Stereospecific Synthesis of α- And β-Hydroxyalkyl P-Stereogenic Phosphine-Boranes and Functionalized Derivatives: Evidence of the P=O Activation in the BH3-Mediated Reduction

Article abstract of DOI:10.1002/chem.201502647

Access to hydroxy-functionalized P-chiral phosphine-boranes has become an important field in the synthesis of P-stereogenic compounds used as ligands in asymmetric catalysis. A family of optically pure α and β-hydroxyalkyl tertiary phosphine-boranes has been prepared by using a three-step procedure from readily accessible enantiopure adamantylphosphinate, obtained by semi-preparative HPLC on multigram scale. Firstly, a two-step one-pot transformation affords the enantiopure hydroxyalkyl tertiary phosphine oxides in good yields and enantioselectivities. The third step, BH₃-mediated reduction, allows the formation of the desired phosphine-boranes with excellent stereospecifity. The mechanistic study of this reduction provides new evidence to elucidate the crucial role of the pendant hydroxy group and the subsequent activation of the P=O bond by the boron atom.

Full text of DOI:10.1002/chem.201502647

DOI: 10.1002/chem.201502647
Full Paper
&
P-Stereogenic Compounds
Stereospecific Synthesis of a- and b-Hydroxyalkyl P-Stereogenic
Phosphine–Boranes and Functionalized Derivatives: Evidence of
the P=O Activation in the BH3-Mediated Reduction
SØbastien Lemouzy,[a] Duc Hanh Nguyen,[a] Valentine Camy,[a] Marion Jean,[a]
David Gatineau,[a] Laurent Giordano,[a] Jean-Val›re Naubron,[b] Nicolas Vanthuyne,[a]
Damien HØrault,*[a] and GØrard Buono*[a]
Abstract: Access to hydroxy-functionalized P-chiral phos-
phine–boranes has become an important field in the synthe-
sis of P-stereogenic compounds used as ligands in asymmet-
ric catalysis. A family of optically pure a and b-hydroxyalkyl
tertiary phosphine–boranes has been prepared by using
a three-step procedure from readily accessible enantiopure
adamantylphosphinate, obtained by semi-preparative HPLC
on multigram scale. Firstly, a two-step one-pot transforma-
tion affords the enantiopure hydroxyalkyl tertiary phosphine
oxides in good yields and enantioselectivities. The third step,
BH3-mediated reduction, allows the formation of the desired
phosphine–boranes with excellent stereospecifity. The mech-
anistic study of this reduction provides new evidence to elu-
cidate the crucial role of the pendant hydroxy group and
the subsequent activation of the P=O bond by the boron
atom.
Introduction
Chiral phosphorus ligands are the most popular chiral ligands
used in asymmetric organometallic catalysis, due to their tuna-
ble steric and electronic properties,[1] and therefore, play an im-
portant role in industrial processes.[2] Among these chiral li-
gands, bidendate or bifunctional phosphorus compounds are
more appreciated, due to their potential to offer opportunities
to construct well-defined and structurally rigid organometallic
complexes. Moreover, P-stereogenic compounds bearing the
chiral center closely bound to the active metal center could
offer better enantioselectivity. For this reason the preparation
of stable P-stereogenic compounds remains a challenge in
asymmetric catalysis as organocatalysts[3] or as ligands.[4] The
first synthesis of enantioenriched a-hydroxymethyl tertiary
phosphine–borane by direct desymmetrization of the dime-
thylphenylphosphine–borane was initially reported by Evans
and co-workers,[5] and pursued by others[6] (Scheme 1, path E).
This class of compounds very recently gained more attention
as they were used as key intermediates during the synthesis of
Scheme 1. Comparative pathways to prepare optically pure functionalized
tertiary phosphine–boranes 4 (path A: this work; path B: ref. [16], [17];
path C: ref. [11]; path D: ref. [12]; path E: ref. [5], [6].
hybrid phosphine–phosphite bidendate chiral ligands, which
have been well developed in the past five years and found to
be active for different catalytic enantioselective transforma-
tions.[7]
Access to enantioenriched hydroxyalkyl tertiary phosphine–
boranes (TPB) is possible by reduction of the corresponding
tertiary phosphine oxides (TPO). Many reagents can reduce the
P=O bond with inversion or retention of configuration at phos-
phorus atom.[8] However, the relatively high temperature re-
quired to obtain the phosphine in high yield is a major draw-
back in terms of chemo- and stereoselectivity. This can be
easily circumvented when the P=O bond bears an alcohol
functionality controlling the reduction achieved by a mixture
[a] S. Lemouzy, Dr. D. H. Nguyen, V. Camy, M. Jean, Dr. D. Gatineau,
Dr. L. Giordano, Dr. N. Vanthuyne, Dr. D. HØrault, Prof. G. Buono
Aix Marseille UniversitØ, Centrale Marseille, CNRS
iSm2 UMR 7313, 13397, Marseille (France)
E-mail: damien.herault@centrale-marseille.fr
gerard.buono@centrale-marseille.fr
[b] Dr. J.-V. Naubron
Spectropole Aix Marseille UniversitØ
13397, Marseille (France)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201502647.
of HSiCl3 and BH3·THF complex.[9] Interestingly Kiełbasinski and
´
Chem. Eur. J. 2015, 21, 15607 – 15621
15607
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
co-workers[10] reported that enantioenriched hydroxyalkyl-TPOs
could be reduced stereoselectively to the corresponding TPBs
at room temperature by using BH3·THF alone. Very recently, by
using this reducing reagent, Pietrusiewicz and co-workers pub-
lished the preparation of a large family of functionalized TPBs
(Scheme 1, path C).[11] At the same time, our group developed
a new methodology for the synthesis of these important mole-
cules throughout three stereoselective steps (Scheme 1,
path D).[12] Starting from optically pure H-adamantylphenyl-
phosphinate 1, we were able to prepare enantiopure hydroxy-
methyl-TPBs. First, optically pure H-adamantyl (hydroxymethyl)-
phosphinates (e.r.>97.5:2.5) were prepared, then reduced by
stereospecific reduction with BH3·THF to obtain the corre-
sponding H-adamantyl(hydroxymethyl)phosphinites boranes
(e.r.>97.5:2.5). The latter afforded by alkylation the hydroxy-
methyl-TPBs (e.r.>99.5:0.5).
with inversion of configurations at phosphorus. Others[16] and
our group[17] have shown that substitution reaction results
from a two-step reaction path involving first a deprotonation
of H-phosphinates followed by a substitution of the menthy-
loxy group. Depending on the reactivity of the organometallic
reagent, we have demonstrated a competitive reaction be-
tween the H-menthylphenylphosphinate and the leaving men-
thylate anion. This degenerate process, whereby the nucleo-
phile and leaving group are the same, causes epimerization of
the phosphorus chiral center and a subsequent decrease in
the enantioselectivity of the SPOs. Therefore we underwent re-
cently the preparation of a more stable phosphinate, the H-
adamantylphenylphosphinate 1.[18] 25 g of each enantiomer
can be prepared by semipreparative chiral HPLC. We demon-
strated its significant reactivity, affording a large variety of P-
stereogenic compounds through
a
divergent strategy.[12]
Herein we report a practical synthesis of functionalized TPBs
4, combining the two-step one-pot synthesis of optically pure
a and b-hydroxyalkyl-TPO 3 followed by their stereospecific
BH3-mediated reduction (Scheme 1, path A). We aim to study
the stereochemistry of the reactions by assigning precisely the
absolute configuration of the P=O 3 and P-BH3 4 compounds
by vibrational circular dichroism (VCD) and X-ray diffraction
(XRD) of the obtained crystals. The dynamic stereochemistry of
the chiral compounds and the NMR studies support the inter-
mediates involving in the borane reduction reaction.
Among these compounds, enantioenriched SPOs were ob-
tained in good yields and enantioselectivities.
We applied herein this strategy to develop the synthesis of
optically pure phosphine oxides 3. Enantiopure (SP)- or (RP)-
1 reacts with 2 equivalent of tert-butyllithium or methyllithium
to form the phosphinito intermediate 2, which then reacts in
situ with various aldehydes or epoxides as electrophiles to
afford the chiral TPO 3 in moderate to good yields (Table 1).
This one-pot synthesis is very convenient, as it avoids the non-
trivial purification of the SPO from 1-adamantanol (derived
from the hydrolysis of 2). Moreover, the reaction is divergent,
as it allows the introduction of two different alkyl groups (tBu
or Me) on the phosphorus atom, as well as various pendant
hydroxyalkyl chains. Remarkably, no erosion of the enantiomer-
ic excess was observed (although a very slight erosion was
noted in the case of the formation of 3b). All compounds
were obtained with high enantioselectivity. When using paraf-
ormaldehyde as an electrophile, the alkylations were complet-
ed in only 2 h (Table 1, entries 1–3), regardless of the alkyl
groups on the phosphorus atom. For the other aldehydes and
epoxides, the alkylations were slower (completed in 15 h). For
acetaldehyde, we observed a low diastereoselectivity (1.4:1) in
favor of the like (SP,S)-diastereoisomer 3d (according to XRD;
see the Supporting Information). For benzaldehyde, a better
diastereoselectivity was obtained (3:1). The addition of 2,2-di-
phenylepoxide (Table 1, entry 11) afforded the phosphine oxide
3h in low yield.
Results and Discussion
Two-step one-pot synthesis of a- and b-hydroxy-functional-
ized phosphine oxides
The preparation of functionalized TPOs 3 was developed first
by Haynes and co-workers.[13] The reaction of the configura-
tionally stable lithiated P-chiral tert-butylphenylphosphine
oxide with aldehydes and a,b-unsaturated carbonyl com-
pounds takes place at À788C, resulting in high yields with
moderate to good diastereoselectivities. These phosphinylation
reactions proceed with retention of configuration at the phos-
phorous atom. From ethylphenylphosphinate, other TPOs have
been prepared by reaction with tert-butyllithium, followed by
addition of propylene oxide.[9,14] Recently, first-rank studies on
crystallization-induced asymmetric transformations developed
by Minnaard and co-workers showed the importance of ob-
taining hydroxy-functionalized TPO 3.[15] Starting from racemic
secondary phosphine oxide (SPO), a family of optically pure a-
hydroxymethyl TPOs was obtained with good yield and diaste-
reoselectivities, thanks to the consecutive crystallization-in-
duced asymmetric transformations.
We also carried out the preparation of analogues of the
phosphine oxide 3a in which the OH group is replaced by vari-
ous functions: ether 6 (Scheme 2), tertiary amine 7, secondary
amine 8, alkene 9, ketone 10 and amide 11 (Table 2).
Synthesis of phosphine–boranes through stereospecific BH3-
mediated reduction
According to these studies, enantioenriched compounds 3
were prepared from SPO or from the lithiated phosphinite 2,
which can be obtained from phosphinates (Scheme 1, path B).
Indeed P-stereogenic SPOs have been synthesized with an ex-
cellent enantioselectivity from diastereoisomerically pure (RP)-
H-menthylphenylphosphinate and organolithium or Grignard
reagents. The nucleophilic substitution of the menthyloxy leav-
ing group of the H-phosphinate proceeds stereospecifically
With a family of optically pure a- or b-hydroxyalkyl TPOs 3 and
a-functionalized TPOs 6–10 in hand, we studied their reduc-
tion with borane complexes. In contrast with the mechanism
[10b]
´
proposed by Kiełbasinski,
who did not consider the partici-
pation of the hydroxy group in the reduction (Scheme 3,
path A), Pietrusiewicz and co-workers[11] suggested that the re-
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15608
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
formation of 4a regularly. With
2 equivalents of BH3·THF, the re-
duction went almost to comple-
tion (Table 3, entry 5) but the
system reached the maximum
conversion when using 3 equiva-
lents of borane. After hydrolysis,
compound 4a was obtained in
94% yield (Table 3, entry 7).
Table 1. One-pot preparation of optically enriched tertiary phosphine oxides (TPO) 3 from enantiopure phos-
phinate 1.
Entry
1
R1
Electrophile
n
R2
R3
t [h]
Yield [%]
d.r.
3 (e.r.)
(RP)-3a (99:1)
To better understand the
nature of different species in-
volved during the reduction pro-
cess, we monitored the reduc-
tion by 31P NMR spectroscopy.
This allowed the observation of
the disappearance of starting
material 3a and the appearance
of the supposed intermediates A
and B (Scheme 3). However, it
appears that the reaction mix-
ture is more complex due to the
formation of the compounds An
and Bn by the disproportionation
equilibria (Scheme 5). As previ-
ously mentioned, when using
0.33 equivalents of BH3·THF, no
reduction of the P=O bond oc-
curred, even if 3a disappeared
completely (Table 3, entry 1). No-
tably, after 90 h, only one narrow
peak at d=41 ppm (31P NMR)
was observed, as well as a broad
peak at d=20 ppm (11B NMR).
1
2
3
4
5
SP
RP
RP
SP
RP
tBu
tBu
Me
tBu
tBu
0
0
0
1
1
H
H
H
H
H
H
H
H
H
H
2
2
66
67
48
67
66
n.a.
n.a.
n.a.
n.a.
n.a.
(SP)-3a (99.5:0.5)
(SP)-3b (96:4)
2[a]
15
15
(RP)-3c (99.5:0.5)
(SP)-3c (99.5:0.5)
6
RP
SP
SP
SP
SP
tBu
tBu
tBu
tBu
tBu
0
1
1
0
1
Me
Me
H
H
H
15
15
15
15
15
58
61
64
67
54
1.4:1
(SP,S)-3d (>99.5:0.5[b]
(RP,R)-3e (99.5:0.5)
(RP,S)-3e (99.5:0.5)
)
7
>20:1[c]
>20:1[c]
3:1
8
Me
Ph
H
9
H
(RP,R)-3 f (99.5:0.5[d]
)
10
Ph
>20:1[e]
(RP,R)-3g (99.5:0.5)
(SP)-3h (99.5:0.5)
11
RP
tBu
1
Ph
Ph
15
20
n.a.
Equation depicts absolute configuration SP for compound 1. [a] Addition of phosphinate was carried out at
À208C; [b] absolute configurations of the major diastereoisomer determined by DRX analysis; e.r. of minor dia-
stereoisomer=98.5:1.5; [c] reaction with racemic phosphinate and epoxide gave a 1.4:1 diastereoisomeric
ratio; [d] absolute configuration assigned by analogy with the compound 3d; e.r. of minor diastereoisomer=
98:2; [e] reaction with racemic phosphinate and epoxide gave a 1.2:1 diastereoisomeric ratio.
Table 2. Preparation of optically enriched functionalized tertiary phos-
phine oxides (TPO) from enantiopure SPO 5.
Scheme 2. Synthesis of a-methoxyether tertiary phosphine oxide 6.
duction of the phosphine oxides 3 is promoted by the pres-
ence of the OH group, which reacts first with BH3 to afford the
5-membered ring key intermediate A. The latter evolves for
further reduction, providing the reduced compound
B
(Scheme 3, path B). Recently, we employed this convenient
method to obtain optically pure hydroxymethylphosphinite–
boranes.[12] Interestingly, this reduction led to the selective re-
duction of the P=O bond with limited reduction of the POAd
bond (Scheme 4).
To gain more information on the mechanism of this reduc-
tion, we examined the influence of the amount of BH3·THF
complex on the conversion of 3a into B (in situ 31P NMR analy-
sis) and on the yield of 4a after 2 h at room temperature
(Table 3 and Figure 1). When using 0.33 equivalents of BH3·THF,
3a was fully converted but no reduction of the P=O bond oc-
curred (Table 3, entry 1). When increasing the amount to
0.66 equiv, a small amount of 4a was detected but not isolated
(Table 3, entry 2). Increasing the amount of borane allowed the
Entry
RR’NH or RX
Method
Yield [%]
TPO (e.r.)
(RP)-7 (99:1)
1
2
Et2NH
BnNH2
A
A
62
66
(RP)-8 (95.5:4.5)
3
B
81
(RP)-9 (99.5:0.5)
4
B
53
10
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15609
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
This suggests the presence of
the P=O species alone without
interaction (due to steric hin-
drance) with the formed B(OR)3
unit. According to this data, we
supposed that the compound A3
had been formed (see NMR
spectra in the Supporting Infor-
mation). When 3a reacts with
0.66 equivalents of borane, the
intermediates
B were formed
after 2 h, according to the
31P NMR spectrum (Figure 2).
The broad peaks detected at
d=27–33 ppm were attributed
to PÀBH3 species indeed the sig-
nals correspond to the one ob-
tained when the compound 4a
is in presence of 0.5 equivalents
of BH3·THF in [D8]THF (see NMR
´
Scheme 3. Proposed mechanism by Kiełbasinski (path A) and Pietrusiewicz (path B) for the BH3-mediated reduc-
tion of a-hydroxymethyl TPO. Molecules of THF that stabilize the boron species are omitted for clarity.
Scheme 4. Stereospecific reduction of a-hydroxymethylphosphinate to a-hy-
droxymethylphosphinite–borane.
Figure 1. Influence of the amount of BH3·THF on the formation of intermedi-
ates B.
Table 3. Influence of the amount of BH3·THF on the conversion of phos-
phine oxide 3a into phosphine–borane 4a.
spectra in the Supporting Information). After 24 h, we detected
a broad and intense peak at d=43–44 ppm, corresponding to
a mixture of compounds A. This chemical shift corresponds to
that of PÀO species with a weak interaction with the neighbor-
ing boron atom. After 70 h, the thermodynamic mixture pres-
ents two major peaks, one at d=41 ppm that corresponds to
the one attributed to A3 and the other at d=27–28 ppm inher-
ent to one of the compounds B.
We have considered the dynamic stereochemistry of the
borane reduction from enantiopure starting compounds. The
reaction is stereospecific, as the reductions on enantiopure
(RP)- and (SP)-3a occurred with inversion of the configuration
at the phosphorus atom and led only to the enantiomers (RP)-
and (SP)-4a, respectively (Table 3, entries 9-12). The inversion
and the absolute configuration of the P-stereogenic centers
were determined by XRD (Figure 3) and confirmed by VCD
spectroscopy (Figure 4), the efficiency of which has been
proven in solving the absolute configurations of numerous
chiral molecules.[19]
Entry e.r. of
Equiv. of
BH3·THF
Conv.
[%][a]
B
Yield
e.r. of
4a
3a
[%][b] [%][c]
[d]
1
2
3
4
5
6
7
8
rac
rac
rac
rac
rac
rac
rac
rac
0.33
0.66
1
1.33
2
2.5
3
6
100
0
12
35
64
93
100
100
100
100
64
–
–
–
–
rac
rac
rac
rac
rac
rac
98:2 (RP)
97:3 (RP)
95:5 (SP)
96:4 (RP)
100
100
100
100
100
100
100
n.d.
n.d.
n.d.
n.d.
31
59
88
91
94
96
91
59
87
97
9
97:3 (RP) 2.5
10
11
12
99:1 (RP) 1.33
97:3 (SP)
99:1 (RP) 6
6
100
100
Equation depicts absolute configuration RP for compound 3a. [a] After
2 h, determined by 31P NMR spectroscopy; [b] after 2 h, presence of the
intermediates B determined by 31P NMR spectroscopy; [c] isolated prod-
uct; [d] 70% of starting material recovered.
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15610
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
able. Although less intense, like
BÀH stretching bands it is isolat-
ed on the VCD spectra and its
negative sign can be related to
the (SP) absolute configuration.
Thus, by analysing the IR and
VCD spectra in the spectral
range 3800–1800 cmÀ1, but also
between 1800 and 1050 cmÀ1
(see the Supporting Informa-
tion), we established unambigu-
ously the absolute configura-
tions (SP) of enantiomer (À)-4a.
Considering that a majority of
calculated bands of (RP)-3a have
the same signs and intensities as
the measured bands of (À)-3a,
we were also able to establish
its absolute configuration.
Scheme 5. Disproportionation during the reduction of 3a with BH3. Only the homodimers or trimers of the P=O
(A2 and A3) and PÀBH3 (B2 and B3) species were drawn for clarity but heterodimers or trimers should be also pres-
ent.
The optimized conditions
(3 equivalents of BH3·THF) were
applied to the reduction of the
enantiopure a- or b-hydroxyalkyl
TPO 3 (Table 4). The main point
of this study is the stereospecifi-
ty of the reaction as observed in
the case of 3a. Here again, the
reactions occurred with inversion
of configuration at the phospho-
rus atom, as confirmed for the
products 4c and 4d by XRD (see
the Supporting Information) and
VCD (Figure 5). Thanks to the
couplet at 2400 cmÀ1, we estab-
lished the absolute configuration
(SP) of (À)-4c and (SP,S) of (À)-
4d.
The reduction of the com-
pounds 3 probably proceeds ac-
cording to the same mechanism.
However, b-hydroxyalkyl TPO
(n=1; Table 4, entries 2, 3, 5, 6,
8, and 9) were much less reac-
tive than a-hydroxyalkyl TPO
Figure 2. 31P NMR spectra from the reaction of 3a with 0.66 equivalents of BH3·THF in [D8]THF at 258C.
The absolute configurations of pure enantiomers (À)-3a and
(À)-4a were obtained by comparing their experimental IR and
VCD spectra with the corresponding average spectra calculat-
ed for (RP)-3a and (SP)-4a enantiomers, respectively. A very in-
teresting couplet at 2400 cmÀ1 can be observed on the spec-
trum of 4a, which is associated to the stretching vibrational
modes of the BÀH bonds of the borane moiety. These bands,
relatively intense and isolated on the spectra, are very good
chirality indicators that have, to our knowledge, not to date
been used for this series of molecules. Indeed the sign of the
couplet (À or +) can be related to the absolute configuration
(SP) of the molecule. The band associated to the stretching vi-
brational mode of the OÀH bond (3600 cmÀ1) is also remark-
(n=0; Table 4, entries 1, 4, and 7). Indeed, a higher tempera-
ture (508C) and more borane (6 equiv) were necessary to
obtain the TPB with moderate yields (34–57%). The difference
in the length of the alkyl chain is probably responsible of this
difference of reactivity. The first step of the reduction is sup-
posed to be the formation of a PÀOÀB key intermediate A (see
Scheme 3, path B). Compounds 3a,b,d,f would form a 5-mem-
bered ring intermediate whereas compounds 3c,e,g,h would
form a 6-membered ring intermediate. It is interesting to com-
pare this difference in reactivity to that observed during the
hydrolysis of cyclic phosphonium species, which is 1300 times
faster for the 5-membered ring than for the 6-membered
ring.[20]
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15611
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Figure 3. Single crystal X-Ray structures of phosphine oxides 3a and corre-
sponding phosphine–boranes 4a. Thermal ellipsoids are set at 50% proba-
bility. Hydrogen atoms are omitted for clarity.
In the case of the reductions of 3d and 3 f (n=0, R3 ¼ H),
racemic secondary phosphine–borane (SPB) tBuPhP(BH3)H was
obtained in 12 and 11 % yields, respectively (Table 4, entries 4
and 7), and the amount does not increase for the prolonged
reaction time. Moreover, 4d does not undergo the retro-phos-
phinylation in the presence of excess BH3, even under heating
conditions, which shows the stability of the protected phos-
phine. Nevertheless, a loss of d.r. was observed during the for-
mation of 4d and 4 f (respectively from >20:1 to 15:1 and
from 3:1 to 2.5:1), and the e.r. of the minor diastereoisomer of
4 f was 87:13 (Table 4, entry 7). These results can be attributed
to the instability of the free a-hydroxyphosphines, which give
Figure 4. VCD spectra of 3a [top; green: measured for (À)-3a; blue: calcu-
lated for (RP)-3a] and 4a [bottom; green: measured for (À)-4a; blue: calcu-
lated for (SP)-4a]
achiral tert-butylphenyphosphide according to a retro-phosphi-
nylation.
To study the BH3 reduction chemoselectivity, different at-
tempts were made to reduce the various a- or b-functionalized
phosphines (ether 6, tertiary amine 7, secondary amine 8,
alkene 9, ketone 10, and amide 11; Scheme 6).
Table 4. Reduction of TPO 3 to TPB 4.
Entry
3 (e.r./d.r.)
n
R1
R2
R3
t [h]
T [8C]
Yield [%]
d.r.[a]
n.a.
n.a.
n.a.
15:1
>20:1
>20:1
2.5:1
4 (e.r.)[b]
1
2
3
4
5
6
7
8
9
(SP)-3b (96:4)
(RP)-3c (99:1)
(SP)-3c (99.5:0.5)
(SP,S)-3d (98.8:1.2/>20:1 d.r.)
(RP,R)-3e (99.5:0.5/>20:1 d.r.)
(RP,S)-3e (99.5:0.5/>20:1 d.r.)
(RP,R)-3 f (99.5:0.5/3:1 d.r.)
(RP,R)-3g (99.5/:0.5/>20:1 d.r.)
(SP)-3h (99.5:0.5)
0
1
1
0
1
1
0
1
1
Me
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
H
H
H
Me
Me
H
Ph
Ph
Ph
H
H
H
H
H
Me
H
H
2[c]
72[d]
72[d]
5
84[d]
84[d]
2
25
50
50
25
50
50
25
50
50
87
56
59
73[e]
51
(SP)-4b (96.5:3.5)
(RP)-4c (99.5:0.5)
(SP)-4c (99.5:0.5)
(SP,S)-4d (99:1)
(SP,R)-4e (99.5:0.5)
(RP,S)-4e (99.5:0.5)
(RP,R)-4 f (98.5:1.5[g]
)
54
63[f]
57
72
72
>20:1
(RP,R)-4g (>99.5:0.5)
(SP)-4h (98.5:1.5)
Ph
41
n.a.
Equation depicts absolute configuration RP for compound 3a–h. [a] Determined by 31P NMR spectroscopy before the workup; [b] e.r. of the major diaste-
reoisomer; [c] with 4 equivalents of BH3·THF; [d] with 6 equivalents of BH3·THF; [e] 12% of racemic SPB was also isolated; [f] 11 % of racemic SPB was also
isolated; [g] e.r. of minor diastereoisomer was 87:13.
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15612
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
The reduction of the b-ketone/phosphine oxide 10 was also
interesting (Scheme 6). At room temperature, only the ketone
function was reduced after 72 h to give the secondary alcohol
3g (57% conversion determined by 31P NMR spectroscopy) in
1.3:1 d.r. At 508C, the reaction went further, affording the
phosphine–borane 4g (35% conversion). This corroborates the
result obtained during the reduction of 3g, which forms the
less reactive 6-membered ring intermediate (Table 4, entry 8).
In the case of a-amide/phosphine oxide 11, the a-secondary
amino phosphine–borane 12 and the a-amide/phosphine–
borane 15 were obtained in 53 and 10% yield, respectively,
after 2 h (Scheme 7 and the Supporting Information). The re-
Scheme 7. a-Functionalized phosphine oxides 7, 9, and 11 and their re-
duced derivatives 12, 13, 14, and 15.
duction of the other functionalized phosphine oxides 7 and 9
was also examined. Surprisingly the a-tertiary amino phos-
phine oxide 7 was reduced to the non-stable a-tertiary amino
phosphine–borane 14 (29% conv. after 60 h). This reactivity
could be explained by the BH3ÀNR3 interaction, which could
be sufficient to activate the neighboring P=O group. The b,g-
alkenyl phosphine oxide 9 was converted by action of BH3 into
the phosphine–borane 13, as a mixture of disproportionation
products (based on 31P NMR of the crude; attempted derivati-
zation with H2O2/NaOH(aq) led only to trace amount of alcohol;
see the Supporting Information).
Figure 5. VCD spectra of 4c [top; green: measured for (À)-4c; blue: calculat-
ed for (SP)-4c] and 4d [bottom; green: measured for (À)-4d; blue: calculat-
ed for (SP,S)-4d]
Isolation of the key intermediate A
To establish the presence of a 5-membered ring intermediate
during the reduction, we undertook the preparation of the spi-
roborate A4, by addition of 1.05 equivalents of pinacolborane
or catecholborane to 3a (Scheme 8). No cyclic intermediate
was isolated with pinacolborane. However, with catecholbor-
Scheme 6. Attempts at reduction of ether 6, amine 8, and ketone 10.
All reactions were carried out with 6 equivalents of BH3·THF
complex. As expected, no reaction occurred with the a-ether/
phosphine oxide 6. This result accounts for the implication of
the hydroxy group in the mechanism of the P=O reduction.
The a-secondary amino phosphine oxide 8 was transformed
into the a-amino phosphine–borane 12 in 84% yield. Starting
from enantioenriched 8 (e.r.=95.5:4.5), the reduction occurred
with a very slight erosion of the enantiomeric excess (e.r.=
93:7). The prior formation of R1R2NHÀBH3 complex could lead
À
to the formation of the dehydrogenated R1R2N+=BH2 with
the assistance of the neighboring P=O bond.[21] This species
could give rise to a 5-membered ring A-type intermediate, as
in the favorable enantioselective reduction of 3a.
Scheme 8. Isolation of the spiroborate A4 during reduction of 3a with vari-
ous types of borane.
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15613
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Table 5. Effect of the nature of the borane on enantioselectivity.
Entry
e.r. of 3a
Step 1
Step 2
Yield [%]
e.r. of 4a
1
2
3
4
99.5:0.5 (SP)
99:1 (RP)
99:1 (RP)
2 equivalents of BH3·SMe2, 6 h
–
87
91
69
0
97:3 (SP)
51:49
82:18 (RP)
n.d.
4 equivalents of catecholborane, 2 h[a]
1.05 equivalents of catecholborane, 1 h
4 equivalents of pinacolborane, 6 h
3 equivalents of BH3·SMe2, 08C, 1 h
1.33 equivalents of BH3·THF, RT, 2 h
–
98.9:1.1 (RP)
Equation depicts absolute configuration RP for compound 3a. [a] The reduced products were detected by 31P NMR before the Step 2 which resulted in
their protection (see the Supporting Information).
ane, the cyclic intermediate 17 was isolated in 68% yield (see
the Supporting Information). The 31P{1H} NMR spectrum dis-
plays a broad signal at d=68 ppm, which is shifted to lower
field with respect to 3a, thus evidencing the interaction be-
tween P=O and B(OR)3.[22] Moreover, the 11B NMR spectrum
showed a more shielded shift (d= +12.7 ppm) compared to
that of catechol–B(OR) (d= +23 ppm).[23] Similarly, reaction of
3c with catecholborane afforded the corresponding 6-mem-
bered ring intermediate as confirmed by the 31P{1H} and
11B NMR at d=67.9 and 13.3 ppm, respectively. Unfortunately,
crystallization attempts were not successful due to the high
moisture sensitivity.
Further experiments were carried out to study the effect of
the nature of borane on the reduction of the P=O bond
(Table 5). As expected, reduction with BH3·SMe2 required
longer reaction time to be completed, although the enantio-
purity was not extensively affected (e.r.=97:3; Table 5, entry 1).
Surprisingly, the catecholborane reduced 3a, also but led to
complete racemization (Table 5, entry 2). In contrast, pinacol-
borane failed to reduce P=O (Table 5, entry 4). Reducing 3a
stepwise with 1.05 equivalents of catecholborane followed by
Scheme 9. Proposed mechanism for the stereospecific BH3-mediated reduc-
1.33 equivalents of BH3·THF afforded compound 4a with a re-
duction of enantiopurity to e.r.=82:18 (Table 5, entry 3). The
racemization process with catecholborane is evident. Although
the exact mechanismrequires further study, we believe that
the free phosphine tBuPhPCH2O–catecholborane, formed
under BH3-deficient conditions, can reversibly undergo the ret-
roaddition reaction to form the symmetrical tBuPhPÀ phos-
phide anion.
tion of 3. Molecules of THF that stabilize the borane species are omitted for
clarity
ular acid–base Lewis interaction between the alkoxyborane
and the oxygen of the P=O bond affords a 5-membered cyclic
zwitterionic phosphonium intermediate “cyclic A.” The latter
reacts with the BH3·THF in the position anti to the PÀO bond
to give a pentacoordinated oxyphosphorane H with an anionic
five membered ring bound at one apical position (through O)
and one equatorial position (through C) of the trigonal bipyra-
midal (TBP) structure and the hydrogen at the other apical po-
sition. The R1 and R2 substituents and the ring carbon are posi-
tioned in favorable equatorial positions with respect to the api-
cophilicity rule.[24] This mechanism involves an inversion of con-
figuration at phosphorus affording the H–phosphonium inter-
mediate I. Ring strain imposed on the intermediate “cyclic A”
may lower the energy difference between the latter and transi-
tion state, if that strain is partly relieved along the reaction co-
ordinate. Indeed the borane reduction rate depends on the
ring size of the intermediate; for n=0, the phosphine oxide is
Mechanistic aspects of BH3-mediated reduction
The above experimental data demonstrates the implication of
one molecule of BH3 in the formation of the 5-membered ring
intermediate “cyclic A,” which activates the P=O bond to allow
its reduction, as suggested by Pietrusiewicz and co-workers.[11]
Therefore, we proposed a mechanism whereby the participa-
tion of the hydroxymethylene chain is a determining factor in
the reduction of the P=O bond (Scheme 9).
In a first step, fast deprotonation of the alcohol group with
borane leads to the formation of an alkoxyborane
R1R2P(O)CH2OBH2 A and hydrogen gas. A favorable intramolec-
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15614
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
yellow mixture was stirred for 15 min at around À758C. Then, a so-
lution of adamantylphosphinate in THF (1 equiv) (0.5m in THF) was
added dropwise at À788C and the reaction mixture was main-
tained at a temperature below À758C for 1 hour. The mixture was
allowed to warm to À308C over 3 h and at that temperature, dis-
tilled water (15 mL) was added and then the reaction was warmed
to room temperature. Then, corresponding aldehyde (1.6 equiv)
was added and the mixture was stirred for 1 h. The reaction mix-
ture was cooled to 0–58C and quenched with saturated aqueous
NH4Cl (30 mL). The aqueous layer was extracted with EtOAc (3”
50 mL), and the organic solutions were dried over MgSO4 and con-
centrated under reduced pressure. The crude product was purified
by column chromatography on silica gel using a combination of
petroleum ether and acetone.
reduced very fast compared with the phosphine oxide with
n=1, for which the reduction is very slow (see Table 4). The
deprotonation of the phosphonium I with the pendant alkoxy–
BH2 anion leads to the free phosphine J, which has to be
quickly protected by BH3 to retain its enantiopurity. The final
hydrolysis releases the desired compound 4. In the case of the
reduction of 3d or 3 f we observed the partial formation of
racemic SPB (Table 4, entries 4 and 7). This could be explained
by the cleavage of the PÀC bond (retro-phosphinylation),
which could occur during the different steps of the reduction,
probably from intermediates A or J. This borane reduction
mechanism, based on the PV phosphorane intermediate, could
also be applied to interpret the reduction of the adamantyl(hy-
droxymethyl)phenylphosphinate (R1 =AdO; R2 =Ph; R3 =H), in
which the departure of AdO was limited. The apical attack of
the hydride on the cyclic phosphonium A’, in line with the
AdO substituent, leads an unfavorable diequatorial positioning
of the five-membered ring, with the hydride and AdO substitu-
ents in the apical positions of the trigonal bipyramid H’. This
unfavorable process is high in energy with respect to a hydride
attack, leading to a privileged phosphorane H (Scheme 10).
(RP)-tert-Butyl(hydroxymethyl)(phenyl)phosphine oxide [(RP)-3a] was
obtained according to procedure A as a white solid (obtained by
washing the crude several times with cold ether instead of column
chromatography) with a 66% yield (405 mg). ½aŠ20 =À16.8 (c=
D
0.53, CHCl3); 1H NMR (400 MHz, CDCl3): d=7.70 (ddd, J=8.4, 7.5,
1.5 Hz, 2H), 7.59–7.36 (m, 3H), 5.51 (td, J=6.7, 3.1 Hz, 1H), 4.43
(dd, J=14.4, 6.6 Hz, 1H), 4.25 (dd, J=14.3, 6.4 Hz, 1H), 1.14 ppm
(d, J=14.4 Hz, 9H); 31P NMR (162 MHz, CDCl3): d=46.42; 13C NMR
(101 MHz, CDCl3): d=131.93 (d, J(C,P)=7.3 Hz), 131.93, 128.88 (d,
J(C,P)=85.3 Hz), 128.48 (d, J(C,P)=10.3 Hz), 57.59 (d, J(C,P)=
72.2 Hz), 32.71 (d, J(C,P)=65.6 Hz), 24.80; HPLC separation (Lux-
Cellulose-2, hexane/isopropanol 50:50, 1 mLminÀ1, UV 254 nm);
tR (SP)=5.24 min, tR (RP)=8.60 min), e.r.=99:1; these data are con-
sistent with those in the literature.[10b]
(SP)-tert-Butyl(hydroxymethyl)(phenyl)phosphine oxide [(SP)-3a]:
½aŠ20 = + 20.3 (c=0.48, CHCl3); e.r.>99.5:0.5; Single crystal growth
D
for X-ray molecular structure determination was carried out into
Et2O/n-hexane at À208C. The absolute configuration of the crystal-
lized molecule is SP.
Scheme 10. Extension of the mechanism to adamantyl(hydroxymethyl)phe-
nylphosphinate.
(SP)-(Hydroxymethyl)(methyl)(phenyl)phosphine oxide [(SP)-3b) was
obtained according to procedure A as a white solid with a 48%
overall yield (147 mg) using methyllithium at À208C as nucleo-
phile. ½aŠ20 =À17.3 (c=1.00, CHCl3); H NMR (400 MHz, CDCl3): d=
1
D
Conclusion
7.77–7.65 (m, 2H), 7.58–7.50 (m, 1H), 7.50–7.43 (m, 2H), 5.78 (d,
J=3.6 Hz, 1H), 4.08 (ddd, J=14.4, 5.4, 4.0 Hz, 1H), 3.99 (dd, J=
14.3, 7.1 Hz, 1H), 1.77 ppm (d, J=12.9 Hz, 3H);31P NMR (121 MHz,
CDCl3): d=37.59; 13C NMR (101 MHz, CDCl3): d=132.10 (d, J(C,P)=
2.7 Hz), 131.28 (d, J(C,P)=93.6 Hz), 130.40 (d, J(C,P)=9.1 Hz),
128.74 (d, J(C,P)=11.4 Hz), 62.27 (d, J(C,P)=81.9 Hz), 12.73 ppm (d,
J(C,P)=68.9 Hz); these data are consistent with those in the litera-
ture;[11] Rf =0.25 (3:1 petroleum ether/acetone); HPLC separation
(Chiralpak AS-H, heptane/ethanol 80:20, 1 mLminÀ1, UV 254 nm;
tR (RP)=6.29 min, tR (SP)=7.61 min), e.r.=96:4.
In summary, we have developed a stereospecific efficient syn-
thesis of a- and b-hydroxy-functionalized P-chiral tertiary phos-
phine–borane complexes from enantiopure H-adamantylphe-
nylphosphinate. We have shown that the a- and b-hydroxy
chain bound to the phosphorus plays a major role in the re-
duction of P=O. This chain controls the stereochemistry of the
reduction by formation of a pentacoordinated PV intermediate.
Indeed the BH3 play three roles: activating, reducing and pro-
tecting agent. We are convinced that this synthetic method
will be used to prepare different functionalized stereogenic PIII
compounds.
(SP)-tert-Butyl-((SC)-1-hydroxyethyl)phenyl)phosphine oxide [(SP,S)-
3d] was obtained according to procedure A as a white solid with
1
a 58% yield. H and 31P{1H} NMR shows d.r. of 1.4:1.0. Major diaste-
reoisomer was isolated by crystallization in CH2Cl2/n-hexane at
1
À208C. (Yield 0.17 g, 13%); H NMR (400 MHz, CDCl3): d=7.69 (m,
2H), 7.51 (m, 1H), 7.45 (m, 2H), 4.82 (br s, 1H, -OH), 4.57 (qd, J=
6.8, 6.8 Hz, 1H), 1.33 (dd, J=6.8, 14.0 Hz, 3H), 1.23 ppm (d, J=
14.4 Hz, 9H); 31P NMR (162 MHz, CDCl3): d=48.12.13C NMR
(101 MHz, CDCl3): d=131.78 (d, J(C,P)=2.2 Hz), 131.70 (d, J(C,P)=
7.3 Hz), 130.09 (d, J(C,P)=80.0 Hz), 128.51 (d, J(C,P)=10.3 Hz),
64.73 (d, J(C,P)=72.6 Hz), 33.42 (d, J(C,P)=64.2 Hz), 25.56,
18.25 ppm; minor diastereoisomer: 1H NMR (400 MHz, CDCl3): d=
7.94 (m, 2H), 7.51 (m, 1H), 7.45 (m, 2H), 4.60 (qd, J=7.2 Hz, 3.2 Hz,
1H), 4.40 (br s, 1H, -OH), 1.50 (dd, J=6.8 Hz, 14.0 Hz, 3H),
1.23 ppm (d, J=14.4 Hz, 9H); 31P NMR (162 MHz, CDCl3): d=47.56;
13C NMR (101 MHz, CDCl3): d=132.81 (d, J(C,P)=7.3 Hz), 131.67 (d,
Experimental Section
General considerations are found in the Supporting Information.
Syntheses
General procedure A: One-pot nucleophilic addition/aldehyde
trapping of adamantyl phosphinate for the preparation of 3a, b,
d, and f
A flame-dried 250 mL two-necked round bottom flask was charged
with dry THF (65 mL), then the flask was cooled to À788C and or-
ganolithium reagent (2.4 equiv) was added slowly. The resulting
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15615
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
J(C,P)=2.9 Hz), 128.96, 128.08 (d, J(C,P)=10.3 Hz), 65.65 (d, J(C,P)=
79.3 Hz), 33.16 (d, J(C,P)=62.9 Hz), 25.28, 18.78 ppm (d, J(C,P)=
1.4 Hz).
87.3 Hz), 118.64 (d, J(C,P)=11.0 Hz), 47.74 (d, J(C,P)=5.9 Hz), 23.09
(d, J(C,P)=69.0 Hz), 15.71 (d, J(C,P)=63.9 Hz), 14.24 ppm; these
data are consistent with those in the literature;[11] Rf =0.2 (1:1 pe-
troleum ether/acetone); HPLC separation (Lux-Cellulose-2, hexane/
Major diastereoisomer (d.r.=50.0:1.0) was isolated by preferential
20
D
isopropanol 50:50, 1 mLminÀ1
, UV 254 nm; tR (RP)=6.67 min,
crystallization for three times in CH2Cl2/n-hexane at À208C. ½aŠ
=
tR (SP)=9.42 min), e.r.=99.5:0.5.
+1.7 (c=0.48, CHCl3); The absolute configuration of the crystal-
lized molecule is (SP,S); HPLC separation (Chiralpak IE, hexane/etha-
nol 95:5, 1 mLminÀ1, UV 254 nm; tR (SP,S)=11.33 min, tR (RP,R)=
12.48 min), e.r.=98.8:1.2.
(SP)-tert-Butyl(2-hydroxyethyl)(phenyl)phosphine oxide [(SP)-3c] was
obtained according to procedure B as a white solid (440 mg, 66%);
½aŠ20 = +61.7 (c=0.50, CHCl3) e.r.=99.5:0.5. Single crystal growth
D
for X-ray molecular structure determination was carried out into
Et2O/n-hexane at À208C. The absolute configuration of the crystal-
lized molecule is SP.
(RP)-tert-Butyl((RC)-hydroxy(phenyl)methyl)phenylphosphine oxide
[(RP,R)-3 f] was obtained according to procedure A as a white solid
1
(700 mg, 67% yield). H and 31P NMR show a d.r. of 3:1.
Major diastereoisomer: 1H NMR (400 MHz, [D6]DMSO, ppm): d=
7.74 (m, 2H), 7.75 (m, 1H), 7.4 (m, 2H), 7.34 (m, 2H), 7.18–7.08 (m,
3H), 6.24 (dd, J=5.6 Hz, 16.0 Hz, 1H), 3.33 (brs, 1H, -OH), 1.13 ppm
(d, J=14.4 Hz, 9H);31P NMR (162 MHz, [D6]DMSO): d=47.97;
13C NMR (101 MHz, [D4]MeOH): d=139.33 (d, J(C,P)=1.8 Hz), 133.21
(d, J(C,P)=7.3 Hz), 133.05 (d, J(C,P)=2.2 Hz), 130.79 (d, J(C,P)=
84.7 Hz), 129.56 (d, J(C,P)=5.1 Hz), 129.36 (d, J(C,P)=10.3 Hz),
128.93, 128.90, 73.78 (d, J(C,P)=78.2 Hz), 35.30 (d, J(C,P)=63.9 Hz),
26.08 ppm; minor diastereoisomer: 1H NMR (400 MHz, [D4]MeOH):
d=7.92 (m, 2H), 7.54 (m, 1H), 7.45 (m, 2H), 7.32 (m, 2H), 7.20-7.12
(m, 3H), 5.55 (d, J=9.6 Hz, 1H), 1.27 ppm (d, 9H, J=14.4 Hz);
31P NMR (162 MHz, [D4]MeOH): d=51 ppm; 13C NMR (101 MHz,
[D4]MeOH): d=139.57 (d, 1C, J(C,P)=2.2 Hz), 134.10 (d, J(C,P)=
8.4 Hz), 133.21 (d, J(C,P)=2.9 Hz), 128.18, 129.03 (d, J(C,P)=
10.3 Hz), 128.94, 128.91, 128.86 (d, J(C,P)=3.0 Hz), 73.36 (d, J(C,P)=
(RP)-tert-Butyl((RC)-2-hydroxypropyl)(phenyl)phosphine oxide [(RP,RC)-
3e] was obtained according to procedure B as a white solid with
a 61% overall yield (400 mg). M.p. 135–137.48C. ½aŠ20 =À58.0 (c=
D
1
1.03, CHCl3); H NMR (400 MHz, CDCl3): d=7.78–7.66 (m, 2H), 7.61–
7.44 (m, 3H), 4.95 (s, 1H), 4.09–3.88 (m, 1H), 2.18 (dt, J=14.8,
10.4 Hz, 1H), 2.09 (ddd, J=14.8, 5.0, 1.7 Hz, 1H), 1.24 (dd, J=6.1,
1.4 Hz, 3H), 1.12 ppm (d, J=15.0 Hz, 9H); 31P NMR (162 MHz,
CDCl3): d=52.93 ppm; 13C NMR (101 MHz, CDCl3): d=131.84,
131.83 (d, J(C,P)=7.8 Hz), 129.33 (d, J(C,P)=86.5 Hz), 128.45 (d,
J(C,P)=10.7 Hz), 63.25 (d, J(C,P)=5.4 Hz), 32.69 (d, J(C,P)=68.4 Hz),
31.14 (d, J(C,P)=63.6 Hz), 24.87 (d, J(C,P)=14.2 Hz), 23.90 ppm;
HRMS (ESI) calcd for [MÀH]+: 241.1352; found: 241.1353; Rf =0.2
(2:1 petroleum ether/acetone); these data are consistent to those
in the literature;[11] HPLC separation (Lux-Amylose 2, heptane/etha-
nol 90:10, 1 mLminÀ1, UV 254 nm; tR (SP,S)=10.34 min, tR (RP,R)=
11.58 min), e.r.>99.5:0.5.
81.5 Hz), 34.73 (d, J(C,P)=63.1 Hz), 25.62 ppm; these data are con-
20
sistent with those in the literature2. ½aŠ n.d. (d.r.=3:1); Rf =
D
(RP)-tert-Butyl((SC)-2-hydroxypropyl)(phenyl)phosphine oxide [(RP,SC)-
3e] was obtained according to procedure B as a white solid with
0.25(1:1 petroleum ether/acetone) HPLC separation (Lux-Cellulose-
4, heptane/ethanol 95:5, 1 mLminÀ1, UV 220 nm; major diastereo-
isomer: tR (RP,R)=12.01 min; tR (SP,S)=15.28 min, e.r.=99.5:0.5;
minor diastereoisomer: tR (RP,S)=18.45 min; tR (SP,R)=13.49 min,
e.r.=98:2.
a 64% overall yield (415 mg). M.p. 123.9-1268C. ½aŠ20 = +3.6 (c=
D
1.055, CHCl3); 1H NMR (400 MHz, CDCl3): d=7.74–7.62 (m, 2H),
7.57–7.41 (m, 3H), 4.51–4.30 (m, 2H OH+CHMe), 2.40 (ddd, J=
15.0, 8.7, 2.9 Hz, 1H), 2.16 (dt, J=15.0, 8.6 Hz, 1H), 1.26 (d, J=
6.2 Hz, 3H), 1.13 ppm (d, J=14.7 Hz, 9H); 31P NMR (162 MHz,
CDCl3): d=49.32; 13C NMR (101 MHz, CDCl3): d=131.62 (d, J(C,P)=
2.7 Hz), 131.57 (d, J(C,P)=87.6 Hz), 131.30 (d, J(C,P)=8.2 Hz),
128.24 (d, J(C,P)=10.8 Hz), 64.80 (d, J(C,P)=5.5 Hz), 33.21 (d,
J(C,P)=68.1 Hz), 32.46 (d, J(C,P)=62.9 Hz), 24.88 (d, J(C,P)=
10.8 Hz), 24.14 ppm; HRMS (ESI) calcd for [MÀH]+: 241.1352;
found: 241.1353; Rf =0.2 (2:1 petroleum ether/acetone); HPLC sep-
aration (Lux-Amylose 2, heptane/ethanol 90:10, 1 mLminÀ1, UV
254 nm tR (SP,R)=8.91 min, tR (RP,S)=9.86 min), e.r.>99.5:0.5.
General procedure B: One-pot nucleophilic addition/epoxide
trapping of adamantylphosphinate for the preparation of 3c, e,
g and h
A 100 mL round-bottom flask was charged with dry THF (25 mL)
under argon, and the flask was cooled to À788C. Then, tBuLi
(2.5 equiv) was added dropwise and the orange-yellow mixture
was stirred for 15 min at around À758C. Then, a solution of ada-
mantylphosphinate (1 equiv) in THF (5 mL) was added dropwise at
À788C and the reaction mixture was maintained at a temperature
below À758C for 1 hour. The mixture was allowed to warm to
À308C over 3 h and, at that temperature, the given epoxide
(4 equiv) was added in one portion. The mixture was warmed to
room temperature and was stirred overnight. The reaction mixture
was quenched with saturated aqueous NH4Cl (15 mL), the layers
were separated and the aqueous layer was extracted with CH2Cl2
(3”30 mL). The organic layers were combined, dried over Na2SO4,
and concentrated under vacuum. The crude mixture was separated
by column chromatography on silica gel using a combination of
petroleum ether and acetone.
(RP)-tert-Butyl((RC)-2-hydroxy-2-phenylethyl)(phenyl)phosphine
oxide [(RP,RC)-3g] was obtained according to procedure B as
a white solid with a 54% overall yield (297 mg). M.p. 93.5–96.18C;
½aŠ20 =À83.0 (c=0.73, CHCl3); H NMR (400 MHz, CDCl3): d=7.65–
1
D
7.58 (m, 2H), 7.54–7.46 (m, 1H), 7.46–7.40 (m, 2H), 7.40–7.34 (m,
2H), 7.29 (dd, J=8.1, 6.8 Hz, 2H), 7.22 (ddd, J=8.5, 2.6, 1.3 Hz, 1H),
5.42 (tt, J=9.8, 2.6 Hz, 1H), 5.03 (d, J=3.0 Hz, 1H), 2.62 (ddd, J=
15.1, 7.5, 2.5 Hz, 1H), 2.43 (ddd, J=15.1, 10.0, 8.7 Hz, 1H),
1.19 ppm (d, J=14.8 Hz, 9H); 31P NMR (162 MHz, CDCl3): d=49.32;
13C NMR (101 MHz, CDCl3): d=144.01 (d, J(C,P)=10.9 Hz), 131.56
(d, J(C,P)=2.7 Hz), 131.34 (d, J(C,P)=88.5 Hz), 131.22 (d, J(C,P)=
8.3 Hz), 128.44, 128.13 (d, J(C,P)=11.0 Hz), 127.54, 125.43, 70.61 (d,
J(C,P)=5.3 Hz), 34.00 (d, J(C,P)=41.1 Hz), 33.37 (d, J(C,P)=48.8 Hz),
(RP)-tert-Butyl(2-hydroxyethyl)(phenyl)phosphine oxide [(RP)-3c] was
obtained according to procedure B as a white solid (70% yield).
½aŠ20 =À51.7 (c=0.49, CHCl3); 1H NMR (400 MHz, CDCl3): d=7.70
D
~
(m, J=1.6, 7.6 Hz, 8.4 Hz, 2H), 7.54 (m, J=6.8 Hz, J=1.2 Hz, 1H),
7.47 (m, J=7.6 Hz, J=2.4 Hz, 2H), 3.98–3.82 (m, 2H), 3.10 (br, 1H,
-OH), 2.50–2.36 (m, J(H,H)=15.2, 8.4, 6.0 Hz, J(H,P)=10.4 Hz, 1H),
2.26–2.15 (m,1H), 1.12 ppm (d, J=14.8 Hz, 9H); 31P NMR (162 MHz,
CDCl3): d=53.14 ppm; 13C NMR (101 MHz, CDCl3): d=132.05 (d,
J(C,P)=2.2 Hz), 132.00 (d, J(C,P)=8.1 Hz), 119.70 (d, J(C,P)=
24.24 ppm; IR (ATR): n=445, 473, 494, 517, 538, 602, 642, 698, 746,
818, 1053, 1107, 1149, 1437, 2869, 2904, 2962, 3035, 3061,
3281 cmÀ1
;
HRMS (ESI) calcd for [MÀNa]+:325.1328; found:
325.1325; Rf =0.15 (3:1 petroleum ether/acetone); HPLC separation
(Chiralpak IC, heptane/ethanol 80:20, 1 mLminÀ1, UV 254 nm;
tR (SP,S)=6.47 min, tR (RP,R)=10.42 min), e.r.>99.5:0.5.
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15616
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
(SP)-tert-Butyl(2-hydroxy-2,2-diphenylethyl)(phenyl)phosphine oxide
[(SP)-3h] was obtained according to procedure B as a white solid
90:10, 1 mLminÀ1, UV 254 nm; tR (SP)=7.23 min, tR (RP)=8.75 min,
e.r.=99.5:0.5.
with a 20% yield (111 mg). M.p. 199.2–205.78C; ½aŠ20 = +6.2 (c=
D
(+/À)-2-(tert-Butyl(phenyl)phosphoryl)-1-phenylethanone (10) was
1
1.02, CHCl3); H NMR (400 MHz, CDCl3): d=7.52–7.43 (m, 2H), 7.43–
obtained according to procedure C as a white solid in a 63% yield
7.12 (m, 10H), 6.95 (br s, 1H, -OH), 6.87–6.73 (m, 3H), 3.13 (dd, J=
14.6, 5.8 Hz, 1H), 3.04 (dd, J=14.6, 10.3 Hz, 1H), 1.12 ppm (d, J=
14.9 Hz, 9H); 31P NMR (162 MHz, CDCl3): d=50.26; 13C NMR
(101 MHz, CDCl3): d=148.05 (d, J(C,P)=10.6 Hz), 144.66 (d, J(C,P)=
2.3 Hz), 131.11 (d, J(C,P)=8.3 Hz), 130.98 (d, J(C,P)=2.8 Hz), 130.03
(d, J(C,P)=88.7 Hz), 128.22, 127.80 (d, J(C,P)=11.2 Hz), 127.26,
127.01, 126.36, 126.28, 125.35, 77.46 (d, J(C,P)=5.4 Hz), 34.14 (d,
1
(188 mg). Rf =0.5 (2:1 petroleum ether/acetone); H NMR (400 MHz,
CDCl3): d=8.20–7.98 (m, 1H), 7.91–7.69 (m, 2H), 7.55–7.49 (m, 2H),
7.49–7.38 (m, 4H), 4.06 (dd, J=15.3, 13.1 Hz, 1H), 3.71 (dd, J=13.0,
11.7 Hz, 1H), 1.21 ppm (d, J=15.5 Hz, 9H); 31P NMR (162 MHz,
CDCl3): d=44.25 ppm; 13C NMR (101 MHz, CDCl3): d=193.75 (d,
J(C,P)=6.0 Hz), 137.07, 133.49, 132.25 (d, J(C,P)=8.3 Hz), 131.89 (d,
J(C,P)=2.7 Hz), 129.59, 128.84 (d, J(C,P)=90.4 Hz), 128.42, 128.06
(d, J(C,P)=11.2 Hz), 38.25 (d, J(C,P)=46.7 Hz), 34.34 (d, J(C,P)=
70.1 Hz), 24.36 ppm; HRMS (ESI) calcd for [MÀH]+: 301.1352;
found: 301.1352; these data are consistent with those in the litera-
ture.[13b]
~
J(C,P)=61.2 Hz), 33.38 (d, J(C,P)=68.9 Hz), 23.80 ppm; IR (ATR): n=
476, 512, 595, 614, 653, 691, 719, 745, 780, 818, 915, 979, 1101,
1136, 1436, 2855, 2924, 2962, 3058, 3228 cmÀ1; HRMS (ESI) calcd
for [MÀH]+: 379.1821; found: 379.1820; Rf =0.25 (100% EtOAc);
HPLC separation (Chiralpak AZ-H, heptane/ethanol 80:20,
1 mLminÀ1, UV 254 nm; tR (SP)=9.70 min, tR (RP)=12.16 min), e.r.=
99:1.
Procedure D: Synthesis of phosphine oxides 7 and 8
A
10 mL Schlenk tube was charged with paraformaldehyde
tert-Butyl(1-methoxymethyl)(phenyl)phosphine oxide (6): To a sus-
pension of NaH (60%, 40 mg) in THF (10 mL) was slowly added the
solution of (+/À)-3a (100 mg) in THF (10 mL, 10 mgmLÀ1) at
À108C. The reaction mixture was allowed to warm to 08C and
stirred for a further 1 h and the resulting mixture was quenched
with excess MeI while maintaining the temperature at 08C. The sol-
vent was removed under reduced pressure to give the solids
which were dissolved in water (20 mL). The product was extracted
with CH2Cl2 (3”20 mL), and the combined organic layers were
dried over MgSO4. After solvent removal, the product was chroma-
(1.5 equiv, 0.5m) in CH2Cl2. To the suspension of paraformaldehyde
was added the amine (1.5 equiv) and the reaction was stirred for
2 h at room temperature. Then, the solvent was removed from the
clear solution under reduced pressure and secondary phosphine
oxide were successively added (0.15m in toluene). The reaction
was heated to 110 8C for 15 h. The crude mixture was reduced in
volume by solvent removal under reduced pressure and purified
by column chromatography on silica gel using a combination of
petroleum ether and acetone as eluent.
1
tographed through a silica gel column. Yield (82 mg, 77%). H NMR
(RP)-tert-Butyl[(diethylamino)methyl](phenyl)phosphine oxide (7)
(400 MHz, CDCl3): d=7.86 (m, 2H), 7.51 (m, 1H), 7.45 (m, 2H), 4.12
(m, 1H), 4.08 (m, 1H), 3.47 (d, 3H, J=0.8 Hz), 1.17 ppm (d, 9H, J=
9.2 Hz); 31P NMR (162 MHz, CDCl3): d=41.88 (s); HRMS (ESI) calcd
for [M+H]+ 227.1195; found 227.1194; these data are consistent to
those in the literature.[11]
was obtained according to procedure D as a pale-yellow solid with
a 62% overall yield (177 mg). M.p. 67.8–70.28C; ½aŠ20 = +11.7 (c=
D
1
1.2, CHCl3); H NMR (400 MHz, CDCl3): d=7.81–7.66 (m, 2H), 7.57–
7.37 (m, 3H), 3.27 (dd, J=15.0, 6.1 Hz, 1H), 3.11 (dd, J=15.0,
4.6 Hz, 1H), 2.79 (dq, J=14.2, 7.1 Hz, 2H), 2.64 (dq, J=13.8, 7.0 Hz,
2H), 1.16 (d, J=14.2 Hz, 9H), 0.97 (t, J=7.1 Hz, 6H); 31P NMR
(162 MHz, CDCl3): d=44.48 ppm; 13C NMR (101 MHz, CDCl3): d=
131.92 (d, J(C,P)=7.4 Hz), 131.23 (d, J(C,P)=2.6 Hz), 130.77 (d,
J(C,P)=84.9 Hz), 127.93 (d, J(C,P)=10.4 Hz), 49.11 (d, J(C,P)=
78.8 Hz), 48.44 (d, J(C,P)=7.2 Hz), 33.23 (d, J(C,P)=66.2 Hz), 24.81,
Procedure C: Phase-transfer catalyzed addition of SPO to alkyl-
halides for the preparation of 9 and 10
Under argon, a 25 mL round bottom flask was charged with a solu-
tion of phosphine oxide (1 equiv, 0.2m) in technical grade toluene.
Then, the same volume of 30% aqueous KOH solution was added
at room temperature, followed by tetrabutylammonium bromide
(TBAB, 10 mol%) and the electrophile (1 equiv). After the required
amount of time, the reaction mixture was dissolved in water, the
organic layer is separated and the pH of the aqueous layer was ad-
justed around 7–8 using aqueous saturated NH4Cl, and extracted
with CH2Cl2. The organic layers were combined and dried over
Na2SO4. The solvent was removed under reduced pressure. The
crude product was purified by column chromatography on silica
gel using a combination of petroleum ether and acetone.
~
11.23 ppm; IR (ATR): n=474, 503, 517, 544, 600, 629, 698, 710, 733,
750, 779, 818, 839, 1068, 1105, 1148, 1167, 1250, 1385, 1391, 1437,
1466, 1475, 2800, 2870, 2968, 3055, 3419 cmÀ1; HRMS (ESI) calcd
for [MÀH]+:268.1825; found: 268.1828; Rf =0.2 (3:1 petroleum
ether/acetone); HPLC separation (Chiralpak AZ-H, heptane/ethanol
95:5, 1 mLminÀ1, UV 220 nm; tR (SP)=10.31 min, tR (RP)=12.41 min),
e.r.=99:1.
(RP)-[(Benzylamino)methyl](tert-butyl)(phenyl)phosphine oxide (8)
was obtained according to procedure D as a pale yellow viscous
(RP)-tert-Butyl(3-methylbut-2-en-1-yl)(phenyl)phosphine oxide [(RP)-
9] was obtained according to procedure C as a white solid with
oil with a 66% overall yield (109 mg). ½aŠ20 = +17.5 (c=0.99,
D
CHCl3,>99.5:0.5 e.r.); 1H NMR (400 MHz, CDCl3): d=7.72–7.60 (m,
2H), 7.57–7.40 (m, 3H), 7.36–7.17 (m, 5H), 3.85 (s, 2H), 3.31 (dd, J=
13.9, 7.0 Hz, 1H), 3.19 (dd, J=13.9, 5.3 Hz, 1H), 1.96 (s, N-H),
1.12 ppm (d, J=14.5 Hz, 9H); 31P NMR (162 MHz, CDCl3): d=
46.50 ppm; 13C NMR (101 MHz, CDCl3): d=139.52, 131.79 (d,
J(C,P)=7.9 Hz), 131.69 (d, J(C,P)=2.7 Hz), 130.01 (d, J(C,P)=
86.8 Hz), 128.48, 128.37, 128.35 (d, J(C,P)=10.6 Hz), 127.23, 55.43
(d, J(C,P)=13.1 Hz), 42.96 (d, J(C,P)=71.1 Hz), 32.79 (d, J(C,P)=
a 81% overall yield (166 mg). M.p. 96.6–98.18C; ½aŠ20 =À34.9 (c=
D
1
0.99, CHCl3); H NMR (400 MHz, CDCl3): d=7.80–7.65 (m, 2H), 7.53–
7.43 (m, 3H), 5.19 (qd, J=6.2, 1.3 Hz, 1H), 3.10–2.70 (m, 2H), 1.65
(m, 6H), 1.14 (d, J=14.4 Hz, 9H); 31P NMR (162 MHz, CDCl3): d=
48.00; 13C NMR (101 MHz, CDCl3): d=136.37 (d, J(C,P)=10.9 Hz),
131.93 (d, J(C,P)=7.8 Hz), 131.28 (d, J(C,P)=2.6 Hz), 130.51 (d,
J(C,P)=86.5 Hz), 128.03 (d, J(C,P)=10.6 Hz), 112.89 (d, J(C,P)=
8.2 Hz), 33.04 (d, J(C,P)=67.4 Hz), 25.84 (d, J(C,P)=2.2 Hz), 24.65,
24.18 (d, J(C,P)=63.3 Hz), 18.32 ppm(d, J(C,P)=1.8 Hz); IR (ATR):
~
67.1 Hz), 24.80 ppm; IR (ATR): n=480, 519, 544, 596, 613, 634, 744,
818, 1109, 1161, 1437, 1462, 2867, 2928, 2970, 3043, 3080, 3348,
n=434, 474, 511, 540, 627, 698, 744, 766, 818, 1107, 1165, 1437,
3446 cmÀ1
;
HRMS (ESI) calcd for [MÀH]+: 302.1668; found:
~
1475, 1634, 1662, 2862, 2904, 2970, 3059 cmÀ1; HRMS (ESI) calcd
for [MÀH]+: 251.1559; found: 251.1558; Rf =0.3 (3:1 petroleum
ether/acetone); HPLC separation (Lux-Amylose 2, heptane/ethanol
302.1668; Rf =0.3(2:1 petroleum ether/acetone); HPLC separation
(Lux-Cellulose 2, heptane/ethanol 90:10, 1 mLminÀ1, UV 254 nm;
tR (SP)=10.40 min, tR (RP)=13.02 min), e.r.=95.5:4.5.
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15617
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
(RP)-N-{[tert-Butyl(phenyl)phosphoryl]methyl}benzamide (11):
A
(128 MHz, CDCl): d=À43.68 ppm (d, J(B,P)=58.4 Hz); Rf =0.2 (5:1
10 mL Schlenk tube was charged with enantiopure tert-butyl petroleum ether/EtOAc); HRMS (EI+) calcd. for C11H20BOP [M+Na]+
phenyl secondary phosphine oxide (120 mg) and the tube was 233.1239; found 247.1233; HPLC separation (Lux-Cellulose-2,
subjected to several vaccum/argon cycles to give an inert atmos- Hexane/isopropanol 70:30, 1 mLminÀ1
phere. Then, anhydrous THF (3.5 mL) was added and the reaction 3.79 min, tR (SP)=4.25 min), e.r.=98:2.
mixture was cooled to À788C. At this temperature, MeLi solution
, UV 254 nm; tR (RP)=
(SP)-tert-Butyl(hydroxymethyl)(phenyl)phosphine–borane [(SP)-4a]:
e.r.=95:5. ½aŠ20 =À7.1 (c=0.51, CHCl3,). Single crystal growth for X-
(370 mL, 1.6m in Et2O, 0.9 equiv) was added slowly, and the reac-
tion mixture was stirred 30 min at À788C. Then, a solution of ben-
zamidomethyl acetate (0.5 gmLÀ1, 300 mL, 1.2 equiv; see the Sup-
porting Information) at À408C was added and the mixture was al-
lowed to warm to room temperature overnight. Then, the reaction
was quenched with saturated NaHCO3 solution and water, and the
water layer was extracted with EtOAc (2”25 mL). The organic
layers were combined, dried over Na2SO4, and filtered. The solvent
was removed under reduced pressure. The crude product was puri-
fied by column chromatography on silica gel using a gradient of
3:1 to 1:1 petroleum ether/acetone to give a white solid with
D
ray molecular structure determination was carried out into Et2O/n-
hexane at À208C. The absolute configuration of the crystallized
molecule is SP.
(SP)-(Hydroxymethyl)(methyl)(phenyl)phosphine–borane (4b) was
obtained according to general procedure E (2 h at 208C) as
a white solid with a 87% overall yield (55 mg). H NMR (400 MHz,
CDCl3): d=7.89–7.67 (m, 2H), 7.51 (m, 3H), 4.08 (s, 2H), 2.12 (O-H,
brs, 1H), 1.65 (d, J=10.5 Hz, 3H), 1.28–0.18 ppm (m, BH3, 3H);
31P NMR (162 MHz, CDCl3): d=10.94 ppm (m); Rf =0.2 (5:1 petrole-
um ether/EtOAc) These data are consistent with the literature.[12]
HPLC separation (Chiralpak AD-H, heptane/ethanol 70:30
1 mLminÀ1 UV 254 nm; tR (SP)=5.08 min, tR (RP)=6.95 min), e.r.=
96.5:3.5.
1
a 58% overall yield (120 mg). M.p. 192.1–200.68C; ½aŠ20 =À6.6 (c=
D
1
0.98, CHCl3); H NMR (400 MHz, CDCl3): d=7.76 (dd, J=9.4, 7.8 Hz,
2H), 7.69 (d, J=7.3 Hz, 2H), 7.57–7.41 (m, 4H), 7.36 (t, J=7.6 Hz,
2H), 6.96 (N-H,brs, 1H), 4.47–4.35 (m, 1H), 4.25–4.12 (m, 1H),
1.19 ppm (d, J=15.0 Hz, 9H); 31P NMR (162 MHz, CDCl3): d=
47.69 ppm; 13C NMR (101 MHz, CDCl3): d=167.60 (d, J=4.8 Hz),
133.77, 132.13 (d, J=2.6 Hz), 131.73 (d, J=4.2 Hz), 131.69 (d, J=
4.1 Hz), 128.53, 128.43 (d, J=11.0 Hz), 128.22 (d, J=89.2 Hz),
127.06, 34.20 (d, J=67.4 Hz), 32.87 (d, J=67.6 Hz), 24.26 ppm; IR
(RP)-tert-Butyl(2-hydroxyethyl)(phenyl)phosphine–borane [(RP)-4c]
was obtained according to general procedure E (72 h at 508C) as
a white solid with a 56% yield (80 mg, RF =0.2; 3:1 EP/EtOAc).
½aŠ20 = +22.7 (c=0.99, CHCl3); 1H NMR (400 MHz, CDCl3): d=7.70
D
(m, 2H), 7.50 (m, 1H), 7.45 (m, 2H), 3.91-3.75 (m, 2H), 2.47 (m,
1H,), 2.24 (brs, 1H, -OH), 2.16 (m, 1H), 1.09 (d, J=14.0 Hz, 9H),
0.74 ppm (m, 3H, BH3); 31P NMR (162 MHz, CDCl3): d=26.64 ppm
(m); 13C NMR (101 MHz, CDCl3): d=133.53 (d, J(C,P)=8.1 Hz),
131.62 (d, J(C,P)=2.9 Hz), 128.66 (d, J(C,P)=9.6 Hz), 125.99 (d,
J(C,P)=49.2 Hz), 58.1 (d, J(C,P)=1.4 Hz), 29.30 (d, J(C,P)=33.7 Hz),
25.5 (d, J(C,P)=2.2 Hz), 22.68 ppm (d, J(C,P)=32.3 Hz); 11B NMR
(128 MHz, CDCl3): d=À41.75 ppm (d, J(B,P)=59.2 Hz); HRMS (EI+)
calcd for C12H22BOP [M+Na]+ 247.1396; found 247.1395; HPLC sep-
aration (Lux-Cellulose 2, heptane/ethanol 90:10, 1 mLminÀ1, UV
254 nm; tR (RP)=9.94 min, tR (SP)=11.25 min), e.r.=99:1.
~
(ATR): n=472, 206, 633, 697, 748, 817, 1109, 1163, 1313, 1437,
1490, 1540, 1651, 2870, 2904, 2966, 3059, 3237 cmÀ1; HRMS (ESI)
calcd for [MÀH]+: 316.1461; found: 316.1461; HPLC separation
(Lux-Amylose 2, heptane/ethanol 90:10, 1 mLminÀ1, UV 254 nm;
tR (SP)=13.59 min, tR (RP)=11.86 min), e.r.=79:21.
General procedure E for the borane-mediated reduction
A 10 mL Schlenk tube equipped with magnetic stirring bar was
charged with phosphine oxide (1 equiv), and the tube was subject-
ed to several vaccum/argon cycles to give an inert atmosphere.
Then, an adjusted volume of anhydrous THF (concentration in
phosphine oxide=0.16m) was added if necessary and the reaction
mixture was cooled to 08C. At this temperature, a solution of
BH3·THF (1m in THF) was added dropwise, and the clear mixture
was stirred for 5 min at 08C. It was then allowed to warm to given
temperature, and stirred for the given time. Then, the reaction mix-
ture was cooled to 08C and quenched with distilled water. A satu-
rated NaHCO3 aqueous solution was then added, and the aqueous
layer was extracted with CH2Cl2 (3”5 mL) The combined organic
layers were dried over Na2SO4, filtered, and concentrated under re-
duced pressure. The crude product was purified by column chro-
matography on silica gel (using a combination of petroleum ether/
ethyl acetate) to yield the desired product.
(SP)-tert-Butyl(2-hydroxyethyl)(phenyl)phosphine–borane [(SP)-4c]:
59% yield (89 mg). ½aŠ20 =À22.7 (c=1.0, CHCl3); e.r.=99:1. Single
D
crystal growth for X-ray molecular structure determination was car-
ried out into Et2O/n-hexane at À208C. The absolute configuration
of the crystallized molecule is SP.
(SP)-tert-Butyl((SC)-1-hydroxyethyl)(phenyl)phosphine–borane (4d)
was obtained according to general procedure E (2 h at 208C) as
a white solid with a 73% yield.
1
Major diastereoisomer: H NMR (400 MHz, CDCl3): d=7.92 (m, 2H),
7.50 (m, 1H), 7.43 (m, 2H), (q, J=6.4 Hz, 1H), 1.85 (br s, 1H, -OH),
1.52 (dd, J=6.8 Hz, J=14.0 Hz, 3H), 1.20 (d, J=13.6 Hz, 9H),
0.60 ppm (m, 3H, BH3); 31P NMR (162 MHz, CDCl3): d=38.85 ppm
(m); 13C NMR (101 MHz, CDCl3): d=134.91 (d, J(C,P)=7.3 Hz),
131.57 (d, J(C,P)=1.8 Hz), 128.43 (d, J(C,P)=9.2 Hz), 125.07 (d,
J(C,P)=48.1 Hz), 65.20 (d, J(C,P)=36.8 Hz), 30.40 (d, J(C,P)=
29.7 Hz), 26.91, 20.80 ppm (d, J(C,P)=4.8 Hz); 11B NMR (128 MHz,
(RP)-tert-Butyl(hydroxymethyl)(phenyl)phosphine–borane [(RP)-4a]
was obtained according to general procedure E (2 h at 208C) as
a white solid with a 91% overall yield (90 mg). ½aŠ20 = +8.4 (c=
D
1
0.51, CHCl3,); H NMR (400 MHz, CDCl3): d=7.70 (m, J(H,H)=8.0 Hz,
CDCl3): d=À43.06 ppm (d, J(B,P)=58.0 Hz); ½aŠ20 =À28.6 (c=0.99,
D
J(H,P)=8.4 Hz, 2H, Ph), 7.51 (m J(H,H)=7.2 Hz, J(H,P)=1.2 Hz, 1H,
Ph), 7.44 (m, J(H,H)=8.0 Hz, J(H,P)=2.0 Hz, 2H, Ph), 4.54 (d,
J(H,H)=13.6 Hz, 1H,>CH2, -CH2OH), 4.27 (dd, J(H,H)=13.6 Hz,
J(H,P)=2.4 Hz, 1H,>CH2, -CH2OH), n.d. (-OH), 1.15 (d, J(H,P)=
13.6 Hz; 9H, tBu), 0.69 ppm (q, J(H,B)=93.6 Hz, 3H, BH3); 31P NMR
(162 MHz, CDCl3): d=31.26 ppm (bq, J(B,P)=53.8 Hz); 13C NMR
CHCl3,); HPLC separation [(S,S)-Whelk-O1 heptane/isopropanol 95:5
1 mLminÀ1 UV 254 nm; tR (SP,S)=8.06 min, tR (RP,R)=10.86 min],
e.r.=99:1. The major diastereoisomer was isolated by crystalliza-
tion into Et2O/n-hexane at À208C. The absolute configuration of
the crystallized molecule is (SP,S).
1
(101 MHz, CDCl3): d=133.69 (d, J(C,P)=7.6 Hz, 2C, =CH-, Ph), Minor diastereoisomer: H NMR (400 MHz, CDCl3): d=7.63 (m, 2H),
131.79 (d, J(C,P)=1.9 Hz, 1C, =CH-, Ph), 128.70 (d, J(C,P)=9.2 Hz, 7.52–7.48 (m, 1H), 7.45–7.39 (m, 2H), 4.84 (m, 1H), 2.15 (br d, J=
2C, =CH-, Ph), 125.10 (d, J(C,P)=49.5 Hz, 1C,>C=, Ph), 56.13 (d, 11.2 Hz, 1H, -OH), 1.29 (dd, J=6.8 Hz, J=13.2 Hz, 3H), 1.18 (d, J=
J(C,P)=38.8 Hz, 1C,>CH2OH), 29.42 (d, J(C,P)=30.1 Hz, 1C,>C<, 13.6 Hz, 9H), 0.62 ppm (m, 3H, BH3); 31P NMR (162 MHz, CDCl3): d=
tBu), 26.07 ppm (brd, 3C, J(C,P)=1.1 Hz, -CH3, tBu); 11B NMR 36.70 ppm (m); 13C NMR (101 MHz, CDCl3): d=133.81 (d, J(C,P)=
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15618
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
7.3 Hz,), 131.65 (d, J(C,P)=2.2 Hz), 128.66 (d, J(C,P)=9.6 Hz), 126.51
(d, J(C,P)=47.0 Hz), 62.90 (d, J(C,P)=39.6 Hz), 30.08 (d, J(C,P)=
30.1 Hz), 26.51 (d, J(C,P)=2.2 Hz), 20.23 ppm (d, J(C,P)=6.0 Hz);
11B NMR (128 MHz, CDCl3): d=À45.61 ppm (d, J(B,P)=58.4 Hz);
these data are consistent with those in the literature.[11]
2.3 Hz), 24.95 ppm (d, J(C,P)=11.5 Hz); 11B NMR (128 MHz, CDCl3):
d=À41.62 ppm (d, J(B,P)=56.2 Hz); HRMS (ESI) calcd for [MÀNa]+:
261.1553; found: 261.1553; Rf =0.2 (10:1 petroleum ether/EtOAc;
HPLC separation (Lux-Cellulose 3, heptane/ethanol 95:5,
1 mLminÀ1
, UV 254 nm; tR (minor)=18.43 min, tR (major)=
13.21 min), e.r.=99.5:0.5.
(RP)-tert-Butyl[(RC)hydroxy(phenyl)methyl](phenyl)phosphine–
borane (4 f) was obtained according to general procedure E (2 h at
208C) as a white solid with a 63% (2.6:1 d.r.) overall yield (186 mg).
(RP)-tert-Butyl[(RC)-2-hydroxy-2-phenylethyl](phenyl)phosphine–
borane [(RP,RC)-4g] was obtained according to general procedure E
(72 h at 508C) as a white solid with a 57% overall yield (68 mg).
1
Major diastereoisomer: H NMR (400 MHz, CDCl3): d=7.99 (m, 2H),
M.p. 113.1–115.28C; ½aŠ20 = +12.7 (c=1.02, CHCl3); 1H NMR
D
7.50 (m, 1H), 7.42 (m, 2H,), 7.37–7.32 (m, 2H), 7.26–7.20 (m, 3H),
5.60 (d, J=4.8 Hz, 1H), 2.59 (br s, 1H, -OH), 1.11 (d, J=13.6 Hz,
9H), 0.59 ppm (m, 3H, BH3); 31P NMR (162 MHz, CDCl3): d=
39.81 ppm (m); 13C NMR (101 MHz, CDCl3): d=138.45 (d, J(C,P)=
2.2 Hz), 135.16 (d, J(C,P)=7.3 Hz), 131.76 (d, J(C,P)=2.9 Hz), 128.96
(d, J(C,P)=2.2 Hz), 128.55 (d, J(C,P)=3.6 Hz), 128.39 (d, J(C,P)=
7.5 Hz), 128.35 (d, J(C,P)=2.9 Hz), 124.87 (d, J(C,P)=46.2 Hz), 71.92
(d, J(C,P)=33.8 Hz), 31.28 (d, J(C,P)=27.9 Hz), 26.87 ppm (d,
J(C,P)=1.5 Hz); 11B NMR (128 MHz, CDCl3): d=À43.07 ppm (d,
J(B,P)=56.1 Hz);
Minor diastereoisomer: 1H NMR (400 MHz, CDCl3): d=7.57 (t, J=
8.0 Hz, J=8.4 Hz, 2H), 7.35–7.29 (m, 4H), 7.3–7.20 (m, 2H), 7.13–
7.08 (m, 2H), 5.62 (1H), 3.04 (t, J=9.2 Hz, J=9.2 Hz, 1H, -OH), 1.26
(d, J=13.6 Hz, 9H), 0.59 ppm (m, 3H, BH3); 31P NMR (162 MHz,
CDCl3): d=39.35 ppm (m); 13C NMR (101 MHz, CDCl3): d=138.08 (d,
J(C,P)=3.7 Hz), 134.39 (d, J(C,P)=7.3 Hz), 131.54 (d, J(C,P)=2.2 Hz),
128.36 (d, J(C,P)=4.3 Hz), 128.24, 128.15, 125.47 (d, J(C,P)=
48.5 Hz), 70.02 (d, J(C,P)=36.1 Hz), 31.16 (d, J(C,P)=28.8 Hz),
26.81 ppm (d, J(C,P)=2.2 Hz); 11B NMR (128 MHz, CDCl3): d=
À44.27 ppm (d, J(B,P)=57.4 Hz); these data are consistent with
those in the literature;[11] Rf =0.28 (9:1 n-hexane/EtOAc).
(400 MHz, CDCl3): d=7.80–7.67 (m, 2H), 7.60–7.45 (m, 3H), 7.35–
7.24 (m, 5H), 4.79 (td, J=9.7, 1.7 Hz, 1H), 3.58 (br s, 1H-OH), 2.60
(t, J=14.6 Hz, 1H), 2.33 (ddd, J=14.9, 9.6, 3.2 Hz, 1H), 1.11 (d, J=
14.2 Hz, 9H), 1.11–0.33 ppm (m, BH3); 31P NMR (162 MHz, CDCl3):
d=27.14 ppm (m); 13C NMR (101 MHz, CDCl3): d=144.17 (d,
J(C,P)=11.0 Hz), 133.49 (d, J(C,P)=7.9 Hz), 131.60 (d, J(C,P)=
2.4 Hz), 128.62, 128.62 (d, J(C,P)=9.5 Hz), 127.75, 125.39, 125.27 (d,
J(C,P)=49.7 Hz), 69.24, 30.49 (d, J(C,P)=30.2 Hz), 29.26 (d, J(C,P)=
33.3 Hz), 25.32 ppm (d, J(C,P)=2.4 Hz); 11B NMR (128 MHz, CDCl3):
~
d=À41.40 ppm (d, J(B,P)=51.2 Hz); IR (ATR): n=424, 440, 486,
530, 565, 617, 629, 696, 743, 750, 814, 976, 1018, 1047, 1067, 1107,
1367, 1437, 2380, 2872, 2906, 2960, 2974, 3028, 3063, 3502 cmÀ1
;
HRMS (ESI) calcd for [MÀNa]+: 323.1710; found: 323.1714; Rf =0.2
(10:1 petroleum ether/EtOAc); HPLC separation (Chiralpak IC, hep-
tane/ethanol 90:10, 1 mLminÀ1, UV 254 nm; tR (SP,S)=6.90 min,
tR (RP,R)=8.33 min), e.r.>99.5:0.5.
(SP)-tert-Butyl(2-hydroxy-2,2-diphenylethyl)(phenyl)phosphine–
borane (4h) was obtained according to general procedure E (72 h
at 508C) as a white solid with a 41% overall yield (33 mg). M.p.
147.1–149.58C; ½aŠ20 =À28.3 (c=0.72, CHCl3); 1H NMR (400 MHz,
D
CDCl3): d=7.60 (dd, J=9.3, 7.9 Hz, 2H), 7.47 (d, J=7.5 Hz, 2H),
7.45–7.38 (m, 1H), 7.31 (t, J=7.6 Hz, 4H), 7.23 (t, J=7.3 Hz, 1H),
7.14 (dd, J=7.6, 1.9 Hz, 2H), 6.95–6.85 (m, 3H), 4.68 (s, 1H-OH),
3.44 (t, J=14.3 Hz, 1H), 2.86 (dd, J=14.9, 6.5 Hz, 1H), 1.14 (d, J=
14.0 Hz, 5H), 1.14–0.24 ppm (m, BH3); 31P NMR (162 MHz, CDCl3):
d=21.62 ppm (m); 13C NMR (101 MHz, CDCl3): d=148.01 (d,
J(C,P)=8.9 Hz), 144.42 (d, J(C,P)=2.1 Hz), 133.34 (d, J(C,P)=8.0 Hz),
131.02 (d, J(C,P)=2.5 Hz), 128.27, 128.09 (d, J(C,P)=9.7 Hz), 127.43,
127.14, 126.70, 126.51 (d, J(C,P)=50.7 Hz), 126.37, 125.47, 77.67,
33.41 (d, J(C,P)=28.4 Hz), 30.27 (d, J(C,P)=34.5 Hz), 25.46 ppm (d,
J(C,P)=2.1 Hz); 11B NMR (128 MHz, CDCl3): d=À41.20 ppm (d,
½aŠ20 =nd (d.r.=2.6:1); HPLC separation (Lux-Amylose 2, heptane/
D
ethanol 80:20, 1 mLminÀ1, UV 254 nm; major diastereoisomer:
tR (SP,S)=4.90 min, tR (RP,R)=5.49 min), e.r.=98.5:1.5; minor diaste-
reoisomer: tR (RP,S)=4.30 min, tR (SP,R)=5.95 min), e.r.=87:13.
(RP)-tert-Butyl((RC)-2-hydroxypropyl)(phenyl)phosphine–borane
[(RP,RC)-4e] was obtained according to general procedure E (72 h at
508C) as a white solid with a 51% overall yield (101 mg). M.p.
79.1–81.38C; ½aŠ20 =À22 (c=1.02, CHCl3); 1H NMR (400 MHz,
D
CDCl3): d=7.81–7.69 (m, 2H), 7.57–7.40 (m, 3H), 4.47–4.21 (m, 1H),
2.35 (ddd, J=14.7, 12.7, 9.1 Hz, 1H), 2.27 (br s, OH), 2.09 (ddd, J=
14.8, 8.6, 2.7 Hz, 1H), 1.32 (dd, J=6.2, 1.6 Hz, 3H), 1.09 (d, J=
13.9 Hz, 9H), 1.09–0.27 ppm (m, BH3); 31P NMR (162 MHz, CDCl3):
d=25.26 ppm (m); 13C NMR (101 MHz, CDCl3): d=133.34 (d,
J(C,P)=8.0 Hz), 131.26 (d, J(C,P)=2.5 Hz), 128.27 (d, J(C,P)=9.5 Hz),
126.95 (d, J(C,P)=50.0 Hz), 64.46, 29.36 (d, J(C,P)=20.4 Hz), 29.03
(d, J(C,P)=19.2 Hz), 25.36 (d, J(C,P)=2.3 Hz), 25.04 ppm (d, J(C,P)=
10.7 Hz); 11B NMR (128 MHz, CDCl3): d=À41.96 ppm (d, J(B,P)=
56.8 Hz); HRMS (ESI) calcd for [MÀNa]+: 261.1553; found:
261.1553; Rf =0.2 (5:1 petroleum ether/EtOAc); HPLC separation
(Lux-Cellulose 3, heptane/ethanol 95:5, 1 mLminÀ1, UV 254 nm;
tR (SP,S)=9.93 min, tR (RP,R)=8.90 min), e.r.=99.5:0.5.
~
J(B,P)=47.8 Hz); IR (ATR): n=428, 491, 564, 591, 635, 693, 739, 793,
989, 1061, 1105, 1168, 1364, 1448, 1491, 2324, 2397, 2869, 2927,
2958, 2977, 3057, 3476 cmÀ1; HRMS (ESI) calcd for [MÀNa]+:
399.2024; found: 399.2031; Rf =0.5 (5:1 petroleum ether/EtOAc);
HPLC separation (Chiralpak AZ-H, heptane/ethanol 80:20,
1 mLminÀ1, UV 254 nm; tR (RP)=4.72 min, tR (SP)=5.38 min), e.r.=
98.5:1.5.
(RP)-[(Benzylamino)methyl](tert-butyl)(phenyl)phosphine–borane
(12) was obtained according to general procedure E (24 h at 208C)
as a white solid with a 84% overall yield (75 mg). M.p. 103.9-
1068C; ½aŠ20 =À23.4 (c=1.00, CHCl3); 1H NMR (400 MHz, CDCl3):
D
(RP)-tert-Butyl[(SC)-2-hydroxypropyl](phenyl)phosphine–borane
[(RP,SC)-4e] was obtained according to general procedure E (72 h at
d=7.72–7.60 (m, 2H), 7.57–7.47 (m, 1H), 7.48–7.39 (m, 2H), 7.36–
7.23 (m, 5H), 3.84 (s, 2H), 3.41–3.20 (m, 2H), 1.10 (d, J=13.6 Hz,
9H), 1.09–0.23 ppm (m, BH3, 3H); 31P NMR (162 MHz, CDCl3): d=
29.46 ppm (m); 13C NMR (101 MHz, CDCl3): d=139.33, 133.36 (d,
J(C,P)=7.7 Hz), 131.27 (d, J(C,P)=2.4 Hz), 128.32 (d, J(C,P)=
16.4 Hz), 128.32 (d, J(C,P)=9.4 Hz), 127.16, 126.15, 125.66, 55.34 (d,
J(C,P)=12.3 Hz), 39.87 (d, J(C,P)=41.0 Hz), 29.12 (d, J(C,P)=
31.3 Hz), 25.82 ppm (d, J(C,P)=1.9 Hz); 11B NMR (128 MHz, CDCl3):
508C) as a colorless viscous oil with a 54% overall yield (107 mg).
1
½aŠ20 = +31.3 (c=1.01, CHCl3); H NMR (400 MHz, CDCl3): d=7.79–
D
7.61 (m, 2H), 7.59–7.40 (m, 3H), 4.04–3.80 (m, 1H), 3.20 (s, 1H, OH),
2.38 (t, J=15.1 Hz, 1H), 2.03 (ddd, J=14.8, 9.1, 3.8 Hz, 1H), 1.25 (d,
J=6.0 Hz, 3H), 1.10 (d, J=14.1 Hz, 9H), 1.11–0.18 ppm (m, BH3);
31P NMR (162 MHz, CDCl3): d=26.29 ppm (m); 13C NMR (101 MHz,
CDCl3): d=133.33 (d, J(C,P)=7.9 Hz), 131.48 (d, J(C,P)=2.5 Hz),
128.55 (d, J(C,P)=9.4 Hz), 125.67 (d, J(C,P)=49.8 Hz), 63.33, 29.09
(d, J(C,P)=33.7 Hz), 28.69 (d, J(C,P)=32.3 Hz), 25.29 (d, J(C,P)=
~
d=À42.81 ppm (d, J(B,P)=52.3 Hz); IR (ATR): n=430, 460, 488,
490, 563, 590, 617, 629, 694, 739, 785, 816, 1001, 1018, 1026, 1067,
1108, 1134, 1184, 1365, 1394, 1437, 1454, 1462, 1475, 2260, 2341,
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15619
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
2375, 2804, 2868, 2943, 2972, 3028, 3061, 3333 cmÀ1; HRMS (ESI)
calcd for [MÀAg]+: 406.1023; found: 406.1019; Rf =0.2 (10:1 petro-
leum ether/EtOAc); HPLC separation (Chiralcel OD-3, heptane/etha-
(SP,S)-4d, C12H22BOP, Mw=224.08 from diethyl ether at 48C; ortho-
rhombic; space group P212121; a=7.2910(1), b=12.9893(2), c=
14.6934(3); a=b=g=908; V=1391.54(4) Š3; Z=4; 1calc
=
nol 90:10, 1 mLminÀ1
,
UV 254 nm; tR (SP)=4.93 min, tR (RP)=
1.070 gcmÀ3; l (MoKa1)=0.71073 Š; F(000)=488.0; m=0.173 mmÀ1
T=293 K.
;
4.59 min), e.r.=93:7.
CCDC 1053124, 1053119, 1053122, 1053123, 1053121 and 1053120
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre.
(+/À)-N-{[tert-Butyl(phenyl)phosphine–borane]methyl}benzamide
(15) was obtained according to general procedure E (24 h at 208C)
as a white solid with a 10% yield (5 mg). M.p. 144.7–152.68C;
1H NMR (400 MHz, CDCl3): d=7.76 (t, J=8.3 Hz, 2H), 7.68 (d, J=
7.2 Hz, 2H), 7.54–7.43 (m, 4H), 7.39 (t, J=7.5 Hz, 2H), 6.64 (br s,
1H, -NH), 4.49 (ddd, J=15.0, 8.4, 6.9 Hz, 1H), 4.18–4.07 (m, 1H),
1.18 (d, J=14.1 Hz, 9H), 1.10–0.60 ppm (m, 3H, -BH3); 31P NMR
(162 MHz, CDCl3): d=32.92 ppm (m); 13C NMR (101 MHz, CDCl3):
d=167.28 (d, J(C,P)=4.4 Hz), 133.62, 133.43 (d, J(C,P)=8.1 Hz),
131.85, 128.68, 128.58, 126.92, 124.04 (d, J(C,P)=50.5 Hz), 30.92 (d,
J(C,P)=40.7 Hz), 29.38 (d, J(C,P)=30.6 Hz), 25.56 ppm (d, J(C,P)=
Acknowledgements
We are grateful to the MESR-Aix-Marseille University (PhD
grant to S.L.), Centrale Marseille (ATER grant to D.H.N.) and
CNRS for funding. This work was supported by the computing
facilities of the CRCMM, ‘Centre RØgional de CompØtences en
ModØlisation MolØculaire de Marseille’. The authors also thank
Roseline Rosas, Dr. Michel Giorgi, Dr. Valerie Monnier, Christo-
phe Chendo, GrØgory Excoffier for NMR studies, X-ray, HRMS
and elemental analyses.
~
2.1 Hz); Rf =0.4 (5:1 petroleum ether/EtOAc); IR (ATR): n=487, 703,
742, 921, 1067, 1263, 1309, 1436, 1487, 1520, 1654, 2343, 2374,
2869, 2928, 2961, 3060, 3335, 3421 cmÀ1; HRMS (ESI) calcd for
[MÀNa]+: 336.1659; found: 336.1657.
(SP)-{(Benzo[d][1,3,2]dioxaborol-2-yloxy)methyl}(tert-butyl)(phenyl)
phosphine oxide (17): To a solution of (SP)-3a (207 mg) in CH2Cl2
(3 mL) was added dropwise a solution of catecholborane in THF
(1.0m, 1.03 mL, 1.05 equiv) at 08C. The resulting mixture was al-
lowed to warm slowly to room temperature and the solution was
further stirred for 2 h at room temperature. The reaction mixture
was then evaporated under reduced pressure to give the residual
solid which was washed with Et2O (4”3 mL) and then dried under
Keywords: boranes
·
phosphanes
·
reduction
·
stereospecificity · vibrationsl spectroscopy
1
vacuum. Yield (219 mg, 68%); H NMR (400 MHz, CD2Cl2): d=7.61
[1] Phosphorus Ligands in Asymmetric Catalysis; Synthesis and Applications
(Ed.: A. Bçrner), Wiley-VCH, Weinheim, 2008.
[2] Metal Catalysis in Industrial Organic Processes (Eds.: G. P. Chiusoli, P. M.
Maitlis), Royal Society Of Chemistry, London, 2006.
[3] a) J. L. Methot, W. R. Roush, Adv. Synth. Catal. 2004, 346, 1035–1050;
b) Y. Wei, M. Shi, Acc. Chem. Res. 2010, 43, 1005–1018; c) A. Marinetti,
A. Voituriez, Synlett 2010, 174–194.
[4] a) Phosphorus(III) Ligands in Homogeneous Catalysis: Design and Synthe-
sis. (Eds.: P. C. J. Kamer, P. W. N. M. van Leeuwen) Wiley, Hoboken, 2012;
b) P-Stereogenic Ligands in Enantioselective Catalysis. (Ed: A. Grabulosa),
Royal Society Of Chemistry, London, 2011.
[5] A. R. Muci, K. R. Campos, D. A. Evans, J. Am. Chem. Soc. 1995, 117,
9075–9076.
[6] a) K. Nagata, S. Matsukawa, T. Imamoto, J. Org. Chem. 2000, 65, 4185–
4188; b) J. J. Gammon, V. H. Gessner, G. R. Barker, J. Granander, A. C.
Whitwood, C. Strohmann, P. O’Brien, B. Kelly, J. Am. Chem. Soc. 2010,
132, 13922–13927.
[7] a) H. Fernµndez-PØrez, M. A. Pericas, A. Vidal-Ferran, Adv. Synth. Catal.
2008, 350, 1984–1990; b) H. Fernµndez-PØrez, S. M. A. Donald, I. J. Mun-
slow, J. Benet-Buchholz, F. Maseras, A. Vidal-Ferran, Chem. Eur. J. 2010,
16, 6495–6508; c) A. Panossian, H. Fernµndez-PØrez, D. Popa, A. Vidal-
Ferran, Tetrahedron: Asymmetry 2010, 21, 2281–2288; d) H. Fernµndez-
PØrez, P. Etayo, A. Panossian, A. Vidal-Ferran, Chem. Rev. 2011, 111,
2119–2176; e) J. L. NfflÇez-Rico, P. Etayo, H. Fernandez-Perez, A. Vidal-
Ferran, Adv. Synth. Catal. 2012, 354, 3025–3035; f) G. M. Noonan, J. A.
Fuentes, C. J. Cobley, M. L. Clarke, Angew. Chem. Int. Ed. 2012, 51, 2477–
2480; Angew. Chem. 2012, 124, 2527–2530; g) H. Fernµndez-PØrez, J.
Benet-Buchholz, A. Vidal-Ferran, Org. Lett. 2013, 15, 3634–3637; h) J. L.
NfflÇez-Rico, A. Vidal-Ferran, Org. Lett. 2013, 15, 2066–2069; M. Dindaro-
glu, A. Falk, H.-G. Schmalz, Synthesis 2013, 527–535; i) R. Aznar, A. Gra-
bulosa, A. Mannu, G. Muller, D. Sainz, V. Moreno, M. Font-Bardia, T.
Calvet, J. Lorenzo, Organometallics 2013, 32, 2344–2362; j) H. Fernµn-
dez-PØrez, J. Benet-Buchholz, A. Vidal-Ferran, Chem. Eur. J. 2014, 20,
15375–15384; k) J. R. Lao, J. Benet-Buchholz, A. Vidal-Ferran, Organome-
tallics 2014, 33, 2960–2963; l) J. L. NfflÇez-Rico, H. Fernµndez-PØrez, A.
Vidal-Ferran, Green Chem. 2014, 16, 1153–1157.
(m, 2H, Ph), 7.58 (m, 1H, Ph), 7.46 (m, 2H, Ph), 6.62 (brd, 4H,
BO2C6H4), 4.66 (dd, J=14.0 Hz, 1H), 4.48 (dd, J=14.0 Hz, 1H),
1.17 ppm (d, J=16.4 Hz, 9H); 31P NMR (162 MHz, CD2Cl2): d=
67.98 ppm (br s); 13C NMR (101 MHz, CD2Cl2): d=133.91, 132.04 (d,
J(C,P)=8.8 Hz), 129.36 (d, J(C,P)=12.3 Hz), 119.81 (br s, BO2C6H4),
110.70 (br s, BO2C6H4), 58.07 (d, J(C,P)=60.1 Hz), 32.49 (d, J(C,P)=
61.6 Hz), 23.92 ppm; 11B NMR (128 MHz, CD2Cl2): d=13.20 ppm (s).
Crystal data
(SP)-3a, C11H17O2P, Mw=212.22 from CH2Cl2/hexane at À208C; or-
thorhombic; space group P212121; a=6.1924(1), b=9.7370(2), c=
19.0102(4); a=b=g=908; V=1146.23(4) Š3; Z=4; 1calc
=
;
1.230 gcmÀ3; l (MoKa1)=0.71073 Š; F(000)=456.0; m=0.214 mmÀ1
T=293 K.
(SP)-3c, C12H19O2P, Mw=226.24 from CH2Cl2/hexane at À208C; or-
thorhombic; space group P212121; a=6.1383(1), b=10.4646(2), c=
19.3716(4); a=b=g=908; V=1244.33(4) Š3; Z=4; 1calc
=
;
1.208 gcmÀ3; l (MoKa1)=0.71073 Š; F(000)=488.0; m=0.201 mmÀ1
T=293 K.
(SP,S)-3d, C12H19O2P, Mw=226.24 from CH2Cl2/hexane at À208C; or-
thorhombic; space group P212121; a=6.5659(1), b=10.2859(2), c=
18.3189(5); a=b=g=908; V=1237.19(5) Š3; Z=4; 1calc
=
;
1.215 gcmÀ3; l (MoKa1)=0.71073 Š; F(000)=488.0; m=0.202 mmÀ1
T=293 K.
(SP)-4a, C11H20BOP, Mw=210.05 from diethyl ether at 48C; ortho-
rhombic; space group P212121; a=9.3013(2), b=21.2793(3), c=
27.0260(5); a=b=g=908; V=5349.13(17) Š3; Z=16; 1calc
=
1.043 gcmÀ3
0.176 mmÀ1; T=293 K.
;
l
(MoKa1)=0.71073 Š;
F(000)=1824.0;
m=
(SP)-4c, C12H22BOP, Mw=224.08 from diethyl ether at 48C; ortho-
rhombic; space group P212121; a=7.4049(1), b=15.1152(2), c=
25.7220(5); a=b=g=908; V=2878.98(8) Š3; Z=8; 1calc
=
;
[8] D. HØrault, D. H. Nguyen, D. Nuel, G. Buono, Chem. Soc. Rev. 2015, 44,
2508–2528.
[9] K. Shioji, Y. Kurauchi, K. Okuma, Bull. Chem. Soc. Jpn. 2003, 76, 833–834.
1.034 gcmÀ3; l (MoKa1)=0.71073 Š; F(000)=976.0; m=0.167 mmÀ1
T=293 K.
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15620
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
´
[10] a) P. Kiełbasinski, M. Albrycht, R. Zurawinski, M. Mikolajczyk, J. Mol.
[21] a) A. Staubitz, A. P. M. Robertson, I. Manners, Chem. Rev. 2010, 110,
4079–4124; b) A. Staubitz, A. P. M. Robertson, M. E. Sloan, I. Manners,
Chem. Rev. 2010, 110, 4023–4078; c) S. Muhammad, S. Moncho, E. N.
Brothers, A. A. Bengali, Chem. Commun. 2014, 50, 5874–5877; d) H. C.
Johnson, E. M. Leitao, G. R. Whittell, I. Manners, G. C. Lloyd-Jones, A. S.
Weller, J. Am. Chem. Soc. 2014, 136, 9078–9093.
[22] The Lewis acid/P=O interaction has already been studied by 31P NMR.
Our observations are consistent with those compiled in this review: I. B.
Sivaev, V. I. Bregadze, Coord. Chem. Rev. 2014, 270–271, 75–88.
[23] a) S. W. Hadebe, R. S. Robinson, Eur. J. Org. Chem. 2006, 4898–4904;
b) S. A. Westcott, H. P. Blom, T. B. Marder, R. T. Baker, J. C. Calabrese,
Inorg. Chem. 1993, 32, 2175–2182; c) R. B. Coapes, F. E. S. Souza, M. A.
Fox, A. S. Batsanov, A. E. Goeta, D. S. Yufit, M. A. Leech, J. A. K. Howard,
A. J. Scott, W. Clegg, T. B. Marder, J. Chem. Soc. Dalton Trans. 2001,
1201–1209.
´
Catal. B 2006, 39, 45–49; b) M. Kwiatkowska, G. Krasinski, M. Cypryk, T.
Cierpiał, P. Kiełbasinski, Tetrahedron: Asymmetry 2011, 22, 1581–1590.
[11] S. Sowa, M. Stankevic, A. Szmigielska, H. Maluszynska, A. E. Koziol, K. M.
Pietrusiewicz, J. Org. Chem. 2015, 80, 1672–1688.
[12] D. Gatineau, D. H. Nguyen, D. HØrault, N. Vanthuyne, J. Leclaire, L. Gior-
dano, G. Buono, J. Org. Chem. 2015, 80, 4132–4141.
[13] a) R. K. Haynes, W. W. L. Lam, L. L. Yeung, Tetrahedron Lett. 1996, 37,
4729–4732; b) R. K. Haynes, T.-L. Au-Yeung, W.-K. Chan, W.-L. Lam, Z.-Y.
Li, L.-L. Yeung, A. S. C. Chan, P. Li, M. Koen, C. R. Mitchell, S. C. Vonwiller,
Eur. J. Org. Chem. 2000, 3205–3216.
[14] K. Shioji, T. Ueyama, N. Ueda, E. Mutoh, T. Kurisaki, H. Wakita, K. Okuma,
J. Mol. Catal. B 2008, 55, 146–151.
´
[15] F. A. Kortmann, M.-C. Chang, E. Otten, E. P. A. Couzijn, M. Lutz, A. J. Min-
naard, Chem. Sci. 2014, 5, 1322–1328.
[16] Q. Xu, C.-Q. Zhao, L.-B. Han, J. Am. Chem. Soc. 2008, 130, 12648–12655.
[17] D. Gatineau, L. Giordano, G. Buono, J. Am. Chem. Soc. 2011, 133,
10728–10731.
[18] D. HØrault, G. Buono, N. Vanthuyne, C. Roussel, L. Giordano, D. Morale-
da, D. Gatineau, J. Leclaire, D. Nuel, P-Stereogenic Chiral Precursor of
Chiral Ligands and Use Thereof., 2014, WO 2014108487.
[19] a) P. J. Stephens, F. J. Devlin, J. J. Pan, Chirality 2008, 20, 643–663; b) D.
Campolo, T. Arif, C. Borie, D. Mouysset, N. Vanthuyne, J.-V. Naubron,
M. P. Bertrand, M. Nechab, Angew. Chem. Int. Ed. 2014, 53, 3227–3231;
Angew. Chem. 2014, 126, 3291–3295; c) M. Ramillien, N. Vanthuyne, M.
Jean, D. Gherase, M. Giorgi, J.-V. Naubron, P. Piras, C. Roussel, J. Chroma-
togr. A 2012, 1269, 82–93.
[24] Apicophilicity is the relative preference of substituents to occupy the
apical positions as opposed to the equatorial positions in trigonal bi-
pyramidal (TBP) structures; a) S. Trippett, Phosphorus Sulfur Relat. Elem.
1976, 1, 89–98; b) R. R. Holmes, ACS Monograph Series, No. 175: Penta-
coordinated Phosphorus, Vol. 1: Structure and Spectroscopy, American
Chemical Society, Washington, DC, 1980; c) R. R. Holmes, ACS Mono-
graph Series, No. 176: Pentacoordinated Phosphorus, Vol. 2: Reaction
Mechanisms, American Chemical Society, Washington, DC, 1980; d) G.
Buono, J. R. Llinas, J. Am. Chem. Soc. 1981, 103, 4532–4540.
Received: June 7, 2015
[20] a) G. Aksnes, K. Bergesen, Acta Chem. Scand. 1965, 19, 931–934; b) G.
Aksnes, K. Bergesen, Acta Chem. Scand. 1966, 20, 2508–2514.
Published online on September 14, 2015
Chem. Eur. J. 2015, 21, 15607 – 15621
www.chemeurj.org
15621
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim