Versatile synthesis of P-chiral (ephedrine) AMPP ligands via their borane complexes. Structural consequences in Rh-catalyzed hydrogenation of methyl α-acetamidocinnamate

Article abstract of DOI:10.1016/S0957-4166(99)00510-8

An efficient and versatile synthesis of aminophosphine phosphinite (AMPP) ligands derived from ephedrine, with possible stereogenic P(III)- center(s) is described, using the borane complex methodology. The reaction of oxazaphospholidine borane with an org

Full text of DOI:10.1016/S0957-4166(99)00510-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 10 (1999) 4729–4743
Versatile synthesis of P-chiral (ephedrine) AMPP ligands via their
borane complexes. Structural consequences in Rh-catalyzed
hydrogenation of methyl α-acetamidocinnamate
∗
Dominique Moulin, Christophe Darcel and Sylvain Jugé
Unité mixte Université de Cergy-Pontoise/ESCOM-‘Synthèse Organique Sélective et Chimie Organométallique’,
EP CNRS 1822, 5 mail Gay Lussac, 95031 Cergy-Pontoise Cedex, France
Received 25 October 1999; accepted 15 November 1999
Abstract
An efficient and versatile synthesis of aminophosphine phosphinite (AMPP) ligands derived from ephedrine,
with possible stereogenic P(III)-center(s) is described, using the borane complex methodology. The reaction of
oxazaphospholidine borane with an organolithium reagent, leads to the formation of the ring-opened product, which
is trapped by a chlorophosphine (borane), to afford the corresponding aminophosphine phosphinite boranes in
good yields. Treatment of the borane complexes with dabco, gives the corresponding aminophosphine phosphinite
ligands in 70–90% yield. These ligands are used for the preparation of Rh catalysts applied to the asymmetric
hydrogenation of methyl α-acetamidocinnamate yielding the phenylalanine derivative with (R) 22% to (S) 99%
e.e. These results show the importance of the structural modification at the P-stereogenic center(s), which could
either amplify or cancel out the asymmetric induction resulting from the ephedrine backbone, for enantioselective
catalysis. © 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
C -Symmetric diphosphines or chelating monophosphines bearing chirality on the carbon backbone
2
1
are today the most currently used chiral ligands in asymmetric reactions catalyzed by transition metals.
Nevertheless, other classes of phosphorus ligands, in which the chirality is induced by planar chirality,
by an aminoalcohol or glucose, also provide highly stereoselective catalysts, particularly for hydro-
formylation, hydrocyanation or cycloaddition reactions.
In spite of the pioneering work of Horner and Knowles, phosphines bearing chirality on the
phosphorus atom have not been used extensively to date in asymmetric catalysis, mainly due to the
difficulty of their stereoselective preparation. Nevertheless, as their asymmetric synthesis has made some
important progress due to the use of borane complexes,7 these ligands again receive particular interest in
2
3
4
5
6
–9
∗
Corresponding author. Fax: 33 1 34 25 70 67; e-mail: sylvain.juge@chim.u-cergy.fr
0
957-4166/99/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00510-8
tetasy 3145

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D. Moulin et al. / Tetrahedron: Asymmetry 10 (1999) 4729–4743
catalysis;10 the stereogenic phosphorus atom being close to the metal center allows a better asymmetric
induction to be expected. It may also be pointed out that the P-chirality allows new classes of chiral
1
1
12
ligand, such as bulky or chelating monophosphines, to be studied. Moreover, it is now possible
to develop ligands with both stereogenic carbon and phosphorus groups, and therefore to increase the
number of possible stereoisomers of a designed ligand, for the optimization of an asymmetric catalyst.
The asymmetric induction of diphosphine rhodium or ruthenium complexes has been attributed to the
conformational chirality of the P-phenyl substituents, oriented in axial or equatorial directions, which
results from the distorted conformation of the ring containing the chelated metal and the bidentate
1
3
ligand (Fig. 1a). If the substituents at phosphorus atom(s) are different, with R larger than R , we
1
2
can observe that the dissymmetry may amplify the influence of the backbone on the conformation of
such a ring, thus favoring one geometry for the catalytic complex and, therefore, a better stereoselectivity
(Fig. 1b).
Fig. 1.
During the last decade, our group has studied the asymmetric synthesis of P-chiral mono and diphos-
phines based on the stereoselective ring opening of the oxazaphospholidine, derived from ephedrine.14
On this basis we report herein a versatile methodology starting from oxazaphospholidine borane complex
3
a,b
1
, affording various aminophosphine phosphinite 5 derivatives of the EPHOS ligand 5a,
bearing one
1
5
or two stereogenic phosphorus atom(s) (Scheme 1). The consequences in asymmetric catalysis of the
structural modifications of these ligands derived from ephedrine, are studied on homogeneous rhodium-
catalytic hydrogenation of methyl α-acetamidocinnamate 6.
Scheme 1.

D. Moulin et al. / Tetrahedron: Asymmetry 10 (1999) 4729–4743
4731
2. Results and discussion
0
The starting complex 1, or its enantiomer 1 , are prepared by condensation of PhP(NMe ) with (+)-
2
2
7
f
or (−)-ephedrine followed by complexation with boranedimethylsulfide (BMS). The synthesis of these
aminophosphine phosphinites, obtained as stable diborane complexes 4, is based on the reaction of the
0
complex 1 (or 1 ) with an organolithium reagent to give the ring opening product 2, which is trapped
with a chlorophosphine borane 3 (Scheme 1b), or a chlorophosphine (R) PCl and then a borane (Scheme
2
1a). Aminophosphine phosphinite complexes 4 are isolated by chromatography; then the borane can
be easily removed by exchange with dabco to yield the corresponding ligand 5. The structure of the
aminophosphine phosphinite borane complexes 4a–k prepared from both (+)- and (−)-ephedrine, are
reported in Table 1.
Table 1
Aminophosphine phosphinite diborane complexes 4 prepared
The reaction of phenyllithium with the complex 1 leads after P–O bond cleavage to the ring opening
product 2a (R =Ph), which is trapped with chlorodiphenylphosphine Ph PCl then with borane, to afford
1
2
the (−)-EPHOS in 63% yield, as a diborane complex 4a (Scheme 1a; Table 1, entry 1). In the same
way, other organolithium reagents (R =methyl, o-anisyl, 1- or 2-naphthyl, t-butyl) lead in 62–78% yield
1
to the corresponding diborane complexes 4b–f, with a stereogenic aminophosphine group and complete
7
e
retention of configuration at the phosphorus atom (entries 2–6). When the o-anisyl ring opening product
c is trapped with chlorodicyclohexylphosphine, the resulting derivative 4i obtained after reaction with
2
borane, has a more sterically hindered phosphinite group (entry 9).
On the other hand, aminophosphine phosphinites bearing a chiral phosphinite group are prepared by
trapping the ring opening intermediate 2 with P-chiral chlorophosphine boranes 3a or 3b, which are
previously prepared by acidolysis of the corresponding aminophosphine borane 27
f,16
(Scheme 1c). This

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D. Moulin et al. / Tetrahedron: Asymmetry 10 (1999) 4729–4743
is illustrated by the preparation of the aminophosphine P-chiral phosphinite complexes 4g, 4j (Scheme
1b; entries 7, 10), or 4h, 4k bearing stereogenicity at both phosphorus centers (entries 8, 11).
Decomplexation of borane complexes 4 is achieved with retention of the configuration, by heating with
1
7
dabco (Scheme 1a,b); then the free aminophosphine phosphinites 5 are purified by filtration through
31
neutral alumina. The diastereomeric purity of the ligands 5 is controlled by P NMR analysis, showing
two signals at around 60 and 110 ppm, which are characteristic of the P–N and P–O groups, respectively.
In order to study the structural modification of aminophosphine phosphinite ligands 5 relative to
the EPHOS ligand 5a, the asymmetric hydrogenation of methyl α-acetamidocinnamate 6 has been
investigated using a cationic rhodium complex (Scheme 2). The results are summarized in Table 2.
Scheme 2.
Table 2
Asymmetric hydrogenation of substrate 6, catalyzed by Rh/AMPP 5 complexes
In dichloromethane, the structural modifications at the phosphorus center are of great influence on the
asymmetric induction. Thus, changing the pro-R phenyl of the (−)-EPHOS 5a aminophosphine group, by
a methyl (ligand 5b), the hydrogenation gives the phenylalanine derivative 7 with the opposite absolute
configuration (e.e. 22% (R), against 11% (S)) for the former 5a (Table 2, entries 1, 3). On the other
hand, when o-anisyl replaces the pro-R phenyl of 5a, the resulting ligand 5c considerably increases the
asymmetric induction for the hydrogenation, since (S)-aminoester 7 is obtained with an enantiomeric

D. Moulin et al. / Tetrahedron: Asymmetry 10 (1999) 4729–4743
4733
excess of 89% (entry 4). Similar results are obtained with the ligand 5d bearing a (R)-1-naphthyl-
aminophosphine group (entry 5), which leads to the (S)-aminoester 7 with 88% e.e. If the hydrogenation
is carried out in benzene, the o-anisyl and the 1-naphthyl ligand provides the (S)-aminoester 7 with 99 and
1
8
9
5% e.e., respectively, compared to 46% e.e. obtained for the (−)-EPHOS (entries 2, 5, 7). However,
when the 2-naphthyl substitutes the pro-R phenyl of the (−)-EPHOS aminophosphine part (ligand 5e),
the (S)-aminoester 7 is obtained with an enantiomeric excess comparable to 5a (e.e. 16% and 11%,
respectively, entries 1, 8). Surprisingly, the introduction of a t-butyl substituent on the aminophosphine
part of 5a leads to the quasi-racemic product 7 (entry 9).
In the case of the ligand 5j bearing an (R)-o-anisyl phenyl phosphinite group, the hydrogenation
catalysis of 6 also leads to the phenylalanine derivative 7 with (S)-absolute configuration and 80%
e.e. (entry 10). The fact that the o-anisyl ligands 5c and 5j, derived from the (+) and (−)-ephedrine,
respectively, both afford the aminoester 7 with the same (S)-absolute configuration and high e.e. (entries
4, 10), clearly shows the predominance of the P-center’s chirality over the carbon backbone effect. It is
likely that these two ligands have similar structures resulting from the relative configuration of the larger
substituents, borne by each stereogenic center of the chelated seven-membered ring (Fig. 2a, b). The
key importance of the configuration of the phosphorus center is also shown from the ligand 5k, bearing
o-anisyl aminophosphine and phosphinite groups with opposite absolute configuration (entry 11). The
(S)- and (R)-configurations of the two phosphorus groups imply a quasi-meso structure for the ligand 5k,
which in this case does not give any asymmetric induction (Fig. 2c).
Fig. 2.
Although the mechanism and the origin of the asymmetric induction must be carefully claimed, we
suggest the following model to explain the structure of AMPP–rhodium complexes in the initial catalytic
step (Fig. 3).
Fig. 3.

4
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D. Moulin et al. / Tetrahedron: Asymmetry 10 (1999) 4729–4743
As the phenyl substituent entails higher 1,3-diaxial interaction in cycloalkane than methyl,19 it
should be reasonable to consider that the (−)-EPHOS 5a–rhodium complex adopts the λ-twist-chair
conformation, with the phenyl group of the (+)-ephedrine backbone in an equatorial position (Fig.
3
a). The formation of a λ-conformation is in good agreement with the asymmetric hydrogenation of
the substrate 6 yielding the phenylalanine derivative 7 with (S)-configuration, which can be predicted
from the well-known empirical correlation established in the case of the rhodium diphosphine
diphosphinite complex. The presence of a sterically hindered substituent R on the aminophosphine
13a
or
1
3c
1
moiety, requires an equatorial position, and consequently favors the λ-conformation of the chelated
ring (Fig. 3a). This is illustrated by the ligands 5c–e bearing o-anisyl, 1-naphthyl or 2-naphthyl as R1
substituents, respectively, which lead, by catalyzed hydrogenation, to the (S)-phenylalanine derivative 7
(
entries 4–8). When R is a methyl (ligand 5b), the δ-twist-chair conformation is then favored by a lower
1
interaction of this substituent in an axial position with the other axial group of the chelate–rhodium
ring complex (Fig. 3b), affording the product 7 in major absolute configuration (R) (entry 2). The poor
results obtained in the case of the t-butyl ligand 5f (entry 6), show the limitation to increase the steric
hindrance of the aminophosphine moiety of the ligand, which must change the conformation of the ring
of the rhodium–chelate and the arrangement of the ligands around the metal center, affording a weak
stereoselective precatalyst species.
3. Conclusion
We have described herein a general and efficient synthesis of chiral aminophosphine phosphinite
ligands 5 derived from (+) and (−)-ephedrine; the key step was the regio- and stereoselective ring opening
of the oxazaphospholidine borane complex 1 by an organolithium reagent, followed by the trapping
of the alcoholate intermediate 2 with a chlorophosphine. The aminophosphine phosphinites obtained
can be easily isolated as stable borane complexes; when necessary the borane protective group can be
removed by an exchange with dabco, to provide the corresponding P(III) ligands, well fitted to be used in
catalysis. The interest of this synthetic method is demonstrated by the possibility of preparing numerous
aminophosphine phosphinites with stereogenic phosphorus atoms. The aminophosphine phosphinite
ligands 5, used for asymmetric catalyzed hydrogenation of methyl α-acetamidocinnamate 6 by rhodium
complexes, reveals the importance of the stereogenic P-center, compared to the effect induced by the
ephedrine backbone. Introducing the o-anisyl or 1-naphthyl groups on the aminophosphine part leads to
the phenylalanine derivative 7 with the e.e. reaching 99%, while the (−)-EPHOS ligand gives 46% e.e.
under the same conditions. Taking into account this new powerful and convenient synthetic method, it
is now possible to prepare numerous P-chiral AMPP derivatives from the same skeletal backbone (i.e.
ephedrine), for the optimization of asymmetric catalysis.
4. Experimental
4.1. General
All reactions were carried out under an argon atmosphere in dried glassware. Solvents were dried and
freshly distilled under a nitrogen atmosphere over sodium/benzophenone for THF, toluene and benzene,
P O for CH Cl and sodium ethylate for EtOH. Hexane and isopropanol for HPLC were of chroma-
2
5
2
2
tographic grade and used without further purification. Methyllithium, s-butyllithium, t-butyllithium and
chlorodicyclohexylphosphine were purchased from Aldrich, Acros and Avocado. Commercially available

D. Moulin et al. / Tetrahedron: Asymmetry 10 (1999) 4729–4743
4735
2-bromoanisole, 1-bromonaphthalene and bromobenzene were distilled before use. The toluene HCl
solution was obtained by bubbling HCl gas and titration of the resulting solution. HPLC analyses were
performed on a Gilson 116 UV detector. Flash chromatography was performed on silica gel (60ACC,
6
–35 microns; SDS) or neutral aluminium oxide (Carlo Erba; ref. 417241). All NMR spectral data
1
13
were obtained on a Bruker DPX 250 spectrometer using TMS as internal reference for H and
C
NMR and 85% phosphoric acid as external reference for 31P NMR. Melting points were measured on a
Büchi melting point apparatus and are uncorrected. Optical rotation values were determined at 20°C on
a Perkin–Elmer 241 polarimeter. Infrared spectra were recorded on a Bruker Equinox 55. Mass spectral
analyses were performed on a NERMAG R10-10C and a JEOL MS 700 for exact mass, at the Mass
Spectroscopy Laboratories of ENSCP and ENS, Paris. The major peak m/z is mentioned with the intensity
as a percentage of the base peak in brackets. Elemental analyses were measured with a precision superior
to 0.3% at the Microanalysis Laboratories of the Pierre and Marie Curie University, Paris.
4.2. Synthesis of aminophosphine phosphinite diborane 4a–k
4.2.1. Preparation of aryllithium reagents
In a two-necked flask equipped with a magnetic stirrer, 1 equivalent of s-butyllithium was added.
The mixture was allowed to cool to 0°C and 1 equivalent of 1-bromoanisole (1-bromonaphthalene
or bromobenzene) was slowly added with a syringe and under stirring. After formation of a white
precipitate, the mixture was stirred for 1 h at 0°C. The organolithium reagent was solubilized with a
minimum of dry THF before use.
In the case of the solid 2-bromonaphthalene, 1 equivalent of arylhalide was introduced into a flask,
then 1 equivalent of s-butyllithium was slowly added with a syringe and under stirring at 0°C. The rest
of the procedure was performed as described above.
4.2.2. Typical procedure for 4a–k
A 100 mL round-bottomed flask equipped with a magnetic stirrer and an argon inlet was charged with
a solution of 1 g of the oxazaphospholidine borane 1 (3.5 mmol) in 6 mL of THF. Then two equivalents
of an organolithium reagent (7 mmol) were added slowly at −78°C under stirring, and the reaction
temperature was slowly warmed to 0°C until complex 1 had completely disappeared. The reaction could
be monitored by TLC over silica (toluene:AcOEt, 9:1). Then 2 equivalents of chlorodiphenylphosphine
(or chlorodicyclohexylphosphine) (7 mmol) were added, and the mixture was stirred for 2 h and warmed
to room temperature. Boranedimethylsulfide (BMS; 10 equivalents) was added and the mixture stirred
overnight. The THF and excess of borane were removed under reduced pressure and the residue was
hydrolyzed at room temperature, then extracted with CH Cl . The combined extracts were dried over
2
2
MgSO and the solvent removed. The residue was purified by chromatography on silica gel using
4
toluene:petroleum ether, 1:1, as eluent, yielding the AMPP diborane complex 4 in 62–79% yield.
4
.2.3. (−)-N-Methyl-N-{(1R,2S)-[2-(diphenylphosphinito borane)-1-methyl-2-phenyl]ethyl}aminodi-
phenylphosphine borane 4a ((−)-EPHOS diborane complex)
2
0
Yield=63%; white solid; mp: 175°C; [α] =−76.3 (c 1.035, CHCl ); R =0.45 (toluene:petroleum
D
3
f
−
1
ether, 1:1); IR (neat, ν cm ): 3054 (w), 2983 (w), 2375 (vs), 2342 (m), 1589 (m), 1483 (w), 1457
1
3
3
(
w), 1436 (vs), 1222 (m); H NMR (CDCl ): δ 1.28 (3H, d, J =6.5, CH ), 2.24 (3H, d, JPNCH=7.6,
3
3
HH
3
3
NCH ), 4.56 (1H, m, NCH), 5.33 (1H, dd, J = J =9.3, OCH), 6.6 (2H, m, H arom), 7.0–7.8 (23H,
POCH
3
HH
3
1
1
1
m, H arom), 7.9 (1H, m, H arom); P NMR (CDCl ): δ 72.5 (q, J =56.7, P–N), 108.0 (q, J =66.3,
3
PB
PB
1
3
2
2
3
P–O); C NMR (CDCl ): δ 16.1 (CH ), 29.4 (d, J =4.8, NCH ), 57.4 (dd, J =8.8, JPOCC=11.0,
3
3
PNC
3
PNC
2
3
NCH), 83.2 (dd, J =3.0, JPNCC=9.0, OCH), 127.0–132.6 (C arom), 138.0 (C arom); MS (DCI; CH4)
POC

4
736
D. Moulin et al. / Tetrahedron: Asymmetry 10 (1999) 4729–4743
+
+
m/z (relative intensity): 560 (M −H; 30), 547 (M −BH ; 11), 362 (20), 346 (70), 334 (65), 256 (25), 231
3
+
(
25), 203 (100), 187 (80), 148 (30); HRMS (DCI, CH ) calcd for C H B NOP [M −H]: 560.2615;
4
34 38
2
2
found: 560.2627; anal. calcd for C H B NOP (561.2605): C 72.76, H 7.00, N 2.50; Found: C 72.76,
3
4
39
2
2
H 6.88, N 2.27.
4
.2.4. (Sp)-(−)-N-Methyl-N-{(1R,2S)-[2-(diphenylphosphinito borane)-1-methyl-2-phenyl]ethyl}-
aminomethylphenylphosphine borane 4b
Yield=79%; white solid; mp=130–132°C (i-PrOH); [α] =−55.3 (c 1.09, CHCl ); R =0.6 (toluene);
2
0
D
3
f
−1
IR (neat, ν cm ): 3050–2900 (w, C–H), 2387 (vs, B–H), 2343 (vs), 1454 (s), 1436 (vs), 1222 (s), 1165
1
2
3
(
s); H NMR (CDCl ): δ 1.34 (3H, d, J =6.6, PCH ), 1.51 (3H, d, J =8.8, CH ), 2.30 (3H, d,
3
PCH
3
HH
3
3
3
3
JPNCH=8.1, NCH ), 4.39 (1H, m, NCH), 5.33 (1H, dd, J
= J =9.4, OCH), 6.6 (2H, m, H arom),
3
POCH
HH
31
1
7
.0–7.6 (16H, m, H arom), 7.73 (2H, m, H arom); P NMR (CDCl ): δ 68.7 (q, J =87, P–N), 108.3
3
PB
1
13
1
2
(
q, J =74.3, P–O); C NMR (CDCl ): δ 11.3 (d, J =39.4, PCH ), 16.3 (CH ), 28 (d, JPNC=3.3,
PB
3
PC
3
3
2
3
NCH ), 57.1 (dd, J = J =10.0, NCH), 82.5 (dd, OCH), 127.8–132.8 (C arom), 138.3 (C arom);
POCC
3
PNC
+
+
MS (DCI, CH ) m/z (relative intensity): 498 (M −H; 35), 484 (M −H−BH ; 10), 362 (5), 298 (5), 284
4
3
(50), 272 (30), 231 (15), 203 (100), 194 (20), 148 (25), 125 (50), 109 (15); HRMS (DCI, CH ) calcd for
4
+
C H B NOP [M −H]: 498.2457; found: m/z 498.2469; anal. calcd for C H B NOP (499.1849):
2
9
36
2
2
29 37
2
2
C 69.78, H 7.47, N 2.81; found: C 69.79, H 7.40, N 2.64.
4
.2.5. (Rp)-(−)-N-Methyl-N-{(1R,2S)-[2-(diphenylphosphinito borane)-1-methyl-2-phenyl]ethyl}-
amino-o-anisylphenylphosphine borane 4c
Yield=62%; white solid; mp=183–184°C; [α] =−64.7 (c 1.32, CHCl ); R =0.5 (toluene); IR (neat,
2
0
D
3
f
−
1
ν cm ): 3050–2900 (w, C–H), 2392 (vs, B–H), 1587 (s), 1570 (s), 1477 (s), 1456 (s), 1436 (s), 1429
1
3
(
s), 1276 (s), 1249 (s), 1222 (s), 1160 (s); H NMR (CDCl ): δ 1.35 (3H, d, J =6.5, CH ), 2.38 (3H,
3
HH
3
3
3
3
d, J
=7.9, NCH ), 3.5 (3H, s, OCH ), 4.6 (1H, m, NCH), 5.40 (1H, dd, J
= J =9.5, OCH),
PNCH
3
3
POCH HH
31
6.6 (2H, m, H arom), 6.9 (1H, m, H arom), 6.95–7.65 (19H, m, H arom), 7.7 (2H, m, H arom);
P
1
13
NMR (CDCl ): δ 70.2 (br, P–N), 107.6 (q, J =72.2, P–O); C NMR (CDCl ): δ 15.6 (CH ), 29.75
3
PB
3
3
2
2
3
2
(
d, J =4.6, NCH ), 54.9 (OCH ), 57.4 (dd, J =8.7, J
JPNCC=9.5, OCH), 111.4 (d, J =4.5, C arom), 118.4 (d, J =54.2, C arom), 120.8 (d, J =10.9, C
=11.9, NCH), 83.4 (dd, JPOC=3.2,
PNC
3
3
PNC
POCC
3
PC
PC
PC
+
arom), 127.5–138 (C arom), 160.9 (C arom), MS (DCI, CH ) m/z (relative intensity): 590 (M −H; 20),
4
+
5
76 (M −H−BH ; 24), 364 (60), 272 (15), 217 (30), 203 (100), 148 (35); HRMS (DCI, CH ), calcd for
3
4
+
C H B NO P [M −H]: 590.2721; found: m/z 590.2733; anal. calcd for C H B NO P (591.2819):
3
5
40
2
2
2
35 41
2
2 2
C 71.10, H 6.99, N 2.37; Found: C 70.94, H 7.07, N 2.23.
4
.2.6. (Rp)-(−)-N-Methyl-N-{(1R,2S)-[2-(diphenylphosphinito borane)-1-methyl-2-phenyl]ethyl}-
amino-1-naphthylphenylphosphine borane 4d
Yield=62%; white solid; mp=160–162°C; [α] =−96.9 (c 1.22, CHCl ); R =0.65 (toluene); IR (neat,
2
0
D
3
f
−
1
ν cm ): 3050–2900 (w, C–H), 2383 (s, B–H), 1436 (s), 1111 (s), 1064 (s), 1010 (s), 980 (s), 953 (m);
1
3
3
H NMR (CDCl ): δ 1.54 (3H, d, J =6.6, CH ), 2.40 (3H, d, J
.42 (1H, dd, J
=7.2, NCH ), 4.8 (1H, m, CHN),
3
HH
3
PNCH
3
3
31
5
=8.9, OCH), 6.85 (2H, m, H arom), 7.0–8.0 (25H, m, H arom); P NMR (CDCl ):
POCH
3
1
3
2
δ 72.9 (br, P–N), 115 (br, P–O); C NMR (CDCl ): δ 15.9 (CH ), 29.8 (d, J =3.9, NCH ), 57.5
3
3
PNC
3
3
2
2
3
(
dd, J
=11, J =8.5, NCH), 83.4 (dd, J =2.6, JPNCC=9.3, OCH), 124.5–137.8 (C arom); MS
POCC
PNC
+
POC
+
(
DCI, CH ) 610 (M −H; 15), 596 (M −H−BH ; 25), 412 (15), 396 (50), 384 (100), 327 (25), 292 (15),
4
3
+
2
37 (45), 203 (100), 148 (20); HRMS (DCI, CH ) calcd for C H ONP B [M −H]: 610.2771; found:
4
38 40
2 2
6
10.2789; anal. calcd for C H B NOP : C 74.66, H 6.76, N 2.29; found: C 74.61, H 6.69, N 2.27.
3
8
41
2
2

D. Moulin et al. / Tetrahedron: Asymmetry 10 (1999) 4729–4743
4737
4
.2.7. (Rp)-(−)-N-Methyl-N-{(1R,2S)-[2-(diphenylphosphinito borane)-1-methyl-2-phenyl]ethyl}-
amino-2-naphthylphenylphosphine borane 4e
2
0
Yield=78%; white solid; mp=71–75°C; [α] =−65.3 (c 1.04, CHCl ); R =0.65 (toluene); IR (neat, ν
D
3
f
−1
cm ): 3050–2900 (w, C–H), 2362 (vs, B–H), 2339 (m, B–H), 1457 (m), 1159 (m), 1109 (m), 1062 (m),
1
3
3
1
4
012 (m), 983 (m); H NMR (CDCl ): δ 1.44 (3H, d, J =6.50, CH ), 2.43 (3H, d, JPNCH=7.7, NCH3),
3
HH
3
3
3
.73 (1H, m, NCH), 5.49 (1H, dd, J
= J =9.3, OCH), 6.75 (2H, m, H arom), 7.0–7.65 (19H, m,
POCH
HH
3
1
H arom), 7.85 (5H, m, H arom), 8.15 (1H, d, J=16.5, H arom); P NMR (CDCl ): δ 72.0 (br, P–N),
3
1
3
2
2
1
07.6 (br, P–O); C NMR (CDCl ): δ 16.16 (CH ), 29.4 (d, J =4.5, NCH ), 57.4 (dd, JPNC=8.8,
3
3
PNC
3
3
2
3
JPOCC=11.3, NCH), 83.4 (dd, J =2.4, J
=8.9, OCH), 124.6–137.9 (C arom); MS (DCI, CH4)
POC
PNCC
+
+
m/z (relative intensity): 610 (M −H; 15), 596 (M −H−BH ; 12), 396 (40), 384 (95), 364 (10), 306 (15),
3
+
2
6
76 (25), 237 (95), 203 (100), 187 (75), 148 (40); HRMS (DCI, CH ) calcd for C H ONP B [M −H]:
4
38 40
2 2
10.2771; found: 610.2783.
4
.2.8. (Sp)-(−)-N-Methyl-N-{(1R,2S)-[2-(diphenylphosphinito borane)-1-methyl-2-phenyl]ethyl}-
amino-tert-butylphenylphosphine borane 4f
Yield=64%; white solid; mp=137–138°C; [α] =−86.1 (c 1.19, CHCl ); R =0.75 (toluene); IR (neat,
2
0
D
3
f
−
1
1
ν cm ): 3050–2900 (m, C–H), 2382 (s), 1436 (s), 1109 (s), 1067 (s), 1015 (s), 978 (s), 949 (s); H NMR
3
3
3
(CDCl ): δ 1.11 (9H, d, J
=13.8, C(CH ) ), 1.33 (3H, d, J =5.5, CH ), 2.62 (3H, d, J
=5.5,
3
PCCH
3 3
3
HH
3
PNCH
3
31
NCH ), 4.38 (1H, m, NCH), 5.40 (1H, dd, J
= J =10.6, OCH), 6.66–7.8 (20H, m, H arom);
P
3
POCH
HH
1
1
13
NMR (CDCl ): δ 87.8 (q, J =72.3, P–N), 107.32 (q, J =77.6, P–O); C NMR (CDCl ): δ 14.8
3
PB
PB
3
2
2
1
(CH ), 28.1 (d, J =2.8, C(CH ) ), 31.9 (d, J =4.3, NCH ), 34.29 (d, J =35.2, C(CH ) ), 58.0
3
2
PCC
3 3
PNC
3
3
PC
3 3
3
2
(dd, J = J
=8.8, NCH), 83.4 (dd, J =3, J
=5.3, OCH), 127.7–136.6 (C arom); MS (DCI,
PNC
PNCC
POC
PNCC
+
+
CH ) m/z (relative intensity): 540 (M −H; 10), 526 (M −H−BH ; 10), 326 (100), 314 (90), 236 (45),
4
3
+
2
03 (90), 187 (25), 146 (15); HRMS (DCI, CH ) calcd for C H ONP B [M −H]: 540.2928; found:
4
32 42
2 2
540.2944; anal. calcd for C H B NOP (541.2594): C 71.01, H 8.01, N 2.59; found: C 71.00, H 8.04,
32 43 2 2
N 2.41.
4
.2.9. (Rp)-(−)-N-Methyl-N-{(1R,2S)-[2-(dicyclohexylphosphinito borane)-1-methyl-2-phenyl]ethyl}-
amino-o-anisylphenylphosphine borane 4i
Yield=67%; white solid; mp=178–181°C; [α] =−37.8 (c 1.02, CHCl ); R =0.5 (toluene); IR (neat, ν
2
0
D
3
f
−
1
1
cm ): 2931 (s), 2850 (s), 2364 (s), 2336 (s), 1456 (m), 1275 (m), 1250 (m), 1065 (s), 1013 (s); H NMR
3
3
(
CDCl ): δ 0.4–2.1 (22H, m, CH (cyclohexyl)) 1.35 (3H, d, J =6.4, CH ), 2.34 (3H, d, JPNCH=8.0,
3
2
HH
3
3
3
NCH ), 3.41 (3H, s, OCH ), 4.5 (1H, m, NCH), 5.07 (1H, dd, J
= J =9.0, OCH), 6.53 (2H, m,
3
3
POCH
HH
3
1
13
H arom), 6.6–7.7 (12H, m, H arom); P NMR (CDCl ): δ 69.7 (br, P–N), 135.6 (br, P–O); C NMR
3
2
1
(
CDCl ): δ 16.2 (CH ), 25.4–26.9 (CH ), 29.7 (d, J =4.8, NCH ), 35.7 (d, J =41.6, PCH), 37.3
3
3
2
PNC
3
PC
1
2
3
2
(d, J =31.4, PCH), 54.9 (s, OCH ), 57.8 (dd, J =8.1, J
=11.5, NCH), 82.3 (dd, JPOC=4.8,
PC
3
PNC
POCC
3
JPNCC=9.7, OCH), 111.4 (d, J =4.3, C arom), 118.6–139 (C arom), 160.8 (C arom); MS (DCI, CH )
PC
+
4
+
m/z (relative intensity): 602 (M −H; 15), 588 (M −H−BH , 15), 376 (60), 364 (85), 272 (15), 243
3
+
(
6
35), 215 (100), 148 (35); HRMS (DCI, CH ) calcd for C H B NO P [M −H]: 602.3660; found:
4
35 52
2
2 2
02.3661; anal. calcd for C H B NO P (603.3767): C 69.67, H 8.85, N 2.32; found: C 69.51, H 8.76,
35 53 2 2 2
N 2.14.
4.3. Synthesis of the aminophosphine phosphinite diborane 4g, 4j–k
4.3.1. Preparation of (Sp)-o-anisylchlorophenylphosphine borane 3b
A 100 mL two-necked flask equipped with a magnetic stirrer, an argon inlet and a rubber septum was
charged with 600 mg of the aminophosphine borane 2b7 (1.52 mmol) and a solution of HCl in toluene
c

4
738
D. Moulin et al. / Tetrahedron: Asymmetry 10 (1999) 4729–4743
(
0.26 M, 35 mL, 9.12 mmol) was directly added (without previous solubilization of the aminophosphine)
at room temperature under strirring. After 1 h, the ephedrine hydrochloride was filtered off on a millipore
µm filter, and the solution was rapidly used without further purification.
4
−1
Colorless viscous oil; R =0.8 (toluene); IR (neat, ν cm ): 3058, 3010, 2941, 2839 (C−H), 2394
f
1
(
B−H), 1589, 1575, 1478, 1433, 1280, 1252, 1181, 1165, 1055; H NMR (CDCl ): δ 0.7–3.2 (3H, br,
3
BH ), 3.06 (3H, s, OCH ), 6.3–6.4 (1H, m, H arom), 6.72–6.83 (1H, m, H arom), 6.95–7.22 (4H, m, H
3
3
31
1
arom), 7.67–7.8 (2H, m, H arom), 8.0–8.1 (1H, m, H arom); P NMR (CDCl ): δ 81 (q, J =57.8);
3
PB
1
3
C NMR (CDCl ): δ 55.7 (OCH ), 111.9–161.1 (C arom).
3
3
4.3.2. Typical procedure for 4g, 4j–k
A 250 mL round-bottomed flask equipped with a magnetic stirrer was charged with 4.28 g of
0
oxazaphospholidine borane 1 (or 1 ; 15 mmol) and 23 mL of dry THF. To this solution cooled at −78°C,
1
equivalent of o-AnLi (or PhLi; 15 mmol) were added, and the reaction stirred during 1 h 30 min. Then
the mixture was warmed to 0°C, and added to o-anisylphenylchlorophosphine borane 3b (1.5 mmol),
previously prepared according to the procedure described in Section 4.5.1. After one night under stirring,
the reaction was hydrolyzed at room temperature, then the THF was removed under reduced pressure,
and the residue extracted with CH Cl . The combined extracts were dried over MgSO and the solvent
2
2
4
was removed under vacuum to give a crude product, which was purified by chromatography on silica gel
using toluene:petroleum ether, 1:1, as eluent. The AMPP diborane complexes were isolated in 40–73%
yield, whereas the excess of aminophosphine 2 was recovered in 60% yield after recrystallization in a
hexane:i-PrOH, 7:3, mixture.
4
.3.3. (−)-N-Methyl-N-{(1R,2S)-[2-((Rp)-o-anisylphenylphosphinito borane)-1-methyl-2-phenyl]-
ethyl}aminodiphenylphosphine borane 4g
Yield=44%; white solid; mp=147–148°C; [α] −72.5 (c 1.01, CHCl ); R =0.4 (toluene); IR (neat, ν
2
0
D
3
f
−
1
cm ): 3050–2900 (w, C–H), 2383 (s, B–H), 2341 (m, B–H), 1589 (m), 1574 (m), 1476 (s), 1454 (s),
1
3
3
1
434 (s), 1279 (s), 1252 (s); H NMR (CDCl ): δ 1.33 (3H, d, J =6.5, CH ), 2.28 (3H, d, JPNCH=7.6,
NCH ), 3.55 (3H, s, OCH ), 4.58 (1H, m, NCH), 5.40 (1H, dd, J = J
H arom), 6.9 (1H, m, H arom), 7.0–7.6 (20H, m, H arom), 7.9 (1H, m, H arom); P NMR (CDCl ):
δ 72.4 (br, P–N), 106.4 (q, J =75.1, P–O); C NMR (CDCl ): δ 16 (CH ), 29.3 (d, JPNC=4.5,
NCH ), 55.4 (OCH ), 57.5 (m, J =9.6, J
3
HH
3
3
3
=9.5, OCH), 6.6 (2H, m,
3
3
HH
POCH
31
3
1
13
2
PB
2
3
3
3
=10.9, NCH), 82.2 (m, OCH), 111.7 (d, J =5.4, C
3
3
PNC
POCC
PC
arom), 119.4–138.3 (C arom), 160.75 (d, J =4.3, C arom); MS (DCI, CH ) m/z (relative intensity): 590
PC
4
+
+
(
(
M −H; 25), 576 (M −H−BH ; 70), 417 (50), 346 (15), 332 (65), 233 (100), 187 (20), 148 (35); HRMS
3
+
DCI, CH ) calcd for C H B NO P [M −H]: 590.2721; found: 590.2733.
4
35 40
2
2 2
4.3.4. (+)-N-Methyl-N-{(1S,2R)-[2-((Rp)-o-anisylphenylphosphinito borane)-1-methyl-2-phenyl]-
ethyl}aminodiphenylphosphine borane 4j
Yield=73%; white solid; mp=162°C; [α] =+104.5 (c 1.07, CHCl ); R =0.45 (toluene); IR (neat, ν
2
0
D
3
f
−
1
cm ): 3050–2900 (m, C–H), 2382 (s, B–H), 2350 (m, B–H), 1592 (s), 1570 (m), 1479 (s), 1455 (s), 1437
1
3
(
s), 1282 (s), 1256 (s), 1136 (s), 1105 (s); H NMR (CDCl ): δ 1.30 (3H, d, J =6.6, CH ), 2.2 (3H, d,
JPNCH=7.5, NCH ), 3.27 (3H, s, OCH ), 4.55 (1H, m, NCH), 5.27 (1H, dd, J = J
.32 (1H, m, H arom), 6.51 (2H, m, H arom), 6.72 (1H, m, H arom), 6.8–7.7 (20H, m, H arom);
NMR (CDCl ): δ 72.6 (br, P–N), 105 (br, P–O); C NMR (CDCl ): δ 16.2 (CH ), 29.3 (d, JPNC=4.8,
NCH ), 54.6 (OCH ), 57.4 (dd, J
3
HH
3
3
3
3
=9.1, OCH),
3
3
HH
POCH
3
1
6
P
1
3
2
3
3
3
2
3
=8.5, J
=10.9, NCH), 82.0 (dd, OCH), 110 (d, J =3.6,
3
3
PNCH
POCC
PC
+
C arom), 118.5–137 (C arom), 160.4 (C arom); MS (DCI, CH ) m/z (relative intensity): 590 (M −H;
4
+
1
00), 576 (M −H−BH ; 70), 346 (40), 334 (40), 242 (25), 233 (50), 157 (20), 185 (20); HRMS (DCI,
3

D. Moulin et al. / Tetrahedron: Asymmetry 10 (1999) 4729–4743
4739
+
CH ) calcd for C H B NO P [M −H]: 590.2720; found: 590.2739; anal. calcd for C H B NO P
4
35 40
2
2
2
35 41
2
2 2
(
591.2819): C 71.10, H 6.99, N 2.37; found: C 70.95, H 7.10, N 2.19.
4.3.5. (Sp)-(+)-N-Methyl-N-{(1S,2R)-[2-((Rp)-o-anisylphenylphosphinito borane)-1-methyl-2-phenyl]-
ethyl}amino-o-anisylphenylphosphine borane 4k
2
0
Yield=40%; white solid; mp=192–193°C; [α] =+92.6 (c 0.84, CHCl ); R =0.5 (toluene); IR (neat,
D
3
f
−
1
ν cm ): 3050–2900 (w, C–H), 2389 (s, B–H), 2340 (w, B–H), 1589 (s), 1573 (m), 1477 (s), 1462 (m),
1
3
1
435 (m), 1427 (m), 1280 (s), 1252 (m), 1010 (m), 983 (s); H NMR (CDCl ): δ 1.43 (3H, d, JHH=6.5,
3
3
CH ), 2.41 (3H, d, J
=7.9, NCH ), 3.37 (3H, s, OCH ), 3.53 (3H, s, OCH ), 4.66 (1H, m, NCH),
3
PNCH
3 3 3
3
5
.4 (1H, dd, J=9.2, OCH), 6.45 (1H, m, H arom), 6.6 (2H, m, H arom), 6.7–7.9 (20H, m, H arom);
3
1
1
13
P NMR (CDCl ): δ 70.0 (br, P–N), 104.6 (q, JP–B=66, P–O); C NMR (CDCl ): δ 15.7 (CH ),
3
3
3
2
2
3
2
9.7 (d, J =4.8, NCH ), 54.6 (OCH ), 54.9 (OCH ), 57.5 (dd, J =9.6, JPOCC=11.5, NCH), 82.3
PNC 3 3 3 PNC
2
3
(dd, J =2.9, J
=9.6, OCH), 110.3 (d, J =4.1, C arom), 111.4 (d, J =4.5, C arom), 118.3 (d,
PNCC PC PC
POC
J =16.3, C arom), 119.7 (d, J =12.8) 119.1 (d, J =15.2, C arom), 120.8 (d, J =10.9, C arom),
PC
PC
PC
PC
1
27.5–137.8 (C arom), 160.4 (C arom), 161 (C arom); MS (DCI, CH ) m/z (relative intensity): 620
4
+
+
(
M −H; 40), 606 (M −H−BH ; 20), 392 (15), 376 (90), 364 (55), 307 (10), 272 (20), 233 (100), 217
3
+
(50), 148 (15); HRMS (DCI, CH ) calcd for C H B NO P [M −H]: 620.2826; found: 620.2827;
4
36 42
2
3 2
anal. calcd for C H B NO P (621.3081): C 69.59; H 6.98, N 2.25; found: C 69.45, H 7.07, N 2.08.
3
6
43
2
3 2
4
.4. (Sp)-(−)-N-Methyl-N-{(1R,2S)-[2-((Sp)-methylphenylphosphinito borane)-1-methyl-2-phenyl]-
ethyl}aminomethylphenylphosphine borane 4h
4
.4.1. Preparation of (Rp)-chloromethylphenylphosphine borane 3a7f
A 250 mL two-necked flask equipped with a magnetic stirrer, an argon inlet and a rubber septum was
charged with 1.2 g (4 mmol) of the aminophosphine borane 2a7c,f and 178 mL of toluene. A solution of
HCl in toluene (0.38 M, 22.1 mL, 8.4 mmol, 2.1 equivalents) was added at room temperature under
stirring (the final concentration of aminophosphine borane had to be about 20 mM). After 1 h, the
ephedrine hydrochloride was filtered off with a millipore 4 µm filter, and the solution rapidly used
without further purification. After removal of the solvent, the chlorophosphine borane can be purified
in poor yield by chromatography on a short column of silica gel, previously dried overnight at 80°C and
washed with acetone then cyclohexane, yielding compound 3a.
−
1
Colorless viscous oil; R =0.8 (toluene); IR (neat, ν cm ): 3080, 3000, 2933, 2940 (C–H), 2383
f
1
(
B–H), 1437, 1119, 1062, 949, 909, 745, 690; H NMR (CDCl ): δ 0.5–2.0 (3H, br, BH ), 1.2 (3H,
3
3
2
31
d, J =11, CH ), 7.3–7.7 (3H, m, H arom), 7.8–8.0 (2H, m, H arom); P NMR (CDCl ): δ 96.8 (q,
PCH
3
3
1
13
1
J =47); C NMR (CDCl ): δ 19.9 (d, J =31, PCH ), 129.1 (d, J =2, C arom), 130.8 (d, J =12,
PB
3
PC
3
PC
PC
+
C arom), 133.1 (d, J =2, C arom); MS (DCI, CH ) m/z (relative intensity): 173 (M ; 1), 140 (20), 125
PC
4
(100), 109 (64).
4
.4.2. Synthesis of 4h
A 100 mL round-bottomed flask equipped with a magnetic stirrer and an argon inlet was charged
with 1 equivalent of oxazaphospholidine borane 1 (3.5 mmol) and 3 mL of THF. CH Li (4.9 mmol,
3
1
.4 equivalents) was added at −78°C and the reaction stirred during 1 h and allowed to warm to 0°C.
The crude product is transferred at −78°C with a syringe to 4.9 mmol of methylphenylchlorophosphine
borane 3a previously prepared as described in Section 4.4.1. The reaction was stirred for 1 h 50 min then
hydrolyzed at room temperature. THF was removed under reduced pressure. After extraction of the crude
product with CH Cl , the organic extracts were dried over anhydrous magnesium sulfate and the solvent
2
2

4
740
D. Moulin et al. / Tetrahedron: Asymmetry 10 (1999) 4729–4743
removed. The residue was purified by chromatography on silica gel using toluene:petroleum ether, 1:1,
as eluent yielding the AMPP in 18% unoptimized yield.
2
0
Yield=18%; white solid; [α] =−22.1 (c 1.03, CHCl ); R =0.4 (toluene); mp=124°C; IR (neat, ν
D
3
f
−1
1
cm ): 3050–2900 (w, C–H), 2396 (s, B–H), 2368 (s, B–H), 1455 (m), 1292 (m), 1063 (m); H NMR
3
2
2
(
CDCl ): δ 1.35 (3H, d, J =6.6, CH ), 1.45 (3H, d, J =8.8, NPCH ), 1.64 (3H, d, JPCH=9.2,
3
HH
3
PCH
3
3
3
OPCH ), 2.22 (3H, d, J
=8.2, NCH ), 4.25 (1H, m, CHN), 5.04 (1H, dd, J=7.3, OCH), 6.5–6.65
3
PNCH
3
3
1
(
(
1
(
2H, m, H arom), 6.9–7.3 (11H, m, H arom), 7.3–7.45 (2H, m, H arom); P NMR (CDCl ): δ 68.6
3
1
1
13
1
q, J =68.7, P–N), 113.1 (q, J =80, P–O); C NMR (62.9 MHz): δ 11.2 (d, J =39.4, NPCH ),
PB
PB
PC
3
1
2
2
3
5.8 (CH ), 16.4 (d, J =50, OPCH ), 28 (d, J =3.3, NCH ), 57 (dd, J = JPOCC=9.6, NCH), 82.1
3 PC 3 PC 3 PNC
2
3
dd, J =3.5, J
=9, OCH), 127.8–132.6 (C arom), 138.1 (C arom); MS (DCI, CH ) m/z (relative
POC
POCC
+
4
+
intensity): 436 (M −H; 100), 422 (M −H−BH ; 35), 298 (25), 270 (25), 194 (15), 180 (20), 141 (40),
3
+
1
25 (15), 107 (5); HRMS (DCI, CH ) calcd for C H B NOP [M −H]: 436.2302; found: 436.2313;
4
24 34
2
2
anal. calcd for C H B NOP (437.1141): C 65.95, H 8.07, N 3.20; found: C 65.96, H 8.14, N 3.14.
2
4
35
2
2
4.5. Typical procedure for the decomplexation of aminophosphineborane phosphinite borane 4a–k.
In a three-necked flask equipped with a reflux condenser, a magnetic stirrer and an argon inlet, 1
equivalent (0.5 mmol) of AMPP borane 4 was charged. Diazabicyclooctane (2 mmol, 4 equivalents) was
added, the flask purged with three cycles of argon and 3 mL of dry toluene added. The mixture was
heated at 70°C for 12 h. The crude product was rapidly filtered off on a neutral alumina column (15 cm
height, 2 cm diameter) using toluene:AcOEt, 9:1, as eluent. AMPP 5 was recovered in isolated yields
varying between 70 and 90%.
4
.5.1. (−)-N-Methyl-N-{(1R,2S)-[2-(diphenylphosphinito)-1-methyl-2-phenyl]ethyl}aminodiphenyl-
phosphine 5a ((−)-EPHOS)
2
0
1
3
[
α] =−57.7 (c 0.75, toluene); H NMR (CDCl ): δ 1.36 (3H, d, J =6.6, CH ), 2.19 (3H, d,
D
3
HH
3
3J
=3.1, NCH ), 4.00 (1H, m, NCH), 4.80 (1H, dd, J = J
3 3
=8.8, OCH), 6.66 (m, 2H), 7.0–7.6
POCH
PNCH
3
HH
3
1
(23H, m, H arom); P NMR (CDCl ): δ 66.0 (P–N), 111.7 (P–O).
3
4.5.2. (Sp)-N-Methyl-N-{(1R,2S)-[2-(diphenylphosphinito)-1-methyl-2-phenyl]ethyl}aminomethyl-
phenylphosphine 5b
1
2
3
H NMR (CDCl ): δ 1.15 (3H, d, J =6, PCH ), 1.29 (3H, d, J =6.6, CH ), 2.09 (3H, d,
3
PCH
3
HH
3
3J
=3.8, NCH ), 3.9 (1H, m, NCH), 4.85 (1H, dd, J = JPOCH=10.0, OCH), 6.55 (2H, m, H arom),
3
3
PNCH
3 HH
3
1
7.0–7.9 (18H, m, H arom); P NMR (CDCl ): δ 52.4 (P–N), 111.9 (P–O).
3
4.5.3. (Rp)-N-Methyl-N-{(1R,2S)-[2-(diphenylphosphinito)-1-methyl-2-phenyl]ethyl}amino-o-
anisylphenylphosphine 5c
1
3
H NMR (CDCl ): δ 1.45 (3H, d, J =6.6, CH ), 2.19 (3H, NCH ), 3.65 (3H, s, OCH ), 4.0 (1H,
3
HH
3
3
3
3
3
31
m, NCH), 4.8 (1H, dd, J = J
=8.8, OCH), 6.6 (2H, m, H arom), 6.75–7.65 (22H, m, H arom); P
HH
POCH
NMR (CDCl ): δ 56 (P–N), 111 (P–O).
3
4.5.4. (Rp)-N-Methyl-N-{(1R,2S)-[2-(diphenylphosphinito)-1-methyl-2-phenyl]ethyl}amino-1-
naphthylphenylphosphine 5d
1
3
3
H NMR (CDCl ): δ 1.30 (3H, d, J =6.6, CH ), 2.15 (3H, d, J
=3, NCH ), 4.0 (1H, m, NCH),
3
3
HH
3
PNCH
3
3
4
.72 (1H, dd, J = J
=8.7, OCH), 6.5 (2H, m, H arom), 6.8–7.8 (24H, m, H arom), 8.1 (1H, m, H
POCH
HH
3
1
13
3
arom); P NMR (CDCl ): δ 57.7 (P–N), 112.1 (P–O); C NMR (CDCl ): δ 16.85 (d, JPNCC=3.8,
3
3

D. Moulin et al. / Tetrahedron: Asymmetry 10 (1999) 4729–4743
4741
CH ), 31.6 (d, J =9.8, NCH ), 65.5 (dd, JPNC=7.5, 3JPOCC=39.8, NCH), 86.4 (dd, 2JPOC=10.3,
2
2
3
PNC
3
3
JPNCC=17.9, OCH), 125–142.1 (C arom).
4.5.5. (Rp)-N-Methyl-N-{(1R,2S)-[2-(diphenylphosphinito)-1-methyl-2-phenyl]ethyl}amino-2-
naphthylphenylphosphine 5e
1
3
3
H NMR (CDCl ): δ 1.37 (3H, d, J =6.6, CH ), 2.24 (3H, d, J
=3, NCH ), 3.97 (1H, m,
3
3
HH
3
PNCH
3
3
NCH), 4.84 (1H, dd, J = JPOCH=9.0, OCH), 6.72–6.75 (2H, m, H arom), 7.1–7.8 (25H, m, H arom);
P NMR (CDCl ): δ 63.6 (P–N), 111.2 (P–O).
HH
3
1
3
4
.5.6. (Sp)-(−)-N-Methyl-N-{(1R,2S)-[2-(diphenylphosphinito)-1-methyl-2-phenyl]ethyl}amino-tert-
butylphenylphosphine 5f
1
3
3
H NMR (CDCl ): δ 0.9 (9H, d, J
=12.7, C(CH ) ), 1.3 (3H, d, J =6.7, CH ), 2.5 (3H, d,
3
PCCH
3 3
3
HH
3
3
3
3
JPNCH=3, NCH ), 3.85 (1H, m, NCH), 4.7 (1H, dd, J = JPOCH=8, OCH), 6.7–7.6 (20H, m, H arom);
3
HH
1
P NMR (CDCl ): δ 89.5 (P–N), 110.8 (P–O).
3
4.5.7. (Rp)-N-Methyl-N-{(1R,2S)-[2-(dicyclohexylphosphinito)-1-methyl-2-phenyl]ethyl}amino-
o-anisylphenylphosphine 5i
3
1
P NMR (CDCl ): δ 56.6 (P–N), 102.7 (P–O).
3
4.5.8. (Sp)-N-Methyl-N-{(1S,2R)-[2-(Rp)-o-anisylphenylphosphinito)-1-methyl-2-phenyl]ethyl}amino-
o-anisylphenylphosphine 5k
3
1
P NMR (CDCl ): δ 56.6 (P–N), 102.7 (P–O).
3
4.5.9. N-Methyl-N-{(1R,2S)-[2-(Rp)-o-anisylphenylphosphinito)-1-methyl-2-phenyl]ethyl}aminodi-
phenylphosphine 5g
1
3
3
H NMR (CDCl ): δ 1.5 (3H, d, J =6.6, CH ), 2.25 (3H, d, J
=3.2, NCH ), 3.75 (3H, s,
3
HH
3
3
PNCH
3
3
31
OCH ), 4.05 (1H, m, NCH), 4.9 (1H, dd, J
= JHH=9.1, OCH), 6.5–7.8 (24H, m, H arom);
POCH
P
3
NMR (CDCl ): δ 66.1 (P–N), 102.5 (P–O).
3
4.5.10. N-Methyl-N-{(1S,2R)-[2-(Rp)-o-anisylphenylphosphinito)-1-methyl-2-phenyl]ethyl}aminodi-
phenylphosphine 5j
1
3
3
H NMR (CDCl ): δ 1.35 (3H, d, J =6.6, CH ), 2.28 (3H, d, J
=3.1, NCH ), 3.6 (3H, s,
3
HH
3
PNCH
3
3
3
OCH ), 4.1 (1H, m, NCH), 4.9 (1H, dd, J
= JHH=9, OCH), 6.6 (2H, m, H arom), 6.9 (1H, H arom),
POCH
3
3
1
7–7.7 (24H, m, H arom); P NMR (CDCl ): δ 66.4 (P–N), 103.2 (P–O).
3
4
4
.6. Preparation of the precatalyst Rh-complexes
+
−
4
.6.1. Preparation of the cationic [Rh(COD) ] BF
2
20
This precatalyst complex was prepared following a modified procedure of Schrock and Osborn. In a
Schlenk tube, under argon atmosphere, 200 mg (0.406 mmol) of [Rh(COD)Cl]221 and 0.40 mL of 1,5-
cyclooctadiene were dissolved in 4 mL of dry and degassed CH Cl . In the dark, AgBF (0.81 mmol)
2
2
4
was added in one portion, and the mixture was stirred for 15–20 min. The solution was filtered through
a bed of Celite which was washed with dry CH Cl . The filtrate was carefully concentrated to 1 mL and
2
2
+
−
.5 mL of ether was added to precipitate (COD) Rh BF as a brown solid. This complex was used for
2 4
1
generating the chiral Rh-complexes.

4
742
D. Moulin et al. / Tetrahedron: Asymmetry 10 (1999) 4729–4743
+
−
4
.6.2. General procedure for the preparation of [Rh(COD)(AMPP 5)] BF4 catalysts
In a Schlenk tube, under an argon atmosphere, a solution of 0.020 mmol of AMPP 5 in 1 mL of dry and
+
−
4
degassed CH Cl was added to 0.0197 mmol (8 mg) of Rh(COD) BF in 1 mL of dry and degassed
2
2
2
CH Cl at room temperature. The mixture was stirred for 1–2 h and used without further purification for
2
2
the asymmetric hydrogenation.
+
−
.6.3. [Rh(COD)(5a)] BF
4
4
3
1
1
2
1
2
P NMR (CDCl ): δ 94.4 (dd, J =163.2, J =21.6, P–N), 120.9 (dd, J =170.6, J =22.6,
3
PRh
PP
PRh
PP
P–O).
+
−
4
.6.4. [Rh(COD)(5d)] BF
4
3
1
1
2
1
2
P NMR (CDCl ): δ 94.3 (dd, J =161.6, J =19.8, P–N), 119.2 (dd, J =168.6, J =19.2,
3
PRh
PP
PRh
PP
P–O).
4
4
.7. Hydrogenation of methyl α-acetamidocinnamate using Rh(COD)(AMPP 5) catalysts
.7.1. Typical procedure
In a 100 mL autoclave, under an argon atmosphere, was introduced 130 mg (0.59 mmol) of Z-methyl
α-acetamidocinnamate, 3% mol (0.0197 mmol) of catalyst (prepared according to the above-mentioned
procedure) and 8 mL of degassed dry CH Cl . When the hydrogenation was performed with benzene
2
2
as the solvent, CH Cl was removed under vacuum before use. The reactor was then connected to a
2
2
hydrogen cylinder, and subjected to six vacuum/H cycles, before pressurizing to an initial pressure of
2
1
5 bars of H . The reaction mixture was allowed to stir for 3 to 13 h at room temperature. Once the
2
reaction was finished, the solvent was removed under reduced pressure, and the residue was purified by
flash chromatography on silica gel using toluene:AcOEt, 3:1, as eluent.
4
.7.2. Methyl α-N-acetylphenylalaninate 722
The enantiomeric excesses and the absolute configuration of compound 7 were determined on a
−1
Chiracel OD column (Daicel), with a hexane:iPrOH, 95:5, mixture as eluent, flow rate 1 mL min
and UV detection λ=254 nm: (S)-enantiomer t =21.9 min, (R)-enantiomer 26.3 min.
R
1
H NMR (CDCl ): δ 1.90 (3H, s, COCH ), 3.04 (2H, m, CH Ph), 3.64 (3H, s, CO CH ), 4.81 (1H,
3
3
2
2
3
13
m, CHCO CH ), 5.90 (1H, br, NHCOCH ), 6.90–7.3 (5H, m, H arom); C NMR (CDCl ): δ 22.9
2
3
3
3
(
COCH ), 37.7 (CH Ph), 52.1 (CHCO CH ), 53.1 (CO CH ), 127 (C arom), 128.4 (C arom), 129.1 (C
3 2 2 3 2 3
arom), 135.8 (C arom), 169.6 (COCH ), 172.0 (CO CH ).
3
2
3
Acknowledgements
We thank Ms. N. Morin and N. Sellier for their help in mass analysis, the Ministry of Research and
the CNRS for financial support to our team.
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0. For recent asymmetric catalysis using chiral tertiary diphosphines, see: (a) Stoop, R. M.; Mezzetti, A.; Spindler, F.
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1
1. For pioneering works concerning P-chiral bulky phosphines, see: Brown, J. M.; Laing, J. C. P. J. Organomet. Chem. 1997,
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29, 435–444.
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1
1
1
4. Jugé, S. French Patent 2 518 100 and international extends.
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1
(a) Ref. 7f . (b) Moulin, D. PhD thesis, 1999, Cergy-Pontoise.
1
1
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0
aminoester 7 in 82% e.e. by Pracejus and colleagues (Ref. 3b).
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2
2
2
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