Modular synthesis of novel chiral phosphorous triamides based on (S)-N(pyrrolidin-2-ylmethyl)aniline and their application in asymmetric catalysis

Article abstract of DOI:10.1002/ejoc.200900477

A set of new P-chiral phosphorous triamides (PTAs) based on the (S)-N-(pyrrolidin-2-ylmethyl)aniline backbone was prepared by modular synthetic procedures. The chirality at: phosphorus can be controlled to a large extent by the synthetic route, and high d

Full text of DOI:10.1002/ejoc.200900477

FULL PAPER
DOI: 10.1002/ejoc.200900477
Modular Synthesis of Novel Chiral Phosphorous Triamides Based on (S)-N-
(Pyrrolidin-2-ylmethyl)aniline and Their Application in Asymmetric Catalysis
Katalin Barta,[a] Markus Hölscher,[a] Giancarlo Franciò,*[a] and Walter Leitner*[a]
Keywords: P ligands / Aminophosphanes / Hydrovinylation / Michael addition / Asymmetric catalysis
A set of new P-chiral phosphorous triamides (PTAs) based on
the (S)-N-(pyrrolidin-2-ylmethyl)aniline backbone was pre-
pared by modular synthetic procedures. The chirality at
phosphorus can be controlled to a large extent by the syn-
thetic route, and high diastereomeric purities were achieved
for most of the reported ligands. This ligand family was
evaluated in the copper-catalysed Michael addition of dieth-
ylzinc to cyclohex-2-enone, and moderate enantioselectivit-
ies were achieved. In the asymmetric nickel-catalysed hydro-
vinylation of styrene, good conversions and chemoselectivi-
ties, together with promising enantioselectivities of up to
60%, were obtained with the new PTA ligands even at rela-
tively high reaction temperatures.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
The P-chiral PTA 3 (Figure 1), based on the (S)-N-(pyr-
rolidin-2-ylmethyl)aniline (6, Scheme 1) moiety, was re-
Introduction
Phosphorous triamides (PTAs) have been known for a ported previously by Buono and co-workers, who used this
long time as ligands for transition metal complexes.[1] How- compound as an intermediate for the synthesis of phosphor-
ever, in sharp contrast with other ligands formally derived ous diamidites[5a,10] and iminoazaphosphorlidine deriva-
from phosphorous acid,[2–6] very few studies on the synthe- tives.[11] This PTA was also used as a derivatising agent for
sis and application of PTAs in asymmetric catalysis have the determination of the enantiomeric purities of chiral
been reported. The first example of their use in transition- alcohols by 31P NMR spectroscopy.[12] This method relies
metal-catalysed enantioselective transformations was de- on the facile cleavage of the exocyclic P–N bond by
scribed by Reetz et al.[7] The binaphthyldiazaphospholidine- alcohols, resulting in the corresponding diastereomeric
based PTA 1 (Figure 1) was found to be very sensitive to phosphorous diamidites and gaseous dimethylamine as the
air and moisture and was isolated as a borane adduct. This by-product. Only recently have P-chiral PTAs also been
ligand gave good activity, but low enantioselectivity in the considered as ligands and applied in asymmetric catalysis.
Rh-catalysed hydroformylation of styrene, whereas no con- SchraderЈs group used 3 in Cu-catalysed Michael additions
version was achieved in the Rh-catalysed hydrogenation of of diethylzinc to enones and obtained low enantioselectivi-
dimethyl itaconate.[7] The introduction of electron-with- ties (10–20%).[13] Tsarev et al. reported a variety of ligands
drawing substituents at the nitrogens greatly improves the based on the (S)-N-(pyrrolidin-2-ylmethyl)aniline moiety,
stability of PTAs towards moisture.[8] Gennari and co- including the PTAs 4 and 5 (Figure 1).[14] In the presence
workers prepared a variety of ligands of general formula 2 of 5, low yields (up to 18%) but fairly good enantio-
(Figure 1), each containing an electron-poor bis(sulfonyl)- selectivities (up to 62%) were achieved in the Pd-catalysed
diazaphospholidine moiety.[9] These phosphorous triamide allylic substitution of 1,3-diphenylallyl acetate, whereas 4
ligands, with different diamine and monoamine backbones, gave much lower ee values.[14]
were applied in the Cu-catalysed conjugate addition of di-
ethylzinc to cyclohex-2-enone. Low enantioselectivities were
obtained with the majority of the ligands, except with a
binaphthyl-based PTA, which led to an enantioselectivity
of 75%.[9]
Here we report a series of new P-chiral PTAs of the gene-
ral formula shown in Scheme 1, based on the (S)-N-(pyrrol-
idin-2-ylmethyl)aniline (6) backbone as the common chelat-
ing diamine scaffold. Because of the C1 symmetry of the
ligands the phosphorous atom is stereogenic and two dif-
ferent epimers at the P-stereocenter are possible. Steric and
electronic tuning of the ligands was accomplished by varia-
tion of the monoamine components, including the incorpo-
ration of a further two chiral structures in this part.[15] The
diastereomeric ratio between the resulting epimers at phos-
phorus can be controlled to a large extent by use of an
[a] Institut für Technische Chemie und Makromolekulare Chemie,
RWTH Aachen University,
Worringerweg 1, 52074, Germany
Fax: +49-241-8022177
E-mail: francio@itmc.rwth-aachen.de
leitner@itmc.rwth-aacchen.de
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Novel Phosphorous Triamides
Figure 1. Chiral PTA ligands applied in asymmetric catalysis.
appropriate synthetic route, and high diastereomeric purit- PCl3 by a literature procedure.[17] Although the formation
ies have been achieved for most of the described ligands.
of 7 was reported to proceed with complete stereoselec-
tion,[17] in our hands compound 7 was repeatedly obtained
as a mixture of the two diastereomers 7a and 7b (Figure 2)
in a ratio of 3.5:1 as indicated by 31P NMR spectroscopy
(δ = 153.9 ppm and 145.3 ppm, respectively). Because ra-
cemisation of the starting enantiomerically pure diamine
under the reaction conditions could be excluded, the two
diastereomers must be epimers at the phosphorus. More-
over, the signals of 7a and 7b were found to be broad in the
1H and 13C NMR spectra at room temperature, indicating a
rapid equilibrium between the two diastereomers. This was
confirmed by EXSY 31P NMR measurements, which clearly
show that the two signals at δ = 153.9 ppm and δ =
145.3 ppm are interconverting (Figure 2). Variable-tempera-
ture NMR measurements also showed that the signals be-
came sharper at low temperature and broadened at higher
temperature but the coalescence temperature could not be
reached up to 70 °C in [D8]toluene. Notably, however, the
addition of triethylamine (0.5 equiv.) led to the coalescence
of the two signals at room temperature, showing that the
presence of a base accelerates the epimerisation process.[18]
Scheme 1. Possible synthetic routes for preparation of PTAs.
This ligand family was evaluated in two benchmark C–C
bond-forming reactions. Moderate enantioselectivities were
achieved in the copper-catalysed Michael addition of di-
ethylzinc to cyclohex-2-enone. In the more challenging
asymmetric nickel-catalysed hydrovinylation of styrene,
though, promising enantioselectivities of up to 60% were
obtained together with good levels of conversion and
chemoselectivity even at relatively high reaction tempera-
tures.
Results and Discussion
Synthesis and Structure
Like other phosphorous[2] or phosphoric acid[16] deriva-
tives, PTAs are in principle accessible by two convergent
synthetic routes starting from PCl3 (Scheme 1).[9] Route A
first involves the formation of chlorodiaminophosphane 7,
which is subsequently converted into the desired PTAs by
treatment with secondary amines. Alternatively, Route B
first entails the synthesis of dichloroaminophosphanes,
which are then treated with the diamine 6. As will be shown
in detail, the two synthetic routes are not in all cases equiva-
lent but are instead complementary.
Ligand Synthesis by Route A
The chlorodiaminophosphane 7 was first synthesised by
treatment of (S)-N-(pyrrolidin-2-ylmethyl)aniline (6) with Figure 2. EXSY 31P NMR spectrum of 7.
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The 31P NMR chemical shift reported for 7 in the literature tially as anti diastereomers. DFT calculations on 7a and 7b
(δ = 153.6 ppm in CDCl3) corresponds to that measured [M052X/6–31G(d); IEF-PCM in toluene solution] con-
after addition of triethylamine.
firmed, however, that 7a (syn) is more stable than 7b (anti)
The signal at δ = 153.9 ppm in 31P NMR was assigned by 2.2 kcalmol–1 in full accordance with the experimental
to the syn diastereomer 7a (absolute configuration SP) and findings.
the signal at δ = 145.3 ppm to the anti diastereomer 7b (ab-
Treatment of the diastereomeric mixture 7 with various
2
solute configuration RP) on the basis of the JC(1),P value secondary amines afforded ligands L1–L11 with high dia-
in low-temperature 13C NMR measurements (0 and 22 Hz, stereomeric purities and in good to excellent yields
respectively).[19] The fact that the syn diastereomer is pre- (Table 1). Although the major epimer of the starting chloro-
dominant over the anti diastereomer is different from the diaminophosphane 7 has a syn configuration, all the re-
situation with the related phosphorous diamidites and tria- sulting PTAs are obtained predominantly as anti dia-
mides based on (S)-pyrrolidin-2-yl-methylamine,[5,10–14] as stereomers, in accordance with related previously reported
well as with phosphorous diamidites and phosphoramidites PTAs.[12,13,17] Ligands L1–L11 show sharp signals in their
based on (S)-prolinol,[20] which were all obtained preferen- 1H, 13C and 31P NMR spectra, and no variation in their
Table 1. Diastereomeric purities of (S)-N-(pyrrolidin-2-ylmethyl)aniline-based PTAs.
[a] Absolute configuration at the phosphorus confirmed by crystal structure measurement. [b] Ligand L3 was also reported in reference 14.
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Novel Phosphorous Triamides
relative peak intensities was observed on standing either as ent) in one-step, in most cases yielding the ligands in high
solids or in solution, excluding epimerisation processes. purity.
Moreover, EXSY 31P NMR measurements of selected li-
Single crystals suitable for X-ray crystal structure analy-
gands showed no exchange, thus confirming configura- sis were obtained for the major diastereomers of L6 and
tional rigidity at the phosphorus centres. These observa- L8 by crystallisation from C6D6 at room temperature. The
tions suggest that dynamic kinetic resolution during the re- molecular structures of both ligands are depicted in Fig-
action between 7 and the secondary amine is responsible ure 3 and each displays the anti configuration, correspond-
for the observed high diastereoselectivities (Scheme 2). An ing to absolute configurations at phosphorus as SP for L6
excess of the secondary amine was used for the preparation and RP for L8. The exocyclic P–N1 bonds are considerably
of ligands L3–L7, acting both as building block and hydro- shorter than the P–N bonds within the phosphorus hetero-
chloride scavenger (Table 1, Entries 3–7). Alternative bases cycles and the P–N3 bonds are again shorter than the P–N2
were used for less basic or more expensive amine units: bonds. In both structures, the nitrogen atoms N1 and N2
DMAP [4-(dimethylamino)pyridine] was chosen as the hy- are almost planar, whereas the N3 nitrogens involved in the
drochloride scavenger for the synthesis of ligands L8–L9 pyrrolidine rings are slightly pyramidal (sums of all angles:
(Table 1, Entries 8–9), whereas deprotonation of the sec- 349.9° and 341.2° for L6 and L8, respectively) and can be
ondary amines with nBuLi was employed for the synthesis considered additional stereocentres, both with S configura-
of ligands L1–L2 and L10–L11 (Table 1, Entries 1–2 and tions. The N2–P–N3 angles around phosphorus in the five-
Entries 10–11). The crude products from the synthesis were membered heterocycles are ca. 90°, leading to significant
purified by filtration through a short pad of neutral alu- distortions from tetrahedral arrangements around the chiral
mina. This purification method allows the removal of the P centres. The five-membered ring in L6 adopts an envelope
hydrochloride salt and of unreacted starting amine (if pres- conformation, whereas in L8 it is twisted.
Scheme 2. Modular synthesis Route A.
Figure 3. Structures of L6 (left) and L8 (right) in the solid state. Hydrogen atoms have been omitted for clarity. Selected atom distances
[Å] and angles [°]: L6: P–N1 1.678(1); P–N2 1.738(1); P–N3 1.711(1); N1–P–N3 108.87°; N1–P–N2 100.59°; N2–P–N3 90.97°; sums of all
angles at nitrogen: N1 359.17°, N2 359.21°, N3 340.46°; L8: P–N1 1.671(1): P–N2 1.739(1); P–N3 1.708(1); selected angles: N1–P–N3
106.44°; N1–P–N2 103.57°; N2–P–N3 89.84°; sums of all angles at nitrogen: N1 359.26°, N2 355.17°, N3 341.24°.
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Ligand Synthesis by Route B
in favour of L1 obtained by Route A is the result of kinetic
control during the P–N bond formation. With introduction
of the bidentate amine in the last step, this differentiation
is not effective and both diastereomers are formed accord-
ing to their relative stabilities. With the dichloroaminophos-
phane (S,S)-8 the diastereomeric mixture M2 was formed;
this even predominantly contains the syn diastereomer L13,
in a 3:1 ratio to L2 (Table 2, Entry 2).
After demonstrating that Route A is especially suitable
for the modular synthesis of ligands L1–L11 with high dia-
stereomeric purity in favour of the anti diastereomers, we
investigated the alternative Route B, in which the bidentate
amine is introduced at the last stage. For this purpose,
structures L1 and L2 (Table 2), each bearing a chiral bis(1-
phenylethyl)amine group, were selected. Firstly, the synthe-
ses of the corresponding dichloroaminophosphane interme-
diates were carried out by treatment of (R,R)-bis(1-phenyl-
ethyl)amine and its enantiomer with PCl3.[9] The syntheses
of these compounds could be optimised by using DMAP as
the base and adjusting the reaction conditions. The desired
dichloroaminophosphane intermediates (R,R)-8 and (S,S)-
8 were obtained in excellent yields (95%) in analytically
pure forms after extraction with pentane. Subsequently,
these precursors were each treated with (S)-N-phenyl-2-
(aminomethyl)pyrrolidine (6) in the presence of 2 equiv. of
DMAP at room temperature (Scheme 3).
Table 2. Chemical shifts and compositions of the diastereomeric
mixtures M1 and M2.
Interestingly, the two synthetic routes were found not to
be equivalent in terms of the stereochemical control over
the product. In contrast with Route A, in which the syn
epimers of ligands L1 and L2 were barely detectable, these
epimers were formed in significant quantities when Route B
was applied. In particular, on starting from (R,R)-8 a dia-
stereomeric mixture (M1) consisting of a 1:1.1 ratio of L1
and its syn diastereomer L12 was obtained (Table 2, En-
try 1). This experimental result could be supported by DFT
[a] The configurations of the ligands are given as follows: firstly the
configuration of the pyrrolidine carbon, secondly and thirdly the
configurations of the carbons on the chiral secondary amine part,
and fourthly the configuration at the phosphorus.
Repeated attempts to isolate the syn diastereomer L12
calculations. Geometry optimizations of L1 and L12 from the mixture M1 by crystallisation and column
showed a negligible difference of 0.02 kcalmol–1 [M052X/ chromatography proved unsuccessful. However, upon con-
6–31G(d); gas phase] in the Gibbs free energies, in favour version of the oily M1 into the corresponding solid borane
of L12. This means in turn that the high diastereoselectivity adduct M1·BH3, it was possible to isolate the L1·BH3 anti
Scheme 3. Synthesis of diastereomeric mixtures M1 and M2 by Route B.
Figure 4. Crystal structure of L1·BH3: front view (left) and rear view (right) showing the proximity of two phenyl rings. Hydrogen atoms
have been omitted for clarity. Selected atom distances [Å] and angles [°]: P–B 1.910(6); P–N1 1.653(4); P–N2 1.658(4); P–N3 1.695(4); N1–
P–N3 111.6(2)°; N1–P–N2 110.43(18)°; N2–P–N3 92.8(2)° sums of all angles around nitrogen: N1 358.1°, N2 356.0°, N3 349.9.
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Novel Phosphorous Triamides
diastereomer in 15% yield by crystallisation. Crystals suit- Table 3. Cu-catalysed addition of ZnEt2 to cyclohex-2-enone.[a]
able for X-ray analysis were obtained by slow diffusion of
pentane into a CDCl3 solution of the pure L1·BH3 dia-
stereomer and the absolute configuration at the phosphorus
was confirmed as SP (Figure 4).
The crystal structure of L1·BH3 shows features similar
to those of L6 and L8: the nitrogen atoms N1 and N2 are
almost planar (angle sums at the nitrogens: 358.1° and 356°,
respectively), whereas N3 embedded in the pyrrolidine ring
is slightly pyramidal (S configuration, angle sum 349.9°).
The P–N bond lengths increase in the order P–N1 Ͻ P–N3
Ͻ P–N2 (1.653 Å, 1.658 Å, 1.695 Å, respectively). The N2–
P–N3 angle in the heterocycle is the smallest at 92.8°,
whereas the other two show very similar values: 110.4° for
N1–P–N2 and 111.6° for N1–P–N3. The two methyl groups
of the chiral secondary amine moiety point in the same di-
rection. Moreover, the phenyl group of the 1-phenylethyl-
amine and the phenyl group of the diazaphospholidine part
are close enough (≈ 4 Å) for a possible extended π–π inter-
action (Figure 4).[21]
Catalytic Applications
Copper-Catalysed Conjugate Addition
The Cu-catalysed conjugate addition of diethylzinc to cy-
clohex-2-enone (Scheme 4) is a well-established reaction for
monodentate PIII ligands, especially for phosphoramid-
ites.[22] Moderate enantioselectivities in a family of electron-
poor bis(sulfonyl)diazaphospholidine PTAs were reported
by Gennari.[9] As part of a kinetic study, Schrader recently
compared the activities of several phosphorous diamidite
ligands based on the chiral (pyrrolidin-2-yl)methylamine
moiety, including PTA 3.[13] The catalysts based on the
phosphorous diamidites resulted in faster formation of 10
than were achieved with 3. However, a very low enantio-
selectivity of 10–20% was obtained in the presence of 3.
Scheme 4. Michael addition of diethylzinc to cyclohex-2-enone.
For a first evaluation of ligands L1–L12, we adopted the
reaction conditions described by Gennari, with Cu(OTf)2
(5 mol-%) in toluene at –20 °C and a 5 h reaction time.[9] In
addition, we also performed the catalytic reactions at a
lower temperature (–35 °C) with a longer reaction time
(12 h). The results are summarised in Table 3.
Full conversion was obtained with all ligands containing
the chiral bis(1-phenylethyl)amine moiety within the indi-
cated times both at –35 °C and –20 °C, and no significant
variation in the enantioselectivity was observed in this tem-
perature range (Table 3, Entries 1–4). Interestingly, the dia-
stereomeric mixtures M1 and M2 both led to the preferen-
tial formation of the R product in 23% and 38% ees, respec- 5 mol-%, ligand 10 mol-%.
[a] Reaction conditions: toluene, substrate: 0.1 mmol, Cu(OTf)2
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tively (Table 3, Entries 1–2). In contrast, pure L1 and L2 Table 4. Cu-catalysed addition of ZnEt2 to cyclohex-2-enone under
optimised conditions.[a]
(both with anti arrangements) led to a product with oppo-
site absolute configuration (S) with slightly lower ee values
(Table 3, Entries 3–4). The switch in the absolute configura-
tion of 10 from R to S with use of the diastereomerically
pure ligands L1 and L2 indicates that the chiral information
at the donor atom has a major impact on the outcome of
the catalysis. Moreover, the slightly higher ee values ob-
tained with M1 and M2 in relation to those achieved with
L1 and L2 suggest that the syn-configured ligands should
represent the “matched” diastereomeric ligands for these
transformations. As discussed above, attempts to isolate the
pure syn-configured diastereomers L12 and L13 from M1
and M2 (also as their copper complexes) were not success-
ful. The use of excesses of M1 and M2 in order to adjust
the ratios of L12:[Cu] and L13:[Cu] precisely to 2:1 did not
improve the enantioselectivity.[23]
[a] Reaction conditions: CH2Cl2, t = 12 h, T = –20 °C, substrate:
0.1 mmol, 5 mol-% CuI, 10 mol-% ligand.
An enantiomeric excess in a similar range was achieved
with ligand L11, bearing the sterically much less de-
manding, achiral pyrrole as secondary amine moiety (En-
try 13). Ligands L3, L4 and L5, structurally similar to L11
but containing the more basic piperidine, pyrrolidine and
morpholine moieties, turned out to lead to low conversions
and enantioselectivities at –35 °C (conv. 46–48%; ee 6–8%;
the performance of L13 in M2 indicates that further activi-
ties should be concentrated on the selective synthesis of the
syn diastereomers as potential lead structures.
Catalytic Applications: Nickel-Catalysed Asymmetric
Hydrovinylation of Styrene
For many years the state of the art in nickel-catalysed
Entries 5–7). Notably, ligands L3 and L4 gave higher asymmetric hydrovinylation[26] was defined by the azaphos-
enantioselectivities at –20 °C.[24] Ligands L6, L7 and L9, pholene ligand developed by Wilke et al. in the early
incorporating the acyclic diisopropyl-, di-n-butyl- and di- 1980s.[27] In 2002, we showed that phosphoramidites such
benzylamino moieties, respectively, gave high levels of con- as Cl-Quinaphos[28] or the Feringa ligand[22b] provide high
version but modest enantioselectivities (Entries 8, 9 and 11). activity and enantioselectivity in the hydrovinylation of styr-
Very low enantioselectivity was achieved with ligand L8 enes,[29] and since then numerous examples of synthetically
bearing (as a monoamine) the chiral (R)-(1-phenylethyl) useful applications of related catalytic systems have been
amino structure (Entry 10). The best performance for this reported.[30] Although the Wilke and the Feringa ligands
ligand class was observed with the (diphenylamino)-substi- may appear rather different at the first glance, superimpo-
tuted ligand L10, with a 50% enantiomeric excess at full sitions of their solid-state structures show important struc-
conversion both at –20 and at –35 °C (Entry 12).
tural similarities.[26] In particular, the ligand regions in-
The most promising ligands for this screening were tested volved in the coordination to the nickel centre are closely
further under the conditions introduced by Buono.[25] The related, both including a (1-phenylethyl)amine moiety and
results are summarized in Table 4. The diastereomeric mix- (at least) one P–N bond. These structural analogies and the
ture M2 performed significantly better with CuI as the cop- similar results in catalysis suggest that the two ligands may
per precursor and with the catalysis carried out in dichloro- operate in essentially the same way.[31] Among the ligands
methane (Table 3, Entry 1 vs. Table 4, Entry 1). The reported here, L8 has the same structural motif, whereas no
enantioselectivity could be improved to 60% under these such unit is present in the related structure L10, as shown
conditions. The use of water as an additive resulted in the in Figure 5.
formation of racemic 10, probably because of the high
In order to assess the potential of PTAs for the hydrovi-
water sensitivity of this ligand. In the case of L10, the nylation of styrene the new ligands L4, L8 and L10 were
enantioselectivity could be slightly improved from 50 to applied by use of [Ni(allyl)Br]2 as precursor with NaBARF
55% under these new conditions and up to 58% ee with as activator at different temperatures ranging from –50 to
addition of water (0.5 equiv. with respect to the substrate).
0 °C (Scheme 5). The same catalyst loading of 0.17 mol-%
In summary, the ee values obtained with the the dia- was used in all experiments. The results are summarised in
stereomeric mixture M2 and with L10 are slightly higher Table 5.
than those achieved with the related QUIPHOS ligands un-
The pyrrolidine-containing ligand L4 provided good
der the same conditions[25] and are at the same time among conversion and good chemoselectivity, but low enantio-
the best values known for PTA ligands.[9] The improve- selectivity (Table 5, Entry 1). The diphenyl-substituted li-
ments achieved upon variation of the monoamine part gand L10 gave the most active catalyst among the tested
nicely demonstrate the potential of the modular synthetic ligands. It provided 68% conversion within 3 hours at
approach. Although the enantiomeric excesses are, cur- –50 °C with 85% selectivity for 12, but the asymmetric in-
rently, not competitive with those achievable with phos- duction remained low at 33% (Entry 2). At higher tempera-
phoramidite ligands, the fact that L2 probably counteracts ture the reaction did not stop at the primary product 12,
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Novel Phosphorous Triamides
Figure 5. Structural analogies between established ligands for hydrovinylation and some PTAs of this study.
Scheme 5. Nickel-catalysed asymmetric hydrovinylation of styrene.
Table 5. Hydrovinylation of styrene with various PTAs.[a]
of 12 (92–99%, Entries 3–4). This subsequent isomerisation
coupled with kinetic resolution is a common side reaction
in hydrovinylation,[32] but is typically much more pro-
nounced for Pd-based catalysts.[33] In contrast with L4 and
L10, the ligand L8 exhibits a lower reactivity, but consider-
ably higher asymmetric induction in the C–C bond-forming
step. At –15 °C, a 60 % ee was achieved for the S isomer,
with a chemoselectivity of 86% and only a small degree of
isomerisation to 13 (Entry 5). Even at 0 °C, which is a rela-
tively high temperature for selective hydrovinylation, good
yields (77%) of 12 and fair enantioselectivities of 63% ee
could be achieved (Entry 6). This finding is in accordance
with the structural similarities of L8 to other suitable hy-
drovinylation ligands as outlined in Figure 5.
Conclusions
A set of new phosphorous triamide (PTA) ligands based
on (S)-pyrrolidin-2-yl-methyl-amine has been prepared
through a modular synthetic approach from readily avail-
able building blocks. The described PTAs each contain an
additional stereocentre at the phosphorus, so each ligand
may be formed as mixture of two diastereomers. We have
shown that the ratio between the diastereomers can be con-
trolled by using different synthetic routes. By starting from
dichloroaminophosphane 7, high diastereomeric purity in
favour of the anti diastereomers can be achieved for ligands
L1–L11. In contrast, by coupling the diamine 6 with the
dichloro-aminophosphanes (R,R)-8 and (S,S)-8, the dia-
stereomeric mixtures M1 and M2, respectively, predomi-
nantly containing the syn diastereomers, were obtained. Li-
gands with anti stereochemical arrangements were structur-
ally characterised by single-crystal X-ray diffraction.
[a] Reaction conditions: CH2Cl2, styrene (0.1 mmol), ethylene
(1 bar), [Ni(allyl)Br]2 (0.17 mol-%), ligand (0.32 mol-%), NaBARF
(0.32 mol-%).
Moderate enantioselectivities of up to 60% could be
achieved in the copper-catalysed conjugate addition of di-
but rapid isomerisation to the thermodynamically more ethylzinc to cyclohex-2-enone. Importantly, the sign of the
stable 13 occurred. Kinetic resolution of the primary prod- enantioselectivity is directly related to the absolute configu-
uct led to very high ees in the remaining small amounts ration at the P atom, and with the diastereomeric mixture
Eur. J. Org. Chem. 2009, 4102–4116
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4109

K. Barta, M. Hölscher, G. Franciò, W. Leitner
FULL PAPER
spectra were recorded at room temperature. The assignment of the
chemical shifts was carried out on the basis of two-dimensional
M2 the presence of the syn diastereomer led to a higher ee
with respect to the pure anti-L2. Among the ligands bearing
an achiral monoamine backbone, L10 turned out to be the
best, giving up to 58% ee in the same reaction. These results
are comparable with those achieved with the best PTA li-
gands.
Moreover, PTA ligands have been applied for the first
time in asymmetric hydrovinylation with promising results.
Good yields (77%) and enantioselectivities of up to 63%
were achieved with L8 even at a relatively high reaction
temperature of 0 °C. The presence of the 1-phenylethyl-
amine moiety was found to be beneficial for the perform-
ance, similar to other P-donor ligands.
This study significantly increases the information on
structure and reactivity relating to the so far underrepre-
sented class of PTA ligands. Further directions should con-
centrate on a selective preparation of the pure syn dia-
stereomers and possible applications requiring similar bind-
ing properties as in the nickel-catalysed hydrovinylation re-
action.
1
NMR spectra (31P-1H HMBC, H-1H COSY, 13C-1H HMBC, 13C-
1H HSQC, NOESY). The atom numbering is defined in the chemi-
cal as shown and does not comply with nomenclature rules.
31P{1H} EXSY spectra were recorded with a modified NOESY
pulse sequence to have 1H broadband decoupling in the phase sen-
sitive mode. A total of 128 scans per FID of 512 or 1 K data points
were used per time increment. A total of 128 increments were col-
lected. The EXSY measurements were repeated with a series of
mixing times: tm = 5 µs, 0.5 ms, 2 ms, 10 ms, 50 ms, 100 ms, 200 ms
and 300 ms.
High-resolution MS measurements were performed with a Finni-
gan-MAT 95 spectrometer (EI, 70 eV). The mass of the molecule
ion is given.
Syntheses
(S)-5-Oxopyrrolidine-2-carboxanilide: The synthesis was carried out
by a modification of the literature procedure because the originally
reported methodology resulted in our hands in scalemic product
mixtures.[10] In a round-bottomed flask fitted with a reflux cooler,
-glutamic acid (10.00 g, 67.9 mmol) was suspended in aniline
(6.2 mL, 67.9 mmol, 1 equiv.) and the mixture was stirred at 150 °C
for three days. The cooler was removed and methanol (100 mL)
was added to the hot viscous brown material. The mixture was
allowed to cool to room temperature, whereupon the product crys-
tallised from the solution. The crystals were filtered off on a
Büchner flask and washed several times with acetone until the fil-
trate appeared colourless. The product was recrystallised from
methanol (100 mL): 9.70 g (70% yield). The spectroscopic data are
in agreement with those described in the literature.
Experimental Section
General Remarks: All reactions involving air-sensitive chemicals
were performed under argon by use of standard Schlenk techniques
or a glove box.
Reagents nBuLi (1  solution in hexane), CuI, Cu(OTf), Cu-
(OTf)2, cyclohex-2-enone, ethylbenzene, BH3 in THF, -glutamic
acid, piperidine, pyrrolidine, diisopropylamine, dibutylamine, di-
benzylamine, pyrrole, aniline, diphenylamine and PCl3 were pur-
chased from Aldrich. 4-(Dimethylamino)pyridine, LiAlH4 and di-
ethylzinc (1  solution in hexane) were purchased from Fluka.
(S)-N-(Pyrrolidin-2-ylmethyl)aniline (6): The reduction of (S)-5-oxo-
pyrrolidine-2-carboxanilide to (S)-N-(pyrrolidin-2-ylmethyl)aniline
(6) was carried out by the procedure described in the literature.[10]
The optical purity of the product was monitored by the following
method. (S)-N-(Pyrrolidin-2-ylmethyl)aniline (10 mg, 0.06 mmol)
was introduced by Pasteur pipette into an NMR tube fitted with a
screw cap. Subsequently, DMAP (14 mg, 0.12 mmol) and [D6]ben-
zene (0.5 mL) were added and the mixture was agitated for 5 min.
Compound (R,R)-8 (37.5 mg, 0.06 mmol) was dissolved in [D6]ben-
zene (0.5 mL) and added under argon to the previous solution by
syringe. The tube was closed, shaken and allowed to stand at room
temperature overnight. The optical purity of the amine was deter-
mined by the integration of the 31P NMR signals of the dia-
stereomeric adducts, with the presence of signals at δ = 108.8 ppm
and 86.3 ppm indicating R-configured amine impurity {d.r:
[(S,R,R,Rp) + (S,R,R,Sp)/(R,R,R,Sp) + (R,R,R,Rp)]}. 31P{1H}
NMR: δ = 108.8 (R,R,R,Sp), 105.8 (S,R,R,Rp), 90.2 (S,R,R,Sp),
86.3 (R,R,R,Rp) ppm.
Reagent Purification Procedures: PCl3 was heated at reflux for 3 h
and distilled under argon. Styrene and ethylbenzene were distilled
under reduced pressure and stored in the dark at –30 °C under
argon and over molecular sieves. Aniline and triethylamine were
distilled under reduced pressure and stored under argon. Liquid
amines and cyclohex-2-enone were transferred to a Schlenk flask
and stored under argon over molecular sieves. DMAP and diben-
zylamine were dried for 1 h in vacuo and stored under argon. The
concentration of nBuLi was determined by titration with phen-
anthroline prior to use. For filtration, neutral alumina (Fluka) with
Brockman activity 1 was used. It was transferred to a Schlenk flask
and dried in vacuo overnight at room temperature. GC analyses
were performed on a Sichromat 1–4 gas chromatograph. 1H, 13C
and 31P NMR spectra were recorded with Bruker DPX 300 and
AV 600 spectrometers. The operating frequencies of these spec-
trometers for NMR measurements are 300.1 MHz for 1H,
75.5 MHz for 13C and 121.5 MHz for 31P with the DPX 300 spec-
trometer and 600.1 MHz for 1H, 150.9 MHz for 13C and
242.9 MHz for 31P with the AV 600 spectrometer. For 1H and
13C{1H } NMR spectroscopy, the chemical shifts (δ) are given in
ppm with use of the residual solvent signals as internal standards.
For 31P NMR spectroscopy the chemical shift values (δ) are given
in ppm relative to 85% phosphoric acid as external standard. The
multiplicities of the signals were assigned by assuming spectra of
first order. The coupling constants (J) are given in Hertz. For the
description of the multiplicity of the signals the following symbols
are used: s = singlet, d = doublet, t = triplet, q = quadruplet, qi =
quintet, m = multiplet, br = broad. Unless otherwise indicated, the
(3aS)-1-Chloro-2-phenyl-hexahydro-1H-pyrrolo[1,2-c][1,3,2]diaza-
phosphole (7): The synthesis was carried out from (S)-N-(pyrrol-
idin-2-ylmethyl)aniline by the procedure described in the litera-
ture.[17]
1H NMR (CDCl3): δ = 1.62–1.82 (br, 1 H, 3-H), 2.00–2.08 (m, 1
H, 2-H), 2.09–2.15 (m, 1 H, 2-H), 2.16–2.33 (br, 1 H, 3-H), 3.17–
3.33 (br, 1 H, 1-H), 3.46–3.61 (m, 2 H, 5-H), 3.77–3.88 (br, 1 H, 1-
3
H), 4.10–4.19 (m, 1 H, 4-H), 7.02 (t, JH8,H7 = 7.8 Hz, 1 H, 8-H),
7.11 (d, 3JH6,H7 = 8.3 Hz, 2 H, 6-H), 7.32 (dd, 3JH7,H6 = 8.3, 3JH7,H8
= 7.8 Hz, 2 H, 7-H) ppm. 13C NMR (CDCl3, T = 298 K): δ = 27.8
(br, C-2), 31.3 (br, C-3), 44.4 (br, C-1), 52.6 (br, C-5), 66.5 (br, C-
3
4), 117.6 (br, C-6), 121.8 (br, C-8), 129.3 (s, C-7), 143.0 (d, JC,P
=
4110
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 4102–4116

Novel Phosphorous Triamides
13 Hz, Cq) ppm. 13C NMR (CDCl3, T = 233 K): δ = 26.9 (C-2b),
(Cphenyl), 128.3 (Cphenyl), 128.5 (C-7b), 129.0 (Cphenyl), 129.1 (C-7a),
129.3 (Cphenyl), 143.9 (Cq-phenyl-b), 146.6 (Cq-phenyl-a), 147.1 (d,
28.2 (C-2a), 30.2 (C-3b), 31.4 (C-3a), 44.0 (C-1a), 44.9 (d, JC,P
22 Hz, C-1b), 51.4 (C-5b), 52.4 (C-5a), 64.9 (C-4b), 66.6 (d, JC,P
=
=
2
2JC,P = 14 Hz, Cq-a), 147.3 (d, JC,P = 14 Hz, Cq-b) ppm. 31P{1H}
NMR (C6D6): δ = 105.8 ppm (L1): 90.2 ppm (L12); ratio 1:1.1.
HRMS: calculated: 429.2334; found: 429.2336.
9 Hz, C-4a), 115.6 (d, JC,P = 14 Hz, C-6b), 117.2 (d, JC,P = 14 Hz,
C-6a), 120.8 (C-8b), 121.7 (C-8a), 129.3 (C-7a and C-7b), 142.5 (d,
JC,P = 11 Hz, Cq-a and Cq-b) ppm. 31P{1H} NMR (CDCl3): δ =
153.9 (a) and 146.2 (b) , ratio 3.5:1 ppm.
Borane Complex of M1 (containing ligands L1 and L12): BH3·THF
(1  solution, 3 mL) was added dropwise by syringe to a solution
of M1 (0.558, 1.3 mmol) in toluene (5 mL), and the mixture was
stirred at room temperature overnight. The volatiles were removed
in vacuo and the yellowish solid was purified by flash chromatog-
raphy over neutral alumina (eluent: pentane/ethyl acetate 5:1). The
product was obtained as a colourless solid, which is stable towards
air and moisture: 0.518 g, 90% yield.
(R,R)-Bis(1-phenylethyl)phosphoramidous Dichloride [(R,R)-8]: The
synthesis was carried out by a modification of a literature pro-
cedure.[9] (R,R)-Bis(1-phenylethyl)amine (1 g, 4.4 mmol) and
DMAP (0.6 g, 4.9 mmol) were dissolved in dry toluene (3 mL). The
mixture was stirred for 10 min and cooled down to 0 °C, and sub-
sequently neat PCl3 (2.3 mL, 3 g, 22 mmol) was introduced by sy-
ringe with vigorous stirring. Formation of a colourless precipitate
was observed immediately. The mixture was heated to 70 °C over-
night, and the solvent and excess of PCl3 were then removed in
vacuo. Pentane (15 mL) was added to the solid residue, and the
suspension was vigorously stirred for 30 min, followed by a fil-
tration through dried celite. The extraction and filtration procedure
was repeated three times with pentane (10 mL). After removal of
the solvent, the product was obtained as a transparent viscous oil,
which is sensitive towards air and moisture: 1.37 g (95% yield). The
compound can be stored under argon at –30 °C for several months.
The spectroscopic data are in agreement with those reported in the
literature.[9]
31P{1H} NMR (CDCl3):
δ = 100.0 (L1·BH3) and 87.4
(R,R)-Bis(1-phenylethyl)phosphoramidous Dichloride [(S,S)-8]: The
same procedure was applied as for the preparation of (R,R)-8.
(S,S)-Bis(1-phenylethyl)amine was used instead of (R,R)-bis(1-
phenylethyl)amine. The spectroscopic data are in agreement with
those reported in the literature.[9]
(L12·BH3) ppm.
Isolation of L1·BH3 by Crystallisation: The diastereomeric mixture
M1·BH3 (268 mg, 0.6 mmol) was dissolved in CHCl3 (5 mL) and
cold pentane was added dropwise. After addition of pentane
(25 mL), colourless crystals started to precipitate. The solution was
kept at –30 °C overnight. After filtration, L1·BH3 was collected as
a colourless solid (40 mg, yield 15%). Crystals for X-ray measure-
ments were obtained by slow diffusion of pentane into a CDCl3
solution.
Diastereomeric Mixture M1 (Containing L1 and L12): DMAP
(0.757 g, 6.2 mmol) and (S)-N-(pyrrolidin-2-ylmethyl)aniline
(0.537 g, 3.1 mmol) were introduced into a Schlenk flask. Toluene
(5 mL) was added and the solution was vigorously stirred for
10 min. Compound (R,R)-2 (1 g, 3.1 mmol) was dissolved in tolu-
ene (3 mL) and this solution was added dropwise, leading to imme-
diate formation of a colourless precipitate. The reaction mixture
was stirred at room temperature overnight and then filtered
through a short pad of alumina (ca. 4 cm, Ø = 3 cm), which was
washed three times with toluene (15 mL). After removal of the sol-
vent in vacuo, the product was obtained as a transparent viscous
oil, which is sensitive towards air and moisture, but can be stored in
cold conditions under inert atmosphere for several months: 1.223 g,
(93% yield).
1H NMR (C6D6): δ = 1.07–1.17 (m, 1 H, 3-H), 1.16–1.32 (m, 3 H,
3
3
13C NMR (C6D6): δ = 21.4 (C-1Јb), 21.7 (d, JC,P = 6 Hz, C-1Јa), BH3-H), 1.22 (d, JH,H = 7 Hz, 1Ј-H, 3Ј-H), 1.31–1.50 (m, 2 H, 2-
2
25.9 (C-2a), 28.3 (C-2b), 29.5 (C-3b), 32.8 (C-3a), 42.2 (d, JC,P
=
H), 1.74–1.89 (m, 1 H, 3-H), 2.59–2.91 (m, 3 H, 1-H, 5-H), 3.08–
3.23 (m, 1 H, 5-H), 3.87–4.03 (m, 1 H, 4-H), 4.91–5.10 (m, 2 H,
2
2
18 Hz, C-5b), 49.7 (d, JC,P = 42 Hz, C-1a), 49.9 (d, JC,P = 5 Hz,
2
2
3
C-1b), 54.0 (d, JC,P = 9 Hz, C-2Јa), 54.2 (d, JC,P = 10 Hz, C-5a), 2Ј-H, 4Ј-H), 6.90 (t, JH,H = 7.6 Hz, 8-H), 6.96–7.28 (m, 12 H,
62.5 (d, 2JC,P = 8 Hz, C-4a), 63.7 (d, JC,P = 6 Hz, C-4b), 115.7 (d,
Hphenyl, 6-H), 7.35–7.48 (m, 2 H, 7-H) ppm. 13C NMR (C6D6): δ
2
3
3
3JC,P = 13 Hz, C-6b), 116.5 (d, JC,P = 12 Hz, C-6a), 117.7 (C-8b),
= 20.2 (C-1Ј), 25.9 (d, JC,P = 3 Hz, C-2), 32.1 (C-3), 46.1 (d, 2JC,P
2
118.0 (C-8a), 125.7 (Cphenyl), 126.7 (Cphenyl), 127.8 (Cphenyl), 127.9
= 11 Hz, C-1), 51.9 (d, JC,P = 3 Hz, C-2Ј), 60.3 (C-4), 119.2 (d,
Eur. J. Org. Chem. 2009, 4102–4116
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4111

K. Barta, M. Hölscher, G. Franciò, W. Leitner
FULL PAPER
3
3JC,P = 5 Hz, C-6), 121.5 (C-8), 127.3 (Cphenyl), 128.4 (Cphenyl), = 7.3 Hz, 2 H, 7-H) ppm. 13C NMR (C6D6): δ = 21.5 (d, JC,P
=
2
3
2
128.9 (C-7), 129.0 (Cphenyl), 142.5 (d, JC,P = 4 Hz, Cq), 143.7 (Cq-
12 Hz, C-1Ј), 25.9 (d, JC,P = 4 Hz, C-2), 32.6 (C-3), 49.5 (d, JC,P
2
2
phenyl) ppm. 31P{1H} NMR (C6D6): δ = 101.4 (m) ppm.
= 42 Hz, C-1), 54.0 (d, JC,P = 9 Hz, C-2Ј), 54.2 (d, JC,P = 7 Hz,
2
3
C-5), 62.5 (d, JC,P = 8 Hz, C-4), 116.1 (d, JC,P = 12 Hz, C-6),
Diastereomeric Mixture M2 (containing L2 and L13): The same
procedure as before was used, but (S,S)-2 was used for the synthesis
instead of (R,R)-2. The product is a colourless solid that is sensitive
towards air and moisture, but can be stored in cold conditions un-
der inert atmosphere for several months: 1.265 g (95% yield).
118.0 (C-8), 127.0 (Cphenyl), 128.1 (Cphenyl), 129.1 (C-7), 129.2
2
(Cphenyl), 146.6 (Cq-phenyl), 147.1 (d, JC,P = 14 Hz, Cq) ppm.
31P{1H} NMR (C6D6): δ = 105.8 (L1): 90.2 (L12) ppm; ratio 20:1.
HRMS: calculated: 429.2334; found: 429.2334.
(3aS)-2-Phenyl-N,N-bis[(S)-1-phenylethyl]-hexahydro-1H-pyrrolo-
[1,2-c][1,3,2]diazaphosphol-1-amine (L2): The same procedure was
applied as for L1, but (S,S)-bis(1-phenylethyl)amine was used as
the monoamine. Quantities: (S,S)-bis(1-phenylethyl)amine: 1.133 g,
1.2 mL, 5.0 mmol; 7: 1.21 g, 5.0 mmol; nBuLi: 3.2 mL (1.56  in
THF), 5.0 mmol. Product: colourless solid (1.793 g, 83% yield).
3
13C NMR (C6D6): δ = 21.4 (d, JC,P = 11 Hz, C-1Ј, L13), 21.5 (d,
3JC,P = 12 Hz, C-1Ј, L2), 25.9 (C-2, L2), 28.3 (C-2, L13), 29.0 (C-
2
3, L13), 32.6 (C-3, L2), 41.9 (d, JC,P = 17 Hz, C-5, L13), 49.5 (d,
2
2JC,P = 42 Hz, C-1, L2), 50.1 (d, JC,P = 3 Hz, C-1, L13), 52.8 (d,
2
2JC,P = 8 Hz, C-2Ј, L13), 53.3 (d, JC,P = 9 Hz, C-2Ј, L2), 54.9 (d,
1H NMR (C6D6): δ = 1.09–1.15 (m, 1 H, 3-H), 1.34–1.44 (m, 2 H,
2-H), 1.55–1.63 (m, 1 H, 3-H), 1.71 (d, 3JH,H = 6.8 Hz, 6 H, 1Ј-H),
2.63–2.68 (m, 1 H, 5-H), 2.98–3.05 (m, 1 H, 1-H), 3.34–3.41 (m, 1
H, 1-H), 3.47–3.53 (m, 1 H, 5-H), 3.69–3.74 (m, 1 H, 4-H), 4.36–
2
2JC,P = 5 Hz, C-5, L2), 61.6 (d, JC,P = 8 Hz, C-4, L2), 63.5 (d,
2JC,P = 8 Hz, C-4, L13), 116.1 (d, JC,P = 12 Hz, C-6, L2), 116.5
3
(d, 3JC,P = 13 Hz, C-6, L13), 118.0 (C-8, L13), 126.6 (Cphenyl, L13),
126.9 (Cphenyl, L2), 128.0 (Cphenyl, L2 and Cphenyl, L13), 128.9 (C-
7, L2), 129.0 (Cphenyl, L2), 129.1 (C-7, L13), 129.3 (Cphenyl, L13),
143.8 (Cq-phenyl, L13), 146.6 (Cq-phenyl, L2), 146.8 (d, 2JC,P = 15 Hz,
3
4.43 (m, 2 H, 2Ј-H), 6.44 (d, JH6,H7 = 7.6 Hz, 2 H, 6-H), 6.82 (t,
3JH7,H8 = 7.3 Hz, 1 H, 8-H), 6.95 (m, 4 H, Hphenyl), 7.03–7.16 (m,
3
3
6 H, Hphenyl), 7.19 (dd, JH6,H7 = 7.6, JH6,H8 = 7.3 Hz, 2 H, 7-
Cq, L2), 147.9 (d, JC,P = 12 Hz, Cq, L13) ppm. 31P{1H} NMR
2
H) ppm. 13C NMR (C6D6): δ = 21.5 (d, JC,P = 11 Hz, C-1Ј), 25.9
(C-2), 32.7 (C-3), 49.5 (d, JC,P = 41 Hz, C-1), 53.3 (d, JC,P
10 Hz, C-2Ј), 54.9 (d, JC,P = 5 Hz, C-5), 61.6 (d, JC,P = 8 Hz, C-
4), 116.1 (d, JC,P = 12 Hz, C-6), 118.0 (C-8), 126.9 (Cphenyl), 127.9
3
(C6D6): δ = 108.8 (L2): 86.4 (L13) ppm; ratio 1:3. HRMS: calcu-
2
2
=
lated: 429.2334; found: 429.2325.
2
2
3
(3aS)-2-Phenyl-N,N-bis[(R)-1-phenylethyl]-hexahydro-1H-pyrrolo-
[1,2-c][1,3,2]diazaphosphol-1-amine (L1): In a 100 mL Schlenk
flask, (R,R)-bis(1-phenylethyl)amine (1.113 g, 1.1 mL, 4.9 mmol)
was dissolved in dry THF (10 mL), and the mixture was cooled
down to –78 °C with a dry ice bath. nBuLi [3.1 mL (1.56  in hex-
ane), 4.8 mmol] was added dropwise and the solution was stirred
for 30 min. Afterwards, 7 (1.19 g, 4.9 mmol) was added dropwise
by syringe as a THF solution (10 mL). The mixture was allowed
to warm to room temperature and stirred overnight, during which
a colourless precipitate formed. The solvent was then removed and
toluene (15 mL) was added. The precipitated LiCl was filtered off
over a short pad of alumina (ca. 5 cm, Ø = 3 cm) and the column
was washed twice with toluene (10 mL). The product (2.008 g, 95%
yield) was obtained as transparent oil after removal of the solvent
in vacuo.
(Cphenyl), 128.9 (C-7), 129.0 (Cphenyl), 146.6 (Cq-phenyl), 146.8 (d,
2JC,P = 15 Hz, Cq) ppm. 31P{1H} NMR (C6D6): δ = 108.8 (L2):
86.5 (L13) ppm; ratio 15:1. HRMS: calculated: 429.2334; found:
429.2334.
(3aS)-2-Phenyl-1-(piperidin-1-yl)-hexahydro-1H-pyrrolo[1,2-c]-
[1,3,2]diazaphosphole (L3): Piperidine (0.5 mL, 0.43 g, 5.0 mmol)
was added by syringe to a stirred solution of 7 (0.600 g, 2.5 mmol)
in toluene (5 mL). The mixture was stirred at room temperature
overnight. Afterwards, the colourless precipitate was removed by
filtration through a short pad of neutral alumina (5 cm, Ø = 3 cm)
and the column was washed twice with toluene (10 mL). The prod-
uct (0.417 g, 58% yield) was obtained as a colourless solid after
removal of the solvent in vacuo.
1H NMR (C6D6): δ = 1.14–1.22 (m, 1 H, 3-H), 1.41–1.51 (m, 2 H, 1H NMR (C6D6): δ = 1.12–1.19 (m, 1 H, 3-H), 1.23–1.41 (m, 8 H,
2-H), 1.52–1.58 (m, 1 H, 3-H), 1.61 (d, 3JH,H = 7.1 Hz, 6 H, 1Ј-H),
2-H, 2Ј-H, 3Ј-H, 4Ј-H), 1.50–1.57 (m, 1 H, 3-H), 2.77–2.81 (m, 1
2.97–3.04 (m, 2 H, 1-H, 5-H), 3.39–3.46 (m, 1 H, 1-H), 3.73–3.78 H, 5-H), 2.95–3.10 (m, 5 H, 1-H, 1Ј-H, 5Ј-H), 3.42–3.48 (m, 2 H,
3
(m, 1 H, 5-H), 3.78–3.84 (m, 1 H, 4-H), 4.42–4.49 (m, 2 H, 2Ј-H), 1-H, 5-H), 3.71–3.76 (m, 1 H, 4-H), 6.97 (t, JH8,H7 = 7.3 Hz, 1 H,
3
3
3
7.00 (t, JH7,H8 = 7.3 Hz, 1 H, 8-H), 7.10–7.34 (m, 10 H, Hphenyl), 8-H), 7.24 (d, JH6,H7 = 7.8 Hz, 2 H, 6-H), 7.39 (dd, JH7,H6 = 7.8,
7.36 (d, 3JH6,H7 = 8.3 Hz, 2 H, 6-H), 7.43 (dd, 3JH7,H6 = 8.3, 3JH7,H8 3JH7,H8 = 7.3 Hz, 2 H, 7-H) ppm. 13C NMR (C6D6): δ = 25.5 (C-
4112
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Eur. J. Org. Chem. 2009, 4102–4116

Novel Phosphorous Triamides
3
3
3Ј), 25.7 (d, JC,P = 5 Hz, C-2), 27.3 (d, JC,P = 5 Hz, C-2Ј), 32.4 as for L3, but diisopropylamine was used for the synthesis instead
2
2
(C-3), 46.3 (d, JC,P = 16 Hz, C-1Ј), 50.4 (d, JC,P = 40 Hz, C-1),
of piperidine. Quantities: diisopropylamine: 0.47 mL, 0.336 g,
2
2
54.3 (d, JC,P = 7 Hz, C-5), 62.7 (d, JC,P = 8 Hz, C-4), 115.6 (d, 3.32 mmol; 7: 0.400 g, 1.66 mmol. Product: colourless solid
3JC,P = 12 Hz, C-6), 118.2 (C-8), 129.2 (C-7), 147.4 (d, JC,P
=
(0.441 g, 87% yield).
2
14 Hz, Cq) ppm. 31P{1H} NMR (C6D6): δ = 114.7 and 95.7 ppm;
ratio 45:1. HRMS: calculated: 289.1708; found: 289.1670.
(3aS)-2-Phenyl-1-(pyrrolidin-1-yl)-hexahydro-1H-pyrrolo[1,2-c]-
[1,3,2]diazaphosphole (L4): The same procedure was applied as for
L3, but pyrrolidine was used for the synthesis instead of piperidine.
Quantities: pyrrolidine: 0.42 mL, 0.356 g, 5.0 mmol; 7: 0.600 g,
2.5 mmol. Product: colourless solid (0.406 g, 59% yield).
3
1H NMR (C6D6): δ = 1.13 (d, JH,H = 7.1 Hz, 6 H, 1Ј-H, 2Ј-H),
3
1.14–1.19 (m, 1 H, 3-H), 1.25 (d, JH,H = 7.1 Hz, 6 H, 4Ј-H, 5Ј-H),
1.36–1.43 (m, 2 H, 2-H), 1.54–1.60 (m, 1 H, 3-H), 2.73–2.77 (m, 1
H, 5-H), 2.94–3.10 (m, 1 H, 1-H), 3.30–3.36 (m, 2 H, 3Ј-H, 6Ј-H),
3.36–3.42 (m, 1 H, 1-H), 3.52–3.55 (m, 1 H, 5-H), 3.69–3.75 (m, 1
3
3
H, 4-H), 6.83 (t, JH8,H7 = 7.3 Hz, 1 H, 8-H), 7.16 (d, JH6,H7
=
3
3
8.3 Hz, 2 H, 6-H), 7.27 (dd, JH7,H6 = 8.3, JH7,H8 = 7.3 Hz, 2 H,
7-H) ppm. 13C NMR (C6D6): δ = 23.7 (d, JC,P = 6 Hz, C-1Ј, C-
3
1H NMR (C6D6): δ = 1.17–1.23 (m, 1 H, 3-H), 1.37–1.47 (m, 5 H,
2Ј-H, 3Ј-H, 2-H), 1.55–1.62 (m, 1 H, 3-H), 2.76–2.80 (m, 1 H, 5-
H), 2.96–3.01 (m, 2 H, 1Ј-H, 4-HЈ), 3.03–3.09 (m, 1 H, 1-H), 3.14–
3.19 (m, 2 H, 1Ј-H, 4Ј-H), 3.39–3.47 (m, 2 H, 5-H, 1-H), 3.78–3.83
(m, 1 H, 4-H), 6.84 (t, 3JH8,H7 = 7.4 Hz, 1 H, 8-H), 7.06 (d, 3JH6,H7
= 8.9 Hz, 2 H, 6-H), 7.27 (dd, JH7,H6 = 8.9, JH7,H8 = 7.4 Hz, 2 H,
2Ј), 24.8 (d, 3JC,P = 10 Hz, C-4Ј, C-5Ј), 25.7 (d, 3JC,P = 5 Hz, C-2),
2
2
32.6 (C-3), 45.3 (d, JC,P = 10 Hz, C-3Ј, C-6Ј), 49.5 (d, JC,P
=
2
2
42 Hz, C-1), 54.7 (d, JC,P = 6 Hz, C-5), 61.8 (d, JC,P = 7 Hz, C-
4), 116.0 (d, 3JC,P = 11 Hz, C-6), 118.1 (C-8), 129.0 (C-7), 147.2 (d,
2JC,P = 14 Hz, Cq) ppm. 31P{1H} NMR (C6D6): δ = 107.0 ppm.
HRMS: calculated: 305.2021; found: 305.2020.
3
7-H) ppm. 13C NMR (C6D6): δ = 25.8 (d, JC,P = 3 Hz, C-2Ј, C-
3
2
3Ј), 26.5 (d, JC,P = 4 Hz, C-2), 32.4 (C-3), 46.6 (d, JC,P = 14 Hz,
(3aS)-N,N-Dibutyl-2-phenyl-hexahydro-1H-pyrrolo[1,2-c][1,3,2]di-
azaphosphol-1-amine (L7): The same procedure was applied as for
L3, but dibutylamine was used for the synthesis instead of piperi-
dine. Quantities: dibutylamine: 0.28 mL, 0.214 g, 1.66 mmol; 1:
0.200 g, 0.83 mmol. Product: colourless oil (0.255 g, 92% yield).
2
2
C-1Ј, C-4Ј), 50.8 (d, JC,P = 40 Hz, C-1), 54.7 (d, JC,P = 5 Hz, C-
2
3
5), 63.1 (d, JC,P = 8 Hz, C-4), 115.2 (d, JC,P = 13 Hz, C-6), 118.0
(C-8), 129.3 (C-7), 147.4 (d, JC,P = 14 Hz, Cq) ppm. 31P{1H}
2
NMR (C6D6): δ = 107.3 and 91.7 ppm; ratio 80:1. HRMS: calcu-
lated: 275.1551; found: 275.1542.
4-[(3aS)-2-Phenyl-hexahydro-1H-pyrrolo[1,2-c][1,3,2]diazaphosphol-
1-yl]morpholine (L5): The same procedure was applied as for L3,
but morpholine was used for the synthesis instead of piperidine.
Quantities: morpholine: 0.150 mL, 0.143 g, 1.66 mmol; 7: 0.200 g,
0.83 mmol. Product: colourless solid (0.148 g, 61% yield).
3
1H NMR (C6D6): δ = 0.84 (t, JH,H = 7.3 Hz, 6 H, 4Ј-H), 1.10–
1.30 (m, 5 H, 3Ј-H, 3-H), 1.31–1.46 (m, 6 H, 2Ј-H, 2-H), 1.53–1.64
(m, 1 H, 3-H), 2.81–2.86 (m, 1 H, 5-H), 2.88–2.95 (m, 2 H, 1Ј-H),
2.98–3.04 (m, 1 H, 1-H), 3.10 (m, 2 H, 5Ј-H), 3.44–3.50 (m, 1 H,
1-H), 3.52–3.56 (m, 1 H, 5-H), 3.78–3.83 (m, 1 H, 4-H), 6.82 (t,
3
3JH8,H7 = 7.3 Hz, 1 H, 8-H), 7.05 (d, JH6,H7 = 8.2 Hz, 2 H, 6-H),
1H NMR (C6D6): δ = 1.10–1.17 (m, 1 H, 3-H), 1.30–1.37 (m, 2 H, 7.26 (dd, 3JH7,H6 = 8.2, 3JH7,H8 = 7.3 Hz, 2 H, 7-H) ppm. 13C NMR
3
2-H), 1.48–1.56 (m, 1 H, 3-H), 2.48 (m, 2 H, 2Ј-H), 2.70–2.74 (m,
1 H, 5-H), 2.82–2.99 (m, 3 H, 3Ј-H, 1-H), 3.31–3.44 (m, 4 H, 1-H,
(C6D6): δ = 14.1 (C-4Ј), 20.6 (C-3Ј), 25.9 (d, JC,P = 4 Hz, C-2),
2
31.4 (C-2Ј), 32.7 (C-3), 46.0 (d, JC,P = 18 Hz, C-1Ј, C-5Ј), 50.1 (d,
5-H, 4Ј-H), 3.45–3.47 (m, 2 H, 1Ј-H), 3.57–3.64 (m, 1 H, 4-H), 6.86 2JC,P = 43 Hz, C-1), 54.4 (d, JC,P = 7 Hz, C-5), 62.5 (d, JC,P
=
2
2
3
3
3
(t, JH8,H7 = 7.3 Hz, 1 H, 8-H), 7.06 (d, JH6,H7 = 7.8 Hz, 2 H, 6-
8 Hz, C-4), 115.6 (d, JC,P = 12 Hz, C-6), 118.1 (C-8), 129.1 (C-7),
H), 7.26 (dd, JH7,H6 = 7.8, JH7,H8 = 7.3 Hz, 2 H, 7-H) ppm. 13C
147.3 (d, 2JC,P = 14 Hz, Cq) ppm. 31P{1H} NMR (C6D6): δ = 118.2
3
3
3
NMR (C6D6): δ = 25.7 (d, JC,P = 4 Hz, C-2), 32.3 (C-3), 45.6 (d, and 97.6 (47:1) ppm. HRMS: calculated: 333.2334; found:
3JC,P = 12 Hz, C-3Ј), 46.4 (C-2Ј), 50.3 (d, 2JC,P = 38 Hz, C-1), 54.4
333.2331.
2
2
2
(d, JC,P = 6 Hz, C-5), 62.8 (d, JC,P = 7 Hz, C-4), 67.7 (d, JC,P
=
(3aS)-N-Methyl-2-phenyl-N-[(R)-1-phenylethyl]-hexahydro-1H-pyr-
rolo[1,2-c][1,3,2]diazaphosphol-1-amine (L8): DMAP (0.406 g,
3.32 mmol) was added to a stirred solution of 1 (0.800 g,
3.32 mmol) in toluene (5 mL), and the mixture was stirred for
10 min. (R)-N-Methyl-1-phenylethylamine (0.48 mL, 0.449 g,
3.32 mmol) was added neat by syringe, and the mixture was stirred
overnight at room temperature. The formed colourless precipitate
2
3
18 Hz, C-4Ј), 67.8 (d, JC,P = 6 Hz, C-1Ј), 115.6 (d, JC,P = 11 Hz,
2
C-6), 118.5 (C-8), 129.2 (C-7), 147.0 (d, JC,P = 14 Hz, Cq) ppm.
31P{1H} NMR (C6D6): δ = 114.5 and 95.0 ppm; ratio 90:1. HRMS:
calculated: 291.1501; found: 291.1493.
(3aS)-N,N-Diisopropyl-2-phenyl-hexahydro-1H-pyrrolo[1,2-c]-
[1,3,2]diazaphosphol-1-amine (L6): The same procedure was applied
Eur. J. Org. Chem. 2009, 4102–4116
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4113

K. Barta, M. Hölscher, G. Franciò, W. Leitner
FULL PAPER
was removed by filtration through a short pad of neutral alumina
(5 cm, Ø = 3 cm) and the column was washed twice with toluene
(10 mL). The product was obtained as a colourless oil after evapo-
ration of the solvent in vacuo: 0.779 g, 70% yield.
diphenylamine: 0.340 g, 2.0 mmol; 7: 0.500 g, 2.0 mmol; nBuLi:
1.25 mL (1.6  in hexane), 2.0 mmol. Product: colourless solid
(0.420 g, 55% yield).
1H NMR (C6D6): δ = 0.86–0.92 (m, 1 H, 3-H), 1.23–1.36 (m, 3 H,
2-H, 3-H), 2.49–2.58 (m, 1 H, 5-H), 2.69–2.75 (m, 1 H, 5-H), 2.91–
3.03 (m, 2 H, 1-H, 4-H), 6.78 (t, 3JH8,H7 = 7.4 Hz, 1 H, 8-H), 6.79–
1H NMR (C6D6): δ = 1.09–1.15 (m, 1 H, 3-H), 1.33–1.44 (m, 2 H,
2-H), 1.40 (d, 3JH,H = 7.0 Hz, 3 H, 2Ј-H), 1.49–1.55 (m, 1 H, 3-H),
2.18 (d, JH,P = 5.2 Hz, 3 H, 1Ј-H), 2.80–2.86 (m, 1 H, 5-H), 3.00–
3
3
6.83 (m, 2 H, Harom), 7.02 (d, JH6,H7 = 8.6 Hz, 2 H, 6-H), 7.05–
3.06 (m, 1 H, 1-H), 3.46–3.53 (m, 2 H, 5-H, 1-H), 3.69–3.72 (m, 1
3
3
7.08 (m, 2 H, Harom), 7.16 (dd, JH7,H6 = 8.6, JH7,H8 = 7.4 Hz, 2
H, 7-H), 7.07–7.11 (m, 4 H, Harom), 7.23–7.27 (m, 2 H, Harom) ppm.
13C NMR (C6D6): δ = 26.1 (C-2), 32.4 (C-3), 49.8 (d, 2JC,P = 41 Hz,
3
H, 4-H), 4.88–4.95 (m, 1 H, 3Ј-H), 6.86 (t, JH8,H7 = 7.3 Hz, 1 H,
3
3
8-H), 7.08 (t, JH8Ј,H7Ј = 7.1 Hz, 1 H, 8Ј-H), 7.11 (d, JH6,H7
=
3
8.7 Hz, 2 H, 6-H), 7.20 (m, 2 H, 7Ј-H), 7.28 (dd, JH7,H6 = 8.7,
2
C-1), 54.1 (d, 2JC,P = 5 Hz, C-5), 62.3 (d, JC,P = 8 Hz, C-4), 115.8
3JH7,H8 = 7.3 Hz, 2 H, 7-H), 7.34 (d, JH6Ј,H7Ј = 8.7 Hz, 2 H, 6Ј-
3
3
(d, 3JC,P = 13 Hz, C-6), 116.2 (d, JC,P = 4 Hz, Carom), 118.8 (C-8),
H) ppm. 13C NMR (C6D6): δ = 18.0 (d, JC,P = 7 Hz, C-2Ј), 25.9
3
123.6 (Carom), 124.9 (d, 3JC,P = 7.7 Hz, Carom), 129.3 (Carom), 129.4
3
2
(d, JC,P = 4 Hz, C-2), 26.9 (C-1Ј), 32.7 (C-3), 50.2 (d, JC,P
=
2
2
(C-7), 146.8 (d, JC,P = 17 Hz, Cq), 146.8 (d, JC,P = 10 Hz, Cq-
arom) ppm. 31P{1H} NMR (C6D6): δ = 103.2 and 90.6 ppm; ratio
100:1.
2
2
40 Hz, C-1), 54.3 (d, JC,P = 7 Hz, C-5), 56.0 (d, JC,P = 36 Hz, C-
3Ј), 62.7 (d, 2JC,P = 8 Hz, C-4), 115.8 (d, 3JC,P = 13 Hz, C-6), 118.3
(C-8), 126.7 (C-8Ј), 127.6 (C-6Ј), 128.3 (C-7Ј), 129.2 (C-7), 144.1
(d, JC,P = 3 Hz, CqЈ), 147.0 (d, JC,P = 13 Hz, Cq) ppm. 31P{1H}
NMR (C6D6): δ = 118.5/97.8 (115:1) ppm. HRMS: calculated:
339.1864; found: 339.1863.
2
2
(3aS)-2-Phenyl-1-(1H-pyrrol-1-yl)-hexahydro-1H-pyrrolo[1,2-c]-
[1,3,2]diazaphosphole (L11): The same procedure was applied as for
L1, but pyrrole was used as the monoamine. Quantities: pyrrole:
0.14 mL, 0.135 g, 2.0 mmol; 7: 0.500 g, 2.0 mmol; nBuLi: 1.25 mL
(1.6  in THF), 2.0 mmol. Product: colourless solid (0.488 g, 90%
yield).
(3aS)-N,N-Dibenzyl-2-phenyl-hexahydro-1H-pyrrolo[1,2-c][1,3,2]di-
azaphosphol-1-amine (L9): The same procedure was applied as for
L8, but dibenzylamine was used for the synthesis instead of (R)-N-
methyl-1-phenylethanamine. Quantities: dibenzylamine: 0.160 mL,
0.163 g, 0.83 mmol; 7: 0.200 g, 0.83 mmol; DMAP: 0.101 g,
0.83 mmol. Product: colourless oil that solidifies upon standing
(0.252 g, 76% yield).
1H NMR (C6D6): δ = 1.03–1.09 (m, 1 H, 3-H), 1.17–1.27 (m, 2 H,
2-H), 1.35–1.43 (m, 1 H, 3-H), 2.61–2.66 (m, 1 H, 5-H), 2.76–2.83
(m, 1 H, 1-H), 3.09–3.17 (m, 1 H, 1-H), 3.19–3.24 (m, 1 H, 5-H),
3
3.70–3.74 (m, 1 H, 4-H), 6.39–6.42 (m, 2 H, 2Ј-H), 6.75 (t, JH8,H7
3
= 7.4 Hz, 2 H, 8-H), 6.86 (d, JH6,H7 = 7.8 Hz, 2 H, 6-H), 7.00–
1H NMR (C6D6): δ = 1.21–1.29 (m, 1 H, 3-H), 1.48–1.57 (m, 2 H,
2-H), 1.61–1.69 (m, 1 H, 3-H), 2.79–2.87 (m, 1 H, 5-H), 3.13–3.20
(m, 1 H, 1-H), 3.51–3.61 (m, 2 H, 1-H, 5-H), 3.77–3.84 (m, 1 H,
7.03 (m, 2 H, 1Ј-H), 7.08 (dd, 3JH7,H6 = 7.8, JH7,H8 = 7.4 Hz, 2 H,
3
7-H) ppm. 13C NMR (C6D6): δ = 26.1 (d, JC,P = 5 Hz, C-2), 31.2
3
(C-3), 49.4 (d, 2JC,P = 37 Hz, C-1), 53.6 (d, 2JC,P = 6 Hz, C-5), 63.1
2
3
4-H), 3.91 (dd, JH,H = 15.5, JH,P = 10.7 Hz, 2 H, 1Ј-H, 2Ј-H),
2
3
(d, JC,P = 8 Hz, C-4), 111.5 (C-2Ј), 115.7 (d, JC,P = 13 Hz, C-6),
2
3
4.33 (dd, JH,H = 15.5, JH,P = 6.7 Hz, 2 H, 1Ј-H, 2Ј-H), 6.90 (t,
3JH8,H7 = 7.3 Hz, 1 H, 8-H), 7.06–7.12 (m, 4 H, 6-H, Harom), 7.13–
7.19 (m, 6 H, 7-H, Harom), 7.28–7.31 (m, 4 H, Harom) ppm. 13C
2
119.7 (C-8), 121.6 (d, JC,P = 14 Hz, C-1Ј), 129.5 (C-7), 145.4 (d,
2JC,P = 15 Hz, Cq) ppm. 31P{1H} NMR (C6D6): δ = 100.8/
89.1 ppm; ratio 15:1. HRMS: calculated: 271.12384; found:
271.12380.
3
NMR (C6D6): δ = 25.9 (d, JC,P = 5 Hz, C-2), 32.5 (C-3), 50.0 (d,
2
2JC,P = 18 Hz, C-1Ј, C-2Ј), 50.2 (d, JC,P = 40 Hz, C-1), 54.5 (d,
2
3
2JC,P = 7 Hz, C-5), 62.3 (d, JC,P = 7 Hz, C-4), 116.0 (d, JC,P
=
Catalysis
13 Hz, C-6), 118.5 (C-8), 126.9 (Carom), 127.2 (Carom), 128.3 (Ca-
General Procedure for Cu-Catalysed Addition of Et2Zn to Cyclohex-
2-enone: [(CuOTf)2·benzene] (2.6 mg, 0.005 mmol) was added to a
ligand solution (0.011 mmol) in dry and degassed toluene (1 mL)
and the resulting mixture was stirred for 1 h at room temperature
until the Cu precursor had dissolved completely. The solution was
then cooled down to the indicated temperature with a cryostat.
After the temperature had stabilised, Et2Zn (400 µL, 1  in toluene,
2
2
rom), 129.3 (C-7), 142.2 (d, JC,P = 8 Hz, Cq,arom), 146.9 (d, JC,P
=
15 Hz, Cq) ppm. 31P{1H} NMR (C6D6): δ = 118.8/96.6 (68:1) ppm.
HRMS: calculated: 401.2021; found: 401.2025.
(3aS)-N,N,2-Triphenyl-hexahydro-1H-pyrrolo[1,2-c][1,3,2]diaza-
phosphol-1-amine (L10): The same procedure was applied as for
L1, but diphenylamine was used as the monoamine. Quantities:
4114
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 4102–4116

Novel Phosphorous Triamides
[4]
[5]
Phosphorus Ligands in Asymmetric Catalysis. Synthesis and Ap-
plications (Ed.: A. Börner), Wiley-VCH, Weinheim, 2008.
For selected examples of diamidophosphite ligands see: a) J. M.
Brunel, T. Constanieux, A. Labande, F. Lubatti, G. Buono,
Tetrahedron Lett. 1997, 38, 5971–5974; b) A. I. Plosukhin,
O. G. Bondarev, S. E. Lyubimov, A. V. Korostylev, K. A. Lys-
senko, V. A. Davankov, K. N. Gavrilov, Tetrahedron: Asym-
metry 2001, 12, 2197–2204; c) R. Pretto, A. Pfaltz, Angew.
Chem. Int. Ed. 1998, 37, 323–325; d) R. Hilgraf, A. Pfaltz, Syn-
lett 1999, 1814–1816.
0.4 mmol) was added by syringe and the resulting yellow solution
was stirred for 10 min. Subsequently, cyclohex-2-enone (20 µL,
19.8 mg, 0.2 mmol) was added by syringe, and the mixture was
stirred at the desired reaction temperature for the indicated time
and finally quenched with saturated aqueous NH4Cl (2 mL). The
organic layer was washed with brine (2 mL) and distilled water
(2 mL) and was dried with Na2SO4. From this solution, a sample
(0.3 mL) was taken and diluted to 1 mL with toluene or dichloro-
methane (both HPLC grade) for GC analysis.
[6]
For selected examples of phosphoramidite ligands see: B. L.
Feringa, M. Pineschi, L. A. Arnold, R. Imbos, A. H. M.
de Vries, Angew. Chem. Int. Ed. Engl. 1997, 36, 2620–2623;
B. L. Feringa, Acc. Chem. Res. 2000, 33, 346–353; D. J. Ager,
A. H. M. de Vries, J. G. de Vries, Platinum Met. Rev. 2006, 50,
54–63; A. Alexakis, C. Benhaim, S. Rosset, M. Humam, J. Am.
Chem. Soc. 2002, 124, 5262–5263.
M. T. Reetz, H. Oka, R. Goddard, Synthesis 2003, 1809–1814.
D. Konya, C. Philouze, Y. Gimbert, A. E. Greene, Acta Crys-
tallogr., Sect. C 2002, 58, o108–o111.
C. Monti, C. Gennari, R. M. Steele, U. Piarulli, Eur. J. Org.
Chem. 2004, 3557–3565.
J. M. Brunel, T. Constantieux, G. Buono, J. Org. Chem. 1999,
64, 8940–8942.
J. M. Brunel, O. Legrand, S. Reymond, G. Buono, J. Am.
Chem. Soc. 1999, 121, 5807–5808.
S. Reymond, J. M. Brunel, G. Buono, Tetrahedron: Asymmetry
2000, 11, 1273–1278.
T. Pfretzschner, L. Kleemann, B. Janza, K. Harms, T. Schrader,
Chem. Eur. J. 2004, 10, 6048–6057.
V. N. Tsarev, S. E. Lyubimov, A. A. Shiryaev, S. V. Zheglov,
O. G. Bondarev, V. A. Davankov, A. A. Kabro, S. K. Moiseev,
V. N. Kalinin, K. N. Gavrilov, Eur. J. Org. Chem. 2004, 2214–
2222.
Conditions for Gas Chromatography: Carrier gas: H2 (0.6 bar); col-
umn: Lipodex E (25 m); temperature program: 90 °C isotherm; de-
tector: FID; retention times: cyclohex-2-enone 6.0 min, (S)-3 ethyl-
cyclohexanone 6.4 min, (R)-3-ethylcyclohexanone 6.8 min.
General Procedure for Ni-Catalysed Hydrovinylation of Styrene:
Under argon, a solution of the PTA ligand (0.012 mmol) in CH2Cl2
(1.5 mL) was added by syringe to a solution of [Ni(allyl)Br]2
(2.0 mg, 0.006 mmol) in the same solvent (1.5 mL). The mixture
was cooled down to the temperature indicated in Table 5 and sty-
rene (0.41 mL, 3.6 mmol) was added by syringe. The resulting solu-
tion was first purged with ethene and then maintained under eth-
ene. NaBARF (12 mg, 0.013 mmol) was added and the reaction
mixture was stirred for the indicated time. Afterwards, the mixture
was quenched with saturated aqueous ammonia, ethylbenzene
(0.41 mL, 3.4 mmol) was added, and the organic phase was washed
with brine and dried with Na2SO4. Finally the slightly yellow or-
ganic phase was filtered through a short pad of silica and analysed
by GC. For determination of the degree of conversion the sample
was injected undiluted. For determination of enantioselectivity, a
portion of the organic phase (0.1 mL) was diluted with HPLC-
grade CH2Cl2 (1 mL) before injection.
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
K. Barta. Synthesis and application of chiral phosphorous tri-
amide ligands, PhD thesis RWTH Aachen, 2008, CAN
150:55452; AN 2008:1347865.
S. E. Denmark, X. Su, Y. Nishigaichi, D. M. Coe, K.-T. Wong,
S. B. D. Winter, J. Y. Choi, J. Org. Chem. 1999, 64, 1958–1967;
S. E. Denmark, R. A. Stavenger, K.-T. Wong, X. Su, J. Am.
Chem. Soc. 1999, 121, 4982–4991.
O. G. Bondarev, N. Gavrilov, V. N. Tsarev, V. A. Davankov,
R. V. Lebedev, S. K. Moiseev, N. Kalinin, Russ. Chem. Bull.
Int. Ed. 2002, 51, 521–525.
Gas-Chromatographic Conditions for Determination of the Conver-
sion: Carrier gas: N2 (1.3 bar); temperature program: 50 °C, 5 min/
8 °Cmin–1/230 °C, 20 min; column: Cp-Sil-Pona (50 m); detector:
FID; internal standard: ethylbenzene. Retention times: ethylben-
zene: 15.6 min, styrene: 16.4 min, 3-phenylbut-1-ene: 20.1 min, (E)-
2-phenylbut-1-ene: 20.5 min, (Z)-2-phenylbut-1-ene: 22.8 min,
oligomers (FW: 160 gmol–1): 24.5–25.3 min, oligomers (FW:
208 gmol–1): 35.7 and 41.3 min, oligomers (FW: 236 gmol–1): 38.1–
38.9 min. The compounds were identified by GC-MS.
[17]
[18]
[19]
V. Sum, T. P. Kee, J. Chem. Soc. Perkin Trans. 1 1993, 2701.
The definitions syn and anti diastereomer refer to the relative
positions of the exocyclic substituent at the phosphorus with
respect to the methylene of the pyrrolidine ring. When they
reside on the same side of the five-membered phosphorus-con-
Gas-Chromatographic Conditions for Determination of the Enantio-
selectivity: Carrier gas: H2 (1 bar); temperature program: 60 °C/
1 °Cmin–1/85 °C/20 °Cmin–1/180 °C, 5 min; column: Pb-OV5
(25 m) + Lipodex 7 (25 m); detector: FID. Retention times: (R)-
3-phenylbut-1-ene: 15.9 min, (S)-3-phenylbut-1-ene: 16.2 min, (E)-
and (Z)-2-phenylbut-1-ene: 16.7 min.
2
taining ring (syn isomer), the JC(1),P coupling has a character-
istic value of between 20 and 40 Hz. In the opposite case (anti
2
isomer), the JC(1),P coupling is nearly zero. The two dia-
stereomers can thus be easily identified by means of 13C NMR
spectroscopy (see ref.[20]). The notation syn/anti is more conve-
nient than the R/S one, because the stereochemical descriptor
for the chirality at the phosphorus can change depending on
the priority of the exocyclic substituent by the Cahn–Ingold–
Prelog rules, although the spatial arrangement around the
phosphorus remains the same.
P. Cros, G. Buono, G. Peiffer, P. Denis, A. Mortreux, F. Petit,
New J. Chem. 1987, 11, 573; H. Arzoumanian, G. Buono, M.
Choukrad, J.-F. Petrignani, Organometallics 1988, 7, 59–62.
C. Janiak, J. Chem. Soc., Dalton Trans. 2000, 3885–3896.
For leading references in this transformation, see: a) A.
Alexakis, J. Frutos, P. Mangeney, Tetrahedron: Asymmetry
1993, 4, 2427–2430; b) B. L. Feringa, M. Pineschi, L. A. Ar-
nold, R. Imbos, A. H. M. de Vries, Angew. Chem. Int. Ed. Engl.
1997, 36, 2620; c) B. L. Feringa, Acc. Chem. Res. 2000, 33, 346;
d) A. Alexakis, S. Rosset, J. Allamand, S. March, F. Guillen,
C. Benhaim, Synlett 2001, 9, 1375.
Acknowledgments
The authors thank Dr. Jürgen Klankermayer for the measurement
of EXSY NMR spectra, Prof. Dr. Ulli Englert and Mr Yutian
Wang for the acquisition of X-ray diffraction raw data, Ms Brigitte
Pütz for the measurement of HRMS data, and Ms Tina Steins
for laboratory assistance. We gratefully acknowledge the European
Union (EU) (STRP 505167-1 LIGBANK) for generous support.
[20]
[21]
[22]
[1] For an assessment of the coordination ability of PTAs see:
K. G. Moloy, J. L. Petersen, J. Am. Chem. Soc. 1995, 117,
7696–7710; M. L. Clarke, D. J. Cole-Hamilton, A. M. Z. Sla-
win, J. D. Woollins, Chem. Commun. 2000, 2065–2066.
[2] J. Ansell, M. Wills, Chem. Soc. Rev. 2002, 31, 259–268.
[3] O. Molt, T. Schrader, Synthesis 2002, 2633.
Eur. J. Org. Chem. 2009, 4102–4116
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4115

K. Barta, M. Hölscher, G. Franciò, W. Leitner
FULL PAPER
[23]
[24]
[25]
[30] R. Kumareswaran, M. Nandi, T. V. RajanBabu, Org. Lett.
2003, 5, 4345; A. Zhang, T. V. RajanBabu, J. Am. Chem. Soc.
2006, 128, 54; C. R. Smith, T. V. RajanBabu, Org. Lett. 2008,
10, 1657; W.-J. Shi, Q. Zhang, J.-H. Xie, S.-F. Zhu, G.-H. Hou,
Q.-L. Zhou, J. Am. Chem. Soc. 2006, 128, 2780; B. Saha, C. R.
Smith, T. V. RajanBabu, J. Am. Chem. Soc. 2008, 130, 9000–
9005; C. R. Smith, T. V. RajanBabu, J. Org. Chem. 2009, 74,
3066–3072.
syn diastereomers react preferentially with rhodium precursors
(unpublished results).
D. J. Berrisford, C. Bolm, K. B. Sharpless, Angew. Chem. Int.
Ed. Engl. 1995, 34, 1059.
G. Delapierre, J. M. Brunel, T. Constantieux, G. Buono, Tetra-
hedron: Asymmetry 2001, 12, 1345–1352.
[26] a) P. W. Jolly, G. Wilke, in: Applied Homogeneous Catalysis with
Organometallic Compounds (Eds.: B. Cornils, W. A. Herrm-
ann), VCH, New York, 1996, vol. 2, p. 1024; b) T. V. Rajan-
Babu, Chem. Rev. 2003, 103, 2854.
[27] G. Wilke, Angew. Chem. Int. Ed. Engl. 1988, 27, 185.
[28] G. Franciò, C. G. Arena, F. Faraone, C. Graiff, M. Lanfranchi,
A. Tiripicchio, Eur. J. Inorg. Chem. 1999, 1219–1227.
[29] a) G. Franciò, F. Faraone, W. Leitner, J. Am. Chem. Soc. 2002,
124, 736–737; b) C. J. Diez-Holz, C. Böing, G. Franciò, M.
Hölscher, W. Leitner, Eur. J. Org. Chem. 2007, 2995.
[31] M. Hölscher, G. Franciò, W. Leitner, Organometallics 2004, 23,
5606–5617.
[32] A. Wegner, W. Leitner, Chem. Commun. 1999, 1583.
[33] R. Bayersdörfer, B. Ganter, U. Englert, W. Keim, D. Vogt, J.
Organomet. Chem. 1998, 552, 187–194; U. Englert, R. Haerter,
D. Vasen, A. Salzer, E. B. Eggeling, D. Vogt, Organometallics
1999, 18, 4390–4398.
Received: May 4, 2009
Published Online: July 9, 2009
4116
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 4102–4116