Enantiodivergent synthesis of P-chirogenic phosphines

Article abstract of DOI:10.1016/j.crci.2010.06.001

Several approaches for the enantiodivergent synthesis of P-chirogenic mono- and diphosphines are described, using ephedrine methodology and phosphine borane chemistry. Firstly, both enantiomers of a tertiary phosphine can be obtained starting from the same oxazaphospholidine borane complex, prepared from (+)-ephedrine, when changing the order of addition of the organolithium reagents during the synthetic pathway. The second approach is based on the chlorophosphine boranes, which react with an organolithium reagent, to afford the corresponding phosphines with inversion of configuration. In the case where the chlorophosphine borane reacts with the t-butyl lithium reagent, a metal-halogen exchange occurs to afford the corresponding phosphide borane with retention of the configuration. The reaction of the phosphide borane with an alkyl halide leads to the same phosphine, but with the opposite configuration. Another approach depends on the diastereoselective preparation of the starting oxazaphospholidine borane complex from (-)-ephedrine, which leads according the case, to either one or the other enantiomer of a phosphine. Finally, the synthesis of (R,R)- and (S,S)-1,2-bis(methylphenylphosphino)ethane is also demonstrated using both enantiomers of the P-chirogenic diphosphinite diborane, which simultaneously allows the introduction of alkyl- or aryl substituents on the phosphorus atoms. In summary, these approaches show the great efficiency of the "ephedrine methodology" for the enantiodivergent synthesis of P-chirogenic mono- and diphosphines, and bearing alkyl or aryl substituents.

Full text of DOI:10.1016/j.crci.2010.06.001

C. R. Chimie 13 (2010) 1213–1226
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www.sciencedirect.com
´
Full paper/Memoire
Enantiodivergent synthesis of P-chirogenic phosphines
Fanny Chaux a, Slawomir Frynas a, Hugo Laureano a,b, Christine Salomon a,
a
a
c,1
c,2
´
`
Gerald Morata , Marie-Laure Auclair , Michel (Massoud) Stephan , Rachid Merdes
,
Philippe Richard a, Marie-Jo Ondel-Eymin a, Jean-Christophe Henry b,
a
a,3
a,
*
´
´ ˆ
Jerome Bayardon , Christophe Darcel , Sylvain Juge
a Institut de chimie mole´culaire de l’universite´ de Bourgogne (UMR-CNRS 5260), 9, avenue Alain-Savary, BP 47870, 21078 Dijon cedex, France
b SYNTHELOR SAS, 102 impasse H.-Becquerel, Dynapoˆle de Ludres-Fle´ville 54510 Ludres, France
c Laboratoire de synthe`se organique, bioconversion et produits naturels, ENSCP, Paris, France
A R T I C L E I N F O
A B S T R A C T
Article history:
Several approaches for the enantiodivergent synthesis of P-chirogenic mono- and
diphosphines are described, using ephedrine methodology and phosphine borane
chemistry. Firstly, both enantiomers of a tertiary phosphine can be obtained starting
from the same oxazaphospholidine borane complex, prepared from (+)-ephedrine, when
changing the order of addition of the organolithium reagents during the synthetic
pathway. The second approach is based on the chlorophosphine boranes, which react with
an organolithium reagent, to afford the corresponding phosphines with inversion of
configuration. In the case where the chlorophosphine borane reacts with the t-butyl
lithium reagent, a metal-halogen exchange occurs to afford the corresponding phosphide
borane with retention of the configuration. The reaction of the phosphide borane with an
alkyl halide leads to the same phosphine, but with the opposite configuration. Another
approach depends on the diastereoselective preparation of the starting oxazapho-
spholidine borane complex from (ꢀ)-ephedrine, which leads according the case, to either
one or the other enantiomer of a phosphine. Finally, the synthesis of (R,R)- and (S,S)-1,2-
bis(methylphenylphosphino)ethane is also demonstrated using both enantiomers of the
P-chirogenic diphosphinite diborane, which simultaneously allows the introduction of
alkyl- or aryl substituents on the phosphorus atoms. In summary, these approaches show
the great efficiency of the ‘‘ephedrine methodology’’ for the enantiodivergent synthesis of
P-chirogenic mono- and diphosphines, and bearing alkyl or aryl substituents.
Received 29 March 2010
Accepted after revision 1 June 2010
Available online 24 July 2010
This paper is dedicated to Pascal Le Floch.
Keywords:
Asymmetric synthesis
Enantiomers
Chiral phosphines
Borane complexes
´
ß 2010 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
´
´
R E S U M E
´
Mots cles :
La synthe`se e´nantiodivergente de mono- et diphosphines P-chiroge´niques utilisant la
`
´
Synthese asymetrique
´
´
´
´
« methode ephedrine » et la chimie des phosphines borane, est decrite selon plusieurs
´
Enantiome`res
`
´
´
`
approches. La premiere est basee sur le principe que les deux enantiomeres d’une
phosphine tertiaire peuvent eˆtre obtenus a` partir du meˆme complexe d’oxazapho-
spholidine borane, pre´pare´ a` partir de (+)-e´phe´drine, par simple changement de l’ordre
Phosphines chirales
Complexes borane
* Corresponding author.
´
E-mail address: sylvain.juge@u-bourgogne.fr (S. Juge).
1
´
Present address: PhosPhoenix SARL, 115, rue de l’Abbe-Groult, 75015 Paris, France ; National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana ,
Slovenia.
2
Present address: Universite´ du 8-mai-1945, boulevard 19-mai-96, BP 401,Guelma, Alge´rie.
3
Present address: Sciences chimiques de Rennes, UMR 6226 CNRS, universite´ de Rennes-1, Campus de Beaulieu, baˆtiment 10C, 263, avenue du Ge´ne´ral-
Leclerc, 35042 Rennes cedex, France.
1631-0748/$ – see front matter ß 2010 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.crci.2010.06.001

1214
F. Chaux et al. / C. R. Chimie 13 (2010) 1213–1226
d’introduction des substituants du phosphore au cours de la synthe`se. Une seconde
´
approche repose sur l’utilisation des chlorophosphines borane qui reagissent avec un
organolithien pour donner les phosphines correspondantes avec inversion de configura-
tion. Dans le cas ou` la chlorophosphine borane re´agit avec le t-butyllithium, un e´change
`
´
´
halogene-metal se produit pour donner un phosphure borane chiral avec retention de la
´
´
configuration ; la reaction du phosphure borane avec un halogenure d’alkyle permet alors
d’obtenir une meˆme phosphine, mais de configuration oppose´e. Une autre approche
`
´
´
´
repose sur la synthese diastereoselective du complexe d’oxazaphospholidine borane de
´
`
`
´
`
depart a partir de (ꢀ)-ephedrine, qui conduit selon le cas, a l’un ou l’autre enantiomere
`
´
`
d’une phosphine. Enfin, la synthese de (R,R)- et (S,S)-1,2-diphosphine P-chirogenique a
pont e´thano est de´crite en utilisant les deux e´nantiome`res d’un diphosphinite diborane,
´
qui permet l’introduction simultanee de substituants alkyles ou aryles sur les deux
´
´
´
`
atomes de phosphore. En resume, ces differentes approches montrent la tres grande
efficacite´ de la « me´thode e´phe´drine » pour la synthe`se e´nantiodivergente de mono- et
´
diphosphines P-chirogeniques, porteuses de groupements alkyles ou aryles.
´
´
´
´
ß 2010 Academie des sciences. Publie par Elsevier Masson SAS. Tous droits reserves.
1. Introduction
chromatography on a chiral column, respectively [12].
However, most of the time, this class of ligands are
Numerous asymmetric catalyzed reactions were devel-
oped with transition metal complexes using chiral
phosphorus ligands [1,2]. This class of ligands is widely
used because their structure can be easily modified on the
prepared by efficient stereoselective synthesis using the
phosphorus borane chemistry [4,6,13–17]. The principle of
these syntheses is based on the preparation of enantio-
merically enriched P-chirogenic organophosphorus borane
building blocks 8–10, acting either as nucleophilic or
electrophilic reagents.
In the first case, the nucleophilic reagents 8 and 9a are
prepared in the presence of (ꢀ)-sparteine, by enantiose-
lective deprotonation of the dimethylphosphine borane 6,
or by dynamic thermodynamic resolution of the secondary
phosphine borane 7, respectively (Scheme 1). The homo-
coupling of the anion 8 in the presence of CuCl2 under air,
or the reaction of 9a with an electrophile, leads to the
preparation of P-chirogenic ligands by C-C or P-C bond
formation, such as in (S,S)-4 or (R,R)-5 (Scheme 1) [13,14].
Noteworthy, these nucleophilic methodologies have been
successfully applied by T. Imamoto and coll. for the
synthesis of several efficient chiral ligands in asymmetric
catalysis, which are currently commercially available
(MiniPHOS, BisP*, Quinox P*) [4,15].
Unfortunately both nucleophilic methodologies are
restricted to bulky alkyl or methyl substituents on the
phosphorus atom. Furthermore, as only (ꢀ)-sparteine is
commercially avalaible, only one enantiomer is accessible.
The stereoselective synthesis of the other enantiomer is
still possible, but using in this case, demanding strategies
[16] or the (+)-sparteine surrogate [17].
In the case of the P-chirogenic electrophilic building
blocks 10, the synthesis is based on subsequent stereo-
selective reactions starting from the oxazaphospholidine
borane complex 11, prepared from (+)-ephedrine (Scheme
2) [6(a,c),18]. After reaction with an organolithium reagent
the starting complex (Sp)-11 affords the ring-opening
product 12, which leads to the P-chirogenic phosphinite
borane 10 by P-N bond cleavage under acidic methanolysis
conditions [6(a,c),18]. The reaction of the phosphinite
borane 10 with an organolithium reagent, leads to the
corresponding P-chirogenic phosphines 13, after decom-
plexation with DABCO (Scheme 2).
phosphorus center, or in its
a- or b-position, owing to
numerous electrophilic or nucleophilic reactions of their
P(III)- or P(IV)-precursors [2–4]. Noteworthy, over the last
decade, the chemistry of phosphorus ligands has made
significant breakthroughs due to the borane used as
protecting group, giving stable complexes, often crystal-
lized, and affording clean reactions [4–6]. In addition, the
chirality of the phosphorus ligands can stem either from
the carbon backbone or from the phosphorus center,
increasing thus the number of possible stereoisomers to
improve asymmetric catalysis results [7].
As the asymmetric catalysis requires the selective
formation of a single enantiomer, the availability of chiral
ligands in both enantiomeric forms is essential to afford
the desired stereoisomer. In most cases, both enantiomers
of the phosphorus ligands are obtained by chemical
resolution (For resolution of BINAP, MeO-BIPHEP or
SYNPHOS, see [8]), or from their chiral original backbone
scaffold (For the synthesis of JOSIPHOS and MonoPHOS
from chiral backbone scaffolds, see [9]). In other cases, the
enantiomers are obtained by stereoselective synthesis
starting from the chiral pool (For representative synthesis
of DIOP and PHOX starting from the pool chiral, see [10]),
or from prochiral precursors (For the asymmetric synthesis
of DuPHOS, see [11]).
In the case of the DIPAMP 1, BIPNOR 2 and Trichick-
enfootphos 3, the P-chirogenic phosphines were obtained
enantiomerically pure by chemical resolution or by
As ephedrine is available in both antipodal forms (+) or
(ꢀ), the stereoselective synthesis of both enantiomeric

[(Scheme_1)TD$FIG]
F. Chaux et al. / C. R. Chimie 13 (2010) 1213–1226
1215
Scheme 1.
[(Scheme_2)TD$FIG]
Scheme 2.
mono- or diphosphines can be achieved. In addition, we
previously reported the enantiodivergent synthesis of both
enantiomers starting from the same complex 11, by simply
changing the order of addition of the organolithium
reagents (i.e. R3Li then R2Li vs R2Li then R3Li) (Scheme
2) [6(a,c), 18]. However, this method was mainly
examplified using aryl substituents on the phosphorus
atom, because in the case of alkyl group, side reactions can
the enantioselective synthesis of both (R) and (S)-
enantiomers of the di- or triaryl-phosphine boranes 15a-
d, reported in Table 1.
Thus, inverting the introduction order of the substi-
tuents during the synthesis, i.e. methyl as former group
then o-anisyl, or reversely, can afford either the (S)- or the
(R)-PAMP borane 15a respectively, with e.e. up to 98%
(entries 1,2; Table 1). Both enantiomers of the tertiary
phosphine boranes 15b and 15c, were separately prepared
using the same procedure starting respectively from o-
anisyl-, ferrocenyl- or m-xylyl-aminophosphine boranes
12b, 12c or 12d, which are derived from the (+)-ephedrine
(Table 1, entries 3–6).4 The X-ray structures of the
phosphine boranes (R)-15b and (S)-15b were obtained
and their ORTEP views are given in Figs. 1 and 2, with
selected structural parameters.
occur by deprotonation in
borane.
a-position of the phosphine
We now wish to report some new efficient routes for
the enantiodivergent synthesis of P-chirogenic mono- and
diphosphines using the ephedrine methodology, giving
easy access to both enantiomers, notably for derivatives
bearing alkyl groups.
2. Results and discussion
2.2. Enantiodivergent synthesis using P-chirogenic phosphide
borane reagents (Route B)
2.1. Enantiodivergent synthesis using P-chirogenic
chlorophosphine boranes as electrophilic reagents (Route A)
Recently, the investigation of the reaction between the t-
butyllithium reagent and the chlorophosphine boranes 14,
led to the discovery of an unexpected new metal-halide
exchange affording the corresponding P-chirogenic phos-
phide boranes 9 with retention of the configuration at the
phosphorus atom (Scheme 3b). Following the subsequent
addition of alkyl halide in excess, the corresponding
phosphine boranes 15 were obtained in good to excellent
yieldsandwithe.e. upto99%(Scheme3b, Table2). Theroute
(B) was also successfully applied for the enantioselective
preparation of the phosphine borane (S)-15a (PAMP.bor-
ane). The latter is obtained by acidolysis with HCl of the
In connection with our on-going work on the asym-
metric synthesis of P-chirogenic phosphorus compounds,
we developed earlier the facile preparation of chloropho-
sphine boranes 14 as new P-chirogenic electrophilic
building blocks [19]. The chlorophosphine boranes 14
are readily obtained by acidolysis of the aminophosphine
boranes 12 with a toluene solution of HCl, leading to the P-
N bond cleavage with inversion of configuration on the
phosphorus atom (Scheme 3) [19].
The reaction of the chlorophosphine boranes 14 with
organolithium reagents stereospecifically provides the
corresponding P-chirogenic phosphine boranes 15, with
inversion of configuration on the phosphorus atom
(Scheme 3a). The route (A) was successfully applied to
4
The o-anisylphenyl-m-xylylphosphine 12d is referred as the Chou-
Phos in the laboratory.

[(Scheme_3)TD$FIG]
1216
F. Chaux et al. / C. R. Chimie 13 (2010) 1213–1226
Scheme 3.
Table 1
Enantiodivergent synthesis of phosphine boranes 15 using chlorophosphine boranes 14.
Entry
Aminophosphine boranes
Chlorophosphine boranes
Phosphine boranes
R1
R2
HCl (equiv)
Time (h)
R3
Yields (%)a
e.e. (%)b
Conf.
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
i-Pr
Me
12a
12b
12b
12b
12c
12d
12ec
12fc
2.1
4
1
1
14a
14b
14b
14b
14c
14d
14e
14e
o-An
Me
80
90
71
79
79
82
68
86
90b
98b
95b
99b
98b
99b
89d
96d
(S)-15a
(R)-15a
(R)-15b
(S)-15c
(S)-15b
(R)-15c
(R)-15d
(S)-15d
o-An
o-An
o-An
Fc
4
1
Fc
4
1
m-Xyl
o-An
o-An
Me
15
6
48
1
m-Xyl
i-Pr
5
12
12
Ph
5
Me
a
Isolated yields.
b
c
Determined by HPLC on a chiral column of the borane complex.
Prepared from (ꢀ)-ephedrine (see Scheme 4).
d
Determined by 31P NMR of the phosphine oxide derivative in presence of reagent 21.
aminophosphine borane 12b, then metal-halide exchange
with t-BuLi reagent, andfinally, trapping with methyl iodide
(Table 2, entry 1). Noteworthy, the phosphine borane (S)-
15a, obtained in this case, is the enantiomer of that prepared
following the route (A) starting from aminophosphine
borane 12b (Table 1, entry 2).
Interestingly, route (B) offers a versatile and efficient
pathway for the enantiodivergent synthesis of P-chiro-
[(Fig._1)TD$FIG]
˚
Fig. 1. Crystal structures: (a) Phosphine borane (R)-15c. Selected bond lengths (A), angles (8): P-B 1.917(2), P-C(1) 1.8138(18), P-C(7) 1.8170(17), P-C(14)
˚
1.8165(16); C(1)-P-B 109.53(9); C(7)-P-B 111.37(8), C(14)-P-B 113.43(9). (b) Phosphine borane (R)-15b. Selected bond lengths (A), angles (8): P-B 1.913(3),
P-C(10) 1.793(2), P-C(11) 1.815(2), P-C(17) 1.810(2), Cp(1)-Fe 1.659(2), Cp(2)-Fe 1.645(2); C(10)-P-B 109.87(12), C(11)-P-B 107.82(11), C(17)-P-B
112.83(13), Cp(1)-Fe-Cp(2) 176.86 (12).

F. Chaux et al. / C. R. Chimie 13 (2010) 1213–1226
1217
Table 2
Enantiodivergent synthesis of phosphine boranes 15 using chlorophosphine boranes 14 as phosphide borane 9 precursors.
Entry
Aminophosphine boranes
Chlorophosphine boranes
Phosphine boranes
R1
R2
HCl (equiv)
Time (h)
R3X
Yields (%)a
e.e. (%)
Conf.
1
2
3
Ph
o-An
i-Pr
Ph
12b
12ec
12fc
4
5
5
1
14b
14e
14e
MeI
MeI
MeI
75
73
71
92b
96d
96d
(S)-15a
(S)-15d
(R)-15d
Ph
12
12
i-Pr
a
Isolated yields.
b
c
Determined by HPLC on a chiral column of the borane complex.
Prepared from (ꢀ)-ephedrine.
d
Determined by 31P NMR of the phosphine oxide derivative in presence of reagent 21.
genic phosphines. Thus, the i-propylaminophosphine
borane 12e, which was prepared from the oxazapho-
spholidine complex (Rp)-11a, leads to both enantiomers of
the phosphine borane 15d (Scheme 4a). On the one hand,
the acidolysis of 12e with HCl, which affords the
corresponding chlorophosphine-borane intermediate, pro-
vides the (S)-methylphenyl-i-propylphosphine borane 15d
after a metal-halogen exchange using t-BuLi reagent, and
then trapping with methyl iodide (Scheme 4a; Table 2,
entry 2). On the other hand, the (R)-methylphenyl-i-
propylphosphine borane 15d was obtained according to
route (A), after HCl acidolysis of the aminophosphine
borane 12e then reaction with MeLi (Scheme 4; Table 1,
entry 7).
tion of the complex 16a was determined by comparison
with the X-Ray structure of the 2-ethyloxazaphospholidine
borane 16b (R1 = Et). This latter compound was prepared
by a similar procedure from (ꢀ)-ephedrine, but using
ethylmagnesium chloride instead of i-propylmagnesium
reagent.5 The reaction of the oxazaphospholidine borane
16a with the phenyllithium reagent affords the phenyl-i-
propylaminophosphine borane 12f by P-O bond cleavage
of the heterocycle (Scheme 4b). The X-ray structure of
compound 12f (Fig. 2) proves the stereochemistry of ring-
opening process with inversion of configuration on the
phosphorus centre (Scheme 4b). After acidolysis with HCl
of the epimer 12f, then metal-halide exchange with t-BuLi
reagent of the chlorophosphine-borane intermediate, and
finally trapping with MeI, the (R)-methylphenyl-i-propyl-
phosphine borane 15d was obtained in 71% yield and with
97% e.e. (Scheme 4b; Table 2, entry 3).
The synthesis of both enantiomers of the phosphine
borane 15d was also achieved starting from the phenyl-i-
propylaminophosphine borane 12f, readily obtained from
the 2-i-propyloxazaphospholidine borane 16a. This new
starting complex 16a was prepared in a diastereomerically
pure form by subsequent reactions of PCl3 with (ꢀ)-
ephedrine [21], then with i-propylmagnesium reagent and
Finally, the (S)-methylphenyl-i-propylphosphine bo-
rane 15d was also obtained from the i-propylaminophos-
phine borane 12f using route (A), by acidolysis with
HCl followed by a reaction with MeLi (Scheme 4; Table 1,
entry 8).
.
finally with BH3 DMS (Scheme 4b). The relative configura-
[(Fig._2)TD$FIG]
2.3. Enantiodivergent synthesis of the P-chirogenic 1,2-
bis(methylphenylphosphino)ethane 4
The synthesis of both enantiomers of the P-chirogenic
1,2-bis(diphosphino)ethane 17 can be achieved by a
Knowles’ like coupling of the corresponding (R)- or (S)-
methylphosphine borane 15, which are prepared accord-
ing to one of the approaches described above (Scheme 5)
[12a,18].
Preliminary results indicate that the C-C bond coupling
can also be achieved with the (R)-methylphenylphos-
phinite borane 10a affording the corresponding (R,R)-1,2-
bis(phenylphosphinito borane)ethane 18 (Scheme 6a)
[21,22]. Interestingly, the reaction of two equivalents of
methyl lithium reagent with the compound 18 leads to the
(S,S)-diphosphine diborane 19 and then, to the (S,S)-(+)-
diphosphine
4 after decomplexation of the borane
protecting group (Scheme 6a, Table 3, entry 6). The other
enantiomer of the diphosphine (R,R)-(ꢀ)-4 was then
prepared using the same pathway, but starting from
(ꢀ)-ephedrine (Scheme 6b, Table 3, entry 7).
Fig. 2. Crystal structure of aminophosphine borane 12f with selected
˚
bond lengths (A), angles (8): P-B 1.9206(19); P-N 1.6755(13), P-C(11)
1.8285(16, P-C(14) 1.8263(16; N-P-B 114.47(8); C(11)-P-B 112.31(8),
C(14)-P-B 110.93(8), C(1)-N-P 118.35(10), C(1)-N-C(10) 116.03(13),
C(10)-N-P 118.84(11).
5
To be published.

[(Scheme_4)TD$FIG]
1218
F. Chaux et al. / C. R. Chimie 13 (2010) 1213–1226
[(Scheme_5)TD$FIG]
Scheme 4.
be achieved from a reaction with an amine [26], a strong
acid [27], EtOH [28] or an olefin [24b,29], to quantitatively
lead to the corresponding P(III)-compound with complete
retention of configuration on the phosphorus atom. The
uncoordinated P-chirogenic mono- 13 and the dipho-
sphine 4 were obtained by heating at 50 8C either in pure
diethyl amine, or in toluene in the presence of DABCO.
Subsequently, the purification is achieved by fast filtration
through neutral alumina (Scheme 2, Table 3). The
enantiomeric excesses of the phosphines were determined
either by HPLC on a chiral column after an additional
complexation with BH3.DMS, or by 31P NMR in presence of
the chiral palladium complex 20 (For the preparation of the
chiral palladium complex 19, see [30a]; For the preparation
of N,N-dimethyl-1-phenylethylamine, see [30b]; For the
31P NMR, see [30c]), or by 31 P NMR of the phosphine oxide
derivatives in presence of the resolving Kagan’s reagent 21
[31].
Scheme 5.
The X-ray structure of the (S,S)-1,2-bis(phenylpho-
sphinito borane)ethane 18 (Fig. 3), exhibits an unfolded
conformation with the substituents disposed anti relative
each other. Moreover, the (S) absolute configuration of the
phosphinite borane fragments is consistent with the
retention of the configuration during the C-C bond
coupling of the anion resulting from 10a (Scheme 6).
2.4. Decomplexation of the borane complexes into P-
chirogenic mono- and diphosphines
The phosphine borane complexes can directly be used
without decomplexation, for the synthesis of quaternary
phosphonium salts [23], (thio)phosphorylated derivatives
[24], and chiral complexes or catalysts derived from
transition metals [25,26b]. When the uncoordinated
phosphines are required, the borane decomplexation can
[(Scheme_6)TD$FIG]
Scheme 6.

F. Chaux et al. / C. R. Chimie 13 (2010) 1213–1226
1219
Table 3
Preparation of free mono- and diphosphines from their borane complexes.
Entry
Borane complex
Conditions
Mono- and diphosphine
½
aꢁD
d31P NMR
ꢀ36
e.e. (%)
20
(R)-15a
HNEt2 50 8C/10h
[
(R)-13a
+46a
98d
1
2
3
4
5
6
(S)-15b
(S)-15c
(S)-15d
(R)-15d
(S,S)-18
(R,R)-18
DABCO 50 8C/10h
DABCO 50 8C/10h
DABCO 50 8C/10h
DABCO 50 8C/10h
DABCO 50 8C/10h
DABCO 50 8C/10h
N
(S)-13b
(S)-13c
(S)-13d
(R)-13d
(S,S)-4
ꢀ4.8b
ꢀ3.8b
ꢀ10b
–
ꢀ28.3
ꢀ16.9
ꢀ19.3
–
98d
99d
93e
96e
99f
99f
+24.5b
ꢀ23.5c
–
7
(R,R)-4
ꢀ32
a
In MeOH.
b
c
d
e
f
In CHCl3.
In CH2Cl2.
Determined by HPLC on a chiral column of the borane complex derivative.
Determined by 31P NMR of the phosphine oxide derivative in presence of reagent 21.
Determined by 31P NMR in presence of chiral palladium complex 20.
[(Fig._3)TD$FIG]
Since the two enantiomers of ephedrine are available,
the stereoselective synthesis of both enantiomers of mono-
or diphosphine is easily performed. Furthermore, both
enantiomers of a phosphine ligand can also be obtained,
starting from the same oxazaphospholidine borane com-
plex derived from (+)-ephedrine, when changing the order
of addition of the organolithium reagents during the
synthetic pathway.
An alternate approach is based on the P-chirogenic
chlorophosphine boranes, which afford one enantiomer of
a phosphine borane with inversion of configuration, by a
reaction with an organolithium reagent. On the other hand,
the chlorophosphine boranes also provide the correspond-
ing P-chirogenic phosphide boranes 9 with retention of
configuration on the phosphorus atom, by an unexpected
metal-halogen exchange using the t-butyllithium reagent.
The addition of alkyl halide to the resulting phosphide
boranes then affords the corresponding phosphine bor-
anes, but with opposite configuration.
Fig. 3. Crystal structure of the (S,S)-diphosphinite diborane 18. Selected
˚
bond lengths (A), angles (8): (a) P(1)-C(1) 1.806(3), P(2)-C(2) 1.804(3),
P(1)-C(5) 1.803(3), P(2)-C(11) 1.805(3), P(1)-O(1) 1.607(3), P(2)-O(2)
1.600(2), P(1)-B(1) 1.895(3), P(2)-B(2) 1.889(4); O(1)-P(1)-C(1)
99.90(14), O(2)-P(2)-C(2) 99.42(13), O(1)-P(1)-C(5) 106.13(13), O(2)-
P(2)-C(11) 105.77(14), O(1)-P(1)-B(1) 116.66(17), O(2)-P(2)-B(2)
116.19(16).
A
third approach is based on the stereoselective
3. Conclusion
synthesis of the starting oxazaphospholidine borane
complex derived from (ꢀ)-ephedrine. In the case where
this complex is prepared using the bis(dimethylamino)-
phosphine, the absolute configuration of phosphorus
centre is (R). When it is prepared by subsequent reactions
of (ꢀ)-ephedrine with PCl3, and then with a Grignard
Several approaches for the enantiodivergent syntheses
of P-chirogenic mono- and diphosphines were described,
using the convenient ephedrine methodology and the
borane complex chemistry.

1220
F. Chaux et al. / C. R. Chimie 13 (2010) 1213–1226
reagent, the configuration of the phosphorus centre is (S).
Consequently, depending on the method for the prepara-
tion of the starting oxazaphospholidine borane, the
convenient synthesis can provide either phosphine enan-
tiomers.
solvents using silica gel 60 A, (35–70 mm; Acros) or
aluminium oxide 90 standardized (Merck). All NMR
spectra data were recorded on BRUKER AM 250, 300
AVANCE, 500 AVANCE DRX and 600 AVANCE II spectro-
meters at ambient temperature. Data are reported as
s = singlet, d = doublet, t = triplet, q = quartet, m = multi-
plet, brs = broad singlet, brd = broad doublet, dhept = -
doublet of heptuplet, coupling constant(s) in Hertz.
Melting points were measured on a Kofler bench melting
point apparatus and are uncorrected. Optical rotations
values were recorded at 20 8C on a Perkin-Elmer 341
polarimeter, using a 10 cm quartz vessel. Infrared spectra
were recorded on a Bruker Vector 22 apparatus. Mass and
HRMS spectra were recorded on Mass, Bruker ESI micro
Finally, the synthesis of (R,R)- and (S,S)-1,2-bis(methyl-
phenylphosphino)ethane 4 was also described, using both
P-chirogenic diphosphinite diborane 18 enantiomers
prepared from (+)- or (ꢀ)-ephedrine.
In summary, the efficiency of the ephedrine methodo-
logy is again highlighted by offering several approaches for
the synthesis of both enantiomeric P-chirogenic mono-
and diphosphines in the desired absolute configuration,
notably bearing alkyl substituents.
´
TOF-Q apparatus, at the Universite de Bourgogne (Dijon).
4. Experimental section
The major peak m/z was mentioned with the intensity as a
percentage of the base peak in brackets. Elemental
analyses were measured with a precision superior to
All reactions were carried out under an Ar atmosphere
in dried glassware. Solvents were dried and freshly
distilled under an Ar atmosphere over sodium/benzophe-
none for THF, diethylether, toluene and benzene, CaH2 for
CH2Cl2. Hexane and isopropanol for HPLC were of
chromatography grade and used without further purifi-
cation. Methyllithium (1.6 M in Et2O), s-butyllithium
(1.4 M in cyclohexane), t-butyllithium (1.6 M in pentane),
phenyllithium (1.8 M in Bu2O), isopropyllithium (0.7 M in
pentane), isopropylmagnesium chloride (2 M in THF),
ethylmagnesium chloride (2 M in THF), ferrocene, 2-
bromoanisole, 5-bromo-m-xylene, methyl iodide,
BH3.SMe2, N-methyl morpholine and 1,4-diazabicy-
clo[2.2.2]octane (DABCO) were purchased from Aldrich,
Acros or Alfa Aesar, and used as received. (+)- and (ꢀ)-
ephedrine were purchased from Aldrich and dried by
azeotropic shift of toluene on rotary evaporator. Phos-
phorus trichloride was distilled and CuCl2 dried at 100 8C
for 12 h, before use. The solution of HCl in toluene (0.2–
0.4 M) was obtained by bubling HCl gas in toluene and
titrated by acidimetry before use. The (2S, 4R, 5S)-(ꢀ)-3,4-
dimethyl-2,5-diphenyl-1,3,2-oxazaphospholidine-2-bo-
rane 11a and its enantiomer (2R, 4S, 5R)-(+)-11a, were
prepared from the appropriate (+)- or (ꢀ)-ephedrine, as
previously described [19a].
´
0.3% at the Microanalysis Laboratories of the Universites
P. & M. Curie (Paris) and Bourgogne (EA 1108 CHNS-O
FISONS Instrument). X-Ray analyses were performed at
the Universite de Bourgogne, and the data were collected
´
at 115 K on a Bruker Nonius Apex II CCD system using
graphite-monochromated Mo-K
a radiation. The struc-
tures were solved by direct methods (SIR92)[33] and
refined with full-matrix least-squares methods based on
F2 (SHELXL-97)[34] with the aid of the WINGX program
[35]. All non-hydrogen atoms were refined with aniso-
tropic thermal parameters. Hydrogen atoms were either
included in theirs calculated positions or found in Fourier
difference maps (CH3 and BH3). Crystallographic data and
structures refinement details for 12f, 15c, 15d and 18 are
summarized in Table 4.
CCDC 768724, 768725, 768726 and 768727 contain the
supplementary crystallographic data for 15d, 15c, 18, 12f.
These data can be obtained free of charge from The
Cambridge Crystallographic Data Center via www.ccdc.ca-
m.ac.uk/data_request/cif.
4.1. Synthesis of (2S,4S,5R)-(ꢀ)-2-isopropyl-3,4-dimethyl-5-
phenyl-1,3,2-oxazaphospholidine borane 16a
The
(Sp)-(+)-N-methyl-N-[(1S,2R)(1-hydroxy-2-
A 250 mL Schlenk flask, equipped with a magnetic
stirrer and a septum, was charged with 50 mL of toluene
and 2.8 mL (25.8 mmol) of N-methylmorpholine. Addi-
tion of PCl3 (1.12 mL, 12.9 mmol) was smoky and the
resulting solution was cooled to ꢀ78 8C. Then (ꢀ)-
ephedrine (2.1 g, 12.9 mmol) in 10 mL of toluene was
added dropwise via syringe. The reaction was allowed to
reach room temperature overnight and N-methylmor-
pholine hydrochloride was filtered under argon. The
resulting crude solution (2R,4S,5R)-2-chloro-3,4-dimeth-
yl-5-phenyl-1,3,2-oxazaphospholidine was used further
without purification. 31P NMR (CDCl3, 121.5 MHz)
methyl-1-phenyl-2-propyl)]aminomethylphenyl phos-
phine borane 12a and (Rp)-(+)-N-methyl-N-[(1S,2R)(1-
hydroxy-2-methyl-1-phenyl-2-propyl)] amino-o-anisyl-
phenylphosphine borane 12b were prepared from the
(+)-ephedrine according to the published procedure
[19c]. (R)-(+) and (S)-(ꢀ)-[(O-methyl)-methylphenylpho-
sphinite]borane 10a were obtained as previously de-
scribed, starting from the (+)- and (ꢀ)-ephedrine
respectively [18(a,b),26c,32]. Chiral HPLC analysis were
performed on SHIMADZU 10-series apparatus, using
chiral columns (Chiralcel OK, Chiralcel OD, Chiralcel
OD-H, Chiralpack AD, Chiralcel OJ, Lux 5
and with hexane/propan-2-ol mixtures as the mobile
phase (Flow rate 1 mL minꢀ1; UV detection
= 254 nm).
Thin layer chromatography (TLC) was performed on
0.25 mm E. Merck precoated silica gel plates and exposed
by UV, potassium permanganate or iodine treatment.
Flash chromatography was performed with the indicated
m
-cellulose-2),
d
+ 168.6 ([20] + 172.4).
A 250 mL Schlenk flask, equipped with a magnetic
l
stirrer and a septum, was charged with crude solution of
(2R,4S,5R)-2-chloro-3,4-dimethyl-5-phenyl-1,3,2-oxaza-
phospholidine in toluene. The mixture was cooled to
ꢀ60 8C and 8 mL of isopropylmagnesium chloride (2 M in
THF; 16.1 mmol) was added. Reaction was stirred at this

F. Chaux et al. / C. R. Chimie 13 (2010) 1213–1226
1221
Table 4
Crystallographic data and structures refinement details for 12f, 15c, 15d and 18.
Compounds
12f
15c
15d
18
Empirical formula
Formula weight
Temperature (K)
Crystal system
Space group
C19H29BNOP
329.21
C21H24BOP
334.18
C23H24BFeOP
414.05
C16H26B2O2P2
333.93
115(2)
115(2)
115(2)
110(2)
Orthorhombic
P212121
Orthorhombic
P212121
Monoclinic
P21
Monoclinic
P21
˚
a (A)
8.2195(4)
14.5616(6)
16.1165(8)
90
10.0720(2)
12.8584(3)
14.5612(3)
90
8.5691(3)
10.4833(3)
11.6417(4)
90
10.9431(5)
8.6606(6)
10.8797(8)
90
˚
b (A)
˚
c (A)
a
b
g
(8)
(8)
(8)
90
90
106.7440(10)
90
90.906(4)
90
90
90
3
˚
Volume (A )
1928.97(16)
4
1885.82(7)
4
1001.46(6)
2
946.19(11)
2
Z
r
m
calc. (g/cm3)
(mmꢀ1
Size (mm3)
F(000)
l
1.134
1.177
1.373
1.172
)
0.146
0.150
0.842
0.232
0.32 ꢂ 0.30 ꢂ 0.12
712
0.20 ꢂ 0.20 ꢂ 0.18
712
0.40 ꢂ 0.30 ꢂ 0.20
432
0.25 ꢂ 0.05 ꢂ 0.05
356
0.71073
0.65
0.71073
0.65
0.71073
0.71073
ꢀ1
˚
sin(
u
)/
l
max; A
0.65
0.65
Index ranges
h: ꢀ10; 10
k: ꢀ18; 18
l: ꢀ20; 20
4310
h: ꢀ13; 13
k: ꢀ16; 16
l: ꢀ18; 18
4307
h: ꢀ11; 10
k: ꢀ13; 13
l: ꢀ15; 14
6351
h: ꢀ12; 13
k: ꢀ8; 11
l: ꢀ14; 14
3302
Reflection collected
Rint
0.017
0.023
0.024
0.026
Reflection with I ꢃ 2
s
(I)
4180
3796
3950
3132
Data/restraints/parameters
4310/0/214
R1 = 0.0341a
wR2 = 0.0773b
R1 = 0.0362a
wR2 = 0.0792b
1.082
4307/0/223
R1 = 0.0364a
wR2 = 0.0816b
R1 = 0.0464a
wR2 = 0.0855b
1.045
4472/1/248
R1 = 0.0329a
wR2 = 0.0614b
R1 = 0.0427a
wR2 = 0.0644b
1.046
3302/1/200
R1 = 0.0439a
wR2 = 0.0939b
R1 = 0.0481a
wR2 = 0.0981b
1.082
R indices (I ꢃ 2s [I])
R indices (all data)
Goodness-of-fitc on F2
Absolute structure parameters
0.04(8)
0.04(8)
0.000(13)
0.217 and ꢀ0.286
768 724
0.00(14)
´
ꢀ3
˚
Dr (e A
)
0.200 and ꢀ0.180
768 727
0.181 and ꢀ0.311
768 725
0.291 and ꢀ0.242
768 726
CCDC deposition No.
a
R1 =
S
(jjFoj-jFcjj)/ jFoj.
S
1=2
2
2
2
2
b
wR2 ¼ ½
S
wðFo2 ꢀ Fc2Þ =
S
½wðFo2Þ ꢁ
where w ¼ 1=½s2ðFo2 þ ð0:0228PÞ þ 0:85Pꢁ for 12f, w ¼ 1=½s2ðFo2 þ ð0:0387PÞ þ 0:39Pꢁ for 15c, w ¼ 1=½s2ðFo2
þ
2
2
ð0:0182PÞ þ 0:11Pꢁ for 15d and w ¼ 1=½s2ðFo2 þ ð0:0149PÞ þ 0:12Pꢁ for18.
c
S = [S
w(Fo2-Fc2)2/(n-p)]1/2 (n = number of reflections, p = number of parameters).
.
temperature for 1 h and then 2 mL of BH3 BMS complex
were added. After 1 h under stirring, the mixture was
hydrolyzed at ꢀ60 8C, and the aqueous layer was extracted
with CH2Cl2. Combined organic phases were dried over
MgSO4, filtered and concentrated in vacuo. The residue
was purified by flash chromatography on silica gel
4.2. Synthesis of the aminophosphine boranes 12
4.2.1. Preparation of organolithium reagents
4.2.1.1. Aryllithium reagents by metal-halogen exchange. In
a two necked-flask equipped with a magnetic stirrer and an
argon inlet, 1 equiv. of sec-butyllithium is added. The
mixture is cooled to 0 8C and 1 equiv. of 1-bromoanisole (1-
bromonaphthalene or bromobenzene) is slowly added with
a syringe while stirring. After the formation of a white
precipitate, the mixture is stirred for 1 h at 0 8C. The
organolithium reagent is dissolved with a minimum of dry
THF before use.
with
a mixture hexane/CH2Cl2 (15:10) as eluent to
afford the oxazaphospholidine borane complex 16a as a
mixture of epimers in a 20:1 ratio (1.76 g, 55% yield).
Crystallisation from hexane gives 1.4 g (43%) of the major
isomer 16a.
½aꢁD
¼ ꢀ12:3 (c 1.9, CHCl3); mp = 50 8C; IR (
n
cmꢀ1):
20
3035, 2978, 2859, 2402, 2372, 2344, 1460, 1385, 1290,
1226, 1190, 965, 875, 836, 739; 1H NMR (CDCl3,
4.2.1.2. Preparation of ferrocenyllithium by deprotonation of
the ferrocene. A 250 mL three-necked flask equipped with
a magnetic stirrer under an argon atmosphere was charged
with ferrocene (0.74 g, 4 mmol) and THF (10 mL). At 0 8C, t-
BuLi (2.75 mL, 1.6 M in hexane, 4.4 mmol) was added
dropwise, and the reaction mixture was stirred at 0 8C for
1 h, before use.
300.13 MHz)
d 0.0–0.90 (m, 3H), 0.59 (d, J = 6.7 Hz, 3H),
1.03 (dd, J = 15.4 and 7.2 Hz, 3H), 1.05 (dd, J = 15.4 and
7.2 Hz, 3H), 1.82 (dhept, J = 9.0 and 7.2 Hz, 1H), 2.58 (d,
J = 9.4 Hz, 3H), 3.55 (dq, J = 17.1 and 6.5 Hz, 1H), 5.35 (dd,
J = 5.8 and 1.6 Hz, 1H), 7.10- 7.23 (m, 5H); 31P NMR (CDCl3,
121.5 MHz)
75.5 MHz)
d
+ 156.1 (q, J = 75.8 Hz); 13C NMR (CDCl3,
12.9 (d, J = 1.8 Hz), 15.8 (d, J = 2.2 Hz), 16.2,
d
30.5 (d, J = 8.1 Hz), 31.7 (d, J = 29.1 Hz), 60.0 (d, J = 2.4 Hz),
84.2 (d, J = 7.4 Hz), 126.3, 126.2, 128.4, 136.5 (d, J = 5.9 Hz);
HRMS (ESI) calcd for C13H23BNNaOP [M + Na]+: 274.1505;
found: 274.1470.
4.2.2. General procedure
Ina100 mLthree-neckedflask,equippedwithamagnetic
stirrerandanargoninlet, 5 mmoloftheoxazaphospholidine

1222
F. Chaux et al. / C. R. Chimie 13 (2010) 1213–1226
borane complex 11a were dissolved in 5 mL of anhydrous
THF. The mixture was cooled at ꢀ78 8C and 2 equiv.
(10 mmol) of the organolithium reagent were slowly added.
The resultingmixturewasstirredandwarmedto0 8C (or RT)
until the starting material had completely reacted. The
reactionwas monitored byTLCoversilica(CH2Cl2 aseluent),
and was finally hydrolyzed at 0 8C with 2 mL of water. The
THF was removed under reduced pressure and the aqueous
layer was extracted several times with dichloromethane.
ThecombinedorganicphasesweredriedoverMgSO4 andthe
solvent was removed. The residue was purified on a short
columnofsilicagel,usingamixtureoftoluene/AcOEt95:5as
eluent, to afford the aminophosphine boranes 12. The
aminophosphine boranes can be recrystallized using a
mixture hexane/isopropanol 7:3.
(C-H), 2380 (B-H), 1453, 1436, 1386, 1220, 1173, 1107,
1071, 1023, 1005, 955, 914, 884, 742, 727, 698, 645, 619,
1
582; H NMR (CDCl3, 300.13 MHz)
d 0.10–0.90 (m, 3H),
0.96 (dd, J = 17.1 and 7.2 Hz, 3H), 1.03 (d, J = 6.9 Hz, 3H),
1.09 (dd, J = 15.3 and 7.2 Hz, 3H), 2.50 (d, J = 7.2 Hz, 3H),
2.47–2.61 (m, 1H), 3.97-–4.09 (m, 1H), 4.68 (d, J = 4.8 Hz,
1H), 7.07–7.19 (m, 3H), 7.23–7.37 (m, 5H), 7.46 (m, 2H);
31P NMR (CDCl3, 121.5 MHz)
d
+ 76.4; 13C NMR (CDCl3,
75.0 MHz) 12.9 (d, J = 3.8 Hz), 17.5 (d, J = 5.3 Hz), 22.8 (d,
d
J = 44.5 Hz), 29.9 (d, J = 3.0 Hz), 59.1 (d, J = 7.6 Hz), 79.2 (d,
J = 2.3 Hz), 126.7, 128.1, 128.9, 129.0 (d, J = 2.3 Hz), 131,7
(d, J = 55.9 Hz), 131.8 (d, J = 9.1 Hz), 143.2; MS (EI) m/z
(relative intensity) 352 (M+ + Na; 100), 338 (M+ - BH3 + Na;
95); HRMS (ESI) calcd for
352.1962; found: 352.1976.
C
19H29BNNaOP [M + Na]+
4.2.3. (Rp)-(+)-N-methyl-N-[(1S,2R)(1-hydroxy-1-phenyl-
prop-2-yl]aminoferrocenylphenyl phosphine borane 12c
(from (Sp)-11a)
4.2.6. (Sp)-(+)-N-methyl-N-[(1R,2S)(1-hydroxy-1-phenyl-
prop-2-yl]aminophenyl-i-propyl phosphine borane 12f
A 50 mL Schlenk flask, equipped with a magnetic stirrer
and a septum, was charged with 15 mL of THF and 0.75 g
(3 mmol) of (2S,4S,5R)-(ꢀ)-2-isopropyl-3,4-dimethyl-5-
phenyl-1,3,2-oxaza phospholidine borane 16a (major iso-
mer). The mixture was cooled to ꢀ78 8C and 3.33 mL
(6 mmol) of phenyllithium was added and stirred over-
night at ambient temperature. After hydrolysis at 0 8C, the
aqueous layer was extracted with CH2Cl2 and the organic
phase was dried over MgSO4, filtered and concentrated in
vacuo. The crude product was purified by flash chroma-
tography using CH2Cl2 as eluent, to afford the aminophos-
phine borane 12f as a mixture of epimers in a 9:1 ratio
(0.81 g, 82% yield). Crystallisation from hexane:isopropa-
nol (7:3) affords 0.51 g (52%) of major isomer 12f.
Yield = 80%; Orange crystals; ½a D
ꢁ
¼ þ113:9 (c 1.0,
20
CHCl3); Rf = 0.62 (toluene/EtOAc [9:1]); IR (KBr,
n
cmꢀ1):
3500 (O-H), 2372 (B-H), 1455, 1437, 1386, 1367, 1217,
1163, 1106, 1063, 1022, 998, 956, 884, 822, 763, 746, 721,
698, 646, 614; 1H NMR (CDCl3, 300.13 MHz)
d 0.20–2.00
(m, 3H), 0.91 (d, J = 6.3 Hz, 3H), 2.05 (brs, 1H), 2.38 (d,
J = 8.4 Hz, 3H), 4.16–4.25 (m, 1H), 4.23–4.27 (m, 1H), 4.30
(brs, 5H), 4.51 (d, J = 11.7 Hz, 2H), 4.58–4.62 (m, 1H), 4.87
(d, J = 5.7 Hz, 1H), 7.28–7.46 (m, 10H); 31P NMR (CDCl3,
121.5 MHz) d d13.7,
+ 70.7 (m); 13C NMR (CDCl3, 75.0 MHz)
31.3, 40.3, 58.4 (d, J = 10.6 Hz), 70.9, 71.9, 73.0, 79.6, 127.3,
128.4, 128.8, 128.9, 129.1, 131.1, 132.2 (d, J = 9.8 Hz),
143.3; Anal. calcd for C26H31BFeNOP (471.17): C 66.28, H
6.63, N 2.97; found: C 66.33, H 6.83, N 3.02.
½
aꢁD
¼ ꢀ14:8 (c 1.1, CHCl3); mp 130 8C; IR (
n
cmꢀ1):
20
3510 (OH), 2417 (BH), 2375 (BH), 2343 (BH), 1387, 1103,
1018, 999, 743, 723, 698, 585. 1H NMR (CDCl3,
4.2.4. (Rp)-(ꢀ)-N-methyl-N-[(1S,2R)(1-hydroxy-1-phenyl-
prop-2-yl]aminophenyl-m-xylylphosphine borane 12d (from
(Sp)-11a)
300.13 MHz)
d 0.1- 0.90 (m, 3H), 0.99 (dd, J = 15.4 and
7.3 Hz, 3H), 1.03 (dd, J = 15.4 and 7.3 Hz, 3H), 1.88 (bs, 1H),
2.53 (d, J = 8.4 Hz, 3H), 2.63 (dhept, J = 16.3 and 7.1 Hz, 1H),
4.11 (dhept, J = 6.8 and 1.2 Hz, 1H), 4.78 (d, J = 5.2 Hz, 1H),
7.24- 7.52 (m, 8H), 7.70–7.76 (m, 2H); 31P NMR (CDCl3,
Yield = 70%; White crystals; ½a D
ꢁ
¼ ꢀ47 (c 0.6, CHCl3);
20
mp = 124 8C; Rf = 0.12 (toluene); IR (KBr,
H), 3055–2796 (C–H), 2394 (B–H), 1596, 1455, 1438, 1270,
1160, 1065, 1037; 1H NMR (CDCl3, 300.13 MHz)
0.20–
n
cmꢀ1): 3549 (O-
d
121.5 MHz)
75.0 MHz)
d
+ 76.3 (brd, J = 88 Hz); 13C NMR (CDCl3,
d 12.1, 15.6, 16.8 (d, J = 5.4 Hz), 21.5 (d,
2.00 (m, 3H), 1.27 (d, J = 6.5 Hz, 3H), 1.90 (bs, 1H), 2.33 (s,
6H), 2.51 (d, J = 7.8 Hz, 3H), 4.30 (m, 1H), 4.83 (brs, 1H),
7.13 (brs, 1H), 7.17–7.24 (m, 3H), 7.28 (brs, 1H), 7.30–7.36
(m, 4H), 7.38–7.40 (m, 1H,), 7.42–7.48 (m, 3H); 31P NMR
J = 47.4 Hz), 29.1 (d, J = 3.5 Hz), 58.0 (d, J = 7.0 Hz), 78.7
(d, J = 6.3 Hz), 126.4, 127.6, 128.3, 128.4, 128.5, 130.5 (d,
J = 47.8 Hz), 130.9 (d, J = 2.3 Hz), 131.4 (d, J = 7.1 Hz), 142.
HRMS (ESI) calc. for C19H29BNNaOP [M+ + Na] 352.19755;
found 352.19823.
(CDCl3, 121.5 MHz)
(CDCl3, 75.0 MHz)
d
+ 70.5 (brd, J = 82.7 Hz); 13C NMR
13.4, 21.4, 30.4 (d, J = 3.6 Hz), 58.1 (d,
d
J = 9.9 Hz), 78.8 (d, J = 5.6 Hz), 126.7, 127.9, 128.2 (d,
J = 10.2 Hz), 128.5, 129.9 (d, J = 10.2 Hz), 130.5 (d,
J = 2.1 Hz), 131.2 (d, J = 31.5 Hz), 132.0 (d, J = 10.7 Hz),
138.0 (d, J = 10.7 Hz), 142.5; MS (EI) m/z (relative intensity)
805 (2 M+ + Na; 15), 414 (M+ + Na; 100), 392 (M+ + H; 13);
HRMS (ESI) calcd for C24H31BNNaOP [M + Na+]: 392.23091;
found: 392.23095; Anal. calcd for C24H31BNOP (391.302):
C 73.67, H 7.99, N 3.58; found: C 73.90, H 8.02, N 3.56.
4.3. Preparation of the chlorophenylphosphine borane 14
4.3.1. General procedure
In a 50 mL two-necked flask equipped with a magnetic
stirrer, an argon inlet and a septum was introduced 2 mmol
of the aminophosphine borane 12. A solution of HCl in
toluene was then added under stirring at room tempera-
ture, without previous dissolution of the compound 12 (see
conditions, Table 1). After reaction (Table 1), the precipi-
tate of ephedrine hydrochloride was filtred off on Millipore
4.2.5. (Rp)-(+)-N-methyl-N-[(1R,2S)(1-hydroxy-1-phenyl-
prop-2-yl]aminophenyl-i-propyl phosphine borane 12e (from
(Rp)-11a)
4
mm filter, and the excess of HCl was removed by several
Yield = 80%; Colorless oil; ½a D
ꢁ
¼ þ31:7 (c 0.6, CHCl3);
vacuum/argon cycles. The toluene solution of chlorophos-
phine borane 14 obtained was immediately used without
20
Rf = 0.25 (CH2Cl2); IR (
n
cmꢀ1): 3510 (O-H), 2974–2874

F. Chaux et al. / C. R. Chimie 13 (2010) 1213–1226
1223
further purification in highly stereoselective synthesis. For
their analyses, the chlorophosphine boranes 14 were
obtained after evaporation of toluene and purification by
filtration on a short column of silica gel.
exhibits satisfactory analytical data in agreement with the
(S)-enantiomer described before.
4.4. Preparation of phosphine boranes 15 from
chlorophosphine boranes 14 (Route A)
4.3.2. (R)-(+)-Chloromethylphenylphosphine borane 14a
14a was prepared from the aminophosphine borane
12a derived from the (+)-ephedrine, according to the
literature [19c].
4.4.1. General procedure
To a solution of chlorophosphine borane 14 in toluene
cooled at ꢀ78 8C was added the organolithium reagent (2.5
equiv). The reaction mixture was let to warm to RT during
1 h, then hydrolysed with water (20 mL). The organic phase
was removed and the aqueous layer was extracted with
CH2Cl2, and the combined extracts were dried over MgSO4,
then concentrated. The residue was purified by chroma-
tography on a short column of silica gel with toluene/
petroleum ether: 7/3 as eluent, to afford the phosphine
boranes 15. Their recrystallisation in a mixture hexane/i-
PrOH, affords the enantiomerically pure phosphine bor-
anes 15.
4.3.3. (S)-o-Anisylchlorophenylphosphine borane 14b (from
12b derived from the (+)-ephedrine)
Yield = 99%; colorless oil; Rf = 0.80 (toluene); 1H NMR
(CDCl3, 300.13 MHz) d 0.40–2.20 (m, 3H), 3.63 (s, 3H), 6.91
(dd, J = 8.3 and 4.6 Hz, 1H), 7.11 (td, J = 7.6 and 2.6 Hz, 1H),
7.39–7.61 (m, 4H), 7.72–7.82 (m, 2H), 7.95 (ddd, J = 14.9,
7.7 and 1.6 Hz, 1H); 31P NMR (CDCl3, + 121.5 MHz)
d
+ 91.9
(brd, J = 51.4 Hz); 13C NMR (CDCl3, 75.0 MHz)
d 55.7, 112.0
(d, J = 4.4 Hz), 117.6 (d, J = 47.7 Hz), 121.1 (d, J = 12.3 Hz),
128.5 (d, J = 11.5 Hz), 128.7 (d, J = 50.8 Hz), 131.1 (d,
J = 12.9 Hz), 132.0 (d, J = 2.6 Hz), 134.6 (d, J = 14.3 Hz),
135.5 (d, J = 1.8 Hz), 161.1 (d, J = 2.4 Hz); MS (EI) m/z
(relative intensity): 263 (M-H+; 9), 250 (M+-BH3; 100),
215 (40), 183 (35), 107 (20), 91 (40), 77 (10); HRMS (ESI)
4.4.2. (S)-(+)- and (R)-(ꢀ)-o-Anisylmethylphenylphosphine
borane 15a
15a were prepared from 14a and 14b respectively,
according to the literature [19a]. This compound exhibit
satisfactory analytical data in agreement with the recent
ones reported in § 4.5.2.
calcd for
250.0298.
C
13H12ClOP [M+-BH3]: 250.0314; found:
4.3.4. (S)-Chloroferrocenylphenylphosphine borane 14c
(from 12c derived from the (+)-ephedrine)
4.4.3. (S)-(ꢀ)-o-Anisylferrocenylphenylphosphine borane
15b (from 12c derived from the (+)-ephedrine)
Yield = 80%; orange oil; Rf = 0.50 (petroleum ether/
Yield = 79%; orange solid; ½a D25
¼ ꢀ70:3 (c 1.0, CHCl3)
ꢁ
AcOEt [3:1]); 1H NMR (CDCl3, 300.13 MHz)
d
0.60–1.80
for 98% e.e.; mp = 140 8C; Rf = 0.46 (toluene); 1H NMR
(m, 3H), 4.20 (s, 5H), 4.44–4.49 (m, 2H), 4.54–4.55 (m, 1H),
4.56–4.64 (m, 1H), 7.41–7.48 (m, 3H), 7.77–7.84 (m, 2H);
(CDCl3, 300.13 MHz) d 0.50–1.60 (m, 3H), 3.47 (s, 3H), 4.02
(s, 5H), 4.47–4.54 (m, 3H), 4.67–4.70 (m, 1H), 6.86–6.89
(m, 1H), 7.03–7.09 (m, 1H), 7.31–7.39 (m, 3H), 7.46–7.56
(m, 3H), 7.75–7.82 (m, 1H); 31P NMR (CDCl3, 121.5 MHz)
+ 14.9 (brs); 13C NMR (CDCl3, 75.0 MHz)
d d 55.9, 69.1 (d,
J = 70.3 Hz), 70.4, 72.0 (d, J = 8.2 Hz), 72.3 (d, J = 7.6 Hz),
74.0 (d, J = 8.4 Hz), 74.5 (d, J = 11.9 Hz), 111.3 (d,
J = 63.4 Hz), 112.4 (d, J = 4.4 Hz), 120.8 (d, J = 25.9 Hz),
121.5 (d, J = 11.5 Hz), 128.5 (d, J = 10.5 Hz), 129.1 (d,
J = 28.4 Hz), 130.5 (d, J = 2.4 Hz), 131.9 (d, J = 9.9 Hz),
133.2 (d, J = 62.8 Hz), 134.1 (d, J = 10.7 Hz), 136.1 (d,
31P NMR (CDCl3, 121.5 MHz)
d
+ 93.3 (brs); 13C NMR
70.6, 71.3 (d, J = 60.0 Hz), 71.4 (d,
(CDCl3, 75.0 MHz)
d
J = 10.2 Hz), 72.7 (d, J = 9.0 Hz), 72.8 (d, J = 8.6 Hz), 73.1 (d,
J = 15.3 Hz), 128.7 (d, J = 11.0 Hz), 131.2 (d, J = 12.2 Hz),
132.4 (d, J = 2.4 Hz), 132.4 (d, J = 50.7 Hz); MS (EI) m/z
(relative intensity): 346 (M-Cl + O + Na+; 15), 333 (M-BH3-
Cl + O + Na+; 100); HRMS (ESI) calcd for C16H17BClNaFeP
[M+ + Na]: 365.0095; found: 365.0090.
4.3.5. (S)-Chlorophenyl-m-xylylphosphine borane 14d (from
12d derived from the (+)-ephedrine)
The resulting crude solution of chlorophosphine borane
14d was used without further purification. 31P NMR
J = 12.3 Hz), 161.5; Anal, calcd for
C23H24FeBOP
(414.075): C 66.72, H 5.84; found: C 66.96, H 6.01.
The enantiomeric excess of o-anisylferrocenylphenyl-
phosphine borane 15b was determined by HPLC analysis
on a Chiralcel AD column, eluent: hexane/i-PrOH (98:2),
(CDCl3, 121.5 MHz)
d + 93.5 (brs).
1 mL/min,
l = 254 nm: (R)-15b, tR = 11.6 min; (S)-15b,
4.3.6. (S)-Chlorophenyl-i-propylphosphine borane 14e (from
12e derived from the (ꢀ)-ephedrine)
tR = 12.3 min.
The (R)-(+)-o-anisylferrocenylphenylphosphine borane
15b, prepared from 12b derived from the (+)-ephedrine,
exhibits satisfactory analytical data in agreement with the
Yield = 78%; colorless oil; Rf = 0.60 (petroleum ether/
AcOEt [3:1]); 1H NMR (CDCl3, 300.13 MHz)
d 0.50–1.60 (m,
3H), 1.12 (dd, J = 19.1 and 7.1 Hz, 3H), 1.28 (dd, J = 17.7 and
(S)-enantiomer: Yield = 71%; ½a D
ꢁ
¼ þ67:2 (c 0.6, CHCl3)
25
7.0 Hz, 3H), 2.39–2.51 (m, 1H), 7.49–7.62 (m, 3H), 7.83–
for 95% e.e.
7.90 (m, 2H); 31P NMR (CDCl3, 121.5 MHz)
d
+ 113.4 (brs);
13C NMR (CDCl3, 75.0 MHz)
d
16.8, 17.2 (d, J = 3.0 Hz), 33.2
4.4.4. (R)-(ꢀ)-o-Anisylphenyl-m-xylylphosphine borane 15c
(from 12d derived from the (+)-ephedrine)
(d, J = 24.9 Hz), 129.5 (d, J = 10.6 Hz), 132.3 (d, J = 11.3 Hz),
133.3 (d, J = 2.3 Hz), 133.6 (d, J = 51 Hz); MS (EI) m/z
(relative intensity): 191 (M-Cl-BH3 + O + Na+; 100).
The (R)-Chlorophenyl-i-propylphosphine borane 14e,
which was prepared from 12f and the (ꢀ)-ephedrine,
Yield = 82%; white solid; ½a D
ꢁ
¼ ꢀ9:6 (c 1.0, CHCl3) for
20
99% e.e.; mp: 174–176 8C; Rf = 0.46 (toluene); 1H NMR
(CDCl3, 300.13 MHz) 0.60–1.80 (m, 3H), 2.32 (s, 6H), 3.57
(s, 3H), 6.92–6.96 (m, 1H), 7.05–7.22 (m, 2H), 7.26–7.28
d

1224
F. Chaux et al. / C. R. Chimie 13 (2010) 1213–1226
(m, 2H), 7.41–7.67 (m, 7H); 31P NMR (CDCl3, 121.5 MHz)
+ 18.1 (brs); 13C NMR (CDCl3, 75.0 MHz)
22.0, 55.9,
ethyl acetate (1 ꢂ 10 mL) and with dichloromethane
(2 ꢂ 10 mL), the combined organic layers were dried over
MgSO4 and the solvent was removed.
d
d
112.4 (d, J = 4.6 Hz), 117.8 (d, J = 56.5 Hz), 121.8 (d,
J = 11.3 Hz), 128.9 (d, J = 10.4 Hz), 129.5 (d, J = 59.9 Hz),
130.6 (d, J = 60.3 Hz), 131.1 (d, J = 9.9 Hz), 131.2 (d,
J = 2.4 Hz), 133.2 (d, J = 2.5 Hz), 133.5 (d, J = 9.8 Hz), 134.3
(d, J = 1.9 Hz), 136.7 (d, J = 11.5 Hz), 138.5 (d, J = 11.0 Hz),
162.1; HRMS (ESI) calcd for C21H24BOP: 334.1733; found:
334.1746. Anal, calcd for C21H24BOP (334.166): C 75.45, H
7.19; found: C 75.50, H 7.41.
4.5.2. (S)-(+)-o-Anisylmethylphenylphosphine borane 15a
(from 12b derived from the (+)-ephedrine)[19a]
Yield = 75%; white crystals (hexane/dichloromethane);
[
a
]
25 = + 25.8 (c 1.3, MeOH) for 92% e.e.; mp = 76–77 8C;
1
Rf = 0.55 (toluene); H NMR (CDCl3, 300.13 MHz)
d 0.40–
1.50 (m, 3H), 1.94 (d, J = 10.6 Hz, 3H), 3.67 (s, 3H), 6.88 (dd,
J = 8.3 and 3.5 Hz, 1H), 7.05 (t, J = 7.4 Hz, 1H), 7.33–7.56 (m,
4H), 7.56–7.69 (m, 2H), 7.87 (ddd, J = 13.8, 7.6 and 1.6 Hz,
The enantiomeric excess of o-anisylphenyl-m-xylyl-
phosphine borane 15c was determined by HPLC analysis
on a Chiralcel OK column, eluent: hexane/i-PrOH 80:20,
1H); 31P NMR (CDCl3, 121.5 MHz)
d + 9.2 (q, J = 66.1 Hz).
40 8C, 0.5 mL/min,
15c, tR = 17.35 min.
The (S)-(+)-o-anisylphenyl-m-xylylphosphine borane 15c,
prepared from 12b derived from the (+)-ephedrine,
exhibits satisfactory analytical data in agreement with
l
= 254 nm: (R)-15c, tR = 9.00 min; (S)-
The enantiomeric excess of o-anisylmethylphenylpho-
sphine borane 15a was determined by HPLC analysis on
a Chiralcel OK column, eluent: hexane/i-PrOH 80:20, 1 mL/
min, 40 8C,
l = 210 nm: (R)-15a, tR = 11 min; (S)-enantio-
mer, tR = 21 min.
the (R)-enantiomer: Yield = 79%;
CHCl3) for 99% e.e..
½
a 2D0
ꢁ
¼ þ10:0 (c 1.0,
4.5.3. (S)-(+)-or (R)-(ꢀ)-Methylphenyl-i-propylphosphine
borane 15d
4.4.5. (S)-(+)-Methylphenyl-i-propylphosphine borane 15d
(from 12f derived from the (ꢀ)-ephedrine)
15d, prepared from 12e or 12f, respectively, exhibits
satisfactory analytical data in agreement with the ones
described in § 4.4.5. S)-(+)-15d: yield = 73%; 96% e.e.; (R)-
Yield = 86%; colorless oil; ½a D
ꢁ
¼ þ17:6 (c 1.4, CHCl3)
20
for 96% e.e.; Rf = 0.75 (petroleum ether/ ethyl acetate
[10:1]); IR (
cmꢀ1) 3207, 2963, 2925, 2873, 2374 (BH),
1463, 1437, 1416, 1262, 1096, 1020, 799, 553, 540, 530; 1H
NMR (CDCl3, 300.13 MHz) 0.10–0.90 (m, 3H), 1.02 (dd,
(ꢀ)-15d: Yield = 71%; ½a D
ꢁ
¼ ꢀ17:0 (c 1.2, CHCl3) for
20
n
97% e.e.
4.6. Preparation of phosphines from their borane complexes
General procedure: In 50 mL two-necked flask
d
J = 15.9 and 7.2 Hz, 3H), 1.15 (dd, J = 15.6 and 7.2 Hz, 3H),
1.54 (d, J = 10.2 Hz, 3H), 2.02–2.11 (m, 1H), 7.46–7.48 (m,
3H), 7.68–7.73 (m, 2H); 31P NMR (CDCl3, 121.5 MHz)
a
equipped with a magnetic stirrer and an argon inlet,
1 mmol of phosphine borane 15 and 3 equiv. of DABCO
were dissolved in 2 mL of toluene. The reaction mixture
was heated at 45 8C overnight. After cooling, the crude
mixture was purified by chromatography on neutral
alumina, using toluene as eluent.
d
+ 16.4 (q, JPB = 59.5 Hz); 13C NMR (CDCl3, 75.0 MHz)
d 8.7
(d, J = 38.2 Hz), 17.2, 26.7 (d, J = 36.1 Hz), 129.3 (d,
J = 9.4 Hz), 129.5 (d, J = 52.4 Hz), 131.8 (d, J = 2.4 Hz),
132.6 (d, J = 8.6 Hz); MS (EI) m/z (relative intensity): 203
(M + Na+; 100); HRMS (ESI) calcd for C10H18BNaP:
203.1133; found: 203.1120.
The enantiomeric excess of the phosphine borane 15d
was determined by 31P NMR (CDCl3, 121.5 MHz) of the
phosphine oxide derivative prepared according reference
[24b], in presence of the Kagan’s reagent (S)-21 [31]:
4.6.1. (R)-(+)-o-Anisylmethylphenylphosphine 13a
Oil; [
8:2); IR (
1462, 1295, 1268, 1241, 1179, 1073, 1043, 882, 753, 696.
1H NMR (CDCl3, 250 MHz),
1.55 (d, J = 4.8, 3H), 3.64 (s,
a
n
]
D + 45.7 (c 1.7, MeOH); Rf = 0.54 (toluene/hexane
cmꢀ1) 3068, 3001, 2964, 2906, 1584, 1574, 1474,
d
+ 44.37 for (S)-15d and + 44.26 for (R)-15d.
d
The (R)-(ꢀ)-methylphenyl-i-propylphosphine borane
3H), 6.70–6.80 (dd, 1H), 6.81 (t, J = 9 Hz, 1H), 7.00–7.10 (m,
15d, prepared from 12e derived from the (ꢀ)-ephedrine,
exhibits satisfactory analytical data in agreement with the
(S)-enantiomer: Yield = 68%; 89% e.e.
1H), 7.15–7.30 (m, 4H), 7.35–7.47 (m, 2H); 31P NMR
(CDCl3, 101 MHz)
d
ꢀ36 (s); 13C NMR (CDCl3, 63 MHz),
d
10.8 (d, J = 13.3). 55.1 (s), 110.0 (s), 120.6 (s), 127.9 (d,
J = 6.7 Hz), 129.5 (s), 131.1 (s), 131.8 (d, 9.5 Hz), 139.0 (brs),
160.6 (d, J = 2.8 Hz).
4.5. Preparation of phosphine boranes 15 from phosphide
boranes 9 (Route B)
4.6.2. (S)-(ꢀ)-o-Anisylferrocenylphenylphosphine 13b
4.5.1. General procedure
Oil; [a
]
D ꢀ4.8 (c 1.0, CHCl3); 1H NMR (CDCl3, 300 MHz),
The solution of chlorophosphine borane 14, prepared
according to the procedure described on § 4.3, was cooled
at ꢀ85 8C and t-butyllithium (0.75 mmol, 3 equiv.) was
added dropwise over 2 minutes. After stirring for 5 min at
ꢀ85 8C, dry THF (0.5 mL) was added dropwise over
30 seconds and the reaction mixture turns deep yellow.
An excess of methyl iodide (0.75 mmol, 3 equiv.) was
finally added in once. The white mixture was stirred for
10 minutes at low temperature before being hydrolyzed
(5 mL of water). The aqueous phase was extracted with
d 3.63 (s, 3H), 3.75–3.76 (m, 1H), 4.03 (s, 5H), 4.19–4.20 (m,
1H), 4.24–4.25 (m, 1H), 4.31–4.32 (m, 1H), 6.73–6.84 (m,
3H), 7.16–7.26 (m, 4H), 7.36–7.40 (m, 2H). 31P NMR
(CDCl3,125 MHz)
d
ꢀ23.3 (s).
4.6.3. (S)-(ꢀ)-o-Anisylphenyl-m-xylylphosphine 13c
Oil; [
a
]
D ꢀ3.8 (c 0.9, CHCl3); 1H NMR (CDCl3, 300 MHz),
d
2.28 (s, 6H), 3.78 (s, 3H), 6.62–6.71 (m, 1H), 6.84–6.97 (m,
5H), 7.24–7.36 (m, 6H); 31P NMR (CDCl3, 125 MHz)
(s); 13C NMR (CDCl3, 75.5 MHz),
21.3, 55.7, 110.2 (d,
d
ꢀ16.9
d

F. Chaux et al. / C. R. Chimie 13 (2010) 1213–1226
1225
J = 1.8 Hz), 121.0, 125.8 (d, J = 11.4 Hz), 128.3 (d, J = 6.9 Hz),
128.4, 130.3 (d, J = 22.8 Hz), 130.6 (d, J = 21.7 Hz), 133.7,
133.8 (d, J = 19.4 Hz), 136.1 (d, J = 9.1 Hz), 137.0 (d,
J = 10.2 Hz), 137.7 (d, J = 8 Hz), 161.2 (d, J = 15.3 Hz).
The (S,S)-(+)-19 was prepared starting from (R,R)-(+)-18
derived from (+)-ephedrine: yield = 95%; solid; mp = 167 8C
(i-PrOH); Rf = 0.44 (hexane/CH2Cl2 [55:45]); ½a D
ꢁ
¼ þ33:8
20
(c 1, CHCl3); IR (KBr,
1457, 1420, 1063, 739, 693; 1H NMR (CDCl3, 300.13 MHz)
n
cmꢀ1): 3056, 2909 (C-H), 2378 (B-H),
d
4.6.4. (S)-(ꢀ)- Methylphenyl-i-propylphosphine 13d,
0.00–1.40 (m, 6H), 1.53 (brd, J = 9.8 Hz, 6H), 1.80–1.88 (m,
2H), 1.96–2.04 (m, 2H), 7.39–7.51 (m, 6H), 7.54–7.64 (m,
4H); 31P NMR (CDCl3, 121.5 MHz) + 12.9 (brs); 13C NMR
d
Oil; [a
]
D ꢀ10 (c 0.3, CHCl3) for 93% e.e.; 1H NMR (CDCl3,
300 MHz),
d
0.93 (dd, 3H, J = 7 and 14.8 Hz), 1.05 (dd, 3H,
J = 7 and 13.7 Hz), 1.30 (d, 3H, J = 13.7 Hz), 1.78 (dhept, 1H,
(CDCl3, 75.0 MHz) d 10.9 (d, J = 38.0 Hz), 20.7 (d,
J = 7 and 4.3 Hz), 7.31–7.38 (m, 3H), 7.45–7.53 (m, 2H); 31
P
J = 35.0 Hz), 128.9–131.7; MS (DCI, CH4) m/z (relative
intensity): 287 (60), 104 (100), 91 (80), 77 (60); Anal.
calcd for C16H26B2P2 (312.17): C 63.54, H 8.67; found: C
63.58, H 8.61.
NMR (CDCl3, 125 MHz)
75.5 MHz),
d
ꢀ19.3 (s); 13C NMR (CDCl3,
d
8.6 (d, J = 15.1 Hz), 18.7 (d, J = 14 Hz), 19.4 (d,
J = 15.3 Hz), 28.5 (d, J = 8.2 Hz), 128.1 (d, J = 7.6 Hz), 128.6,
132.3 (d, J = 18.1 Hz), 139.1 (d, J = 15.1 Hz).
The (R,R)-(ꢀ)-19 was prepared starting from (S,S)-(ꢀ)-
18 derived from the (ꢀ)-ephedrine: yield = 76%;
4.7. Preparation of 1,2-bis(methylphenylphosphino)ethane 4
mp = 162 8C (Hexane); ½a D20
ꢁ
¼ ꢀ33:4 (c 0.3, CHCl3); 31P
NMR (CDCl3, 121.5 MHz)
d + 12.2 (brd, J = 64 Hz).
4.7.1. Synthesis of 1,2-bis(methoxyphenylphosphino
borane)ethane 18
4.7.3. 1,2-bis(Methylphenylphosphino borane)ethane 4 [13a]
In a 50 mL two-necked flask, with a magnetic stirrer and
an argon inlet, 1 mmol of diphosphine diborane 19 and 3
equiv. of DABCO were dissolved in 2 mL of toluene. The
reaction mixture was heated at 45 8C overnight. After
cooling, the crude mixture was purified by chromatogra-
phy on neutral alumina, using toluene as eluent.
The diphosphinite diborane 18 was prepared by
coupling the
a-carbanion derived from the (O-methyl)-
methylphenylphosphinite borane 10a, in presence of CuCl2
under air, according to the procedure described in
reference [23].
In a 50 mL two-necked flask equipped with a magnetic
stirrer and an argon inlet, 1 mmol of 10a was dissolved in
2 mL of dry THF at ꢀ78 8C. Then, 1 mmol of s-butyllithium
was slowly added under stirring. The temperature of the
mixture was kept at ꢀ78 8C for 15 min, then allowed to
warm at ꢀ30 8C. After 1 hour in these conditions, dry CuCl2
(1.1 mmol) was added and the temperature was brought to
0 8C and allowed under air. After 12 hours, the mixture was
hydrolyzed by HCl 10%, and extracted with CH2Cl2. The
solvent was removed and the residue purified by
chromatography on silica gel using hexane/CH2Cl2 (6:4)
as eluent.
(S,S)-(+)-1,2-bis(Methylphenylphosphino)ethane 4: yield
= 95%; oil; ½a D
ꢁ
¼ þ24:5 (c 0.9, CHCl3); Rf = 0.85 (hexane/
25
toluene/ethyl acetate [20:70:10]); IR (KBr,
2961 (C-H), 2899, 1485, 1433, 1096, 1069, 1027, 879,
748, 695; 1H NMR (CDCl3, 300 MHz)
1.19 (d, J = 2.0 Hz,
6H), 1.53 (q, J = 3 Hz, 4H), 7.17–7.51 (m, 10H); 31P NMR
(CDCl3, 125 MHz)
– 32.0; 13C NMR (CDCl3, 75.5 MHz)
n
cmꢀ1): 3071,
d
d
d
11.3, 25.8, 128.3–131.6; MS (DCI, CH4) m/z (relative
intensity): 274 (35), 259 (65), 244 (50), 227 (65), 200
(40), 185 (30), 121 (100), 91 (50), 75 (55); HRMS (ESI) calcd
for C16H20P2: 274.1040; found: 274.1041. Anal. calcd
for C16H20P2 (274.10): C 70.04, H 7.35; found: C 70.03, H
7.44.
The (S,S)-(ꢀ)-18 was prepared as previously described
starting from (ꢀ)-ephedrine [22].
The (R,R)-(+)-1,2-Bis(methoxyphenylphosphino bora-
ne)ethane 18 was prepared starting from (+)-ephedrine:
(R,R)-(ꢀ)-1,2-bis(Methylphenylphosphino)ethane 4: yield
= 95%; ½a 2D5
ꢁ
¼ ꢀ23:5 (c 0.9, CHCl3); 31P NMR (CDCl3,
yield = 80%; solid;
mp = 115 8C; Rf = 0.48 (hexane/CH2Cl2 [55:45]); 1H NMR
(CDCl3, 300.13 MHz) 0.00–1.50 (m, 6H), 1.91–2.07 (m,
½
a D
ꢁ
¼ þ115:0 (c 1.3, CHCl3);
125 MHz) d d 1.28
– 32 (s). 1H –NMR (CDCl3, 300 MHz),
20
(d, J = 2 Hz, 6H), 1.67 (q, J = 4 Hz, 4 H), 7.30–7.35 (m, 6 H),
13
d
7.37–7.43 (m, 4 H);
C NMR (CDCl3, 75.5 MHz), d (11.4,
2H), 2.07–2.24 (m, 2H), 3.58 (dd, J = 6.0 and 6.0 Hz, 6H),
25.9, 128.3, 128.4, 131.4, 139.6.
7.45–7.59 (m, 6H), 7.59–7.73 (m, 4H); 31P NMR (CDCl3,
The enantiomeric purity was checked by 31P NMR in
121.5 MHz)
75.0 MHz)
d
+ 118.1 (brd, J = 58.0 Hz); 13C NMR (CDCl3,
presence of the chiral palladium complex 20. 31P –NMR
d
23.3 (d, J = 43.0 Hz), 54.1, 128.2–132.4.
(CDCl3, 125 MHz)
d
(ppm) ꢀ32 (s),
4.7.2. Synthesis of 1,2-bis(methylphenylphosphino
borane)ethane 19 [13a]
Acknowledgments
In a 50 mL two-necked flask equipped with a magnetic
stirrer and an argon inlet, 1 mmol of diphosphinite borane
18 was dissolved in 2 mL of dry THF at ꢀ78 8C. Then,
2 mmol of the methyl lithium reagent was added dropwise
under stirring. The temperature of the mixture was kept at
ꢀ78 8C for 15 min, then allowed to warm at 0 8C. The
mixture was hydrolyzed and extracted with CH2Cl2. The
organic phase was dried over MgSO4 and the solvent
evaporated. The residue was purified by flash chromatog-
raphy on silica gel using hexane/dichloromethane as
eluent.
The authors gratefully acknowledge the ANR Met-
ChirPhos, the Ministry of Research, the CNRS and the
Bourgogne country council for financial supports. We
´
thank Miss M.J. Penouilh and E. Remond for their technical
assistance, MM. A. Tessier and P. Harvey for their help in
the preparation of the manuscript.
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