Diastereoselective synthesis of new P-stereogenic (ortho-hydroxyaryl)- diazaphospholidine-borane complexes by a totally stereoselective P-O to P-C migration rearrangement

Article abstract of DOI:10.1002/ejoc.200500844

The totally diastereoselective synthesis of new P-stereogenic (o-hydroxyaryl)diazaphospholidines, in the form of their borane complexes 4a-4h, is described. The efficiency of this procedure is based both, on a one-pot and totally diastereoselective synthe

Full text of DOI:10.1002/ejoc.200500844

FULL PAPER
DOI: 10.1002/ejoc.200500844
Diastereoselective Synthesis of New P-Stereogenic (ortho-Hydroxyaryl)-
diazaphospholidine–Borane Complexes by a Totally Stereoselective P–O to
P–C Migration Rearrangement
Christian J. Ngono,[a] Thierry Constantieux,[a,b] and Gérard Buono*[a]
Keywords: Asymmetric synthesis / Chiral ligand design / Organophosphorus compounds / P,O ligands / 1,3-Carbanionic
rearrangements
The totally diastereoselective synthesis of new P-stereogenic
(o-hydroxyaryl)diazaphospholidines, in the form of their bor-
ane complexes 4a–4h, is described. The efficiency of this pro-
cedure is based both, on a one-pot and totally diastereoselec-
tive synthesis of the precursors (ortho-bromoaryloxy)diaza-
phosphospholidine–borane complexes 3a–3h, and on a ster-
eoselective P–O to P–C migration rearrangement. A X-ray
diffraction study of the structures of the product 4f and his
precursor 3f shows unambiguously the totally stereoselectiv-
ity of the P–O to P–C rearrangement with clean retention of
the phosphorus configuration.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
oxides,[12] and more recently chiral (ortho-hydroxyaryl)-
phosphane–borane complexes.[13]
Introduction
During the last three decades, there was a great interest
in the design and the development of numerous chiral or-
ganophosphorus compounds,[1] which have found broad ap-
plications in asymmetric catalysis, either as ligands of tran-
sition metals[2] or as catalysts.[3] In this area, chiral phos-
phanes,[4] bearing the chirality on the carbon backbone are
the most commonly used. More recently, P-stereogenic
phosphorus ligands, bearing the chirality closer to the metal
centre, have been synthesised owing to the use of borane as
protecting group,[5] and have received interest in catalysis.[6]
By this way, the asymmetric induction of the catalyst may
be increased.[7] In recent years, a new generation of ligands
bearing two different sites of coordination appeared, such
as P,N[8] or P,O[9] bidentate compounds, which are interest-
ing because of their ability to offer a selection of hard–soft
donors atoms that are capable of adapting to the character
of the metal centre.[10] In this context, we were interested
in the development and the applications in enantioselective
catalysis of P-stereogenic bidentate organophosphorus
compounds, such as chiral P-pyridine and P-quinoline
phosphane ligands,[11] chiral (ortho-hydroxyaryl)phosphane
These complexes are the protected forms of ortho-phos-
phanylphenols,[14] which are ambident molecules with two
different nucleophilic sites, a hard oxygen atom and a soft
phosphorus atom. Because they can react at oxygen or
phosphorus or at both nucleophilic sites and also because
their electronic and steric properties can easily be modu-
lated by varying the substituents on the phosphorus atom
and on the aromatic ring, they are of great interest in cataly-
sis[15] and in complex chemistry.[16] However, only few syn-
thetic approaches to ortho-phosphanylphenols have been
developed. The preparation of these compounds could be
achieved by the deprotection of suitable (ortho-phosphanyl-
aryl)alkyl ethers[16a,16b] or trimethylsilyl ethers,[17] or by the
reaction of a C,O-phenol dilithium reagent with a chloro-
phosphane.[18] On the basis of these results, we have recently
reported a totally diastereoselective synthesis of (ortho-hy-
droxyaryl)diazaphospholidines, in the form of their borane
complexes (Scheme 1).[13] Unless this approach represents
the first accurate and totally diastereoselective method for
the preparation of P-stereogenic 2-hydroxyarylphosphane
ligands, it suffers from several limitations. For example,
overall yields are quite good but not excellent, and the
choice of the chiral auxiliary is limited to diamines.
Another general way of preparation of ortho-phosphan-
ylphenols consists of an intramolecular 1,3-carbanionic re-
arrangement of ortho-metallated phenoxyphosphorus com-
pounds (Scheme 2).[19]
[a] UMR CNRS 6180, “Chirotechnologies: Catalyse et Biocata-
lyse”, Université Paul Cézanne (Aix-Marseille III), Faculté des
Sciences et Techniques, EGIM, Case A62,
Av. Escadrille Normandie Niémen, 13397 Marseille Cedex 20,
France
Fax: +33-4-9128-2742
E-mail: gerard.buono@univ.u-3mrs.fr
[b] UMR CNRS 6178, “SYMBIO”, Université Paul Cézanne (Aix-
Marseille III), Faculté des Sciences et Techniques, Case D12,
Av. Escadrille Normandie Niémen, 13397 Marseille Cedex 20,
France
In this context, Jugé et al. reported a stereoselective syn-
thesis of P-stereogenic 2-hydroxyarylphosphane ligands,
using the borane complexation methodology (Scheme 3).[20]
E-mail: thierry.constantieux@univ.u-3mrs.fr
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C. J. Ngono, T. Constantieux, G. Buono
FULL PAPER
product and its precursor shows unambiguously the stereo-
selectivity of the P–O to P–C rearrangement at the phos-
phorus atom.
Results and Discussion
The new chiral ligands (ortho-hydroxyaryl)diazaphos-
pholidines may be prepared according to the following ge-
neral procedure (Scheme 4). On the basis of a previously
described procedure,[12d] the precursors 2 could be obtained
in a diastereomerically pure form from the (dimethylami-
no)-
Scheme 1. Totally diastereoselective synthesis of (ortho-hy-
droxyaryl)diazaphospholidine–borane complexes.[13]
diazaphospholidine 1 and various mono- and disubstituted
ortho-bromophenols. Halogen–metal exchange in the pre-
cursor 2 could lead to an unstable ortho-metallated interme-
diate, which could in turn undergo a fast 1,3-carbanionic
rearrangement with cleavage of the P–O bond and forma-
tion of the new P–C bond, and with total retention of the
configuration at the phosphorus atom.
Scheme 2. Intramolecular 1,3-carbanionic rearrangement of ortho-
metallated phenoxyphosphorus compounds.[19]
This method is based on an intramolecular ortho-Fries-like
rearrangement of enantio-enriched ortho-bromoaryl phos-
phinite–borane complexes. Nevertheless, only one (ortho-
hydroxyaryl)phosphane–borane complex could be obtained
in pure enantiomeric form by this way. Although the P–O
to P–C migration rearrangement proceeds with total reten-
tion of the configuration at the phosphorus atom, this ap-
proach suffers from the non-totally enantioselective prepa-
ration of the ortho-bromoaryl phosphinite–borane precur-
sors.
Scheme 4. General procedure for the synthesis of chiral (ortho-hy-
droxyaryl)diazaphospholidines.
The synthesis of the precursors 2a–h was readily achieved
by the exchange reaction in refluxing toluene between tris-
(dimethylamino)phosphane and (S)-2-(anilinomethyl)pyr-
rolidine.[21] The reaction was monitored by 31P NMR spec-
troscopy. After two hours, analysis revealed the presence of
only one organophosphorus compound, with a δp value of
118.0 ppm, which was identified as the diazaphospholidine
1.[22] Subsequent addition of one equivalent of the appro-
priated ortho-bromophenol led, after one hour in refluxing
toluene, to the desired (ortho-bromoaryloxy)diazaphosphol-
idine 2. The products were purified by column chromatog-
Scheme 3. Intramolecular ortho-Fries-like rearrangement of en-
antio-enriched ortho-bromoaryl phosphinite–borane complexes.[20]
In this paper, we wish to report a totally diastereoselec- raphy on silica gel and isolated in good chemical yields
tive synthesis of new P-stereogenic (o-hydroxyaryl)diaza- (Scheme 4 and Table 1). In all cases, only one diastereomer
phospholidine–borane complexes, based on an intramol- was obtained, which was characterised as the thermo-
ecular ortho-Fries-like rearrangement of diastereomerically dynamic anti diastereomer.[11,12] Moreover, these new PIII
-
pure
(ortho-bromoaryloxy)diazaphospholidine–borane stereogenic aryloxydiazaphospholidines are quite stable to
complexes. The X-ray diffraction of the structures of one air and moisture.
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New P-Stereogenic (o-Hydroxyaryl)diazaphospholidine–Borane Complexes
FULL PAPER
Table 1. One-pot synthesis of precursors 2a–h and o-bromoaryloxy-
diazaphospholidine–borane complexes 3a–3h.
The P–O to P–C migration rearrangement reaction was
first tested with precursor 2a as test substrate. On the basis
of Heinicke’s results,[19] the treatment of (ortho-bromoary-
loxy)diazaphospholidine 2a with two equivalents of an al-
kali metal such as sodium or lithium in dioxane, may lead
to the corresponding free (ortho-hydroxyaryl)diazaphos-
pholidine after hydrolysis. Unfortunately, all attempts gave
complex mixtures of unidentified organophosphorus com-
pounds (Scheme 5). The use of chlorotrimethylsilane in-
stead of water to quench the reaction did not give the corre-
sponding silylether, but the same complex mixture was ob-
tained. The treatment of 2a with alkyllithium compounds
such as n-butyllithium, sec-butyllithium or tert-butyllithium
was also unsucessful.
To overcome this problem, we decided to protect the
phosphane moiety in the precursors 2 prior to the re-
arrangement procedure, with the borane complex method-
ology. Thus, after the completion of the exchange reaction
leading to the diazaphospholidines 2 (Scheme 4), the reac-
tion mixture was cooled to room temperature and 1.3
equivalent of borane–dimethyl sulfide was added
(Scheme 6). After one hour stirring and evaporation of the
solvent, the crude products were purified by column
chromatography, affording the desired diastereomerically
pure
(ortho-bromoaryloxy)diazaphospholidine–borane
complexes 3a–3h in yields ranging from 70 to 92%
(Table 1). These values can be considered as good to excel-
lent owing to the one-pot procedure.
With these new chiral compounds 3a–3h in hands, we
studied the P–O to P–C rearrangement reaction. Treatment
of precursors 3 with tert-butyllithium in THF at –78 °C re-
sulted in the totally diastereoselective synthesis of ortho-hy-
droxyaryldiazaphospholidine–boranes 4a–h, isolated in
good yields (Scheme 6 and Table 2).
In all cases, only one diastereomer was formed, and the
reaction was found to proceed with total retention of the
configuration at the phosphorus atom, as particularly illus
[a] Isolated yield after purification by column chromatography on
silica gel.
Scheme 5. Unsuccessful preliminary attempts for the P–O to P–C migration rearrangement.
Scheme 6. One-pot synthesis of (ortho-bromoaryloxy)diazaphospholidine–borane complexes 3a–3h and totally diastereoselective P–O to
P–C rearrangement.
Eur. J. Org. Chem. 2006, 1499–1507
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C. J. Ngono, T. Constantieux, G. Buono
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Table 2. Diastereoselective synthesis of (ortho-hydroxyaryl)diaza-
phospholidine–boranes 4a–4h.
Figure 1. ORTEP drawing of the crystal structure of compound 3f
(the numbering does not correspond with the correct nomencla-
ture); selected bond lengths [Å] and angles [°]: P2–B13 1.883, P2–
N6 1.639, P2–N7 1.682, P2–O3 1.610, O3–C10 1.390; B13–P2–N6
119.2, B13–P2–N7 121.1, B13–P2–O3 106.0, N6–P2–N7 94.0, O3–
P2–N6 109.8, O3–P2–N7 105.8, P2–O3–C10 125.1. The sum of the
bond angles around N6 and N7 is 351.5° and 358.6°, respectively.
[a] Isolated yield after purification by column chromatography on
silica gel.
Figure 2. ORTEP drawing of the crystal structure of compound 4f;
selected bond lengths [Å] and angles [°]: P1–B1 1.906, P1–N1 1.651,
P1–N2 1.683, P1–C1 1.808; B1–P1–N1 113.6, B1–P1–N2 117.5,
B1–P1–C1 111.3, N1–P1–N2 94.8, N2–P1–C1 108.1, N1–P1–C1
110.3. The sum of the bond angles around N1 and N2 is 348.0°
and 358.7°, respectively.
trated for the rearrangement of precursor 3f. X-ray analysis
of borane complex 3f[23] (Figure 1) and borane complex
4f[24] (Figure 2), obtained through treatment of 3f with tert-
butyllithium, shows unambiguously that these two com-
pounds present the same RP configuration.
tion of a trigonal-bipyramidal intermediate II spanning
These results show similar stereospecificity of the re- both diazaphospholidine and oxaphosphetene rings in api-
arrangement for the diazaphospholidine–borane complexes, cal-equatorial positions. The isomerisation by pseudorota-
with respect to the phosphate series[25] or the phosphinite– tion of this intermediate II into III maintains the equatorial
borane complexes.[20,26] As previously described,[12c,20,26]
a
P–BH3 bond as pivot and allows to place the oxygen ring
mechanism involving a trigonal-bipyramidal (TBP) inter- in a favourable apical position. The loss of the aryloxy leav-
mediate can be postulated (Scheme 7). This retention of ing group from III leads to the observed product with a
configuration may be explained in terms of an apical ad- retention of stereochemistry at phosphorus. An inversion of
dition to the phosphorus of the anion ortho to the aryloxy stereochemistry at phosphorus from the intermediate II or
substituent, generated by halogen–metal exchange. This in- III would involve energetically unfavourable placement of
tramolecular nucleophilic attack may result in the forma- the rings in the diequatorial positions.[27]
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New P-Stereogenic (o-Hydroxyaryl)diazaphospholidine–Borane Complexes
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General Procedure for the Synthesis of Compounds 2a–2h: In a 25-
.mL two-necked round-bottomed flask was added tris(dimethylam-
ino)phosphane (5 mmol) and (S)-2-anilinomethylpyrrolidine
(5 mmol), each dissolved in 2.5 mL of dry toluene. The solution
was heated to reflux for two hours, and the reaction was monitored
by 31P NMR spectroscopy. After completion of the reaction,
1 equiv. (5 mmol) of the appropriate ortho-bromophenol[28] dis-
solved in 2.5 mL of dry toluene was added. After one hour stirring
and evaporation of the solvent, the crude products were purified
by column chromatography (eluent: ethyl acetate/petroleum ether,
20:80), affording the diastereomerically pure (ortho-bromoaryloxy)-
diazaphospholidines 2a–2h.
(2R,5S)-2-(2-Bromophenoxy)-3-phenyl-1,3-diaza-2-phosphabicy-
clo[3.3.01,5]octane (2a): Prepared by the general procedure from 2-
bromophenol (0.87 g, 5 mmol) in 94% yield (1.77 g). White solid,
m.p. 64–66 °C. [α]2D5 = –304.1 (c = 1.0, CH2Cl2). 1H NMR
(200 MHz, CDCl3): δ = 1.4–1.5 (m, 1 H), 1.7–1.9 (m, 3 H), 3.0–3.1
(m, 1 H), 3.2–3.3 (m, 1 H), 3.5–3.7 (m, 3 H), 6.8–7.5 (m, 9 H) ppm.
13C NMR (50.30 MHz, CDCl3): δ = 26.7 (d, J = 5 Hz), 31.9, 48.2
(d, J = 35 Hz), 54.2 (d, J = 8 Hz), 62.9 (d, J = 13 Hz), 115.6 (d, J
= 13 Hz), 117.1, 119.6, 123.2 (d, J = 7 Hz), 124.3, 128.1, 129.3,
133.0, 145.3 (d, J = 16 Hz), 151.4 (d, J = 6 Hz) ppm. 31P NMR
(40.50 MHz, CDCl3): δ = 123.9 ppm. C17H18BrN2OP (377.22):
calcd. C 54.13, H 4.81; found C 54.07, H 4.75.
Scheme 7. Mechanism for the P–O to P–C rearrangement.
Conclusion
In this paper, we have described a totally diastereoselec-
tive synthesis of new P-stereogenic (o-hydroxyaryl)diaza-
phospholidines, in the form of their borane complexes. The
efficiency of this procedure is based on two key steps: firstly,
a one-pot and totally diastereoselective synthesis of the pre-
cursors (ortho-bromoaryloxy)diazaphospholidine–borane
complexes 3a–3h; secondly, a stereoselective P–O to P–C
migration rearrangement. The stereospecificity of the re-
arrangement has been clearly illustrated by X-ray analysis
of the product 4f and his precursor 3f, showing unambigu-
ously that these two compounds present the same RP con-
figuration. We are currently extending this procedure to the
use of other chiral auxiliaries such as amino alcohols and
diols. In the same time, investigations of the catalytic ac-
tivity of these new chiral compounds 4a–h in enantioselec-
tive processes are in progress. In this context, tests are di-
rected to the use of these compounds either as ligands or
as nonmetallic catalysts.
(2R,5S)-2-(2-Bromo-4-methylphenoxy)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane (2b): Prepared by the general procedure
from 2-bromo-4-methylphenol (0.94 g, 5 mmol) in 91 % yield
(1.78 g). White solid, m.p. 90–94 °C. [α]2D5 = –443.3 (c = 1.0,
1
CH2Cl2). H NMR (200 MHz, CDCl3): δ = 1.4–1.5 (m, 1 H), 1.7–
1.9 (m, 3 H), 2.2 (s, 3 H), 3.0–3.1 (m, 1 H), 3.2–3.3 (m, 1 H), 3.4–3.6
(m, 3 H), 6.7–7.3 (m, 8 H) ppm. 13C NMR (50.30 MHz, CDCl3): δ
= 20.3, 26.5 (d, J = 4 Hz), 31.9, 47.8 (d, J = 34 Hz), 54.0 (d, J =
8 Hz), 62.7 (d, J = 9 Hz), 115.3 (d, J = 13 Hz), 116.5, 119.4, 122.7
(d, J = 6 Hz), 128.7, 129.1, 133.0, 134.0, 145.1 (d, J = 16 Hz), 148.8
(d, J = 8 Hz) ppm. 31P NMR (40.50 MHz, CDCl3): δ = 125.7 ppm.
C18H20BrN2OP (391.24): calcd. C 55.26, H 5.15; found C 55.23, H
5.12.
(2R,5S)-2-(2-Bromo-4-phenylphenoxy)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane (2c): Prepared by the general procedure
from 3-bromo-4-hydroxybiphenyl (1.25 g, 5 mmol) in 85% yield
(1.92 g). White solid, m.p. 88–90 °C. [α]2D5 = –429.6 (c = 1.0,
1
CH2Cl2). H NMR (200 MHz, CDCl3): δ = 1.5–1.7 (m, 1 H), 1.8–
2.1 (m, 3 H), 3.1–3.3 (m, 1 H), 3.3–3.5 (m, 1 H), 3.6–3.9 (m, 3 H),
6.9–8.0 (m, 13 H) ppm. 13C NMR (50.30 MHz, CDCl3): δ = 26.6
(d, J = 4 Hz), 31.9, 47.8 (d, J = 34 Hz), 54.0 (d, J = 8 Hz), 62.8 (d,
J = 8 Hz), 115.5 (d, J = 13 Hz), 116.4, 117.4, 119.6 (d, J = 2 Hz),
123.2 (d, J = 6 Hz), 126.6, 126.7, 126.8, 127.3, 128.8, 129.2, 131.4,
137.4 (d, J = 1 Hz), 139.4, 145.0 (d, J = 16 Hz), 150.7 (d, J = 5 Hz)
p p m. 3 1 P NMR (40. 50 MHz, CDCl 3 ) : δ = 124.6 ppm.
C23H22BrN2OP (453.31): calcd. C 60.94, H 4.89; found C 61.05, H
4.93.
Experimental Section
General: All reactions are conducted under dry argon by using the
Schlenk techniques. All solvents were purified according to re-
ported procedures, and reagents were used as commercially avail-
able. Ethyl acetate and petroleum ether (35–65 °C) were purchased
from SDS and used without any further purification. Column
chromatography was performed on SDS silica gel (70–230 mesh).
1H and 13C NMR spectra were recorded in CDCl3 solution at
200.00 and 50.30 MHz with a Bruker AC200 spectrometer. 31P
NMR spectra were recorded in CDCl3 solution at 40.50 MHz with
a Bruker AC100 spectrometer (the usual abbreviations are used: s,
singlet; d, doublet; t, triplet; q, quadruplet; m, multiplet). The
chemical shift values are given in ppm, and were determined, rela-
tive to TMS (1H), CDCl3 (13C), and 85% H3PO4 (31P). IR spectra
were recorded with a Perkin–Elmer 298 IR spectrometer. Optical
rotations were determined with a Perkin–Elmer 241 MC polarime-
ter. All melting points were taken with a Büchi apparatus, and are
uncorrected.
(2R,5S)-2-(2-Bromo-4-chlorophenoxy)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane (2d): Prepared by the general procedure
from 2-bromo-4-chlorophenol (1.04 g, 5 mmol) in 93 % yield
(1.91 g). Yellow oil. [α]2D5 = –415.8 (c = 1.0, CH2Cl2). 1H NMR
(200 MHz, CDCl3): δ = 1.6–1.7 (m, 1 H), 1.9–2.1 (m, 3 H), 3.2–3.3
(m, 1 H), 3.4–3.5 (m, 1 H), 3.6–3.9 (m, 3 H), 6.8–7.8 (m, 8 H) ppm.
13C NMR (50.30 MHz, CDCl3): δ = 26.5, 31.7, 47.5 (d, J = 35 Hz),
53.8 (d, J = 9 Hz), 62.6 (d, J = 9 Hz), 115.2 (d, J = 14 Hz), 117.4,
119.6 (d, J = 1 Hz), 123.6 (d, J = 7 Hz), 127.9, 128.3 (d, J = 1 Hz),
129.1, 132.2, 144.6 (d, J = 16 Hz), 150.2 (d, J = 6 Hz) ppm. 31P
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C. J. Ngono, T. Constantieux, G. Buono
NMR (40.50 MHz, CDCl3): δ = 123.5 ppm. C17H17BrClN2OP (2R,5S)-2-(2-Bromophenoxy)-3-phenyl-1,3-diaza-2-phosphabicyclo-
FULL PAPER
(411.66): calcd. C 49.60, H 4.16; found C 49.75, H 4.21.
[3.3.01,5]octane–Borane (3a): Yield 90% (1.75 g). White solid, m.p.
102 °C. [α]2D5 = –171.8 (c = 1, CH2Cl2). 1H NMR (200 MHz,
CDCl3): δ = 0.0–1.5 (m, 3 H), 1.6–1.7 (m, 1 H), 1.9–2.1 (m, 3 H),
3.2–3.5 (m, 3 H), 3.6–3.7 (m, 1 H), 3.8–4.0 (m, 1 H), 6.5–7.7 (m, 9
H) ppm. 13C NMR (50.30 MHz, CDCl3): δ = 26.4 (d, J = 5 Hz),
31.5 (d, J = 3 Hz), 46.9 (d, J = 11 Hz), 54.1, 59.8, 116.8 (d, J =
6 Hz), 117.0 (d, J = 4 Hz), 121.5, 122.5 (d, J = 4 Hz), 126.0 (d, J
= 2 Hz), 128.3 (d, J = 2 Hz), 129.2, 133.4 (d, J = 2 Hz), 141.7 (d,
J = 10 hz), 143.8 (d, J = 15 Hz) ppm. 31P NMR (40.50 MHz,
(2R,5S)-2-(2-Bromo-4-fluorophenoxy)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane (2e): Prepared by the general procedure
from 2-bromo-4-fluorophenol (0.96 g, 5 mmol) in 95 % yield
(1.88 g). Colorless oil. [α]2D5 = –423.6 (c = 1.0, CH2Cl2). H NMR
1
(200 MHz, CDCl3): δ = 1.5–1.7 (m, 1 H), 1.7–2.1 (m, 3 H), 2.9–3.2
(m, 2 H), 3.3–3.5 (m, 2 H), 3.6–3.8 (m, 1 H), 6.4–7.5 (m, 8 H). 13C
NMR (50.30 MHz, CDCl3): δ = 23.6, 27.8, 44.6, 44.8, 59.3, 109.4
(d, J = 10 Hz), 112.7, 115.1 (d, J = 22 Hz), 115.3, 116.3 (d, J =
8 Hz), 117.7, 119.2 (d, J = 25 Hz), 129.2, 147.5, 150.0 (d, J = 3 Hz).
31P NMR (40.50 MHz, CDCl3): δ = 123.2 ppm. C17H17BrFN2OP
(395.21): calcd. C 51.66, H 4.34; found C 51.43, H 4.36.
CDCl ): δ = 108.9 (broad) ppm. IR (neat, cm–1): ν = 884 (s), 1050
˜
3
(s), 1136 (s), 1222 (s), 1293 (s), 1467 (s), 1497 (s), 1602 (s), 1631
(m), 2339 (m, BH), 2366 (m, BH), 2422 (m, BH), 2885 (m), 2916
(m), 2984 (m), 3039 (w). C17H21BBrN2OP (391.05): calcd. C 52.21,
H 5.41; found C 52.16, H 5.36.
(2R,5S)-2-(2-Bromo-4-tert-butylphenoxy)-3-phenyl-1,3-diaza-2-
phosphabicyclo[3.3.01,5]octane (2f): Prepared by the general pro-
cedure from 2-bromo-4-tert-butylphenol (1.15 g, 5 mmol) in 85%
yield (1.84 g). White solid, m.p. 126–130 °C. [α]2D5 = –408.5 (c = 1.0,
CH2Cl2). 1H NMR (200 MHz, CDCl3): δ = 1.3 (s, 9 H), 1.5–1.8
(m, 1 H), 1.9–2.1 (m, 3 H), 3.2–3.3 (m, 1 H), 3.4–3.5 (m, 1 H), 3.6–
3.8 (m, 3 H), 7.4–7.8 (m, 8 H) ppm. 13C NMR (50.30 MHz,
CDCl3): δ = 26.5 (d, J = 4 Hz), 31.3, 31.9, 34.3, 47.8 (d, J = 35 Hz),
54.0 (d, J = 8 Hz), 62.7 (d, J = 9 Hz), 115.5 (d, J = 13 Hz), 116.3
(d, J = 2 Hz), 119.4 (d, J = 2 Hz), 122.2 (d, J = 7 Hz), 125.1, 129.1,
129.9, 145.2 (d, J = 16 Hz), 147.5, 148.7 (d, J = 4 Hz) ppm. 31P
NMR (40.50 MHz, CDCl3): δ = 126.5 ppm. C21H26BrN2OP
(433.32): calcd. C 58.21, H 6.05, N 6.46; found C 57.90, H 6.21;
N. 6.55.
(2R,5S)-2-(2-Bromo-4-methylphenoxy)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane–Borane (3b): Yield 85% (1.72 g). White
1
solid, m.p. 102–103 °C. [α]2D5 = –167.6 (c = 1, CH2Cl2). H NMR
(200 MHz, CDCl3): δ = 0.0–1.4 (m, 2 H), 1.5–1.7 (m, 1 H), 1.8–2.1
(m, 4 H), 2.3 (s, 3 H), 3.1–3.5 (m, 3 H), 3.6–3.7 (m, 1 H), 3.8–
4.0 (m, 1 H), 6.7–7.1 (m, 3 H), 7.2–7.6 (m, 5 H) ppm. 13C NMR
(50.30 MHz, CDCl3): δ = 20.4, 26.5 (d, J = 5 Hz), 31.6 (d, J =
3 Hz), 47.0 (d, J = 10 Hz), 54.1, 59.9, 116.5, 116.9 (d, J = 6 Hz),
121.5, 122.1 (d, J = 3 Hz), 128.9 (d, J = 2 Hz), 129.3, 133.7 (d, J
= 2 Hz), 136.0 (d, J = 2 Hz), 149.1 (d, J = 10 Hz), 146.0 (d, J =
15 Hz) ppm. 31P NMR (40.50 MHz, CDCl3): δ = 110.7 (broad)
ppm. IR (neat, cm–1): ν = 884 (s), 1050 (s), 1136 (s), 1222 (s), 1293
˜
(s), 1467 (s), 1497 (s), 1602 (s), 1631 (m), 2339 (m, BH), 2366 (m,
BH), 2422 (m, BH), 2885 (m), 2916 (m), 2984 (m), 3039 (w).
C18H23BBrN2OP (405.08): calcd. C 53.37, H 5.72; found C 53.31,
H 5.69.
(2R,5S)-2-(2-Bromo-4-methoxyphenoxy)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane (2 g): Prepared by the general procedure
from 2-bromo-4-methoxyphenol (1.02 g, 5 mmol) in 96 % yield
(1.95 g). White solid, m.p. 66–68 °C. [α]2D5 = –309.4 (c = 1.0,
1
(2R,5S)-2-(2-Bromo-4-phenylphenoxy)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane–Borane (3c): Yield 85% (1.99 g). White
CH2Cl2). H NMR (200 MHz, CDCl3): δ = 1.5–1.7 (m, 1 H), 1.7–
2.1 (m, 3 H), 3.1–3.2 (m, 1 H), 3.3–3.5 (m, 1 H), 3.5–3.7 (m, 3 H),
3.8 (s, 3 H), 6.6–7.5 (m, 8 H) ppm. 13C NMR (50.30 MHz, CDCl3):
δ = 26.6 (d, J = 5 Hz), 31.9, 47.7 (d, J = 35 Hz), 54.0 (d, J = 8 Hz),
55.6, 62.6 (d, J = 8 Hz), 113.8, 115.2 (d, J = 13 Hz), 117.0 (d, J =
2 Hz), 117.8, 119.4, 123.3 (d, J = 5 Hz), 129.1, 144.7 (d, J = 6 Hz),
145.1 (d, J = 16 Hz), 155.7 ppm. 31P NMR (40.50 MHz, CDCl3):
δ = 125.1 ppm. C18H20BrN2O2P (407.24): calcd. C 53.09, H 4.95;
found C 53.21, H 4.87.
1
solid, m.p. 136–142 °C. [α]2D5 = –141.7 (c = 1, CH2Cl2). H NMR
(200 MHz, CDCl3): δ = 0.1–1.6 (m, 3 H), 1.2–2.2 (m, 4 H), 2.3 (s,
3 H), 3.2–3.5 (m, 3 H), 3.6–3.7 (m, 1 H), 3.7–3.8 (m, 1 H), 6.9–7.8
(m, 13 H) ppm. 13C NMR (50.30 MHz, CDCl3): δ = 26.4 (d, J =
2 Hz), 31.6, 47.1 (d, J = 10 Hz), 54.1, 59.9, 116.9 (d, J = 5 Hz),
117.4 (d, J = 3 Hz), 121.4, 122.7, 126.8, 127.8, 128.7, 128.9, 129.3,
131.8, 138.7, 139.2, 141.9 (d, J = 10 Hz), 147.7 (d, J = 15 Hz) ppm.
31P NMR (40.50 MHz, CDCl3): δ = 108.2 (broad) ppm. IR (neat,
(2S,5R)-2-(1-Bromo-2-naphthoxy)-3-phenyl-1,3-diaza-2-phosphabi-
cyclo[3.3.01,5]octane (2h): Prepared by the general procedure from
1-bromonaphth-2-ol (1.16 g, 5 mmol) in 60% yield (1.28 g). Uncol-
cm–1): ν = 884 (s), 1050 (s), 1136 (s), 1222 (s), 1293 (s), 1467 (s),
˜
1497 (s), 1602 (s), 1631 (m), 2339 (m, BH), 2366 (m, BH), 2422 (m,
BH), 2885 (m), 2916 (m), 2984 (m), 3039 (w). C23H25BBrN2OP
(467.15): calcd. C 59.13, H 5.39; found C 59.04, H 5.44.
1
oured oil. [α]2D5 = –433.5 (c = 1.0, CH2Cl2). H NMR (200 MHz,
CDCl3): δ = 1.4–1.6 (m, 1 H), 1.7–2.0 (m, 3 H), 3.0–3.3 (m, 1 H),
3.3–3.5 (m, 1 H), 3.6–3.8 (m, 3 H), 7.0–7.9 (m, 11 H) ppm. 13C
NMR (50.30 MHz, CDCl3): δ = 26.6 (d, J = 4 Hz), 31.9, 47.8 (d,
J = 34 Hz), 54.0 (d, J = 8 Hz), 62.8 (d, J = 8 Hz), 115.3 (d, J =
13 Hz), 117.0, 119.4, 124.7, 126.6, 127.0, 127.4 (d, J = 8 Hz), 127.7,
128.0, 129.0, 130.8 (d, J = 1 Hz), 132.8, 145.0 (d, J = 16 Hz), 149.5
(d, J = 6 Hz) ppm. 31P NMR (40.50 MHz, CDCl3): δ = 124.3 ppm.
C21H20BrN2OP (427.27): calcd. C 59.03, H 4.72; found C 59.09, H
4.80.
(2R,5S)-2-(2-Bromo-4-chlorophenoxy)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane (3d): Yield 88 % (1.87 g). White solid,
m.p. 82–87 °C. [α]2D5 = –137.9 (c = 1, CH2Cl2). 1H NMR (200 MHz,
CDCl3): δ = –0.1–1.3 (m, 3 H), 1.4–1.6 (m, 1 H), 1.7–2.2 (m, 3 H),
3.0–3.4 (m, 3 H), 3.5–3.9 (m, 2 H), 6.7–7.6 (m, 8 H) ppm. 13C
NMR (50.30 MHz, CDCl3): δ = 26.5 (d, J = 4 Hz), 31.6 (d, J =
3 Hz), 46.2 (d, J = 10 Hz), 54.1, 60.0, 117.0 (d, J = 5 Hz), 117.8
(d, J = 2 Hz), 121.9, 123.4 (d, J = 3 Hz), 128.4, 129.4, 130.7, 133.0,
141.7 (d, J = 10 Hz), 147.3 (d, J = 15 Hz) ppm. 31P NMR
General Procedure for the Synthesis of Compounds 3a–3h: After
completion of the exchange reaction leading to the (ortho-bromoar-
yloxy)diazaphospholidines 2, the reaction mixture was cooled to
room temperature and 1.3 equiv. of borane–dimethyl sulfide was
added. After one hour stirring and evaporation of the solvent, the
crude products were purified by column chromatography (eluent:
ethyl acetate/petroleum ether, from 5:95 to 20:80), affording the
diastereomerically pure (ortho-bromoaryloxy)diazaphospholidine–
borane complexes 3a–3h.
(40.50 MHz, CDCl ): δ = 111.2 (broad) ppm. IR (neat, cm–1): ν =
˜
3
884 (s), 1050 (s), 1136 (s), 1222 (s), 1293 (s), 1467 (s), 1497 (s), 1602
(s), 1631 (m), 2339 (m, BH), 2366 (m, BH), 2422 (m, BH), 2885 (m),
2916 (m), 2984 (m), 3039 (w). C17H20BBrClN2OP (425.5): calcd. C
47.99, H 4.74; found C 47.87, H 4.81.
(2R,5S)-2-(2-Bromo-4-fluorophenoxy)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane (3e): Yield 83 % (1.70 g). White solid,
m.p. 100–105 °C. [α]2D5 = –153.8 (c = 1, CH2Cl2). 1H NMR
1504
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 1499–1507

New P-Stereogenic (o-Hydroxyaryl)diazaphospholidine–Borane Complexes
FULL PAPER
(200 MHz, CDCl3): δ = 0.1–1.4 (m, 3 H), 1.5–1.6 (m, 1 H), 1.7–1.9
(m, 3 H), 3.0–3.4 (m, 3 H), 3.5–3.6 (m, 1 H), 3.7–3.9 (m, 1 H), 6.7–
rated solution of NH4Cl. The product was extracted with CH2Cl2.
The combined organic phases were dried with MgSO4 and the sol-
7.4 (m, 8 H) ppm. 13C NMR (50.30 MHz, CDCl3): δ = 26.5 (d, J vent was removed in vacuo. The residue was purified by column
= 5 Hz), 31.6 (d, J = 3 Hz), 47.1 (d, J = 11 Hz), 54.1, 59.9, 115.2 chromatography (eluent: ethyl acetate/petroleum ether, from 5:95
(d, J = 22 Hz), 116.8 (d, J = 6 Hz), 117.4 (d, J = 10 Hz), 120.4 (d,
J = 25 Hz), 121.8, 123.8 (d, J = 8 Hz), 129.4, 141.6 (d, J = 10 Hz),
144.8 (d, J = 18 Hz), 156.6 (d, J = 12 Hz) ppm. 31P NMR
to 20:80), affording the corresponding o-hydroxyphenyldiazaphos-
pholidine–borane complex 4. In all cases only one diastereoisomer
was obtained.
(40.50 MHz, CDCl ): δ = 110.9 (broad) ppm. IR (neat, cm–1): ν =
˜
3
(2R,5S)-2-(2-Hydroxyphenyl)-3-phenyl-1,3-diaza-2-phosphabicyclo-
[3.3.01,5]octane–Borane (4a): Prepared by general procedure from
3a (0.98 g, 2.5 mmol) in 86% yield (0.67 g). White solid, m.p. 115–
122 °C. [α]2D5 = +164.2 (c = 1, CH2Cl2). 1H NMR (200 MHz,
CDCl3): δ = 0.1–1.1 (m, 3 H), 1.7–2.2 (m, 4 H), 3.1–3.4 (m, 2 H),
884 (s), 1050 (s), 1136 (s), 1222 (s), 1293 (s), 1467 (s), 1497 (s), 1602
(s), 1631 (m), 2339 (m, BH), 2366 (m, BH), 2422 (m, BH), 2885 (m),
2916 (m), 2984 (m), 3039 (w). C17H20BBrFN2OP (409.04): calcd. C
49.92, H 4.93; found C 49.98, H 4.88.
(2R,5S)-2-(2-Bromo-4-tert-butylphenoxy)-3-phenyl-1,3-diaza-2- 3.6–3.9 (m, 2 H), 4.0–4.1 (m, 1 H), 6.7–7.6 (m, 9 H), 9.8 (s, 1 H)
phosphabicyclo[3.3.01,5]octane–Borane (3f): Yield 85 % (1.90 g).
ppm. 13C NMR (50.30 MHz, CDCl3): δ = 26.3 (d, J = 4 Hz), 31.7,
48.6 (d, J = 4 Hz), 52.4 (d, J = 3 Hz), 61.9 (d, J = 3 Hz), 116.5 (d,
1
White solid, m.p. 136–142 °C. [α]2D5 = –139.4 (c = 1, CH2Cl2). H
NMR (200 MHz, CDCl3): δ = 1.0 (m, 3 H), 1.2 (s, 9 H), 1.4–1.6 J = 35 Hz), 117.7 (d, J = 5 Hz), 118.9 (d, J = 4 Hz), 119.8 (d, J =
(m, 1 H), 1.8–2.0 (m, 3 H), 3.0–3.2 (m, 3 H), 3.3–3.6 (m, 1 H), 3.7–
3.8 (m, 1 H), 6.6–7.5 (m, 8 H) ppm. 13C NMR (50.30 MHz,
CDCl3): δ = 26.4 (d, J = 4 Hz), 31.2, 32.0 (d, J = 3 Hz), 34.4, 47.0
(d, J = 11 Hz), 54.0, 59.8, 116.4 (d, J = 4 Hz), 116.8 (d, J = 5 Hz),
121.4, 121.8 (d, J = 3 Hz), 125.3, 129.2, 130.3, 141.9 (d, J = 10 Hz),
145.8 (d, J = 15 Hz), 149.4 ppm. 31P NMR (40.50 MHz, CDCl3):
19 Hz), 122.3, 129.4, 132.1 (d, J = 15 Hz), 134.0, 142.0 (d, J =
7 Hz), 159.2 ppm. 31P NMR (40.50 MHz, CDCl3): δ = 106.5
(broad) ppm. IR (neat, cm–1): ν = 1187 (s), 1287 (s), 1310 (s), 1501
˜
(s), 1602 (s), 1630 (m), 2348 (m, BH), 2387 (s, BH), 2883 (m), 2950
(m), 2975 (m), 3095 (m), 3470 (s, OH). C17H22BN2OP (312.15):
calcd. C 65.41, H 7.10; found C 65.33, H 7.07.
δ = 109.3 (broad) ppm. IR (neat, cm–1): ν = 884 (s), 1050 (s), 1136
˜
(2R,5S)-2-(2-Hydroxy-5-methylphenyl)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane–Borane (4b): Prepared by the general pro-
cedure from 3b (1.02 g, 2.5 mmol) in 70% yield (0.57 g). White so-
lid, m.p. 124–126 °C. [α]2D5 = –187.5 (c = 1, CH2Cl2). 1H NMR
(200 MHz, CDCl3): δ = 0.5–1.5 (m, 2 H), 1.6–1.9 (m, 5 H), 2.0 (s,
3 H), 3.0–3.3 (m, 2 H), 3.5–3.7 (m, 2 H), 3.9 (m, 1 H), 6.7–7.3 (m,
8 H), 9.9 (s, 1 H) ppm. 13C NMR (50.30 MHz, CDCl3): δ = 16.0,
26.3 (d, J = 4 Hz), 31.7 (d, J = 3 Hz), 48.6 (d, J = 4 Hz), 52.4, 61.9
(d, J = 3 Hz), 115.5 (d, J = 56 Hz), 118.9 (d, J = 4 Hz), 119.5 (d,
J = 12 Hz), 122.3, 126.5 (d, J = 5 Hz), 129.1, 129.7 (d, J = 15 Hz),
(s), 1222 (s), 1293 (s), 1467 (s), 1497 (s), 1602 (s), 1631 (m), 2339
(m, BH), 2366 (m, BH), 2422 (m, BH), 2885 (m), 2916 (m), 2984
(m), 3039 (w). C21H29BBrN2OP (447.16): calcd. C 56.41, H 6.54,
N 6.26; found C 56, 55, H 6.38, N 6.51.
(2R,5S)-2-(2-Bromo-4-methoxyphenoxy)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane–Borane (3 g): Yield, 92% (1.94 g). White
solid, m.p. 103–108 °C. [α]2D5 = –123.2 (c = 1, CH2Cl2). H NMR
1
(200 MHz, CDCl3): δ = 0.3–1.3 (m, 3 H), 1.5–1.8 (m, 1 H), 1.9–2.1
(m, 3 H), 3.1–3.5 (m, 3 H), 3.6–3.7 (m, 1 H), 3.8 (s, 3 H), 3.8–4.2
(m, 1 H), 6.6–6.9 (m, 3 H), 7.0–7.2 (m, 2 H), 7.3–7.7 (m, 3 H) ppm. 135.0 (d, J = 2 Hz), 142.2 (d, J = 6 Hz), 157.4 (d, J = 3 Hz) ppm.
13C NMR (50.30 MHz, CDCl3): δ = 26.4 (d, J = 5 Hz), 31.5 (d, J
= 3 Hz), 46.9 (d, J = 11 Hz), 54.0, 55.6, 59.8, 113.8 (d, J = 2 Hz),
116.8 (d, J = 6 Hz), 117.2 (d, J = 4 Hz), 118.3 (d, J = 2 Hz), 121.5,
31P NMR (40.50 MHz, CDCl3): δ = 105.6 (broad) ppm. IR (neat,
cm–1): ν = 1187 (s), 1287 (s), 1310 (s), 1501 (s), 1602 (s), 1630 (m),
˜
2348 (m, BH), 2387 (s, BH), 2883 (m), 2950 (m), 2975 (m), 3095
122.7 (d, J = 3 Hz), 129.2, 141.8 (d, J = 16 Hz), 141.9 (d, J = (m), 3470 (s, OH). C18H24BN2OP (326.18): calcd. C 66.28, H 7.42;
10 Hz), 156.8 (d, J = 2 Hz) ppm. IR (neat, cm–1): ν = 884 (s), 1028
found C 66.31, H 7.45.
˜
(s), 1119 (s), 1199 (s), 1259 (m), 1298 (s), 1487 (m), 1503 (s), 1598
(s), 2339 (m, BH), 2366 (m, BH), 2422 (m, BH), 2832 (m), 2967
(m), 2975 (m), 3094 (w). C18H23BBrN2O2P (420.08): calcd. C 51.34,
H 5.51; found C 51.46, H 5.48.
(2R,5S)-2-(2-Hydroxy-5-phenylphenyl)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane–Borane (4c): Prepared by the general pro-
cedure from 3c (1.17 g, 2.5 mmol) in 78% yield (0.76 g). White so-
lid, m.p. 132–134 °C. [α]2D5 = –172.0 (c = 1, CH2Cl2). 1H NMR
(2R,5S)-2-(2-Bromo-1-naphthoxy)-3-phenyl-1,3-diaza-2-phosphabi- (200 MHz, CDCl3): δ = 0.9 (m, 1 H); 1.1–1.5 (m, 2 H), 2.4–2.6 (m,
cyclo[3.3.01,5]octane–Borane (3h): Yield 70% (1.54 g). White solid,
m.p. 150–152 °C. [α]2D5 = –88.0 (c = 1, CH2Cl2). 1H NMR
(200 MHz, CDCl3): δ = 0.1–1.3 (m, 3 H), 1.5–1.6 (m, 1 H), 1.8–2.0
(m, 3 H), 3.0–3.4 (m, 3 H), 3.5–3.7 (m, 1 H), 3.8–3.9 (m, 1 H), 7.0–
4 H), 3.1–3.5 (m, 2 H), 3.5–3.9 (m, 2 H), 3.9–4.2 (m, 1 H), 6.7–7.9
(m, 13 H), 9.9 (s, 1 H) ppm. 13C NMR (50.30 MHz, CDCl3): δ =
26.3, 31.7, 48.8, 52.0, 60.0, 116.2 (d, J = 55 Hz), 117.9, 119.2, 122.5,
126.2, 126.7, 128.4, 129.2, 130.3 (d, J = 15 Hz), 132.4, 132.7, 139.6,
7.8 (m, 11 H) ppm. 13C NMR (50.30 MHz, CDCl3): δ = 26.4 (d, J 141.8 (d, J = 7 Hz), 158.6 (d, J = 3 Hz) ppm. 3 1 P NMR
= 5 Hz), 31.5 (d, J = 2 Hz), 46.9 (d, J = 10 Hz), 53.9, 59.8, 115.6 (40.50 MHz, CDCl ): δ = 107.6 (broad) ppm. IR (neat, cm–1): ν =
˜
3
(d, J = 6 Hz), 116.9 (d, J = 6 Hz), 121.2 (d, J = 3 Hz), 121.6, 126.0,
127.1, 127.7, 128.0, 128.6, 129.3, 131.6, 132.8, 141.9 (d, J = 10 Hz), BH), 2387 (s, BH), 2883 (m), 2950 (m), 2975 (m), 3095 (m), 3470
146.5 (d, J = 15 Hz) ppm. IR (neat, cm–1): ν = 884 (s), 1050 (s),
(s, OH). C23H26BN2OP (388.25): calcd. C 71.15, H 6.75; found C
1187 (s), 1287 (s), 1310 (s), 1501 (s), 1602 (s), 1630 (m), 2348 (m,
˜
1136 (s), 1222 (s), 1293 (s), 1467 (s), 1497 (s), 1602 (s), 1631 (m), 71.23, H 6.83.
2339 (m, BH), 2366 (m, BH), 2422 (m, BH), 2885 (m), 2916 (m),
(2R,5S)-2-(5-Chlorophenyl-2-hydroxy)-3-phenyl-1,3-diaza-2-phos-
2984 (m), 3039 (w). C21H23BBrN2OP (441.11): calcd. C 57.18, H
5.26; found C 57.25, H 5.32.
phabicyclo[3.3.01,5]octane–Borane (4d): Prepared by the general pro-
cedure from 3d (1.06 g, 2.5 mmol) in 76% yield (0.66 g). White so-
General Procedure for the Synthesis of Compounds 4a–4h: To a 25- lid, m.p. 80–85 °C– [α]2D5 = –171.8 (c = 1, CH2Cl2). 1H NMR
mL two-necked round -bottomed flask were added compound 3
(2.5 mmol) dissolved in dry THF (10 mL). The solution was cooled
to –78 °C and 2 equiv. of tert-butyllithium (1.7  in diethyl ether)
were added dropwise. The solution was stirred overnight at room
temperature and then hydrolysed with 10 mL of an aqueous satu-
(200 MHz, CDCl3): δ = 0.1–1.2 (m, 3 H), 1.7–2.2 (m, 4 H), 3.0–3.4
(m, 2 H), 3.5–3.9 (m, 2 H), 4.0 (m, 1 H), 6.7–7.4 (m, 8 H), 9.2 (s,
1 H) ppm. 13C NMR (50.30 MHz, CDCl3): δ = 26.3, 31.8, 48.5 (d,
J = 4 Hz), 52.5, 62.0, 118.7 (d, J = 4 Hz), 119.3 (d, J = 5 Hz),
122.5, 124.8 (d, J = 15 Hz), 129.4, 131.2 (d, J = 15 Hz), 133.8,
Eur. J. Org. Chem. 2006, 1499–1507
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1505

C. J. Ngono, T. Constantieux, G. Buono
FULL PAPER
141.7 (d, J = 10 Hz), 157.7 (d, J = 3 Hz) ppm. 31P NMR
(m), 2950 (m), 2975 (m), 3095 (m), 3470 (s, OH). C21H24BN2OP
(362.17): calcd. C 69.63, H 6.68; found C 69.72, H 6.56.
(40.50 MHz, CDCl ): δ = 105.1 (broad) ppm. IR (neat, cm–1): ν =
˜
3
1187 (s), 1287 (s), 1310 (s), 1501 (s), 1602 (s), 1630 (m), 2348 (m,
BH), 2387 (s, BH), 2883 (m), 2950 (m), 2975 (m), 3095 (m), 3470
(s, OH). C17H21BClN2OP (346.6): calcd. C 58.91, H 6.11; found C
58.95, H 6.18.
Acknowledgments
The authors would like to thank Inspec Fine Chemical Company
and Dr. Brigitte Saliva for financial support. Thanks are also due
to Dr. Michel Giorgi for his kind assistance with X-ray analysis of
compounds 3f and 4f. C. J. N. thanks CNRS and Region PACA
for a doctoral fellowship.
(2R,5S)-2-(5-Fluorophenyl-2-hydroxy)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane–Borane (4e): Prepared by the general pro-
cedure from 3e (1.02 g, 2.5 mmol) in 76% yield (0.63 g). White so-
lid, m.p. 80–85 °C. [α]2D5 = –171.8 (c = 1, CH2Cl2). 1H NMR
(200 MHz, CDCl3): δ = 0.0–0.8 (m, 1 H), 1.0–1.2 (m, 2 H), 1.7–2.1
(m, 4 H), 3.1–3.4 (m, 2 H), 3.6–3.9 (m, 2 H), 4.0–4.1 (m, 1 H), 6.7–
7.2 (m, 8 H), 9.3 (s, 1 H) ppm. 13C NMR (50.30 MHz, CDCl3): δ
= 26.4 (d, J = 3 Hz), 31.8, 48.6 (d, J = 4 Hz), 52.5 (d, J = 2 Hz),
62.1, 116.4 (d, J = 35 Hz), 117.3 (d, J = 3 Hz), 18.7 (d, J = 2 Hz),
119.1 (d, J = 2 Hz), 119.3, 120.9 (d, J = 15 Hz), 122.4, 129.2, 141.7
(d, J = 6 Hz), 157.9 ppm. 31P NMR (40.50 MHz, CDCl3): δ = 105.4
[1]
[2]
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(broad) ppm. IR (neat, cm–1): ν = 1187 (s), 1287 (s), 1310 (s), 1501
˜
(s), 1602 (s), 1630 (m), 2348 (m, BH), 2387 (s, BH), 2883 (m), 2950
(m), 2975 (m), 3095 (m), 3470 (s, OH). C17H21BFN2OP (330.14):
calcd. C 61.85, H 6.41; found C 61.78, H 6.56.
(2R,5S)-2-(5-tert-Butylphenyl-2-hydroxy)-3-phenyl-1,3-diaza-2-
phosphabicyclo[3.3.01,5]octane–Borane (4f): Prepared by the general
procedure from 3f (1.12 g, 2.5 mmol) in 80% yield (0.74 g). White
solid, m.p. 134–140 °C. [α]2D5 = –170.0 (c = 1, CH2Cl2). H NMR
1
(200 MHz, CDCl3): δ = 0.2–1.0 (m, 2 H), 1.0 (s, 9 H), 1.1–1.3 (m,
1 H), 1.6–2.2 (m, 4 H), 3.1–3.4 (m, 2 H), 3.6–3.8 (m, 1 H), 3.8–3.9
(m, 1 H), 4.0–4.1 (m, 1 H), 6.6–6.7 (m, 1 H), 6.9–7.3 (m, 7 H), 9.8
(m, 1 H) ppm. 13C NMR (50.30 MHz, CDCl3): δ = 26.3, 31.0, 31.9,
33.8, 48.9 (d, J = 4 Hz), 51.7, 62.1 (d, J = 4 Hz), 114.3 (d, J =
54 Hz), 116.8 (d, J = 3 Hz), 119.4 (d, J = 2 Hz), 122.6, 128.5 (d, J
= 16 Hz), 129.0, 131.0, 141.9, 142.0 (d, J = 5 Hz), 156.9 ppm. 31P
NMR (40.50 MHz, CDCl3): δ = 107.5 (broad) ppm. IR (neat,
[3]
a) G. Buono, O. Chiodi, M. Wills, Synlett 1999, 377–388; b)
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For some recent reviews, see: a) J. M. Brunel, B. Faure, M.
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[4]
[5]
cm–1): ν = 1187 (s), 1287 (s), 1310 (s), 1501 (s), 1602 (s), 1630 (m),
˜
2348 (m, BH), 2387 (s, BH), 2883 (m), 2950 (m), 2975 (m), 3095
(m), 3470 (s, OH). C21H30BN2OP (368.26): calcd. C 68.49, H 8.21;
7.61; found C 68.36, H 8.32, N 7.56.
(2R,5S)-2-(2-Hydroxy-5-methoxyphenyl)-3-phenyl-1,3-diaza-2-phos-
phabicyclo[3.3.01,5]octane–Borane (4 g): Prepared by the general
procedure from 3 g (1.05 g, 2.5 mmol) in 84% yield (0.72 g). White
solid, m.p. 129–134 °C 1H NMR (200 MHz, CDCl3): δ = 0.1–1.1
(m, 3 H), 1.7–2.2 (m, 4 H), 3.1–3.5 (m, 2 H), 3.5 (s, 3 H), 3.6–4.1
(m, 3 H), 6.6–7.3 (m, 8 H), 8.5 (s, 1 H) ppm. 1 3 C NMR
(50.30 MHz, CDCl3): δ = 26.3 (d, J = 3 Hz), 31.8 (d, J = 1 Hz),
48.6 (d, J = 4 Hz), 52.2 (d, J = 2 Hz), 55.4, 62.0 (d, J = 3 Hz),
114.7 (d, J = 15 Hz), 116.2 (d, J = 32 Hz), 118.6 (d, J = 6 Hz),
119.0 (d, J = 4 Hz), 121.0 (d, J = 2 Hz), 122.4, 129.1, 142.0 (d, J
= 6 Hz), 152.4 (d, J = 14 Hz), 153.0 (d, J = 3 Hz) ppm. 31P NMR
[6]
a) R. M. Stoop, A. Mezzetti, F. Spindler, Organometallics 1998,
17, 668–675; b) U. Nettekoven, P. C. J. Kamer, P. W.
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hedron: Asymmetry 2004, 15, 2213–2218.
(40.50 MHz, CDCl ): δ = 104.9 (broad) ppm. IR (neat, cm–1): ν =
˜
3
1187 (s), 1287 (s), 1310 (s), 1501 (s), 1602 (s), 1630 (m), 2348 (m,
BH), 2387 (s, BH), 2883 (m), 2950 (m), 2975 (m), 3095 (m), 3470
(s, OH). C18H24BN2O2P (342.18): calcd. C 63.18, H 7.07; found C
63.26, H 6.96.
[7]
[8]
D. Moulin, C. Darcel, S. Jugé, Tetrahedron: Asymmetry 1999,
(2R,5S)-2-(1-Hydroxy-2-naphthyl)-3-phenyl-1,3-diaza-2-phospha-
bicyclo[3.3.01,5]octane–Borane (4h): Prepared by the general pro-
cedure from 3h (1.10 g, 2.5 mmol) in 40% yield (0.36 g). White so-
lid, m.p. 146–152 °C. 1H NMR (200 MHz, CDCl3): δ = 0.3–1.1 (m,
3 H), 1.6–2.2 (m, 4 H), 3.3–3.7 (m, 3 H), 3.9–4.1 (m, 2 H), 6.8–7.8
(m, 11 H), 12.7 (s, 1 H) ppm. 31P NMR (40.50 MHz, CDCl3): δ =
10, 4729–4743.
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[9]
108.9 (broad) ppm. IR (neat, cm–1): ν = 1187 (s), 1287 (s), 1310
˜
(s), 1501 (s), 1602 (s), 1630 (m), 2348 (m, BH), 2387 (s, BH), 2883
1506
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 1499–1507

New P-Stereogenic (o-Hydroxyaryl)diazaphospholidine–Borane Complexes
FULL PAPER
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.
[22] In order to optimise the yield, the reaction was conducted in a
one-pot procedure. Nevertheless, compound 1 can be isolated
and purified by distillation under reduced pressure. Colorless
oil; b. p. 120 °C (0.01 mbar). 1H NMR (200 MHz, CDCl3): δ =
1.6–1.9 (m, 3 H), 2.0–2.2 (m, 1 H), 2.7 (d, J = 9 Hz, 6 H), 3.2–
3.4 (m, 2 H), 3.5–3.7 (m, 1 H), 3.8–3.9 (m, 1 H), 4.1–4.3 (m, 1
H), 6.8–7.1 (m, 3 H), 7.3–7.4 (m, 2 H) ppm. 13C NMR
(50.30 MHz, CDCl3): δ = 25.3 (d, J = 4 Hz), 32.1, 36.6 (d, J =
17 Hz), 50.1 (d, J = 40 Hz), 54.2 (d, J = 6 Hz), 62.1 (d, J =
7 Hz), 114.3 (d, J = 11 Hz), 117.4, 128.7, 146.3 (d, J = 14 Hz)
ppm. 31P NMR (40.50 MHz, CDCl3): δ = 118.0 ppm.
[23] CCDC-287827 (for 3f) contains the supplementary crystallo-
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charge from The Cambridge Crystallographic Data Centre via
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Received: October 28, 2005
Published Online: December 30, 2005
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Eur. J. Org. Chem. 2006, 1499–1507
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1507