Asymmetric Diels-Alder cycloaddition of a di-P-stereogenic dienophile with cyclopentadiene

Article abstract of DOI:10.1016/j.tetasy.2009.03.022

The Diels-Alder cycloaddition of the di-P-stereogenic dienophile (S_P,S_P)-1 leads to novel di-P-stereogenic norbornene derivatives and proceeds with moderate diastereoselectivity in the absence of a catalyst. In the presence of TiCl

Full text of DOI:10.1016/j.tetasy.2009.03.022

Tetrahedron: Asymmetry 20 (2009) 1081–1085
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Asymmetric Diels–Alder cycloaddition of a di-P-stereogenic
dienophile with cyclopentadiene
Nikolai Vinokurov a, K. Michal Pietrusiewicz b, Holger Butenschön a,
*
a Institut für Organische Chemie, Leibniz Universität Hannover, Schneiderberg 1B, D-30167 Hannover, Germany
b Department of Organic Chemistry, Maria Curie-Sklodowska-University Lublin, ul. Gliniana 33, Lublin, PL-20-614, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
The Diels–Alder cycloaddition of the di-P-stereogenic dienophile (SP,SP)-1 leads to novel di-P-stereogenic
norbornene derivatives and proceeds with moderate diastereoselectivity in the absence of a catalyst. In
the presence of TiCl4, however, the diastereoselectivity was raised to 9:1. The major diastereoisomer has
been characterized crystallographically. The separation of the diastereomeric cycloadducts was possible
by fractional crystallization in the presence of (ꢀ)-O,O-dibenzoyltartaric acid monohydrate.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 11 February 2009
Accepted 10 March 2009
Available online 22 April 2009
Dedicated to Professor Ihsan Erden on the
occasion of his 60th birthday
PPh2
1. Introduction
Me
Me
O
Me
Me
PPh2
PPh2
Asymmetric hydrogenation1 plays a vital role in fundamental
research2–4 as well as in pharmaceutical and chemical industries
in providing enantiomerically pure compounds.5–8 Chiral diphos-
phines,9 which constitute the main family of ligands for catalysis,
have chirality normally resident in the carbon backbone10 or, less
commonly, at the phosphorus atoms.11–16 Although optically ac-
tive diphosphines such as CHIRAPHOS, DIOP, and NORPHOS are
very efficient ligands for asymmetric catalysis, ligand scaffolds, in
which stereogenic phosphorus atoms are bound to a rigid 1,2-eth-
ane backbone remain rare17,18 (Scheme 1).
Ph2P
PPh2
O
PPh2
(R,R) -DIOP
(R,R)-NORPHOS
(S,S)-CHIRAPHOS
Scheme 1. Common optically active diphosphines.
we report on our results in using (SP,SP)-1 as a dienophile in
Diels–Alder cycloadditions.
2. Results and discussion
Organophosphorus compounds bearing a vinyl group are a
promising class of simple alkenes due to their reactivity in many
types of cycloadditions and other important transformations. For
example, NORPHOS was synthesized by a Diels–Alder cycloaddi-
tion of trans-1,2-bis(diphenylphosphinoyl)ethene with cyclopenta-
diene.19,20 Similarly, the 1,3-dipolar cycloaddition reactions of
nitrones with enantiomerically pure P-stereogenic vinylphosphine
oxides have been well established.21–24 Recently, we have demon-
strated that the homo-metathesis of (SP)-methylphenylvinylphos-
phine oxide in the presence of modern olefin metathesis
precatalysts allows the efficient synthesis of enantiopure P-stereo-
genic diphosphine dioxide (SP,SP)-1.25–27 In addition, we have
developed an approach to novel C,P-stereogenic diphosphines by
the asymmetric 1,3-dipolar cycloaddition of (SP,SP)-1 to C,N-diphe-
nylnitrone followed by stereospecific reduction of the rigid diphos-
phine dioxides with Ti(OiPr)4/polymethylhydrosiloxane.28 Herein
We decided to apply the Diels–Alder cycloaddition to access the
rigid carbocyclic skeleton of a precursor for the novel P-stereogenic
ligand system. Thus, the enantiomerically pure dienophile (SP,SP)-1
was subjected to a Diels–Alder reaction with cyclopentadiene. The
cycloaddition proceeded smoothly at 25 °C in CH2Cl2 to give two
diastereomeric products (SP,SP,2R,3R)-2 and (SP,SP,2S,3S)-3 in a ra-
tio of 1.3:1 (31P NMR, 1H NMR) in 92% (Scheme 2).
Unfortunately we did not succeed in separation of the diaste-
reomers by column chromatography. To separate (SP,SP,2R,3R)-2
and (SP,SP,2S,3S)-3 a method developed by Brunner for separation
of enantiomers of NORPHOS was applied.29,30 By means of
(ꢀ)-O,O-dibenzoyltartaric acid monohydrate [(ꢀ)-DBTA] in boiling
methanol, the diastereomeric cycloadducts were separated afford-
ing (SP,SP,2R,3R)-2 in 96% de and (SP,SP,2S,3S)-3 in 90% de after
hydrolysis with 2 M NaOH. This separation is based on the differ-
ence in solubility of the complexed diastereomeric cycloadducts
and relies on the formation of hydrogen bridges between the car-
boxyl group of (ꢀ)-DBTA and the P@O groups20,19 (Scheme 3).
It was not possible to assign the configuration to (SP,SP,2R,3R)-2
and (SP,SP,2S,3S)-3 by 1H NMR. Fortunately, the major diastereoiso-
* Corresponding author. Tel.: +49 511 762 4661; fax: +49 511 762 4616.
E-mail address: holger.butenschoen@mbox.oci.uni-hannover.de (H. Butenschön).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.03.022

1082
N. Vinokurov et al. / Tetrahedron: Asymmetry 20 (2009) 1081–1085
Ph
O
Me
Ph
O
P
Me
P
O
P
Ph
CH2Cl2, 25 °C, 21 h
92 %
Ph
+
P
Me
Me
P
P
O
Ph
Me
Me
O
O
Ph
1
3
(SP,SP,2S,3S)-
2
(SP,SP)-
(SP,SP,2R,3R)-
1.3 : 1
Scheme 2. Asymmetric Diels–Alder reaction of (SP,SP)-1 with cyclopentadiene.
Me
Ph
Ph
Me
Ph
Ph
O
O
O
O
P
Me
P
P
P
Me
1. (–)-DBTA, MeOH, 5 h, reflux
+
+
2. fract. crystallization
3. 2 M NaOH
P
P
P
P
Ph
Me
Me
Me
O
O
Ph
O
O
Ph
Me
Ph
(SP,SP,2R,3R)-2
31 %, 96 % de
(SP,SP,2S,3S)-3
41 %, 90 % de
2
3
(SP,SP,2S,3S)-
(SP,SP,2R,3R)-
1.3 : 1
Scheme 3. Separation of diastereoisomeric cycloadducts by means of (ꢀ)-DBTA.
mer (SP,SP,2R,3R)-2 crystallized from the solvent mixture (CHCl3/
MeOH 9:1) to give crystals suitable for an X-ray crystal structure
analysis (Fig. 1). The analysis of the structure confirms that the
(SP)-methyl(phenyl)phosphinoyl groups are in exo and endo posi-
tions, trans to one another and that the absolute configurations
at the C2, C3 carbon atoms in 2 are (R). The molecule adopts a con-
formation with the smallest substituents at the phosphorus cen-
ters, that is, phosphoryl oxygen atoms, pointing toward the
sterically demanding norbornene scaffold. This results in the place-
ment of the P@O dipoles away from one another as well as in the
placement of the most bulky phenyl groups in the most distant
positions. The phosphorus tetrahedron is deformed in the usual
way showing increased O–P–C angles and decreased C–P–C angles
with the corresponding values ranging from 114.1(5) to 109.6(4)°
(Scheme 4).
Ph
O
P
Me
O
P
Ph
Ph
0.5 equiv. TiCl 4
P
CH2Cl2, 25 °C, 17 h
Me
Me
P
O
Me
87 %, 80 % de
O
Ph
(SP,SP)-1
(SP,SP,2R,3R)-2
Scheme 4. TiCl4-assisted asymmetric Diels–Alder reaction.
In addition, (SP,SP,2R,3R)-2 (96% de) was characterized by 1H,
13C, and 31P NMR spectroscopies. In the 1H NMR spectrum the sig-
nals assigned to the methyl groups appeared as two doublets, with
2JPH = 12.7 Hz. The olefinic protons gave rise to two multiplets at
d = 5.59 and 6.02 ppm. The 13C NMR spectrum showed the ex-
pected P,C spin couplings: the methyl groups gave doublets at
1
d = 9.2 and 13.2 ppm with JPC = 64.2 and 65.3 Hz, respectively.
The carbon atoms bearing the phosphinoyl substituents gave dou-
blets at d = 41.9 and 42.1 ppm with coupling constants of
1JPC = 73.9 and 65.2 Hz, respectively. The bridgehead carbon atom
next to the endo-phosphinoyl group gave doublet of doublets with
2JPC = 3JPC = 1.2 Hz whereas the one next to the exo substituent gave
2
a doublet with JPC = 4.4 Hz. Since both stereogenic phosphorus
atoms are chemically nonequivalent, there are two doublets
appearing in the 31P NMR spectrum at d = +38.6 and +39.8 ppm,
respectively, with a coupling constant JPP = 8.9 Hz.
Figure 1. Structure of (SP,SP,2R,3R)-2 in the crystal.31,32 Selected bond lengths [pm],
angles [°], and dihedral angles [°]: P1–O1 153.9(6), P1–C9 180.0(10), P1–C8
180.5(7), P1–C2 181.6(9), P2–O2 149.5(7), P2–C15 181.6(8), P2–C16 182.0(9), P2–
C3 182.9(9), C1–C6 139.0(2), C1–C7 157.8(13), C1–C2 162.7(13), C2–C3 154.2(9),
C3–C4 161.1(12), C4–C5 145.5(13), C4–C7 158.8(12), C5–C6 126.4(14), C9–C14
137.1(11), C9–C10 142.9(11), O1–P1–C9 109.6(4), O1–P1–C8 113.1(4), C9–P1–C8
105.7(5), O1–P1–C2 114.3(4), C9–P1–C2 105.9(4), C8–P1–C2 107.7(4), O2–P2–C15
113.7(4), O2–P2–C16 110.6(5), C15–P2–C16 104.7(5), O2–P2–C3 114.1(5), C15–P2–
C3 106.5(4), C6–P2–C3 106.5(4), P1–C2–C3–P2 116.9(1), C15–P2–C3–C2 72.9(1),
C8–P1–C2–C3 71.4(1).
3
A classical method to enhance the diastereoselectivity of Diels–
Alder cycloadditions is based on Lewis acid catalysis.33–36 Also, it
has been shown that the endo/exo ratio of cycloadducts can be
influenced by the addition of various Lewis acids.37
To increase the diastereoselectivity of the Diels–Alder cycload-
dition studied, we tested several Lewis acids such as AlCl3,
Sc(OTf)3, SnCl4, and TiCl4. After some screening it was found that

N. Vinokurov et al. / Tetrahedron: Asymmetry 20 (2009) 1081–1085
1083
Table 1
Figure 2 (left). The analysis clearly shows that the major (2R,3R)-
configured product results from a transition state in which cyclo-
pentadiene faces steric interactions with the phenyl substituents
rather than the methyl groups of the incoming dienophile. In con-
trast, the respective cycloaddition of di-s-trans-(SP,SP)-1 leads to
the major (2R,3R) diastereomer via a transition state involving ste-
ric interactions of cyclopentadiene with the methyl substituents of
the dienophile. As the steric bulk of the phenyl group is considered
to be more dominant than that of the methyl group we conclude
that the dienophile reacts preferentially in its di-s-trans
conformation.
The asymmetric Diels–Alder cycloaddition of (SP,SP)-1 with cyclopentadiene
TiCl4 (equiv)
Solvent/T (°C)
t (h)
(SP,SP,2R,3R)-2:(SP,SP,2S,3S)-3a
Yield (%)
—
—
0.5
1.0
1.5
2.0
Toluene/110
CH2Cl2/20
CH2Cl2/20
CH2Cl2/20
CH2Cl2/20
CH2Cl2/20
18
21
17
19
24
48
1.3:1
1.3:1
9:1
7:1
5:1
95
90
87
85
82
70
3:1
a
The diastereomeric ratio was determined by 31P NMR.
This conclusion is further corroborated by the observed increase
in selectivity of the cycloadditions carried out in the presence of
TiCl4. In these cycloadditions, the preferred di-s-trans conforma-
tion, in which the phosphoryl oxygen atoms are pointed outside
the dienophile core should be favored over the di-s-cis conforma-
tion to an even larger extent because of the added steric bulk of
the complexed Lewis acid.
TiCl4 can be successfully used to improve the diastereomeric ratio
of the cycloadducts (SP,SP,2R,3R)-2 and (SP,SP,2S,3S)-3 (Table 1). The
best results were obtained by addition of only 0.5 equiv of TiCl4,
which resulted in a significant increase of the ratio of diastereoiso-
mers to 9:1 whereas the addition of larger amounts of Lewis acid
resulted in lower diastereoselectivities.
The formation of the two diastereomeric adducts in unequal
amounts indicates asymmetric induction by the chiral dienophile
(SP,SP)-1. Stereochemical studies concerning asymmetric cycload-
dition reactions involving vinylphosphine oxides and related
dienophiles revealed that under thermal reaction conditions the
reactive conformations of the dienophiles reflect their ground state
conformations, which are s-cis for the majority of the systems
studied.21,38,23,39 However, recently (SP)-methylphenylvinylphos-
phine oxide was used for the thermal Diels–Alder reaction with
cyclopentadiene, and the structure of the major endo adduct was
analyzed by single-crystal X-ray diffraction showing the (2S)-con-
figuration at the carbon atom bearing the phosphine oxide substi-
tuent. This led to the conclusion that the P-stereogenic vinyl
phosphine oxide adopted an s-trans conformation during the
Diels–Alder reaction,40 thus contrasting with its ground state con-
formation.41 As (SP,SP)-1 differs from the vinylphosphine oxides
studied so far in the presence of two polar phosphine oxide units
instead of only one, we recently carried out an X-ray crystallo-
graphic analysis of the structure of (SP,SP)-1 in the solid state,
which clearly established the di-s-cis conformation of the
dienophile.42
3. Conclusion
A new bicyclic enantiopure P-stereogenic diphosphine dioxide
is now accessible by an asymmetric Diels–Alder reaction of cyclo-
pentadiene with a homochiral P-stereogenic dienophile. It has
been shown, that a high diastereoselectivity (9:1) can be conve-
niently achieved by using 0.5 equiv of TiCl4 as a Lewis acid catalyst.
The absolute configuration of the major diastereomer has been
established crystallographically. The diastereomeric cycloadducts
could be separated with the help of (ꢀ)-O,O-dibenzoyltartaric acid
monohydrate by fractional crystallization providing high de of
both cycloadducts.
4. Experimental
4.1. General
All glassware was flame-dried at reduced pressure and filled
with N2. Dichloromethane was distilled from calcium hydride. 1H
NMR, 13C NMR, and 31P NMR spectra were measured at 25 °C with
Bruker AM 400 (1H: 400.1, 13C: 100.1, 31P NMR: 162 MHz), 500 (1H:
500, 13C: 125 MHz) or WP 200 SY (1H: 200.1, 13C: 50.3 MHz) spec-
trometers. The chemical shifts refer to dTMS = 0 ppm or to residual
For the stereochemical analysis of the studied cycloaddition
both di-s-cis and di-s-trans conformations of (SP,SP)-1 as the reac-
tive conformations were considered. If the cycloaddition took place
with di-s-cis-(SP,SP)-1 one would expect a situation as shown in
Me
Me
Ph
O
Me
P
H
P
O
P
H
P
Ph
Ph
P
P
H
H
O
Me
O
Ph
(SP,SP,R,R)-2
major
Me
Me
O
Ph
Me
Ph
P
H
P
O
P
H
P
Ph
H
P
P
H
O
Me
O
Ph
(SP,SP,S,S)-3
di-s-cis
minor
di-s-trans
Figure 2. Stereochemistry of the Diels–Alder cycloaddition of cyclopentadiene with di-s-cis-(SP,SP)-1 (left) and with di-s-trans-(SP,SP)-1 (right). P Substituents in the
cycloadducts are omitted for clarity.

1084
N. Vinokurov et al. / Tetrahedron: Asymmetry 20 (2009) 1081–1085
solvent signals as internal standard. For 31P NMR a solution of
H3PO4 30% in water is used as an external reference. The multiplic-
ity of the peaks is abbreviated as s = singlet, d = doublet, t = triplet,
q = quartet, m = multiplet, br = broad. Infrared spectra (IR) were re-
corded on a Perkin–Elmer FT-IR 580 and 1710 spectrometers. Sig-
nal intensities are abbreviated s (strong), m (medium) or w (weak).
Mass spectra (MS) were measured on a Micromass LCT with Lock-
Spray-unit (ESI). The injection was made in Loop-Modes in a HPLC-
Alliance 2695 (Waters). All values are given in atomic units of mass
per elemental charge (m/z). The intensity is given as a percentage
of the base peak. High resolution mass spectra (HRMS) were re-
corded with the peak-matching method in Micromass LCT with
Lock-Spray-unit (ESI). All values are given in atomic units of mass
per elemental charge (m/z). Optical rotations were determined
with a Perkin–Elmer PE-241 instrument at 20 °C with the light fre-
quency of 589 nm (D-line of a sodium vapor lamp) in a cuvette
(length d = 1 dm or d = 0.1 dm; concentration (c) is given in g/
100 mL). Melting points were determined with the Electrothermal
IA 9200. Microanalyses were conducted with a Elementar Vario EL
instrument with acetamide as standard.
The reaction mixture was stirred at ꢀ78 °C for 10 min, and freshly
distilled cyclopentadiene (10 equiv, 108.3 mg, 1.6 mmol) was
added as a ꢀ50 to ꢀ60 °C cold solution in dichloromethane
(5 mL) over 15 min. After addition was completed the reaction
mixture was allowed to warm to 20 °C and was stirred for 17 h
under TLC control (benzene/EtOH 4:1). The reaction was
quenched by addition of water (5 mL). The organic layer was sep-
arated, and the aqueous layer was extracted with CH2Cl2
(3 ꢁ 30 mL). The combined organic extracts were washed with
brine (30 mL) and dried with anhydrous MgSO4, and the solvents
were removed under reduced pressure. The crude product was
purified by flash chromatography (SiO2, 25 ꢁ 2 cm, CHCl3/MeOH
9:1) to afford (SP,SP,2R,3R)-2 (major product) and (SP,SP,2S,3S)-3
(minor product) as a white powder (55.6 mg, 0.15 mmol, 91%,
80% de). ½a 2D0
ꢂ
¼ ꢀ119 (c 0.5, CHCl3), mp = 191–192 °C. IR (ATR):
= 3050 (w) cmꢀ1, 2973 (w), 1483 (w), 1335 (w), 1299 (w),
~
m
1173 (s, P@O), 1112 (s), 1070 (w), 891 (s), 857 (w), 792 (w),
729 (s), 685 (s), 643 (w). 1H NMR (CDCl3, 400.1 MHz): d = 1.06
(m, 1H, CH2), 1.46 (d, JHH = ꢀ8.7 Hz, 1H, CH2), 1.86 (d,
2
2JPH = 12.7 Hz, endo-PCH3), 1.87 (d, JPH = 12.7 Hz, exo-PCH3), 2.34
(m, 1H, CHendo), 2.76 (m, 1H, CH2CHCHendo), 2.80 (br s, 1H,
CH2CHCHexo), 2.93 (m, 1H, CHexo), 5.59 (m, 1H, @CHCHexo), 6.02
(m, 1H, @CHCHendo), 7.48 (m, 6H, HPh), 7.70 (m, 4H, HPh) ppm.
13C NMR (100.6 MHz BB, DEPT, HMQC, HMBC, HH-COSY, NOE,
4.2. Asymmetric Diels–Alder cycloaddition of (SP,SP)-1 with
cyclopentadiene
1
1
A
solution of freshly distilled cyclopentadiene (10 equiv,
CDCl3): d = 9.2 (d, JPC = 64.2 Hz, endo-PCH3), 13.2 (d, JPC =
1
108.3 mg, 1.6 mmol) and (SP,SP)-125–27,43 (50 mg, 0.2 mmol) in
dichloromethane (3 mL) was stirred at 20 °C for 24 h under TLC
control (benzene/EtOH 4:1). The solvent was removed at reduced
pressure, and the yellow residue was purified by flash chromatog-
raphy (SiO2, 20 ꢁ 2 cm, CHCl3/MeOH 9:1) to afford 58.0 mg
(0.19 mmol, 95%) of (SP,SP,2R,3R)-2 and (SP,SP,2S,3S)-3 as a mixture
of diastereoisomers (1.3:1) as a colorless powder.31
65.3 Hz, exo-PCH3), 41.9 (d, JPC = 73.9 Hz, CHPexo), 42.1 (dd,
1
2
1JPC = 65.2 Hz, JPC = 1.2 Hz, CHPendo), 45.8 (dd, JPC = 3JPC = 1.2 Hz,
CHCHPexo), 45.9 (d, 2JPC = 4.4 Hz, CHCHPendo), 48.1 (d, 3JPC = 11.3 Hz,
CH2), 128.5 (d, 3JPC = 11.3 Hz, m-CHPhPendo), 128.6 (d, 3JPC = 11.3 Hz,
4
m-CHPhPexo), 130.4 (d, JPC = 1.3 Hz, p-CHPhPendo), 130.5 (d,
4JPC = 1.3 Hz, p-CHPhPexo), 131.6 (d, JPC = 2.7 Hz, o-CHPhPendo),
2
131.7 (d, 2JPC = 2.7 Hz, o-CHPhPexo), 132.5 (d, 1JPC = 90.1 Hz, PendoCq),
133.5 (d, 1JPC = 90.1 Hz, PexoCq), 135.1 (d, 3JPC = 4.0 Hz,
3
4.3. Separation of diastereoisomers (SP,SP,2R,3R)-2 and
@CHCHCPendo), 137.1 (d, JPC = 11.9 Hz, @CHCHCPexo) ppm. 31P
3
(SP,SP,2S,3S)-3 with (ꢀ)-O,O-dibenzoyl-
L
-tartaric acid
NMR (CDCl3, 162 MHz): d = +38.6, (d, JP,P = 8.9 Hz), +39.8,
3
monohydrate
(d, JP,P = 8.9 Hz) ppm. MS (EI) m/z (%): 370 (11) [M+], 305 (17)
[M+ꢀC5H5], 231 (100) [M+ꢀP(O)MePh], 165 (28), 139 (37), 91
(18), 77 (20) [Ph+]. HRMS (ESI) calcd for: [M+H]+ (C21H24O2P2Na):
calcd 393.1149, found 393.1152. Anal. Calcd for C21H24O2P2: C,
68.10; H, 6.53. Found: C, 67.46; H, 6.61.
(ꢀ)-O,O-Dibenzoyl-L-tartaric acid monohydrate (101.6 mg,
0.27 mmol) was added as a powder to a solution of (SP,SP,2R,3R)-
2 and (SP,SP,2S,3S)-3 (1.3:1, 100 mg, 0.27 mmol) in methanol
(4 mL). The resulting suspension was stirred at reflux for 5 h and
cooled to 25 °C. After addition of ethyl acetate (2 mL) the mixture
was heated at reflux for 2 h and cooled to 25 °C. The white precip-
itate formed was filtered off and washed with ethyl acetate
(10 mL). The precipitate was then treated with 2 M aq NaOH solu-
tion (3 mL) and extracted with CH2Cl2 (3 ꢁ 10 mL) and dried with
anhydrous MgSO4. After solvent removal at reduced pressure
(SP,SP,2R,3R)-2 was obtained as a colorless solid 31 mg (0.10 mmol,
4.4.1. Crystal structure analysis of (SP,SP,2R,3R)-231,32
Single crystals of (SP,SP,2R,3R)-2 were obtained by slow evapora-
tion from chloroform/MeOH (9:1) at 20 °C. Empirical formula
C21H24O2P2 , formula weight 370.34 g/mol, crystal system ortho-
rhombic, space group P212121, unit cell dimensions a = 11.857(3),
b = 16.383(13), c = 20.093(8) Å,
a
= 90°, b = 90°,
l
c = 90°, V =
3903(4) Å3, Z = 8, dcalcd = 1.260 g/cm3,
= 0.234 mmꢀ1, crystal size
31%, 96% de). ½a 2D0
¼ ꢀ83:5 (c 0.69, CHCl3), mp = 207–208 °C.
ꢂ
0.15 ꢁ 0.15 ꢁ 0.18 mm, F(000) = 1568, refinement method full-ma-
The filtrate was also treated with 2 M aq NaOH (5 mL), ex-
tracted with CH2Cl2 (3 ꢁ 10 mL), and dried over MgSO4 to give
(SP,SP,2S,3S)-3 as a colorless solid after solvent removal at reduced
trix least-squares on F2, STOE IPDS one-axis diffractometer with
imaging plate detector, T = 300(2) K, Mo
Ka radiation (k =
pressure (41 mg, 0.11 mmol, 41%, 90% de). ½a D20
¼ þ15:4 (c 0.72,
ꢂ
0.71073 Å), h-range 1.99–24.32°, reflections collected/unique
12,481/6266 [Rint = 0.1301], completeness of data h = 24.3° (99.7%),
index ranges ꢀ13 6 h 6 13, 0 6 k 6 18, 0 6 l 6 23, direct methods,
full-matrix least-squares refinement on F2, goodness-of-fit on
CHCl3), mp = 211.5–212 °C. 31P NMR (CDCl3, 162 MHz): d = 38.3,
(d, 3J = 9.5 Hz), 39.5, (d, 3J = 9.5 Hz) ppm. 1H NMR (CDCl3,
2
400.1 MHz): d = 1.42 (m, 1H, CH2), 1.49 (d, JPH = 12.6 Hz, endo-
F2 = 0.729, R1 = 0.0623 (I > 2
rI), wR2 = 0.0879, R-indices [all data]
2
PCH3), 1.68 (d, JPH = 12.6 Hz, exo-PCH3), 1.79 (d, JHH = 7.8 Hz, 1H,
2
2
R1 = 0.2372 , wR2 = 0.1144, final difference electron density map
CH2), 2.26 (dd, 1H, JPH = 16.3 Hz; JHH = 6.0 Hz CHendo), 2.90 (m,
1H, CHexo), 3.30 (br s, 1H, CH2CHCHexo), 3.34 (m, 1H, CH2CHCHendo),
6.31 (m, 2H, @CHCHendo, @CHCHexo), 7.15–7.42 (m, 10H, HPh) ppm.
0.347 and ꢀ0.229 e Åꢀ3
.
Acknowledgments
4.4. TiCl4-assisted asymmetric Diels–Alder cycloadditon
This research was kindly supported by the Gottlieb Daimler and
Karl Benz-Foundation (doctoral fellowship to N.V.) and by the
Deutsche Forschungsgemeinschaft.
At first, TiCl4 (0.5 equiv, 15.6 mg, 0.1 mmol,1 M in CH2Cl2) was
carefully added dropwise over 3 min at ꢀ78 °C to a stirred solu-
tion of (SP,SP)-1 (50 mg, 0.2 mmol) in dichloromethane (5 mL).

N. Vinokurov et al. / Tetrahedron: Asymmetry 20 (2009) 1081–1085
1085
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