Formation of diastereoisomerically pure oxazaphospholes and their reaction to chiral phosphane-borane adducts

Article abstract of DOI:10.1002/(SICI)1522-2675(20000216)83:2<311::AID-HLCA311>3.0.CO;2-I

Starting with achiral phosphines and (1S,2S)-2-(methylamino)-1- phenylpropan-1-ol ((+)-pseudoephedrine) or (1R,2S)-2-(methylamino)-1- phenylpropan-1-ol ((-)-ephedrine), as chiral auxiliaries, diastereoisomerically pure oxazaphospholes were prepared (Schem

Full text of DOI:10.1002/(SICI)1522-2675(20000216)83:2<311::AID-HLCA311>3.0.CO;2-I

Helvetica Chimica Acta ± Vol. 83 (2000)
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Formation of Diastereoisomerically Pure Oxazaphospholes and Their
Reaction to Chiral Phosphane-Borane Adducts
1
by Andreas Johannes Rippert ), Anthony Linden, and Hans-Jürgen Hansen*
Organisch-chemisches Institut der Universität Zürich, Winterthurerstr. 190, CH-8057 Zürich
Starting with achiral phosphines and (1S,2S)-2-(methylamino)-1-phenylpropan-1-ol ((‡)-pseudoephe-
drine) or (1R,2S)-2-(methylamino)-1-phenylpropan-1-ol (( )-ephedrine), as chiral auxiliaries, diastereoiso-
merically pure oxazaphospholes were prepared (Scheme 1). The configuration at the P-atom is controlled by the
configuration at the Ph-substituted C(1) of (‡)-pseudoephedrine or ( )-ephedrine, respectively. This was
confirmed by X-ray crystal-structure analyses of two intermediate compounds in the synthesis route to the chiral
triarylborane-phosphane adducts.
1. Introduction. ± Optically active bis[phosphines] [1] such as diop [2], binap [3],
biphemp [4], chiraphos [5], bppfa [6], duphos [7], dipamp [8], or a similar, new C2-
symmetric chiral P-ligand [9] and new P^N-ligands [10] are useful for asymmetric
catalysis of bulk and laboratory-scale reactions [11]. Only dipamp and some of the new
P^P- or P^N-ligands (cf. [9] [10c]) have the P-atom as the center of chirality, whereas
all the other ligands possess an inherently chiral backbone. In transition-metal catalysis
with various kinds of substrates, atropisomeric bis[phosphanes] with additional centers
of chirality at the P-atoms, where different steric and electronic properties are tunable,
can be crucial for the attainment of high degrees of stereoselectivity. For the best
matching and selective recognition of the catalytically active transition-metal complex,
bis[phosphanes] with a chiral backbone and equipped with additional centers of
chirality at the P-atoms are of great interest. However, not many compounds of this
class have been reported so far [8][9][12]. Therefore, it is important to further develop
accessibility to asymmetrically substituted phosphines. Since phosphanes, due to their
oxophilicity, exhibit a strong tendency in air to form the corresponding phosphane
oxides, and because of their lability in the presence of aryl- or alkyl halides, it is
necessary to perform their synthesis with protective groups. In recent years, there has
been a rebirth in the use of BH3 as a protective group for phosphines [13], even though
the extraordinary stability and inertness of the P B bond has long been known [14].
Â
Using ( )- and (‡)-ephedrine as chiral auxiliaries, Juge et al. developed an elegant and
flexible synthesis for enantiomerically pure phosphines [15]. However, to the best of
our knowledge, the use of the commercially available (‡)-pseudoephedrine, with the
(1S,2S)-configuration, which is a diastereoisomer of ( )-ephedrine (opposite config-
uration at C(1)), has not been reported so far. In this work, we show that the control of
the formation of the diastereoisomerically pure oxazaphospholes from the two b-amino
alcohols is controlled by the Ph-substituted C(1) atom of both stereoisomers.
1
)
Part of the Ph. D. thesis of A.J.R., University of Zurich.

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Helvetica Chimica Acta ± Vol. 83 (2000)
2. Results and Discussion. ± The reaction of N,N,N',N'-tetraethyl-P-phenylphos-
phinediamine, (‡)-pseudoephedrine or ( )-ephedrine, and the dimethylsulfide-borane
complex in toluene yielded the corresponding crystalline and diastereoisomerically
pure heterocycles (2S,4S,5S)-2,3,4,5-tetrahydro-3,4-dimethyl-2,5-diphenyl-1,3,2-oxaza-
phosphole P-borane (1/1) ((S,S,S)-1; up to 95% isolated yield) and (2R,4S,5R)-
2,3,4,5-tetrahydro-3,4-dimethyl-2,5-diphenyl-1,3,2-oxazaphosphole P-borane (1/1)
((R,S,R)-2; 82%), respectively (cf. Scheme 1) [15].
Scheme 1
The two diastereoisomers (S,S,S)-1 and (R,S,R)-2 were not distinguishable on the
1
basis of their H-NMR spectra, but the chemical shifts and coupling constants in the
31P- and 11B-NMR spectra were distinctly different (see Table 1). Also, the opposite
sign of the [a]2D5 values in CHCl3 for (S,S,S)-1 ( 10.0) and ((R,S,R)-2 (‡4.5) confirmed
that they were diastereoisomers. An X-ray crystal-structure analysis has been published
for (R,S,R)-2 [16]. It revealed the trans-relationship between the two Ph groups at P(2)
and C(5) and led to the conclusion that the sense of chirality at the P-atom is (R). As a
consequence, a trans-relationship between the Ph substituents in its diastereoisomer,
(S,S,S)-1, would require the (S)-configuration at P(2).
Unfortunately, no suitable crystals of (S,S,S)-1 could be obtained for an X-ray
crystal-structure analysis. However, the configuration at P(2) could be deduced from
the X-ray crystal-structure analyses of compounds that were derived from (S,S,S)-1,
because it is known that, in chiral phosphane-borane compounds, the P O linkage can
be cleaved with retention of the configuration at the P-atom [13] by using aryl- or
alkyllithium reagents (cf. Scheme 1). Thus, (S,S,S)-1 and (R,S,R)-2 reacted with either
o-anisyllithium or t-BuLi to give the corresponding o-anisyl (ˆ2-methoxyphenyl)
derivatives (R,S,S)-3 and (S,R,S)-5, respectively, or their tert-butyl analogues (S,S,S)-4
and (R,R,S)-6, respectively, in high yields (93 ± 97%; Scheme 1).

Helvetica Chimica Acta ± Vol. 83 (2000)
313
Table 1. Chemical Shifts and Coupling Constants in the 31P{H}- and 11B{H}-NMR Spectra of Compounds 1 ± 8
Compound
d(31P)a) [ppm]
1J(31P, 11B)b) [Hz]
d(11B)c) [ppm]
1J(31P, 11B)d) [Hz]
(S,S,S)-1
139.9
133.0
71.5
85.5
71.1
86.5
107.0
18.4
75.8
74.0
55.2
68.0
59.0
67.0
64.5
54.0
41.1
40.3
36.9
39.4
36.8
20.1
39.8
37.1
75.2
74.0
56.5
69.5
58.7
68.0
65.0
55.3
(R,S,R)-2
(R,S,S)-3
(S,S,S)-4
(S,R,S)-5
(R,R,S)-6
(R)-7/(S)-7
(R)-8/(S)-8
a
)
31P-NMR Chemical shifts relative to H3PO4 as external standard.
b) The signals for the P-atom are q.
c
)
11B-NMR Chemical shifts relative to BF3 ´ OEt2 as external standard.
d) The signals for the B-atom are d.
1
The H-NMR spectra of these compounds clearly showed their diastereoisomeric
relationship (e.g., (R,S,S)-3 and (S,R,S)-5 on one hand and (S,S,S)-4 and (R,R,S)-6 on
the other hand). As an example, the singlet of Me C(2) in the compounds derived
from (‡)-pseudoephedrine appears at 0.8 ppm, whereas it is found at 1.2 ppm for the
compounds derived from ( )-ephedrine (cf. Exper. Part). In contrast to their
precursors, (S,S,S)-1 and (R,S,R)-2, the pairwise diastereoisomeric relationship of the
new products 3 ± 6 is not obvious from their 31P- and 11B-NMR data (see Table 1).
It was possible to grow suitable crystals of (R,S,S)-3 for an X-ray crystal-structure
analysis (Fig. 1, and Tables 2 and 3). This experiment independently confirmed the
absolute configuration of the molecule and revealed that the configuration at the P-
atom was indeed R (see Fig. 1). In turn, this finding requires the (S)-configuration at
P(2) in (S,S,S)-1, since the described substitution reactions occur with retention of
configuration at the P-atom2).
The observed bond lengths between the P-atom and its ligands in (R,S,S)-3 are in
good agreement with other structures of a similar type (cf. [15b][16]). There is a high
rotational barrier around the P B bond (cf. [14]) due to hyperconjugation of the B
H
orbitals with the d-orbitals of the P-atom. This effect should cause a high dipole
moment in such compounds. Indeed, they possess high boiling and melting points
compared with their phosphane and borane analogues [14c].
The molecular structure of (R,S,S)-3 revealed two intramolecular H-bonds. The H-
atom of the OH group of the (‡)-pseudoephedrine moiety interacts with the N-atom
and the O-atom of the anisyl moiety (cf. Fig. 1). These H-bonds are part of an anellated
five- and six-membered ring system with the H ´´´ N bond common to both rings.
Because of this H-bonding, the H-atoms at C(1) and C(2) are in an anti-periplanar
arrangement to each other (for numbering, see Fig. 1). Their dihedral angle is 171(2)8
in the crystal structure. The 1H-NMR spectrum (CDCl3) of (R,S,S)-3 discloses a vicinal
coupling constant of 9.1 Hz between these two H-atoms, which leads to a dihedral
angle of 1708 according to the Karplus-Conroy equation [17], in excellent agreement
3
with the solid-state structure. As expected, (S,R,S)-5 shows J(1,2) ˆ 5.5 Hz, which
2
)
Note that the priority rules of the CIP notation of absolute configurations lead in our cases to a formal
change of the sense of chirality at the P-atom.

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Fig. 1. Molecular structure of (R,S,S)-3. Arbitrary numbering of the atoms; 50% probability ellipsoids.
Table 2. Bond Lengths [pm] and Angles [8] around the P-Atom of (R,S,S)-3a)
P
P
P
P
B
N
C(11)
C(18)
192.3 (2)
167.0 (2)
182.1 (2)
182.4 (2)
N
N
N
C(11)
C(18)
C(11)
P
P
P
B
C(11)
C(18)
P
P
P
112.9(1)
105.20(9)
109.24(8)
113.4(1)
111.6(1)
103.96(8)
B
B
C(18)
a) E.s.d. in parentheses.
Table 3. Interatomic Distances [pm] and Angles [8] at the H-Bonded OH Group of (R,S,S)-3a)
O(1)H ´´´ O(2)
O(1)H ´´´ N
O(1) ´´´ O(2)
O(1) ´´´ N
218 (3)
217 (2)
296.0 (3)
273.2 (2)
O(1) H ´´´ O(2)
O(1) H ´´´ N
O(2) ´´´ H ´´´ N
152(2)
123(2)
85.6(9)
110.8(7)
137.3(6)
76.2(7)
O(1)H ´´´ N
P
O(1)H ´´´ O(2) C(12)
O(1)H ´´´ N C(2)
a) E.s.d. in parentheses.

Helvetica Chimica Acta ± Vol. 83 (2000)
315
would correspond with a dihedral angle for H C(1) C(2) H of 408. Molecular
models demonstrate that this dihedral angle, which is controlled by the (R)-
configuration at C(1), will also allow intramolecular H-bonding between the OH
group at C(1) and N C(2) as well as MeO of the o-anisyl moiety.
Evidence for H-bonding was also found for (S,S,S)-4 and (R,R,S)-6. The dihedral
angles of H C(1) C(2) H, calculated from 3J(1,2) of their 1H-NMR spectra, are 1808
for (S,S,S)-4 (3J ˆ 9.6 Hz) and 508 for (R,R,S)-6 (3J ˆ 3.4 Hz). In these compounds,
only the five-membered ring with N C(2) can be formed upon H-bonding.
By acid-catalyzed methanolysis at room temperature, the P N bond could easily be
cleaved in (R,S,S)-3 and (S,R,S)-5 to form (S)-7 and (R)-7, respectively, in excellent
yields (97%). By contrast, (S,S,S)-4 and (R,R,S)-6 showed no reaction at all, even after
prolonged times under reflux conditions. The starting materials could be isolated
without any evidence of decomposition. With a t-Bu substituent at the P-atom, it is inert
to further substitution reactions (ꢀneopentyl ruleꢁ) (see Scheme 2; (R,S,S)-3 vs. (R,S,S)-
4). It is noteworthy that the reaction of (R,S,S)-3 and (S,R,S)-5 with MeOH in acidic
media restores the chiral auxiliaries (‡)-pseudoephedrine and ( )-ephedrine, which
can be recycled. The methanolysis proceeds with inversion of the configuration at the
P-atom. Very characteristic for (S)-7 and (R)-7 is the observed 3J(H,P) value (between
the H-atoms of the MeO group and the P-atom) of 12.1 Hz. The antipodal character
and enantiomeric purity of (S)-7 and (R)-7 are obvious from their [a]2D5 values.
Scheme 2
The newly formed P O bond in (S)-7 and (R)-7 can be transformed stereospecifi-
cally into P C bonds by using aryl- or alkyllithium reagents, again with retention of the
configuration at the P-atom. For example, (3,4-dimethoxyphenyl)lithium reacted with
(S)-7 or (R)-7 to give (R)-8 or (S)-8, respectively, in yields up to 80% (Scheme 3)2).
The new phosphane-borane adducts with three C-substituents at the P-atom are
characterized by their d(31P) value of ca. 20 ppm. In cases where P X bonds are
involved, e.g., X ˆ N or O, d(31P) values are above 100 ppm (cf. Table 1). However,
remarkable chemical-shift differences are not found in the 11B-NMR spectra of our
compounds. They all exhibit d(11B) values of ca. 38 ppm (see Table 1).

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Scheme 3
Fig. 2. Molecular structure of (S)-8. Arbitrary numbering of the atoms; 50% probability ellipsoids.
Compound (S)-8 crystallized well from hexane/AcOEt solution so that it could be
subjected to an X-ray crystal-structure determination (Fig. 2 and Table 4). The
geometric parameters of (S)-8 are in good agreement with those of other phosphane-
borane adducts [16], as well as with those of (R,S,S)-3. Remarkable is that all MeO
groups are pointing away from the borane group. This crystal effect may provide
evidence for the fact that a BH3 moiety bound to the phosphane carries a high
proportion of the electron density of the B P bond. The absolute configuration of (S)-
8 could be confirmed by the X-ray analysis, which also ascertained the stereochemical
outcome of the whole reaction sequence starting with (R,S,S)-2, where the chiral
auxiliary has been ( )-ephedrine.
3. Conclusion. ± It has been shown that (‡)-pseudoephedrine can be used as a chiral
auxiliary to form enantiomerically pure phosphane-borane adducts with different
substitution patterns. The opposite configuration at the P-atom can be obtained with
( )-ephedrine as the chiral auxiliary [15]. With (‡)-pseudoephedrine as a chiral

Helvetica Chimica Acta ± Vol. 83 (2000)
317
Table 4. Bond Lengths [pm] and Angles [8] at the P-Atom of (S)-8a)
P
P
P
P
B
193.3 (2)
181.8 (2)
181.0 (1)
181.1 (2)
C(1)
C(1)
C(1)
C(8)
C(8)
C(16)
P
P
P
P
P
B
112.06(8)
106.03(7)
108.50(7)
113.18(8)
107.70(7)
109.17(8)
C(1)
C(8)
C(16)
C(8)
C(16)
B
C(16)
B
P
a) E.s.d. in parentheses.
auxiliary, an improvement in the isolated yield (95% vs. 82% with ( )-ephedrine) of
the diastereoisomerically and enantiomerically pure oxazaphospholes was achieved.
Furthermore, it was found that a trans-relationship of the Ph substituents in the
diastereoisomerically pure oxazaphospholes is crucial for control of the stereoselection.
The smaller groups at other positions have no significant influence on the creation of a
single configuration at the P-atom by the chiral auxiliaries that have been used.
If a t-Bu substituent in an enantiomerically pure phosphane is required, and (‡)-
pseudoephedrine or ( )-ephedrine are to be used as the chiral auxiliaries, they have to be
introduced in the final step. Both enantiomers of such phosphanes are only accessible
when both configurations at the P-atom in the five-membered ring of the oxazaphos-
pholes (see (S,S,S)-1 and (R,S,R)-2 in Scheme 1) are synthetically available. In other
cases, where a reversal of the sequence of the substitution reactions at the P-atom is
possible, working in the one or the other diastereoisomeric series would be sufficient.
We thank Prof. W. von Philipsborn and his former co-workers for 11B- and 31P-NMR spectra, Prof. M. Hesse
and his co-workers for mass spectra, and the late H. Frohofer for elemental analyses. The financial support of
this work by the Swiss National Science Foundation is gratefully acknowledged.
Experimental Part
1. General. All reactions were performed under N2. N,N,N',N'-Tetraethyl-P-phenylphosphinediamine was
synthesized from P,P-dichlorophenylphosphine (Fluka, pract.) and Et2NH (Fluka, purum) in Et2O. THF
(Fluka, puriss. p.a.) was purified over Al2O3 (Act. I). Toluene, AcOEt, hexane, i-PrOH, and Et2O were distilled
prior to use. ( )-Ephedrine (ˆ(1R,2S)-2-(methylamino)-1-phenylpropan-1-ol; Fluka, purum), (‡)-pseudoe-
phedrine (ˆ(1S,2S)-2-(methylamino)-1-phenylpropan-1-ol; Fluka, purum), BH3 ´ SMe2 (Fluka), t-BuLi (Fluka,
pract. ca. 1.4m in pentane), 2-bromoanisole (ˆ1-bromo-2-methoxybenzene; Fluka, purum), Li sand (Alfa, in
oil; washed with hexane prior to use), and 4-bromoveratrole (ˆ4-bromo-1,2-dimethoxybenzene; Fluka, purum)
were used without further purification. Flash-column chromatography (FC): silica gel (230 ± 400 mesh, ASTM).
M.p.: Büchi apparatus (model FP5); uncorrected. [a]D: Perkin Elmer 241 MC polarimeter. NMR Spectra:
Bruker AC 300 (1H), ARX 300 (1H), and AM 400 spectrometers (11B, 31P) (11B: 128 MHz, 31P: 161 MHz). d(H)
values relative to internal Me4Si, d(B) and d(P) values relative to BF3 ´ OEt2 and H3PO4, resp., as external
standards; J in Hz; f.s.: fine structure. MS: Finnigan instrument model MAT SSQ 700; EI at 70 eV; ions in m/z
(rel. %).
3
2. Crystal-Structure Determinations of (R,S,S)-3 and (S)-8 ). The data collection and refinement
parameters are summarized in Table 5. All measurements were conducted on a Rigaku AFC5R diffractometer
fitted with a 12-kW rotating anode generator. The intensities were collected during w/2q scans, and three
3
)
Crystallographic data (excluding structure factors) for the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as supplementary publication No. CCDC-
134227 and CCDC-134228 for (R,S,S)-3 and (S)-8, resp. Copies of the data can be obtained, free of charge,
on application to the CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: ‡44-(0)1223-336033, e-mail:
deposit@ccdc.cam.ac.uk).

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Table 5. Crystallographic Data of (R,S,S)-3 and (S)-8
(R,S,S)-3
(S)-8
Crystallized from
Empirical formula
Formula weight
CHCl3
C23H29BNO2P
393.27
hexane/AcOEt
C21H24BO3P
366.20
Crystal color, habit
Crystal dimensions [mm]
Temp. [K]
Radiation, wavelength [Š]
Crystal system
colorless, prism
0.20 Â 0.30 Â 0.33
173 (1)
MoKa, 0.71069
orthorhombic
P212121
4
colorless, prism
0.20 Â 0.23 Â 0.50
173 (1)
MoKa, 0.71069
orthorhombic
P212121
Space group
Z
4
Reflections for cell determination
2q Range for cell determination [8]
Unit cell parameters: a [Š]
b [Š]
24
24 ± 40
23
32 ± 36
14.658(5)
16.715(8)
8.713(5)
2135(1)
1.224
12.984(2)
14.2447(9)
10.780(1)
1993.8(3)
1.220
c [Š]
V [Š3]
3
Dx [g cm
]
1
m [mm
]
0.141
0.149
2q(max) [8]
55
60
Total reflections measured
Symmetry-independent reflections
Reflections used (I > 3s(I))
Parameters refined
R
5913
4466
3616
369
6263
4929
4346
331
0.0313
0.0306
wR
0.0268
0.0298
Goodness of fit
1.297
1.575
Final Dmax/s
D1 (max; min) [e Š
0.0007
0.15; 0.19
0.01
0.23; 0.19
3
]
standard reflections measured after every 150 reflections showed negligible variation in intensity. Each data
collection included the measurement of the Friedel opposites of all unique reflections with 2q < 508. The
intensities were corrected for Lorentz and polarization effects, but not for absorption and equivalent reflections,
other than Friedel pairs, were merged. Each structure was solved by direct methods with SHELXS86 [18], which
revealed the positions of all non-H-atoms. The non-H-atoms were refined anisotropically. The H-atoms were
located in difference-electron-density maps, and their positions were refined together with individual isotropic
displacement parameters. Corrections for secondary extinction were not applied. All refinements were carried
out on F with full-matrix least-squares procedures, which minimized the function Sw(j Fo j j Fc j )2, where 1/w ˆ
[s2(Fo) ‡ (0.005Fo)2]. Neutral-atom scattering factors for non-H-atoms were taken from [19a] and the scattering
factors for H-atoms from [20]. Anomalous dispersion effects were included in Fc [21]; the values for f ' and f ''
were taken from [19b]. All calculations were performed using the TEXSAN [22] crystallographic software
package, and the figures were produced with ORTEPII [23].
For each structure, the absolute configuration was determined by refinement [24] of the completed model
together with the absolute structure parameter [25], which refined to values of 0.02(8) and 0.09(7) for (R,S,S)-3
and (S)-8, resp., and thereby confirmed that the refined coordinates for each structure represent the true
enantiomorph.
3. Syntheses. 3.1. (2S,4S,5S)-2,3,4,5-Tetrahydro-3,4-dimethyl-2,5-diphenyl-1,3,2-oxazaphosphole ± P-borane
(1/1) ((S,S,S)-1). In a three-neck round bottle, a mixture of (‡)-pseudoephedrine (10.0 g, 60.5 mmol) and
N,N,N',N'-tetraethyl-P-phenylphosphinediamine (15.5 ml, 60.5 mmol) in toluene (300 ml) was refluxed over-
night. The reaction was monitored by measuring the pH, corresponding to the evolution of Et2NH. After 16 h,
no further Et2NH could be detected. The slightly yellow soln. was cooled to r.t., and BH3 ´ SMe2 (5.8 ml,
60.5 mmol) in toluene (25 ml) was added dropwise. Then, stirring was continued for further 5 h. The solvent was
evaporated, and the yellowish, oily residue was crystallized from hexane/i-PrOH, to give (S,S,S)-1 (16.4 g, 95%).

Helvetica Chimica Acta ± Vol. 83 (2000)
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Colorless crystals. M.p. 103.9 ± 104.78 (hexane/i-PrOH). [a]D25
ˆ
10.0 (c ˆ 0.2, CHCl3). 1H-NMR (300 MHz,
CDCl3): 7.30 ± 7.85 (m, 10 arom. H); 5.60 (dd, 3J(4,5) ˆ 9.1, 3J(5,P) ˆ 2.9, H C(5)); 3.68 (sext. with f.s., 3J(4,5) ˆ
9.1, 3J(4,Me C(4)) ˆ 6.5, 3J(4,P) ˆ 4.2, 4J(4,Me N) ˆ 11.0, H C(4)); 2.68 (d, 4J(4,Me N) ˆ 11.0, MeN); 1.7 ±
0.2 (br. q, BH3); 0.83 (d, 3J(4,Me C(4)) ˆ 6.5, Me C(4)). 1H-NOE (400 MHz, CDCl3): 5.60 (dd, H C(5)) !
3.68 (s, H C(4)); 2.68 (MeN) ! 3.68 (m, H C(4)); 0.83 (Me C(4)) ! 5.60 (m, H C(5)), 3.68 (s, H C(4)).
11B-NMR (CDCl3): 41.1 (d, 1J(B,P) ˆ 75.2, BH3). 31P-NMR: 139.9 (d, 1J(B,P) ˆ 75.8, P(2)).
3.2. (2R,4S,5R)-2,3,4,5-Tetrahydro-3,4-dimethyl-2,5-diphenyl-1,3,2-oxazaphosphole P-borane (1/1)
((R,S,R)-2 (cf. [15]). As described in 3.1, with ( )-ephedrine (12.73 g, 78 mmol), N,N,N',N'-tetraethyl-P-
phenylphosphinediamine (19.5 ml, 78 mmol) in toluene (500 ml), and BH3 ´ SMe2 (7.4 ml, 78 mmol) in toluene
(32 ml). Crystallization from hexane/i-PrOH gave (R,S,R)-2 (18.24 g, 82%). White, microcrystalline compound.
M.p. 104.7 ± 105.78 (hexane/i-PrOH). [a]D25 ˆ ‡4.5 (c ˆ 0.1, CHCl3). 1H-NMR (300 MHz, CDCl3): 7.30 ± 7.85
(m, 10 arom. H); 5.60 (dd, 3J(4,5) ˆ 9.1, 3J(5,P) ˆ 2.9,
H
C(5)); 3.68 (sext. with f.s., 3J(4,5) ˆ 9.1,
3J(4,Me C(4)) ˆ 6.5, J(4,P) ˆ 4.2, J(4,Me N) ˆ 11.0, H C(4)); 2.67 (d, 4J(4,Me N) ˆ 11.0, MeN); 1.7 ± 0.2
(br. q, BH3); 0.82 (d, 3J(4,Me C(4)) ˆ 6.5, Me C(4)). 1H-NOE (400 MHz, CDCl3): 5.60 (dd, H C(5)) ! 3.68
(s, H C(4)); 2.67 (MeN) ! 3.68 (m, H C(4)); 0.82 (Me C(4)) ! 5.60 (m, H C(5)), 3.68 (s, H C(4)). 11B-
NMR (CDCl3): 40.3 (d, 1J(B,P) ˆ 74, BH3). 31P-NMR: 133.0 (d, 1J(B,P) ˆ 74, P(2)).
3
4
3.3. (1S,2S)-2-{[(R)-(2-Methoxyphenyl)phenylphosphanyl]methylamino}-1-phenylpropan-1-ol ± P-borane
(1/1) ((R,S,S)-3) (cf. [15]). To
a
soln. of (S,S,S)-1 (1.424 g, 5 mmol) in THF (20 ml) at
788, 2-
methoxyphenyllithium (from 2-bromoanisole (0.62 ml, 5 mmol) and Li sand (35 mg, 5 mmol)) in THF (5 ml)
were added dropwise during 10 min. The mixture was stirred for 30 min at 788, then cooling was stopped. As
soon as the mixture reached r.t., the reaction was quenched by addition of H2O (1 ml). After extraction with
Et2O (3 Â 20 ml), the org. phase was dried (MgSO4), and the solvent was removed, and the residue was purified
by FC (toluene/AcOEt 10 :1). Upon standing, the clear soln. solidified to a white mass: (R,S,S)-3 (1.91 g, 97%).
From CHCl3, colorless crystals were obtained. M.p. 148.6 ± 149.18 (CHCl3). Rf (toluene/AcOEt 10 :1): 0.40.
[a]2D5 ˆ ‡16 (c ˆ 0.1, CH2Cl2). 1H-NMR (300 MHz, (D6)DMSO): 7.68 ± 7.00 (m, 14 arom. H); 5.15
(d, 3J(1,HO) ˆ 3.6, OH); 4.52 (dd, 3J(1,2) ˆ 8.3, 3J(1,OH) ˆ 3.5, H C(1)); 4.08 (m, H C(2)); 3.48 (s, MeO);
2.42 (d, 4J(2,MeN) ˆ 8.05, MeN); 1.7 ± 0.2 (br. q, BH3); 0.86 (d, 3J(2,Me C(2)) ˆ 6.7, Me C(2)). 1H-NMR
(300 MHz, CDCl3): 7.80 ± 6.95 (m, 14 arom. H); 4.45 (d, 3J(1,2) ˆ 9.6, H C(1)); 4.22 (m, H C(2)); 3.93
(s, MeO); 2.64 (d, 4J(2,MeN) ˆ 7.6, MeN); 2.16 (br. s, OH); 1.7 ± 0.2 (br. q, BH3); 0.81 (d, 3J(2,Me C(2)) ˆ 6.7,
Me C(2)). 11B-NMR (CDCl3): 36.9 (d, 1J(B,P) ˆ 56.5, BH3). 31P-NMR: 71.5 (d, 1J(B,P) ˆ 55.2). CI-MS
‡
(NH3): 394.2 (100, [M ‡ 1] ). Anal. calc. for C23H29BNOP (393.28): C 70.24, H 7.43, N 3.56; found: C 70.35,
H 7.55, N 3.61.
3.4. (1S,2S)-{[(S)-(tert-Butyl)phenylphosphanyl]methylamino}-1-phenylpropan-1-ol ± P-borane (1/1)
((S,S,S)-4). According to 3.3, with (S,S,S)-1 (1.424 g, 5 mmol) in THF (20 ml) and t-BuLi (3.7 ml, 5 mmol of
a 1.4m soln.). The clear oil solidified upon standing: (S,S,S)-4 (1.65 g, 94%). M.p. 136.8 ± 138.38. Rf (toluene/
AcOEt 10 :1): 0.50. 1H-NMR (300 MHz, (D6)DMSO): 7.84 ± 7.24 (m, 10 arom. H); 5.31 (d, 1J(1,OH) ˆ 3.5,
OH); 4.51 (dd, 3J(1,2) ˆ 8.8, 3J(1,OH) ˆ 3.5, H C(1)); 3.94 (m, H C(2)); 2.58 (d, 4J(2,MeN) ˆ 6.87, MeN);
1.29 (d, 3J(Me3C,P) ˆ 14.0, Me3C); 1.7 ± 0.2 (br. q, BH3); 0.82 (d, 3J(2,Me C(2)) ˆ 6.6, Me C(2)). 1H-NMR
(300 MHz, CDCl3): 7.90 ± 7.23 (m, 10 arom. H); 4.46 (d, 3J(1,2) ˆ 9.6, H C(1)); 4.10 (m, H C(2)); 2.95 (br. s,
OH); 2.78 (d, 4J(2,MeN) ˆ 7.5, MeN); 1.7 ± 0.2 (br. q, BH3); 1.38 (d, 3J(Me3C,P) ˆ 14.2, Me3C); 0.86
(d, 3J(2,Me C(2)) ˆ 6.6, Me C(2)). 11B-NMR (CDCl3):
(d, 1J(B,P) ˆ 68.0).
39.4 (d, 1J(B,P) ˆ 69.5, BH3). 31P-NMR: 85.5
3.5. (1R,2S)-2-{[(S)-(2-Methoxyphenyl)phenylphosphanyl]methylamino}-1-phenylpropan-1-ol P-borane
(1/1) ((S,R,S)-5) (cf. [10c][15]). According to 3.3. The clear oil solidified: (S,R,S)-5 (0.366 g, 93%). M.p.
139.6 ± 140.28. Rf(toluene/AcOEt 10 :1): 0.42. 1H-NMR (300 MHz, CDCl3): 7.60 ± 6.80 (m, 14 arom. H); 4.89
(d, 3J(1,2) ˆ 5.5, H C(1)); 4.32 (m, H C(2)); 3.56 (s, MeO); 2.53 (d, 4J(2,MeN) ˆ 8.1, MeN); 2.10 (br. s, OH);
1.7 ± 0.2 (br. q, BH3); 1.21 (d, 3J(2,Me C(2)) ˆ 6.8, Me C(2)). 11B-NMR (CDCl3): 36.8 (d, 1J(B,P) ˆ 58.7,
BH3). 31P-NMR: 71.1 (d, 1J(B,P) ˆ 59.0).
3.6. (1R,2S)-2-{[(R)-(tert-Butyl)phenylphosphanyl]methylamino}-1-phenylpropan-1-ol P-borane (1/1)
((R,R,S)-6). According to 3.3, with (R,S,R)-2 (0.285 g, 1 mmol) in THF (5 ml), and t-BuLi (7.2 ml; 1.4m in
pentane): (R,R,S)-6 (0.315 g, 93%). M.p. 139.5 ± 140.58. Rf (toluene/AcOEt 10 :1) 0.51. 1H-NMR (300 MHz,
CDCl3): 7.20 ± 7.70 (m, 10 arom. H); 5.18 (d, 3J(1,2) ˆ 3.4, H C(1)); 4.14 (m, H C(2)); 2.88 (d, 4J(2,MeN) ˆ
6.36, MeN); 2.08 (br. s, OH); 1.32 (d, 3J(Me3C,P) ˆ 13.8, Me3C); 1.7 ± 0.2 (br. q, BH3); 1.16 (d, 3J(2,Me C(2)) ˆ
7.0, Me C(2)). 11B-NMR (CDCl3): 20.1 (d, 1J(B,P) ˆ 68.0, BH3). 31P-NMR: 86.5 (d, 1J(B,P) ˆ 67.0).
3.7. (R)- or (S)-Methoxy(2-methoxyphenyl)phenylphosphane borane (1/1) ((R)- or (S)-7) (cf. [10c][15]).
In a two-neck flask (25 ml), (R,S,S)-3 (0.64 g, 1.63 mmol) or (S,R,S)-5 (0.64 g, 1.63 mmol) was dissolved in

320
Helvetica Chimica Acta ± Vol. 83 (2000)
MeOH (15 ml). To this soln., conc. H2SO4 was added (0.16 g, 1.63 mmol), and the mixture was stirred at r.t. for
16 h. At the beginning of the reaction, a white precipitate appeared, which dissolved during the reaction. The
mixture was extracted with CH2Cl2 (30 ml) and H2O (with 1 ml of 20% H2SO4). The aq. phase was extracted
with CH2Cl2 (2 Â 30 ml). The combined org. phase was washed with NaHCO3 (2 Â 20 ml). The org. phase was
dried (MgSO4), and the solvent was removed to yield (R)-7 or (S)-7 (0.411 g, 97%). Colorless oils. Rf (hexane/
1
AcOEt 3 :1) 0.35. [a]D25
ˆ
25.8 (c ˆ 0.1, CHCl3) for (R)-7; [a]2D5 ˆ ‡26.1 (c ˆ 0.1, CHCl3) for (S)-7. H-NMR
(300 MHz, CDCl3) 7.93 ± 6.85 (m, 9 arom. H); 3.73 (d, 3J(MeO,P) ˆ 12.1, MeOP); 3.62 (s, MeO); 1.7 ± 0.6 (br. q,
BH3). 11B-NMR (CDCl3): 39.8 (d, 1J(B,P) ˆ 65.0, BH3). 31P-NMR: 107.0 (q, 1J(B,P) ˆ 64.5).
3.8. (R)- or (S)-(3,4-Dimethoxyphenyl)(2-methoxyphenyl)phenylphosphane ± borane (1/1) ((R)-7 or (S)-
8). In a two-neck flask BuLi (1.4 ml, 2.2 mmol; 1.6m in hexane) was added dropwise to a soln. of 4-bromo-1,2-
dimethoxybenzene (0.28 ml, 2.25 mmol) in THF (2 ml) at 788. The mixture was stirred for 1 h at 788. Then,
(R)-8 or (S)-8 (0.48 g, 1.85 mmol) was added dropwise. The mixture was allowed to warm to 08 and kept at this
temp. for 2 h. Then, the reaction was quenched by addition of H2O (1 ml). After extraction with Et2O (3 Â
30 ml) and H2O, the org. phase was dried (MgSO4). The solvent was removed, and the residue was purified by
FC (hexane/AcOEt 3 :1): (R)-8 or (S)-8 (0.49 g, 80%). Colorless crystals. (S)-8 was crystallized from hexane/
AcOEt. M.p. 140.8 ± 141.68 (CHCl3). Rf (hexane/AcOEt 3 :1) 0.12. [a]2D5 ˆ ‡43.5 (c ˆ 0.5, CHCl3) for (S)-8;
[a]2D5
ˆ
43.4 (c ˆ 0.5, CHCl3) for (R)-8. H-NMR (300 MHz, CDCl3): 7.60 ± 6.84 (m, 12 arom. H); 3.90, 3.81,
1
3.57 (3s, MeO); 1.7 ± 0.5 (br. q, BH3). 11B-NMR (CDCl3): 37.1 (d, 1J(B,P) ˆ 55.3, BH3). 31P-NMR: 18.4 (q,
.
.
‡
1J(B,P) ˆ 54.0). EI-MS: 365.0 (7, M ), 352.0 (100, [M BH3] ). Anal. calc. for C18H24BO3P (329.97): C 65.52,
‡
H 7.33; found: C 65.43, H 7.29.
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Received September 9, 1999