Bromotriphenylphosphonium salt promoted tandem one-pot cyclization to optically active 2-Aryl-1,3-oxazolines

Article abstract of DOI:10.1002/ejoc.201000162

Optically active 2-aryl-1,3-oxazolines, such as aromatic carbocycles, heterocycle-binding 4-benzyl (or phenyl)-1,3oxazolines and their 5-benzyl (or phenyl)-l,3-oxazoline isomers were successfully prepared through a bromotriphenylphosphonium salt promoted aziridine ring formation and ring opening sequential process involving tandem one pot cyclization of chiral 2-amino-3-phenylpropanol or 2amino-2-phenylethanol with various aromatic acids in toluene at 90 °C in moderate to excellent yields. The mechanism of this tandem process was also substantiated experimentally.

Full text of DOI:10.1002/ejoc.201000162

FULL PAPER
DOI: 10.1002/ejoc.201000162
Bromotriphenylphosphonium Salt Promoted Tandem One-Pot Cyclization to
Optically Active 2-Aryl-1,3-oxazolines
Haizhen Jiang,[a] Shijie Yuan,[a] Wen Wan,[a,b] Kun Yang,[a] Hongmei Deng,[c] and
Jian Hao*[a,b]
Keywords: Heterocycles / Chirality / Cyclization / Amino alcohols
Optically active 2-aryl-1,3-oxazolines, such as aromatic
carbocycles, heterocycle-binding 4-benzyl (or phenyl)-1,3-
oxazolines and their 5-benzyl (or phenyl)-1,3-oxazoline iso-
pot cyclization of chiral 2-amino-3-phenylpropanol or 2-
amino-2-phenylethanol with various aromatic acids in tolu-
ene at 90 °C in moderate to excellent yields. The mechanism
mers were successfully prepared through
a bromotri- of this tandem process was also substantiated experimen-
phenylphosphonium salt promoted aziridine ring formation
and ring opening sequential process involving tandem one-
tally.
efficient, most of these cyclization conditions have draw-
backs in that they use harmful solvents, complicated reac-
tion systems, or produce low yields.
Introduction
Optically active 2-aryl-1,3-oxazoline derivatives, such as
chiral pyridine–oxazoline 1 and thiophene–oxazoline 2, are
frequently employed as chiral ligands in many transition-
metal-catalyzed asymmetric syntheses.[1] Moreover, the 1,3-
oxazoline moiety also widely serves as a fundamental skel-
eton in many bioactive molecules, natural products, and or-
ganomaterials.[2] Bisheterocycles in which the 1,3-oxazoline
unit is bound to another heterocyclic moiety exhibit a
broad spectrum of biological activities with demonstrable
therapeutic value. For example, tubulin polymerization in-
hibitor (A-289099) 3, which contains the 1,3-oxazoline moi-
ety, is an antimitotic agent and exhibits some anticancer
properties (Figure 1).[3] Moreover, some 1,3-oxazoline–aryl
derivatives are also reported to be used as basic materials
for the preparation of organic light-emitting diode de-
vices.[4] Up to now, a number of synthetic methods have
been established for the construction of the 1,3-oxazoline
ring skeleton.[5] Typical methods include the thermal cycli-
zation of N-(2-hydroxyethyl)amide intermediates[6] or cycli-
zations prompted by the Burgess reagent, PPh3/DIAD,
DIC/Cu(OTf)2, DAST/Deoxo-Fluor, or even conducted in
SOCl2.[7] Cyclizations of β-hydroxy carboxylic acid deriva-
tives under certain conditions could also yield the corre-
sponding 1,3-oxazolines.[8] Although these approaches are
Figure 1. Structures of some chiral ligands and bioactive bishetero-
cycles containing a 1,3-oxazoline moiety.
On the other hand, chlorotriphenylphosphonium car-
–
bontrichloride ([Ph3P+Cl]CCl3 ), which is known to be eas-
ily generated in situ by the reaction of triphenylphosphane
with carbon tetrachloride, serves as chlorination reagent
and transforms alcohols and carboxylic acid derivatives
into the corresponding chlorides, acyl chlorides, or imidoyl
–
chlorides,[9] Furthermore, [Ph3P+Cl]CCl3 can also serve as
a reagent for the ring-opening reaction of either activated
or nonactivated aziridines.[10]
Our recent results revealed that the reaction of amino
alcohols with carboxylic acids in the presence of a chlorotri-
phenylphosphonium salt in CCl4 represents a direct and ef-
ficient approach towards aryl-fused oxazoles and oxazol-
ines.[11] However, the overuse of CCl4 in these experiments
raised great environmental concern. Therefore, the develop-
ment of a general, reliable, and environmentally friendly
method for the synthesis of optically active 2-aryl-1,3-oxaz-
olines is still highly desirable.
[a] Department of Chemistry, Shanghai University,
99 Shangda Road, Shanghai 200444, China
Fax: +86-21-66133380
E-mail: jhao@staff.shu.edu.cn
[b] Key Laboratory of Organofluorine Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Lingling Road, Shanghai 200032, China
[c] Instrumental Analysis & Research Center, Shanghai University,
99 Shangda Road, Shanghai 200444, China
In this paper, we wish to report our results on this tan-
dem one-pot approach, which involves bromotriphenyl-
phosphonium salt promoted aziridine ring formation and
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000162.
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H. Jiang, S. Yuan, W. Wan, K. Yang, H. Deng, J. Hao
FULL PAPER
ring opening, to afford optically active 2-aryl-1,3-oxazoline performed better nonpolar solvents, such as toluene. There-
compounds by cyclization of chiral β-amino alcohols with fore, 3 equiv. of CBr4 in toluene at 90 °C was finally chosen
various aromatic heterocyclic acids or carboxylic acids as the optimized conditions for the preparation of 2-aryl-
(Scheme 1).
1,3-oxazolines (Table 1, Entry 7).
Table 1. Optimization conditions for the synthesis of (S)-4-benzyl-
2-(2-naphthyl)-1,3-oxazoline.
Scheme 1. Synthesis of 2-aryl-1,3-oxazolines by a one-pot process.
Entry
CX4
Solvent Time Temp.
Yield [%][a]
6af
[h]
[°C]
6afЈ[b]
1
2
3
4
5
6
7
8
CCl4
CCl4
16
4
3
48
76
1
reflux
reflux
reflux
90
90
reflux
90
90
90
reflux
40
73
82
58
31
11
30
83
71
45
64
30
–
trace
trace
–
–
5
13
10
trace
22
trace
Results and Discussion
CCl4 (10 equiv.) CH3CN
CCl4 (3 equiv.) CH3CN
CCl4 (10 equiv.) toluene
Our previous study has already shown that intramolecu-
lar cyclizations of fluorinated β-hydroxy aryl imidoyl chlo-
ride intermediates, which can be generated in situ by
CCl4 (3 equiv.)
toluene
CBr4 (3 equiv.) CH3CN
CBr4 (3 equiv.) toluene
CBr4 (2 equiv.) toluene
CBr4 (1 equiv.) toluene
CBr4 (3 equiv.) toluene
CBr4 (3 equiv.) toluene
–
[Ph3P+Cl]CCl3 formed from the reaction of PPh3 with a
1
10
10
1
large excess amount of CCl4, could result in the formation
9
10
11
of aryl-ring-fused 1,3-diazoles in good yields.[11]
However, when non-fluorinated aryl acids were used to
replace the fluorinated carboxylic acids, the formation of
the corresponding aryl imidoyl chloride intermediates were
not clearly detected, though the reactions still provided
good formation of 1,3-oxazolines as final products. Instead,
72
[a] Isolated yield. [b] Benzyl-migrated byproducts (S)-5-benzyl-2-
(2-naphthyl)-1,3-oxazoline.
It is noteworthy that the benzyl group migrated byprod-
the formation of N-aroyl aziridines was distinctly observed, uct 6afЈ was also obtained in 5–22% yield under these opti-
and they were separable as relatively stable intermediates mized conditions (Table 1, Entries 6–9); however, only a
in this tandem one-pot cyclization of aromatic acids with trace amount of rearranged byproduct 6afЈ was detected in
aliphatic β-amino alcohols. This initial result revealed that the reaction performed with the use of CCl4 in CH3CN
the cyclizations with fluorinated carboxylic acids or non- (Table 1, Entries 2 and 3). Benzyl migrated byproduct 6afЈ
fluorinated aromatic acids should proceed through different was easily isolated by column chromatography on silica gel
reaction pathways. Carbon tetrachloride in such cyclization (ethyl acetate/petroleum ether, 1:8) with retention of its con-
reactions was used as both the reactant and the solvent, figuration (98%ee). The structure of 6afЈ was also con-
and although it was evident that the overuse of CCl4 repre- firmed by X-ray diffraction. The opposite result was ob-
sents a serious environmental problem, the reactions pro- tained in when (S)-2-amino-2-phenyl-1-ethanol was used in-
vided reasonable results. To reduce the use of CCl4, a paral- stead of (S)-2-amino-3-phenyl-1-propanol under same reac-
lel optimization of the reaction condition was made in two tion conditions (3 equiv. of PPh3/CBr4 at 90 °C). Phenyl
ways (Table 1). One was to use toluene or CH3CN as the group migrated product 6bfЈ was obtained as the major
solvent to replace CCl4. The reaction of (S)-2-amino-3- product (62% yield). Compound 6bf was formed reversely
phenyl-1-propanol (4a) with naphthalene-2-carboxylic acid as the minor product (28% yield, Scheme 2).
(5f) in the presence of 10 equiv. of CCl4 provided (S)-4-ben-
Further study of the mechanism found that intermediate
zyl-2-(2-naphthyl)-1,3-oxazoline (6af) in 82% yield in re- 7bf, which was formed and isolated from the reaction of
fluxing CH3CN (Table 1, Entry 2). Furthermore, the reac- (S)-(+)-2-amino-2-phenyl-1-ethanol with naphthalene-2-
tion time was significantly shortened in CH3CN. In con- carboxylic acid, could undergo quick and quantitative con-
trast, the yield of 6af was reduced to 58% when the volume version into 5-phenyl-1,3-oxazolines 6bfЈ with retention of
of CCl4 was reduced to a theoretical value of 3 equiv. The configuration if treated with one equivalent of the bromo-
other optimization examined was the use of CBr4 as a sub- triphenylphosphonium salt at 90 °C. However, the forma-
stitute for CCl4 as the reactant with the use of toluene or tion of benzyl or phenyl group migrated (rearranged) by-
CH3CN as the solvent. The reaction went to completion product 6Ј was hard to realize in the presence of a chlorotri-
within 1 h in the presence of 3 equiv. of CBr4 in toluene. It phenylphosphonium salt. This showed that the reaction
is quite interesting that the reaction with the use of CCl4 that led to the formation of 6 and rearranged 6Ј should
as the reactant performed better in polar solvents, such as undergo different reaction pathways (Scheme 3, paths A
CH3CN, whereas the reaction with CBr4 as the reactant and B). N-Aroyl aziridine 7 should be a key intermediate
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Tandem One-Pot Cyclization to Optically Active 2-Aryl-1,3-oxazolines
Scheme 2. The reaction of (S)-2-amino-3-phenyl-1-ethanol (4b) with naphthalene-2-carboxylic acid (5f).
Scheme 3. A postulated mechanism for the transformation of β-amino alcohols 4 into 2-aryl-1,3-oxazolines 6 and 6Ј.
and dominate the formation of 6 and its corresponding phenylphosphonium salt was then involved as a nucleophile
structural isomer 6Ј in Path A. On the basis of this con- (equivalent of halide anion) in the subsequent ring-opening
sideration, a proposed mechanism for the formation of 4- reaction of 7. As shown in Scheme 3, if R = benzyl in
benzyl-1,3-oxazolines 6 and 5-benzyl-1,3-oxazolines 6Ј is path A, the halide anion prefers to attack the less sterically
assumed in Scheme 3. A reaction initially occurred between hindered position of 7 (route a) and yields ring-opened in-
chiral β-amino alcohol 4 and salt N to form halogenated termediate 8, which further leads to cyclized 2-aryl-1,3-ox-
1,2-haloamine O. Haloamine O then underwent chemose- azoline 6 as the major product. The regioselective aziridine
lective intramolecular nucleophilic cyclization followed by ring-opening reaction also results in the partial formation
amidation with the aromatic acid to 7 (path A). The halotri- of 6Ј as the minor product if the attacking halide is bro-
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H. Jiang, S. Yuan, W. Wan, K. Yang, H. Deng, J. Hao
Table 2. Synthesis of 2-aryl-1,3-diazolines 6 and 6Ј in the presence of halotriphenylphosphonium salts.[a]
FULL PAPER
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Tandem One-Pot Cyclization to Optically Active 2-Aryl-1,3-oxazolines
Table 2. (Continued)
[a] The reactions were carried in toluene with bromotriphenylphosphonium carbontrichloride (3 equiv.) at 90 °C when X = Br; or in the
refluxing CH3CN solvent with chlorotriphenylphosphonium carbontrichloride (10 equiv.) when X = Cl. [b] Isolated yield after column
chromatography. [c] No benzyl migrated byproducts were observed.
mide. In route b of path A, the configuration of the stereo- group.[12] Thus, as already mentioned, the ring-opening re-
genic center of 7 is inverted twice (ring opening of 7 and action of intermediate 7bf only produced 6bfЈ quantitatively
ring closure of T). This is the reason why the configuration and no 6bf can be detected during this transformation. In
of the stereogenic center of 6Ј is retained. The bromotri- reality, however, we still isolated 6bf in 28% yield when we
phenylphosphonium salt exhibits much more flexibility in start the reaction from (S)-2-amino-2-phenyl-1-ethanol.
this ring-opening and ring-closing process (route b) than This result strongly suggests that 6bf should only be pro-
the chlorotriphenylphosphonium salt. If R = phenyl, re- duced from path B. Similar amidation of intermediate O
arranged product 6bfЈ is experimentally proved as the sole with an aromatic acid should also occur simultaneously to
product from path A. The direct nucleophilic ring-opening form noncyclized amide intermediate 8, which is followed
reaction of 7 at arylmethyl carbon atom has priority as a by ring closure to produce cyclized 6bf. The selective forma-
result of the stabilization of the corresponding SN2 reaction tion of intermediate 7 in path A or noncyclized intermedi-
transition state through p–π conjugation by the aryl ate 8 could competitively depend on the acidity of the aro-
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H. Jiang, S. Yuan, W. Wan, K. Yang, H. Deng, J. Hao
FULL PAPER
matic acid, which dominates its amidation ability. In gene- toluene to provide much shorter reaction times and higher
ral, relatively stronger aromatic acids (smaller pKa value) yields of products. Other β-amino alcohols, such as 2-
prefer to undergo amidation of 1,2-haloamine intermediate amino-2-phenyl-1-ethanol, could also be employed in this
O to form amide intermediate 8 first (path B), but in con- tandem one-pot cyclization.
trast, weaker aromatic acids (larger pKa value) have lower
amidation ability and therefore prefer to undergo aziridina-
tion and to form N-aroyl aziridine 7 first (path A).
Experimental Section
The difficulty of carbon–halogen bond cleavage should
be a crucial point in determining reaction speed. In com-
parison to the strength of the C–Cl bond in chlorinated
intermediate O, the C–Br bond is weaker and is obviously
1
General Comments: H, 13C, and 19F NMR spectra were recorded
1
with a Bruker AV-500 spectrometer. Chemical shifts for H NMR
spectra are reported in ppm downfield from TMS, chemical shifts
for 13C NMR spectra are reported in ppm relative to internal chlo-
much easier to cleave by attack of the nucleophilic amine roform (δ = 77.2 ppm for 13C), and chemical shifts for 19F NMR
spectra are reported in ppm downfield from internal fluorotrichlo-
romethane (CFCl3). Infrared spectra (IR) were recorded as KBr
pellets. Silica gel (200–400 mesh) was used for flash column
chromatography. Elemental analyses were performed with an Ele-
mental Vario EL III instrument. Single-crystal XRD was per-
to form the aziridine (path A). This should be a reason why
the reaction is much faster when CBr4 is used over CCl4.
On the other hand, the weaker nucleophilic chloride anion
shows higher regioselectivity in the attack of the less steri-
cally hindered position of 7. This could possibly be a reason
why structural isomer 6Ј is only detected when weaker aro-
matic acids are used. This hypothesis is consistent with the
results in this tandem reaction.
formed with graphite-monochromatic Mo-Kα radiation (λ
=
0.71073 Å) with a Bruker Smart ApexII CCD diffractometer at T
= 273(2) K. The structures were solved by direct methods with the
SHELXS-97 program and refined by full-matrix least-squares on
F2 with SHELXL-97. All non-hydrogen atoms were refined aniso-
This tandem one-pot cyclization process was generally
applicable to normal aromatic carbocyclic acids and hetero- tropically and hydrogen atoms were located and included at their
calculated position. Optical rotations were recorded on a highly
sensitive polarimeter with a 200-mm cell. The enantiomeric purity
was determined by chiral HPLC (Sino-Chiral AD 0.46 cmϫ25 cm
column, n-hexane/2-propanol as mobile phase).
cyclic acids. Reaction of (S)- or (R)-2-amino-3-phenylpro-
panol or (S)-2-amino-2-phenyl-1-ethanol with different aro-
matic acids under promotion of bromotriphenylphospho-
nium salt in toluene at 90 °C provided moderate to excellent
overall yields of the desired products in a short reaction
times (Table 2). Non-fluorinated aliphatic carboxylic acids
failed to yield target products under the same reaction con-
ditions. Structural isomers 6Ј were isolable, whereas only a
trace amount of 6Ј was detected in cases where CCl4 was
used as the reactant in CH3CN (Table 2). Further applica-
tion of benzyl or phenyl migrated byproducts 6Ј as new
types of chiral ligands has potential. In addition, the chemi-
cal shift of the N–H group in 6am appeared at δ =
CCDC-764713 (for 6afЈ) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
General Procedure for the Preparation of 2-Aryl-1,3-oxazolines 6
with the use of Chlorotriphenylphosphonium Salts: A 200-mL, three-
necked flask equipped with a condenser was charged with Ph3P
(2.20 g, 8.4 mmol), Et3N (0.85 g, 8.4 mmol), CCl4 (4.3 g), substrate
4 (3.3 mmol), and aromatic acid 5 (2.8 mmol) in CH3CN (15.0 mL)
under a nitrogen atmosphere. The solution was stirred for about
10 min at room temperature, and the mixture was then heated at
reflux with stirring for 3–10 h. The solvent was evaporated under
reduced pressure, and the residue was diluted with petroleum ether
(60–90 °C) and filtered. The residual Ph3PO and Et3N·HCl solids
1
10.20 ppm in the H NMR spectrum, which is unusually
downfield shifted. This suggests that a strong hydrogen
bond between the hydrogen and oxygen atoms exists. This
interaction fixes the nitrogen side of the indole ring and the
oxygen side of the 1,3-oxazoline stereoselectively on the were washed with petroleum ether (3ϫ). The filtrate was concen-
trated, and the residue was then purified by column chromatog-
raphy to afford product 6.
same side.
General Procedure for the Preparation of 2-Aryl-1,3-oxazolines 6
and 6Ј with the use of Bromotriphenylphosphonium Salts: A 200-mL,
three-necked flask equipped with a condenser was charged with
Ph3P (2.20 g, 8.4 mmol), Et3N (0.85 g, 8.4 mmol), CBr4 (16.8 g,
8.4 mmol), substrate 4 (3.3 mmol), and aromatic acid 5 (2.8 mmol)
in toluene (15.0 mL) under a nitrogen atmosphere. The solution
was stirred for about 10 min at room temperature, and the mixture
was then heated at 90 °C with stirring for 1–3 h. The solvent was
evaporated under reduced pressure, and the residue was diluted
with petroleum ether (60–90 °C) and filtered. The residual Ph3PO
and Et3N·HCl solids were washed with petroleum ether (3ϫ). The
filtrate was concentrated, and the residue was then separated by
Conclusions
In conclusion, optically active 2-aryl-1,3-oxazolines, such
as aromatic carbocycles, heterocycle-bound 4-benzyl-1,3-
oxazolines, and structural isomers of 5-benzyl-1,3-oxazol-
ines were successfully prepared through a sequential process column chromatography (ethyl acetate/petroleum ether, 1:8) to af-
ford products 6 and 6Ј.
involving aziridine ring formation and ring opening from
the tandem one-pot cyclization of chiral 2-amino-3-phenyl-
propanol with various aryl acids. The reaction can be
(S)-4-Benzyl-2-phenyl-1,3-oxazoline (6aa): Clear oil.[14] Yield:
1
0.46 g, 70%. H NMR (500 MHz, CDCl3): δ = 7.95 (dd, J = 8.0,
mildly promoted by a bromotriphenylphosphonium salt in 1.0 Hz, 2 H, HAr), 7.48–7.45 (m, 1 H, HAr), 7.38–7.41 (m, 2 H,
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Tandem One-Pot Cyclization to Optically Active 2-Aryl-1,3-oxazolines
HAr), 7.30 (d, J = 7.5 Hz, 1 H, HAr), 7.29 (d, J = 7.0 Hz, 1 H, 128.6, 126.5, 120.3, 113.7, 71.8, 67.8, 55.3, 41.9 ppm. IR (KBr): ν =
˜
HAr), 7.25–7.21 (m, 3 H, HAr), 4.61–4.54 (m, 1 H, CH), 4.33 (dd,
J = 8.5, 8.5 Hz, 1 H, OCH2), 4.13 (dd, J = 8.0, 8.0 Hz, 1 H. OCH2),
3.24 (dd, J = 13.5, 5.0 Hz, 1 H, ArCH2), 2.72 (dd, J = 13.5, 8.5 Hz,
1 H, ArCH2) ppm. 13C NMR (125 MHz, CDCl3): δ = 164.1, 138.1,
131.4, 129.4, 128.6, 128.4, 128.3, 127.8, 126.6, 71.9, 67.9, 41.9 ppm.
3024, 2963, 1642, 1605, 1250, 1032, 845, 757, 705 cm–1. C17H17NO2
(267.13): calcd. C 76.38, H 6.41, N 5.24; found C 76.25, H 6.12, N
5.19.
(S)-5-Benzyl-2-(4-methoxyphenyl)-1,3-oxazoline (6acЈ): Thick yel-
low oil. Yield: 0.11 g, 15%. [α]10 = –22.5 (c = 1.070, CHCl3). 1H
NMR (500 MHz, CDCl3): δ = 7.88 (d, J = 9.0 Hz, 2 H, HAr), 7.31
(d, J = 8.0 Hz, 1 H, HAr), 7.30 (d, J = 7.0 Hz, 1 H, HAr), 7.23–
7.25 (m, 3 H, HAr), 6.90 (d, J = 8.5 Hz, 2 H, HAr), 4.85–4.91 (m,
IR (KBr): ν = 3027, 2962, 1649, 1603, 1495, 1450, 1358, 1084, 780,
˜
697 cm–1.
(S)-5-Benzyl-2-phenyl-1,3-oxazoline (6aaЈ): Clear oil. Yield: 0.12 g,
18%. [α]10 = –28.6 (c = 0.826, CHCl3). 1H NMR (500 MHz, 1 H, CH), 4.03 (dd, J = 14.0, 9.0 Hz, 1 H, NCH2), 3.80 (s, 3 H,
CDCl3): δ = 7.96 (dd, J = 8.0 Hz, 2 H, HAr), 7.43–7.50 (m, 1 H,
OCH3), 3.74 (dd, J = 14.5, 7.0 Hz, 1 H, NCH2), 3.08 (dd, J = 14.0,
HAr), 7.41–7.42 (m, 2 H, HAr), 7.33–7.37 (m, 2 H, HAr), 7.27–7.29 7.0 Hz, 1 H, ArCH2), 2.86 (dd, J = 13.5, 6.0 Hz, 1 H, ArCH2) ppm.
(m, 3 H, HAr), 4.92–4.98 (m, 1 H, CH), 4.09 (dd, J = 9.5, 14.5 Hz,
1 H, NCH2), 3.80 (dd, J = 7.0, 14.5 Hz, 1 H, NCH2), 3.12 (dd, J
= 7.5, 14.0 Hz, 1 H, ArCH2), 2.91 (dd, J = 6.0, 14.0 Hz, 1 H,
ArCH2) ppm. 13C NMR (125 MHz, CDCl3): δ = 163.9, 136.9,
131.3, 129.4, 128.7, 128.4, 128.2, 128.0, 126.8, 80.3, 59.6, 41.5 ppm.
13C NMR (125 MHz, CDCl3): δ = 163.7, 162.0, 137.0, 129.9, 129.4,
128.6, 126.7, 120.4, 113.7, 80.1, 59.5, 55.3, 41.5 ppm. IR (KBr): ν
˜
= 3027, 2935, 1647, 1608, 1512, 1256, 1074, 841, 738, 700 cm–1.
C17H17NO2 (267.13): calcd. C 76.38, H 6.41, N 5.24; found C
76.52, H 6.23, N 5.12.
IR (KBr): ν = 3028, 2940, 1649, 1603, 1495, 1451, 1258, 1062, 780,
˜
(S)-4-Benzyl-2-(4-fluorphenyl)-1,3-oxazoline (6ad): Pale-yellow so-
lid. Yield: 0.53 g, 75%. M.p. 46.3–49.5 °C [α]10 = +10.1 (c = 0.801,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.96 (dd, J = 5.0,
2.5 Hz, 1 H, HAr), 7.93 (dd, J = 5.5, 3.0 Hz, 1 H, HAr), 7.31 (d, J
= 7.5 Hz, 1 H, HAr), 7.29 (d, J = 7.5 Hz, 1 H, HAr), 7.21–7.25 (m,
3 H, HAr), 7.01–7.10 (m, 2 H, HAr), 4.54–4.60 (m, 1 H, CH), 4.33
(dd, J = 8.5, 8.5 Hz, 1 H, OCH2), 4.13 (dd, J = 7.5, 8.0 Hz, 1 H,
OCH2), 3.22 (dd, J = 14.0, 5.0 Hz, 1 H, ArCH2), 2.72 (dd, J =
14.0, 9.0 Hz, 1 H, ArCH2) ppm. 19F NMR (470 MHz, CDCl3): δ
= –108.1–108.2 (m) ppm. 13C NMR (125 MHz, CDCl3): δ = 165.8,
697 cm–1. C16H15NO (237.12): calcd. C 80.98, H 6.37, N 5.90;
found C 80.76, H 6.29, N 5.97.
(R)-4-Benzyl-2-(4-nitrophenyl)-1,3-oxazoline [(R)-6ab]: White solid.
Yield: 0.55 g, 71%. M.p. 100.7–101.7 °C. 1H NMR (500 MHz,
CDCl3): δ = 8.26 (d, J = 9.0 Hz, 2 H, HAr), 8.11 (d, J = 9.0 Hz, 2
H, HAr), 7.32 (d, J = 8.0 Hz, 1 H, HAr), 7.30 (d, J = 6.5 Hz, 1 H,
HAr), 7.23–7.26 (m, 3 H, HAr), 4.68–4.62 (m, 1 H, CH), 4.43 (dd,
J = 9.0, 9.0 Hz, 1 H, OCH2), 4.20 (dd, J = 8.0, 8.0 Hz, 1 H, OCH2),
3.23 (dd, J = 14.0, 5.0 Hz, 1 H, ArCH2), 2.79 (dd, J = 14.0, 8.5 Hz,
1 H, ArCH2) ppm. 13C NMR (125 MHz, CDCl3): δ = 162.3, 149.6, 163.8, 163.2, 138.0, 130.6, 130.6, 129.4, 128.7, 126.6, 115.6, 115.5,
137.6, 133.7, 129.4, 128.7, 126.8, 123.6, 72.5, 68.3, 41.7 ppm. IR 72.1, 68.0, 41.9 ppm. IR (KBr): ν = 3028, 2965, 1650, 1604, 1509,
(KBr): ν = 3026, 2954, 1646, 1521, 1338, 1077, 972, 863, 700 cm–1. 1356, 1079, 912, 795, 687 cm–1. C16H14FNO (255.11): calcd. C
˜
˜
C16H14N2O3 (282.10): calcd. C 68.07, H 5.00, N 9.92; found C
67.91, H 5.21, N 9.97.
75.28, H 5.53, N 5.49; found C 75.44, H 5.38, N 5.32.
(S)-5-Benzyl-2-(4-fluorphenyl)-1,3-oxazoline (6adЈ): Pale-yellow so-
lid. Yield: 0.11 g, 15%. M.p. 51.3–52.9 °C. [α]10 = –6.8 (c = 0.500,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.91–7.94 (m, 2 H, HAr),
(S)-4-Benzyl-2-(4-nitrophenyl)-1,3-oxazoline [(S)-6ab]: Pale-green
solid.[14] Yield: 0.57 g, 73%. M.p. 100.7–101.7 °C. [α]10 = +9.2 (c =
0.822, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 8.23 (d, J = 7.30–7.33 (m, 2 H, HAr), 7.23–7.26 (m, 3 H, HAr) 7.05–7.09 (m, 2
9.0 Hz, 2 H, HAr), 8.09 (d, J = 8.5 Hz, 2 H, HAr), 7.32–7.22 (m, 5 H, HAr), 4.90–4.95 (m, 1 H, CH), 4.05 (dd, J = 15.0, 9.5 Hz, 1 H,
H, HAr), 4.67–4.61 (m, 1 H, CH), 4.41 (dd, J = 9.0, 9.0 Hz, 1 H, NCH2), 3.76 (dd, J = 14.5, 7.0 Hz, 1 H, NCH2), 3.08 (dd, J = 14.0,
OCH2), 4.19 (dd, J = 8.0, 8.0 Hz, 1 H, OCH2), 3.22 (dd, J = 14.0,
5.5 Hz, 1 H, ArCH2), 2.78 (dd, J = 13.5, 8.5 Hz, 1 H, ArCH2) ppm.
7.0 Hz, 1 H, ArCH2), 2.88 (dd, J = 14.0, 6.0 Hz, 1 H, ArCH2) ppm.
13C NMR (125 MHz, CDCl3): δ = 165.7, 163.7, 163.0, 136.8, 130.4,
13C NMR (125 MHz, CDCl3): δ = 162.1, 149.5, 137.6, 133.6, 129.3, 129.4, 128.7, 126.8, 124.2, 115.6, 115.4, 80.5, 59.6, 41.5 ppm. 19F
129.2, 128.6, 126.7, 123.5, 72.4, 68.2, 41.6 ppm. IR (KBr): ν = 3026,
NMR (470 MHz, CDCl3): δ = –108.23–108.17 (m) ppm. IR (KBr):
˜
2923, 1647, 1521, 1338, 1257, 1078, 758, 701 cm–1.
ν = 3031, 2951, 1649, 1603, 1506, 1407, 1218, 1068, 846, 733,
˜
699 cm–1. C16H14FNO (255.11): calcd. C 75.28, H 5.53, N 5.49;
found C 76.07, H 5.38, N 5.60.
(S)-4-Benzyl-2-(4-methoxyphenyl)-1,3-oxazoline [(S)-6ac]: Pale-yel-
low solid.[14] Yield: 0.49 g, 66%. M.p. 41.2–42.5 °C [α]10 = +12.8 (c
= 0.641, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.92 (d, J =
(S,S)-1,4-Bis[2-(4-benzyl-1,3-oxazoline)]benzene (6ae): White solid,
8.5 Hz, 2 H, HAr), 7.34 (d, J = 7.5 Hz, 1 H, HAr), 7.32 (d, J = Yield: 0.26 g, 47%. M.p. 122.0–123.9 °C. 1H NMR (500 MHz,
7.0 Hz, 1 H, HAr),7.24–7.29 (m, 1 H, HAr), 6.94 (d, J = 8.5 Hz, 2 CDCl3): δ = 7.99 (s, 4 H, HAr), 7.32 (d, J = 7.5 Hz, 2 H, HAr), 7.30
H, HAr), 4.55–4.61 (m, 1 H, CH), 4.34 (dd, J = 8.0, 8.0 Hz, 1 H, (d, J = 7.5 Hz, 2 H, HAr), 7.22–7.26 (m, 6 H, HAr), 4.58–4.64 (m,
OCH2), 4.14 (dd, J = 7.5, 7.5 Hz, 1 H, OCH2), 3.87 (s, 3 H, OCH3),
3.27 (dd, J = 13.5, 5.0 Hz, 1 H, ArCH2), 2.74 (dd, J = 14.0, 9.0 Hz,
2 H, CH), 4.37 (dd, J = 9.0, 9.0 Hz, 2 H, OCH2), 4.16 (dd, J =
8.0, 8.0 Hz, 2 H, OCH2), 3.25 (dd, J = 14.0, 5.0 Hz, 2 H, ArCH2),
1 H, ArCH2) ppm. 13C NMR (125 MHz, CDCl3): δ = 163.9, 162.2, 2.73 (dd, J = 14.0, 8.5 Hz, 2 H, ArCH2) ppm. 13C NMR (125 MHz,
138.2, 130.1, 129.4, 128.6, 126.6, 120.3, 113.8, 71.9, 55.4, 42.0 ppm.
CDCl3): δ = 163.6, 138.0, 130.4, 129.4, 128.7, 128.4, 126.7, 72.2,
IR(KBr): ν = 3026, 2959, 1647, 1608, 1255, 1029, 840, 756, 68.1, 41.9 ppm. IR (KBr): ν = 3026, 2986, 1644, 1357, 1081, 762,
˜
˜
701 cm–1.
697 cm–1. C26H24N2O2 (396.18): calcd. C 78.76, H 6.10, N 7.07;
found C 78.57, H 5.94, N 7.12.
(R)-4-Benzyl-2-(4-methoxyphenyl)-1,3-oxazoline [(R)-6ac]: Thick
yellow oil. Yield: 0.46 g, 64%. 1H NMR (500 MHz, CDCl3): δ =
7.89 (d, J = 9.0 Hz, 2 H, HAr), 7.30 (dd, J = 7.5, 7.0 Hz, 2 H, HAr),
(R)-4-Benzyl-2-(2-naphthyl)-1,3-oxazoline [(R)-6af]: White solid.
Yield: 0.64 g, 80%. M.p. 82.3–83.8. [α]25 = –14.9 (c = 1.400,
7.21–7.26 (m, 1 H, HAr), 6.91 (d, J = 9.0 Hz, 2 H, HAr), 4.58–4.52 CHCl3). 1H NMR (500 MHz, CDCl3): δ = 8.45 (s, 1 H, HAr), 8.06
(m, 1 H, CH), 4.32 (dd, J = 8.5, 8.5 Hz, 1 H, OCH2), 4.12 (dd, J (dd, J = 8.5, 1.5 Hz, 1 H, HAr), 7.92–7.86 (m, 3 H, HAr), 7.57–7.51
= 7.0, 8.5 Hz, 1 H, OCH2), 3.85 (s, 3 H, OCH3), 3.24 (dd, J = 14.0,
5.0 Hz, 1 H, ArCH2), 2.72 (dd, J = 13.5, 9.0 Hz, 1 H, ArCH2) ppm.
(m, 2 H, HAr), 7.34–7.25 (m, 5 H, HAr), 4.68–4.62 (m, 1 H, CH),
4.41 (dd, J = 8.5, 9 Hz, 1 H, OCH2), 4.21 (dd, J = 7.5, 8 Hz, 1 H,
13C NMR (125 MHz, CDCl3): δ = 163.8, 162.1, 138.1, 130.0, 129.3, OCH2), 3.30 (dd, J = 14, 5 Hz, 1 H, ArCH2), 2.79 (dd, J = 13.5,
Eur. J. Org. Chem. 2010, 4227–4236
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4233

H. Jiang, S. Yuan, W. Wan, K. Yang, H. Deng, J. Hao
FULL PAPER
9 Hz, 1 H, ArCH2) ppm. 13C NMR (500 MHz, CDCl3): δ = 164.2,
138.1, 134.9, 132.8, 129.4, 129.0, 128.9, 128.7, 128.2, 127.9, 127.7,
3.41 (dd, J = 6.5, 14.0 Hz, 1 H, ArCH2), 3.16 (dd, J = 6.5, 14.0 Hz,
1 H, ArCH2) ppm. 13C NMR (500 MHz, CDCl3): δ = 163.4, 131.1,
130.1, 129.7, 129.5, 128.8, 128.5, 126.9, 126.7, 125.5, 125.4, 80.4,
126.7, 126.6, 125.2, 125.0, 72.1, 68.1, 42.0 ppm. IR: ν = 3055, 2923,
˜
1649, 1365, 1193, 1060, 968, 748, 697 cm–1. C20H17NO (287.13): 60.1, 41.5 ppm. IR (KBr): ν = 3027, 2924, 1654, 1453, 1300, 1194,
˜
calcd. C 83.59, H 5.96, N 4.87; found C 83.66, H 6.13, N 4.65.
736, 698 cm–1. C24H19NO (337.15): calcd. C 85.43, H 5.68, N 4.15;
found C 85.60, H 5.51, N 4.28.
(S)-4-Benzyl-2-(2-naphthyl)-1,3-oxazoline [(S)-6af]: White solid.
Yield: 0.65 g, 83%. M.p. 83.9–85.5 °C.[14] [α]25 = +14.8 (c = 1.450,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 8.44 (s, 1 H, HAr), 8.05
(dd, J = 7.0, 1.5 Hz, 1 H, HAr), 7.90 (d, J = 8.0 Hz, 1 H, HAr),
(S)-4-(4-Benzyl-4,5-dihydrooxazol-2-yl)-fluoren-9-one (6ah): Green
solid. Yield: 0.58 g, 62%. M.p. 111.4–113.6 °C. [α]10 = –23.0 (c =
0.802, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 8.22 (d, J =
7.86 (d, J = 8.0 Hz, 2 H, HAr), 7.49–7.56 (m, 2 H, HAr), 7.22–7.33 7.5 Hz, 1 H, HAr), 7.85 (dd, J = 6.5, 1.0 Hz, 1 H, HAr), 7.6 (dd, J
(m, 5 H, HAr), 4.61–4.67 (m, 1 H, CH), 4.40 (dd, J = 8.5, 8.5 Hz,
1 H, OCH2), 4.20 (dd, J = 7.5, 8.5 Hz, 1 H, OCH2), 3.29 (dd, J =
14.0, 5.0 Hz, 1 H, ArCH2), 2.78 (dd, J = 14.0, 9.0 Hz, 1 H,
ArCH2) ppm. 13C NMR (500 MHz, CDCl3): δ = 164.0, 138.0,
134.7, 132.7, 129.3, 128.9, 128.7, 128.5, 128.1, 127.7, 127.5, 126.5,
= 7.0, 1.0 Hz, 1 H, HAr), 7.67 (ddd, J = 7.0, 1.0, 0.5 Hz, 1 H, HAr),
7.40 (ddd, J = 7.5, 7.5, 1.0 Hz, 1 H, HAr), 7.31–7.36 (m, 6 H, HAr),
7.26–7.30 (m, 1 H, HAr), 4.75–4.81 (m, 1 H, CH), 4.48 (dd, J =
8.5, 9.5 Hz, 1 H, OCH2), 4.24 (dd, J = 7.5, 8.5 Hz, 1 H, OCH2),
3.24 (dd, J = 14.0, 5.5 Hz, 1 H, ArCH2), 2.95 (dd, J = 14.0, 7.5 Hz,
1 H, ArCH2) ppm. 13C NMR (500 MHz, CDCl3): δ = 162.9, 157.5,
143.5, 142.6, 141.5, 136.8, 129.4, 128.9, 127.2, 50.4, 38.8, 36.8 ppm.
125.1, 124.9, 71.9, 67.9, 41.8 ppm. IR (KBr): ν = 3026, 2981, 1649,
˜
1363, 1259, 1057, 968, 748, 697 cm–1.
IR (KBr): ν = 3039, 2925, 1657, 1547, 1520, 1194, 984, 875,
˜
(R)-5-Benzyl-2-(2-naphthyl)-1,3-oxazoline [(R)-6afЈ]: White solid.
Yield: 0.11 g, 13%. M.p. 82.8–83.8 °C. [α]25 = +14.4 (c = 1.050,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 8.44 (s, 1 H, HAr), 8.03
735 cm–1. C23H17NO2 (339.13): calcd. C 81.40, H 5.05, N 4.13;
found C 81.54, H 4.97, N 4.09.
(d, J = 8.5 Hz, 1 H, HAr), 7.92 (d, J = 8 Hz, 1 H, HAr), 7.87 (dd, (S)-5-(4-Benzyl-4,5-dihydrooxazol-2-yl)-fluoren-9-one (6ahЈ): Pale-
J = 8.5, 3 Hz, 2 H, HAr), 7.57–7.51 (m, 2 H, HAr), 7.37–7.27 (m, 5
H, HAr), 5.05–4.99 (m, 1 H, CH), 4.14 (dd, J = 14.5, 15 Hz, 1 H,
NCH2), 3.85 (dd, J = 14.5, 14.5 Hz, 1 H, NCH2), 3.18 (dd, J = 14,
green solid. Yield: 0.10 g, 10%. M.p. 124.6–126.1 °C. [α]10 = –53.4
(c = 0.550, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 8.27 (d, J =
8.0 Hz, 1 H, HAr), 7.84 (dd, J = 8.0, 1.5 Hz, 1 H, HAr), 7.77 (dd,
7 Hz, 1 H, ArCH2), 2.96 (dd, J = 14, 6 Hz, 1 H, ArCH2) ppm. 13C J = 7.5, 1.0 Hz, 1 H, HAr), 7.68 (dd, J = 7.0, 1.0 Hz, 1 H, HAr),
NMR (500 MHz, CDCl3): δ = 164.1, 136.9, 134.8, 132.8, 129.5,
129.0, 128.8, 128.3, 127.9, 127.6, 126.9, 126.7, 125.3, 124.9, 80.5,
7.42 (ddd, J = 7.5, 7.5, 1.0 Hz, 1 H, HAr), 7.35–7.25 (m, 7 H, HAr),
5.11–5.05 (m, 1 H, CH), 4.25 (dd, J = 15.0, 10.0 Hz, 1 H, NCH2),
3.95 (dd, J = 14.5, 7.0 Hz, 1 H, NCH2), 3.16 (dd, J = 14.0, 6.5 Hz,
1 H, ArCH2), 3.04 (dd, J = 14.0, 6.0 Hz, 1 H, ArCH2) ppm. 13C
NMR (125 MHz, CDCl3): δ = 193.4, 163.0, 143.8, 143.1, 136.4,
136.2, 135.5, 135.0, 134.4, 129.6, 129.5, 128.8, 128.7, 127.1, 126.3,
59.8, 41.6 ppm. IR: ν = 3060, 2924, 1644, 1354, 1271, 1061, 968,
˜
754, 706 cm–1. C20H17NO (287.13): calcd. C 83.59, H 5.96, N 4.87;
found C 83.47, H 5.77, N 4.69.
(S)-5-Benzyl-2-(2-naphthyl)-1,3-oxazoline [(S)-6afЈ]: White solid.
Yield: 0.11 g, 14%. M.p. 82.3–84.1 °C. [α]25 = –14.1 (c = 1.000,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 8.48 (s, 1 H, HAr), 8.08
(d, J = 8.5 Hz, 1 H, HAr), 7.94 (d, J = 7.5 Hz, 1 H, HAr), 7.89 (d,
126.2, 124.4, 124.1, 80.2, 60.0, 41.4 ppm. IR: ν = 3063, 2927, 1716,
˜
1646, 1565, 1239, 1114, 740, 697 cm–1. C23H17NO2 (339.13): calcd.
C 81.40, H 5.05, N 4.13; found C 81.26, H 4.93, N 4.37.
J = 8.5 Hz, 1 H, HAr), 7.87 (d, J = 8.5 Hz, 1 H, HAr), 7.52–7.58 (S)-4-Benzyl-2-(2-thienyl)-1,3-oxazoline (6ai): Yellow oil.[19] Yield:
(m, 2 H, HAr), 7.38 (d, J = 7.5 Hz, 1 H, HAr), 7.36 (d, J = 7.0 Hz, 0.41 g, 61%. [α]10 = +23.1 (c = 0.806, CHCl3). 1H NMR (500 MHz,
1 H, HAr), 7.29–7.32 (m, 3 H, HAr), 4.98–5.04 (m, 1 H, CH), 4.15 CDCl3): δ = 7.58 (d, J = 3.5 Hz, 1 H, HAr), 7.42 (dd, J = 5.0,
(dd, J = 15.0, 9.5 Hz, 1 H, NCH2), 3.87 (dd, J = 15.0, 7.5 Hz, 1 1.0 Hz, 1 H, HAr), 7.30 (d, J = 8.5 Hz, 1 H, HAr), 7.28 (d, J =
H, NCH2), 3.18 (dd, J = 14.0, 7.0 Hz, 1 H, ArCH2), 2.96 (dd, J =
14.0, 6.5 Hz, 1 H, ArCH2) ppm. 13C NMR (125 MHz, CDCl3): δ
= 164.0, 136.8, 134.7, 132.7, 129.4, 128.9, 128.7, 128.2, 127.8, 127.5,
6.5 Hz, 1 H, HAr), 7.21–7.23 (m, 3 H, HAr), 7.05 (dd, J = 5.0,
3.5 Hz, 1 H, HAr), 4.58–4.52 (m, 1 H, CH), 4.30 (dd, J = 9.0,
9.0 Hz, 1 H, OCH2), 4.12 (dd, J = 8.0 8.0 Hz, 1 H, OCH2), 3.24
(dd, J = 14.0, 5.0 Hz, 1 H, ArCH2), 2.71 (dd, J = 14.0, 9.0 Hz, 1
H, ArCH2) ppm. 13C NMR (125 MHz, CDCl3): δ = 159.7, 137.8,
130.4, 130.3, 129.9, 129.3, 128.6, 127.6, 126.6, 72.2, 68.0, 41.7 ppm.
126.8, 126.5, 125.2, 124.8, 80.4, 59.7, 41.5 ppm. IR (KBr): ν = 3060,
˜
2924, 1643, 1625, 1353, 1192, 1060, 967, 753, 705 cm–1. C20H17NO
(287.13): calcd. C 83.59, H 5.96, N 4.87; found C 83.34, H 5.87, N
4.59.
IR (KBr): ν = 3027, 2924, 1648, 1432, 1256, 1058, 852, 702 cm–1.
˜
(S)-4-Benzyl-2-(9-anthryl)-1,3-oxazoline (6ag): Pale-green solid.
Yield: 0.69 g, 75%. M.p. 93.5–96.1 °C.[17] 1H NMR (500 MHz,
CDCl3): δ = 8.54 (s, 1 H, HAr), 8.06 (d, J = 8.0 Hz, 2 H, HAr), 8.02
(d, J = 7.5 Hz, 2 H, HAr), 7.48–7.55 (m, 4 H, HAr), 7.40 (d, J =
(S)-5-Benzyl-2-(2-thienyl)-1,3-oxazoline (6aiЈ): Yellow oil. Yield:
0.08 g, 12%. [α]10 = –16.1 (c = 0.816, CHCl3). 1H NMR (500 MHz,
CDCl3): δ = 7.58 (d, J = 3.0 Hz, 1 H, HAr), 7.45 (d, J = 5.0 Hz, 1
H, HAr), 7.33 (d, J = 8.0 Hz, 1 H, HAr), 7.31 (d, J = 7.0 Hz, 1 H,
8.0 Hz, 2 H, HAr), 7.34–7.35 (m, 3 H, HAr), 5.03–5.00 (m, 1 H, HAr), 7.25–7.27 (m, 3 H, HAr), 7.07 (dd, J = 5.0, 1.0 Hz, 1 H, HAr),
CH), 4.64 (dd, J = 9.0, 9.0 Hz, 1 H, OCH2), 4.45 (dd, J = 8.0, 4.91–4.97 (m, 1 H, CH), 4.05 (dd, J = 14.5, 9.5 Hz, 1 H, NCH2),
8.0 Hz, 1 H, OCH2), 3.41 (dd, J = 14.0, 5.0 Hz, 1 H, ArCH2), 3.16
(dd, J = 13.0, 7.5 Hz, 1 H, ArCH2) ppm. 13C NMR (500 MHz,
CDCl3): δ = 163.5, 137.6, 131.1, 130.1, 129.9, 129.6, 128.8, 128.6,
3.77 (dd, J = 14.5, 6.5 Hz, 1 H, NCH2), 3.13 (dd, J = 14.0, 7.0 Hz,
1 H, ArCH2), 2.90 (dd, J = 14.0, 6.5 Hz, 1 H, ArCH2) ppm. 13C
NMR (125 MHz, CDCl3): δ = 159.8, 136.7, 130.7, 130.3, 129.9,
126.8, 126.8, 125.5, 125.4, 122.8, 71.6, 68.6, 41.7 ppm. IR (KBr): ν
129.5, 128.7, 127.7, 126.9, 80.9, 59.7, 41.4 ppm. IR (KBr): ν = 3027,
˜
˜
= 3063, 2989, 1657, 1598, 1453, 1194, 984, 735, 679 cm–1.
2926, 1646, 1604, 1523, 1432, 1252, 1057, 966, 853, 746, 699 cm–1.
C14H13NOS (243.07): calcd. C 69.11, H 5.39, N 5.76; found C
69.35, H 4.97, N 5.98.
(S)-4-Benzyl-2-(9-anthryl)-1,3-oxazoline (6agЈ): Pale-green oil.
Yield: 0.10 g, 11%. [α]10 = –18.6 (c = 0.802, CHCl3)1H NMR
(500 MHz, CDCl3): δ = 8.54 (s, 1 H, HAr), 8.08 (d, J = 8.0 Hz, 2
H, HAr), 8.02 (d, J = 7.5 Hz, 2 H, HAr), 7.47–7.53 (m, 4 H, HAr),
7.27–7.32 (m, 5 H, HAr), 5.21–5.27 (m, 1 H, CH), 4.41 (dd, J =
10.0, 14.5 Hz, 1 H, NCH2), 4.14 (dd, J = 8.0, 15.0 Hz, 1 H, NCH2),
(S)-4-Benzyl-2-(2-furyl)-1,3-oxazoline [(S)-6aj]: Yellow oil. Yield:
0.48 g, 76%. [α]10 = +21.9 (c = 0.806, CHCl3). 1H NMR (500 MHz,
CDCl3): δ = 7.50 (dd, J = 1.5, 1.0 Hz, 1 H, HAr), 7.28–7.17 (m, 5
H, HAr), 6.92 (dd, J = 3.5, 1.0 Hz, 1 H, HAr), 6.43 (dd, J = 3.5,
4234
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4227–4236

Tandem One-Pot Cyclization to Optically Active 2-Aryl-1,3-oxazolines
2.0 Hz, 1 H, HAr), 4.58–4.52 (m, 1 H, CH), 4.26 (dd, J = 9.0,
8.5 Hz, 1 H, OCH2), 4.06 (dd, J = 9.0, 8.5 Hz, 1 H, OCH2), 3.24
(dd, J = 13.5, 5.0 Hz, 1 H, ArCH2), 2.70 (dd, J = 13.5, 9.0 Hz, 1
(dd, J = 14.0, 5.5 Hz,1 H, ArCH2), 2.82 (dd, J = 14.0, 8.5 Hz, 1
H, ArCH2) ppm. 13C NMR (500 MHz, CDCl3): δ = 159.7, 137.6,
129.3, 128.5, 127.8, 126.6, 125.4, 124.4, 122.0, 120.3, 111.7, 106.6,
H, ArCH2) ppm. 13C NMR (125 MHz, CDCl3): δ = 155.9, 144.9, 72.3, 67.5, 41.9 ppm. IR (KBr): ν = 3064, 2963, 1651, 1598, 1426,
˜
142.7, 137.5, 128.9, 128.3, 126.2, 114.1, 111.2, 71.6, 67.5, 41.3 ppm.
1242, 1191, 702, 698 cm–1.
IR (KBr): ν = 3027, 2903, 1670, 1622, 1483, 1169, 1093, 966, 752,
˜
(S)-4-Phenyl-2-(2-naphthyl)-1,3-oxazoline (6bf): White solid. Yield:
0.20 g, 28%. M.p. 110.6–112.0.[15] [α]25 = –55.5 (c = 1.016, CHCl3).
1H NMR (500 MHz, CDCl3): δ = 8.55 (s, 1 H, HAr), 8.14 (dd, J =
8.5, 1.5 Hz, 1 H, HAr), 7.94–7.88 (m, 3 H, HAr), 7.59–7.52 (m, 2
H, HAr), 7.40–7.31 (m, 5 H, HAr), 5.45 (dd, J = 10.0, 10.0 Hz, 1
H, OCH2), 4.87 (dd, J = 10.0, 10.0 Hz, 1 H, OCH2), 4.35 (t, J =
8.0 Hz, 1 H, CH) ppm. 13C NMR (500 MHz, CDCl3): δ = 165.0,
142.5, 135.0, 132.8, 129.2, 129.1, 128.9, 128.3, 127.9, 127.8, 127.7,
704 cm–1. C14H13NO2 (227.09): calcd. C 73.99, H 5.77, N 6.16;
found C 74.08, H 5.81, N 6.35.
(R)-4-Benzyl-2-(2-furyl)-1,3-oxazoline [(R)-6aj]: Yellow oil. Yield:
0.46 g, 75%. 1H NMR (500 MHz, CDCl3): δ = 7.55 (d, J = 1.0 Hz,
1 H, HAr), 7.31 (d, J = 8.5 Hz, 1 H, HAr), 7.30 (d, J = 8.0 Hz, 1
H, HAr), 7.23–7.24 (m, 3 H, HAr), 6.95 (d, J = 3.5 Hz, 1 H, HAr),
6.49 (dd, J = 3.5, 1.0 Hz, 1 H, HAr), 4.56–4.62 (m, 1 H, CH), 4.32
(dd, J = 8.5, 8.5 Hz, 1 H, OCH2), 4.12 (dd, J = 8.0, 8.0 Hz, 1 H,
OCH2), 3.28 (dd, J = 14.0, 5.0 Hz, 1 H, ArCH2), 2.72 (dd, J =
13.5, 9.0 Hz, 1 H, ArCH2) ppm. 13C NMR (125 MHz, CDCl3): δ
= 156.2, 145.2, 142.9, 137.7, 129.1, 128.5, 126.5, 114.4, 111.4, 71.9,
127.0, 126.7, 125.1, 125.0, 75.1, 70.4 ppm. IR: ν = 3026, 2912, 1642,
˜
1361, 1194, 1064, 757, 694 cm–1.
(S)-5-Phenyl-2-(2-naphthyl)-1,3-oxazoline (6bfЈ): White solid. Yield:
0.44 g, 62%. M.p. 73.2–76.7 °C.[15] [α]25 = +28.4 (c = 0.984,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 8.53 (s, 1 H, HAr), 8.12
(dd, J = 8.5, 1.5 Hz, 1 H, HAr), 7.93–7.87 (m, 3 H, HAr), 7.58–7.51
(m, 2 H, HAr), 7.41–7.34 (m, 5 H, HAr), 5.73 (dd, J = 10.0, 10.0 Hz,
1 H, NCH2), 4.55 (dd, J = 15.0, 10.0 Hz, 1 H, NCH2), 4.07 (dd, J
= 15.0, 8.0 Hz, 1 H, CH) ppm. 13C NMR (500 MHz, CDCl3): δ =
164.3, 141.2, 134.9, 132.8, 129.1, 129.0, 128.9, 128.5, 128.4, 128.0,
67.8, 41.6 ppm. IR (KBr): ν = 3027, 2903, 1670, 1622, 1169, 1093,
˜
752, 704 cm–1. C14H13NO2 (227.09): calcd. C 73.99, H 5.77, N 6.16;
found C 73.71, H 5.62, N 6.29.
(S)-5-Benzyl-2-(2-furyl)-1,3-oxazoline (6ajЈ): Yellow oil. Yield:
0.08 g, 13%. [α]10 = –14.5 (c = 1.090, CHCl3). 1H NMR (500 MHz,
CDCl3): δ = 7.53 (d, J = 1.0 Hz, 1 H, HAr), 7.23–7.33 (m, 5 H,
HAr), 6.93 (d, J = 3.5 Hz, 1 H, HAr), 6.47 (dd, J = 3.5, 2.0 Hz, 1
H, HAr), 4.89–4.94 (m, 1 H, CH), 4.05 (dd, J = 15.0, 9.5 Hz, 1 H,
NCH2), 3.77 (dd, J = 14.5, 7.0 Hz, 1 H, NCH2), 3.11 (dd, J = 14.0,
6.5 Hz, 1 H, ArCH2), 2.88 (dd, J = 14.0, 7.0 Hz, 1 H, ArCH2) ppm.
13C NMR (125 MHz, CDCl3): δ = 156.3, 145.2, 143.2, 136.5, 129.4,
127.7, 126.7, 126.0, 125.0, 124.9, 81.3, 63.5 ppm. IR: ν = 3033,
˜
2927, 1641, 1354, 1191, 1062, 962, 761, 699 cm–1.
2-(2-Naphthyl)-5,6-dihydro-4H-[1,3]oxazine (6cf): Yellow oil.[20]
1
Yield: 0.64 g, 55%. H NMR (500 MHz, CDCl3): δ = 8.40 (s, 1 H,
HAr), 8.03 (dd, J = 8.5, 2.0 Hz, 1 H, HAr), 7.90 (d, J = 7.0 Hz, 1
H, HAr), 7.89 (d, J = 7.0 Hz, 1 H, HAr), 7.83 (d, J = 8.5 Hz, 2 H,
128.7, 126.9, 114.2, 111.5, 80.6, 59.4, 41.2 ppm. IR (KBr): ν = 3028,
˜
2940, 1671, 1649, 1483, 1265, 1091, 753, 702 cm–1. C14H13NO2
(227.09): calcd. C 73.99, H 5.77, N 6.16; found C 73.67, H 5.58, N
6.28.
HAr), 7.52–7.46 (m, 2 H, HAr), 4.40 (t, J = 5.5 Hz, 2 H, OCH2),
3.66 (t, J = 6.0 Hz, 2 H, NCH2), 1.98–2.02 (m, 2 H, CH2) ppm.
13C NMR (125 MHz, CDCl3): δ = 155.7, 134.4, 132.9, 131.4, 129.0,
127.7, 127.7, 127.0, 126.2, 124.2, 65.4, 42.9, 22.0 ppm.
(R)-5-(4-Benzyl-4,5-dihydrooxazol-2-yl)-2,3-dichloropyridine (6ak):
1
Yellow oil. Yield: 0.59 g, 70%. H NMR (500 MHz, CDCl3): δ =
General Procedure for the Preparation of N-Aroyl Aziridine 7 with
the use of Bromotriphenylphosphonium Salts: A 200-mL, three-
necked flask equipped with a condenser was charged with Ph3P
(2.20 g, 8.4 mmol), Et3N (0.85 g, 8.4 mmol), CBr4 (16.8 g,
8.4 mmol), substrate 4 (3.3 mmol), and aromatic acid 5 (2.8 mmol)
in toluene (15.0 mL) under a nitrogen atmosphere. The solution
was stirred for about 10 min at room temperature, and the mixture
was then heated at 90 °C with stirring for 0.5 h. The solvent was
evaporated under reduced pressure, and the residue was diluted
with petroleum ether (60–90 °C) and filtered. The filtrate was con-
centrated, and the residue was then separated by column
chromatography (ethyl acetate/petroleum ether, 1:8) to afford prod-
ucts 7.
(2S)-2-Benzyl-1-(2-naphthoyl)aziridine (7af): Pale-yellow solid.[16]
M.p. 43.6–47.5 °C. [α]25 = +30.3 (c = 0.930, CHCl3);1H NMR
(500 MHz, CDCl3): δ = 8.06 (dd, J = 9.0, 2.0 Hz, 1 H, HAr), 7.87–
7.92 (m, 3 H, HAr), 7.60 (dd, J = 7.5, 1.0 Hz, 1 H, HAr), 7.55 (dd,
J = 7.5, 1.0 Hz, 1 H, HAr), 7.27–7.35 (m, 5 H, HAr), 3.24 (dd, J =
14.0, 5.0 Hz, 1 H, ArCH2), 2.89–2.93 (m, 1 H), 2.84 (dd, J = 14.5,
7.0 Hz, 1 H, ArCH2), 2.62 (d, J = 6.0 Hz, 1 H, NCH2), 2.36 (d, J
= 3.5 Hz, 1 H, NCH2) ppm. 13C NMR (125 MHz, CDCl3): δ =
179.3, 137.4, 135.5, 132.6, 130.5, 129.5, 128.9, 128.7, 128.3, 128.2,
8.79 (d, J = 2.0 Hz, 1 H, HAr), 8.30 (d, J = 2.0 Hz, 1 H, HAr),
7.30–7.33 (m, 2 H, HAr),7.23–7.26 (m, 3 H, HAr), 4.59–4.65 (m, 1
H, CH), 4.40 (dd, J = 9.0, 9.0 Hz, 1 H, OCH2), 4.18 (dd, J = 8.0,
8.5 Hz, 1 H, OCH2), 3.19 (dd, J = 14.0, 5.5 Hz, 1 H, ArCH2), 2.77
(dd, J = 13.5, 8.5 Hz, 1 H, ArCH2) ppm. 13C NMR (125 MHz,
CDCl3): δ = 160.3, 151.7, 146.9, 138.1, 137.4, 130.6, 129.4, 128.8,
126.9, 124.3, 72.5, 68.1, 41.6 ppm. IR (KBr): ν = 3027, 2963, 1654,
˜
1608, 1365, 1264, 1043, 701, 697 cm–1. C15H12Cl2N2O (306.03):
calcd. C 58.65, H 3.94, N 9.12; found C 58.88, H 4.19, N 9.33.
(S)-5-(4-Benzyl-4,5-dihydrooxazol-2-yl)-2-chloropyridine (6al): Pale-
yellow solid. Yield: 0.53 g, 71%. M.p. 65.0–67.0 °C. [α]10 = +7.7 (c
= 0.812, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 8.89 (d, J =
2.0 Hz, 1 H, HAr), 8.12 (dd, J = 8.5, 2.5 Hz, 1 H, HAr), 7.30 (dd,
J = 8.5, 8.0 Hz, 1 H, HAr), 7.28–7.19 (m, 5 H, HAr), 4.61–4.55 (m,
1 H, CH), 4.35 (dd, J = 8.5, 8.5 Hz, 1 H, OCH2), 4.13 (dd, J =
8.5, 8.0 Hz, 1 H, OCH2), 3.17 (dd, J = 14.0, 5.5 Hz, 1 H, ArCH2),
2.74 (dd, J = 14.0, 8.5 Hz, 1 H, ArCH2) ppm. 13C NMR (500 MHz,
CDCl3): δ = 160.8, 153.7, 149.3, 138.0, 137.3, 129.0, 128.4, 126.4,
123.8, 122.7, 71.9, 67.7, 41.4 ppm. IR (KBr): ν = 3027, 2962, 1647,
˜
1585, 1368, 1278, 1105, 745, 699 cm–1. C15H13ClN2O (272.07):
calcd. C 66.06, H 4.80, N 10.27; found C 66.38, H 4.65, N 9.96.
127.8, 126.9, 126.7, 125.0, 38.9, 38.6, 31.8 ppm. IR (KBr): ν = 3056,
˜
(S)-4-Benzyl-2-(2-indolyl)-1,3-oxazoline (6am): Yellow solid. Yield:
0.46 g, 60%. M.p. 92.1–93.7 °C.[18] [α]10 = +23.7 (c = 0.803,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 10.20 (s, 1 H, NH), 7.68
(d, J = 8.0 Hz, 1 H, HAr), 7.39 (dd, J = 8.5, 1.0 Hz, 1 H, HAr),
7.26–7.30 (m, 3 H, HAr), 7.13–7.23 (m, 3 H, HAr), 7.06 (d, J =
1.0 Hz, 1 H, HAr), 4.66–4.72 (m, 1 H, CH), 4.47 (dd, J = 8.0,
8.0 Hz, 1 H, OCH2), 4.24 (dd, J = 7.5, 8.5 Hz, 1 H, OCH2), 3.15
2933, 1655, 1571, 1399, 1360, 1128, 782, 739, 697 cm–1. MS (EI,
70 eV): m/z (%) = 287 (2) [M]+, 196 (27), 155 (100), 127 (47), 91 (9),
77(7). C20H17NO (287.13): calcd. C 83.59, H 5.96, N 4.87; found C
83.68, H 5.83, N 4.65.
(2S)-1-(2-Naphthoyl)-2-phenylaziridine (7bf): White solid.[16] M.p.
106.1–107.6 °C. [α]25 = +150.6 (c = 0.336, CHCl3). 1H NMR
Eur. J. Org. Chem. 2010, 4227–4236
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4235

H. Jiang, S. Yuan, W. Wan, K. Yang, H. Deng, J. Hao
FULL PAPER
Gwaltney, D. J. Frost, H. L. Sham, S. H. Rosenberg, S. C. Ng,
Mol. Cancer Ther. 2003, 2, 227–233.
[4] a) A. Bettencourt-Dias, S. Viswanathan, A. Rollett, J. Am.
Chem. Soc. 2007, 129, 15436–15437; b) H. Masashi, T. Takao,
O. Shinjiro, U.S. Pat. 2007228940, 2007.
[5] a) L. H. Gade, S. B. Laponnaz, Coord. Chem. Rev. 2007, 251,
718–725; b) G. Desimoni, G. Faita, K. A. Jorgensen, Chem.
Rev. 2006, 106, 3561–3651; c) T. Gant, A. I. Meyers, Tetrahe-
dron 1994, 50, 2297–2360; d) A. I. Meyers, Acc. Chem. Res.
1978, 11, 375–381; e) A. I. Meyers, E. D. Mihelich, Angew.
Chem. 1976, 88, 321–332; f) J. A. Frump, Chem. Rev. 1971, 71,
483–506; g) A. J. Phillips, Y. Uto, P. Wipf, M. J. Reno, D. R.
Williams, Org. Lett. 2000, 2, 1165–1168; h) H. Vorbrüggen, K.
Krolikiewicz, Tetrahedron 1993, 49, 9353–9372; i) P. Wipf, C. P.
Miller, Tetrahedron Lett. 1992, 33, 907–910.
(500 MHz, CDCl3): δ = 8.53 (s, 1 H, HAr), 8.00 (dd, J = 8.5,
1.5 Hz, 1 H, HAr), 7.85–7.78 (m, 3 H, HAr), 7.57 (td, J = 7.0,
1.5 Hz, 1 H, HAr), 7.49 (td, J = 8.5, 1.0 Hz, 1 H, HAr), 7.44–7.37
(m, 5 H, HAr), 3.53 (dd, J = 6.0, 6.0 Hz, 1 H, CH), 3.04 (d, J =
6.0 Hz, 1 H, NCH2), 2.52 (d, J = 3.5 Hz, 1 H, NCH2) ppm. 13C
NMR (125 MHz, CDCl3): δ = 179.3, 137.3, 135.7, 132.6, 130.9,
130.1, 129.6, 129.0, 128.4, 128.3, 127.9, 126.8, 126.4, 125.1, 40.6,
35.5 ppm. IR (KBr): ν = 3055, 2993, 1675, 1629, 1391 1303, 1286,
˜
833, 785, 705 cm–1. C19H15NO (273.12): calcd. C 83.49, H 5.53, N
5.12; found C 83.55, H 5.42, N 5.29.
Supporting Information (see footnote on the first page of this arti-
cle): 1H, 13C and 19F NMR spectra of all compounds, ORTEP plot
of 6afЈand its packing diagram, HPLC traces of (R)- and (S)-6af
and -6afЈ.
[6] J. A. Frump, Chem. Rev. 1971, 71, 483–505.
[7]
Burgess reagent: P. Wipf, C. P. Miller, Tetrahedron Lett. 1992,
33, 907–910; PPh3/DIAD: D. M. Roush, M. M. Patel, Synth.
Commun. 1985, 15, 675–679; DIC/Cu(OTf)2: S. Crosignani,
A. C. Young, B. Linclau, Tetrahedron Lett. 2004, 45, 9611–
9615; DAST/Deoxo-Fluor: A. J. Phillips, Y. Uto, P. Wipf, M. J.
Reno, D. R. Williams, Org. Lett. 2000, 2, 1165–1168; SOCl2:
H. Wenker, J. Am. Chem. Soc. 1935, 57, 1079–1080.
Carboxylic esters: R. E. Lowenthal, A. Abiko, S. Masamune,
Tetrahedron Lett. 1990, 31, 6005–6008; nitriles: C. Bolm, K.
Weickhardt, M. Zehnder, T. Ranff, Chem. Ber. 1991, 124, 1173–
1180; aldehydes: J. G. Badiang, J. Aube, J. Org. Chem. 1996,
61, 2484–2487.
a) R. Rabinowitz, R. Marcus, J. Am. Chem. Soc. 1962, 84,
1312–1313; b) F. Ramirez, N. B. Desai, N. Mckelvie, J. Am.
Chem. Soc. 1962, 84, 1745–1747; c) L. F. Fieser, M. Fieser, Rea-
gents for Organic Synthesis, Wiley, New York, 1972, vol. 3, pp.
320–332; d) J. I. G. Gadogan, R. K. Mackie, Chem. Soc. Rev.
1974, 3, 87–137.
Acknowledgments
This work was financially supported by the National Natural Sci-
ence Foundation of China (20772079), Science and Technology
Commission of Shanghai Municipality (07JC14020, 07ZR14040,
08JC1409900) and Shanghai Municipal Education Commission.
The authors also thank the Instrumental Analysis & Research Cen-
ter of Shanghai University for structural analysis and the Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, for
the enantiomeric purity measurement by HPLC.
[8]
[9]
[1] a) H. A. McManus, P. J. Guiry, Chem. Rev. 2004, 104, 4151–
4202; b) B. T. Hahn, F. Tewes, R. Fröhlich, F. Glorius, Angew.
Chem. Int. Ed. 2009, 48, 1–5; c) M. Benaglia, T. Benincori, P.
Mussini, T. Pilati, S. Rizzo, F. Sannicolo, J. Org. Chem. 2005,
70, 7488–7495; d) Z. Chai, X. Y. Liu, X. Y. Yu, G. Zhao, Tetra-
hedron: Asymmetry 2006, 17, 2442–2447; e) M. Inoue, T. Su-
zuki, M. Nakada, J. Am. Chem. Soc. 2003, 125, 1140–1141; f)
D. W. Dodd, H. E. Toews, F. d. S. Carneiro, M. C. Jennings,
N. D. Jones, Inorg. Chim. Acta 2006, 359, 2850–2858; g) N.
Paschke, A. Röndigs, H. Poppenborg, J. E. A. Wolff, B. Krebs,
Inorg. Chim. Acta 1997, 264, 239–248; h) K. Hallman, E. Ma-
[10]
[11]
[12]
M. Kumar, S. K. Pandey, S. Gandhi, V. K. Singh, Tetrahedron
Lett. 2009, 50, 363–365.
F. L. Ge, Z. X. Wang, W. Wan, W. C. Lu, J. Hao, Tetrahedron
Lett. 2007, 48, 3251–3254.
a) M. K. Ghorai, A. Kumar, D. P. Tiwari, J. Org. Chem. 2010,
75, 137–151; b) Saha, J. P. Nandy, S. Shukla, J. Org. Chem.
2002, 67, 7858–7860.
cedo, K. Nordström, C. Moberg, Tetrahedron: Asymmetry [13] R. Appel, R. Kleinstück, Chem. Ber. 1974, 107, 5–12.
1999, 10, 4037–4046; i) C. Jönsson, K. Hallman, H. Andersson,
G. Stemme, M. Malkoch, E. Malmström, A. Hultc, C. Mob-
erga, Bioorg. Med. Chem. Lett. 2002, 12, 1857–1861.
[14] A. E. May, P. H. Willoughby, T. R. Hoye, J. Org. Chem. 2008,
73, 3292–3294.
[15] H. Vorbrüggen, K. Krolikiewicz, Tetrahedron 1993, 49, 9353–
9372.
[2] a) H. R. Onishi, B. A. Pelak, L. L. Silver, F. M. Kahan, M. H.
Chen, A. A. Patchett, S. M. Galloway, S. A. Hyland, M. S. An-
derson, C. R. H. Raetz, Science 1996, 274, 980–982; b) M. C.
Pirrung, L. N. Tumey, A. L. McClerran, C. R. H. Raetz, J. Am.
Chem. Soc. 2003, 125, 1575–1586; c) M. Reuman, A. I. Meyers,
Tetrahedron 1985, 41, 837–860; d) T. G. Gant, A. I. Meyers,
Tetrahedron 1994, 50, 2297–2360; e) J. P. Genet, S. Thorimbert,
A. M. Touzin, Tetrahedron Lett. 1993, 34, 1159–1162; f) Y. J.
Lee, J. Y. Lee, M. J. Kim, T. S. Kim, H. G. Park, S. S. Jew, Org.
Lett. 2005, 7, 1557–1560; g) M. Locatelli, P. G. Cozzi, Angew.
Chem. Int. Ed. 2003, 42, 4928–4930.
[16] F. Crestey, M. Witt, K. Frydenvang, D. Stærk, J. W. Jaroszew-
ski, H. Franzyk, J. Org. Chem. 2008, 73, 3566–3569.
[17] R. A. Bawa, S. Jones, Tetrahedron 2004, 60, 2765–2770.
[18] a) D. V. Kashelikar, J. Am. Chem. Soc. 1960, 82, 4930–4931; b)
M. J. Oila, J. E. Tois, A. M. P. Koskinen, Synth. Commun.
2008, 38, 361–370.
[19] C. G. Frost, J. M. J. Williams, Tetrahedron Lett. 1993, 34, 2015–
2018.
[20] Z. Eckstein, Roczniki Chemii 1962, 36, 73–85; ISSN: 0035-
7677.
[3] S. K. Tahir, M. A. Nukkala, N. A. Z. Mozny, R. B. Credo,
R. B. Warner, Q. Li, K. W. Woods, A. Claiborne, S. L.
Received: February 4, 2010
Published Online: June 15, 2010
4236
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4227–4236