Steric effects in enantioselective allylic alkylation catalysed by cationic (η3-allyl)palladium complexes bearing chiral pyridine-aziridine ligands

Article abstract of DOI:10.1002/ejoc.200400716

Enantiopure N,N′-bidentate ligands (N,N′)*, containing substituted aziridine and aza-aromatic rings, were prepared from imines derived from (S)-valinol or (R)-phenylglycinol and heteroaromatic aldehydes (2-pyridine-, 6-benzyl-2-pyridine-, 2- and 8-quinoli

Full text of DOI:10.1002/ejoc.200400716

FULL PAPER
Steric Effects in Enantioselective Allylic Alkylation Catalysed by Cationic
(η3-Allyl)palladium Complexes Bearing Chiral Pyridine-Aziridine Ligands
Federico Ferioli,[a] Claudio Fiorelli,[a] Gianluca Martelli,[a] Magda Monari,[a]
Diego Savoia*[a] and Paolo Tobaldin[a]
Keywords: Asymmetric catalysis / Imines / N ligands / Palladium
Enantiopure N,NЈ-bidentate ligands (N,NЈ)*, containing sub-
stituted aziridine and aza-aromatic rings, were prepared
from imines derived from (S)-valinol or (R)-phenylglycinol
and heteroaromatic aldehydes (2-pyridine-, 6-benzyl-2-pyri-
dine-, 2- and 8-quinolinecarbaldehyde) by the addition of
iPrMgCl and subsequent cyclisation of the 1,2-amino alcohol
moiety to aziridine. Crystalline [(N,NЈ)*(η3-allyl)Pd][SbF6]
complexes were prepared from these ligands and used as
catalysts in the alkylation of sodium dimethyl malonate with
1,3-diphenyl-2-propenyl acetate and carbonate. By compar-
ing the performances of two complexes bearing similar pyri-
dine-aziridine ligands but with a different C2-aziridine sub-
stituent (Ph vs. iPr), a better enantioselectivity was provided
by the Ph-substituted ligand (90% vs. 41% ee), whereas the
presence of a C6-pyridine benzyl substituent caused inver-
sion of the enantioselectivity.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
complexes, whereas six-membered chelate rings are formed
with the ligands 8–10. In the case of 8-quinolineoxazolines
8, an unexpected effect of the substitution was observed, as
Introduction
C2-Symmetric enantiopure N,N-bidentate ligands have
been used in Pd-catalysed allylic substitution reactions, typ-
ically the reaction of 1,3-diphenylpropenyl acetate (1a) with
the dimethyl malonate anion, in the presence of allylpalla-
dium chloride dimer to give the substitution product 2
(Scheme 1). Selected examples of ligands containing either
an aziridine or a pyridine ring are shown below as they
will be compared with the ligands prepared in this paper.
Notably, the C2-symmetric bis(aziridine) 3[1] affords com-
plete enantioselectivity. Substituted pyridines, for example
the ligand 4, where the pyridine substituent bears the trans-
2,5-disubstituted pyrrolidine ring,[2] provide greater
enantioselectivity (64% ee) than C2-symmetric 6,6Ј-disub-
stituted-2,2Ј-bipyridines.[3] With C1-symmetric 2-(2Ј-pyri-
dyl)oxazolines 5a,b[4] and 6[4c,5] a remarkable effect of the
substituent in both rings was observed. In fact, substitution
of Ph for the iPr group in the oxazoline was beneficial for
enantioselectivity as, with the same pyridine substituent (R
= H), a better ee was provided by 6. Most importantly, the
presence of a (chiral) bulky substituent at the pyridine-C6
of both ligands, or the presence of a benzo[b]-fused ring as
in 7, caused an increase in the enantioselectivity.[4,5] It
should be noted that the ligands 5–7 form a rigid, five-
membered chelate ring in the cationic (η3-allyl)palladium
when
R =
Me[6] and with the benzo[b]-derivative
(acridininyloxazoline)[4] the opposite enantiomer of 2 was
produced. Similarly, the 2-(quinolylmethyl)oxazoline 10 dis-
played the opposite enantioselectivity with respect to 9.[6]
Scheme 1.
We observed that (N,NЈ)* ligands containing both pyri-
dine and aziridine rings had not been described in the litera-
ture and envisioned a simple two-step route to (S)-1-[(S)-
(2-pyridyl)alkyl]isopropylaziridines, such as 11, from N-(2-
pyridylmethylidene)-(S)-valinol.[7] In a preliminary report
we have described the preparation of 11 and its cationic (η3-
allyl)palladium complex 12, which is more effective than
the free base in the above mentioned Pd-catalysed allylic
substitution reaction, and provides (R)-2 with moderate
yield and 41% ee (Table 1, entry 1).[8] The ligand 11 differs
from 3–10 in the presence of a stereocentre in the carbon
chain linking the two nitrogen atoms, besides the one pres-
ent on the aziridine carbon. The two stereocentres in 11
have a combined role and compel the aziridine nitrogen to
[a] Dipartimento di Chimica “G. Ciamician”, Università di
Bologna,
via Selmi 2, 40126 Bologna, Italy
Fax: +39-051-2099456
E-mail: diego.savoia@unibo.it
Supporting information for this article is available on the
WWW under http://www.eurjic.org or from the author.
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DOI: 10.1002/ejoc.200400716
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Enantioselective Allylic Alkylation Catalysed by Cationic Pd Complexes
FULL PAPER
(ring-substituted aza-heteroaromatic aldehyde and chiral
1,2-amino alcohol) and in the tether connecting them (or-
ganometallic reagent). Similarly, the influence of a new sub-
stituent R1 or a benzo[b]-fused pyridine ring can be studied
by preparing the ligand from a suitable aldehyde. As a cor-
ollary of this study, owing to the low reactivity of the ace-
tate 1 in the reaction catalysed by 12, we have checked the
more reactive 1,3-diphenyl-2-propenyl ethyl carbonate 1b as
the substrate in the same substitution reaction.
Scheme 2.
assume the NR configuration when forming the Pd com-
plex, as shown by the X-ray structural analysis of 12. This
happens to avoid the severe interaction of the two iPr sub-
stituents that would occur in the alternative complex with
the NS configuration.
Results and Discussion
Influence of the Aziridine Ring Substituent
In order to determine the effect of the aziridine C2-sub-
Since then, we have directed our efforts to the prepara- stituent on the enantioselectivity we chose to replace the iPr
tion of other C1-symmetrical (N,NЈ)* ligands and their pal- group, present in the prototypical ligand 2, with a phenyl
ladium complexes (general structures 14 and 15, respec- group. This was accomplished by preparing the free imine
tively) by the same route. This is described in Scheme 2 and 16 and the O-protected one (18), from 2-pyridinylaldehyde
involves the preliminary organometallic addition step to the and (R)-phenylglycinol, and optimising the preparation of
imine 13 to give the 1,2-amino alcohol 14, from which the the amino alcohol 17 from them (Scheme 3). Although
aziridine ring is constructed. This route is flexible, as it al- phenylglycinol has been widely exploited for the diastereo-
lows variation of the ligand skeleton, the size of the Pd selective addition of organometallic reagents to imines,[9] in
chelate ring (starting from the appropriate aldehyde) and our hands the addition of iPrMgCl to 16 in THF at 0 °C
all the substituents, especially those in the heterocyclic rings gave the secondary amines 17 with moderate stereocontrol.
Table 1. Pd-catalysed enantioselective allylic substitution reactions of 1,3-diphenyl-2-propenyl acetate and carbonate 1a,b with sodium
dimethyl malonate (1.5 equiv., THF, 25 °C).
Entry
Substrate
Catalyst [equiv.]
Time [h]
Product
Yield [%]
ee [%]
1
2
3
4
5
6
7
8
1a
1b
1b
1b
1a
1a
1b
1b
12 (0.1)
12 (0.05)
36
3
(R)-2
(R)-2
(S)-2
(S)-2
(R)-2
(S)-2
(S)-2
(S)-2
50
85
42
19
90
86
Ͻ5
23
42
35
20 (0.1)
12
12
36
24
18
6[b]
70[a]
74
[(allyl)PdCl]2 (0.05), 19 (0.1)
25a (0.1)
22
35
43
75
25b (0.1)
25c (0.1)
25c (0.1)
[a] Almost no reaction occurred at 0 °C or when using 10 mol-% of sodium hydride. [b] The reaction was performed at 50 °C.
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FULL PAPER
Scheme 3.
No attempt was made to separate the main (S,S)-dia- 1a (entry 1); unfortunately, almost no reaction took place
stereomer. The experimental conditions used by Spero[10] with 1b at 0 °C. The reaction of carbonate 1b with dimethyl
for similar Grignard reactions with 2-pyridylketimines were malonate in the presence of 10 mol-% each of sodium hy-
then applied to 16, with the use of CH2Cl2 as the solvent dride[12] and complex 20 at 25 °C stopped after a few hours
and the presence of MgBr2.[10] In this manner a 95% yield when a black Pd precipitate had formed; only small
and a 75:25 dr (1H NMR spectroscopy) were obtained for amounts of 2 were detected by TLC analysis. The reaction
17. Also, the addition of iPrMgCl to the O-protected imine of 1b with sodium dimethyl malonate (1.5 equiv.) in the
18 in THF at –78 °C gave 17 with a moderate diastereose- presence of allylpalladium chloride dimer (5 mol-%) and li-
lectivity (65:35), although a better dr (80:20) was finally ob- gand 19 (10 mol-%), i.e. forming the reactive complex 21 in
tained by applying the Spero protocol to the protected im- situ, gave (S)-2 with 74% yield and 86% ee (entry 4). On
ine 18, and the main diastereomer of 17 was isolated pure the other hand, the reaction of 1b with dimethyl malonate
in 45% yield by column chromatography of the reaction salt
(2.5 equiv.),
bis(trimethylsilyl)acetamide
(BSA,
mixture. 3 equiv.), potassium acetate (1 mol-%) and the palladium
The conversion of the amino alcohol 17 to the aziridine complex 20 (10 mol-%) gave a largely incomplete conver-
19 by treatment with carbonyl diimidazole (CDI)[8,11] was sion to (S)-2, which was isolated after 12 h with only 33%
not satisfactory. In this case, a better result was achieved yield although with high ee (90%). It should be underlined
from the reaction with mesyl chloride and triethylamine at that the two complexes 12 and 20 have opposite chirality.
–78 °C, which gave 19 in 55% yield. The cationic (η3-allyl) Consequently, they induce the same sense of asymmetric
palladium complex 20 was then prepared by the routine induction in the formation of (R)-2 and (S)-2, respectively.
procedure. The complex 20 (10 mol-%) was used for the
catalytic allylation of sodium dimethyl malonate with the
acetate 1a, but almost no reaction was observed after one
day at 25 °C. However, using the carbonate 1b, almost com-
plete conversion (TLC) after 12 h at 25 °C in THF was ob-
served and the product (S)-2 was isolated by column
Influence of the Ligand Skeleton and C6-Pyridine
Substituent
chromatography with 70% yield and 90% ee (Table 1, en-
We aimed to assess the effect of the modified N,N-ligand
try 3). It is noteworthy that with 12 as the catalyst (5 mol- skeleton or pyridine-substitution pattern on the enantio-
%) the malonate 2 was obtained with 85% yield from the selectivity of the substitution reaction, hence we prepared
carbonate 1b after only 3 h at 25 °C, but with lower ee the imines 22a–c from commercially available 2- and 8-qui-
(19%, entry 2) with respect to the reaction with the acetate nolinaldehydes and ad hoc prepared 6-benzyl-2-pyridinal-
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Enantioselective Allylic Alkylation Catalysed by Cationic Pd Complexes
FULL PAPER
dehyde, respectively. In the case of 22a and 22c we envi-
The reactions carried out with the acetate 1a catalysed
sioned a steric interaction of the pyridine-fused benzene by complexes 25a–c gave unexpected results. A low enantio-
ring or the C6-benzyl substituent with the phenyl group of selectivity for (R)-2 was obtained using 25a (4% ee, Table 1,
the η3-allyl ligand in the reactive allylic complex. A six- entry 5), and an inversion of the enantioselectivity was ob-
membered Pd-chelation complex should be formed with the served in the reaction catalysed by 25b: in fact, (S)-2 was
ligand 24b derived from 22b, which might result in a modi- prevalently formed, although with low ee (23%, entry 6). In
fied structure of the allylic complex.
both cases, the pyridine substituent caused an increase of
The usual route was followed to prepare the new (N,NЈ)* the reaction time needed to achieve a satisfactory conver-
ligands (Scheme 4). However, the addition of iPrMgCl to sion. An even more sluggish reaction was observed with the
24a was plagued by poor chemoselectivity, affording the β- 6-benzylpyridine derivative 25c, so in this case we worked
amino alcohol 23a with 25% yield after chromatographic with the more-reactive carbonate 1b and obtained (S)-2
separation from several unidentified by-products and its with reasonable yield and moderate enantioselectivity (47%
diastereomer (75:25 dr, as determined by GC-MS analysis ee, entry 7). When the same reaction was performed at
of the crude product). A more selective addition of the same higher temperature (50 °C) the reaction rate increased con-
Grignard reagent was observed to the 8-quinolineimine 22b siderably and (S)-2 was isolated with 75% yield, but slightly
(85:15 dr) and the pure diastereomer 23b was isolated with lower ee (37%, entry 8).
38% yield. Finally, the imine 22c was prepared from 6-ben-
zyl-2-bromopyridine[13] by bromine–lithium exchange at
low temperature, followed by reaction with DMF. The reac-
tion of 22c with iPrMgCl gave the amino alcohol 23c with
good yield and diastereoselectivity (90:10 dr), and the pure
diastereomer was isolated with 56% yield by column
chromatography. The aziridines 24a–c and their cationic
(η3-allyl)palladium complexes 25a–c were readily prepared
X-ray Studies of (η3-1,3-Diphenylallyl)palladium
Complexes: A Tentative Explanation of the Divergent
Enantioselectivity
The stereochemical outcomes of the reactions catalysed
by the routine sequence in good yields (Scheme 4). X-ray by the (N,NЈ)*(η3-allyl)palladium salts 12 and 25a,b are not
analyses of the recrystallised salts 25a,b (see Supporting In- correlated to their crystallographic parameters (bond
formation) showed structures similar to that of 12.[8] How- lengths and angles).[14] Therefore, with the aim of finding
ever, two independent cations are present in the crystals of clues to explain the remarkable inverted enantioselectivity
the 2-quinoline derivative 25a, and in both of them the obtained with catalyst 25c with respect to 20, we prepared
endo-allyl rotamer predominates. In the crystal of the 8- the corresponding cationic (η3-1,3-diphenylallyl)palladium
quinoline derivative 25b, which features a six-membered Pd complexes, which are the possible intermediates in the en-
chelate ring, a 56:44 exo/endo ratio of the allyl rotamers was antio-discriminating steps, as their hexafluoroantimonate
observed. It is noteworthy that the ligands in the salts 12[8] salts 26 (Scheme 4) and 21 (Scheme 3), respectively. X-ray
and 25a,b present similar envelope or puckered conforma- diffraction analysis (Figure 1 for 21 and Figure 2 for 26)
tions.
showed that the structures of these complexes are similar to
Scheme 4.
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F. Ferioli, C. Fiorelli, G. Martelli, M. Monari, D. Savoia, P. Tobaldin
FULL PAPER
each other as well as to those of 12[8] and 25a,b.[14] How-
ever, only the endo rotamers of the 1,3-diphenylallyl ligand
are present in 21 and 26. For clarity, throughout the paper
the aziridine and pyridine nitrogen atoms are indicated as
NA and NP, respectively, and the allylic carbons CA (trans
to aziridine) and CP (trans to pyridine).
Figure 2. ORTEP drawing of one of the independent cations of 26.
Thermal ellipsoids at 30% probability level. The following conven-
tions have been adopted: N1 = NA, N2 = NP, C2 = Cendo, C1 =
CP, C3 = CA.
Figure 1. ORTEP drawing of one of the cations of 21. Thermal
ellipsoids at 30% probability level. The following conventions have
been adopted: N1 = NA, N2 = NP, C2 = Cendo, C1 = CP, C3 = CA.
are longer than the corresponding Pd–NA bonds. For exam-
ple, in the (η3-1,3-diphenylallyl)palladium complex 26,
where two independent cations are present, the Pd–NP
bonds are in the range 2.180–2.200(5) Å and are consider-
A common feature of all the ionic Pd complexes is the ably longer than the Pd–NA bonds [2.133–2.152(6) Å]. This
unique configuration of NA, which is (R) for the complexes is noteworthy because NP and NA use sp2- and sp3-type
12, 25a,b and 26 derived from (S)-valinol, and (S) for the orbitals, respectively. The lengths of the two Pd–NA bonds
complex 21 derived from (R)-phenylglycinol.[15] This avoids in the calculated structure of the complex [(η3-1,3-di-
the steric interaction between the iPr group present in the phenylallyl)Pd(3)][SbF6] are 2.131 and 2.134 Å,[1b,1f] which
tether linking the nitrogen atoms and the aziridine substitu- are similar to the values observed in 21 and 26. On the
ent (iPr or Ph). It should also be noted that in all our cat- contrary, in the reported X-ray structure of an [(N,NЈ)(η3-
ionic allylic Pd complexes, apart from 21, the Pd–NP bonds 1,3-diphenylallyl)Pd]+ cation, the metal forms a longer
Scheme 5.
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Enantioselective Allylic Alkylation Catalysed by Cationic Pd Complexes
FULL PAPER
bond with pyrrolidine (2.15 Å) than with pyridine alcohols. The ligands were then converted into the
(2.08 Å).[2a] Moreover, the two Pd–N bonds in the [(sparte- [(N,NЈ)*(η3-allyl)Pd][SbF6] complexes, which were used as
ine)(η3-1,3-diphenylallyl)Pd]+ cation are 2.19 and 2.24 Å.[16] catalysts in the allylic substitution reaction of 1,3-diphenyl-
Hence, it appears that the aziridine nitrogen generally forms 2-propenyl esters with sodium dimethyl malonate in
a shorter bond a with palladium cation than other sp3-hy- THF.[16,23] Although the synthetic route to the ligand
bridised nitrogen atoms.
proved to be more efficient and stereoselective when start-
In order to understand the enantioselectivity of the alky- ing from (S)-valinol as the chiral precursor, it was observed
lation reaction, several points should be considered. In all that the analogous ligand prepared from (R)-phenylglycinol
the endo and exo rotamers of the unsubstituted allyl com- was considerably more enantioselective in the catalytic ap-
plexes 12 and 25a,b, and particularly in endo-21 and endo- plication (90% ee), as a consequence of the more-de-
26, the CA–Pd bond is longer than the CP–Pd bond, thus manding steric effects of the phenyl substituent in the aziri-
indicating an apparently greater trans influence of aziridine dine ring, which is oriented towards the allyl ligand. On the
with respect to pyridine and a more electrophilic character other hand, structural variations in the starting heterocyclic
of CA.[17–19] It should also be considered that complexes 21 aldehyde, the capability of the ligand to form either a five-
and 26 in CDCl3 solution are present as syn,syn-endo/syn, or six-membered ring with palladium and the substitution
syn-exo mixtures (72:28 and 85:15, respectively), and that pattern in the aza-heteroaromatic ring affect either the reac-
in no case were anti,syn-allyl species detected. The endo/exo tivity and/or stereocontrol. In particular, inversion of
ratios and the Pd–C bond lengths are determined by steric enantioselectivity was observed using the ligand bearing a
effects, i.e. the non-bonding interactions of the (N,NЈ)* and 6-benzyl-substituted pyridine. The X-ray diffraction studies
allyl ligands, whereas electronic effects are not relevant.
of the two [(N,NЈ)*(η3-1,3-diphenylallyl)Pd][SbF6] com-
In the hypothesis that the endo and exo rotamers have plexes that afforded the most marked difference in enantio-
the same reactivity and undergo a completely regioselective selectivity showed the similarity of their structures and the
attack, the ee’s of the product should be correlated to the presence of only the endo-allylic rotamers, contrary to the
endo/exo ratio. This is true, for example, in reactions cata- unsubstituted allylpalladium complexes. Hence, the solid-
lysed by 8-(2-oxazoline)quinoline ligands.[20] In the case of state structure does not always correspond to the more re-
our ligands, the preferred formation of (R)-2 with 12 and active conformer in solution, and the steric effects of the
(S)-2 with 20 can be rationalised by assuming a highly re- different skeleton or substituents on the regio- and stereo-
gioselective attack at the more electrophilic allylic termini selectivity are not easily evaluated.[24] Interestingly, the Pd–
CA of the most abundant rotamers, e.g. endo-21, as shown N(aziridine) bonds in most allylic complexes studied are
in Scheme 5. Conversely, the opposite enantioselectivity ob- shorter than the Pd–N(pyridine) bonds.
tained in the case of 26, which has the same chirality as 12
A lack of reactivity was observed with cyclohexenyl ace-
but mainly affords (S)-2, requires a different interpretation. tate, as previously reported for the reaction catalysed by the
In this case, the relative ratio and reactivity of endo and bis(aziridine) 3.[1] The moderate efficiency of the alkylation
exo rotamers of 26 must be considered.[21] This different reactions catalysed by our ligands/complexes can be attrib-
reactivity is probably associated to the relative stability of uted to the weakness of the Pd–N(pyridine) bond(s), which
the late transition states leading to the alternative η2-com- affects the stability of the chelated [(N,NЈ)*(η3-allyl)Pd]+
plexes, which are precursors of the product 2 (Scheme 5). It cations. Similarly, the absence of a π-acceptor N ligand in
should be noted that the formation of the η2-complex 28 (N,NЈ)* probably does not allow the effective stabilization/
by attack on the less-abundant rotamer exo-26 occurs by dissolution of the Pd0 species that are formed by nucleo-
“preferential rotation”[22] and does not suffer from severe philic attack on the intermediate cationic complex. With
steric interactions, contrary to the alternative η2-complex regard to this, it would be worthwhile to study the effect of
derived from endo-26. In our opinion, the high enantio- electron-withdrawing substituents on the pyridine ring of
selectivity observed for (S)-2 in the reaction catalysed by the ligand, particularly at C4, where steric effects are ab-
complex 20 is the result of two convergent factors: the pre- sent.
valence of the rotamer endo-21 in solution, and the rela-
tively low activation energy of the transition state derived
from the nucleophilic attack at the more electrophilic CA
allylic terminus leading to the η2-complex 27.
Experimental Section
General Remarks: Melting points are uncorrected. Solvents were
distilled from the appropriate drying agent under N2 before use:
THF (sodium benzophenone ketyl, then LiAlH4), CH2Cl2 (P2O5).
Conclusions
Optical rotations were measured on a digital polarimeter in a 1-dm
1
cell and [α]D values are given in 10–1 degcm3 g–1. H NMR spectra
We have investigated a synthetic route to enantiopure C1-
were recorded on a Varian Gemini instrument at 300 or 200 MHz
symmetric N,NЈ-bidentate ligands carrying either a 1,2-di-
substituted aziridine or an aza-aromatic ring. The ligands
were prepared from imines derived from pyridine- and
for samples in CDCl3 which was stored over Mg. 1H chemical shifts
are reported in ppm relative to CHCl3 (δH = 7.27 ppm) and coup-
ling constants are given in hertz. Mass spectra were measured at
quinolinecarbaldehydes and optically pure β-amino an ionising voltage of 70 eV on a Hewlett–Packard 5970 or 5890
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F. Ferioli, C. Fiorelli, G. Martelli, M. Monari, D. Savoia, P. Tobaldin
spectrometer with GLC injection. Chromatographic separations (24), 65 (11), 83 (10), 139 (9). nBuLi (1.6 m in hexanes, 3.44 mL,
FULL PAPER
were performed on columns of SiO2 (Merck, 230–400 mesh) at me-
dium pressure. The following materials were purchased from Ald-
rich: nBuLi (1.6 m in hexanes), iPrMgCl (2 m in THF), [(allyl)-
PdCl]2, AgSbF6, 3-methyl-2-butenyl bromide, 2-pyridinaldehyde, 2-
quinolinaldehyde, (S)-valinol, (S)-phenylglycinol, 1,1Ј-carbonyl-
diimidazole, thionyl chloride. 8-Quinolinecarbaldehyde was pre-
pared from 8-methylquinoline by oxidation with SeO2.[25] η3-(1,3-
Diphenylallyl)palladium chloride dimer was prepared from the allyl
chloride by reaction with PdCl2/SnCl2/NaCl in DMF following a
procedure described for the preparation of different η3-allylpalladi-
um(ii) complexes.[26] All the organometallic reactions were per-
formed in a flame-dried apparatus under a static atmosphere of
dry N2.
5.5 mmol) was slowly added to the solution of this compound
(1.36 g, 5.5 mmol) in THF (8 mL) cooled to –78 °C while magneti-
cally stirring. The mixture was stirred for 1 h at –78 °C, then dry
DMF (0.66 mL) was directly added to the solution. After stirring
for 1 h, H2O (10 mL) was added and the organic phase was ex-
tracted with Et2O (3×10 mL). The collected organic layers were
dried (Na2SO4) and concentrated to leave an oily residue.
Chromatography on a silica gel column, eluting with cyclohexane/
ethyl acetate (10:1), gave 6-benzyl-2-pyridinecarbaldehyde as an oil
(0.65 g, 60%). 1H NMR (200 MHz, CDCl3): δ = 10.10 (s, 1 H,
CHO), 7.80 (m, 2 H, Py), 7.48–7.10 (m, 6 H, Ar), 4.27 (s, 2 H,
CH2). MS: m/z (%) 196 (100), 197 (28), 167 (21), 168 (15), 166 (14),
91 (9), 65 (7), 115 (5). The imine 22c was then obtained from the
aldehyde by the previously described procedure as a yellowish oil
(1.08 g, 90%). [α]2D0 = –9.4 (c = 0. 38, CHCl3). 1H NMR (200 MHz,
CDCl3): δ = 8.32 (s, 1 H, CH=N), 7.89 (d, J = 7.6 Hz, 1 H, Py),7.60
(t, J = 7.6 Hz, 1 H, Py), 7.40–7.17 (m, 5 H, Ph), 7.08 (d, J = 7.8 Hz,
1 H, Py), 4.20 (s, 2 H, CH2), 3.87 (dd, J = 4.4 and 10.2 Hz, 1 H,
CH2O), 3.67 (t, J = 10.2 Hz, 1 H, CH2O), 3.09 (m, 1 H,
NCHCH2O), 1.97 (m, 1 H, CHMe2), 0.94 and 0.93 (2 d, J = 6.6 Hz,
6 H, CHMe2), 0.06 (s, 9 H, SiMe3) ppm. GC-MS: m/z (%) = 251
(100), 73 (26), 209 (18), 183 (11), 221 (10), 354 (9) [M+], 339 (7),
311 (5).
Preparation of the Imines: The imines were prepared on a 5 mmol
scale by a previously described procedure[27] and used without fur-
ther purification.
(S)-N-[(2-Pyridyl)methylidenephenylglycinol (16):[28] Yellow oil:
100%. [α]2D0 = +19.6 (c = 0.83, CHCl3). We observed a 55:45 mix-
ture of imine and 1,3-oxazolidine by 1H NMR in CDCl3
(200 MHz): δ = 8.49 (s, 1 H, CH=N), 5.65 (s, 1 H, NCHO) ppm.
1
The H NMR spectra in CDCl3 and [D8]THF have been partially
described previously.[28]
Preparation of Secondary Amines by Addition of iPrMgCl to Imines.
Synthesis of (R)-N-[(R)-2-methyl-1-(2-pyridyl)propyl]phenylglycinol
(17): Anhydrous MgBr2 (1.656 g, 9 mmol) was added to the solu-
tion of the imine 18 (1.782 g, 6 mmol) in CH2Cl2 (60 mL), cooled
to 0 °C, and the mixture was stirred for 1 h while the temperature
rose to 20 °C. Then, iPrMgCl (2 m in Et2O, 9.0 mL, 18 mmol) was
added over 10 min, the mixture was stirred for a further 3 h, and
then quenched with sat. NaHCO3 (20 mL). The organic layer was
separated and the organic material was extracted from the aqueous
phase with CH2Cl2 (3×20 mL). The collected organic layers were
concentrated and the residue was treated with NH4F (2.0 g) in
MeOH/H2O (1:1, 20 mL) for 6 h, then solid NaOH was added to
reach pH 11 and the organic material was extracted with Et2O
(3×20 mL). The collected ethereal layers were dried (Na2SO4) and
concentrated to leave an oily residue. The diastereomeric ratio
(80:20) was determined by GC-MS and 1H NMR spectroscopy.
Chromatography on a SiO2 column eluting with cyclohexane/ethyl
acetate (85:15) gave compound 17 as a pure diastereomer. Yellow-
(S)-N-[(2-Pyridyl)methylidene]-O-trimethylsilylphenylglycinol (18):
Yellow oil: 84%. [α]2D0 = –15.5 (c = 0.62, CHCl3). 1H NMR
(300 MHz, CDCl3): δ = 8.63 (d, J = 4 Hz, 1 H, Py), 8.43 (s, 1 H,
CH=N), 8.15 (d, J = 8 Hz, 1 H, Py), 7.73 (t, J = 8 Hz, Py), 7.55–
7.20 (m, 6 H, Py and Ph), 4.50 (m, 1 H, CHPh), 3.84 (m, 2 H,
CH2O), 0.0 (s, 9 H, SiMe3) ppm. GC-MS: m/z (%) = 195 (100)
[M+ – CH2OSiMe3], 92 (30), 73 (18), 66 (12), 163 (10), 298 (4)
[M+ – 1].
(S)-N-[(2-Quinolyl)methylidene]-O-trimethylsilylvalinol (22a): Yel-
low oil; 94%. [α]2D0 = –23.2 (c = 1.1, CHCl3). H NMR (200 MHz,
1
CDCl3): δ = 8.48 (s, 1 H, CH=N), 8.15 (m, 3 H, quinoline), 7.90–
7.50 (m, 3 H, quinoline), 3.92 (dd, J = 4.2 and 10.5 Hz, 1 H,
CH2O), 3.75 (dd, J = 8.1 and 10.5 Hz, 1 H, CH2O), 3.18 (m, 1 H,
CHN), 2.0 (m, 1 H, CHMe2), 0.95 (2 d, J = 6.7 Hz, 6 H, CHMe2),
0.05 (s, 9 H, SiMe3) ppm. GC-MS: m/z (%) = 211 (100) [M+
–
CH2OSiMe3], 169 (42), 142 (34), 73 (31), 181 (25), 271 (10), 115
1
ish oil: 0.736 g, (45%);. [α]2D0 = –23.3 (c = 1.0, CHCl3). H NMR
(5), 299 (5) [M+ – Me]
(300 MHz, CDCl3): δ = 8.46 (d, J = 4.8 Hz, 1 H, Py), 7.46 (t, J =
7.6 Hz, 1 H, Py), 7.2–7.0 (m, 6 H, Ar), 7.95 (d, J = 7.6 Hz, Py),
3.8–3.5 (m, 3 H, CHCH2), 3.41 (d, J = 7.2 Hz, 1 H, CHiPr), 2.01
(m, 1 H, CHMe2), 1.25 (broad, 2 H, OH and NH), 1.05 and 0.79
(2 d, J = 6.9 Hz, CHMe2). C17H22N2O: calcd. C 75.52; H 8.20, N
10.36; found C 75.30, H 8.10, N 10.31. The product decomposed
during GC-MS analysis. The minor diastereomer could not be iso-
lated in a pure state by column chromatography.
(S)-N-[(8-Quinolyl)methylidene]-O-trimethylsilylvalinol (22b): Yel-
1
low oil: 98%. [α]2D0 = –32 (c = 1.80, CHCl3). H NMR (200 MHz,
CDCl3): δ = 9.58 (s, 1 H, CH=N), 8.98 (dd, J = 2.0 and 4.2 Hz, 1
H, quinoline), 8.46 (dd, J = 1.6 and 7.4 Hz, 1 H, quinoline), 8.19
(dd, J = 4.8 and 8.0 Hz, 1 H, quinoline), 7.90 (dd, J = 1.4 Hz0 and
8.0 Hz, 1 H, quinoline), 7.60 (t, J = 7.4 Hz, 1 H, quinoline), 7.44
(dd, J = 4.4 and 8.4 Hz, 1 H, quinoline), 3.95 (dd, J = 6.6 and
10.6 Hz, 1 H, CH2O), 3.75 (dd, J = 7.8 and 10.2 Hz, 1 H, CH2O),
3.25 (m, 1 H, N–CH), 2.05 (m, 1 H, CHMe2), 1.00 (d. J = 7.0 Hz,
6 H, CHMe2), 0.07 (s, 9 H, SiMe3) ppm. GC-MS: m/z (%) = 155
(100), 211 (38) [M+ – CH2OSiMe3], 142 (36), 156 (18), 73 (17), 299
(4) [M+ – Me].
Preparation of the Amines 23a–c: iPrMgCl (6 mmol) was added to
a solution of the imine (3 mmol) in THF (10 mL) and magnetically
stirred and cooled to –78 °C. After 1.5 h, the reaction mixture was
quenched by adding saturated aq. NaHCO3 (10 mL) and the or-
ganic phase was extracted with diethyl ether (3×10 mL). The col-
lected ethereal phases were dried with Na2SO4 and concentrated to
(S)-N-[(6-Benzyl-2-pyridyl)methylidene]-O-trimethylsilylvalinol leave a yellowish oil. Treatment with 1 n HCl (6 mL) at 25 °C for
(22c): 6-Benzyl-2-bromopyridine was prepared from 2,6-dibro-
2 h, addition of NaOH until pH 11, extraction with Et2O
(3×5 mL), drying (Na2SO4) and evaporation of the solvent gave a
thick, yellow oil. The diastereomeric ratios were determined byGC-
MS and 1H NMR analysis: 23a 75:25, 23b 85:15, 23c 90:10. The
major diastereomers of 23a–c were separated by column
mopyridine according to the reported procedure:[13] yellowish oil
1
(61%). H NMR (200 MHz, CDCl3): δ = 7.48–7.18 (m, 7 H, Ar),
7.00 (d, J = 7.0 Hz, 1 H, Py), 4.15 (s, 2 H, CH2) ppm. MS: m/z (%)
= 248 (100), 246 (95), 247 (44), 167 (43), 249 (41), 166 (27), 168
1422
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 1416–1426

Enantioselective Allylic Alkylation Catalysed by Cationic Pd Complexes
FULL PAPER
chromatography (SiO2; hexane/ethyl acetate with increasing po-
larity) with dr Ͼ 95:5 and were used as such in the subsequent step.
For analytical purposes, the pure diastereomers were obtained by
repeated chromatography with slightly decreased yield. No attempt
was made to isolate the minor diastereomers as they could not be
isolated in a pure state by column chromatography.
Preparation of the Aziridines 24a–c: A solution of 1,2-amino
alcohol (3 mmol) and 1,1Ј-carbonyldiimidazole (0.540 g, 3.3 mmol)
in dry CH2Cl2 (10 mL) was stirred at room temperature for 1.5 h,
then the solvent was evaporated and the yellow-brown residue was
dissolved in a 1:3 THF/H2O mixture (80 mL). The mixture was
vigorously stirred overnight, then THF was evaporated under re-
duced pressure and the organic phase was extracted with Et2O
(3×30 mL). The collected organic phases were dried (Na2SO4),
(S)-N-[(S)-2-Methyl-1-(2-quinolyl)propyl]valinol (23a): Yellowish
oil; 0.215 g (25%). [α]2D0 = –70.7 (c = 1.05, CHCl3). 1H NMR
(200 MHz, CDCl3): δ = 8.08 (dd, J = 5.4 and 8.0 Hz, Ar), 7.80 (dd, then evaporated to leave an oily residue, which was chromato-
J = 1.2 and 8.0 Hz, 1 H, Ar), 7.70 (m, 1 H, Ar), 7.51 (m, 1 H, Ar),
7.31 (d, J = 8.4 Hz, 1 H, Ar), 3.70 (dd, J = 3.6 and 10.6 Hz, 1 H,
CH2O), 3.61 (d, J = 6.6 Hz, 1 H, ArCHN), 3.45 (dd, J = 3.8 and
10.8 Hz, 1 H, CH2OH), 2.5 (broad, 2 H, OH and NH), 2.13 (m, 1
H, CHN), 2.06 (m, 1 H, CHMe2), 1.32 (s, 1 H, NH), 1.65 (m, 1 H,
CHMe2), 1.04 (d, J = 6.6 Hz, 3 H, CHMe2), 0.86, 0.84 and 0.77 (3
d, J = 7.0 Hz, 9 H, CHMe2) ppm. GC-MS: m/z (%) = 243 (100)
[M+ – iPr], 184 (98), 142 (51), 199 (50), 154 (30), 158 (28), 157 (20),
169 (19), 170 (18), 255 (10) [M+ – CH2OH]. C18H26N2O: calcd. C
75.48; H 9.15, N 9.78; found C 75.55, H 9.18, N 9.70.
(S)-N-[(S)-2-methyl-1-(8-quinolyl)propyl]valinol (23b): Yellowish oil;
0.325 g (1.14 mmol, 38%). [α]2D0 = –49.1 (c = 1.05, CHCl3). 1H
NMR (200 MHz, CDCl3): δ = 8.87 (dd, J = 1.8 and 4.4 Hz, Ar),
8.16 (dd, J = 1.8 and 8.4 Hz, 1 H, Ar), 7.72 (m, 1 H, Ar), 7.47 (d,
J = 5.2 Hz, 2 H, Ar), 7.39 (dd, J = 4.4 and 8.0 Hz, 1 H, Ar), 3.95
(broad, 1 H, OH), 3.71 (dd, J = 4.0 and 10.6 Hz, 1 H, CH2O), 3.43
(dd, J = 1.8 and 10.6 Hz, 1 H, CH2O), 2.55 (m, 2 H, ArCHN and
NH), 1.99 (m, 1 H, CHMe2), 1.55 (m, 1 H, CHMe2), 1.24 (d, J =
6.6 Hz, 3 H, CHMe), 0.64, 0.59 and 0.56 (3 d, J = 6.6 Hz, 9 H,
CHMe2) ppm. GC-MS: m/z (%) = 243 (100) [M+ – iPr], 184 (98),
142 (51), 199 (51), 158 (28), 154 (26), 157 (20), 167 (19), 168 (18).
C18H26N2O: calcd. C 75.48; H 9.15, N 9.78; found C 75.34, H 9.17,
N 9.72.
(S)-N-[(S)-1-(6-Benzyl-2-pyridyl)-2-methylpropyl]valinol (23c): Yel-
lowish oil; 0.546 g (56%). [α]2D0 = –64.4 (c = 0.68, CHCl3). 1H NMR
(200 MHz, CDCl3): δ = 7.49 (t, J = 7.6 Hz, 1 H, Py), 7.36–7.14 (m,
5 H, Ph), 6.94 (t, J = 7.6 Hz, 2 H, Py), 4.14 (s, 2 H, CH2Ph), 3.60
and 3.41 (2 dd, J = 3.8 and 10.8 Hz, 2 H, CH2O), 3.30 (d, J =
7.4 Hz, 1 H, ArCHN), 2.15 (m, 1 H, NCHCH2), 1.96 and 1.56 (2
m, 2 H, CHMe2), 1.42 (broad, 2 H, NH and OH), 1.04, 0.77, 0.75
and 0.74 (4 d, J = 7.0 Hz, 12 H, CHMe2) ppm. C21H30N2O: calcd.
C 77.25; H 9.26, N 8.58; found C 77.33, H 9.32, N 8.52. The pro-
duct decomposed during the GC-MS analysis.
graphed on a SiO2 column, eluting with cyclohexane/ethyl acetate
mixtures.
(S)-1-[(S)-2-Methyl-1-(2-quinolyl)propyl]isopropylaziridine
(24a):
Yellowish oil; 0.507 g (63%), dr = 95:5 (GC/MS). [α]2D0 = –32.6 (c
= 1.05, CHCl3). 1H NMR (200 MHz, CDCl3): δ = 8.12 (dd, J =
8.8 Hz and 15.8 Hz, 1 H, Ar), 7.82 (d, J = 8.0 Hz, 1 H, Ar), 7.71
(d, J = 8.4 Hz, 2 H, Ar), 7.53 (t, J = 7.6 Hz, 1 H, Ar), 2.41 (m, 1
H, NCHCH2), 2.20 (d, J = 8.5 Hz, 1 H, PyCH), 1.85 (d, J = 3.6
Hz, 1 H, NCH2), 1.64 (d, J = 6.2 Hz, 1 H, NCH2), 1.22 (d, J =
5.6 Hz, 3 H, CHMe2), 1.22 (m, 1 H, CHMe2), 1.15 (m, 1 H,
CHMe2), 0.74 (t, J = Hz, 6 H, CHMe2), 0.35 (d, J = 6.4 Hz, 3 H,
ArCHCHMe2) ppm. GC-MS: m/z (%) = 155 (100), 197 (60), 142
(50), 168 (22), 225 (18) [M+ – iPr]. C18H24N2: calcd. C 80.55; H
9.01, N 10.40; found C 80.59, H 9.06, N 10.42.
(S)-1-[(S)-2-Methyl-1-(8-quinolyl)propyl]isopropylaziridine
(24b):
Yellowish oil; 0.523 g (65%), dr = 96:4 (GC/MS). [α]2D0 = +15.7 (c
1
= 0.53, CHCl3). H NMR (200 MHz, CDCl3): δ = 8.89 (m, 1 H,
Ar), 8.15 (d, J = 8.1 Hz, 1 H, Ar), 8.05 (d, J = 6.4 Hz, 1 H, Ar),
7.70 (d, J = 8.1 Hz, 1 H, Ar), 7.60 (m, 1 H, Ar), 7.38 (m, 1 H, Ar),
3.86 (d, J = 8.7 Hz, 1 H, ArCHN), 2.38 (m, 1 H, NCHCH2), 1.80
(m, 2 H, NCHCH2), 1.22 (d, J = 6.6 Hz, 3 H, CHMe2), 1.03 (m,
2 H, CHMe2), 0.67 and 0.66 (2 d, J = 6.6 Hz, 6 H, CHMe2), 0.26
(d, J = 6.6 Hz, 3 H, CHMe2) ppm. GC-MS: m/z (%) = 155 (100),
197 (60), 142 (50), 225 (18), 168 (15), 184 (13), 268 (10) [M+], 253
(5). C18H24N2: calcd. C 80.55; H 9.01, N 10.44; found C 80.61, H
9.03, N 10.42.
(S)-1-[(S)-1-(6-Benzyl-2-pyridyl)-2-methylpropyl]isopropylaziridine
(24c): Yellowish oil; 0.545 g (59%), dr 98:2 (GC/MS). [α]2D0 = –44.5
1
(c = 0.63, CHCl3). H NMR (200 MHz, CDCl3): δ = 7.53 (t, J =
7.8 Hz, 1 H, 7.35–7–13 (m, 6 H, Ar), 6.93 (d, J = 7.8 Hz, 1 H, Py),
4.14 (s, 2 H, CH2Ph), 2.28 (m, 1 H, CHCH2), 2.18 (d, J = 8.8 Hz,
1 H, NCHAr), 1.77 (d, J = 3.6 Hz, 1 H, CHCH2), 1.54 (d, J =
6.2 Hz, 1 H, CHCH2), 1.20 and 1.05 (2 m, 2 H, CHMe2), 1.14,
0.74, 0.69 and 0.34 (4 d, J = 6.6 Hz, 12 H, CHMe2) ppm. GC-MS:
m/z (%) = 225 (100), 265 (88), 210 (58), 84 (47), 236 (35), 197 (33),
91 (20), 55 (17), 182 (16), 167 (13). C21H28N2: calcd. C 81.77; H
9.15, N 9.08; found C 81.83, H 9.18, N 9.04.
Preparation of [(N,NЈ)*(η3-allyl)Pd][SbF6] Complexes: Allylpalla-
dium chloride dimer (0.157 g, 0.43 mmol) was added to a solution
of the aziridine (0.86 mmol) in CH2Cl2 (15 mL). After stirring for
1 h the solution became green, then a solution of silver hexafluo-
roantimonate (0.300 g, 0.86 mmol) in THF (6 mL) was added and
the mixture was stirred for 30 min, during which time a white pre-
cipitate formed. The solid was filtered off through a small pad of
celite. The organic phase was washed with brine, dried (Na2SO4)
and evaporated to leave a solid residue, which was then crystallised.
Complex 12 has been described previously.[8]
(R)-1-[(R)-2-methyl-1-(2-pyridyl)propyl]phenylaziridine (19): Trieth-
ylamine (0.755 g, 7.4 mmol) and methanesulfonyl chloride (0.493 g,
4,44 mmol) were added to a solution of the diastereomerically pure
amino alcohol 17 (0.400 g, 1.48 mmol) in CH2Cl2 (12 mL) cooled
to –78 °C and the mixture was stirred for 3 h. After quenching
with sat. NaHCO3 (5 mL), the organic layer was separated and the
organic bases were extracted from the aqueous layer with CH2Cl2
(3×5 mL). The collected organic layers were dried (CaCl2) and
concentrated to leave an oil, which was chromatographed on a SiO2
column eluting with cyclohexane/ethyl acetate (85:15) to obtain
compound 19 as a yellowish oil. Yield: 0.202 g, (55%). [α]2D0
=
1
–129.6 (c = 0.44, CHCl3). H NMR (300 MHz, CDCl3): δ = 8.51
(d, J = 4.5 Hz, 1 H, Py), 7.56 (dt, J = 1.5 and 7.5 Hz, 1 H, Py),
7.42 (d, J = 7.5 Hz, 1 H, Py), 7.35–7.0 (m, 6 H, Ar), 2.71 (d, J =
6.0 Hz, 1 H, NCHPy), 2.35 (dd, J = 3.3 and 6.5 Hz, PhCHCH2),
2.28 (m, 1 H, CHMe2), 2.16 (d, J = 3.3 Hz, 1.H, CHCH2), 2.02 (d, Complex 20: Colourless crystals (CH2Cl2/Et2O), 57% yield; m.p.
J = 6.5 Hz, 1 H, CHCH2), 1.10 and 0.97 (2 d, J = 6.6 Hz, 6 H,
CHMe2) ppm. GC-MS: m/z (%) = 118 (100) [PhCHCH2N], 91 (86),
213–214 °C (dec.). [α]2D0 = –31.6 (c = 0.4, CHCl3). The 1H NMR
spectrum (300 MHz, CDCl3) shows the presence of two rotamers
136 (21), 119 (8), 78 (6), 182 (5), 104 (5), 209 (4) [M+ – iPr]. in a 60:40 ratio (the absorptions of the prevalent rotamer are re-
C17H20N2: calcd. C 80.91, H 7.99, N 11.10; found C 80.97, H 8.04,
N 11.05.
ported in bold): δ = 8.58 and 8.46 (2 d, J = 5.6 Hz, 1 H, Ar), 8.08
(m, 1 H, Ar), 7.77 (m, 1 H, Ar), 7.52 (m, 1 H, Ar), 7.47 (m, 1 H,
Eur. J. Org. Chem. 2005, 1416–1426
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1423

F. Ferioli, C. Fiorelli, G. Martelli, M. Monari, D. Savoia, P. Tobaldin
FULL PAPER
Ar), 7.30 (m, 4 H, Ar), 7.10 (m, 1 H, Ar), 6.96 (m, 1 H, Ar), 5.53
and 4.55 (m, 1 H, CH2CHCH2), 3.93 and 3.73 (2 d, J = 6.6 Hz, 1
H, CH2CHCH2), 3.68 and 3.59 (2 d, J = 6.6 Hz, 1 H, PyCH), 3.58
CH2CHCH2), 4.06 and 3.89 (2 d, J = 6.6 Hz, 1 H, CH2CHCH2),
3.34, 3.22, 3.14 and 3.10 (4 d, J = 12.4 Hz, 2 H, 2 CH2CHCH2),
3.24 and 3.13 (2 d, J = 8.2 Hz, 1 H, NCHAr), 2.84 and 2.50 (2 m,
and 3.26 (2 d, J = 6.6 Hx, 1 H, CH2CHCH2), 3.50 and 3.38 (2 dd, 1 H, NCHCH2), 2.68 and 2.38 (2 m, 2 H, CHCH2), 1.88, 1.81, 1.45
J = 7.3 and 5.0 Hz, 1 H, NCHCH2), 3.11 and 3.0 (2 m, 2 H,
NCHCH2), 2.85 and 2.56 (2 d, J = 12.6 Hz, 1 H, CH2CHCH2),
2.55 and 2.27 (2 m, 1 H, CHMe2), 1.44 (d, J = 12.6 Hz, 1 H,
CH2CHCH2), 1.23, 1.16, 1.09 and 0.87 (4 d, J = 6.8 Hz, CHMe2)
ppm.
and 1.18 (4 m, 2 H, CHMe2), 1.37, 1.25, 1.05, 1.03, 0.94, 0.90, 0.89
and 0.65 (8 d, J = 6.7 Hz, 12 H, CHMe2) ppm.
Complex 26: Orange crystals (MeOH), 77% yield; m.p. 218–219 °C
(dec.). [α]2D0 = +84.9 (c = 0.68, CHCl ). IR (KBr): ν = 2950, 1607,
˜
3
1570, 1540, 1491, 1464, 1023, 889, 756, 697 cm–1. The 1H NMR
spectrum (300 MHz, CDCl3) shows the presence of two rotamers
in an 85:15 ratio (the absorptions of the prevalent rotamer are re-
ported in bold): δ = 7.80–7.10 (m, 16 H, Ar), 6.90–6.60 (m, 2 H,
Ar), 6.55 and 6.44 (2 dd, J = 11.2 and 11.4 Hz, 1 H, CHCHCH),
5.33 and 4.86 (2 d, J = 10.8 Hz, 1 H, CHCHCH), 4.78 and 4.72
(d, J = 12.0 Hz, 1 H, CHCHCH), 4.29, 3.75, 3.21 and 3.01 (4 d, J
= 17.0 and 14.0 Hz, 2 H, CH2Ph), 2.91 (d, J = 8.7 Hz, 1 H,
NCHPy), 2.72 (m, 1 H, NCHCH2), 1.60–1.40 (m, 4 H, 2 CHMe2
and NCHCH2), 1.14, 1.02, 0.91, 0.89, 0.87, 0.55. 0.50 and 0.40 (8
d, J = 6.6 Hz, CHMe2) ppm. 13C NMR (75 MHz, [D6]DMSO): δ
(major diastereomer) = 162.1, 160.5, 139.8, 137.2, 136.1, 132–128,
123.8, 122.6, 107.9, 81.8, 80.0, 76.9, 45.9, 35.9, 33.1, 21.1, 21.0,
20.0, 19.6 ppm. C36H41F6N2PdSb: calcd. C 51.24, H 4.90, N 3.32;
found C 51.35, H 5.02, N 3.42.
Complex 21: Orange crystals (MeOH), 72% yield; m.p. 225–227 °C
(dec.). [α]2D0 = +26.5 (c = 0.58, CHCl ). IR (KBr): ν = 2980, 1607,
˜
3
1533, 1490, 1474, 1446, 1388, 1159, 1015, 758, 698 cm–1. The 1H
NMR spectrum (200 MHz, CDCl3) shows the presence of two rota-
mers in a 70:30 ratio (the absorptions of the prevalent rotamer are
reported in bold): δ = 7.95 (t, J = 6.6 Hz, 1 H, Ar), 7.80–6.95 (m,
17 H, Ar), 6.50 and 6.31 (2 d, J = 5.2 and 7.4 Hz, 1 H, Ar), 6.25
and 5.67 (2 dd, J = 11.0 and 11.4 Hz, 12.4 and 10.6 Hz, 1 H,
CHCHCH), 5.03 and 3.82 (2 d, J = 12.4 and 11.4 Hz, 1 H,
CHCHCH), 4.47 and 2.82 (2 d, J = 10.6 and 11.0 Hz, 1 H,
CHCHCH), 3.73 and 3.37 (d, J = 6.8 and 7.2 Hz,1 H, CHPy), 3.33
and 2.90 (2 m, 2 H, NCHCH2), 2.83 and 2.11 (m, 1 H, CHMe2),
2.43 and 2.27 (2 dd, J = 2.2, 8.0 Hz, 2.2 and 7.4 Hz, 1 H,
NCHCH2), 1.34, 1.0, 0.96 and 0.86 (4 d, J = 6.6 and 7.0 Hz, 6 H,
CHMe2) ppm. 13C NMR (75 MHz, CDCl3):
δ (major dia-
X-ray Crystallography: The diffraction experiments for 21 were car-
ried out at room temperature on a Bruker AXS SMART 2000 CCD
diffractometer using graphite-monochromated Mo-Kα radiation (λ
= 0.71073 Å). Intensity data were measured over full diffraction
spheres using 0.3°-wide ω scans at a crystal-to-detector distance of
5.0 cm. The SMART[29] software package was used for collecting
frames of data, indexing reflections and determination of lattice
parameters. The collected frames were then processed for integra-
tion with SAINT[29] and an empirical absorption correction was
applied with SADABS.[30] The diffraction experiments for 26 were
carried out on an Enraf–Nonius CAD4 diffractometer at room
temperature, using graphite-monochromatized Mo-Kα radiation (λ
= 0.71069 Å). The unit cell was determined by a least-squares fit-
ting procedure using 25 randomly selected strong reflections. The
diffracted intensities were corrected for Lorentz and polarization
effects. An empirical absorption correction was applied using the
azimuthal scan method. The structures were solved by direct meth-
ods (SIR 97)[31] and subsequent Fourier syntheses, and refined by
full-matrix least-squares calculations on F2 (SHELXTL)[32] with
anisotropic thermal parameters for the non-hydrogen atoms. One
stereomer) = 159.7, 149.0, 139.2, 136.2, 136.1, 132–126 (m), 125.0,
124.7, 106.0, 81.4, 75.8, 45.2, 34.85, 20.1, 18.8 ppm.
C32H33F6N2PdSb: calcd. C 48.79; H 4.22, N 3.56; found C 48.68,
H 4.40, N 3.48.
Complex 25a: Colourless crystals (CH2Cl2/Et2O), 70% yield; m.p.
182–185 °C (dec.). [α]2D0 = +101.1 (c = 1.06, CHCl3). The 1H NMR
spectrum (300 MHz, CDCl3) shows the presence of two rotamers
in a 65:35 ratio (the absorptions of the prevalent rotamer are re-
ported in bold): δ = 8.50 (2 d, J = 8 Hz, 1 H, Ar), 8.18–7.88 (m, 3
H, Ar), 7.70 (m, 2 H, Ar), 5.88 and 5.75 (2 m, 1 H, CH2CHCH2),
4.79 and 4.50 (2 d, J = 7.2 and 7.2 Hz, 1 H, CH2CHCH2), 4.13
and 3.95 (2 d, J = 6.6 and 7.2 Hz, 1 H, CH2CHCH2), 3.53 and
3.43 (2 d, J = 7.8 Hz, 1 H, ArCH), 3.45, 3.38, 3.32 and 3.16 (4 d,
J = 12.6 Hz, 2 H, CH2CHCH2), 2.82 and 2.49 (2 m, 1 H,
NCHCH2), 2.75 and 2.40 (2 m, 2 H, NCHCH2), 1.92 and 1.86 (2
m, 1 H, CHMe2), 1.41, 1.28, 1.10, 1.00, 0.93, 0.91, 0.74 and 0.51
(8 d, J = 6.6 Hz, 12 H, CHMe2) ppm.
Complex 25b: Colourless crystals (CHCl3), 79% yield; m.p. 215–
218 °C (dec.). [α]2D0 = +54.5 (c = 0.58, CHCl3). The 1H NMR spec-
trum (200 MHz, CD2Cl2) shows the presence of two rotamers in a
55:45 ratio (the absorptions of the prevalent rotamer are reported
in bold): δ = 9.29 and 9.21 (2 d, J = 5.0 Hz, 1 H, Ar), 8.51 (t, J =
8.7 Hz, 1 H, Ar), 7.99 (d, J = 5.7 Hz, 1 H, Ar), 7.63 (m, 3 H, Ar),
6.12 (m, 1 H, CH2CHCH2), 4.12 and 4.01 (2 d, J = 7.4 and 5.8 Hz,
1 H, CH2CHCH2), 3.76 (m, 1 H, CH2CHCH2), 3.53 (d, J = 7.0 Hz,
1 H, ArCH), 3.43 and 3.31 (2 d, J = 12.2 and 12.4 Hz, 1 H,
CH2CHCH2), 3.10 (m, 1 H, NCHCH2), 3.09 and 3.67 (2 d, J =
11.8 and 10.4 Hz, 1 H, CH2CHCH2), 2.55 and 2.42 (2 m, 2 H,
NCHCH2), 1.61 and 1.25 (2 m, 2 H, CHMe2), 1.50, 1.33, 0.91,
0.84, 0.61, 0.57, 0.20, 0.07 (8 d, J = 6.6 Hz, 12 H, CHMe2) ppm.
–
of the two SbF6 anions present in the asymmetric unit of 26 was
found to be disordered over two orientations yielding two distinct
F6 octahedra around the Sb centre (0.59 and 0.41 occupation fac-
tors, respectively). The methyl, methylene and aromatic hydrogen
atoms were placed in calculated positions and refined with ideal-
ized geometry, whereas the other H-atoms were located in the Fou-
rier map and refined isotropically. Crystal data and details of the
data collection for both structures are reported in Table S2 (see
Supporting Information). CCDC-244030 ... -244033 (for 21, 26 and
25a,b respectively) contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif. Further data are available as Supporting Infor-
Complex 25c: Colourless crystals (MeOH), 61% yield; m.p. 223–
mation[14]
.
1
224 °C (dec.). [α]2D0 = +4.2 (c = 1.0, CHCl3). The H NMR spec-
trum (300 MHz, CDCl3) shows the presence of two rotamers in
55:45 ratio (the absorptions of the prevalent rotamer are reported
in bold): δ = 7.85 (2 t, J = 7.8 Hz, 1 H, Py), 7.53–7.28 (m, 4 H,
Ethyl (E)-1,3-Diphenyl-2-propen-1-yl Carbonate: Ethyl chloro-
formate (1.84 g, 17 mmol) was slowly added to a stirred solution
of 1,3-diphenyl-2-propen-1-ol (1.05 g, 5 mmol), pyridine (1.5 g,
Ar), 7.15 (m (3 H, Ar), 5.72 (m, 1 H, CH2CHCH2), 4.36 and 4.27 19 mmol), and 4-(dimethylamino)pyridine (10 mg) in THF (10 mL)
(2 s, 2 H, CH2Ph), 4.35 and 4.28 (2 d, J = 6.6 Hz, 1 H, at 0 °C. The mixture was stirred at 20 °C for 48 h, after which time
1424
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 1416–1426

Enantioselective Allylic Alkylation Catalysed by Cationic Pd Complexes
FULL PAPER
3183; c) G. Chelucci, G. A. Pinna, A. Saba, R. Valenti, Tetrahe-
dron: Asymmetry 2000, 11, 4027.
U. Bremberg, F. Rahm, F. C. Moberg, Tetrahedron: Asymmetry
1998, 9, 3437.
G. Alvaro, G. Martelli, D. Savoia, J. Chem. Soc., Perkin Trans.
1 1998, 775.
K. Fiore, G. Martelli, M. Monari, D. Savoia, Tetrahedron:
Asymmetry 1999, 10, 4803.
H2O was added and the organic phase extracted with Et2O
(3×10 mL). The collected organic layers were washed with 1 n HCl
(10 mL), with sat. NaHCO3 and brine, then dried (Na2SO4) and
concentrated to leave 1b in almost quantitative yield. The com-
[6]
[7]
pound decomposed during GC analysis, but a purity of Ͼ95% was
determined by 1H NMR analysis and therefore the product was
[8]
1
used without further purification. H NMR (200 MHz, CDCl3): δ
= 7.60–7.20 (m, 10 H, Ph), 6.82 (d, J = 15.4 Hz, 1 H, PhCH=CH),
6.42 (d, J = 8.4 Hz, 1 H, CHO), 6.27 (dd, J = 15.4 and 8.4 Hz, 1
H, PhCH=CHCHPh), 4.21 (dq, J = 1.0 and 6.2 Hz, CH2O), 1.31
(t, J = 6.2 Hz, 3 H, CH3) ppm.
[9]
[10]
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The scope and mechanism of this reaction have been investi-
gated previously: S. Cutugno, G. Martelli, L. Negro, D. Savoia,
Eur. J. Org. Chem. 2001, 517.
In principle, a catalytic amount of sodium hydride should be
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Acc. Chem. Res. 1987, 20, 140; b) K. Tanikaga, T. X. Jun, A.
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angles for all the PdII complexes structurally characterised,
crystal data and ORTEP drawings of 25a,b.
Several examples of (N,N)-bound metal complexes have been
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ligands: a) P. J. Walsh, A. Lurain, J. Balsells, Chem. Rev. 2003,
103, 3297; b) S. Kobayashi, R. Matsubara, Y. Nakamura, H.
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[11]
[12]
Palladium-Catalysed Allylic Substitution Reactions. Preparation of
(S)-2: The palladium salt 20 (0.061 g, 0.1 mmol) was added to a
stirred solution of 1b (0.28 g, 1 mmol) in THF (5 mL) under Ar at
room temperature. Then, a solution of sodium dimethyl malonate,
generated from dimethyl malonate (0.198 g, 1.5 mmol) and NaH
(0.036 g, 1.5 mmol) in THF 6 mL), was added dropwise and the
mixture was magnetically stirred overnight. 1 n HCl (5 mL) was
added and the mixture was extracted with Et2O (3×10 mL), the
organic phase was dried (Na2SO4) and the solvents evaporated.
Chromatography of the residue on a SiO2 column eluting with cy-
clohexane/ethyl acetate (15:1) gave the product (S)-2: 0.227 g
(70%). [α]2D5 = –15.4 (c = 0.42, EtOH); the ee (90%) was determined
by HPLC analysis (Daicel ChiralcelTM OD column, n-hexane/
iPrOH, 99:1, flow rate 0.5 mLmin–1; the product eluted at 21.15
[(R)-enantiomer] and 22.22 min [(S)-enantiomer].
[13]
[14]
[15]
Acknowledgments
This work was carried out in the field of the FIRB Project “Proget-
tazione, preparazione e valutazione biologica e farmacologica di
nuove molecole organiche quali potenziali farmaci innovativi”. F.F.
is grateful to the Consorzio Interuniversitario Nazionale Metodol-
ogie e Processi Innovativi di Sintesi for a scholarship. We also thank
the University of Bologna for financial support.
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Eur. J. Org. Chem. 2005, 1416–1426
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1425

F. Ferioli, C. Fiorelli, G. Martelli, M. Monari, D. Savoia, P. Tobaldin
FULL PAPER
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Received: October 09, 2004
1426
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 1416–1426