Enantioselective cycloadditions of 2-alkenoylpyridine-N-oxides catalysed by a bis(oxazoline)/CuII complex: Structure of the reactive intermediate

Article abstract of DOI:10.1002/chem.201002017

Diels-Alder and 1,3-dipolar cycloadditions involving (E)-3-aryl-1-(pyridin- 2-yl-N-oxide)prop-2-en-1-ones as the 2π components are efficiently catalysed by bis(oxazoline)-Cu^II complexes. The cycloadducts are obtained in quantitative yields with

Full text of DOI:10.1002/chem.201002017

DOI: 10.1002/chem.201002017
Enantioselective Cycloadditions of 2-Alkenoylpyridine-N-oxides Catalysed
by a Bis(oxazoline)/CuII Complex: Structure of the Reactive Intermediate
Alessandro Livieri,[a] Massimo Boiocchi,[b] Giovanni Desimoni,[a] and Giuseppe Faita*[a]
Abstract: Diels–Alder and 1,3-dipolar cycloadditions involving (E)-3-aryl-1-(pyri-
din-2-yl-N-oxide)prop-2-en-1-ones as the 2p components are efficiently catalysed
by bis(oxazoline)–CuII complexes. The cycloadducts are obtained in quantitative
yields with up to 98% ee; absolute configurations were determined by X-ray anal-
ysis. The structure of the reactive complex, determined by X-ray analysis, is fully
consistent with the stereochemical outcome of the catalysed process (approach of
the diene or nitrone to the less hindered face of the coordinated pyridine-N-oxide
derivative).
Keywords: asymmetric catalysis
copper · cycloaddition · nitrogen
heterocycles
·
Introduction
In our previous paper, we reported the synthesis of a new
BOX ligand 1; the structure of its metal complex with Cu-
The ability of amine-N-oxides to act as electron-pair donors
in metal-ion complexation[1] has been exploited in metal-
based asymmetric catalytic processes by using pyridine-N-
oxides either as chiral ligands[2] or as coordinating sub-
strates.[3–7] When pyridine-N-oxides are used as reagents, an-
other coordinating centre is required in the 2-position of the
pyridine ring (e.g., a carbonyl moiety) and very high eeꢀs
have been achieved by using either chiral bis(oxazoline)
(BOX)[8]- or pyridine-2,6-bis(oxazoline) (PYBOX)-based
catalysts in several enantioselective reactions. Indeed,
BOX–CuII catalysts have been usefully applied to the enan-
tioselective aldol reactions[3] and hetero-Diels–Alder (HDA)
cycloadditions of pyridine-N-oxide-2-carbaldehyde[4] and in
Diels–Alder (DA)[5] and HDA[6] cycloadditions of 2-alkeno-
yl-pyridine-N-oxide. PYBOX-based chiral catalysts have
found applications in the Friedel–Crafts alkylations of in-
ACHTUNGRTEN(NGNU OTf)2 was resolved by X-ray analysis (2) and, for the first
time, the structure of the reactive complex in the asymmet-
ric reactions of alkenoyloxazolidinone derivatives was deter-
mined (3, Scheme 1), which allowed us to rationalise the ste-
reochemical outcome of the DA reaction.[9] The coordina-
tion sphere around CuII has a square-pyramidal geometry in
complex 2 with the four equatorial positions occupied by
the two BOX nitrogen atoms, the oxygen of the water mole-
cule and one triflate anion; the second triflate was in the
ACHTUNGTRENNUNG
dole[7a] and pyrrole[7b] (CuII and ZnII, respectively, were the
cation of choice).
[a] Dr. A. Livieri, Prof. G. Desimoni, Prof. G. Faita
Department of Organic Chemistry, University of Pavia
V.le Taramelli, 10, 27100 Pavia (Italy)
Fax : (+39)0-382-987-323
E-mail: faita@unipv.it
[b] Dr. M. Boiocchi
Centro Grandi Strumenti, University of Pavia
v. Bassi, 8, 27100 Pavia (Italy)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002017.
Scheme 1. Crystal structures of the complex between BOX 1 and Cu-
AHCTUNRTGEG(NNNU OTf)2 (2) and of the reactive intermediate with acryloyloxazolidone (3).
516
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 516 – 520

FULL PAPER
À
apical position, but with a longer Cu O distance than that
3); only when the catalyst was derived from CuII perchlorate
was a lower reactivity observed, although the stereo- and
enantioselectivity were very similar to those obtained by
using CuII triflate (Table 1, entry 4).
observed for the equatorial one. In the reactive complex 3,
the BOX nitrogen atoms and the oxazolidinone carbonyl
oxygen atoms occupied the four equatorial positions and a
water molecule filled the apical position. The appreciable
enantioselectivities obtained for DA and 1,3-dipolar cyclo-
addition (1,3-DC) reactions are consistent with an approach
of the second reagent from the less hindered double-bond
face of 3. Herein, we report the results obtained by using
complex 2 for enantioselective reactions involving aryli-
dene–pyridine-N-oxide derivatives as the 2p components in
DA and 1,3-DC reactions.
Since both lithium triflate[10] and water[9] have been found
to stabilise pentacoordination around CuII, the effect of
added LiOTf (5 equiv) or water (10 equiv) on the catalytic
efficiency of complex 3 was tested. As reported in Table 1,
entries 5 and 6, neither endo selectivity nor ee were affected
by the presence of these additives.
Catalyst 2 was also found to be efficient in the DA reac-
tions of p-substituted derivatives 4b and c and the levorota-
tory main adducts 6b and c were obtained in up to 97% ee
(Table 1, entries 7 and 8). The crystallisation of 6b from
benzene/n-hexane gave an enantiomerically pure sample
suitable for X-ray analysis. From the crystal structure shown
in Figure 1 the absolute configuration of (À)-6b was deter-
mined to be 1S,2R,3R,4R.
Results and Discussion
(E)-3-Aryl-1-(pyridin-2-yl-N-oxide)prop-2-en-1-ones 4a–c,
that is, the 2p components in the investigated cycloaddition
reactions, were prepared, in accordance with the procedure
reported in the literature, by condensation under basic con-
ditions of 2-acetylpyridine-N-oxide with the appropriate aro-
matic aldehyde.[6] Catalysed DA reactions were run at
À208C by using either the pre-formed complex 2 or the cat-
alyst prepared in situ from 1 and CuII salts, either in the
presence or absence of 3 ꢂ molecular sieves (MS). All reac-
tions of 4a with 5 proceeded with quantitative yields and
high endo selectivities to form endo-6 (Scheme 2 and
Table 1). In all cases the enantioselectivities were excellent
and independent from the use of pre-formed or in situ
formed catalyst or the presence of MS (Table 1, entries 1–
Figure 1. ORTEP diagram of the X-ray structure of (1S,2R,3R,4R)-endo-
6b (ellipsoids for non-H atoms are drawn at the 10% probability level).
The catalytic efficiency of [BOX/CuII] catalysts was then
tested for the 1,3-DC reaction between arylidene derivatives
4a–c and diphenylnitrone 8 (Scheme 3). The reactions were
run at À208C in CH2Cl2 and in the presence of MS, which
were required to avoid decomposition of the nitrone. Quan-
titative yields of the reaction products were obtained from
the reaction of 4a after the lengths of time reported in
Table 2. The cycloaddition reaction is endo-selective and 9a
Scheme 2. DA reaction between arylidene–pyridine-N-oxides 4a–c and
cyclopentadiene 5.
Table 1. DA reaction between 4a–c and 5 in CH2Cl2 at À208C catalysed
by 5 mol% catalyst.
4
Catalyst
t [h][a]
[6]:[7]
ee of 6 [%][b]
1
2
3
4
5
6
7
8
4a
4a
4a
4a
4a
4a
4b
4c
2
20
16
24
60
18
18
18
7
99:1
98:2
99:1
98:2
99:1
99:1
99:1
98:2
97
97
98
97
97
98
96
97
2/MS
1+Cu
1+CuACHTUNGTRENNUNG
ACHTUNGTRENNUNG
2/MS+LiOTf[c]
2+H2O[d]
2/MS
2/MS
[a] All reactions give quantitative yields. [b] Determined by chiral HPLC
(see the Experimental Section); all products are levorotatory. [c] LiOTf
(5 equiv) was added. [d] H2O (10 equiv) was added.
Scheme 3. 1,3-DC reaction between arylidene–pyridine-N-oxides 4a–c
and diphenylnitrone 8.
Chem. Eur. J. 2011, 17, 516 – 520
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
517

G. Faita et al.
Table 2. 1,3-DC reaction between 4a–c and 8 in CH2Cl2 at À208C cata-
lysed by 10 mol% catalyst.
4
Catalyst
t [h][a] [9]:[10] ee of 9 [%][b] ee of 10 [%]
1
2
3
4
5
6
4a 2/MS 48
4a 1+Cu(OTf)2/MS 40
4a 1+CuACHTUNGTRENNUNG(ClO4)2/MS 50
88:12
87:13
84:16
80:20
81:19
85:15
93
94
84
93
94
97
52
G
n.d.[c]
80
4a 2/MS+LiOTf[d]
4b 2/MS
55
24
15
20
62
65
4c 2/MS
[a] All reactions give quantitative yields. [b] Determined by chiral HPLC
(see the Experimental Section); all products are levorotatory. [c] n.d.=
not determined. [d] LiOTf (5 equiv) was added.
was obtained in up to 94% ee, independent from the use of
pre-formed or in situ formed catalyst (Table 2, entries 1 and
2). The use of perchlorate instead of copper triflate in this
reaction slightly lowers the enantioselectivity (Table 2,
entry 3 vs. 2), whereas the addition of LiOTf slightly de-
creases the endo selectivity (Table 2, entry 4 vs. 1).
Scheme 4. Stereochemical outcome of the DA reaction of 4a–c catalysed
by BOX-CuII catalysts.
The opposite stereochemical outcome obtained by using
Catalyst 2 was also found to be efficient in the 1,3-DC re-
action of p-substituted-derivatives 4b and c (94 and 97% ee,
respectively, Table 2, entries 5 and 6). The crystallisation of
9b from ethyl acetate gave an enantiomerically pure sample
suitable for X-ray analysis. From the crystal structure shown
in Figure 2 the absolute configuration of (À)-9b was deter-
mined to be 3S,4R,5R.
11 instead of 12 as ligands in CuACTHUGNTERNNU(G OTf)2-based chiral cata-
lysts, despite the same configuration of the C4 of the oxazo-
line unit, has frequently been observed in enantioselective
reactions.[8b] Two different hypotheses have been proposed
as a rationale for this switching of selectivity. Evans[11] pro-
posed, for both the reactive complexes of CuII with either
BOX 11 or 12, a square-planar structure; in the case of
BOX 12 the 2p partner approaches the coordinated hetero-
diene on the opposite face to the sterically demanding tert-
butyl group, while, for complexes involving 11, the dieno-
phileꢀs approach is syn to the phenyl group of the oxazoline
ring due to stabilisation of the partial positive charge arising
form the asynchronous transition state. Jørgensen[12] pro-
posed that the observed reversal in enantioselectivity de-
pends 1) on the flexibility of the reactive complexes that can
twist from square-planar to tetrahedral geometry and 2) on
the ability of the chiral substituent to rock between pseudo-
axial and pseudo-equatorial positions. The stereochemical
outcome obtained by using 2 as the enantioselective catalyst
of the DA reaction between 4a–c and 5 is analogous to that
reported by using the 12/CuII catalyst; hence, in BOX 1 the
effect determining the stereochemical outcome is the steric
hindrance of the alkyl substituent in the 4-position of the
oxazoline ring, as is the case in tBu-BOX 12.
Figure 2. ORTEP diagram of the X-ray structure of (3S,4R,5R)-endo-9b
(ellipsoids for non-H atoms are drawn at the 10% probability level).
When 1, CuACTHNUGTRENUNG(OTf)2 and 4a were mixed in an equimolar
ratio, crystals of reactive complex 13, suitable for an X-ray
crystal structure determination, were isolated (Figure 3).
The elongated octahedral structure shows the behaviour of
4 as a bidentate reagent, with its carbonyl group and N-
oxide in the equatorial positions, and confirms the cisoid
conformation of the a,b-unsaturated carbonyl fragment. Re-
active complex 13 keeps a nearly untwisted elongated octa-
hedral structure: the four equatorial donor atoms are
The enantioselectivity levels obtained for the DA reac-
tions of 4a–c are comparable to those reported for the same
DA cycloaddition reactions in which CuACTHNURTGNENG(U OTf)2 and either
(4S)-phenyl-BOX (11) or (4S)-tBu-BOX (12) were used by
Pedro and co-workers.[5] BOXs 11 and 12 gave opposite
enantioselectivities and the main enantiomer obtained with
tBu-BOX 12 was the enantiomer achieved by using com-
pound 2, that is, the 1S,2R,3R,4R absolute configuration.
This stereochemical outcome requires approach by cyclo-
pentadiene to the Ca-Re face of the coordinated dienophile
(Scheme 4).
À
strongly bound to the metal centre (Cu O,N distances are
in the range 1.95(1)–1.98(1) ꢂ), whereas the triflate anions
À
are weakly bound to copper in the two axial positions (Cu
OTf=2.45(1) and 2.50(1) ꢂ). A comparison of the struc-
tures of reactive complexes 13 and 3 indicates some intrigu-
518
www.chemeurj.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 516 – 520

Enantioselective Cycloadditions
FULL PAPER
Elmer 241 polarimeter. Separation and purification of the products were
carried out by column chromatography by using Merck silica gel 60 (230–
400 mesh). The enantiomeric excess (ee) of the products was determined
by HPLC on Daicel columns.
Materials: Dichloromethane (hydrocarbon-stabilised Aldrich ACS grade)
was distilled from calcium hydride and used immediately. Other solvents
were dried according to standard procedures. Copper triflate was bought
from Aldrich (ACS reagent). Powdered 3 ꢂ molecular sieves (Aldrich)
were heated under vacuum at 3008C for 5 h and kept in sealed vials in a
dryer. 2-Alkenoyl-pyridine-N-oxides 4a and c were prepared as reported
in the literature.[7]
(E)-2-[3-(4-bromophenyl)prop-2-enoyl]pyridine 1-oxide (4b): The bromo
derivate 4b was prepared according to the same standard procedure as
4a and c, but starting from p-bromo-benzaldehyde. The product was iso-
lated by column chromatography with ethyl acetate (52%). M.p. 162–
1638C; 1H NMR (CDCl3, 300 MHz): d=8.24 (m, 1H), 7.74 (s, 2H), 7.71
(dd, J=2.6, 5.5 Hz, 1H), 7.51 (m, 4H), 7.44–7.36 ppm (m, 2H); 13C NMR
(CDCl3, 75 MHz): d=185.5, 146.6, 142.0, 140.0, 133.1, 131.6, 129.6, 127.4,
126.9, 125.2, 124.6, 124.3 ppm; elemental analysis calcd (%) for
C14H10BrNO2 (304.1): C 55.29, H 3.31, N 4.61; found: C 55.35, H 3.28, N,
4.56.
Figure 3. ORTEP diagram of the X-ray structure of reactive complex 13
(ellipsoids are drawn at the 10% probability level).
ing differences, even if both are formed from the same start-
ing complex 1: 1) complex 3 has a square-pyramidal struc-
À
ture with one water molecule as the apical ligand (Cu
O
General method for DA and 1,3-DC reactions: Anhydrous glassware was
used in the following reactions. BOX 1 (0.010 g, 0.02 mmol), copper tri-
flate (0.007 g, 0.02 mmol) and pyridine-N-oxide derivates 4a–c
(0.4 mmol) were added to a test tube. If the pre-formed complex was the
water =2.28(1) ꢂ), with CuII placed 0.10(1) ꢂ above the
plane of the equatorial donor atoms and the metal centre
displaced towards the apical water molecule, whereas 13 has
an elongated octahedral structure (i.e., an elongated square-
bipyramidal geometry) with two triflate anions occupying
the axial positions and CuII lying at only 0.06(1) ꢂ from the
plane of the equatorial donor atoms; 2) the different geome-
try of the N-oxygen atom in 4a–c with respect to that of the
oxazolidinone carbonyl oxygen (sp3 vs. sp2) demonstrates a
twisting of the coordinated substrate clearly showing the
favoured cyclopentadiene (or nitrone) approach to the less
shielded Ca-Re face to give the observed cycloadducts.
catalyst,
2 (0.020 g, 0.02 mmol) and pyridine-N-oxide derivates 4a–c
(0.4 mmol) were added to the test tube. The reactants were dissolved in
freshly dried dichloromethane (0.5 mL) and magnetically stirred for
10 min at room temperature. Then, 3 ꢂ molecular sieves (40 mg) were
added to the reaction mixture, which was then cooled to À208C. After
20 min, cyclopentadiene
5 (100 mL) or diphenylnitrone 8 (0.094 g,
0.48 mmol) was added to the tube. The reaction was stopped after com-
pletion, as monitored by TLC. The reaction mixture was quenched in
water and extracted with dichloromethane (3ꢃ10 mL) and the organic
phase was dried over sodium sulfate. Products were isolated by column
chromatography (ethyl acetate/cyclohexane=1:1).
DA reaction of 4a and c: Separation and characterisation of DA adducts
(6a, 7a, 6c and 7c) were performed as reported in the literature;[5] NMR
spectra are in accordance with those reported in reference [5].
Conclusion
DA reaction of 4b: (1S,2R,3R,4R)-2-[3-(4-Bromophenyl)bicyclo
ACHTUNGTRENNUNG[2.2.1]-
AHCTUNGERTGhNNUN ept-5-enecarbonyl]pyridine-1-oxide (6b) was obtained after column
The complex derived from BOX 1 and CuACTHNUTRGENUG(N OTf)2 has been
chromatography as a white solid, recrystallised from benzene (80%,
99% ee). M.p. 96–978C; [a]2D5 =À198.4 (c=0.010 gmLÀ1 in CHCl3);
1H NMR (CDCl3, 300 MHz): d=8.19 (dd, J=1.1, 6.3 Hz, 1H), 7.41 (m,
3H), 7.35 (m, 2H), 7.24 (d, J=8.3 Hz, 2H), 6.46 (dd, J=3.2, 5.5 Hz, 1H),
5.87 (dd, J=2.6, 5.5 Hz, 1H), 4.45 (dd, J=3.2, 4.9 Hz, 1H), 3.36 (s, 1H),
3.31 (d, J=4.3 Hz, 1H), 3.07 (s, 1H), 1.83 (d, J=8.6 Hz, 1H), 1.56 ppm
(dd, J=1.6, 8.6 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=197.8, 146.8,
142.5, 139.8, 139.3, 132.6, 130.9, 128.9, 127.0, 125.7, 125.2, 119.2, 57.8,
48.4, 47.1, 45.9, 45.3 ppm; elemental analysis calcd (%) for C19H16BrNO2
(370.2): C 61.64, H 4.36, N 3.78; found: C 61.58, H 4.38, N 3.72; chiral
HPLC analysis on Chiralpak OJ, 20% isopropanol/80% hexane,
1.0 mLminÀ1; tR endo-6b: 18.0 (major) and 21.9 min (minor).
found to be a useful enantioselective catalyst for cycloaddi-
tion reactions involving pyridine-N-oxide derivatives 4a–c
as either the dienophile or the dipolarophile. The DA cyclo-
addition reactions are highly endo-selective and the cycload-
ducts are obtained with eeꢀs ranging from 96–98%. The 1,3-
DC reactions exhibit good control of the endo selectivity
with the eeꢀs of the main adducts 9a–c in the range 94–97%.
The structure of the intermediate reactive complex was
demonstrated to have an elongated octahedral geometry by
X-ray analysis. The absolute configurations of cycloadducts
6b and 9b have been determined by X-ray analysis and are
consistent with a cyclopentadiene (or nitrone) approach
from the less hindered Ca-Re face of the coordinated pyri-
dine-N-oxides.
1,3-DC reaction of 4a: 2-[(3S,4R,5R)-2,3,5-Triphenylisoxazolidine-4-car-
bonyl]pyridine-1-oxide (9a) was obtained as a colourless oil after column
chromatography. [a]D25 =À32.9 (c=0.014 gmLÀ1 in CHCl3); 1H NMR
(CDCl3, 300 MHz): d=7.89 (d, J=6.0 Hz, 1H), 7.60 (d, J=7.2 Hz, 2H),
7.37 (m, 5H), 7.28 (m, 5H), 7.15 (m, 6H), 5.47 (d, J=7.6 Hz, 1H), 5.36
(d, J=5.6 Hz, 1H), 5.16 ppm (dd, J=7.6, 5.6 Hz, 1H); 13C NMR (CDCl3,
75 MHz): d=195.4, 150.6, 140.3, 139.2, 136.2, 128.8, 128.5, 128.2, 128.1,
128.0, 127.8, 127.2, 126.7, 126.3, 125.6, 124.7, 121.5, 114.1, 82.8, 72.9,
69.5 ppm; elemental analysis calcd (%) for C27H22N2O3 (422.5): C 76.76,
H 5.25, N 6.63; found: C 76.73, H 5.18, N, 6.67; chiral HPLC analysis on
Chiralpak AD, 10% isopropanol/90% hexane, 1.0 mLminÀ1; tR endo-9a:
43.7 (major) and 54.2 min (minor); tR exo-10a=49.5 (major) and
59.0 min (minor).
Experimental Section
General: Melting points were determined by the capillary method and
are uncorrected. 1H and 13C NMR spectra were recorded at 300 and
75 MHz, respectively. IR spectra were registered on a Perkin–Elmer
RX I spectrophotometer. Optical rotations were measured on a Perkin–
NMR data for exo-10a: The most relevant signals detected from a mix-
ture of 9a and 10a: 1H NMR (CDCl3, 300 MHz): d=8.04 (d, J=6.5 Hz,
Chem. Eur. J. 2011, 17, 516 – 520
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
519

G. Faita et al.
1H), 7.61 (d, J=6.6 Hz, 2H), 7.50 (dd, J=7.6, 1.2 Hz, 2H), 7.36 (m, 4H),
7.28 (s, 2H), 7.19 (m, 4H), 7.05 (m, 4H), 5.99 (d, J=9.1 Hz, 1H), 5.49 (d,
J=10.2 Hz, 1H), 5.36 ppm (dd, J=10.2, 9.1 Hz, 1H).
(No. 19), a=8.179(3), b=22.742(3), c=12.396(3) ꢂ, V=2305.7(11) ꢂ3,
Z=4, 1calcd =1.444 gcmÀ3 (MoKa)=1.815 mmÀ1
, mACHUTNRTEGNNUNG , 2qmax =608, min/max
transmission 0.466/0.579, 5044 reflections collected, 4656 independent re-
flections (Rint =0.013), 2477 strong reflections [Fo >2s(Fo)], 298 refined
parameters, R1/wR2=0.0455/0.0698 (strong reflections) and 0.1292/
0.0869 (all reflections), goodness of fit=1.03; max/min residuals 0.37/
1,3-DC reaction of 4b: 2-[(3S,4R,5R)-5-(4-Bromophenyl)-2,3-diphenyl-
ACHTUNGTRENNUNGisoxACHTUNGTRENNUNGazolidine-4-carbonyl]pyridine-1-oxide (9b), recrystallised from ethyl
acetate (75%, 99% ee). M.p. 170–1728C; [a]2D5 =À72.4 (c=0.010 gmLÀ1
in CHCl3); 1H NMR (CDCl3, 300 MHz): d=7.95 (dd, J=6.3, 0.4 Hz,
1H), 7.53 (dd, J=7.7, 0.9 Hz, 2H), 7.42 (d, J=8.5 Hz, 2H), 7.25 (m,
10H), 7.03 (m, 3H), 5.54 (d, J=6.7 Hz, 1H), 5.26 (d, J=5.3 Hz, 1H),
5.08 ppm (dd, J=6.7, 5.3 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=195.4,
150.16, 145.6, 139.8, 139.3, 136.2, 131.0, 128.5, 128.3, 128.2, 127.5, 127.3,
126.3, 125.9, 124.9, 121.9, 121.8, 114.4, 81.5, 73.0, 69.4 ppm; elemental
analysis calcd (%) for C27H21BrN2O3 (501.4): C 64.68, H 4.22, N 5.59;
found: C 64.72, H 4.17, N 5.56; chiral HPLC analysis on Chiralpak OD,
4% isopropanol/96% hexane, 1.0 mLminÀ1; tR exo-10b: 45.5 (minor) and
60.5 min (major); tR endo-9b: 72.6 (minor) and 99.1 min (major).
À0.48 eꢂÀ3
,
Flackꢀs parameter À0.02(1). Crystal data for 13:
C57H77CuF6N3O12S2Si2, Mr =1294.09, monoclinic P21 (No. 4), a=
14.592(3), b=16.182(5), c=15.220(4) ꢂ, b=108.23(2)8 V=3413.4(16) ꢂ3,
Z=2, 1calcd =1.259 gcmÀ3 (MoKa)=0.489 mmÀ1
, mACHUTNRTEGNNUNG , 2qmax =608, min/max
transmission 0.778/0.843, 12011 reflections collected, 11448 independent
reflections (Rint =0.032), 8021 strong reflections [Fo >2s(Fo)], 748 refined
parameters, R1/wR2=0.0731/0.1687 (strong reflections) and 0.1026/
0.1981 (all reflections), goodness of fit=1.15; max/min residuals 0.52/
À0.30 eꢂÀ3, Flackꢀs parameter À0.02(2). CCDC-781076 (6b), 781077
(9b) and 781078 (13) contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
NMR data for exo-adduct-10b: The most relevant signals detected from
a mixture of 9b and 10b were 1H NMR (CDCl3, 300 MHz): d=8.07 (d,
J=7 Hz, 1H), 5.96 (d, J=7 Hz, 1H), 5.45 (d, J=7 Hz, 1H), 5.31 ppm (d,
J=7 Hz, 1H).
1,3-DC reaction of 4c: 2-[(3S,4R,5R)-5-(4-Nitrophenyl)-2,3-diphenylisox-
azolidine-4-carbonyl]pyridine-1-oxide (9c) was obtained as a colourless
oil after column chromatography (72%). [a]2D5 =À105.0 (c=0.010 gmLÀ1
in CHCl3); 1H NMR (CDCl3, 300 MHz): d=8.17 (m, 2H), 8.01 (dd, J=
6.4, 0.4 Hz, 1H), 7.67 (d, J=8.5 Hz, 2H), 7.41 (m, 2H), 7.26 (m, 8H),
7.03 (m, 3H), 5.85 (d, J=5.1 Hz, 1H), 5.13 (d, J=4.8 Hz, 1H), 5.03 ppm
(t, J=5.0 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=195.3, 149.4, 147.0,
146.2, 145.4, 139.3, 139.0, 128.5, 128.3, 127.8, 127.5, 127.1, 126.3, 125.2,
123.1, 122.4, 115.2, 79.9, 73.0, 69.5 ppm; elemental analysis calcd (%) for
C27H21N3O5 (467.5): C 69.37, H 4.53, N 8.99; found: C, 69.31, H 4.56, N,
9.03; chiral HPLC analysis on Chiralpak OD, 30% isopropanol/70%
hexane, 1.0 mLminÀ1; exo-10c: tR =17.7 (minor) and 24.4 min (major);
endo-9c: tR =22.8 (minor) and 59.0 min (major).
Acknowledgements
This work was supported by the Ministero dell’Universitꢄ e della Ricerca
(MiUR) (PRIN 2008) and by the University of Pavia.
[1] A. Albini, Synthesis 1993, 263–267.
[2] a) G. Chelucci, G. Murineddu, G. A. Pinna, Tetrahedron: Asymmetry
2004, 15, 1373–1389; b) J. Chen, N. Takenaka, Chem. Eur. J. 2009,
15, 7268–7276.
[3] A. Landa, A. Minkkilꢅ, G. Blay, K. A. Jørgensen, Chem. Eur. J.
2006, 12, 3472–3483.
[4] A. Landa, B. Richter, R. L. Johansen, A. Minkkilꢅ, K. A. Jørgensen,
J. Org. Chem. 2007, 72, 240–245.
[5] S. Barroso, G. Blay, J. R. Pedro, Org. Lett. 2007, 9, 1983–1986.
[6] S. Barroso, G. Blay, M. C. MuÇoz, J. R. Pedro, Adv. Synth. Catal.
2009, 351, 107–111.
1
NMR data for exo-adduct-10c: H NMR (CDCl3, 300 MHz): d=8.24 (dd,
J=8.8, 1.9 Hz, 2H), 8.04 (dd, J=6.5, 0.7 Hz, 1H), 7.79 (dd, J=7.1,
1.5 Hz, 2H), 7.43 (m, 2H), 7.23 (m, 3H), 7.14 (m, 3H), 7.02 (m, 5H),
6.12 (d, J=8.9 Hz, 1H), 5.47 (d, J=10.2 Hz, 1H), 5.33 ppm (dd, J=10.1,
8.8 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d=192.0, 148.6, 147.3, 145.3,
139.6, 137.6, 128.3, 128.1, 127.8, 127.6, 127.4, 126.8, 124.6, 123.2, 122.3,
116.0, 78.5, 70.7, 67.8 ppm.
[7] a) P. K. Singh, V. N. Singh, Org. Lett. 2008, 10, 4121–4124; b) P. K.
Singh, V. N. Singh, Org. Lett. 2010, 12, 80–83.
Complex of 2 and 4a (13): (E)-2-(3-Phenylprop-2-enoyl)pyridine-1-oxide
(4a; 9.8 mg, 0.043 mmol) and complex 2 (33.0 mg, 0.033 mmol) were dis-
solved in a few drops of dichloromethane. The mixture was heated to
boiling point for 2 min and then cooled to room temperature. A dark
brown solid precipitated. The solid was recrystallised from toluene to
give brown crystals (15.1 mg, 36%). M.p. 198–1998C; [a]2D5 =À5.96 (c=
0.008 gmLÀ1 in CHCl3), UV/Vis (CH2Cl2) lmax =394 nm.
[8] For general reviews on bis(oxazoline)s as chiral ligands in asymmet-
ric catalysis, see: a) G. Desimoni, G. Faita, P. Quadrelli, Chem. Rev.
2003, 103, 3119–3154; b) G. Desimoni, G. Faita, K. A. Jørgensen,
Chem. Rev. 2006, 106, 3561–3651; c) G. C. Hargaden, P. J. Guiry,
Chem. Rev. 2009, 109, 2505–2550; d) R. Rasappan, D. Laventine, O.
Reiser, Coord. Chem. Rev. 2008, 252, 702–714.
[9] G. Desimoni, G. Faita, M. Toscanini, M. Boiocchi, Chem. Eur. J.
2009, 15, 9674–9677.
[10] A. Schꢅtz, R. Rasappan, M. Hager, A. Gissibl, O. Reiser, Chem.
Eur. J. 2008, 14, 7259–7265.
[11] D. A. Evans, J. S. Johnson, E. J. Olhava, J. Am. Chem. Soc. 2000,
122, 1635–1649.
[12] J. Thorhauge, M. Roberson, R. G. Hazell, K. A. Jørgensen, Chem.
Eur. J. 2002, 8, 1888–1898.
[13] A. Altomare, M. C. Burla, M. Camalli, G. L. Cascarano, C. Giaco-
vazzo, A. Guagliardi, A. G. G. Moliterni, G. Polidori, R. Spagna, J.
Appl. Crystallogr. 1999, 32, 115–119.
X-ray diffraction studies of 6b, 9b and 13: All crystal structures were
solved by direct methods (SIR97)[13] and refined with full-matrix least-
square procedures on F2 (SHELXL-97)[14] by using all reflections collect-
ed on an Enraf–Nonius CAD4 diffractometer (l=0.71073 ꢂ, T=293 K).
Lorentz, polarisation and absorption effect (psi-scan method)[15] correc-
tions were applied. H atoms were placed at the calculated positions. The
absolute configuration was established by anomalous dispersion effects in
the diffraction data. Crystal data for 6b: C19H16BrNO2, Mr =370.23, mo-
A
ACHTUNGTRENNUNG
,
mACHTUNGTRENNUNG
2.485 mmÀ1, 2qmax =608, min/max transmission 0.261/0.418, 3720 reflec-
tions collected, 3275 independent reflections (Rint =0.012), 1942 strong re-
flections [Fo >2s(Fo)], 208 refined parameters, R1/wR2=0.0391/0.0765
(strong reflections) and 0.0907/0.0909 (all reflections), goodness of fit=
1.02; max/min residuals 0.39/À0.43 eꢂÀ3, Flackꢀs parameter À0.01(1).
Crystal data for 9b: C27H21BrN2O3, Mr =501.36, orthorhombic P212121
[14] Sheldrick, G. M. SHELXL-97, Program for Crystal Structure Re-
finement, University of Gçttingen, Gçttingen, Germany, 1997.
[15] A. C. T. North, D. C. Phillips, F. S. Mathews, Acta Crystallogr. A
1968, A24, 351–359.
Received: July 16, 2010
Published online: November 4, 2010
520
www.chemeurj.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 516 – 520