(Thiolan-2-yl)diphenylmethyl benzyl ether/N,N′-diarylurea cocatalyzed asymmetric aziridination of cinnamyl bromide and aryl aldimine

Article abstract of DOI:10.1016/j.tet.2014.12.063

A dual catalyst system using THT-based chiral sulfide 2a and H-bond donor 10a was developed for the asymmetric imino Corey-Chaykovsky reaction. Under the optimum reaction conditions, cinnamyl bromide reacted with a wide scope of N-diphenylphosphinic aldim

Full text of DOI:10.1016/j.tet.2014.12.063

Tetrahedron xxx (2014) 1e9
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Tetrahedron
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(Thiolan-2-yl)diphenylmethyl benzyl ether/N,N0-diarylurea
cocatalyzed asymmetric aziridination of cinnamyl bromide and aryl
aldimine
,
Shang-Hua Wang a, Rong-Jie Chein b
*
a Department of Chemistry, National Taiwan Normal University, 162, Heping East Road Section 1, Taipei 10610, Taiwan
b Institute of Chemistry, Academia Sinica, 128 Academia Road Sec. 2, Taipei 11529, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
A dual catalyst system using THT-based chiral sulfide 2a and H-bond donor 10a was developed for the
asymmetric imino CoreyeChaykovsky reaction. Under the optimum reaction conditions, cinnamyl bro-
mide reacted with a wide scope of N-diphenylphosphinic aldimines, to give the major trans-aryl cin-
namyl aziridines with up to 98% ee. The role of H-bond donor 10a was demonstrated empirically as well.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 13 October 2014
Received in revised form 15 December 2014
Accepted 17 December 2014
Available online xxx
Keywords:
Chiral sulfide
Sulfur ylide
Asymmetric aziridination
CoreyeChaykovsky
H-bind donor
1. Introduction
2. Results and discussions
Chiral sulfur ligands are becoming a versatile tool in organic
chemistry due to the blossomed development achieved in the past
years. These sulfur catalysts are being used less than the more
developed phosphorus- or nitrogen-based ligands in view of elec-
tronic and steric considerations, but have proved to be as useful as
other classical chiral ligands in a broad variety of asymmetric re-
actions.1 We recently reported an efficient preparation of
tetrahydrothiophene(THT)-based chiral sulfide 1a (Fig. 1A) and its
benzyl ether derivative 2a that shows excellent activity in cata-
lyzing different enantioselective transformations, thus allowing
access to various synthetically useful compounds such as diaryl
epoxides and diaryl aziridines.2 In 2008, Connon et al. demon-
strated that N,N0-diarylureas and thioureas are capable of the effi-
cient catalysis of sulfonium ylide-mediated aldehyde epoxidation
(CoreyeChaykovsky reaction3) through the stabilization of the
rate-determining transition state.4 In the present study, we have
now evaluated the compatibility of the same family of chiral sul-
fides and N,N0-diaryl(thio)ureas in the asymmetric imino Cor-
eyeChaykovsky reaction of cinnamyl bromide and aryl aldimines
(Fig. 1B), the stereo control of which is more challenging than that
of the diaryl aziridine formation.5
2.1. Synthesis of chiral sulfide catalysts
A series of THT-based sulfides (2ae2f) were readily synthesized
according to our previously reported procedure, as depicted in
Scheme 1.2 Commercially available ethyl 5-bromovalerate (3) was
reacted with an excess amount of arylmagnesium bromide to afford
diarylalcohols 4ae4c that were dehydrated in hot toluene in the
presence of PTSA. The resulting diphenylethylenes 5ae5c were
* Corresponding author. Tel.: þ886 2 2789 8526; fax: þ886 2 2783 1237; e-mail
Fig. 1. A. Structures of THT-based chiral sulfides 1a and 2a. B. Concept of the dual
catalysis in this work.
address: rjchein@chem.sinica.edu.tw (R.-J. Chein).
http://dx.doi.org/10.1016/j.tet.2014.12.063
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.
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2
S.-H. Wang, R.-J. Chein / Tetrahedron xxx (2014) 1e9
then subjected to Shi epoxidation condition to furnish optically
active epoxides 6ae6c.6 After THT-ring formation with Na2S, the
hydroxy groups were protected by benzyl bromide, 4-butylbenzyl
bromide, pentafluorobenzyl bromide, and picolyl bromide re-
spectively under basic conditions in DMF, yielding catalysts 2aef
for the subsequent aziridination process.
remained high. Apparently, the increase of the bulkiness on the side
chain didn’t supply a better chiral environment for the rate-
determining transition state. Notably, the nitrogen atom on the
picolyl group of sulfide 2f even deteriorated the ee from 89% to 56%.
8a was then reduced with an excess amount of LiAlH4 in THF to
25
afford deprotected aziridine 9a with dextrorotation ([
a]
þ103ꢀ),
D
of which the (S,S)-enantiomer has been reported to be levorotatory
25
([a
]
ꢁ105ꢀ).7 Therefore, the absolute stereochemistry of 8a was
D
determined as (R,R) (Scheme 2).
Scheme 2. Deprotection of aziridine 8a for absolute configuration determination.
The catalytic cycle is proposed in Fig. 2 to provide a mechanistic
rationale for the high asymmetric induction observed in this azir-
idination. The sulfide is initially transformed to sulfonium salts I,
which is then subsequently deprotonated by base to provide the
corresponding ylide II. Intermediate IIb should be favored as the
phenyl group pointing at equatorial position is located away from
the bulky substituent of the sulfide. The ylide carbon of IIb then
attacks the Si face of the imine with both diphenylphosphonyl and
phenyl groups pointing away from the congested area to give the
(R,R)-aziridine.
Scheme 1. Syntheses of chiral sulfide catalysts 2ae2f. Reagents and conditions: a)
ArMgBr, THF. b) PTSA(cat.) toluene, 70 ꢀC. c) Shi epoxidation. d) Na2S$9H2O, EtOH,
sonication. e) NaH, RBr, DMF.
2.2. Screening of sulfide catalysts for imino Cor-
eyeChaykovsky reaction and absolute configuration de-
termination of the resulting aziridine 8a
We first compared the catalytic performance of THT-catalysts
2ae2f in the imino CoreyeChaykovsky reaction of cinnamyl bro-
mide and N-diphenylphosphinic aldimine 7a. As shown in Table 1,
2a was the best compound that catalyzed the aziridination smoothly
in acetonitrile in the presence of K2CO3 (entry 1). The reaction was
completed within 24 h, providing trans-aziridine 8a (89% ee) and its
cis-isomer in 82% yield, 66/33 dr. Catalyst 2b (entry 2) was compa-
rable to 2a in terms of both the stereo-chemical outcome and cat-
alytic activity. Sulfides 2ce2e (entries 3e5) mediated the reaction
with lower diastereoselectivity, while the enantioselectivity
Table 1
Screening of sulfide catalysts
Entry
Sulfide
trans/cisa
ee %b
Yield %c
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
66/34
66/34
55/45
59/41
61/39
60/40
89
87
87
90
89
56
82
81
63
66
64
60
Fig. 2. Plausible mechanism of thiolane catalyzed asymmetric aziridination (arrows
may be considered equilibria).
2.3. Screening of reaction solvents
Further optimization of 2a-catalyzed aziridination of cinnamyl
bromide and (E)-N-benzylidene-P,P-diphenylphosphinic amide
(7a) showed that dichloromethane was a slightly better solvent
a
Ratios were determined by 1H NMR.
ee of trans aziridine was determined by HPLC with a Chiralcel-OD column.
Isolated yields of trans and cis isomers.
b
c
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S.-H. Wang, R.-J. Chein / Tetrahedron xxx (2014) 1e9
3
Table 3
Screening of urea catalysts
than acetonitrile (Table 2, entry 2). Reaction in THF and DMF
resulted in much slower reaction rate, albeit DMF led to the highest
stereoselectivity (entries 3 and 4). No reaction happened and the
starting material was recovered when toluene was used (entry 5).
Accordingly, dichloromethane was selected as the optimum solvent
for the following experiments.
Table 2
Entry Urea catalyst
pKa
trans/cisb ee%c Yield%d
a
Effect of solvent on the diastereoselectivity, enantioselectivity, and yield
1
None
NA
68/32
90
78
2
13.8 (Est.) 71/29
13.8 (Est.) 73/27
92
80
Entry
Solvent
trans/cisa
ee (%)b
Yield (%)c
1
2
3
4
5
CH3CN
CH2Cl2
THF
DMF
Toluene
66/34
68/32
65/35
76/24
N/A
89
90
91
92
82
78
12
7
3
4
5
93
86
92
82
N/A
0d
a
Ratios were determined by 1H NMR.
ee of trans aziridine was determined by HPLC with a Chiralcel-OD column.
Isolated yields of trans and cis isomers.
No reaction.
b
c
16.1
8.5
68/32
71/29
76
48
d
2.4. Screening of urea catalysts
As mentioned above, Connon et al. has disclosed that N,N0-dia-
ryl(thio)ureas, especially those incorporating electron deficient
aromatic substituents, are good catalysts for the Cor-
eyeChaykovsky reaction between trimethylsulfonium iodide and
benzaldehyde. We therefore examined the compatibility of ureas
10a and 10b, and thiourea 10c with the aziridination process. We
were delighted to find that higher diastereoselectivity, enantiose-
lectivity, and yield were obtained when 10e20 mol % of N,N0-
bis(3,5-bis(trifluoromethyl)phenyl)urea (10a) was applied to the
optimum protocol (Table 3, entries 2 and 3) whilst urea 10b (entry
4), having a more electron rich phenyl group, showed a slightly
negative effect to the reaction. In agreement with Connon’s results,
the more acidic thiourea 10c (entry 5) was a less active catalyst than
urea 10a, which could be due to the high acidity of the thiourea
derivatives relative to the sulfonium ion.
a
b
c
Ref. 8.
Ratios were determined by 1H NMR.
ee of trans aziridine was determined by HPLC with a Chiralcel-OD column.
Isolated yields of trans and cis isomers.
d
substituted aryl imines 7f, 7m, and 2-naphthalenyl imine 7n was
doubled, and the ee of the resulting products 8f, 8m, and 8n was
improved by 15e22%.
3. Conclusions
We have demonstrated that the dual catalytic system of chiral
sulfide 2a and urea 10a is highly effective for the asymmetric imino
CoreyeChaykovsky reaction of cinnamyl bromide and aryl N-
diphenylphosphinic imines. We believe that this work should pave
the way for the development of new strategies for sulfur-ylide
chemistry.
2.5. Substrate scope
Having developed a highly efficient process for asymmetric
aziridination, we now turned our attention to the question of
substrate scope. Gratifyingly, the dual-catalyst system catalyzed the
reaction of cinnamyl bromide with various imines bearing electron
deficient (7be7f), neutral (7a, 7m, 7n), and electron rich (7ge7l,
7o) aromatic substituents, giving diastereomer- and enantiomer-
enriched aziridines in good to high yields (80e98%). Except for
aziridines 8f, 8g and 8j having moderate to good ee (70e80%), all
other dominant trans products were obtained with high enantio-
selectivity (89e98%). Evidently, the steric effect of the ortho sub-
stituent of the aryl aldimines 7g and 7j eroded the
enantioselectivity of the asymmetric aziridination. However, the
reason why para-nitrile group was detrimental to the stereo-
selectivity is not clear. We have also inspected the substrate scope
of the same reactions in the absence of urea 10a. The results in Table
4 show that 10a indeed universally promoted the asymmetric
sulfonium ylide mediated aziridination in both reaction rate and
stereochemical outcome. Notably, with the assistance of H-bonding
catalyst 10a, the reaction rate of the aziridination of para-
4. Experimental section
4.1. General
All reactions were carried out under an inert atmosphere unless
mentioned otherwise, and standard syringeesepta techniques
were followed. Solvents were freshly dried and purified by con-
ventional methods prior to use. The progress of all the reactions
were monitored by TLC, using TLC glass plates precoated with silica
gel 60 F254 (Merck). Column chromatography was performed on
silica gel GeduranÒ Si 60 (Merck). Optical rotation values were
measured with Jasco P-2000 polarimeter, and IR spectra were
recorded with Thermo Nicolet iS-5 FTIR spectrophotometer, lmax in
cmꢁ1. 1H, 13C and 31P NMR spectra were recorded with Bruker AV-III
400 MHz, Bruker AV-400, or AV-500 MHz spectrometers and
chemical shifts were measured in
solvent peaks as internal standards (CDCl3,
d
(parts per million) with residual
d
7.26 ppm in 1H NMR,
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4
S.-H. Wang, R.-J. Chein / Tetrahedron xxx (2014) 1e9
ESCiÒ (ESI/APCi) source options, Waters LCT premier XE (Waters
Corp., Manchester, UK). Melting points were recorded on Buchi M-
565 apparatus. The determination of ee was performed via chiral
phase HPLC analysis using Agilent 1200 series HPLC workstation.
Table 4
Substrate scope of asymmetric aziridination
4.2. General procedure for the synthesis of (S)-2-((benzyloxy)
diarylmethyl)tetrahydrothiophene 2ae2f
((S)-Thiolan-2-yl)diarylmethanol 1ae1c were prepared accord-
ing the procedures reported by our lab earlier.2 To a stirred solution
of ((S)-thiolan-2-yl)diarylmethanol (3.7 mmol) in DMF (7.4 mL) at
0
ꢀC was added sodium hydride (296 mg, 7.4 mmol). The reaction
mixture was warmed to room temperature and stirred for 1 h. The
corresponding bromide (0.53 mL, 4.4 mmol) was then slowly added
to the reaction mixture. After 16 h, the reaction mixture was
quenched with satd NH4Cl (5 mL) at 0 ꢀC, extracted with Et2O
(5 mLꢂ3), dried over Na2SO4, and concentrated in vacuo. The res-
idue was purified by column chromatography (EtOAc/hexane, 1:49)
to give pure product.
4.2.1. (S)-2-((Benzyloxy)diphenylmethyl)tetrahydrothiophene
(2a).2 White solid; Yieldd92% (1.2 g); Rf (10% EtOAc/hexane) 0.5;
Prepared as shown in general experimental procedure.; 1H NMR
(400 MHz, CDCl3)
d
7.57e7.55 (m, 2H), 7.44 (d, J¼7.2 Hz, 2H),
7.34e7.16 (m,11H), 4.66 (t, J¼7.2 Hz,1H), 4.38 (d, J¼11.6 Hz,1H), 4.21
(d, J¼11.5 Hz, 1H), 2.63 (m, 1H), 2.32 (ddd, J¼10.1, 8.2, 6.1 Hz, 1H),
1.98 (td, J¼12.7, 6.0 Hz, 1H), 1.84 (m, 1H), 1.64 (m, 1H), 1.34 (tt,
J¼11.9, 5.9 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 129.3, 128.8, 128.0,
127.4, 127.2, 127.1, 127.0, 126.9, 126.9, 85.9, 65.5, 53.8, 32.6, 31.6,
30.2.
4.2.2. (S)-2-((Benzyloxy)bis(4-(tert-utyl)phenyl)methyl)tetrahy-
drothiophene (2b). Colorless liquid; Yieldd95% (1.7 g); Rf (2%
EtOAc/hexane) 0.35; Prepared as shown in general experimental
30
procedure; [
a
]
D
5.86 (c 1.0, CHCl3); IR (neat): 3443, 1650, 1538,
1504, 1383, 1176, 1084, 727, 696 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
7.44 (d, J¼8.3 Hz, 2H), 7.38e7.27 (m, 6H), 7.27e7.20 (m, 1H), 7.10
(dd, J¼8.2, 5.1 Hz, 4H), 4.66 (t, J¼7.1 Hz, 1H), 4.37 (d, J¼11.7 Hz, 1H),
4.19 (d, J¼11.7 Hz, 1H), 2.73e2.64 (m, 1H), 2.60 (dd, J¼15.7, 8.0 Hz,
4H), 2.38 (ddd, J¼10.2, 8.0, 6.2 Hz, 1H), 2.01 (td, J¼12.9, 5.9 Hz, 1H),
1.85 (ddd, J¼20.0, 12.9, 7.3 Hz, 1H), 1.76e1.65 (m, 1H), 1.60 (ddd,
J¼19.8, 10.3, 4.8 Hz, 4H), 1.37 (dtd, J¼12.0, 7.4, 5.0 Hz, 5H), 0.93 (td,
J¼7.3, 3.8 Hz, 6H); 13C NMR (100 MHz, CDCl3)
d141.9, 141.7, 140.5,
139.6, 138.7, 129.3, 128.9, 128.1, 127.4, 127.0, 127.0, 126.9, 85.9, 65.5,
54.4, 35.2, 35.2, 33.5, 33.4, 32.7, 31.8, 30.3, 29.7, 22.4, 14.0, 14.0;
HRMS-ESI (m/z): Calcd for C32H40OS [(MþNa)þ] 495.2698, found
[(MþNa)þ] 495.2691.
4.2.3. (S)-2-(Di([1,10:30,100-terphenyl]-50-yl) (benzyloxy)methyl)tetra-
hydrothiophene (2c). White solid; Yieldd93% (2.3 g); Rf (5% EtOAc/
hexane) 0.38; Prepared as shown in general experimental pro-
30
cedure.; Mp 99e101 ꢀC; [
a]
7.44 (c 1.0, CHCl3); IR (neat): 3424,
D
1658,1594,1496,1383,1180,1028, 879, 758, 737, 696 cmꢁ1; 1H NMR
(400 MHz, CDCl3)
d
7.95 (d, J¼1.6 Hz, 2H), 7.81 (dd, J¼3.3, 1.6 Hz,
3H), 7.77 (t, J¼1.6 Hz, 1H), 7.70e7.60 (m, 8H), 7.45 (dd, J¼16.1,
8.6 Hz, 10H), 7.37 (dd, J¼8.3, 6.6 Hz, 6H), 7.32e7.26 (m, 1H), 4.88 (t,
J¼7.2 Hz, 1H), 4.63 (d, J¼11.9 Hz, 1H), 4.52 (d, J¼11.9 Hz, 1H),
2.87e2.76 (m, 1H), 2.53 (ddd, J¼10.2, 8.3, 6.0 Hz, 1H), 2.18 (td,
J¼12.7, 5.9 Hz, 1H), 2.10e1.98 (m, 1H), 1.87e1.73 (m, 1H), 1.64e1.53
d
77 ppm in 13C NMR). Coupling constants J, measured in Hertz.
(m, 1H); 13C NMR (100 MHz, CDCl3)
d 144.3, 142.5, 141.2, 141.3, 141.1,
MALDI-mass spectra were conducted on an Applied Biosystems
4800 Proteomics Analyzer (Applied Biosystem, Foster City) equip-
ped with an Nd/YAG laser (335 nm) operating at a repetition rate of
200 Hz. HR EI (LR EI)-mass spectra were recorded on a JMS-700
double focusing mass spectrometer (JEOL, Tokyo, Japan) with
a resolution of 8000(3000) (5% valley definition) and HR (LR) ESI
(Electrospray)-mass spectra were recorded using dual ionization
141.1, 140.4, 139.3, 128.7, 128.3, 127.3, 127.3, 127.1, 127.0, 126.9, 125.4,
125.1, 86.7, 66.1, 54.3, 33.1, 31.9, 30.4; MALDI (m/z): Calcd for
C
48H40OS [(MþNa)þ] 687.2692, found [(MþNa)þ] 687.2694.
4.2.4. (S)-2-(((4-(tert-Butyl)benzyl)oxy)diphenylmethyl)tetrahy-
drothiophene (2d). Coloress liquid; Yieldd66% (1.0 g); Rf (5% EtOAc/
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S.-H. Wang, R.-J. Chein / Tetrahedron xxx (2014) 1e9
5
hexane) 0.55; Prepared as shown in general experimental pro-
1H), 3.31 (ddd, J¼12.4, 9.6, 2.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
30
cedure.; [
a]
5.41 (c 1.0, CHCl3); IR (neat): 3441, 1650, 1540, 1443,
d
137.2 (d, JCeP¼3.4 Hz), 136.3, 134.8, 133.8 (d, JCeP¼48.1 Hz), 132.6
D
1383, 1077, 752, 699 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
7.66e7.60
(d, JCeP¼42.6 Hz), 131.7, 131.6, 131.5, 131.4, 128.5 (d, JCeP¼2.2 Hz),
128.4, 128.3, 128.3, 128.2, 127.7 (d, JCeP¼1.8 Hz), 126.4, 126.1, 125.9
(d, JCeP¼7.4 Hz), 52.4 (d, JCeP¼7.8 Hz), 43.7 (d, JCeP¼5.2 Hz); 31P
(m, 2H), 7.54e7.47 (m, 2H), 7.40e7.26 (m, 8H), 7.19 (d, J¼8.0 Hz, 2H),
4.74 (t, J¼7.2 Hz, 1H), 4.41 (d, J¼11.3 Hz, 1H), 4.25 (d, J¼11.3 Hz, 1H),
2.79e2.69 (m, 1H), 2.68e2.61 (m, 2H), 2.43 (ddd, J¼10.2, 8.1, 6.1 Hz,
1H), 2.09 (td, J¼12.8, 5.8 Hz, 1H), 1.92 (dddd, J¼13.0, 9.0, 7.1, 5.9 Hz,
1H), 1.83e1.69 (m, 1H), 1.69e1.59 (m, 2H), 1.51e1.34 (m, 3H), 0.98 (t,
NMR (162 MHz, CDCl3)
C
enantioselectivity was determined by HPLC analysis (Chiralcel-OD,
1.0 mL/min, 254 nm, hexane/i-PrOH 20/1); retention time: 10.5 min
(enantiomer) and 20.8 min (major).
d 30.77; HRMS-ESI (m/z): Calcd for
28H24NOP [(MþNa)þ] 444.1493, found [(MþNa)þ] 444.1499;
J¼7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 143.4, 142.2, 141.7, 141.7,
136.4, 135.5, 129.4, 129.0, 128.4, 128.2, 127.8, 127.5, 127.3, 127.1,
127.0, 85.9, 65.5, 53.9, 35.3, 33.6, 32.8, 31.7, 30.3, 22.3, 13.9; MALDI
(m/z): Calcd for C48H40OS [(MþNa)þ] 439.2066, found [(MþNa)þ]
439.2065.
4.3.1.1. cis-8a. White foam; 1H NMR (400 MHz, CDCl3)
d
8.01e7.93 (m, 4H), 7.52e7.16 (m,16H), 6.63 (d, J¼15.9 Hz,1H), 5.78
(dd, J¼15.9, 8.4 Hz, 1H), 4.17 (dd, J¼16.5, 6.2 Hz, 1H), 3.76e3.68 (m,
1H); 13C NMR (100 MHz, CDCl3)
136.4, 135.5, 134.8 (d,
4.2.5. (S)-2-(((Perfluorophenyl)methoxy)diphenylmethyl)tetrahy-
drothiophene (2e). White solid; Yieldd64% (1.1 g); Rf (2% EtOAc/
hexane) 0.48; Prepared as shown in general experimental pro-
d
JCeP¼4.5 Hz), 133.0 (d, JCeP¼37.7 Hz), 132.0, 131.7, 131.6, 131.5, 128.6,
128.5, 128.5, 128.4, 128.2, 127.8, 127.6, 126.4, 123.7 (d, JCeP¼4.8 Hz),
43.5 (d, JCeP¼22.3 Hz), 42.7 (d, JCeP¼24.6 Hz); 31P NMR (162 MHz,
30
cedure.; Mp 65e68 ꢀC; [
a
]
6.07 (c 1.0, CHCl3); IR (neat): 3439,
D
1642, 1504, 1445, 1383, 1129, 1056, 938, 755, 702 cmꢁ1
(400 MHz, CDCl3)
;
1H NMR
CDCl3)
d
33.40; HRMS-MALDI (m/z): Calcd for C28H24NOP [(MþH)þ]
d
7.51 (dt, J¼4.5, 2.5 Hz, 2H), 7.41e7.23 (m, 8H),
422.1668, found [(MþH)þ] 422.1656.
4.62 (t, J¼7.2 Hz, 1H), 4.52 (d, J¼10.1 Hz, 1H), 4.31 (d, J¼10.1 Hz, 1H),
2.79e2.67 (m, 1H), 2.44 (ddd, J¼10.2, 8.3, 6.0 Hz, 1H), 1.98 (td,
J¼12.7, 5.7 Hz, 1H), 1.90e1.78 (m, 1H), 1.72 (dddd, J¼15.1, 12.3, 8.6,
6.2 Hz, 1H), 1.48 (dt, J¼11.6, 5.5 Hz, 1H); 13C NMR (100 MHz, CDCl3)
4.3.2. ((2R,3R)-2-((E)-Styryl)-3-(4-(trifluoromethyl)phenyl)aziridin-
1-yl)diphenylphosphine oxide (8b). White solid; Yieldd80%
(52 mg); Rf (50% EtOAc/hexane) 0.45; Prepared as shown in general
26
d
146.9, 144.4, 142.9, 141.0, 138.6, 136.2, 129.3, 128.6, 127.6, 127.6,
experimental procedure.; Mp 152e156 ꢀC; [
a
]
ꢁ36.59 (c 1.0,
D
127.4, 127.2, 112.1, 86.5, 53.8, 53.5, 32.9, 31.5, 30.3; MALDI (m/z):
CHCl3); IR (neat): 3058, 1619, 1438, 1324, 1166, 1123, 932, 826, 728,
Calcd for
473.0957.
C
24H19OSF5 [(MþNa)þ] 473.0968, found [(MþNa)þ]
693 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
7.95e7.87 (m, 4H),
7.60e7.58 (m, 2H), 7.47e7.26 (m, 13H), 6.71 (dd, J¼16.0, 9.6 Hz, 1H),
6.52 (d, J¼16.0 Hz, 1H), 4.06 (dd, J¼15.6, 2.8 Hz, 1H), 3.30 (ddd,
4.2.6. (S)-2-((Diphenyl(tetrahydrothiophen-2-yl)methoxy)methyl)
J¼12.4, 9.6, 2.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 141.4, 136.1,
pyridine (2f). Colorless liquid; Yieldd71% (950 mg); Rf (10% EtOAc/
135.3, 133.5 (d, JCeP¼60.3 Hz), 132.5, 131.9, 131.6, 131.5, 131.5, 131.4,
130.0 (q, JC-F¼32.1 Hz), 128.5, 128.4, 128.3, 128.0, 126.4 (d,
JCeP¼2.1 Hz), 125.5 (d, JCeP¼3.3 Hz), 125.2 (d, JCeP¼7.2 Hz), 121.3 (d,
JC-F¼270.4 Hz), 52.7 (d, JCeP¼7.6 Hz), 43.0 (d, JCeP¼4.8 Hz); 31P NMR
30
hexane) 0.35; [
a
]
D
6.10 (c 1.0, CHCl3); IR (neat): 3591, 3439, 1650,
1590, 1433, 1383, 1100, 756, 701 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
8.48 (d, J¼4.9 Hz, 1H), 7.72 (td, J¼7.7, 1.8 Hz, 1H), 7.64 (d, J¼7.8 Hz,
1H), 7.58 (dt, J¼4.6, 2.5 Hz, 2H), 7.51e7.43 (m, 2H), 7.38e7.24 (m,
6H), 7.20e7.13 (m, 1H), 4.73 (t, J¼7.2 Hz, 1H), 4.51 (d, J¼13.4 Hz, 1H),
4.40 (d, J¼13.4 Hz, 1H), 2.77e2.66 (m, 1H), 2.41 (ddd, J¼10.2, 8.1,
6.1 Hz, 1H), 2.08 (td, J¼12.8, 5.8 Hz, 1H), 1.95e1.83 (m, 1H), 1.74 (tdd,
J¼8.7, 7.1, 4.3 Hz, 1H), 1.43 (dt, J¼11.8, 5.7 Hz, 1H); 13C NMR
(162 MHz, CDCl3) d 30.89; HRMS-ESI (m/z): Calcd for C29H23NOPF3
[(MþNa)þ] 512.1367, found [(MþNa)þ] 512.1372; enantioselectivity
was determined by HPLC analysis (Chiralcel-AD, 1.0 mL/min,
254 nm, hexane/i-PrOH 4/1); retention time: 12.1 min (enantio-
mer) and 24.8 min (major).
(100 MHz, CDCl3)
d 159.4, 148.6, 142.8, 141.3, 136.5, 129.3, 129.0,
127.5, 127.5, 127.3, 127.1, 121.9, 120.8, 86.3, 66.7, 53.8, 32.7, 31.7, 30.2;
MALDI (m/z): Calcd for C23H23OS [(MþNa)þ] 384.1392, found
[(MþNa)þ] 384.1396.
4.3.2.1. cis-8b. White foam; 1H NMR (400 MHz, CDCl3)
d
8.01e7.92 (m, 4H), 7.59e7.45 (m, 9H), 7.26e7.17 (m, 6H), 6.66 (d,
J¼15.8 Hz, 1H), 5.72 (dd, J¼15.8, 8.3 Hz, 1H), 4.19 (dd, J¼16.2, 5.9 Hz,
1H), 3.81e3.74 (m, 1H); 13C NMR (125 MHz, CDCl3)
139.0, 136.2,
d
4.3. General procedure for the synthesis of aziridine 8ae8o
136.0, 132.5, 132.2, 131.7, 131.6, 131.5, 131.4, 129.8 (q, JC-F¼32.3 Hz),
128.6 (d, JCeP¼3.8 Hz), 128.5, 128.1, 127.9, 126.3, 125.2 (d,
JCeP¼3.1 Hz), 122.6 (d, JCeP¼4.6 Hz), 43.7 (d, JCeP¼5.3 Hz), 42.1 (d,
To a flame-dried Schlenk tube containing K2CO3(67.9 mg,
0.49 mmol), O-benzyl(Thiolan-2-yl)diphenylmethyl ether (11.8 mg,
0.03 mmol), 1,3-bis(3,5-bis(trifluoromethyl)phenyl)urea (7.9 mg,
0.02 mmol), corresponding imine (0.16 mmol) and dichloro-
methane (0.5 mL) were added at room temperature. To the
JCeP¼5.8 Hz); 31P NMR (162 MHz, CDCl3)
d 33.47; HRMS-MALDI (m/
z): Calcd for C29H23NOPF3 [(MþH)þ] 490.1542, found [(MþH)þ]
490.1539.
resulting mixture, cinnamyl bromide (48.5
mL, 0.33 mmol) was
4.3.3. ((2R,3R)-2-(4-Fluorophenyl)-3-((E)-styryl)aziridin-1-yl)diphe-
added and the reaction was monitored by TLC. Upon completion,
the reaction mixture was diluted with dichloromethane (5 mL) and
filtered through CeliteÒ. The filtrate was evaporated in vacuo to
afford the crude product. The crude products were further purified
by column chromatography (EtOAc/hexane, 1:3) to yield the pure
corresponding aziridine.
nylphosphine oxide (8c). White solid; Yieldd95% (65 mg); Rf (30%
EtOAc/hexane) 0.30; Prepared as shown in general experimental
23
procedure.; Mp 147e150 ꢀC; [
a
]
D
ꢁ57.48 (c 1.0, CHCl3); IR(neat):
3058,1606,1511, 1438, 1193, 1125, 932, 840, 753, 693 cmꢁ1; 1H NMR
(400 MHz, CDCl3) 7.92e7.85 (m, 4H), 7.43e7.22 (m, 13H), 7.02 (t,
d
J¼8.4 Hz, 2H), 6.68 (dd, J¼16.0, 9.6 Hz, 1H), 6.50 (d, J¼15.6 Hz, 1H),
3.98 (dd, J¼16.0, 2.8 Hz, 1H), 3.27 (ddd, J¼12.4, 9.6, 2.8 Hz, 1H); 13
C
4.3.1. ((2R,3R)-2-Phenyl-3-((E)-styryl)aziridin-1-yl)diphenylphos-
phine oxide (8a). White solid; Yieldd80% (55 mg); Rf (30% EtOAc/
hexane) 0.43; Prepared as shown in general experimental pro-
NMR (100 MHz, CDCl3)
d
162.4 (d, JC-F¼244.7 Hz), 136.2,134.9, 133.7
(d, JCeP¼61.0 Hz), 132.9, 132.4 (d, JCeP¼55.5 Hz), 131.7, 131.6, 131.5
(d, JCeP¼6.8 Hz), 131.4, 128.5, 128.4, 128.3 (d, JCeP¼4.1 Hz), 128.2,
127.7, 127.6, 126.4, 125.6 (d, JCeP¼7.3 Hz), 115.4 (d, JCeP¼21.6 Hz),
52.3 (d, JCeP¼7.7 Hz), 43.0 (d, JCeP¼5.1 Hz); 31P NMR (162 MHz,
cedure.; Mp 151e152 ꢀC; [
a]
26 ꢁ55.87 (c 1.0, CHCl3); IR (neat): 3061,
D
1637, 1454, 1437, 1193, 1124, 1070, 967, 934, 752, 693 cmꢁ1; 1H NMR
(400 MHz, CDCl3)
d
7.92e7.87 (m, 4H), 7.44e7.20 (m, 16H), 6.73 (dd,
CDCl3)
d
30.81; HRMS-ESI (m/z): Calcd for C28H23NOPF [(MþNa)þ]
J¼16.0, 9.6 Hz, 1H), 6.50 (d, J¼16.0 Hz, 1H), 4.03 (dd, J¼16.0, 2.8 Hz,
462.1399, found [(MþNa)þ] 462.1400; enantioselectivity was
Please cite this article in press as: Wang, S.-H.; Chein, R.-J., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.12.063

6
S.-H. Wang, R.-J. Chein / Tetrahedron xxx (2014) 1e9
determined by HPLC analysis (Chiralcel-OD, 1.0 mL/min, 254 nm,
hexane/i-PrOH 9/1); retention time: 6.9 min (enantiomer) and
21.0 min (major).
133.9 (d, JCeP¼4.2 Hz), 132.7, 132.0, 131.6 (d, JCeP¼9.5 Hz), 131.4 (d,
JCeP¼9.2 Hz), 131.3, 129.2, 128.4, 127.9, 126.3, 122.9, (d, JCeP¼4.4 Hz),
121.5, 43.4 (d, JCeP¼5.4 Hz), 42.0 (d, JCeP¼5.7 Hz); 31P NMR
(162 MHz, CDCl3)
d 33.46; HRMS-MALDI (m/z): Calcd for
4.3.3.1. cis-8c. White foam; 1H NMR (400 MHz, CDCl3)
C
28H23NOPBr [(MþH)þ] 500.0773, found [(MþH)þ] 500.0772.
d
8.01e7.91 (m, 4H), 7.51e7.40 (m, 6H), 7.35e7.31 (m, 2H), 7.27e7.17
(m, 5H), 7.02e6.98 (m, 2H), 6.63 (d, J¼15.9 Hz, 1H), 5.75 (dd, J¼15.9,
4.3.6. 4-((2R,3R)-1-(Diphenylphosphoryl)-3-((E)-styryl)aziridin-2-
yl)benzonitrile (8f). White solid; Yieldd93% (63 mg); Rf (30%
8.4 Hz, 1H), 4.13 (dd, J¼16.6, 6.1 Hz, 1H), 3.75e3.67 (m, 1H); 13C
NMR (100 MHz, CDCl3)
d
162.2 (d, JC-F¼244.5 Hz), 136.2, 135.7, 132.8
EtOAc/hexane) 0.33 Prepared as shown in general experimental
29
(d, JCeP¼5.2 Hz), 132.0, 131.7, 131.6, 131.5, 131.4, 130.5, 129.1 (d,
JCeP¼8.0 Hz), 128.6, 128.5, 128.5, 128.5, 128.4, 127.9, 126.3, 123.2, (d,
JCeP¼4.7 Hz), 115.2 (d, JCeP¼21.5 Hz), 43.4 (d, JCeP¼5.5 Hz), 42.0 (d,
procedure.; Mp 181e182 ꢀC; [
a
]
D
ꢁ10.28 (c 1.0, CHCl3); IR (neat):
3050, 2226, 1640, 1609, 1438, 1194, 1124, 930, 827, 754, 693,
597 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d7.90e7.84 (m, 4H), 7.63e7.61
JCeP¼6.0 Hz); 31P NMR (162 MHz, CDCl3)
d
33.40; HRMS-MALDI (m/
(m, 2H), 7.46e7.41 (m, 4H),7.39e7.30 (m, 4H), 7.28e7.23 (m, 5H),
6.68 (dd, J¼16.0, 9.6 Hz, 1H), 6.52 (d, J¼16.0 Hz, 1H), 4.03 (dd,
J¼15.6, 2.8 Hz, 1H), 3.29 (ddd, J¼12.4, 9.6, 2.8 Hz, 1H); 13C NMR
z): Calcd for C28H23NOPF [(MþH)þ] 440.1574, found [(MþH)þ]
440.1554.
(100 MHz, CDCl3)
d
142.8, 135.9, 135.6, 133.3 (d, JCeP¼67.8 Hz),
4.3.4. ((2R,3R)-2-(4-Chlorophenyl)-3-((E)-styryl)aziridin-1-yl)diphe-
nylphosphine oxide (8d). White solid; Yieldd90% (60 mg); Rf (50%
132.2, 132.0 (d, JCeP¼64.2 Hz), 131.9, 131.7, 131.4, 131.3, 128.5, 128.4
(d, JCeP¼2.4 Hz), 128.3, 128.0, 126.8, 126.4, 124.9 (d, JCeP¼7.1 Hz),
118.6, 111.5, 52.9 (d, JCeP¼7.6 Hz), 42.9 (d, JCeP¼4.8 Hz); 31P NMR
EtOAc/hexane) 0.33; Prepared as shown in general experimental
27
procedure.; Mp 141e145 ꢀC; [
a]
ꢁ35.08 (c 1.0, CHCl3); IR (neat):
(162 MHz, CDCl3) d 30.89; HRMS-ESI (m/z): Calcd for C29H23N2OP
D
3058, 1596, 1493, 1192, 1124, 932, 838, 753, 693, 539 cmꢁ1; 1H NMR
(400 MHz, CDCl3) 7.89e7.85 (m, 4H), 7.44e7.22 (m, 16H), 6.68 (dd,
[(MþH)þ] 447.1620, found [(MþH)þ] 447.1628; enantioselectivity
was determined by HPLC analysis (Chiralcel-AS, 0.7 mL/min,
254 nm, hexane/i-PrOH 9/1); retention time: 19.8 min (major) and
24.8 min (enantiomer).
d
J¼16.0, 9.6 Hz, 1H), 6.50 (d, J¼16.0 Hz, 1H), 3.98 (dd, J¼16.0, 2.8 Hz,
1H), 3.27 (ddd, J¼12.4, 9.6, 2.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
136.2, 135.8, 135.1, 133.6 (d, JCeP¼59.5 Hz), 133.5, 132.4 (d,
JCeP¼54.1 Hz), 131.8, 131.7, 131.5 (d, JCeP¼4.6 Hz), 131.4, 128.5, 128.3,
128.2, 127.8, 127.5, 126.4, 125.5 (d, JCeP¼7.3 Hz), 52.4 (d,
JCeP¼7.8 Hz), 43.0 (d, JCeP¼5.1 Hz); 31P NMR (162 MHz, CDCl3)
4.3.6.1. cis-8f. White solid; Mp 52e54 ꢀC; 1H NMR (400 MHz,
CDCl3)
d 8.00e7.90 (m, 4H), 7.61e7.59 (m, 2H), 7.54e7.40 (m, 8H),
7.27e7.19 (m, 3H), 7.17e7.15 (m, 2H), 6.65 (d, J¼15.9 Hz, 1H), 5.67
d
30.87; HRMS-ESI (m/z): Calcd for C28H23NOPCl [(MþH)þ]
(dd, J¼15.9, 8.3 Hz, 1H), 4.16 (dd, J¼16.0, 6.1 Hz, 1H), 3.82e3.75 (m,
456.1284, found [(MþH)þ] 456.1277; enantioselectivity was de-
termined by HPLC analysis (Chiralcel-AD, 1.0 mL/min, 254 nm,
hexane/i-PrOH 4/1); retention time: 15.7 min (enantiomer) and
33.4 min (major).
1H); 13C NMR (100 MHz, CDCl3)
d
140.5 (d, JCeP¼4.5 Hz),136.4,
135.9, 132.4 (d, JCeP¼10.5 Hz), 132.2, 132.0, 131.6, 131.5 (d,
JCeP¼6.3 Hz), 131.4, 131.1 (d, JCeP¼11.8 Hz), 128.6, 128.5, 128.3, 128.1,
126.3, 122.2, (d, JCeP¼4.6 Hz), 118.6, 111.5, 43.8 (d, JCeP¼5.5 Hz), 42.1
(d, JCeP¼5.7 Hz); 31P NMR (162 MHz, CDCl3)
d 33.46; HRMS-MALDI
4.3.4.1. cis-8d. White foam; 1H NMR (400 MHz, CDCl3)
(m/z): Calcd for C29H23N2OP [(MþH)þ] 447.1621, found [(MþH)þ]
d
8.02e7.92 (m, 4H), 7.51e7.39 (m, 6H), 7.33e7.18 (m, 9H), 6.64 (d,
J¼15.9 Hz, 1H), 5.76 (dd, J¼16.1, 8.5 Hz, 1H), 4.13 (dd, J¼16.2, 6.1 Hz,
1H), 3.78e3.70 (m, 1H); 13C NMR (100 MHz, CDCl3)
136.1, 135.8,
447.1630.
d
4.3.7. ((2R,3R)-2-(2-Methoxyphenyl)-3-((E)-styryl)aziridin-1-yl)di-
133.3, 132.0, 131.6, 131.5 (d, JCeP¼5.7 Hz), 131.4, 128.8, 128.5 (d,
JCeP¼3.6 Hz),128.4,128.4,128.4,127.9,126.3,122.9, (d, JCeP¼4.4 Hz),
43.5 (d, JCeP¼5.4 Hz), 42.0 (d, JCeP¼5.9 Hz); 31P NMR (162 MHz,
phenylphosphine oxide (8g). Colorless liquid; Yieldd92% (62 mg);
Rf (30% EtOAc/hexane) 0.30; Prepared as shown in general experi-
27
mental procedure.; [
a
]
ꢁ62.34 (c 0.9, CHCl3); IR (neat): 3056,
D
CDCl3)
d
33.42; HRMS-MALDI (m/z): Calcd for C28H23NOPCl
1587, 1494, 1438, 1247, 1194, 1124, 935, 754, 693 cmꢁ1
;
1H NMR
[(MþH)þ] 456.1279, found [(MþH)þ] 456.1285.
(400 MHz, CDCl3) 7.95e7.91 (m, 4H), 7.41e7.20 (m, 13H), 6.94 (t,
d
J¼7.6 Hz, 1H), 6.81 (d, J¼8.0 Hz, 1H), 6.73 (dd, J¼16.0, 9.6 Hz, 1H),
6.49 (d, J¼16.0 Hz, 1H), 4.41 (dd, J¼16.0, 2.8 Hz, 1H), 3.69 (s, 3H),
3.25 (ddd, J¼12.4, 9.6, 2.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
4.3.5. ((2R,3R)-2-(4-Bromophenyl)-3-((E)-styryl)aziridin-1-yl)diphe-
nylphosphine oxide (8e). White solid; Yieldd97% (64 mg); Rf (30%
EtOAc/hexane) 0.48 Prepared as shown in general experimental
d
158.3,136.5,134.4,134.2 (d, JCeP¼54.7 Hz),132.9 (d, JCeP¼49.2 Hz),
26
procedure.; Mp 150e153 ꢀC; [
a]
ꢁ3.55 (c 1.0, CHCl3); IR (neat):
131.8, 131.7, 131.6, 131.5, 128.5,128.4,128.3 (d, JCeP¼4.6 Hz),128.1 (d,
JCeP¼4.4 Hz), 127.6, 126.5, 126.4, 125.6, 120.4, 110.2, 55.2, 51.5 (d,
JCeP¼7.6 Hz), 39.4 (d, JCeP¼5.1 Hz); 31P NMR (162 MHz, CDCl3)
D
3439, 1642, 1484, 1383, 1180, 1124, 923, 757, 729, 690, 593 cmꢁ1; 1H
NMR (400 MHz, CDCl3) 7.92e7.84 (m, 4H), 7.46e7.21 (m, 15H),
d
6.67 (dd, J¼16.0, 9.6 Hz, 1H), 6.50 (d, J¼15.6 Hz, 1H), 3.96 (dd,
d
30.53; HRMS-ESI (m/z): Calcd for C29H26NO2P [(MþH)þ] 452.1799,
J¼16.0, 2.8 Hz, 1H), 3.26 (ddd, J¼12.0, 9.2, 2.8 Hz, 1H); 13C NMR
found [(MþH)þ] 452.1781; enantioselectivity was determined by
HPLC analysis (Chiralcel-OD, 1.0 mL/min, 254 nm, hexane/i-PrOH 9/
1); retention time: 9.1 min (enantiomer) and 13.7 min (major).
(100 MHz, CDCl3)
d
136.3, 136.1, 135.0, 133.5 (d, JCeP¼61.0 Hz), 132.3
(d, JCeP¼55.7 Hz), 131.7, 131.6, 131.5 (d, JCeP¼3.7 Hz), 131.3, 128.4,
128.3, 128.2, 127.7, 126.4, 125.4 (d, JCeP¼7.3 Hz), 121.5, 52.3 (d,
JCeP¼7.7 Hz), 43.0 (d, JCeP¼5.0 Hz); 31P NMR (162 MHz, CDCl3)
4.3.7.1. cis-8g. White solid; Mp 53e56 ꢀC; 1H NMR (400 MHz,
CDCl3) d 8.04e7.94 (m, 4H), 7.49e7.39 (m, 7H), 7.26e7.16 (m, 6H),
d
30.45; HRMS-MALDI (m/z): Calcd for C28H23NOPBr[(MþH)þ]
500.0773, found [(MþH)þ] 500.0771; enantioselectivity was de-
termined by HPLC analysis (Chiralcel-OD, 1.0 mL/min, 254 nm,
hexane/i-PrOH 9/1); retention time: 6.8 min (enantiomer) and
26.9 min (major).
6.93 (t, J¼7.2 Hz, 1H), 6.80 (d, J¼8.0 Hz, 1H), 6.63 (d, J¼16.0 Hz, 1H),
5.76 (dd, J¼15.9, 8.4 Hz, 1H), 4.37 (dd, J¼16.4, 6.2 Hz, 1H), 3.82e3.74
(m,1H), 3.18 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 158.4,136.5,135.0,
133.2 (d, JCeP¼42.0 Hz), 132.0, 131.9, 131.8 (d, JCeP¼4.4 Hz), 131.6 (d,
JCeP¼3.3 Hz), 131.5, 128.5, 128.4, 128.3, 127.9, 127.6, 126.3, 124.0 (d,
JCeP¼4.7 Hz), 123.3 (d, JCeP¼4.7 Hz), 119.9, 110.1, 55.2, 43.8 (d,
JCeP¼5.5 Hz), 39.5 (d, JCeP¼5.9 Hz); 31P NMR (162 MHz, CDCl3)
4.3.5.1. cis-8e. White foam; 1H NMR (400 MHz, CDCl3)
d
8.01e7.91 (m, 4H), 7.50e7.39 (m, 8H), 7.26e7.17 (m, 7H), 6.64 (d,
J¼15.9 Hz, 1H), 5.75 (dd, J¼15.9, 8.3 Hz, 1H), 4.11 (dd, J¼16.4, 6.1 Hz,
1H), 3.78e3.70 (m, 1H); 13C NMR (100 MHz, CDCl3)
136.1, 135.9,
d
33.28; HRMS-MALDI (m/z): Calcd for C29H26NO2P [(MþH)þ]
d
452.1774, found [(MþH)þ] 452.1794.
Please cite this article in press as: Wang, S.-H.; Chein, R.-J., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.12.063

S.-H. Wang, R.-J. Chein / Tetrahedron xxx (2014) 1e9
7
4.3.8. ((2R,3R)-2-(3-Methoxyphenyl)-3-((E)-styryl)aziridin-1-yl)di-
phenylphosphine oxide (8h). White solid; Yieldd94% (63 mg); Rf
(50% EtOAc/hexane) 0.50; Prepared as shown in general experi-
(dd, J¼16.0, 2.8 Hz, 1H), 3.20 (ddd, J¼12.4, 9.6, 2.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3)
d
136.7, 136.3, 135.5 (d, JCeP¼3.4 Hz), 132.7, 133.8
(d, JCeP¼75.6 Hz), 132.6 (d, JCeP¼70.6 Hz), 131.7, 131.7, 131.6, 131.5,
129.8, 128.4, 128.4 (d, JCeP¼6.9 Hz), 128.2 (d, JCeP¼6.4 Hz), 127.7,
127.3, 126.4, 126.0 (d, JCeP¼7.7 Hz), 126.0, 124.7, 51.6 (d,
JCeP¼7.6 Hz), 42.0 (d, JCeP¼5.0 Hz), 19.1; 31P NMR (162 MHz, CDCl3)
mental procedure.; Mp 145e146 ꢀC; [
a]
26 ꢁ48.63 (c 1.0, CHCl3); IR
D
(neat): 3056, 1601, 1491, 1438, 1198, 1124, 936, 753, 695 cmꢁ1
;
1H
NMR (400 MHz, CDCl3)
d 7.93e7.88 (m, 4H), 7.43e7.21 (m, 12H),
6.95 (d, J¼7.6 Hz, 1H), 6.88 (s, 1H), 6.82 (dd, J¼8.0, 2.4 Hz, 1H), 6.69
(dd, J¼16.0, 9.6 Hz, 1H), 6.49 (d, J¼16.0 Hz, 1H), 3.99 (dd, J¼16.0,
2.8 Hz, 1H), 3.79 (s, 3H), 3.29 (ddd, J¼12.4, 9.6, 2.8 Hz, 1H); 13C NMR
d
30.69; HRMS-ESI (m/z): Calcd for C29H26NOP[(MþNa)þ] 458.1674,
found [(MþNa)þ] 458.1665; enantioselectivity was determined by
HPLC analysis (Chiralcel-OD, 1.0 mL/min, 254 nm, hexane/i-PrOH 9/
1); retention time: 5.2 min (enantiomer) and 7.9 min (major).
(100 MHz, CDCl3)
d
159.8, 138.9 (d, JCeP¼3.5 Hz), 136.2, 134.8, 133.8
(d, JCeP¼54.9 Hz), 132.5 (d, JCeP¼49.4 Hz), 131.7, 131.6, 131.5, 131.4,
129.5, 128.4, 128.4, 128.3 (d, JCeP¼2.7 Hz), 128.2, 127.7, 126.4, 125.8
(d, JCeP¼7.4 Hz), 118.5, 113.3, 111.5, 55.2, 52.2 (d, JCeP¼7.8 Hz), 43.6
4.3.10.1. cis-8j. White foam; 1H NMR (400 MHz, CDCl3)
d
8.04e7.96 (m, 4H), 7.51e7.42 (m, 6H), 7.37e7.35 (m, 1H),
(d, JCeP¼5.1 Hz); 31P NMR (162 MHz, CDCl3)
d
30.81; HRMS-ESI (m/
7.26e7.08 (m, 8H), 6.64 (d, J¼16.0 Hz, 1H), 5.61 (dd, J¼16.0, 8.7 Hz,
z): Calcd for C29H26NO2P [(MþNa)þ] 474.1599, found [(MþNa)þ]
474.1598; enantioselectivity was determined by HPLC analysis
(Chiralcel-OD, 1.0 mL/min, 254 nm, hexane/i-PrOH 9/1); retention
time: 7.8 min (enantiomer) and 12.5 min (major).
1H), 4.18 (dd, J¼16.2, 6.1 Hz,1H), 3.84e3.76 (m,1H), 2.30 (s, 3H); 13
C
NMR (100 MHz, CDCl3)
d
136.8, 136.3, 135.3, 133.1 (d, JCeP¼4.6 Hz),
132.9 (d, JCeP¼9.6 Hz), 132.0, 131.8, 131.7, 131.6, 131.5, 129.7, 128.5 (d,
JCeP¼6.4 Hz), 128.4, 128.4, 127.8, 127.4, 126.3, 123.8 (d, JCeP¼4.8 Hz),
43.1 (d, JCeP¼5.5 Hz), 41.7 (d, JCeP¼6.1 Hz); 31P NMR (162 MHz,
4.3.8.1. cis-8h. Colorless liquid; 1H NMR (400 MHz, CDCl3)
CDCl3)
d
33.60; HRMS-MALDI (m/z): Calcd for C29H26NOP [(MþH)þ]
d
8.01e7.93 (m, 4H), 7.50e7.39 (m, 6H), 7.26e7.18 (m, 6H), 6.98 (d,
436.1825, found [(MþH)þ] 436.1823.
J¼7.6 Hz, 1H), 6.91 (d, J¼1.9 Hz, 1H), 6.80 (dd, J¼8.1, 2.5 Hz, 1H), 6.64
(d, J¼15.9 Hz, 1H), 5.81 (dd, J¼15.8, 8.4 Hz, 1H), 4.15 (dd, J¼16.3,
6.2 Hz, 1H), 3.76 (s, 3H), 3.74e3.68 (m, 1H); 13C NMR (100 MHz,
4.3.11. ((2R,3R)-2-((E)-Styryl)-3-(m-tolyl)aziridin-1-yl)diphenyl-
phosphine oxid (8k). White solid; Yieldd92% (63 mg); Rf (30%
CDCl3)
d
159.5, 136.5 (d, JCeP¼4.5 Hz), 136.4, 135.5, 133.0, 131.9,
EtOAc/hexane) 0.38 Prepared as shown in general experimental
29
131.7,131.6, 131.5, 129.2,128.5,128.5, 128.4,128.4,127.8, 126.3,123.7
(d, JCeP¼4.4 Hz), 119.9, 113.1 (d, JCeP¼4.9 Hz), 55.2, 43.5 (d,
JCeP¼5.6 Hz), 42.6 (d, JCeP¼6.1 Hz); 31P NMR (162 MHz, CDCl3)
procedure. Mp 144e146 ꢀC; [
a
]
ꢁ74.95 (c 1.0, CHCl3); IR (neat):
D
3057, 1640, 1608, 1438, 1197, 1124, 937, 753, 716, 693 cmꢁ1; 1H NMR
(400 MHz, CDCl3) 7.92e7.88 (m, 4H), 7.43e7.20 (m, 12H), 7.15 (d,
d
d
33.28; HRMS-MALDI (m/z): Calcd for C29H26NO2P [(MþH)þ]
J¼7.6 Hz, 2H), 7.09 (d, J¼7.2 Hz, 1H), 6.70 (dd, J¼16.0, 9.6 Hz, 1H),
452.1774, found [(MþH)þ] 452.1782.
6.49 (d, J¼15.6 Hz, 1H), 3.98 (dd, J¼15.6, 2.8 Hz, 1H), 3.29 (ddd,
J¼12.4, 9.6, 2.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 138.2, 137.2,
4.3.9. ((2R,3R)-2-(4-Methoxyphenyl)-3-((E)-styryl)aziridin-1-yl)di-
phenylphosphineoxide (8i). White solid; Yieldd88% (59 mg); Rf
(50% EtOAc/hexane) 0.50; Prepared as shown in general experi-
136.4, 134.7, 134.0 (d, JCeP¼50.0 Hz), 132.7 (d, JCeP¼44.1 Hz), 131.8,
131.6, 131.6, 131.5, 128.5, 128.3 (d, JCeP¼4.3 Hz), 128.2, 127.7, 127.0,
126.4, 126.0 (d, JCeP¼7.3 Hz), 121.1, 52.3 (d, JCeP¼7.8 Hz), 43.8, 21.4;
mental procedure.; Mp 149e152 ꢀC; [
a]
26 ꢁ42.02 (c 0.8, CHCl3); IR
31P NMR (162 MHz, CDCl3)
d 30.79; HRMS-ESI (m/z): Calcd for
D
(neat): 3050, 1612, 1514, 1438, 1302, 1250, 933, 836, 752, 693 cmꢁ1
;
C
29H26NOP [(MþNa)þ] 458.1650, found [(MþNa)þ] 458.1653;
1H NMR (400 MHz, CDCl3)
d
7.88e7.86 (m, 4H), 7.42e7.21 (m, 13H),
enantioselectivity was determined by HPLC analysis (Chiralcel-OD,
1.0 mL/min, 254 nm, hexane/i-PrOH 9/1); retention time: 6.3 min
(enantiomer) and 12.1 min (major).
6.88e6.86 (m, 2H), 6.70 (dd, J¼16.0, 9.6 Hz, 1H), 6.49 (d, J¼15.6 Hz,
1H), 3.97 (dd, J¼16.0, 2.8 Hz, 1H), 3.80 (s, 3H), 3.28 (ddd, J¼12.4, 9.6,
2.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 159.3, 136.4, 134.6, 133.9
(d, JCeP¼53.2 Hz), 132.7 (d, JCeP¼47.7 Hz), 131.7, 131.6, 131.5, 131.4,
129.2 (d, JCeP¼3.6 Hz), 128.5, 128.4, 128.3 (d, JCeP¼3.2 Hz), 128.2,
127.7, 127.3, 126.4, 126.0 (d, JCeP¼7.4 Hz), 114.0, 55.3, 52.1 (d,
JCeP¼7.8 Hz), 43.5 (d, JCeP¼5.3 Hz); 31P NMR (162 MHz, CDCl3)
4.3.11.1. cis-8k. White foam; 1H NMR (400 MHz, CDCl3)
d
8.01e7.93 (m, 4H), 7.48e7.41 (m, 6H), 7.26e7.14 (m, 8H),
7.07e7.06 (m, 1H), 6.63 (d, J¼15.9 Hz, 1H), 5.80 (dd, J¼16.0, 8.6 Hz,
1H), 4.14 (dd, J¼16.5, 6.1 Hz,1H), 3.75e3.67 (m,1H), 2.32 (s, 3H); 13
C
d
30.79; HRMS-ESI (m/z): Calcd for C29H26NO2P [(MþH)þ] 452.1779,
NMR (100 MHz, CDCl3)
d
137.8, 136.4, 135.5, 134.7 (d, JCeP¼4.4 Hz),
found [(MþH)þ] 452.1782; enantioselectivity was determined by
HPLC analysis (Chiralcel-OD, 1.0 mL/min, 254 nm, hexane/i-PrOH 9/
1); retention time: 7.5 min (enantiomer) and 22.7 min (major).
132.9 (d, JCeP¼10.6 Hz), 131.9, 131.8, 131.7, 131.6, 131.5, 128.5, 128.4,
128.4, 128.3, 128.0, 127.8, 126.3, 124.4, 123.8 (d, JCeP¼4.8 Hz), 43.5
(d, JCeP¼5.5 Hz), 42.6 (d, JCeP¼6.0 Hz); 31P NMR (162 MHz, CDCl3)
d
33.40; HRMS-MALDI (m/z): Calcd for C29H26NOP [(MþH)þ]
4.3.9.1. cis-8i. Colorless liquid; 1H NMR (400 MHz, CDCl3)
436.1825, found [(MþH)þ] 436.1826.
d
8.00e7.91 (m, 4H), 7.50e7.40 (m, 5H), 7.30e7.17 (m, 8H),
6.86e6.84 (m, 2H), 6.62 (d, J¼16.0 Hz, 1H), 5.80 (dd, J¼16.0, 8.4 Hz,
4.3.12. ((2R,3R)-2-((E)-Styryl)-3-(p-tolyl)aziridin-1-yl)diphenylphos-
phine oxide (8l). White solid; Yieldd88% (60 mg); Rf (30% EtOAc/
1H), 4.11 (dd, J¼16.0, 6.8 Hz,1H), 3.79 (s, 3H), 3.72e3.64 (m,1H); 13
C
NMR (100 MHz, CDCl3)
d
159.0, 136.4, 135.4, 131.9, 131.7, 131.6 (d,
hexane) 0.40 Prepared as shown in general experimental pro-
26
JCeP¼4.5 Hz), 131.5, 128.6, 128.4, 127.8, 126.8 (d, JCeP¼5.3 Hz), 126.3,
cedure.; Mp 146e148 ꢀC; [
a
]
ꢁ43.98 (c 1.0, CHCl3); IR (neat):
D
123.8 (d, JCeP¼6.4 Hz), 113.7, 55.2, 43.5 (d, JCeP¼5.4 Hz), 42.3 (d,
3056, 3026, 1682, 1574, 1493, 1392, 1193, 932, 829, 751, 693 cmꢁ1
;
JCeP¼6.8 Hz); 31P NMR (162 MHz, CDCl3)
d
33.30; HRMS-MALDI (m/
1H NMR (400 MHz, CDCl3)
d
7.92e7.87 (m, 4H), 7.42e7.12 (m, 13H),
z): Calcd for C29H26NO2P [Mþ] 451.1696, found [Mþ] 451.1698.
7.15e7.13 (m, 2H) 6.70 (dd, J¼16.0, 9.6 Hz, 1H), 6.48 (d, J¼15.6 Hz,
1H), 3.98 (dd, J¼16.0, 2.8 Hz, 1H), 3.27 (ddd, J¼12.3, 9.6, 2.8 Hz, 1H);
4.3.10. ((2R,3R)-2-((E)-Styryl)-3-(o-tolyl)aziridin-1-yl)diphenylphos-
phine oxide (8j). White solid; Yieldd95% (65 mg); Rf (30% EtOAc/
hexane) 0.40 Prepared as shown in general experimental pro-
13C NMR (100 MHz, CDCl3)
d 137.4, 136.3, 134.6, 133.9 (d,
JCeP¼48.4 Hz), 132.6 (d, JCeP¼42.8 Hz), 131.7, 131.6, 131.5, 131.4,
129.2, 128.4, 128.4, 128.4, 128.3, 128.2, 128.1, 127.6, 126.4, 126.0, 52.3
(d, JCeP¼7.8 Hz), 43.6 (d, JCeP¼5.2 Hz), 21.1; 31P NMR (162 MHz,
cedure.; Mp 144e146 ꢀC; [
a
]
26 ꢁ72.29 (c 1.0, CHCl3); IR(neat): 3075,
D
3058, 1642, 1633, 1438, 1380, 1195, 1124, 951, 933, 751, 729, 693,
CDCl3)
d
30.79; HRMS-ESI (m/z): Calcd for C29H26NOP [(MþH)þ]
593 cmꢁ1; 1H NMR (400 MHz, CDCl3)
(m, 15H), 6.77 (dd, J¼15.6, 9.6 Hz, 1H), 6.51 (d, J¼16.0 Hz, 1H), 4.17
d
8.01e7.96 (m, 4H), 7.46e7.10
436.1830, found [(MþH)þ] 436.1825; enantioselectivity was de-
termined by HPLC analysis (Chiralcel-OD, 1.0 mL/min, 254 nm,
Please cite this article in press as: Wang, S.-H.; Chein, R.-J., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.12.063

8
S.-H. Wang, R.-J. Chein / Tetrahedron xxx (2014) 1e9
hexane/i-PrOH 100/7); retention time: 7.2 min (enantiomer) and
20.2 min (major).
1H), 4.33 (dd, J¼16.4, 6.1 Hz, 1H), 3.85e3.78 (m, 1H); 13C NMR
(100 MHz, CDCl3) d 136.2, 135.7, 133.1, 132.9, 132.8, 132.4 (d,
JCeP¼4.7 Hz), 132.0, 131.7, 131.7, 131.6, 131.5, 128.6, 128.5 (d,
JCeP¼3.3 Hz), 128.4, 127.9, 127.8, 127.7, 126.7, 126.3, 126.2, 125.9,
125.3, 123.5 (d, JCeP¼4.6 Hz), 43.8 (d, JCeP¼5.4 Hz), 42.8 (d,
4.3.12.1. cis-8l. White foam; 1H NMR (400 MHz, CDCl3)
8.00e7.91 (m, 4H), 7.50e7.38 (m, 6H), 7.27e7.17 (m, 7H), 7.11 (d,
d
J¼7.9 Hz, 1H), 6.62 (d, J¼16.0 Hz, 1H), 5.80 (dd, J¼15.9, 8.5 Hz, 1H),
JCeP¼5.9 Hz); 31P NMR (162 MHz, CDCl3)
d 33.57; HRMS-MALDI (m/
4.13 (dd, J¼16.4, 6.2 Hz, 1H), 3.73e3.65 (m, 1H), 2.32 (s, 3H); 13C
z): Calcd for C32H26NOP [(MþH)þ] 472.1825, found [(MþH)þ]
NMR (100 MHz, CDCl3)
131.9, 131.7, 131.6, 131.5, 128.9, 128.5, 128.5, 128.4, 128.3, 127.7, 127.4,
d
137.2, 136.4, 135.4, 133.0 (d, JCeP¼11.0 Hz),
472.1819.
126.3, 123.8 (d, JCeP¼4.7 Hz), 43.5 (d, JCeP¼5.6 Hz), 42.5 (d,
4.3.15. ((2R,3R)-2-(3,4-Dimethoxyphenyl)-3-((E)-styryl)aziridin-1-
yl)diphenylphosphine oxide (8o). White solid; Yieldd95% (63 mg);
JCeP¼6.0 Hz); 31P NMR (162 MHz, CDCl3)
d
33.36; HRMS-MALDI (m/
z): Calcd for C29H26NOP [(MþH)þ] 436.1825, found [(MþH)þ]
Rf (50% EtOAc/hexane) 0.55 Prepared as shown in general experi-
28
436.1831.
mental procedure.; Mp 48e60 ꢀC; [
a
]
ꢁ32.56(c 1.0, CHCl3); IR
D
(neat): 3050, 1640, 1515, 1438, 1124, 1026, 932, 754, 693, 534 cmꢁ1
;
4.3.13. ((2R,3R)-2-([1,10-Biphenyl]-4-yl)-3-((E)-styryl)aziridin-1-yl)
1H NMR (400 MHz, CDCl3)
d
7.93e7.88 (m, 4H), 7.43e7.19 (m, 11H),
diphenylphosphine oxide (8m). White solid; Yieldd91% (59 mg); Rf
6.93e6.91 (m, 1H), 6.83e6.81 (m, 2H), 6.69 (dd, J¼15.6, 9.2 Hz, 1H),
6.52 (d, J¼16.0 Hz, 1H), 3.99 (dd, J¼16.0, 2.8 Hz, 1H), 3.86 (s, 3H),
3.85 (s, 3H), 3.32 (ddd, J¼12.4, 9.6, 2.8 Hz, 1H); 13C NMR (100 MHz,
(30% EtOAc/hexane) 0.35 Prepared as shown in general experi-
27
mental procedure.; Mp 155e158 ꢀC; [
a
]
D
ꢁ6.16 (c 1.0, CHCl3); IR
(neat): 3052, 1642, 1492, 1439, 1194, 1124, 932, 845, 756, 692,
CDCl3)
d
149.0, 148.6, 136.2, 134.7, 133.8 (d, JCeP¼70.7 Hz), 132.5 (d,
602 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.93e7.90 (m, 4H), 7.60e7.56
JCeP¼64.8 Hz), 131.7, 131.6, 131.5, 131.4, 129.6 (d, JCeP¼3.6 Hz), 128.4,
128.2 (d, JCeP¼3.3 Hz), 128.1, 127.7, 126.3, 125.9 (d, JCeP¼7.4 Hz),
118.6, 111.2, 109.3, 55.8 (d, JCeP¼6.0 Hz), 51.8 (d, JCeP¼7.8 Hz), 43.7
(m, 4H), 7.46e7.20 (m, 16H), 6.72 (dd, J¼16.0, 9.6 Hz, 1H), 6.51 (d,
J¼15.6 Hz, 1H), 4.06 (dd, J¼16.0, 2.8 Hz, 1H), 3.34 (ddd, J¼12.4, 9.6,
2.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
140.6 (d, JCeP¼6.8 Hz),
(d, JCeP¼5.2 Hz); 31P NMR (162 MHz, CDCl3)
d 30.89; MALDI (m/z):
136.3, 134.8, 133.8 (d, JCeP¼51.4 Hz), 132.5 (d, JCeP¼45.8 Hz), 131.7,
131.6 (d, JCeP¼3.7 Hz), 131.5, 131.4, 128.8, 128.4 (d, JCeP¼3.0 Hz),
128.3, 128.2, 127.7, 127.3, 127.2, 127.0, 126.5, 126.4, 125.8 (d,
JCeP¼7.3 Hz), 52.4 (d, JCeP¼7.8 Hz), 43.5 (d, JCeP¼5.1 Hz); 31P NMR
Calcd for
C
30H28NO3P [(MþH)þ] 482.1879, found [(MþH)þ]
482.1881; enantioselectivity was determined by HPLC analysis
(Chiralcel-ODH, 1.0 mL/min, 254 nm, hexane/i-PrOH 9/1); retention
time: 12.4 min (enantiomer) and 45.4 min (major).
(162 MHz, CDCl3)
d 30.85; HRMS-ESI (m/z): Calcd for C34H28NOP
[(MþNa)þ] 520.1806, found [(MþNa)þ] 520.1807; enantiose-
lectivity was determined by HPLC analysis (Chiralcel-OD, 1.0 mL/
min, 254 nm, hexane/i-PrOH 4/1); retention time: 5.6 min (enan-
tiomer) and 20.7 min (major).
4.3.15.1. cis-8o. Colorless liquid; 1H NMR (400 MHz, CDCl3)
d
8.00e7.93 (m, 4H), 7.50e7.39 (m, 7H), 7.27e7.18 (m, 5H),
6.93e6.90 (m, 1H), 6.82e6.80 (m, 1H), 6.64 (d, J¼16.0 Hz, 1H), 5.80
(dd, J¼16.0, 8.4 Hz, 1H), 4.12 (dd, J¼16.5, 6.1 Hz, 1H), 3.86 (s,3H),
3.79 (s,1H), 3.72e3.64 (m, 1H); 13C NMR (100 MHz, CDCl3)
d 148.6,
4.3.13.1. cis-8m. White solid; Mp 56e60 ꢀC; 1H NMR (400 MHz,
148.4, 136.3, 135.3, 132.8 (d, JCeP¼28.2 Hz), 132.5, 132.0, 131.7 (d,
JCeP¼11.8 Hz), 131.6, 131.5, 128.9, 128.5, 128.5, 128.4, 127.8, 127.2 (d,
JCeP¼4.5 Hz), 126.3, 123.9 (d, JCeP¼4.6 Hz), 119.8, 110.9 (d,
JCeP¼13.4 Hz), 55.8 (d, JCeP¼5.9 Hz), 43.5 (d, JCeP¼5.6 Hz), 42.3 (d,
CDCl3)
d 8.03e7.95 (m, 4H), 7.60e7.53 (m, 4H), 7.48e7.40 (m, 8H),
7.36e7.32 (m, 1H), 7.26e7.17 (m, 5H), 6.66 (d, J¼15.9 Hz, 1H), 5.85
(dd, J¼15.9, 8.5 Hz, 1H), 4.21 (dd, J¼16.4, 6.1 Hz, 1H), 3.80e3.72 (m,
1H); 13C NMR (100 MHz, CDCl3)
d
140.5 (d, JCeP¼22.3 Hz), 136.3,
JCeP¼5.9 Hz); 31P NMR (162 MHz, CDCl3)
d 33.40; HRMS-MALDI (m/
135.6, 133.9 (d, JCeP¼4.7 Hz), 133.0 (d, JCeP¼7.5 Hz), 132.0, 131.7,
131.6, 131.5, 128.7, 128.6, 128.5, 128.0, 127.8, 127.3 (d, JCeP¼7.5 Hz),
126.3, 123.8 (d, JCeP¼4.7 Hz), 43.6 (d, JCeP¼5.6 Hz), 42.5 (d,
z): Calcd for C30H28NO3P [(MþH)þ] 482.1880, found [(MþH)þ]
482.1870.
JCeP¼6.0 Hz); 31P NMR (162 MHz, CDCl3)
d
33.41; HRMS-MALDI (m/
4.4. (2R,3R)-2-Phenyl-3-((E)-styryl)aziridine (9a)
z): Calcd for C34H28NOP [(MþH)þ] 498.1981, found [(MþH)þ]
498.1968.
To a suspension of LiAlH4 (8.1 mg, 0.21 mmol) in THF (0.2 mL)
under nitrogen at 0 ꢀC, a solutionofaziridine 8a (30mg, 0.07 mmol) in
THF (0.7 mL) was added dropwise. The mixturewas stirred at 0 ꢀC and
monitored by TLC. Upon completion (0.75 h), the reaction mixture
was diluted with satd NH4Cl (1 mL), extracted with EtOAc (5 mLꢂ3),
dried over Na2SO4, and concentrated in vacuo. The residue was pu-
rified by column chromatography (EtOAc/hexane, 1:9) to give 9a as
a colorless liquid (10.2 mg, 65% yield); Rf (30% EtOAc/hexane) 0.58;
4.3.14. ((2R,3R)-2-(Naphthalen-2-yl)-3-((E)-styryl)aziridin-1-yl)di-
phenylphosphine oxide (8n). White solid; Yieldd88% (58 mg); Rf
(30% EtOAc/hexane) 0.45 Prepared as shown in general experi-
29
mental procedure.; Mp 157e160 ꢀC; [
a]
ꢁ18.78(c 1.0, CHCl3); IR
D
(neat): 3056, 1630, 1509, 1437, 1408, 1383, 1195, 1123, 959, 933, 751,
727, 692, 596, 537 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
8.00e7.91 (m,
4H), 7.90e7.80 (m, 4H), 7.51e7.21 (m, 14H), 6.79 (dd, J¼16.0, 9.6 Hz,
1H), 6.54 (d, J¼16.0 Hz, 1H), 4.20 (dd, J¼16.0, 2.8 Hz, 1H), 3.20 (ddd,
[
a
]
25 þ103.1 (c 0.6, CHCl3); 1H NMR (400 MHz, CDCl3)
d 7.38e7.22 (m,
D
10H), 6.71e6.67 (d, J¼16.0 Hz, 1H), 5.95e5.89 (dd, J¼16.0, 8.0, 1H),
J¼12.4, 9.6, 2.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 136.3, 134.9,
3.07e3.06 (d, J¼2.0 Hz, 1H), 2.72e2.70 (d, J¼7.2 Hz, 1H).
134.7 (d, JCeP¼3.4 Hz), 133.8 (d, JCeP¼49.9 Hz), 133.2,133.0, 132.5 (d,
JCeP¼44.3 Hz),131.7,131.6 (d, JCeP¼2.4 Hz), 131.5, 128.5,128.4,128.3,
128.3, 128.2, 127.7, 126.4, 126.3, 125.9, 125.9, 125.8, 125.7, 123.4, 52.3
(d, JCeP¼7.8 Hz), 43.9 (d, JCeP¼5.1 Hz); 31P NMR (162 MHz, CDCl3)
Acknowledgements
We thank Academia Sinica and Ministry of Science and Tech-
nology, Taiwan (MOST-103-2113-M-001-027) for financial support
and the MS laboratory of the Institute of Chemistry, Academia
Sinica for MS analysis.
d
30.93; MALDI (m/z): Calcd for C32H26NOP [(MþH)þ] 472.1824,
found [(MþH)þ] 472.1831; enantioselectivity was determined by
HPLC analysis (Chiralcel-ODH, 1.0 mL/min, 254 nm, hexane/i-PrOH
9/1); retention time: 9.4 min (enantiomer) and 26.7 min (major).
Supplementary data
4.3.14.1. cis-8n. White solid; Mp 55e58 ꢀC; 1H NMR (400 MHz,
CDCl3)
d
8.06e7.98 (m, 4H), 7.84e7.79 (m, 4H), 7.52e7.39 (m, 9H),
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.12.063.
7.26e7.13 (m, 5H), 6.67 (d, J¼15.9 Hz, 1H), 5.84 (dd, J¼16.0, 8.6 Hz,
Please cite this article in press as: Wang, S.-H.; Chein, R.-J., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.12.063

S.-H. Wang, R.-J. Chein / Tetrahedron xxx (2014) 1e9
9
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Y.; Shen, S.; Wang, H.-Y.; Li, Z.-Y.; Huang, Z.-Z. Chem. Lett. 2007, 36, 1436e1437;
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