Synthesis of a novel C2-symmetric bis-oxazoline (=bis[4,5-dihydrooxazole]) and its application as chiral ligand in asymmetric transition metal catalysis

Article abstract of DOI:10.1002/hlca.201100440

The new C₂-symmetric bis-oxazoline (=bis[4,5-dihydrooxazole]) 2 with a chiral trans-(2R,3R)-2,3-bis(3,5-diphenylphenyl)cyclopropylidene (=trans-(2R,3R)-2,3-bis([1,1′: 3′,1″-terphenyl]-5′-yl) cyclopropylidene) backbone was efficiently synthesized (Scheme). All synthetic steps were easy to perform and led to the desired product in good overall yields. Compound 2 was tested and compared as ligand in several enantioselective catalytic reactions such as palladium(0)-catalyzed enantioselective allylic alkylations and copper(I)-catalyzed enantioselective cyclopropanations and aziridinations. Copyright

Full text of DOI:10.1002/hlca.201100440

Helvetica Chimica Acta – Vol. 95 (2012)
831
Synthesis of a Novel C2-Symmetric Bis-oxazoline (¼ Bis[4,5-dihydrooxazole])
and Its Application as Chiral Ligand in Asymmetric Transition Metal
Catalysis
by Yas¸ar Gçk*a)b) and Johan Van der Eyckena)
a) Laboratory for Organic and Bioorganic Synthesis, Department of Organic Chemistry, Ghent
University, Krijgslaan 281 (S.4), B-9000 Ghent
b) Department of Chemistry, Faculty of Arts and Sciences, Osmaniye Korkut Ata University,
Karacaoglan Yerleskesi, 80000 Osmaniye, Turkey
(phone: þ 90-328-8271000/2541; fax: þ 90-328-8250097; e-mail: yasargok@osmaniye.edu.tr)
The new C2-symmetric bis-oxazoline (¼ bis[4,5-dihydrooxazole]) 2 with a chiral trans-(2R,3R)-2,3-
bis(3,5-diphenylphenyl)cyclopropylidene (¼trans-(2R,3R)-2,3-bis([1,1’:3’,1’’-terphenyl]-5’-yl)cyclopro-
pylidene) backbone was efficiently synthesized (Scheme). All synthetic steps were easy to perform
and led to the desired product in good overall yields. Compound 2 was tested and compared as ligand in
several enantioselective catalytic reactions such as palladium(0)-catalyzed enantioselective allylic
alkylations and copper(I)-catalyzed enantioselective cyclopropanations and aziridinations.
Introduction. – Bis-oxazoline (¼ bis[4,5-dihydrooxazole]; box) ligands have
received the greatest share of attention in N-containing ligands, e.g. semicorrins [1],
diimines [2], salen [3], 2,2’-bipyridines [4], amidines [5], sulfoximines [6], and,
recently, imidates with an exocyclic coordinating N-atom [7]. They are known as cheap,
easily accessible, and stable ligands [8]. As a result, the design, synthesis, and
application of C2-symmetric box ligands has received a lot of attention [9]. Since their
initial report, a lot of research has been devoted towards the synthesis and application
of these box ligands. During the last decade, numerous chiral box ligands with different
backbones, such as aliphatic chains [10], aromatic rings [11], 4,5-dioxolane [12],
dibenzo[a,c]cycloheptene [13], biphenyl and binaphthyl [14], and cyclic rings [15] have
been reported.
Generally, the large majority of box ligands are derived from optically active b-
amino alcohols to produce a 4,5-dihydrooxazole ring with a chiral center. As a
consequence, the presence of a stereogenic center next to the coordinating N-atom of
the dihydrooxazole ring directly influences the stereochemical outcome of the
enantioselective reaction. Recently, we investigated the efficiency of backbone chirality
of the bis[dihydrooxazole] containing no extra chiral center at the dihydrooxazole
moiety. Therefore, C2-symmetric bis[dihydrooxazole] ligand 1 (Fig.) with a trans-
(2R,3R)-2,3-diphenylcyclopropylidene backbone was developed and evaluated in
palladium(0)-catalyzed asymmetric allylic alkylations, copper(I)-catalyzed cyclopro-
panations, and copper(I)-catalyzed aziridinations by our group [16]. Our results
established that ligand 1 showed poor enantioselectivities. The highest enantioselec-
tivity in the catalysis of ligand 1 was obtained in asymmetric allylic alkylation of a cyclic
ꢀ 2012 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 95 (2012)
substrate 9 (67% ee; see Table 1, below). Increasing of the bulky groups at the
cyclopropane moiety may be one of the options to obtain high enantioselectivities due
to the steric-hindrance effect. Therefore, in the present article, we describe the
synthesis of the new box ligand 2 (Fig.) with a more bulky cyclopropane backbone than
in the earlier reported ligand 1, i.e., 2 contains a (trans-(2R,3R)-2,3-bis(3,5-diphenyl-
phenyl)cyclopropylidene
(¼trans-(2R,3R)-2,3-bis([1,1’:3’,1’’-terphenyl]-5’-yl)cyclo-
propylidene) moiety. This new box ligand 2 was tested in the same enantioselective
catalytic reactions as 1, such as palladium(0)-catalyzed asymmetric allylic alkylations,
copper(I)-catalyzed cyclopropanations, and copper(I)-catalyzed aziridinations.
Figure. Bis[dihydrooxazole] ligands
Results and Discussion. – The synthetic route towards enantiomerically pure bis-
[dihydrooxazole] 2 started with acid ester 3 which was earlier described by our group
(Scheme) [17]. The most widely used method to develop bis[dihydrooxazoles] is the
reaction of diacid derivatives with chiral amino alcohols followed by a cyclization.
According to this general procedure, acid ester 3 was first converted by saponification
to the corresponding diacid 4 and then to the bis(acyl chloride) by treatment with oxalyl
chloride. Without further purification, this bis(acyl chloride) was used in the next step.
Within 1 h, with 2 equiv. of amino alcohol in the presence of triethylamine, the bis(acyl
chloride) was converted smoothly into the corresponding bis(hydroxyamide) 5 [18].
The alcohol functions therein were further transformed into good leaving groups by
treatment with mesyl chloride. Subsequent cyclization in an aqueous MeOH solution of
sodium hydroxide gave the tetrabromo-substituted bis[dihydrooxazole] 6 in good yield
(82%). The last step of our synthetic route was the introduction of four phenyl groups
via a Suzuki cross-coupling reaction. Thus, 6 was treated with phenylboronic acid and
K2CO3 in the presence of [Pd(PPh3)4] in EtOH/H2O/toluene 1:2 :4 at reflux
temperature, yielding tetraphenyl-substituted bis[dihydrooxazole] 2 in excellent yield
(81%).
The palladium(0)-catalyzed asymmetric allylic alkylation is one of the most
versatile methods for the formation of CꢀC bonds (for reviews about asymmetric allylic
substitution, see [19]). We began with this catalytic test reaction to determine the
efficiency of the new bis[dihydrooxazole] ligand 2. The first substrate was 1,3-
diphenylprop-2-en-1-yl acetate (7) in the reaction with dimethyl malonate (¼dimethyl
propanedioate), which is regarded as a standard test substrate for evaluating
enantioselective catalysts (Table 1). The nucleophile was generated from dimethyl
malonate (3 equiv.) in the presence of N,O-bis(trimethylsilyl)acetamide (BSA;

Helvetica Chimica Acta – Vol. 95 (2012)
833
Scheme. Synthesis of Bis[dihydrooxazole] Ligand 2
3 equiv.) and BSA activator (0.1 mol-%). The catalytic system palladium(0)/bis[dihy-
drooxazole] 2 exhibited a high conversion but poor enantioselectivity (Table 1,
Entry 1). When we used AcOLi as a BSA activator, a sharp decrease in conversion was
obtained; however, the enantioselectivity was roughly the same (Table 1, Entry 2).
Although highly selective catalysts have been developed for cyclic substrates, e.g.,
Trostꢂs ligand, they generally exhibit low enantioselectivity in more hindered substrates,
such as substrate 7. Ligands with a broad substrate scope are very rare [20]. When we
performed the reaction with our bis[dihydrooxazole] ligand 2, we observed moderate
enantioselectivity with low conversion (Table 1, Entry 3). To our disappointment, we
observed no conversion when we used unhindered linear acetate 11 (Table 1, Entry 4).
The bis[dihydrooxazole] ligand 2 was further tested in CuI-catalyzed enantiose-
lective reactions. The first reaction was enantioselective cyclopropanation of olefins.
The enantioselective cyclopropanation of styrene (13) with ethyl diazoacetate is
considered as another benchmark reaction to determine the efficiency of newly
developed ligands [10a][21]. To prevent the formation of diethyl malonate, we added
the solution of ethyl diazoacetate slowly over 5 h with a syringe pump to an excess of
styrene (13). A moderate yield of 14 and 15 and poor enantioselectivity were observed
(Table 2, Entry 1). Aziridines are very versatile building blocks in organic chemistry as
they exhibit a similar reactivity pattern as epoxides [22]. An interesting methodology to
obtain chiral aziridines is the CuI-catalyzed asymmetric aziridination of alkenes [23].

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Helvetica Chimica Acta – Vol. 95 (2012)
Table 1. Pd0-Catalyzed Asymmetric Allylic Alkylation of 7, 9, and 11 with Dimethyl Malonate in the
Presence of Bis[dihydrooxazole] Ligand 2
Entry
Substrate
BSA Activator
Yielda) [%]
eeb)c) [%]
1
2
3
4
7
7
9
AcOK
AcOLi
AcOLi
AcOLi
89
19
22 (S)
18 (S)
52d) (R)
–
2
11
n.d.e)
a) Isolated yield. b) Determined by HPLC analysis with a chiral stationary phase (Chiralpak AD-H).
c) The absolute configuration was assigned by the sign of the optical rotation. d) Determined by GC
analysis with a chiral stationary phase (Supelco b-Dex). e) n.d. ¼ not determined.
Thus the catalytic asymmetric aziridination of styrene (13) and methyl cinnamate (17)
was carried out with [(p-toluenesulfonyl)imino]phenyl-l3-iodane (¼4-methyl-N-
(phenyl-l3-iodanylidene)benzenesulfonamide ¼ {[(4-methylphenyl)sulfonyl]imino}-
phenyliodine; PhINTs) as a nitrene precursor at room temperature. In contrast with the
asymmetric cyclopropanation reaction, the best yield was obtained in the CuI-catalyzed
enantioselective aziridination of 13 (!16). Although the conversion was noteworthy,
the enantioselectivity was very poor (Table 2, Entry 2). We obtained also poor results
in the asymmetric aziridination of methyl cinnamate (17) in MeCN (!18; Table 2,
Entry 3). Changing the solvent to benzene resulted in a slightly better result (Table 2,
Entry 4).
In summary, our aim was to develop an efficient chiral bis[dihydrooxazole] ligand
containing no stereogenic center at the dihydrooxazole moiety. Therefore, we focused
on the backbone chirality by increasing the bulky groups at the chiral backbone group
of a bis[dihydrooxazole] ligand to determine if the steric-hindrance effect played a role
in asymmetric induction. For this purpose, we synthesized the new bis[dihydrooxazole]
ligand 2 containing a chiral trans-(2R,3R)-2,3-bis-(3,5-diphenylphenyl)cyclopropyli-
dene moiety as bulky backbone and evaluated this ligand in Pd0-catalyzed asymmetric
allylic alkylations, CuI-catalyzed cyclopropanations and CuI-catalyzed aziridina-
tions. The best catalytic result with ligand 2 was obtained in the Pd0-catalyzed
asymmetric allylic alkylations (ee up to 52%). We demonstrated that the steric-
hindrance effect of the bulky chiral backbone did not help to obtain acceptable
enantioselectivities.

Helvetica Chimica Acta – Vol. 95 (2012)
835
Table 2. CuI-Catalyzed Enantioselective Reactions: Cyclopropanation and Aziridination of Styrene (13)
and Aziridination of Methyl Cinnamate (17) in the Presence of Bis[dihydrooxazole] Ligand 2
Entry (Eqn.) Solvent Yielda) [%] eeb) [%]
cis/trans ratioc) ee cisc)d) [%] ee transc)d) [%]
1 (i)
CH2Cl2 57
C6H6 95
MeCN 11
C6H6 26
36 : 64
7 (1S,2R)
13 (1S,2S)
2 (ii)
3 (iii)
4 (iii)
6 (2R)
rac
7 (2R,3S)
–
–
–
–
–
–
–
–
–
a) Isolated yield. b) Determined by HPLC analysis with a chiral stationary phase (Chiralcel OD-H or
c
Chiralpak AD-H). The absolute configuration was assigned by the sign of the optical rotation. ) The cis/
trans ratio and the enantioselectivity were determined by GC analysis with a chiral stationary phase
(Cyclosil-b). d) The absolute configuration was assigned by the sign of the optical rotation.
Y. G. and J. V. D. E wish to thank Ghent University and COST-Chemistry (Action D.40-ꢃInnovative
Catalysisꢂ) for financial support. Prof. Dr. Erik Van der Eycken (Laboratory for Organic & Microwave-
Assisted Chemistry (LOMAC), Department of Chemistry, Katholieke Universiteit Leuven) is kindly
acknowledged for performing the HR-MS measurements.
Experimental Part
General. All reactions were carried out under Ar in dry solvents under anh. conditions, unless stated
otherwise. All reagents were purchased and used without purification, unless noted otherwise. Anal.
TLC: Macherey-Nagel-SIL-G-25-UV254 plates. Flash chromatography (FC): Rocc silica gel (SiO2; 0.040 –
0.063 mm). Anal. HPLC: Agilent-1100 HPLC system with DAD detection; tR in min. M.p.: Kofler
melting-point apparatus. Optical rotations: Perkin-Elmer-241 polarimeter. IR Spectra: Perkin-Elmer
Spectrum-1000 FT-IR spectrometer with a pike miracle horizontal attenuated total reflectance (HATR)
1
module; in cmꢀ1. H- and 13C-NMR Spectra: Bruker-Avance-300 or Bruker-DRX-500 spectrometer as
indicated; d in ppm rel. to Me4Si as internal standard, J in Hz; attached-proton test for 13C-NMR. EI-MS:
Hewlett-Packard-5988A mass spectrometer for EI-MS; Agilent-1100 HPLC with quaternary pump, DAD
and single-quadrupole MS detector type VL with an API-ES source, and Phenomenex-Luna-C18(2)
column (250 ꢁ 4.6 mm, particle size 5 mm) for LC/ESI-MS; quadrupole/orthogonal-acceleration time-of-
flight (Q/oaTOF) tandem mass spectrometer (qTof 2, Micromass, Manchester, UK), equipped with a
standard electrospray-ionization (ESI) interface for HR-ESI-MS; in m/z.
(2R,3R)-2,3-Bis(3,5-dibromophenyl)cyclopropane-1,1-dicarboxylic Acid (4). To a soln. of acid ester
3 [17] (0.83 g, 1.33 mmol) in MeOH (5 ml) was added 2n aq. NaOH (5 ml). The mixture was refluxed for
24 h, and subsequently, MeOH was evaporated. The residue was cooled to 08 and acidified with 6n aq.
HCl. The acidified mixture was extracted with Et2O (3 ꢁ 20 ml), and the org. phase dried (Na2SO4) and
concentrated: 4 (0.65 g, 82%). Colorless oil-like foam. The crude 4 was used in the next step without

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Helvetica Chimica Acta – Vol. 95 (2012)
further purification. [a]2D0 ¼ þ18.2 (c ¼ 1.0, CHCl3). IR (HATR): 2929, 1700, 1583, 1552, 1409, 1361, 1253,
1211, 1134, 1100, 1052, 853, 739, 674, 656. 1H-NMR (300 MHz, CDCl3): 3.72 (s, 2 H); 7.35 (s, 4 H); 7.55 (s,
2 H). 13C-NMR (75.4 MHz, CDCl3): 35.53 (CH); 45.18 (C); 123.02 (C); 132.06 (CH); 133.34 (CH);
141.09 (C); 168.65 (C). ESI-MS: 598.7 ([M þ H]þ), 615.8 ([M þ NH4]þ).
(2R,3R)-2,3-Bis(3,5-dibromophenyl)-N,N’-bis(2-hydroxyethyl)cyclopropane-1,1-dicarboxamide (5).
Oxalyl chloride (0.388 g, 3.06 mmol) was added dropwise over 20 min to a soln. of 4 (0.63 g, 1.05 mmol)
and DMF (30 ml) in CH2Cl2 (5 ml) at 08 under Ar. The mixture was allowed to warm to r.t. and stirred for
another 5 h. The volatiles were evaporated, affording the crude acyl chloride. The acyl chloride was
dissolved in CH2Cl2 (6 ml), and this soln. added dropwise over 40 min to a mixture of 2-aminoethanol
(0.116 g, 1.09 mmol) and Et3N (0.481 g, 4.75 mmol) in CH2Cl2 (12 ml). After 1 h, the resulting suspension
was diluted with CH2Cl2 and washed with 1n HCl (15 ml), sat. NaHCO3 soln. (15 ml), and brine (15 ml).
The combined org. phase was dried (Na2SO4) and concentrated, and the crude product purified by FC
(CH2Cl2/MeOH 94 :6): 0.50 g (80%) of pure 5. White solid. M.p. 120 – 1228. [a]2D0 ¼ þ43 (c ¼ 1.0, EtOH).
IR (HATR): 3282, 3069, 2175, 1633, 1583, 1550, 1412, 1304, 1209, 1054, 854, 740, 679. 1H-NMR
(300 MHz, CDCl3): 2.85 – 2.95 (m, 2 H); 3.05 – 3.25 (m, 4 H); 3.3 – 3.4 (m, 2 H); 3.45 (s, 2 H); 7.1 (t, J ¼
5.5, 2 H); 7.25 (d, J ¼ 1.5, 4 H); 7.35 (t, J ¼ 1.5, 2 H). 13C-NMR (75.4 MHz, CDCl3): 32.41 (CH); 42.63
(CH2); 48.93 (C); 61.38 (CH2); 122.93 (C); 130.38 (CH); 133.21 (CH); 138.88 (C); 166.15 (C). HR-EI-
MS: 684.8242 (C21H20Br4N2Oþ4 ; calc. 684.8231).
2,2’-[(2R,3R)-2,3-Bis(3,5-dibromophenyl)cyclopropylidene]bis[4,5-dihydrooxazole] (6). A mixture
of 5 (0.45 g, 0.66 mmol) and Et3N (0.748 g, 7.4 mmol) in CH2Cl2 (12 ml) was stirred at 08. MsCl (0.151 g,
1.32 mmol) was added dropwise over 10 min. The mixture was allowed to warm to r.t. and stirred for an
additional hour. The mixture was washed with H2O, and the org. phase dried (Na2SO4) and concentrated
to give the corresponding crude bis-mesylate as a yellow oil. The crude bis-mesylate was dissolved in
MeOH (10 ml) and treated with 1n aq. NaOH (2 ml) at r.t. for 2 h. After evaporation of MeOH, CH2Cl2
was added, and the mixture washed with H2O. The org. phase was dried (Na2SO4) and concentrated, and
the crude product purified by FC (CH2Cl2/MeOH 95 :5): 0.35 g (82%) of pure 6. Colorless viscous oil-like
foam. [a]2D0 ¼ þ43.49 (c ¼ 1.0, CHCl3). IR (HATR): 2916, 2341, 2005, 1663, 1584, 1550, 1412, 1256, 1151,
1
1090, 990, 924, 854, 743, 677. H-NMR (300 MHz, CDCl3): 3.36 – 3.46 (m, 2 H); 3.49 (s, 2 H); 3.58 – 3.7
(m, 2 H); 3.86 – 3.95 (m, 4 H); 7.25 (d, J ¼ 1.51, 4 H); 7.38 (t, J ¼ 1.51, 2 H). 13C-NMR (75.4 MHz, CDCl3):
33.71 (CH); 34.35 (C); 54.07 (CH2); 68.38 (CH2); 122.57 (C); 130.60 (CH); 133.11 (CH); 138.64 (C);
162.25 (C). ESI-MS: 648.7 ([M þ H]þ). HR-ESI-MS: 648.8004 (C21H16Br4N2Oþ2 ; calc. 648.8020).
2,2’-[(2R,3R)-2,3-Bis([1,1’:3’:1’’-terphenyl]-5’-yl)cyclopropylidene]bis[4,5-dihydrooxazole] (2).
Phenylboronic acid (0.123 g, 0.99 mmol) in EtOH (2.8 ml) and 2m aq. K2CO3 (5 ml) was added to a
soln. of 6 (0.108 g, 0.166 mmol) and [Pd(PPh3)4] (0.024 g, 0.02 mmol) in toluene (11 ml) under Ar. The
mixture was refluxed for 4 h. After addition of H2O, the aq. layer was extracted with CH2Cl2 (3 ꢁ 50 ml),
the combined org. phase washed with brine (10 ml), dried (MgSO4), and concentrated, and the crude
product purified by FC (toluene/AcOEt/Et3N 1:1:0.01): 0.085 g (81%) of pure 2. Light yellow viscous
oil. [a]2D0 ¼ þ74.2 (c ¼ 1.0, CHCl3). IR (HATR): 3038, 2972, 2360, 1661, 1595, 1576, 1497, 1457, 1356, 1258,
1196, 1146, 1077, 993, 930, 907, 759, 730, 700. 1H-NMR (300 MHz, CDCl3): 3.4 – 3.55 (m, 2 H); 3.65 – 3.77
(m, 2 H); 3.85 – 3.94 (m, 4 H); 4.04 (s, 2 H); 7.25 – 7.42 (m, 12 H); 7.55 – 7.62 (m, 12 H); 7.66 (t, (app. s),
2 H). 13C-NMR (75.4 MHz, CDCl3): 34.41 (C); 34.70 (CH); 54.21 (CH2); 68.02 (CH2); 124.80 (CH);
126.72 (CH); 127.16 (CH); 127.50 (CH); 128.81 (CH); 136.25 (C); 140.81 (C); 141.45 (C); 163.41 (C).
ESI-MS: 637 ([M þ H]þ). HR-ESI-MS: 637.2876 (C45H36N2Oþ2 ; calc. 637.2849).
Pd0-Catalyzed Asymmetric Allylic Alkylation: General Procedure. Ligand 2 (0.05 mmol) and [Pd(h3-
C3H5)Cl]2 (0.02 mmol) were dissolved in degassed CH2Cl2 under Ar by using Schlenk techniques. The
mixture was stirred for 1 h at 508 and then cooled to r.t. Racemic 1,3-diphenylprop-2-en-1-yl acetate (7;
1 mmol) in CH2Cl2 was added, and the mixture stirred at r.t. for 30 min. Finally, a soln. of BSA (3 mmol),
AcOLi (0.1 mmol), and dimethyl malonate (3 mmol) were added, and the mixture was stirred for 16 h at
r.t. Next, Et2O was added, the org. phase washed with sat. NH4Cl soln, dried (MgSO4), and concentrated,
and the crude product purified by FC (SiO2, hexane/AcOEt 9 :1) to afford the target compound. All
adducts were fully characterized by comparison of their spectral data with those reported in the
literature. The absolute configurations were assigned via correlation of their optical rotation with
literature values [24].

Helvetica Chimica Acta – Vol. 95 (2012)
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Dimethyl 2-[(2E)-1,3-Diphenylprop-2-en-1-yl]propanedioate (8): The ee was determined by HPLC
(Chiralpak AD-H (250 ꢁ 4.6 mm, particle size 10 mm), hexane/EtOH 7:3, flow rate 1 ml/min, T¼ 358): tR
9.7 ((ꢀ)-(S)-8), and 15.2 ((þ)-(R)-8).
Dimethyl 2-(Cyclohex-2-en-1-yl)propanedioate (10): The ee was determined by GC (Supelco b-Dex
120 (30m ꢁ 0.25 mm ꢁ 0.25 mm), 1208 (isothermic)): tR 36.7 ((ꢀ)-(S)-10) and 37.2 ((þ)-(R)-10).
1
Dimethyl 2-[(2E)-1-Methylbut-2-en-1-yl]propanedioate (12): The ee was determined by H-NMR
(300 MHz, CDCl3) with (þ)-Eu(hfc)3 as a resolving agent.
Asymmetric Cyclopropanation: General Procedure. A suspension of CuOTf · 1ꢄ2 C6H6 (0.01 mmol)
and ligand 2 (0.012 mmol) in CH2Cl2 was stirred under Ar at r.t. After 1 h, styrene (13; 7.5 mmol) was
added to the resulting green soln. Next, ethyl diazoacetate (1 mmol) was slowly added over 5 h via a
syringe pump. The mixture was stirred at r.t. overnight. The excess 13 and CH2Cl2 were evaporated and
the crude product was purified by FC (pentane/AcOEt 96 :4) to afford the cyclopropane esters. All
adducts were fully characterized by comparison of their spectral data with those reported in the
literature. The absolute configurations were assigned via correlation of their optical rotation with
literature values [10a].
Ethyl cis- and trans-2-Phenylcyclopropanecarboxylate (14 and 15): The ee was determined by GC
(Cyclosil B (30 m ꢁ 0.25 mm ꢁ 0.25 mm); 508 for 3 min, then increasing to 2408 (58/min), and then 2408
for 3 min): tR 26.6 ((1S,2R)-14), 26.88 ((1R,2S)-14), 27.93 ((1R,2R)-15), and 29.99 ((1S,2S)-15).
Asymmetric Aziridination: General Procedure. Ligand 2 (0.150 mmol) and CuOTf · 1ꢄ2 C6H6
(0.125 mmol) were dissolved in MeCN or benzene (1 ml) and stirred for 1 h at r.t. To this soln. were
added styrene (13; 25 mmol) or methyl cinnamate (17; 25 mmol) and activated 4-ꢅ molecular sieves.
Subsequently, PhI ¼ NTs (5 mmol) was added, and the mixture was stirred at r.t. for 16 h. The crude
product was purified by FC (SiO2, hexane/AcOEt 9 :1). The adducts 16 and 18 were fully characterized
by comparison of their spectral data with those reported in the literature. The absolute configurations
were assigned via correlation of their optical rotation with literature values [23a][25].
1-[(4-Methylphenyl)sulfonyl]-2-phenylaziridine (16): The ee was determined by HPLC (Chiralpak
AD-H, hexane/EtOH 9 :1, flow rate 1 ml/min, T 358): tR 14.6 ((R)-16) and 15.2 ((S)-16).
Methyl 1-[(4-Methylphenyl)sulfonyl]-3-phenylaziridine-2-carboxylate (18): The ee was determined
by HPLC: Chiralcel OD-H (250 ꢁ 4.6 mm, particle size 10 mm), hexane/EtOH 9 :1, flow rate 1 ml/min, T
358): tR 10.7 ((2R,3S)-18) and 16.4 ((2S,3R)-18).
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Received November 11, 2011