (8a).
Prepared according to general procedure from 7b (1 mmol), after
workup yielded 0.1219 g ( 67% 0.670 mmol) as colourless oil. TLC
Rf =0.52(hexane-ethyl acetate 10-1). HPLC 82%ee Daicell OJÀ H
(4.5×250 mm); 99:1 hexane:i-PrOH; 1 mL/min tR =12.5 min and tR =
14.2 min. ORP [α]D = +83.3 (c=1.64 in CHCl3) (82%ee). 1H NMR
°
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
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(500 MHz, CDCl3) δ=0.44–1.13 (m, 3 H), 1.70 (d, J=9.1 Hz, 3 H),
2.42 (s, 3 H), 3.55 (d, J=12.3 Hz, 3 H), 7.32 (d, J=7.6 Hz, 2 H), 7.64–
7.74 (m, 2 H) ppm. 31P NMR (202 MHz, CDCl3) δ=112.40(m) ppm.
13C NMR (126 MHz, CDCl3) δ=16.02 (d, J=47.2 Hz), 21.61, 53.48 (d,
J=2.7 Hz), 128.63 (d, J=41.8 Hz), 129.51 (d, J=10.0 Hz), 130.80 (d,
J=11.8 Hz), 142.81 (d, J=1.8 Hz) ppm. HRMS [M-BH3 +O+Na]
predicted 207.0545 found 207.0545
(S)-Phenyl-p-Tollyll boranephosphinous acid methyl ester (8aa).
Prepared according to general procedure from 7aa (1.478 mmol),
after workup yielded 0.2813 g (78%) as colourless oil. TLC Rf =
0.58(hexane-ethyl acetate 10-1). HPLC 82%ee Daicell ASÀ H (4.5×
250 mm); hexane:MeOH:i-PrOH 98:1:1; 0.25 mL/min tR =23.2 min
P-(S)-(2-(hydroxymethyl)pyrrolidin-1-yl)quinolin-2-ol-P-(methyl)-P-(2-
methoxyphenyl) Phosphine borane(7b). Prepared according to
general procedure from 6b (0.5 mmol), after workup yielded
0.0187 g ( 14% 0.07 mmol) as colourless oil. TLC Rf =0.19(hexane-
and tR =23.9 min ORP [α]D = +8.3 (c=0.965 in CHCl3) 1H NMR
°
ethyl acetate 2-1). ORP [α]D =À 1.90 (c=1.05 in CHCl3) 1H NMR
°
(500 MHz, CDCl3) δ=ppm 0.67–1.42 (m, 3 H), 2.40 (s, 3 H), 3.73 (d,
J=12.0 Hz, 3 H), 7.28 (d, J=8.5 Hz, 2 H), 7.42–7.48 (m, 2 H), 7.48–
7.55 (m, 1 H), 7.64 (dd, J=10.4, 8.2 Hz, 2 H), 7.73 (dd, J=9.9, 8.7 Hz,
2 H) ppm. 31P NMR (202 MHz, CDCl3) δ=107.21 ppm. 13C NMR
(126 MHz, CDCl3) δ=21.57 (s), 53.94 (d, J=2.7 Hz), 128.10 (d, J=
64.5 Hz), 128.58 (d, J=10.9 Hz), 129.41 (d, J=10.9 Hz), 131.17 (d, J=
11.8 Hz), 131.38 (d, J=10.9 Hz), 131.74 (d, J=2.7 Hz), 131.81 (d, J=
64.5 Hz), 142.52 (d, J=1.8 Hz) ppm. HRMS [2M-BH3+O+Na]
predicted 515.1512 found 515.1518 Other data are in accordance
with reported in literature.[16]
(500 MHz, CDCl3) δ=0.49–1.14 (3 H, m), 1.69–1.78 (2 H, m), 1.81
(3 H, d, J=9.5 Hz), 1.82–1.91 (2 H, m), 1.91–2.04 (1 H, bm), 3.08–3.14
(1 H, m), 3.15–3.22 (1 H, m), 3.36–3.41 (1 H, m), 3.46–3.50 (1 H, m),
3.80–3.87 (1 H, m), 3.90 (3 H, s), 6.94–6.97 (1 H, m), 7.02–7.06 (1 H,
m), 7.45–7.49 (1 H, m), 7.69–7.74 (1 H, m) ppm. 31P NMR (202 MHz,
CDCl3) δ=55.77 ppm. 13C NMR (126 MHz, CDCl3) δ=12.36 (d, J=
47.2 Hz), 25.49 (d, J=4.5 Hz), 29.28 (d, J=4.5 Hz), 48.29, 55.50,
60.79 (d, J=3.6 Hz), 65.31 (d, J=1.8 Hz), 111.17 (d, J=4.5 Hz),
120.42 (d, J=55.4 Hz), 121.00 (d, J=10.9 Hz), 133.24 (d, J=1.8 Hz),
133.88 (d, J=11.8 Hz), 160.79 ppm. HRMS [M+Na] predicted
290.1449 found 290.1446
(S)-1-Naphtylmethyl boranephosphinous acid methyl ester (8c).
Prepared according to general procedure from 7b (1 mmol), after
workup yielded 0,057 g ( 25% 0.2614 mmol) as colourless oil. TLC
Rf =0.70 (hexane-chloroform-methanol 50-50-1). ORP [α]D = +36.08
(c=1.02 in CHCl3) HPLC 89%ee Daicell OJÀ H (4.5×250 mm); 95:5
P-(S)-(2-(methoxymethyl)pyrrolidin-1-yl)quinolin-2-ol-P-(methyl)-P-
(1-t-Butyl) Phosphine borane(7d). Prepared according to general
procedure from 6d (0.9529 mmol), after workup yielded 0.0271 g
(13%) as colourless oil. TLC Rf =0.72(hexane-i-PrOH-chloroform 10-
1-1). ORP [α]D =À 41.46 (c=1.365 in CHCl3) 1H NMR (500 MHz,
CDCl3) δ=ppm 0.21–0.90 (m, 3 H), 1.16 (d, J=13.9 Hz, 3 H) (major
dia), 1.17 (d, J=13.9 Hz, 3 H) (minor dia), 1.36 (d, J=8.5 Hz, 1 H)
(major dia), 1.43 (d, J=8.8 Hz, 1 H) (minor dia), 1.68–1.75 (m, 1 H)
(mixed), 1.79–1.93 (m, 4 H) (mixed), 3.05–3.15 (m,1 H) (mixed), 3.18
(dd, J=9.3, 8.4 Hz, 1 H) (minor dia), 3.24 (dd, J=9.5, 7.6 Hz, 1 H)
(major dia), 3.35 (s, 1 H) (major dia), 3.35 (s, 1 H) (minor dia), 3.39
(dd, J=9.5, 3.8 Hz, 1 H) (major dia), 3.51 (dd, J=9.3, 4.3 Hz, 1 H)
(minor dia), 3.79–3.85 (m, 1 H) (minor dia), 4.00–4.07 (m, 1 H) (major
dia). 31P NMR (202 MHz, CDCl3) δ=72.4 (major dia),72.3 (minor dia)
ppm. 13C NMR (126 MHz, CDCl3) δ=6.80 (d, J=38.1 Hz) (minor
dia), 7.94 (d, J=42.7 Hz) (major dia), 23.71 (d, J=3.6 Hz) (major dia),
24.72 (d, J=3.6 Hz) (minor dia), 25.71 (d, J=2.7 Hz) (major dia),
26.00 (d, J=2.7 Hz) (minor dia), 26.16 (d, J=3.6 Hz) (major dia),
28.08 (d, J=1.8 Hz) (major dia), 28.30 (d, J=5.4 Hz), 28.87 (d, J=
4.5 Hz) (minor dia), 32.79 (d, J=42.7 Hz), 33.93 (d, J=32.7 Hz)
(minor dia), 48.36 (s), 48.80 (d, J=3.6 Hz) (minor dia), 58.82 (d, J=
7.3 Hz) (mixed), 59.15 (d, J=6.4 Hz), 59.48 (d, J=4.5 Hz) (minor dia),
75.00 (minor dia), 76.15 (major dia) ppm. HRMS [MÀ H] predicted
230.1837 found 230.1836
1
hexane:i-PrOH; 0.5 mL/min tR =24.4 min and tR =25.3 min H NMR
(500 MHz, CDCl3) δ=0.65–1.33 (m, 3 H), 1.94 (d, J=9.1 Hz, 3 H),
3.57–3.65 (m, 3 H), 7.52–7.68 (m, 3 H), 7.96 (d, J=8.2 Hz, 1 H), 8.03–
8.08 (m, 1 H), 8.22 (ddd, J=15.9, 7.1, 0.9 Hz, 1 H), 8.51 (dd, J=8.4,
1.1 Hz, 1 H) ppm. 31P NMR (202 MHz, CDCl3) δ=116.67 ppm. 13C
NMR (126 MHz, CDCl3) δ=15.81 (d, J=51.8 Hz), 53.59 (d, J=
3.6 Hz), 124.85 (d, J=14.5 Hz), 125.26 (d, J=4.5 Hz), 126.32–126.49
(m), 127.02 (d, J=48.1 Hz), 127.56, 129.38–129.52 (m), 132.67 (d, J=
2.7 Hz), 133.62, 133.65 (d, J=2.7 Hz), 134.86 (d, J=20.0 Hz) ppm.
HRMS [2M-BH3+O+Na] predicted 463.1199 found 463.1187
(S)-cyclo-Hexylmethyl boranephosphinous acid methyl ester (8e).
Prepared according to general procedure from 7e (1 mmol), after
workup yielded 0,057 g ( 25% 0,2614 mmol) as colourless oil. TLC
°
Rf =0.85(toluene-ethyl acetate 10-1). ORP [α]D =À 2.3 (c=0.95 in
CHCl3) HPLC enatiomeric excess was not determinated, compound
1
does not absorb an UV-Vis radiation H NMR (500 MHz, CDCl3) δ=
0.14–0.77 (m, 3 H), 1.19–1.36 (m, 5 H), 1.40 (d, J=8.8 Hz, 3 H), 1.69–
1.77 (m, 2 H), 1.85 (d, J=4.7 Hz, 2 H), 1.88–1.96 (m, 2 H), 3.63 (d, J=
11.3 Hz, 3 H) ppm. 31P NMR (202 MHz, CDCl3) δ=126.36 ppm. 13C
NMR (126 MHz, CDCl3) δ=11.05 (d, J=39.1 Hz), 25.24, 25.32, 25.84,
26.29 (d, J=15.4 Hz), 26.29 (d, J=9.1 Hz), 37.97 (d, J=41.8 Hz),
54.10 (d, J=3.6 Hz) ppm. HRMS [2M-BH3+O+Na] predicted
463.1199 found 463.1187(S)-cyclo-Pentylmethyl boranephosphi-
nous acid methyl ester (8f). Prepared according to general
procedure from 7f (1 mmol), after workup yielded 0.0528 g ( 33%,
General procedure for the synthesis of methylphosphinite boranes
amide (8a–h): In
a flame dried, argon filled flask substrate
(0.1 mmol) was placed, 5 mL of dry methanol was added to vessel,
and next concentrated sulfuric acid (0.1 mmol) was added with
micropipete. Flask was closed with a glass stopper and was placed
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1939
© 2021 Wiley-VCH GmbH

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doi.org/10.1002/ejoc.202100196
0.33 mol) as colourless oil. TLC Rf =0.49(hexane:ethyl acetate 10:1).
through a plug of celite evaporated and analyzed with chiral
stationary phase HPLC to determinate enantiomeric excess.
1
2
3
4
5
6
7
8
ORP [α]D = +2,6 (c=1 in CHCl3) HPLC enatiomeric excess was not
1
determinated, compound does not absorb an UV-Vis radiation H
Deposition Number 2038641 (for 6a) contains the supplementary
crystallographic data for this paper. These data are provided free of
charge by the joint Cambridge Crystallographic Data Centre and
Fachinformationszentrum Karlsruhe Access Structures service
www.ccdc.cam.ac.uk/structures.
NMR (500 MHz, CDCl3) δ=0.13–0.77 (m, 3 H), 1.42 (d, J=8.8 Hz,
3 H), 1.57–1.79 (m, 6 H), 1.83–1.91 (m, 2 H), 2.10–2.19 (m, 1 H), 3.63
(d, J=11.3 Hz, 3 H) ppm. 31P NMR (202 MHz, CDCl3) δ=
127.22 ppm. 13C NMR (126 MHz, CDCl3) δ=12.39 (d, J=39.06 Hz),
26.43 (d, J=20.89 Hz), 26.76 (d, J=2.72 Hz), 37.94 (d, J=43.60 Hz),
54.01 (d, J=3.63 Hz) ppm. EA calculated: C 55.52 H 11.34 O 10.00
found: C 55.49 H 11.36 O 10.05.
9
General procedure for the synthesis of tertiary Phosphineboranes
Acknowledgements
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In a flame dried, argon filled schlenck flask equipped with a
magnetic stirrer, the substrate was placed and the flask was deaired
with triple vaccum/argon flushing sequence. Next, about 5 mL of
THF was added and flask was left for several minutes to let the
substrate dissolve. Flask was then cooled in dry ice acetone mixture
and when it was cold, appropriate volume of organolithium reagent
(2 equivalents) solution was added and left to stir overnight (ca.
16 h) and let to warm to room temperature. On a next day, a pinch
(about 200 mg) of solid NH4Cl was added to quench the reaction
and was let to stir for about 5 minutes. Solution was then
transferred to funnel with celite plug and was filtered from solid
residues. Supernatant was then condensed with rotary evaporator
and resulted oil was purified with column chromatography with
chloroform:methanol 50:1 (vol.) as eluent.
National Science Centre is gratefully acknowledged for financial
support of research project Preludium 122016/23/N/ST5/02716.
A.W. would like to kindly acknowledge prof. Marek Stankevič for
scientific supervision and help in preparation of this manuscript.
Conflict of Interest
The authors declare no conflict of interest.
Keywords: Chiral phosphorous
Phosphineoxazolines · Prolinol
·
Phosphine boranes
·
Methylphenyl-p-tollyl phosphine borane (9). Prepared according to
general procedure from 8aa (1.478 mmol), after workup yielded
0.1449 g (43%) as colourless oil. TLC Rf =0.58(hexane-ethyl acetate
10–1). HPLC Daicell OJ-H (4.5×250 mm); 99:1 hexane:i-PrOH; 1 mL/
min tR =37.0 min and tR =40.0 min. Daicell ODÀ H (4.5×250 mm);
99:1 hexane:iPrOH; 1 mL/min tR =8.16 min and tR =8.61 min 1H
NMR (500 MHz, CDCl3) δ=0.64–1.33 (m, 3 H), 1.85 (d, J=10.1 Hz,
3 H), 2.39 (s, 3 H), 7.24–7.29 (m, 2 H), 7.41–7.51 (m, 3 H), 7.56 (dd,
J=10.6, 8.0 Hz, 2 H), 7.62–7.68 (m, 2 H) ppm. 31P NMR (202 MHz,
CDCl3) δ=9.21(m) ppm. 13C NMR (126 MHz, CDCl3) δ=12.02 (d, J=
41.8 Hz), 21.47, 126.88 (d, J=58.1 Hz), 128.77 (d, J=10.0 Hz), 129.61
(d, J=10.9 Hz), 130.94 (d, J=56.3 Hz), 131.00 (d, J=2.7 Hz), 131.64
(d, J=9.1 Hz), 131.78 (d, J=10.0 Hz), 141.62 (d, J=1.8 Hz) ppm.
HRMS [2M-BH3+O+Na] predicted 483.1613 found 483.1605 Other
data are in accordance with reported in literature.[17]
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1600.
General procedure for catalytic hydrogenation : In a flame dried
argon filled, equipped with a stirrer Schlenck flask 0.1 mmol of
proper phosphonic acid bis(N,N)-diethylamide (3a–f) was placed
with proline (4) (0.1 mmol) and 5 mL of toluene. Flask was heated
°
at 110 C for about 16 hours to complete exchange of diamide
(monitored with 31P NMR). Next the reaction was evaporated till
dryness with vacuum pump to dispose of toluene and amine, and
residual oil was dissolved in 10 mL of dry and degassed dichloro-
methane. In a second flame dried argon filled Schlenck flask
0.025 mmol (0.0167 g) of [Ir(COD)Cl]2 was placed and 5 mL of dry
and degassed dichloromethane was added to flask, then vessel was
cooled in acetone/dry ice bath. To cold mixture (0.05 mmol,
0.010 g) of AgBF4 was added and mixture was stirred for 30 minutes
°
in À 78 C. From first flask 5 mL of solution was taken with syringe
and was added to second Schlenck flask and was left to stir for
°
additional 30 minutes in À 78 C. 10 mL volume of second flask
contains 0.05 mmol of catalyst as a solution in dichloromethane,
necessary amount of catalyst can be easily calculated. In a glass vial
α-Acetamidocinnamic acid methyl ester(0.2 mmol, 0.044 g) or 1-
phenyl-N-(1-phenylethylidene)methanamine (0.2 mmol, 0.042 g)
was placed and vial was flushed with argon. From second Schlenck
flask 2 mL of solution of catalyst was transferred with a syringe to
vial, and vial was placed in autoclave and was pressurized with
40 bar of Hydrogen. After 24 hours solution from vial was filtered
[13] Y. Takahashi, Y. Yamamoto, K. Katagiri, H. Danjo, K. Yamaguchi, T.
Imamoto, J. Org. Chem. 2005, 70, 9009–9012.
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Full Papers
doi.org/10.1002/ejoc.202100196
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Manuscript received: February 18, 2021
Revised manuscript received: March 8, 2021
Accepted manuscript online: March 12, 2021
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