Highly enantiomerically enriched chlorophosphine boranes: Synthesis and applications as P-chirogenic electrophilic blocks

Article abstract of DOI:10.1021/jo026355d

The stereoselective synthesis of P-chirogenic chlorophosphine boranes 4 was investigated by HCl acidolysis of the corresponding aminophosphine boranes 10. The reaction afforded the P-N bond cleavage with inversion of the configuration at the phosphorus center, leading to the chlorophosphine boranes 4 with high to excellent enantiomeric purities (80-99% ee), except in the case of the chloro1-naphthylphenylphosphine borane 4d. Reaction conditions and workup significantly influence the enantiomeric purity of the product, with the exception of the o-anisyl- and o-tolylchlorophenylphosphine boranes, 4b and 4c, which were found to be particularly stable even after purification by chromatography on silica gel. Reaction of the chlorophosphine boranes 4 with various nucleophiles, such as carbanions, phenolates, thiophenolates, or amides, afforded the corresponding organophosphorus borane complexes via P-C, P-O, P-S, and P-N bond formation, respectively, in 34-93% yield and with up to 99% ee. This work demonstrates the importance of chlorophosphine boranes 4 as new and powerful electrophilic building blocks for the highly stereoselective synthesis of P-chirogenic organophosphorus compounds.

Full text of DOI:10.1021/jo026355d

High ly En a n tiom er ica lly En r ich ed Ch lor op h osp h in e Bor a n es:
Syn th esis a n d Ap p lica tion s a s P -Ch ir ogen ic Electr op h ilic Block s
Christophe Bauduin,† Dominique Moulin,† El Bachir Kaloun,† Christophe Darcel,‡ and
Sylvain J uge´*,‡
Laboratoire de Synthe`se et d’Electrosynthe`se Organome´talliques, UMR 5632, Universite´ de Bourgogne,
6 Bd Gabriel, BP 138, 21100 Dijon, France, and Universite´ de Cergy Pontoise, 5 mail Gay Lussac,
95031 Cergy Pontoise, France
sylvain.juge@u-bourgogne.fr
Received August 26, 2002
The stereoselective synthesis of P-chirogenic chlorophosphine boranes 4 was investigated by HCl
acidolysis of the corresponding aminophosphine boranes 10. The reaction afforded the P-N bond
cleavage with inversion of the configuration at the phosphorus center, leading to the chlorophosphine
boranes 4 with high to excellent enantiomeric purities (80-99% ee), except in the case of the chloro-
1-naphthylphenylphosphine borane 4d . Reaction conditions and workup significantly influence the
enantiomeric purity of the product, with the exception of the o-anisyl- and o-tolylchlorophenylphos-
phine boranes, 4b and 4c, which were found to be particularly stable even after purification by
chromatography on silica gel. Reaction of the chlorophosphine boranes 4 with various nucleophiles,
such as carbanions, phenolates, thiophenolates, or amides, afforded the corresponding organophos-
phorus borane complexes via P-C, P-O, P-S, and P-N bond formation, respectively, in 34-93%
yield and with up to 99% ee. This work demonstrates the importance of chlorophosphine boranes
4 as new and powerful electrophilic building blocks for the highly stereoselective synthesis of
P-chirogenic organophosphorus compounds.
In tr od u ction
highly stereoselective catalysts. The synthesis of these
ligands is usually performed with the achiral chlorophos-
phines 1, either as electrophilic6 (R1 ) R2, Scheme 1a) or
nucleophilic reagents,7 through the formation, in the
latter case, of the phosphides 2 (Scheme 1b).
If the enantiomerically enriched chlorophosphines 1
(Scheme 1, R1 * R2) could be obtained, they would be
useful in the synthesis of a new classes of bulky or
chelating monophosphines, hybrid or functionalized
ligands, with a P-chirogenic atom. It should be pointed
out that the stereoselective synthesis of P-chirogenic
ligands is also of particular interest for catalysts bearing
only a monophosphine8 or to increase the number of
availables stereoisomers from a designated ligand.9
Unfortunately, the synthesis of chiral chlorophosphine
1 proceeds with complete racemization,10,11 and only the
partially enantiomerically enriched tert-butylchlorophe-
C2-Symmetric diphosphines or (phosphinoaryl) oxazo-
lines with a stereogenic carbon backbone are widely used
as chiral ligands in asymmetric reactions for C-H or
C-C bond formation catalyzed by transition-metal com-
plexes.1,2 Nevertheless, other classes of phosphorus ligands,
in which the chirality comes from a planar chirality,3 an
amino alcohol,4 or a carbohydrate,5 could also lead to
* To whom correspondence should be addressed. Fax: 33-1-03-80-
39-60-98.
† Universite´ de Cergy Pontoise.
‡ Universite´ de Bourgogne.
(1) (a) Brunner, H.; Zettlmeier, W. Handbook of Enantioselective
Catalysis with Transition Metal Compounds, Products and Catalysis;
VCH: Basel, 1993; Vol. 1. (b) Brunner, H.; Zettlmeier, W. Handbook
of Enantioselective Catalysis with Transition Metal Compounds,
Ligands-References; VCH: Basel, 1993; Vol. 2.
(2) (a) Ojima, I. Catalytic Asymmetric Synthesis; VCH: New York,
1993. (b) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley
& Sons: New York, 1994. (c) Palmer, M. J .; Wills, M. Tetrahedron:
Asymmetry 1999, 10, 2045-2061. (d) Tenaglia, A.; Heumann, A.
Angew. Chem., Int. Ed. Engl. 1999, 38, 2180-2184. (e) McCarthy, M.;
Guiry, P. J . Tetrahedron 2001, 57, 3809-3844.
(3) Togni, A.; Breutel, C.; Schnyder, A.; Spindler, F.; Landert, H.;
Tijani, A. J . Am. Chem. Soc. 1994, 116, 4062-4066. (b) Togni, A.;
Hayashi, T. Ferrocenes; VCH: Basel, 1995.
(4) (a) Agbossou, F.; Carpentier, J . F.; Hapiot, F.; Suisse, I.;
Mortreux, A. Coord. Chem. Rev. 1998, 178-180, 1615-1645. (b)
Devocelle, M.; Mortreux, A.; Agbossou, F.; Dormoy, J . R. Tetrahedron
Lett. 1999, 40, 4551-4554.
(5) (a) Selke, R.; Ohff, M.; Riepe, A. Tetrahedron, 1996, 52, 15079-
15102. (b) RajanBabu, T. V.; Radetich, B.; You, K. K.; Ayers, T. A.;
Casalnuovo, A. L.; Calabrese, J . C. J . Org. Chem. 1999, 64, 3429-
3447. (c) Deerenberg, S.; Pamies, O.; Dieguez, M.; Claver, C.; Kamer,
P. C. J .; van Leeuwen, P. W. N. M. J . Org. Chem. 2001, 66, 7626-
7631.
(6) For selected examples of synthesis of phosphorus ligands using
chlorophosphine as electrophilic blocks, see: (a) Sprinz, J .; Helmchen,
G. Tetrahedron Lett. 1993, 34, 1769-1772. (b) Deaton, D. N. In
Encyclopedia of Reagents for Organic Synthesis; Paquette, L. A., Ed.;
Wiley: Chichester, 1995; Vol. 2. (c) See also refs 4 and 5.
(7) For a typical synthesis of phosphorus ligands using chlorophos-
phine as the phosphide precursor, see: Peer, M.; de J ong J . C.; Kiefer,
M.; Langer, T.; Rieck, H.; Schell, H.; Sennhenn, P.; Sprinz, J .;
Steinhagen, H.; Wiese, B.; Helmchen, G. Tetrahedron 1996, 52, 7547-
7583.
(8) For a pertinent review on monophosphines or derivative ligands,
see: (a) Lagasse, F.; Kagan, H. B. Chem. Pharm. Bull. 2000, 48 (3),
315-324. (b) Komarov, I. V., Bo¨rner, A. Angew. Chem., Int. Ed. Engl.
2001, 40, 1197-1200.
(9) Moulin, D.; Darcel, C.; J uge´, S. Tetrahedron: Asymmetry 1999,
10, 4729-4743.
(10) Horner, L.; J ordan, M. Phosphorus Sulfur 1980, 8, 235-242.
10.1021/jo026355d CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/02/2003
J . Org. Chem. 2003, 68, 4293-4301
4293

Bauduin et al.
TABLE 1. In flu en ce of Acid olysis Con d ition s on th e Ster eoselectivity
aminophosphine borane
R1
acidolysis conditions
phosphine borane
yields (%)
entry
HCl (equiv)
[11] (mM)
time (h)
R3
eea (%)
abs config
1
2
3
4
5
6
7
8
9
Me
Me
Me
11a
11a
11a
11b
11b
11b
11c
11d
11e
11f
11g
11h
6
2
2.1
6
6
2.1
6
2.1
3
6
6
20
50
20
60
60
180
60
20
130
20
60
24
1.3
1
24
1
1
1
1
1
o-An
o-An
o-An
Me
Me
Me
Me
Me
Me
Me
12a
12a
12a
12bb
12b
12b
12c
12d
12e
12f
0
R,S
S
S
R
R
R
R
R,S
R
R
82
80
80
90
87
95
98
98
0
85
99
80
o-An
o-An
o-An
o-Tol
1-Np
2-Np
o-PhPh
c-Hex
t-But
75
90
61
50
46
41c
46
10
11
12
1
3
24
Me
12g
R
6
60
a
b
Determined by HPLC with Chiralcel OK. 12a and 12b are enantiomers. c Isolated yield for 50% conversion.
SCHEME 1
In earlier works, we reported preliminary results on
the use of the chlorophosphine boranes 4 for the stereo-
selective synthesis of phosphorus ligands.18a-c Although
the borane complexation confers a better configurational
stability on the chlorophosphines, they must be prepared
and handled with caution. This may be why there are so
few applications of chiral chlorophosphine boranes in the
literature.19
We wish to report here the stereoselective preparation
of the alkyl and aryl chlorophenylphosphine boranes 4
and their reactions with various nucleophiles (Scheme
2).
Resu lts a n d Discu ssion
nyl phosphine 1a (R1 ) Ph, R2 ) t-Bu) has been described
to date.12,13 However, this compound slowly racemized in
24 h at room temperature. The racemization of the
chlorophosphine can be explained by trace amounts of
HCl implying reversible protonation of the phosphorus
atom, with a concerted backside attack of the chlorine,
resulting in the achiral pentacoordinated intermediate
311 (Scheme 1c).
Complexed to the borane moiety, the chlorophosphines
4 produce stable compounds that have similar reactivity
to the PIII derivatives (Scheme 2).14 Since the borane
complexes 5 allow the free tricoordinate phosphorus
compounds 6 to retain their configuration,15 and since
these complexes can be used directly for organic16 or
coordination chemistry17 (Scheme 2), the potentially
versatile applications of P-chirogenic chlorophosphine
boranes 4 were studied.
P r ep a r a tion of th e Ch lor op h osp h in e Bor a n es.
Several years ago, we described20 the diastereospecific
synthesis of the aminophosphine boranes 11 by the
reaction of organolithium reagents with the oxazaphos-
pholidine borane complex 10 (Scheme 3).
Under acidic conditions, the methanolysis of com-
pounds 11 induces the P-N bond cleavage to give the
methyl phosphinite borane R1PhP(BH3)OMe with inver-
sion of the configuration at the phosphorus center.
Consequently, we decided to investigate the acidolysis
of the aminophosphine boranes 11 in various solvents in
the presence of different Lewis acids or halide reagents,
such as BCl3, PCl5, AcCl, PPh3‚HBr, or with the mixed
reagents LiCl/H2SO4 and TMSCl/iPrOH. In most cases,
these reaction conditions led to partial conversions,
racemization, or the formation of byproducts. Finally, the
acidolysis of compounds 11 was realized with a toluene
solution of HCl to produce the corresponding chlorophos-
phine boranes 4 in 41-90% isolated yields (Tables 1 and
(11) Humbel, S.; Bertrand, C.; Darcel, C.; Bauduin, C.; J uge´, S.
Inorg. Chem. 2003, 42, 420-427.
(12) Omelanczuk, J . J . Chem. Soc., Chem. Commun. 1992, 1718-
1719.
(13) For kinetic resolution studies of chlorophosphine 1, see: (a)
Kolodiazhnyi, O. I. Tetrahedron 1998, 9, 1279-1332. (b) Perlikowska,
W. Gouygou, M.; Daran, J . C.; Balavoine, G.; Mikolajczyk, M. Tetra-
hedron Lett. 2001, 42, 7841-7845.
(14) (a) Schmidbaur, H. J . Organomet. Chem. 1980, 200, 287-306.
(b) Yoder, C. H.; Miller, L. A. J . Organomet. Chem. 1982, 228, 31-35.
(c) Knochel, P.; Langer, F.; Longeau, A.; Rottla¨nder, M.; Stu¨demann.
Chem. Ber. 1997, 130, 1021-1027. (d) Ohff, M.; Holz, J .; Quirmbach,
M.; Bo¨rner, A. Synthesis 1998, 1391-1415.
(15) (a) Imamoto, T.; Kusumoto, T.; Suzuki, N.; Sato, K. J . Am.
Chem. Soc. 1985, 107, 5301-5303. (b) For a recent review of borane
decomplexation with amines, olefins, ethanol, or acids, see ref 16c.
(16) (a) Imamoto, T.; Hirose, K.; Amano, H. Main Group Chem. 1996,
1, 331-338. (b) Uziel, J .; Riegel, N.; Aka, B.; Figuie`re, P.; J uge´, S.
Tetrahedron Lett. 1997, 38, 3405-3408. (c) Uziel, J .; Darcel, C.; Moulin,
D.; Bauduin, C.; J uge´, S. Tetrahedron: Asymmetry 2001, 12, 1441-
1449.
(17) (a) Ste´phan, O.; Riegel, N.; J uge´, S. J . Electroanal. Chem. 1997,
421, 5-8. (b) Hamada, Y.; Matsuura, F.; Oku, M.; Hatano, K.; Shioiri,
T. Tetrahedron Lett. 1997, 38, 8961-8964. (c) Riegel, N.; Darcel, C.;
Ste´phan, O.; J uge´. S. J . Organomet. Chem. 1998, 567, 219-233. (d)
Brodie, N.; J uge´, S. Inorg. Chem. 1998, 37, 2438-2442. (e) Darcel, C.;
Kaloun, E. B.; Merde`s, R.; Moulin, D.; Riegel, N.; Thorimbert, S.; Geneˆt,
J . P.; J uge´, S. J . Organomet. Chem. 2001, 624, 333-343.
(18) (a) Kaloun, E. B.; Merde`s, R.; Geneˆt, J . P.; Uziel, J .; J uge´, S. J .
Organomet. Chem. 1997, 529, 455-463. (b) Moulin, D.; Darcel, C.; J uge´,
S., Tetrahedron: Asymmetry 1999, 10, 4729-4743. (c) Moulin, D.; Bago,
S.; Bauduin, C.; Darcel, C.; J uge´, S. Tetrahedron: Asymmetry 2000,
11, 3939-3956.
(19) (a) Schuman, M.; Trevitt, M.; Redd, A.; Gouverneur, V. Angew.
Chem., Int. Ed. 2000, 39, 2491-2493. (b) Maienza, F.; Spindler, F.;
Thommen, M.; Pugin, B.; Malan, C., Mezzetti, A. J . Org. Chem. 2002,
67, 5239-5249.
4294 J . Org. Chem., Vol. 68, No. 11, 2003

Chlorophosphine Boranes as P-Chirogenic Electrophilic Blocks
SCHEME 2
SCHEME 3
TABLE 2. In flu en ce of P u r ifica tion of th e Ch lor op h osp h in e Bor a n e 4 on Its En a n tiom er ic P u r ity
chlorophosphine‚BH3
4
compd 11
R1
Me
o-An
o-Tol
1-Np
2-Np
eeb (%)
without purif
isolated
absolute
config
entry
aspect
yieldsa (%)
with purif
1
2
3
4
5
6
7
11a
11b
11c
11d
11e
11f
11g
4a
4b
4c
4d
4e
4f
oil
solid
oil
oil
oil
85
99
87
68
61
45
74
R
S
S
S
S
S
R
63
95
95
0
68
59
-
90
98
98
0
85
99
80
o-PhPh
c-Hex
solid
oil
4g
a
b
After filtration on a short column of silica gel. Determined by HPLC with Chiralcel OK of the corresponding phosphine borane
derivatives 12a -g.
2). The enantiomeric purity of the compounds 4 was
determined by HPLC on a chiral column of the corre-
sponding phosphine boranes 12, resulting from the
reaction of 4 with an organolithium reagent (Table 1,
Scheme 3).21
First, it should be noted that the extent of acidolysis
depends on the steric hindrance of the substituents on
the phosphorus atom. Thus, the chemical yields of the
products decrease from methyl to biphenylaminophos-
phine borane (i.e., 11a -f, Table 1, entries 1-10). In the
case of the cyclohexyl analogues 11g, acidolysis requires
3 h for a satisfactory yield, while no reaction was
observed with the tert-butyl aminophosphine borane 11h
(Table 1, entries 11 and 12).
acidolysis of 11a with 6 equiv of HCl, the o-anisylmeth-
ylphenylphosphine borane (PAMP borane) 12a resulting
from reaction with o-anisyllithium was obtained in
racemic form (Table 1, entry 1). In the case of the
acidolysis of 11a at a concentration of 50 mM, with 2
equiv of HCl, the chlorophosphine borane 4a leads to the
(S)-12a with 80% ee (Table 1, entry 2). Finally, the (S)-
PAMP borane 12a was obtained with 90% ee when the
acidolysis step of 11a was carried out for 1 h at a
concentration of 20 mM and in the presence of 2.1 equiv
of HCl (Table 1, entry 3). The absolute configuration of
the phosphine 12a suggests that inversion of configura-
tion occurs both in the acidolysis step and in the nucleo-
philic substitution of 4a . To the best of our knowledge,
that is in good agreement with the stereochemistry of
the single nucleophilic displacement at P-center in acyclic
phosphinous derivatives, including borane complexes.22
The stereoselectivity depends on the excess of HCl
used. When chlorophosphine borane 4a was formed from
(20) (a) J uge´, S.; Stephan, M.; Laffitte, J . A.; Geneˆt, J . P. Tetrahe-
dron Lett. 1990, 31, 6357-6360. (b) J uge´, S.; Stephan, M.; Merde`s, R.;
Geneˆt, J . P.; Halut-Desportes, S. J . Chem. Soc., Chem. Commun. 1993,
531-532.
(21) The high enantiomeric excesses obtained in most cases prove
the stereospecificity of the organolithium reaction with the chloro-
phosphine boranes 4.
In the case of compound 11b, the concentration and
reaction time have less influence for the stereoselectivity
of the acidolysis. Thus, in the presence of 6 equiv of HCl,
11b at a concentration of 60 mM leads to the chlorophos-
phine 4b, which affords the (R)-PAMPborane 12b (enan-
J . Org. Chem, Vol. 68, No. 11, 2003 4295

Bauduin et al.
tiomer of 12a ) with 87% ee by trapping 4b after 24 h
with methyllithium (Table 1, entry 4). In addition, if the
chlorophosphine borane 4b is quenched after 1 h, or if
the concentration of the starting aminophosphine borane
11b is higher (170 mM), the (R)-PAMPborane 12b is
obtained with up to 98% ee (Table 1, entries 5 and 6).
Acidolysis of the o-tolylaminophosphine borane 11c
with 6 equiv of HCl affords 4c and, after quenching with
methyllithium, the phosphine borane 12c with 98% ee
(Table 1, entry 7). Surprisingly, the acidolysis of the
1-naphthylaminophosphine borane 11d gives racemic
products (Table 1, entry 8), whereas the 2-naphthyl
analogous 11e leads to the methyl-2-naphthylphenylphos-
phine borane 12e with 85% ee (Table 1, entry 9).
Although the mechanism and the origin of the racem-
ization remain to be determined, we would suggest that
the racemization of the chloro-1-naphthylphosphine bo-
rane 4d occurs because of a particularly low energy
barrier for the stereopermutation of the pentacoordinate
intermediate 13.23
The acidolysis of the aminophosphine boranes 11a -g
with HCl furnishes the corresponding chlorophosphine
boranes 4a -g in moderate to excellent isolated yields
(Table 2). However, the short chromatography affords the
chlorophosphine boranes 4a , 4e, and 4f with 63, 68, and
59% ee, respectively, versus 85-99% ee without purifica-
tion (Table 2, entries 1, 5, and 6). Nevertheless, the enan-
tiomeric excess of the o-anisyl and o-tolyl chlorophosphine
boranes, 4b and 4c, decreases only slightly with purifica-
tion (95% ee), thus demonstrating their excellent con-
figurational stability (Table 2, entries 2 and 3).
Finally, since the chlorophosphine boranes 4 were
obtained with better stereoselectivity without purifica-
tion, the excess of HCl was eliminated by several vacuum/
argon cycles, after filtration of the ephedrine hydrochlo-
ride, and the toluene solution was used without further
purification or storage.
Ap p lica tion s of th e Ch lor op h osp h in e Bor a n es 4.
The reactions of the chlorophosphine boranes 4 with
various nucleophiles were investigated in order to explore
their synthetic potential. The chlorophosphine boranes
4 were previously prepared in toluene solution, degassed
as described above, and used without delay. The results
are reported in the Table 3.
We have shown that the reaction of o-anisyl- or
methyllithium reagent with the chlorophosphine boranes
4 (except the naphthyl derivative 4d ) furnishes the
corresponding phosphine boranes 12 in good yields and
with enantiomeric excesses higher than 80% (Table 2).
When the chlorophosphine borane 4c was reacted with
the o-anisyllithium reagent, a mixture of the triarylphos-
phine (R)-14 and its borane complex was obtained. After
complete decomplexation of the mixture in ethanol at
room temperature, the enantiomerically pure phosphine
(R)-14 was isolated in 93% yield (Table 3, entry 3). The
easy decomplexation of the phosphine 14 must come from
the steric crowding, which was calculated at 182° using
the Tolman’s cone angle concept.24 The absolute config-
uration of the phosphine 14 was assigned assuming a
stereochemistry with inversion during the nucleophilic
substitution of 4c, and this was in good agreement with
the X-ray structure.
When the phosphine borane was prepared from aci-
dolysis of the biphenyl aminophosphine borane 11f in the
presence of 6 equiv of HCl, for 1 h, followed by the
reaction with methyllithium, compound 12f was obtained
with 99% ee (Table 1, entry 10). However, the acidolysis
of 11f was slow, and a conversion of only 50% was
observed after 1 h. Finally, the acidolysis of the amino-
c-hexylphosphine borane 11g with HCl (3 equiv) for 3 h
produced the chlorophosphine borane 4g and then the
phosphine complex 12g with 80% ee (Table 1, entry 11).
This result confirms that by increasing the reaction time,
even if the conversion is higher, the enantiomeric purity
of the chlorophosphine borane and its derivatives de-
creases.
On the other hand, the chlorophosphine boranes 4
could be readily isolated and purified. Thus, the acidolysis
of the aminophosphine boranes 11a -g was carried out
following the conditions described in Table 1 (entries 3,
6, and 7-11). After filtration of the ephedrine hydrochlo-
ride, half of the chlorophosphine 4 was trapped by
reaction with o-anisyl- or methyllithium to afford the
corresponding phosphine borane 12. The other half of the
solution of the chlorophosphine borane 4 was quickly
purified by filtration on a short column of silica gel before
quenching with the organolithium reagent. In both cases,
the enantiomeric purity of the phosphine borane 12 was
determined by HPLC chromatography on Chiralcel OK.
We have shown in preliminary work that the (R)-
chlorophosphine borane 4a produces the (R)-cyclopenta-
dienylphosphine borane 1518a or the (S)-1-bromo-2-
naphthyl phosphinite borane 1618b with ee up to 91%, on
reaction with the cyclopentadienyl anion or the 1-bromo-
2-naphthoate, respectively (Table 3, entries 4 and 5).
Similarly, when the (S)-chlorophosphine borane 4b reacts
with the sodium p-cresolate, the (R)-O-p-tolyl phosphinite
borane 17 is obtained in 85% yield and with 97% ee
(Table 3, entry 6). The enantiomeric excess of 17 and its
absolute configuration were established by chemical
correlation to the (S)-PAMPborane 12a which was pre-
pared by reaction with methyllithium. In addition, the
reaction of two equiv of (R)-4a with the lithium catecho-
late provides the (S, S)-diphosphinite 18 in 86% yield
(Table 3, entry 7). If the enantiomeric purity has not been
(22) For pertinent reviews on the stereochemistry of single nucleo-
philic displacement at P-chirogenic phosphinous derivatives, see: (a)
Pietrusiewicz, K. M.; Zablocka, M. Chem. Rev. 1994, 94, 1375-1411.
(b) Kolodiazhnyi, O. I. Tetrahedron: Asymmetry 1998, 9, 1279-1332.
In the case of phosphinous borane derivatives, see: (a) ref 14c. (b)
Brunel, J . M.; Faure, B.; Maffei, M. Coord. Chem. Rev. 1998, 178-
180, 665-698.
(23) Further calculations on the stereochemical pathways of the
halogeno pentacoordinate intermediates 3 and analogues indicate low
energy barriers (<10 kcal mol-1).11 For an example of calculations
involving pentacoordinate phosphorus borane adducts, see: Solling,
T. I.; Wild, S. B.; Radom, L. J . Organomet. Chem. 1999, 580, 320-
327.
(24) (a) Tolman, C. A. Chem. Rev. 1977, 77, 313-348. (b) The cone
angle data for the tris(o-methoxyphenyl)phosphine (i.e., 205°) was
taken from: Hirsivaara, L.; Guerricabeitia, L.; Haukka, M.; Suoma-
lainen, P.; Laitinen, R. H.; Pakkanen, T. A.; Pursiainen, J . Inorg. Chim.
Acta 2000, 307, 47-56.
4296 J . Org. Chem., Vol. 68, No. 11, 2003

Chlorophosphine Boranes as P-Chirogenic Electrophilic Blocks
TABLE 3. Rea ction of Ch lor op h osp h in e Bor a n es 4 w ith Va r iou s Nu cleop h iles
a
b
d
Determined by31P NMRwith a chiral palladium complex. See ref 18a. c See ref 18c. Determined by HPLC on Chiralcel OK of the
PAMP borane (S)-12a (or (R)-12b). e Determined by HPLC on Chiralcel OK.
determined in this case, the C2 symmetric structure was
proved by the X-ray analysis.
Con clu sion
In summary, we have described the stereoselective
synthesis and applications of the P-chirogenic chloro-
phosphine boranes 4. These compounds were prepared
by P-N cleavage of the aminophosphine borane 11,
under HCl acidolysis conditions. This reaction is thought
to proceed with inversion of the configuration at the
phosphorus center and leads to the chlorophosphine
boranes 4 with high to excellent enantiomeric purity (80-
99% ee), with the exception of the chloro-1-naphthylphe-
nylphosphine borane 4d . A study of the acidolysis shows
the importance of reaction conditions and workup on the
enantiomeric purity of the product. Thus, better results
were obtained when the toluene was not removed after
the reaction, and when the chlorophosphine borane 4 was
used immediately. However, the o-anisyl- and o-tolyl-
chlorophosphine boranes, 4b and 4c, are relatively stable
and can be purifed by chromatography on silica gel.
Reactions of the chlorophosphine boranes 4 with various
nucleophiles, such as carbanions, phenoxides, phenylthi-
olates, or amides, afforded the corresponding organo-
On the other hand, the reaction of the chlorophosphine
(R)-4a with the lithium thiophenolate produces the
thiophosphinite borane (S)-19 in 87% yield and with
60% ee (Table 3, entry 8). The loss of enantiomeric
purity observed here comes from the lower configura-
tional stability of the chlorophosphine borane 4a .
Finally, (S)-4b was treated with the diamide salts,
prepared from ethylenediamine, to give the diaminophos-
phine borane (R,R)-20 in 89% yield and with 96% ee
(Table 3, entry 9). The C2-symmetric structure of the
compound 20 was established by X-ray analysis, and its
absolute configuration and enantiomeric excess were
determined by correlation to the PAMP borane (R)-12b,
after acidic methanolysis25 and reaction with methyl-
lithium.
(25) The acidic methanolysis of 20 into o-anisyl-O-methylphe-
nylphosphinite borane was considered to proceed with inversion of
configuration, as observed for various examples of aminophosphine
boranes.20
J . Org. Chem, Vol. 68, No. 11, 2003 4297

Bauduin et al.
1055, 911, 784, 744, 691; H NMR (CDCl3) δ (ppm) 1.20 (3H,
1
phosphorus borane complexes by P-C, P-O, P-S, and
P-N bond formation, respectively, in 34-87% yields and
with ee up to 99% ee.
Finally, the chlorophosphine boranes are new, useful
electrophilic building blocks for the stereoselective syn-
thesis of the P-chirogenic organophosphorus compounds.
1
2
br q, J BH ) 97.0), 2.05 (3H, d, J PH ) 12.9), 7.44-7.64 (3H,
m), 7.82-7.88 (2H, m); 13C NMR (CDCl3) δ (ppm) 20.0 (d, 1J PC
1
) 30.8), 129.1 (d, J PC ) 10.8), 130.8 (d, J PC ) 45.8), 130.9 (d,
J PC ) 12.0), 133.2 (d, J PC ) 2.4); 31P NMR (CDCl3) δ (ppm)
1
+96.8 (q, J BP ) 46.6); MS (EI) m/z (relative intensity) 160
(M+ - BH3; 37Cl; 30), 158 (M+ - BH3; 35Cl; 90), 153 (40), 145
(M+ - BH3 - CH3; 37Cl; 10), 143 (M+ - BH3 - CH3; 35Cl; 30),
140 (100), 123 (68), 121 (30), 107 (50), 77 (65); HRMS (EI) calcd
for C7H835ClP [M+ - BH3] 158.0052, found 158.0061; calcd for
C7H837ClP [M+ - BH3] 160.0023, found 160.0029.
Exp er im en ta l Section
Gen er a l P r oced u r es. 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, diethyl ether, toluene, and benzene,
P2O5 for CH2Cl2, calcium hydride for hexane, and sodium
alcoholate for methanol, ethanol, and 2-propanol. Hexane and
2-propanol for HPLC were of chromatographic grade and used
without further purification. Commercially available 2-bro-
moanisole and 2-bromotoluene were distilled before use,
whereas 1-bromonaphthalene, 2-bromonaphthalene, 2-bromo-
biphenyl, and bromocyclohexane were used without purifica-
tion. The toluene HCl solution was obtained by bubbling HCl
gas, and the resulting solution was titrated with an indicator.
Bis-dimethylaminophenylphosphine,18a (2S,4R,5S)-(-)-3,4-
dimethyl-2,5-diphenyl-1,3,2-oxazaphospholidine-2-borane 10,18a
and the N-methyl[(1R,2S)-(2-hydroxy-1-phenyl)ethyl]ami-
nophenylphosphine boranes 11a -h were prepared according
to the literature.18,20 The characteristics of the compounds 11
are reported in the Supporting Information.
The enantiomeric purity of the chloromethylphenylphos-
phine borane 4a was determined by HPLC analysis on chiral
column of the PAMP borane (S)-12a , resulting from reaction
with o-anisyllithium (vide infra).
P r epar ation of (S)-(-)-o-An isylch lor oph en ylph osph in e
Bor a n e 4b.18b In a 50 mL two-necked flask, equipped with a
magnetic stirrer, an argon inlet, and a rubber septum was
introduced 2.0 mmol of the aminophosphine borane 11b. A
solution of HCl in toluene (0.38 M, 11.05 mL, 4.2 mmol, 2.1
equiv) was next added under stirring at room temperature,
without previous dissolution of 11b. After 1 h, the precipitate
of ephedrine hydrochloride was filtered off with a Millipore 4
µm filter, and the excess HCl was removed by several vacuum/
argon cycles. The toluene solution of 4b was used for synthetic
applications without further purification. The analysis was
carried out after purification by filtration on a short column
of silica gel with toluene as eluent: yield ) 99%; colorless
viscous oil; Rf ) 0.8 (toluene); [R]20 ) -11.1 (c 8.6, CHCl3),
D
HPLC analyses were performed on chromatographs equipped
with UV detectors. The enantiomeric excess of the optically
active derivatives was determined on Chiralcel OD and OK
columns, with a hexane/iPrOH mixture as the mobile phase,
flow rate 1 mL‚min-1, and UV detection λ ) 254 nm. Thin-
layer chromatography was performed on silica chromagel (60
for ee ) 95 ( 2%; IR (NaCl, ν cm-1) 3058-3010, 2941-2839,
2394, 1589, 1575, 1478, 1433, 1280, 1252, 1181, 1165, 1136,
1055, 1020, 900; 1H NMR (CDCl3) δ (ppm) 0.40-2.20 (3H, m),
3.63 (3H, s), 6.91 (1H, dd, J ) 4.6, 8.3), 7.11 (1H, td, J ) 2.6,
7.6), 7.39-7.61 (4H, m), 7.72-7.82 (2H, m), 7.95 (1H, ddd, J
) 1.6, 7.7, 14.9); 13C NMR (CDCl3) δ (ppm) 55.7, 112.0 (d, J PC
F
254) and visualized by UV, iodine, or permanganate treatment.
1
) 4.4), 117.6 (d, J PC ) 47.7), 121.1 (d, J PC ) 12.3), 128.5 (d,
Flash chromatography was performed on silica gel (60ACC,
6-35 µm and 35-70 µms). NMR spectra data were obtained
on DPX 250 and Avance 300-500 spectrometers, using TMS
as the internal reference for 1H and 13C NMR and 85%
phosphoric acid as the external reference for 31P NMR.
Coupling constants (J ) are reported in Hz. Melting points were
measured on a Bu¨chi 530 melting point apparatus and are
uncorrected. Optical rotations values were determined at 20
°C on a 241 polarimeter. Infrared spectra were recorded on
Equinox 55 and Vector 22. Mass spectral analyses were
performed on R10-10C, MS 700, and Concept S at the ENSCP
(Paris), ENS (Paris), and Burgundy University (Dijon), re-
spectively. The major peak m/z is reported 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 P. & M. Curie (Paris) and
Burgundy (Dijon) Universities. The X-ray structures were
determined on MACH3, CAD4, and KappaCCD diffractome-
ters at the P. & M. Curie (Paris) and Burgundy (Dijon)
Universities.
1
J P-C ) 11.5), 128.7 (d, J P-C ) 50.8), 131.1 (d, J P-C ) 12.9),
132.0 (d, J PC ) 2.6), 134.6 (d, J PC ) 14.3), 135.5 (d, J PC ) 1.8),
161.1 (d, J PC ) 2.4); 31P NMR (CDCl3) δ (ppm) +91.9 (br d,
1J PB ) 51.4); MS (EI) m/z (relative intensity) 265 (M - H+;
37Cl; 3), 263 (M - H+; 35Cl; 9), 252 (M+ - BH3; 37Cl; 33), 250
(M+ - BH3; 35Cl; 100), 215 (40), 183 (35), 107 (20), 91(40), 77
(10); HRMS (EI) calcd for C13H1235ClOP [M+ - BH3] 250.0314,
found 250.0298.
The enantiomeric purity of the o-anisylchlorophenylphos-
phine borane 4b was determined by HPLC analysis on a chiral
column of the crude PAMP borane (R)-12b, resulting from
reaction with methyllithium (vide infra).
P r ep a r a tion of (S)-(-)-Ch lor op h en yl-o-tolylp h osp h in e
Bor a n e 4c.18c The preparation, use, and purification of 4c
were carried out starting from the aminophosphine borane 11c
(2 mmol) under conditions similar to those described for 4b,
using 31.6 mL of HCl solution in toluene (0.38 M, 12 mmol, 6
equiv) instead of 11.05 mL: yield ) 87%; colorless viscous oil;
Rf ) 0.80 (toluene); [R]20 ) -8.0 (c 1.05, CHCl3), ee ) 95 (
D
5%; IR (NaCl, ν cm-1) 3050-2850, 2374, 1592, 1437, 1285,
1163, 1138, 1111, 1064, 923, 807, 745, 713, 693; 1H NMR
(CDCl3) δ (ppm) 0.60-2.20 (3H, br), 2.32 (3H, s), 7.28-7.42
P r ep a r a tion of (R)-(+)-Ch lor om eth ylp h en ylp h osp h in e
Bor a n e 4a .18a In a 250 mL two-necked flask, equipped with a
magnetic stirrer, an argon inlet, and a rubber septum was
dissolved 0.6 g (2 mmol) of the aminophosphine borane 11a
in 89 mL of toluene. A solution of HCl in toluene (0.38 M, 11.05
mL, 4.2 mmol, 2.1 equiv) was added at room temperature
under stirring, so that the final concentration of 11a was about
20 mM. The mixture was stirred for 1 h at room temperature,
and the precipitate of ephedrine hydrochloride was filtered off
with a Millipore 4 µm filter. The excess of HCl was then
removed by several vacuum/argon cycles, and the toluene
solution of chlorophosphine borane 4a was immediately used
for synthetic applications. The analysis was carried out after
purification by filtration on a short column of silica gel with
toluene as eluent: yield ) 85%; colorless viscous oil; Rf ) 0.80
(2H, m), 7.47-7.63 (4H, m), 7.71-7.80 (2H, m), 8.02 (1H, ddd,
3
J ) 1.1, 7.4, 14.8); 13C NMR (CDCl3) δ (ppm) 21.6 (d, J PC
)
1
4.8), 126.1 (d, J PC ) 12.6), 127.3 (d, J PC ) 43.0), 128.9 (d, J PC
1
) 10.9), 131.0 (d, J PC ) 48.9), 131.0 (d, J PC ) 12.3), 132.1-
132.3, 133.3 (d, J PC ) 2.1), 134.2 (d, J PC ) 18.0), 142.3 (d, J PC
) 7.9); 31P NMR (CDCl3) δ (ppm) +96.7 (d, J PB ) 50.6); MS
1
(DCI, CH4) m/z (relative intensity) 217 (68), 216 (37), 201 (M+
+ 2H - BH3 - Cl; 45), 200 (M+ + H - BH3 - Cl; 100), 199
(18), 139 (9), 123 (30), 109 (29); HRMS (DCI, CH4) calcd for
C
13H14P [M+ + 2H - BH3 - Cl] 201.0833, found 201.0835.
Anal. Calcd for C13H15BClP (248.4983): C, 62.83; H, 6.08.
Found: C, 62.60; H, 6.30.
(toluene); [R]20 ) +31.2 (c 2.4, CHCl3), for ee ) 63 ( 2%; IR
The enantiomeric excess of 4c was determined by HPLC
analysis on a chiral column of the methylphenyl-o-tolylphos-
D
(NaCl, ν cm-1) 3059-2920, 2383, 1438, 1419, 1295, 1122, 1114,
4298 J . Org. Chem., Vol. 68, No. 11, 2003

Chlorophosphine Boranes as P-Chirogenic Electrophilic Blocks
phine borane (R)-12c, resulting from reaction with methyl-
lithium (vide infra).
7.41 (7H, m), 7.45-7.63 (2H, m), 8.24-8.33 (1H, m); 13C NMR
(CDCl3) δ (ppm) 127.4, 127.5, 128.3 (d, J PC ) 31.5), 128.4 (d,
J PC ) 11.5), 129.3 (d, J PC ) 8.1), 129.7, 131.0 (d, J PC ) 12.8),
131.6 (d, J PC ) 2.5), 131.7, 132.1 (d, J PC ) 7.6), 132.4 (d, J PC
) 2.1), 134.0 (d, J PC ) 16.8), 139.3 (d, J PC ) 3.7), 146.9 (d, J PC
P r ep a r a t ion of (()-Ch lor o-1-n a p h t h ylp h en ylp h os-
p h in e Bor a n e 4d . The preparation, use, and purification of
4d were carried out starting from the aminophosphine borane
11d (2 mmol) under conditions similar to those described for
4b, using 31.6 mL of HCl solution in toluene (0.38 M, 12 mmol,
6 equiv) and 3 h reaction time: yield ) 68%; colorless viscous
oil; Rf ) 0.77 (toluene); IR (KBr, ν cm-1) 3060-2924, 2419-
2342, 1589, 1508, 1484, 1437, 1336, 1263, 1208, 1149, 1123,
1105, 1048, 1027; 1H NMR (CDCl3) δ (ppm) 0.80-2.10 (3H,
br), 7.40-7.63 (6H, m), 7.67-7.75 (2H, m), 7.92-7.95 (1H, m),
8.04-8.14 (2H, m), 8.27-8.37 (1H, m); 13C NMR (CDCl3) δ
(ppm) 124.7 (d, J PC ) 15.0), 125.2, 126.5 (d, J PC ) 6.0), 126.7,
127.3, 128.6 (d, J PC ) 50.9), 129.0 (d, J PC ) 10.9), 129.5 (d,
J PC ) 0.9), 131.2 (d, J PC ) 4.9), 131.1 (d, J PC ) 12.2), 132.3 (d,
J PC ) 2.3), 134.0 (d, J PC ) 6.6), 135.0 (d, J PC ) 2.5), 136.0 (d,
1
) 8.5); 31P NMR (CDCl3) δ (ppm) +97.1 (d, J PB ) 40.1); MS
(DCI, CH4) m/z (relative intensity) 279 (M+ + 2H + CH4
BH3 - Cl; 77), 277 (M+ + CH4 - BH3 - Cl; 100), 261 (M+
-
-
BH3 - Cl; 15), 183 (12); MS (DCI, NH3) m/z (relative intensity)
294 (24), 279 (M+ + NH3 - BH3 - Cl; 95), 278 (45), 277 (100),
263 (24), 216 (8), 201 (9), 170 (13); HRMS (DCI, NH3) calcd
for C18H14P [M+ - BH3 - Cl] 261.0833, found 261.0840. Anal.
Calcd for C18H17BClP (310.5691): C, 69.61; H, 5.52. Found:
C, 70.34; H, 6.18.
The enantiomeric excess of the chloro-o-biphenylphenylphos-
phine borane 4f was determined by HPLC analysis on a chiral
column of the methyl-o-biphenylphenylphosphine borane 12e,
resulting from reaction with methyllithium (vide infra).
1
J PC ) 20.0); 31P NMR (CDCl3) δ (ppm) +94.4 (d, J PB ) 45.7);
MS (DCI, NH3) m/z (relative intensity) 268 (M+ + H + NH3 -
Cl; 16), 253 (M+ - BH3 - Cl; 100), 237 (M+ + 2H - BH3 - Cl;
P r ep a r a tion of (R)-(+)-Ch lor ocycloh exylp h en ylp h os-
p h in e Bor a n e 4g. The preparation, use, and purification of
4g were carried out starting from the aminophosphine borane
11g (2 mmol) under conditions similar to those described for
4b, using 31.6 mL of HCl solution in toluene (0.38 M, 12 mmol,
6 equiv) and 3 h reaction time: yield ) 74%; colorless viscous
45); HRMS (DCI, NH3) calcd for C16H14P [M+ + 2H - BH3
-
Cl] 237.0833, found: 237.0833. Anal. Calcd for C16H15BClP
(284.5313): C, 67.54; H, 5.31. Found: C, 68.20; H, 5.68.
The racemization of the chloro-1-naphthylphenylphosphine
borane 4d was shown by HPLC analysis on a chiral column
of the methyl-1-naphthylphenylphosphine borane 12d , result-
ing from reaction with methyllithium (vide infra).
oil; Rf ) 0.78 (toluene); [R]20 ) +61.8 (c 1.8, CHCl3), after
D
purification; IR (KBr, ν cm-1) 3019-2860, 2402-2347, 1451,
1438, 1216, 1056, 754, 691, 669; 1H NMR (CDCl3) δ (ppm)
0.30-2.00 (3H, br), 1.10-2.25 (11H, m), 7.48-7.62 (3H, m),
P r ep a r a tion of (S)-(-)-Ch lor o-2-n a p h th ylp h en ylp h os-
p h in e Bor a n e 4e. The preparation, use, and purification of
4e were carried out starting from the aminophosphine borane
11e (2 mmol) under similar conditions as described for 4b,
using 15.8 mL of HCl solution in toluene (0.38 M, 6 mmol, 3
equiv) instead of 11.05 mL: yield ) 61%; colorless viscous oil;
7.83-7.91 (2H, m); 13C NMR (CDCl3) δ (ppm) 25.5 (d, J PC
)
1.6), 25.8, 26.0 (d, J PC ) 1.1), 26.1 (d, J PC ) 1.7), 26.3 (d, J PC
1
1
) 2.8), 42.0 (d, J PC ) 23.8), 128.7 (d, J PC ) 42.8), 128.9 (d,
J PC ) 10.7), 131.8 (d, J PC ) 11.3), 132.7 (d, J PC ) 2.6); 31P NMR
Rf ) 0.83 (toluene); [R]20 ) -7.7 (c 2.4, CHCl3), for ee ) 68 (
D
1
(CDCl3) δ (ppm) +110.5 (br d, J PB ) 51.0); MS (EI) m/z
2%; IR (KBr, ν cm-1) 2924, 2361-2338, 1653, 1559, 1506, 1457,
(relative intensity) 239 (M+ -3H; 5), 237 (M+ - 3H; 15), 228
(M+ - BH3; 40), 226 (M+ - BH3; 100), 208 (10), 191 (10), 169
(10), 145 (35), 144 (40); HRMS (EI) calcd for C12H16B37ClP [M+
- 3H] 239.0746, found 239.0757; calcd for C12H16B35ClP [M+
1
1271, 1157, 1114, 1087, 953; H NMR (CDCl3) δ (ppm) 0.80-
2.30 (3H, br), 7.45-7.99 (11H, m), 8.43 (1H, d, J ) 14.6); 13C
NMR (CDCl3) δ (ppm) 126.2 (d, J PC ) 9.8), 127.5 (d, J PC
)
48.4), 127.5, 128.0, 129.0, 129.1, 129.2 (d, J PC ) 1.2), 129.3,
- 3H] 237.0774, found 237.0779; calcd for C12H1637ClP [M+
BH3] 228.0651, found 228.0650; calcd for C12H1635ClP [M+
BH3] 226.0678, found 226.0684.
-
-
130.9 (d, J PC ) 48.9), 131.9 (d, J PC ) 12.3), 132.4 (d, J PC
3.3), 132.8 (d, J PC ) 2.4), 134.3 (d, J PC ) 15.6), 135.0 (d, J PC
)
)
2.2); 31P NMR (CDCl3) δ (ppm) +94.7 (d, 1J PB ) 45.9); MS (EI)
m/z (relative intensity) 272 (M+ - BH3; 37Cl; 30), 270 (M+
-
The enantiomeric purity of the chlorocyclohexylphenylphos-
phine borane 4g was determined from the corresponding
phosphine oxide, resulting from reaction with methyllithium,
then oxidation of the phosphine by the tert-butylhydro-
peroxide.16c The enantiomeric purity was determined by 1H
NMR and 31P NMR analysis, using the chemical shift reagent
described by Kagan [(S)-(+)-N-(3,5-dinitrobenzoyl)-R-phenyl-
ethylamine].26
BH3; 35Cl; 95), 236 (M+ + H - BH3 - Cl; 100), 233 (M+ - BH3
- Cl; 50), 204 (100), 158 (M+ - BH3 - Ph - Cl; 65); HRMS
(EI) calcd for C16H1235ClP [M+ - BH3] 270.0365, found 270.0374;
calcd for C16H1237ClP [M+ - BH3] 272.0336, found 272.0333.
The enantiomeric excess of the chloro-2-naphthylphenylphos-
phine borane 4e was determined by HPLC analysis on a chiral
column of the crude methyl-2-naphthylphenylphosphine bo-
rane 12e, resulting from reaction with methyllithium (vide
infra).
P r ep a r a tion of Ter tia r y P h osp h in e Bor a n es 12 fr om
th e Ch lor op h osp h in e Bor a n es 4. Gen er a l P r oced u r e. The
organolithium reagent (2.5 equiv) is slowly added at -78 °C
to the toluene solution of chlorophosphine borane 4 previously
prepared. It should be noted that the enantiomer (S)-12a ,
which was obtained under similar conditions from 4a , requires
an excess of o-anisyllithium to make up for the deprotonation
of the methyl substituent. The mixture is allowed to warm to
room temperature then hydrolyzed with 20 mL of water. The
aqueous layer is extracted twice with dichloromethane. The
combined organic phases were dried over magnesium sulfate,
and the solvent was evapored under reduced pressure. The
residue was purified over silica gel using toluene/petroleum
ether 7:3 as eluent.
P r ep a r a tion of (S)-(+)-Ch lor o-o-bip h en ylp h en ylp h os-
p h in e Bor a n e 4f. In a 250 mL two-necked flask, equipped
with a magnetic stirrer, an argon inlet, and a rubber septum
was introduced a solution of the aminophosphine borane 11f
(2 mmol) in dry toluene (68 mL). A solution of HCl in toluene
(0.38 M, 31.6 mL, 12 mmol, 6 equiv) was then added at room
temperature under stirring, making the final concentration
of 11f approximatively 20 mM. After 1 h, the ephedrine
hydrochloride was filtered off with a Millipore 4 µm filter, and
the excess HCl was eliminated by several vacuum/argon cycles.
The toluene solution of chlorophosphine borane 4f was used
for synthetic applications without further purification. The
analysis of 4f was carried out after purification by fast
chromatography on a short column of silica gel using toluene
as eluent: yield ) 45% (for a 50% conversion of the amino-
phosphine borane 11f); colorless viscous oil; Rf ) 0.77 (toluene);
The following phosphine boranes exhibit satisfactory ana-
lytical data in agreement with the literature: o-anisylmeth-
ylphenylphosphine boranes (S)-(+)-12a or (R)-(-)-12b,15a,18a
[R]20 ) +12.9 (c 1.9, CHCl3), for ee ) 59 ( 2%; IR (KBr, ν
D
cm-1) 2963-2853, 2409-2344, 1462, 1436, 1384, 1261, 1127,
1105, 1086, 1052, 1026, 1008; 1H NMR (CDCl3) δ (ppm) 0.70-
2.10 (3H, br), 6.83-6.86 (2H, m), 7.01-7.07 (2H, m), 7.14-
(26) Dunach, E.; Kagan, H. B. Tetrahedron Lett. 1985, 26, 2649-
2652.
J . Org. Chem, Vol. 68, No. 11, 2003 4299

Bauduin et al.
(R)-(-)-methylphenyl-o-tolylphosphine borane 12c,17e,27 (()-
oxide was obtained by a one-pot procedure previously de-
scribed, involving decomplexation of 12g with DABCO and
then oxidation with tert-butyl hydroperoxide.16c
28
methyl-1-naphthylphenylphosphine borane 12d .27,
Their enantiomeric excesses have been determined by HPLC
analysis on a Chiralcel OK Daicel column, eluent: hexane/
ethanol 8:2, 1 mL/min, λ ) 254 nm: (R)-12b, tR ) 11 min;
(S)-12a , tR ) 21 min (12a is the enantiomer of 12b); (R)-12c,
tR ) 11 min; (S)-enantiomer, tR ) 15 min; (R)-12d , tR ) 21
min; (S)-enantiomer, tR ) 30 min.
(R)-(-)-o-An isylp h en yl-o-tolylp h osp h in e 14. The prepa-
ration of the phosphine 14 from the chlorophosphine borane
4c was achieved as described above for the phosphine borane.
However, after workup, a mixture of 14 and its borane complex
1
(31P NMR δ(ppm) 19.6, J PB ) 68.5) was obtained which was
(R)-(+)-Meth yl-2-n aph th ylph en ylph osph in e bor an e 12e:
taken up in ethanol and stirred overnight to complete the
20
yield ) 46%; colorless viscous oil; Rf ) 0.61 (toluene); [R]20
decomplexation: yield ) 92%; white crystals (EtOH); Rf ) 0.68
D
) +19.0 (c 1.3, CHCl3) for 81% ee; IR (KBr, ν cm-1) 3052-
2915, 2368-2337, 1437, 1089, 1068; 1H NMR (CDCl3) δ (ppm)
0.20-1.60 (3H, br), 1.82 (3H, d, 2J PH ) 10.1), 7.10-7.90 (11H,
m), 8.05-8.30 (1H, m); 13C NMR (CDCl3) δ (ppm) 11.9 (d, 1J PC
) 40.2), 126.8 (d, J PC ) 8.6), 127.0-129.0, 130.7 (d, J PC ) 56.3),
131.2 (d, J PC ) 2.4), 131.8 (d, J PC ) 9.6), 132.8 (d, J PC ) 11.7),
133.4 (d, J PC ) 10.9), 134.3 (d, J PC ) 2.0); 31P NMR (CDCl3) δ
(toluene); mp ) 134 °C; [R]25 ) -2.88 (c 1.0, CHCl3) for 99%
D
ee; IR (KBr, ν cm-1) 3035-2830, 1580, 1570, 1457, 1434, 1271,
1240, 1165, 1021, 794, 763, 745, 699; 1H NMR (CDCl3) δ (ppm)
2.33 (3H, s), 3.68 (3H, s), 6.53-6.58 (1H, m), 6.66-6.70 (1H,
m), 6.74-6.85 (2H, m), 6.95-7.05 (1H, m), 7.08-7.30 (8H, m);
13C NMR (CDCl3) δ (ppm) 21.2 (d, 3J PC ) 21.3), 55.7, 110.2 (d,
J PC ) 1.7), 121.1, 124.7 (d, J PC ) 11.6, 125.9, 128.3-128.6,
129.9 (d, J PC ) 4.6), 130.3, 132.8, 133.7, 134.0, 134.3, 135.3-
136.0, 142.3 (d, J PC ) 26.0), 161.3 (d, J PC ) 15.7); 31P NMR
(CDCl3) δ (ppm) -23.1; MS (DCI, CH4) m/z (relative intensity)
323 (M+ + H + CH4; 15), 307 (M+ + H; 100), 215 (M+ - o-Tol;
8), 199 (M+ - o-An; 6); HRMS (DCI, CH4) calcd for C20H20OP
[M+ + H] 307.1252, found 307.1255.
1
(ppm) +11.7 (q, J PB ) 67.5); MS (DCI, CH4) m/z (relative
intensity) 263 (M+ - H; 100), 250 (M+ - BH3; 20); HRMS (DCI,
CH4) calcd for C17H17BP [M+ - H] 263.1161, found 263.1168.
The enantiomeric excess of the methyl-2-naphthylphe-
nylphosphine borane 12e was determined by HPLC analysis
on a Chiralcel OK Daicel column, eluent: hexane/ethanol 8:2,
1 mL/min, λ ) 254 nm: (R)-12e, tR ) 19 min; (S)-enantiomer,
tR ) 27 min.
The enantiomeric purity of 14 was analyzed by comparison
with a racemic sample, by 31P NMR in the presence of (+)-di-
µ-chlorobis[2-[1-(dimethylamino)ethyl]phenyl-C,N]dipalladi-
um.30
(R)-(-)-Cyclop en t a d ien ylm et h ylp h en ylp h osp h in e
Bor a n e 15. The preparation of this compound from the
chlorophosphine borane 4a was carried out as previously
described.18a
P r ep a r a tion of th e P h osp h in ite Bor a n es 16-18. (S)-
(-)-Met h yl-O-(1-b r om o-2-n a p h t h yl)p h en ylp h osp h in it e
Bor a n e 16. The preparation of the compound 16 from the
chlorophosphine borane 4a has been previously described by
our group.18c
(R)-(-)-Meth yl-o-biph en ylph en ylph osph in e bor an e 12f:
29
yield ) 41%; white powder; Rf ) 0.70 (toluene); mp ) 117
°C; [R]20 ) -42.1 (c 1.0, CHCl3) for 99% ee; IR (KBr, ν cm-1
)
D
2964-2854, 2391-2330, 1437, 1073, 1061, 895, 888; 1H NMR
2
(CDCl3) δ (ppm) 0.10-1.81 (3H, br), 1.32 (3H, d, J PH ) 10.1),
6.90 (2H, m), 7.10-7.60 (11H, m), 8.00 (1H, m); 13C NMR
1
(CDCl3) δ (ppm) 11.8 (d, J PC ) 41.0), 127.4 (d, J PC ) 11.6),
127.6, 128.4 (d, J PC ) 10.2), 128.5 (d, J PC ) 52.1), 129.5, 130.4
(d, J PC ) 2.5), 130.9 (d, J PC ) 2.4), 131.2 (d, J PC ) 9.6), 131.5
(d, J PC ) 6.7), 132.3 (d, J PC ) 57.5), 134.4 (d, J PC ) 15.3), 140.6
(d, J PC ) 3.1), 146.9 (d, J PC ) 3.8); 31P NMR (CDCl3) δ (ppm)
1
+14.4 (q, J PB ) 77.3); MS (EI) m/z (relative intensity) 290
(R)-(-)-o-An isylp h en yl-O-p -t olylp h osp h in it e Bor a n e
17. In a 50 mL two-necked flask equipped with a magnetic
stirrer and an argon inlet was added 60 mg of NaH (60% in
mineral oil, 1,5 mmol), and the mixture was washed several
times with small amounts of dry pentane. A solution of 162
mg of p-cresol (1.5 mmol) in 8 mL of dry THF was then
introduced, and the mixture was stirred at room temperature
for 4 h. The p-cresolate was then added at -78 °C to a toluene
solution of chlorophosphine borane 4b (0.5 mmol) previously
prepared as described above. The resulting mixture was
progressively warmed to room temperature and stirred over-
night. After hydrolysis, the aqueous phase was extracted
several times with CH2Cl2. The combined organic layers were
dried over MgSO4, and the solvent was removed. The residue
was purified by chromatography on neutral aluminum oxide
using toluene as eluent to yield 142 mg of the phosphinite
borane 17: yield ) 85%; colorless crystals; mp ) 68 °C; Rf )
(M+; 15), 287 (M+ - 3H; 20), 276 (M+ - BH3; 60), 275 (M+
-
BH3 - H; 100), 183 (35), 163 (15), 123 (10); HRMS (EI) calcd
for C19H20BP [M+] 290.1400, found 290.1396. Anal. Calcd for
C
19H20BP (290.1508): C, 78.65; H, 6.95. Found: C, 78.76; H,
7.03.
The enantiomeric excess of the methyl-o-biphenylphenylphos-
phine borane 12f was determined by HPLC analysis on a
Chiralcel OK Daicel column, eluent: hexane/ethanol 70:30, 1
mL/min, λ ) 254 nm: (R)-12f, tR ) 10 min; (S)-enantiomer, tR
) 30 min.
(S)-(+)-Cycloh exylm eth ylph en ylph osph in e bor an e 12g:
yield ) 46%; colorless viscous oil; Rf ) 0.61 (toluene); [R]20
)
D
+9.1 (c 1.0, CHCl3) for 80% ee; IR (KBr, ν cm-1) 2930-2854,
2376, 1449, 1437, 1300, 1119, 1064, 1001, 920, 898, 881, 746,
1
694; H NMR (CDCl3) δ (ppm) 0.10-1.40 (3H, br), 1.08-1.39
2
(6H, m), 1.53 (3H, d, J PH ) 9.9), 1.57-1.94 (5H, m), 7.40-
7.55 (3H, m), 7.65-7.73 (2H, m); 13C NMR (CDCl3) δ (ppm)
0.6 (toluene); [R]20 ) -19.2 (c 1.1, CHCl3) for 97% ee; IR (ν
D
1
cm-1) 3060-2837 (CH), 2390, 2347, 1589, 1574, 1505, 1477,
7.7 (d, J PC ) 38.8), 25.8 (d, J PC ) 1.8), 26.3 (d, J PC ) 4.8),
1
26.4 (d, J PC ) 4.2), 26.6 (d, J PC ) 4.2), 35.8 (d, J PC ) 35.8),
1462, 1431, 1279, 1263, 1203, 1164, 1019, 904, 824, 757, 733,
1
128.6 (d, J PC ) 9.7), 128.8 (d, J PC ) 52.1), 131.0 (d, J PC ) 2.4),
693; H NMR (CDCl3) δ (ppm) 0.40-1.86 (3H, br), 2.24 (3H,
1
132.0 (d, J PC ) 8.5); 31P NMR (CDCl3) δ (ppm) +16.2 (q, J PB
s), 3.59 (3H, s), 6.86-7.97 (13H, m); 13C NMR (CDCl3) δ (ppm)
20.7 (s), 55.4 (s), 111.7 (s), 112.1 (d, J PC ) 4.8), 115-136, 150.6
(d, J PC ) 5), 161.5 (d, J PC ) 2.6); 31P NMR (CDCl3) δ (ppm)
) 40.1); MS (DCI, CH4) m/z (relative intensity) 236 (M+ + CH4;
25), 217 (M+ - 3H; 75), 206 (M+ - BH3; 8), 171 (25), 154 (100),
136 (16), 124 (18); HRMS (DCI, CH4) calcd for C13H19BP [M+
- 3H] 217.1317, found 217.1324. Anal. Calcd for C13H22BP
(220.1006): C, 70.94; H, 10.07. Found: C, 70.94; H, 10.24.
The enantiomeric excess of the cyclohexylmethylphenylphos-
1
108,72 (q, J PB ) 74.4); MS (EI) m/z (relative intensity) 335
(M+ - H; 100), 323 (66), 216 (29), 215 (99), 91 (85). Anal. Calcd
(29) Hideyuki, T.; Imamoto, T. Synlett 2001, 999-1002.
(30) Dunina, V. V.; Kuz′mina, L. G.; Kazakova, M. Y.; Grishin, Y.
K.; Veits, Y. A.; Kazakova, E. I. Tetrahedron: Asymmetry 1997, 8,
2537-2545.
(31) (a) Neetkoven, U.; Kamer, P. C. J .; van Leeuwen, Piet W. N.
M.; Widhalm, M.; Spek, A. L.; Lutz, M. J . Org. Chem. 1999, 64, 3996-
4004. (b) Ewalds, R.; Eggeling, E. B.; Hewat, A. C.; Kamer, P. C. J .;
van Leeuwen, Piet W. N. M.; Vogt, D. Chem. Eur. J . 2000, 6, 1496-
1504.
1
phine borane 12g was determined by H NMR and 31P NMR
analysis of the crude methylcyclohexyl phenylphosphine oxide,
in the presence of the (S)-(+)-N-(3,5-dinitrobenzoyl)-R-phenyl-
ethylamine as the chemical shift reagent.26 The phosphine
(27) Al-Masum, M.; Kumaraswamy, G.; Livinghouse, T. J . Org.
Chem. 2000, 65, 4776-4778.
(28) Stoop, R.; Mezzetti, A.; Spindler, F. Organometallics 1998, 17,
668-675.
(32) Rippert, A. J .; Linden, A.; Hansen, H. J . Helv. Chim. Acta 2000,
83, 311-321.
4300 J . Org. Chem., Vol. 68, No. 11, 2003

Chlorophosphine Boranes as P-Chirogenic Electrophilic Blocks
for C20H22BO2P (336.1722): C, 71.46; H, 6.60; B, 3.22; P, 9.21.
Found: C, 70.01; H, 6.51; B, 3.32; P, 9.15.
The enantiomeric excess of the thiophosphinite borane 19
was determined by HPLC analysis on a Chiralcel OK Daicel
column, eluent: hexane/ethanol 9:1, by comparison with a
racemic sample: 1 mL/min, λ ) 254 nm: (S)-19, tR ) 17 min;
(R)-enantiomer, tR ) 21 min.
The enantiomeric excess and the absolute configuration of
the p-tolyl phosphinite borane (R)-17 were determined by
HPLC analysis on a Chiracel OK Daicel column of the PAMP
borane (S)-12a , resulting from reaction at low temperature
(<-50 °C) with methyllithium.
(+)-N ,N ′-Bis[(R )-o-An isylp h e n ylp h osp h in ob or a n e ]-
eth ylen ed ia m in e 20. In a two-necked flask, equipped with
a magnetic stirrer and an argon inlet, 2.2 mmol (152 mg) of
sodium hydride (60% in mineral oil) was washed twice with 2
mL of dry pentane and dissolved in 2 mL of anhydrous THF.
Ethylenediamine (1 mmol, 67 µL) was then added. The
resulting mixture was stirred at room temperature for 3.25 h.
A solution of the chlorophosphine borane (3 mmol), freshly
prepared following the previously described procedure, was
cooled at -78 °C, and a solution of the freshly prepared dianion
in 4 mL of dry THF was added dropwise. The mixture was
allowed to warm to rt for 17 h. The reaction was hydrolyzed
with 10 mL of water. THF was removed under reduced
pressure, and the aqueous layer was extracted three times
with dichloromethane. The combined organic phases were
dried over magnesium sulfate, and the solvent was removed.
The residue was purified by chromatography on silica gel,
using a mixture of toluene/petroleum ether 7:3, followed by
an 8:2 mixture, and finally toluene as eluent, to yield the bis-
aminophosphine borane as a white solid which could be
recrystallized from a CH2Cl2/hexane mixture: yield ) 89%;
(S,S)-(-)-1,2-Bis(m et h ylp h en ylp h osp h in it ob or a n e)-
ben zen e 18. In a 50 mL two-necked flask equipped with a
magnetic stirrer and an argon inlet was added 2.2 mmol of
sec-butyllithium under stirring at 0 °C to a solution of catechol
(1 mmol) in 2 mL of THF. After 1 h, THF was added to dissolve
the catecholate, and the resulting solution was cooled to -78
°C. The catecholate was then added at -78 °C to a toluene
solution of the chlorophosphine borane 4a (3 mmol), previously
prepared as described above. The resulting mixture was
progressively warmed to 0 °C and stirred for 1 h. After
hydrolysis with 5 mL of water, the aqueous phase was
extracted several times with CH2Cl2. The combined organic
layers were dried over MgSO4, and the solvents were removed.
The residue was purified by chromatography on silica gel using
toluene/petroleum ether 7:3 as eluent, yielding the phosphinite
borane 18 in 86% yield: white crystals (CH2Cl2/hexane); mp
) 135 °C; Rf ) 0.45 (toluene); [R]20 ) -64.5 (c 1.0, CHCl3);
D
IR (ν cm-1) 3056-2918, 2410-2341, 1589, 1489, 1450, 1436,
1401, 1314, 1297, 1249, 1180, 1137, 1115, 1102, 1057, 1029,
1
905, 860, 799, 768, 743, 692; H NMR (CDCl3) δ (ppm) 0.20-
white solid; Rf ) 0.22 (toluene); [R]25 ) +24.5 (c 1.0; CHCl3);
D
2
1.80 (6H, sl), 1.90 (6H, d, J HP ) 8.8), 6.90 (4H, s), 7.40-7.70
IR (KBr, ν cm-1) 3353, 3329, 3065, 2969-2838, 2371, 1590,
(6H, m), 7.80-7.95 (4H, m); 13C NMR (CDCl3): δ(ppm) 16.5
1575, 1477, 1459, 1432, 1396, 1382, 1278, 1247, 1135, 1107,
1
1
(d, J PC ) 44.1), 122.2 (d, J PC ) 4.2), 125.1, 129.0 (d, J PC
)
1098, 1066, 1044, 1020, 881, 821, 800, 762, 746, 700, 688; H
10.4), 131.2 (d, J PC ) 11.6), 131.3 (d, J PC ) 55.3), 132.8 (d, J PC
NMR (CDCl3) δ (ppm) 0.20-1.80 (6H, br), 3.00-3.30 (6H, m),
3.46 (6H, s), 6.75 (2H, dd, J ) 3.1, 8.2), 6.96 (2H, m), 7.20-
7.45 (12H, m), 7.86 (2H, ddd, J ) 1.6, 7.5, 13.5); 13C NMR
(CDCl3) δ (ppm) 44.7 (dd, J ) 1.9, 6.8), 55.5, 111.2 (d, J )
) 2.2), 143.6 (m); 31P NMR (CDCl3) δ(ppm) +119.4 (q, J PB
)
1
55.7); MS (EI, 70 eV) m/z (relative intensity) 381 (M+ - H; 5),
367 (M+ - H - BH3; 25), 243 (30), 227 (30), 217 (10), 149 (25),
139 (20), 123 (100); HRMS (DCI, CH4) calcd for C20H25B2O2P2
[M+ - H] 381.1523, found 381.1541.
4.0), 120.4 (d, J PC ) 58.7), 121.0 (d, J ) 12.7), 128.0 (d, J PC
)
10.9), 130.1 (d, J PC ) 10.9), 130.1 (d, J PC ) 2.4), 133.5 (d, J PC
1
(S )-(-)-M e t h y lp h e n y l-S -p h e n y lt h i o p h o s p h i n i t e
Bor a n e 19. In a 50 mL two-necked flask equipped with a
magnetic stirrer and an argon inlet was added 2.9 mmol of
n-butyllithium under stirring at 0 °C to a solution of thiophenol
(3 mmol) in 5 mL of THF. After 1 h, the thiophenolate was
cooled to -78 °C. It was then added at -78 °C to a toluene
solution of the chlorophosphine borane 4a (2 mmol), previously
prepared as described above. After an additional 1 h, the
mixture was hydrolyzed by water (10 mL), and the aqueous
phase was extracted several times with CH2Cl2. The combined
organic layers were dried over MgSO4, and the solvent was
removed. The residue was purified by chromatography on silica
gel using toluene as eluent, yielding the thiophosphinite
borane 19 in 87% yield: white powder; mp ) 66-69 °C; Rf )
0.65 (toluene); IR (ν cm-1) 3077-3061, 2385-2337, 1475, 1438,
1109, 1050, 1024; 1H NMR (CDCl3) δ (ppm) 0.30-1.70 (3H,
) 2.0),134.5 (d, J PC ) 69.5), 134.7 (d, J PC ) 16.3), 160.7 (d,
J PC ) 1.7); 31P NMR (CDCl3) δ (ppm) +55.29 (d, J ) 80.8).
Anal. Calcd for C28H36N2B2P2O2 (516.177): C, 65.15; H, 7.03;
N, 5.43. Found: C, 65.04; H, 7.10; N, 5.43. The enantiomeric
excess and the absolute configuration of the diaminophosphine
borane 20 were determined by HPLC analysis on a Chiracel
OK Daicel column of the PAMP borane (R)-12b, resulting from
acid methanolysis18,20 then reaction at low temperature (<-
50 °C), with methyllithium.
Ack n ow led gm en t. We thank S. Hallut, P. Herson,
B. Rebie`re, and P. Richard for the X-ray crystallographic
analyses, and A. J ung for his help in the preparation of
this manuscript. This work was supported by the French
Ministry of Research (Fund and Fellowship for C.B.),
the Burgundy Country Council and the CNRS.
2
br), 1.80 (3H, d, J HP ) 8.9), 7.20-7.67 (10H, m); 13C NMR
(CDCl3) δ (ppm) 13.7 (d, 1J CP ) 32.9), 126.9 (d, J CP ) 5.2), 129.0
(d, J CP ) 10.3), 129.5 (d, J CP ) 1.7), 130.0 (d, J CP ) 2.3), 130.5
Su p p or tin g In for m a tion Ava ila ble: Synthesis of the
aminophosphine boranes 11a -h . Structures and crystal data
for the (SP)-(+)-N-methyl[(1R,2S)(2-hydroxy-1-phenyl)ethyl]-
amino-tert-butylphenylphosphine borane 11h , (R)-o-anisylphe-
nyl-o-tolylphosphine 14, (S,S)-(-)-1,2-bis(methylphenylphos-
phinitoborane)benzene 18, and (+)-N,N′-bis[(R)-o-anisyl-
phenylphosphinoborane]ethylenediamine 20. This material is
available free of charge via the Internet at http://pubs.acs.org.
1
(d, J CP ) 45.7), 131.9 (d, J CP ) 10.5), 132.3 (d, J CP ) 2.3),
1
136.6 (d, J CP ) 2.6); 31P NMR (CDCl3) δ (ppm) 47.7 (q, J PB
)
56.4); MS (EI) m/z (relative intensity) 243 (M+ - 3H; 30), 232
(M+ - BH3; 100), 217 (M+ - BH3 - CH3; 50), 200 (25), 183
(12), 155 (12), 139 (17), 124 (60), 109 (22), 89 (22), 77 (72), 65
(42), 51 (57), 39 (37). Anal. Calcd for C13H16BPS (246.115): C,
63.44; H, 6.55; B, 4.39; P, 12.59. Found: C, 62.23; H, 6.48; B,
4.50; P, 12.62.
J O026355D
J . Org. Chem, Vol. 68, No. 11, 2003 4301