Iridium-catalyzed allylic alkylation of monosubstituted allylic acetates with azlactone, and separation of diastereoisomers by sequential aza-Cope rearrangement

Article abstract of DOI:10.1016/j.tet.2011.08.016

The iridium-catalyzed allylic alkylation with azlactone and sequential aza-Cope rearrangement was demonstrated. The sequential reaction was effective in separating of diastereoisomers and afforded a diastereomerically pure azlactone derivative and oxazoli

Full text of DOI:10.1016/j.tet.2011.08.016

Tetrahedron 67 (2011) 7686e7691
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Iridium-catalyzed allylic alkylation of monosubstituted allylic acetates with
azlactone, and separation of diastereoisomers by sequential aza-Cope
rearrangement
*
*
Motoi Kawatsura , Hiroaki Tsuji, Kenta Uchida, Toshiyuki Itoh
Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Koyama, Tottori 680-8552, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 June 2011
Received in revised form 5 August 2011
Accepted 5 August 2011
Available online 12 August 2011
The iridium-catalyzed allylic alkylation with azlactone and sequential aza-Cope rearrangement was
demonstrated. The sequential reaction was effective in separating of diastereoisomers and afforded
a diastereomerically pure azlactone derivative and oxazolinone derivative.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Azlactones are useful compounds because they can be used to
construct peptides or amino acid derivatives, and -disubstituted
Several iridium catalysts were evaluated for the allylic alkylation
of racemic allylic acetate rac-1a with azlactone 2. The screening of
iridium catalysts revealed that the [IrCl(cod)]2 exhibited a catalyst
activity for the desired alkylation reaction.6 Based on this initial
result, we started our investigation of the iridium-catalyzed regio-
and diastereo-selective allylic alkylation of monosubstituted allylic
acetates 1a with 2. As shown in Table 1, the reaction by [IrCl(cod)]2
gave a branch-type product as a mixture of two diastereomers, 3a-
B17 and 3a-B2, with high regioselectivity, but low diaster-
eoselectivity (Table 1, entry 1). Although we examined the reaction
with the addition of several ligands, the diastereoselectivity did not
increase (entries 2e5). However, when the reaction was conducted
at 60 ꢀC, we confirmed that decreasing the amount of 3a-B2 caused
the formation of a new product (E)-5a (entry 6). The structure of
(E)-5a was determined to be an oxazolinone derivative based on its
NMR spectra and X-ray crystallographic analysis.8 Again, the ad-
dition of ligands did not have any influence on the ratio of the
products (entries 7e10). We next conducted the reaction at 80 ꢀC
with dioxane or toluene as the solvent, and confirmed that toluene
inhibited the formation of linear-type product 4a (entry 13), and
the reaction in the dioxane solvent gave the branch-type product
3a-B1 as a single diastereoisomer (entry 14). However, we found no
significant differences in the ratio of 3a-B1 and (E)-5a between
results obtained from the dioxane or toluene solvent system.9 On
the other hand, the separation of 3a-B1 and 3a-B2 was very diffi-
cult, while 3a-B1 and (E)-5a were easily separated by silica gel
column chromatography.
a,a
azlactones can potentially be used to convert quaternary amino acid
derivatives.1 While several types of transition metal-catalyzed car-
bonecarbon bond formation reactions have been developed, there
are still only limited examples of the transition metal-catalyzed
construction of a,a
-disubstituted azlactones.2,3 For example, Trost
reported the palladium or molybdenum-catalyzed regio- and/or
enantioselective allylic alkylation of allylic esters with azlactones.2
However, the transition metal-catalyzed allylic alkylation of mono-
substituted allylic esters with an
a-substituted azlactone usually
gives a mixture of regio- and diastereoisomers. According to the
pioneering work by Trost and Dogra, they discovered the
C7H8Mo(CO)3/ligand catalyst produces a branch-type product with
a high diastereoselectivity,2a but the result of their molybdenum
catalyst system is an exceptional case, and usually two types of di-
astereomeric isomers will be obtained simultaneously. We also
confirmed that an allylic alkylation of monosubstituted allylic ace-
tates with azlactones using several transition metal catalysts showed
no diastereoselectivity. In addition, the separation of two di-
astereoisomers required careful silica gel column chromatography. In
further investigation, we found that the one of the diastereoisomers,
which was obtained from an iridium-catalyzed allylic alkylation4,5
with azlactone, was selectively rearranged into oxazolinone de-
rivatives. We now report the iridium-catalyzed allylic alkylationwith
azlactones, and accomplishment of the easy separation of di-
astereoisomers using the sequential aza-Cope rearrangement.
Concerning the formation of the oxazolinone derivative (E)-5a,
we assumed that the one diastereoisomer 3a-B2 might selectively
rearrange to (E)-5a, because the aza-Cope rearrangement10 of 3a-
* Corresponding authors. E-mail addresses: kawatsur@chem.tottori-u.ac.jp
B2 easily occurred through
a chair-like transition state T2
(M. Kawatsura), titoh@chem.tottori-u.ac.jp (T. Itoh).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.016

M. Kawatsura et al. / Tetrahedron 67 (2011) 7686e7691
7687
Table 1
Reaction conditions and product ratios for the Ir-catalyzed allylic alkylation of 2 with
1aa,b
Scheme 2. Separation of branch type azlactone derivative 3a-B via aza-Cope
rearrangement.
rearrangement step. Although the rearrangement smoothly pro-
ceeded even without [IrCl(cod)]2, the NMR yield of 3a-B1 and (E)-
5a was slightly increased when the reaction was conducted in the
presence the iridium catalyst. Based on the results, we concluded
that the rearrangement might have been occurred as a result of
a thermal effect, and that the contribution of the iridium catalyst
was low.
We next demonstrated the iridium-catalyzed allylic alkylation
with azlactone and the sequential aza-Cope rearrangement using
several allylic acetates. As shown in Table 2, most of the aryl group
substituted allylic acetates 1bei gave the expected results (entries
1e9). In all the reactions, the expected diastereomerically pure
azlactone derivatives and rearranged oxazolinone derivatives were
obtained. For example, the allylic acetate 1b, which contained an
electron-donating group at the para-position on the aromatic ring,
gave a 39% of 3b-B1 and 58% of (E)-5b, respectively (entry 1). Re-
actions of 1cee, which have an electron-withdrawing group at the
para-position on the aromatic ring, also gave two types of products
with a reasonably good yield (entries 2, 4, and 5). The reaction
proceeded without any change in the yield and ratio even with
0.5 mol % [IrCl(cod)]2 (entry 3). The reactions of 1f and 1g, bearing
an ortho-substituted aromatic group, also gave the desired products
Entry
Ligand
Temp (ꢀC)
3a-B1c
3a-B2
4a
5ac
1
2
3
4
5
6
7
8
d
rt
rt
rt
rt
62
33
69
63
47
57
57
59
56
44
50
53 (57)
42 (35)
38 (33)
38
31
31
37
42
8
8
7
13
11
10
8
<1
<1
<1
<1
<1
2
<1
<1
<1
<1
2
<1
<1
<1
<1
<1
33
34
34
29
36
37
37 (32)
45 (43)
53 (50)
PPh3
PtBu3
P(OPh)3
DPPEd
d
rt
60
60
60
60
60
60
60
80
80
PPh3
PtBu3
P(OPh)3
DPPEd
d
9
10
11e
12f
13e
14f
d
2
<1
3
d
3
<1
d
a
Reaction conditions: azlactone 2 (0.42 mmol), allylic acetate rac-1a (0.28 mmol),
LiHMDS (0.4 mmol, 1.0 M in THF), 5 mol % of [IrCl(cod)]2 and 20 mol % ligand in
solvent (0.5 mL).
b
Product ratios were determined by 1H NMR using an internal standard
(trioxane).
c
Isolated yield is in parentheses.
With 10 mol % of DPPE.
Toluene was used as the solvent.
Dioxane was used as the solvent.
d
e
f
(Scheme 1). To prove this expectation, we demonstrated the rear-
rangement reaction with 3a (Scheme 2). When 3a-B1, which is
a mixture of two diastereoisomers, was treated at 60 ꢀC in dioxane,
we observed the disappearance of 3a-B2 and formation of (E)-5a.
We also examined the role of the iridium catalyst in the
Table 2
Ir-catalyzed alkylation of 1, and sequential aza-Cope rearrangementa
Entry
R
Yield (%) of 3-B1
Yield (%) of 5
1
4-MeOC6H4 (1b)
4-CF3C6H4 (1c)
4-CF3C6H4 (1c)
4-ClC6H4 (1d)
4-BrC6H4 (1e)
2-MeOC6H4 (1f)
2-ClC6H4 (1g)
1-Naphthyl (1h)
2-Naphthyl (1i)
PhCH2CH2 (1j)
39
46
46
45
46
54
48
47
39
22
58
34
34
41
38
41
23
40
37
<1
2
3b
4
5
6
7
8
9
10c
a
Reaction conditions: 2 (0.42 mmol), 1bej (0.28 mmol), LiHMDS (0.4 mmol, 1.0 M
in THF), and 5 mol % of [IrCl(cod)]2 in toluene (0.5 mL) at room temperature for 12 h,
then heated to 80 ꢀC for 12 h.
b
[IrCl(cod)]2 (0.5 mol %) was used.
Allylated product 3j-B2 (29% yield) was obtained.
c
Scheme 1. Aza-Cope rearrangement.

7688
M. Kawatsura et al. / Tetrahedron 67 (2011) 7686e7691
(entries 6 and 7). Unfortunately, the alkyl group substituted allylic
acetate 1j did not produce the rearranged product 5j, while it gave
the alkylated products as an unseparable mixture of 3j-B1 and 3j-
B2 (entry 10). This result suggested that azlactone derivative, which
was formed from the reaction of alkyl group substituted allyl ester,
is not appropriate for the aza-Cope rearrangements.
We further examined the reaction of the chiral allylic acetate to
obtain both the chiral azlactone and chiral rearranged oxazolinone
derivatives. Our preliminary results revealed that the reaction at
80 ꢀC decreased the chirality of the products. However, we found
that the reaction retained the chirality when carried out at room
temperature for the allylic alkylation, then the temperature was
raised to 60 ꢀC for the aza-Cope rearrangement. The reaction of (R)-
1a (99% ee) gave (4S,10R)-3a-B1 and (S)-5a,11 but the enantiomeric
excess of the products dropped slightly to 86% ee and 79% ee, re-
spectively (Table 3, entry 1). The chirality of both products in the
reaction with (R)-1b was significantly lower (entry 2), but we
3. Conclusion
We demonstrated the iridium-catalyzed allylic alkylation of
monosubstituted allylic acetates with azlactone, and sequential
aza-Cope rearrangement. This consecutive reaction protocol made
it possible to obtain the diastereomerically pure alkylated azlactone
derivatives and oxazolinone derivatives. We also succeeded in
obtaining both the alkylated and rearranged products with 98% ee
and 93% ee, respectively.
4. Experimental section
4.1. General
All manipulations were carried out under a nitrogen atmosphere.
NMR spectra were recorded on a 600 MHz (for 1H),151 MHz (for 13C)
and 565 MHz (for 19F) NMR spectrometer. Chemical shifts are
reported in
d
parts per million referenced to an internal SiMe4 stan-
dard for 1H NMR, and internal C6F6 standard for 19F NMR. Residual
chloroform (
d
77.0 for 13C) was used as internal reference for 13C NMR.
Table 3
1H and 13C NMR spectra were recorded in CDCl3 at 25 ꢀC unless
otherwise noted. [IrCl(cod)]2, PPh3, P(OPh)3, DPPE, and otherreagents
and solvents were purchased from common commercial sources and
were used without further purification. Allylic acetates13e17 and
azlactone 218 were prepared according to the literature.
Allylic alkylation of 2 with (R)-1aec,k
4.2. General procedure for the iridium-catalyzed allylic
alkylation of allylic acetates with azlactones, and sequential
aza-Cope rearrangement
Entry
1
(R)-1
B1a
70% Yieldb
86% ee
47% Yield
44% ee
50% Yield
93% ee
5a
Ar]Ph (1a)
(99% ee)
Ar]4-MeOC6H4 (1b)
(98% ee)
Ar]4-FC6H4 (1k)
(99% ee)
Ar]4-CF3C6H4 (1c)
(99% ee)
25% Yield
79% ee
39% Yield
38% ee
27% Yield
88% ee
32% Yield
93% ee
A typical procedure is given for the reaction of rac-1b with 2
(Table 2, entry 1). To a solution of [IrCl(cod)]2 (9.4 mg, 0.014 mmol)
and azlactone 2 (74 mg, 0.42 mmol) in anhydrous dioxane (0.5 mL)
was added rac-1b (50 mg, 0.28 mmol). LiHMDS (0.39 mmol, 0.39 mL
of 1M in THF) was slowly added at 0 ꢀC, and stirred at room tem-
perature for 12 h. After complete conversion of allylic acetate 1b, as
indicated by TLC, the reaction mixture was heated to 80 ꢀC and
stirred for 12 h. The reaction mixture was quenched with saturated
aqueous NaHCO3, and extracted with ethyl acetate (3ꢁ2 mL). The
combined organic layers were dried over MgSO4 and evaporated.
The residue was chromatographed on silica gel (hexane/diethyl
ether¼4/1) to give 34.8 mg (39%) of 3b-B1 and 52.4 mg (58%) of 5b.
2
3
4
57% Yield
98% ee
a
Enatiomeric excess was determined by the chiral HPLC analysis.
Mixture of B1 (65%) and B2 (5%).
b
confirmed that the enantiomeric excess of the allylic acetates,
which possess an electron-withdrawing group on the phenyl
group, was effectively transferred to the azlactone derivative and
oxazolinone derivatives. When (R)-1k was used as a substrate, we
could obtain the chiral azlactone derivative (4S,10R)-3k-B1 and (S)-
5k with 93% ee and 88% ee, respectively. The best result was
obtained in the reaction of (R)-1c (99% ee), and provided (4S,10R)-
3c-B1 and (S)-5c with 98% ee and 93% ee, respectively (entry 4).
Unfortunately, the chirality transfer is not perfect and the detailed
mechanism of loosing the chirality has not yet been clarified. From
these results and the allylic alkylation at room temperature (Eq. 1),
it seems that chirality might be lost during both the alkylation and
rearrangement steps.12 However, it should be emphasized that we
did succeed in obtaining diastereomerically pure chiral azlactone
derivatives together with chiral oxazolinone derivatives.
4.2.1. (S*)-4-Methyl-2-phenyl-4-((R*)-1-phenylallyl)oxazol-5(4H)-
one (3a-B1). Colorless oil. 1H NMR (600 MHz, CDCl3)
d 1.35 (s, 3H),
3.69 (d, J¼9.5 Hz, 1H), 5.09 (dd, J¼1.3, 10.1 Hz, 1H), 5.19 (d,
J¼16.9 Hz,1H), 6.01 (ddd, J¼9.5,10.1,16.9 Hz,1H), 7.26 (d, J¼14.7 Hz,
1H), 7.33 (t, J¼7.7 Hz, 2H), 7.45e7.50 (m, 4H), 7.57 (t, J¼7.7 Hz, 1H),
8.01 (dd, J¼1.4, 8.2 Hz, 2H). 13C NMR (151 MHz, CDCl3)
d 22.5, 57.6,
73.6, 118.9, 125.9, 127.4, 128.0, 128.5, 128.8, 129.2, 132.7, 135.6, 138.4,
159.9, 180.7. IR (neat) 3405, 2980, 1815, 1739, 1653, 1581, 1493, 1241,
1003, 927, 703. HRMS (ESI): m/z: calcd for C19H18NOþ2 [MþH]þ
292.1338, found 292.1328. The alkylated product 3a-B1 was sol-
volyzed by K2CO3/MeOH, and the relative configuration was de-
termined by the comparison with the reported 1H NMR data.
4.2.2. (S)-4-Methyl-2-phenyl-4-((R)-1-phenylallyl)oxazol-5(4H)-one
((4S,10R)-3a-B1). Colorless oil. ½a 2D6
ꢃ39.6 (c 3.5, CHCl3) (86% ee).
ꢂ
Enantiomer ratio was determined by HPLC using a Daicel CHIR-
ALCEL OJ-H (hexane/2-propanol¼25/1, flow: 1.0 mL/min, 254 nm,
35 ꢀC, tR 19.1 min (minor); tR 23.7 min (major)).
4.2.3. (R*)-4-Methyl-2-phenyl-4-((R*)-1-phenylallyl)oxazol-5(4H)-
one (3a-B2). Colorless oil. 1H NMR (600 MHz, CDCl3)
d 1.58 (s, 3H),
3.71 (d, J¼6.6 Hz,1H), 5.30 (d, J¼16.8 Hz,1H), 5.32 (dd, J¼1.2, 9.6 Hz,
1H), 6.38 (ddd, J¼6.6, 9.6, 16.8 Hz, 1H), 7.11e7.19 (m, 5H), 7.44 (t,

M. Kawatsura et al. / Tetrahedron 67 (2011) 7686e7691
7689
J¼8.4 Hz, 2H), 7.52e7.87 (m, 1H), 7.88 (d, J¼8.4 Hz, 2H). 13C NMR
1652, 1494, 1452, 1326, 1167, 1006, 929, 708. HRMS (ESI): m/z: calcd
for C20H17F3NOþ2 [MþH]þ 360.1211, found 360.1200.
(151 MHz, CDCl3)
d 22.6, 57.5, 72.9, 119.4, 125.8, 127.5, 127.9, 128.3,
128.7, 128.7, 132.6, 135.3, 138.1, 160.2, 180.1. IR (neat) 3064, 2979,
1822, 1652, 1452, 1295, 1004, 707. HRMS (ESI): m/z: calcd for
C19H18NOþ2 [MþH]þ 292.1338, found 292.1327.
4.2.11. (S)-4-Methyl-2-phenyl-4-((R)-1-(4-(trifluoromethyl)phenyl)
allyl)oxazol-5(4H)-one ((4S,10R)-3c-B1). Colorless oil. ½a 2D5
ꢃ43.3 (c
ꢂ
3.6, CHCl3) (98% ee). Enantiomer ratio was determined by HPLC
using a Daicel CHIRALCEL OJ-H (hexane/2-propanol¼250/1, flow:
0.5 mL/min, 254 nm, 35 ꢀC, tR 42.1 min (major); tR 49.6 min (minor)).
4.2.4. 2-(3-Phenyl-2-propenyl)-4-methyl-2-phenyloxazol-5(2H)-one
(5a). Colorless oil. 1H NMR (600 MHz, CDCl3)
d 2.27 (s, 3H), 2.99
(ddd, J¼1.1, 7.5, 14.2 Hz, 1H), 3.05 (ddd, J¼1.1, 7.5, 14.2 Hz, 1H), 5.90
(dt, J¼7.5, 15.8 Hz, 1H), 6.39 (d, J¼15.8 Hz, 1H), 7.22e7.29 (m, 5H),
7.36e7.41 (m, 3H), 7.58 (d, J¼6.9 Hz, 2H). 13C NMR (151 MHz, CDCl3)
4.2.12. (R)-4-Methyl-2-phenyl-4-((R)-1-(4-(trifluoromethyl)phenyl)
allyl)oxazol-5(4H)-one ((4R,10R)-3c-B2). Colorless oil. 1H NMR
(600 MHz, CDCl3)
d
1.59 (s, 3H), 3.78 (d, J¼9.6 Hz, 1H), 5.32 (d,
d
14.0, 44.8, 107.2, 120.5, 125.9, 126.3, 127.8, 128.6, 128.6, 128.9,
J¼16.8 Hz, 1H), 5.36 (dd, J¼0.9, 10.1 Hz, 1H), 6.36 (ddd, J¼9.6, 10.1,
16.8 Hz, 1H), 7.31 (d, J¼8.2 Hz, 2H), 7.42 (d, J¼8.2 Hz, 2H), 7.46 (t,
J¼7.5 Hz, 2H), 7.57 (t, J¼7.5 Hz, 1H), 7.88 (d, J¼7.5 Hz, 2H). 13C NMR
136.4, 136.8, 138.5, 160.4, 165.2. IR (neat) 3060, 3030, 1784, 1654,
1449, 1308, 1148, 967, 747, 695. HRMS (ESI): m/z: calcd for
C19H18NOþ2 [MþH]þ 292.1338, foundx292.1329.
(151 MHz, CDCl3)
d
22.7, 57.0, 72.6, 120.2, 124.0 (q, JCeF¼272.1 Hz),
125.2 (q, JCeF¼3.3 Hz), 125.5, 127.8, 128.8, 129.1, 129.6 (q,
4.2.5. (S)-2-(3-Phenyl-2-propenyl)-4-methyl-2-phenyloxazol-5(2H)-
JCeF¼32.4 Hz), 130.1, 132.9, 134.5, 142.3, 160.5. 19F NMR (565 MHz,
one ((S)-5a). Colorless oil. ½a D26
ꢃ5.6 (c 2.3, CHCl3) (79% ee). En-
ꢂ
CDCl3)
d 99.1. IR (neat) 3063, 2938, 1819, 1654, 1329, 1160, 1127,
antiomer ratio was determined by HPLC using a Daicel CHIRALCEL
OJ-H (hexane/2-propanol¼25/1, flow: 1.0 mL/min, 254 nm, 35 ꢀC, tR
26.3 min (minor); tR 34.4 min (major)).
1069, 1006, 905, 708. HRMS (ESI): m/z: calcd for C20H17F3NO2þ
[MþH]þ 360.1211, found 360.1202. ½a 2D5
ꢃ69.5 (c 0.6, CHCl3) (95%
ꢂ
ee). Enantiomer ratio was determined by HPLC using a Daicel
CHIRALCEL OD-H (hexane/2-propanol¼500/1, flow: 0.2 mL/min,
254 nm, 35 ꢀC, tR 44.6 min (major); tR 49.8 min (minor)).
4.2.6. (S*)-4-((R*)-1-(4-Methoxyphenyl)allyl)-4-methyl-2-
phenyloxazol-5(4H)-one (3b-B1). Colorless oil. 1H NMR (600 MHz,
CDCl3)
d
1.35 (s, 3H), 3.65 (d, J¼9.4 Hz, 1H), 3.79 (s, 3H), 5.07 (d,
4.2.13. (E)-4-Methyl-2-phenyl-2-(3-(4-(trifluoromethyl)phenyl)allyl)
oxazol-5(2H)-one ((5c)). White solid. Mp 124e126. 1H NMR
J¼10.1 Hz, 1H), 5.17 (d, J¼16.9 Hz, 1H), 5.98 (ddd, J¼9.4, 10.1, 16.9 Hz,
1H), 6.87 (d, J¼8.6 Hz, 2H), 7.37 (d, J¼8.6 Hz, 2H), 7.49 (dd, J¼7.4,
7.4 Hz, 2H), 7.57 (dd, J¼7.4, 7.4 Hz,1H), 8.01 (d, J¼7.5 Hz, 2H).13C NMR
(600 MHz, CDCl3)
d
2.28 (s, 3H), 3.00 (ddd, J¼0.9, 7.5, 14.2 Hz, 1H),
3.09 (ddd, J¼0.9, 7.5, 14.2 Hz, 1H), 6.01 (dt, J¼7.5, 15.9 Hz, 1H), 6.42
(151 MHz, CDCl3)
d 22.5, 55.2, 56.7, 73.6, 113.9, 118.6, 125.9, 128.0,
(d, J¼15.9 Hz, 1H), 7.34e7.42 (m, 5H), 7.53 (d, J¼8.2 Hz, 2H), 7.57 (d,
J¼6.9 Hz, 2H). 13C NMR (151 MHz, CDCl3)
d 13.9, 44.7, 107.0, 123.5,
128.8, 130.2, 130.5, 132.7, 135.8, 158.9, 159.8, 180.8. IR (neat) 3072,
2933, 2836, 1814, 1736, 1611, 1512, 1451, 1247, 1004, 925, 704. HRMS
(ESI): m/z: calcd for C20H20NOþ3 [MþH]þ 322.1443, found 322.1433.
124.2 (q, JCeF¼272.0 Hz), 125.6 (q, JCeF¼3.9 Hz), 125.9, 126.5, 128.6,
129.0, 129.5 (q, JCeF¼32.2 Hz), 135.0, 138.2, 140.1, 160.5, 165.1. 19F
NMR (565 MHz, CDCl3)
d 99.3. IR (neat) 3062, 3043, 2905, 1793,
4.2.7. (S)-4-((R)-1-(4-Methoxyphenyl)allyl)-4-methyl-2-
1655, 1616, 1451, 1415, 1337, 1122, 981, 764, 700. HRMS (ESI): m/z:
phenyloxazol-5(4H)-one ((4S,10R)-3b-B1). Colorless oil. ½a 2D7
ꢃ26.2
ꢂ
calcd for C20H17F3NOþ2 [MþH]þ 360.1211, found 360.1216.
(c 4.3, CHCl3) (44% ee). Enantiomer ratio was determined by HPLC
using a Daicel CHIRALPAK AD-H (hexane/2-propanol¼99/1, flow:
1.0 mL/min, 254 nm, 35 ꢀC, tR 8.5 min (major); tR 10.2 min (minor)).
4.2.14. (S,E)-4-Methyl-2-phenyl-2-(3-(4-(trifluoromethyl)phenyl)al-
lyl)oxazol-5(2H)-one ((S)-5c). Colorless oil. ½a D24
ꢃ2.8 (c 2.6, CHCl3)
ꢂ
(93% ee). Enantiomer ratio was determined by HPLC using a Daicel
CHIRALPAK AD-H (hexane/2-propanol¼99/1, flow: 1.0 mL/min,
254 nm, 35 ꢀC, tR 14.6 min (major); tR 20.8 min (minor)).
4.2.8. (E)-2-(3-(4-Methoxyphenyl)allyl)-4-methyl-2-phenyloxazol-
5(2H)-one (5b). White solid. Mp 115e117 ꢀC. 1H NMR (600 MHz,
CDCl3)
d
2.27 (s, 3H), 2.97 (ddd, J¼1.0, 7.5, 14.2 Hz, 1H), 3.04 (ddd,
J¼1.0, 7.5, 14.2 Hz, 1H), 3.79 (s, 3H), 5.74 (dt, J¼7.5, 15.8 Hz, 1H), 6.33
(d, J¼15.8 Hz, 1H), 6.82 (d, J¼8.8 Hz, 2H), 7.2 (d, J¼8.8 Hz, 2H),
7.35e7.4 (m, 3H), 7.58 (d, J¼7.1, 2H). 13C NMR (151 MHz, CDCl3)
4.2.15. (S*)-4-((R*)-1-(4-Chlorophenyl)allyl)-4-methyl-2-
phenyloxazol-5(4H)-one (3d-B1). White solid. Mp 106e114 ꢀC. 1H
NMR (600 MHz, CDCl3)
d
1.34 (s, 3H), 3.67 (d, J¼9.3 Hz, 1H), 5.1 (dd,
d
14.0, 44.8, 55.3, 107.3, 114.1, 118.2, 125.9, 127.5, 128.6, 128.9, 129.6,
J¼1.0, 10.1 Hz, 1H), 5.18 (d, 16.9 Hz, 1H), 5.94 (ddd, J¼9.3, 10.1,
16,9 Hz, 1H), 7.31 (d, J¼8.5 Hz, 2H), 7.4 (d, J¼8.5 Hz, 2H), 7.5 (t,
J¼7.5 Hz, 2H), 7.59 (t, J¼7.5 Hz, 1H), 8.01 (d, J¼7.1 Hz, 2H). 13C NMR
135.9, 138.6, 159.4, 160.4, 165.2. IR (neat) 3037, 2903, 2840, 1784,
1654, 1609, 1515, 1443, 1296, 1242, 978, 758. HRMS (ESI): m/z: calcd
for C20H20NOþ3 [MþH]þ 322.1443, found 322.1446.
(151 MHz, CDCl3)
d 22.5, 56.8, 73.3, 119.3, 125.8, 128.1, 128.7, 128.8,
130.6, 132.8, 133.3, 135.2, 137.0, 160.1, 180.4. IR (neat) 3064, 1810,
1654, 1493, 1452, 1287, 1004, 919, 848. HRMS (ESI): m/z: calcd for
C19H17ClNOþ2 [MþH]þ 326.0948, found 326.0945.
4.2.9. (S,E)-2-(3-(4-Methoxyphenyl)allyl)-4-methyl-2-phenyloxazol-
5(2H)-one ((S)-5b). White solid. ½a D27
ꢃ4.2 (c 3.2, CHCl3) (38% ee).
ꢂ
Enantiomer ratio was determined by HPLC using a Daicel CHIR-
ALPAK AD-H (hexane/2-propanol¼19/1, flow: 1.0 mL/min, 254 nm,
35 ꢀC, tR 9.5 min (minor); tR 11.1 min (major)).
4.2.16. (E)-2-(3-(4-Chlorophenyl)allyl)-4-methyl-2-phenyloxazol-
5(2H)-one (5d). White solid. Mp 158e163 ꢀC. 1H NMR (600 MHz,
CDCl3)
d
2.27 (s, 3H), 2.97 (ddd, J¼1.1, 7.5, 14.2 Hz, 1H), 3.05 (ddd,
4.2.10. (S*)-4-Methyl-2-phenyl-4-((R*)-1-(4-(trifluoromethyl)phe-
nyl)allyl)oxazol-5(4H)-one (3c-B1). Colorless oil. 1H NMR
J¼1.1, 7.5,14.2 Hz,1H), 5.88 (dt, J¼7.5,15.8 Hz,1H), 6.34 (d, J¼15.8 Hz,
1H), 7.19 (d, J¼8.5 Hz, 2H), 7.25 (d, J¼8.5 Hz, 2H), 7.34e7.41 (m, 3H),
(600 MHz, CDCl3)
d
1.34 (s, 3H), 3.77 (d, J¼9.6 Hz, 1H), 5.13 (dd,
7.57 (d, J¼6.9 Hz, 2H). 13C NMR (151 MHz, CDCl3)
d 14.0, 44.7, 107.1,
J¼0.9, 10.1 Hz, 1H), 5.21 (d, J¼16.8 Hz, 1H), 5.95 (ddd, J¼9.6, 10.1,
16.8 Hz, 1H), 7.50 (t, J¼7.6 Hz, 2H), 7.60e7.61 (m, 5H), 8.03 (d,
121.3,125.9,127.5,128.6,128.8,129.0,133.4,135.1,135.2,138.3,160.4,
165.1. IR (neat) 3064, 1784, 1488, 1148, 978, 758. HRMS (ESI): m/z:
calcd for C19H17ClNOþ2 [MþH]þ 326.0948, found 326.0946.
J¼11.4 Hz, 2H). 13C NMR (151 MHz, CDCl3)
d 22.4, 57.2, 73.2, 119.7,
124.2 (q, JCeF¼272.0 Hz), 125.5 (q, JCeF¼4.0 Hz), 125.7, 128.0, 128.9,
129.7, 129.7 (q, JCeF¼32.5 Hz), 132.9, 134.8, 142.6, 160.2, 180.2. 19F
4.2.17. (S*)-4-((R*)-1-(4-Bromophenyl)allyl)-4-methyl-2-
NMR (565 MHz, CDCl3)
d
99.2. IR (neat) 3071, 2982, 1818, 1734,
phenyloxazol-5(4H)-one (3e-B1). White solid. Mp 116e122 ꢀC. 1H

7690
M. Kawatsura et al. / Tetrahedron 67 (2011) 7686e7691
NMR (600 MHz, CDCl3)
d
1.55 (s, 3H), 3.66 (d, J¼9.4 Hz, 1H), 5.1 (dd,
1470, 1449, 1308, 1149, 967, 752, 699. HRMS (ESI): m/z: calcd for
C
J¼1.0, 10.1 Hz, 1H), 5.18 (d, J¼16.9 Hz, 1H), 5.92 (ddd, J¼9.4, 10.1,
16.9 Hz, 1H), 7.35 (d, J¼8.5 Hz, 2H), 7.46e7.51 (m, 4H), 7.59 (t,
J¼7.4 Hz, 1H), 8.01 (d, J¼7.9 Hz, 2H). 13C NMR (151 MHz, CDCl3)
19H17ClNOþ2 [MþH]þ 326.0948, found 326.0938.
4.2.23. (S*)-4-Methyl-4-((R*)-1-(naphthalen-1-yl)allyl)-2-
d
22.5, 56.8, 73.2, 119.4, 121.5, 125.8, 128.0, 128.8, 131.0, 131.7, 132.9,
phenyloxazol-5(4H)-one (3h-B1). White solid. Mp 112e119 ꢀC. 1H
135.1,137.5,160.1,180.4. IR (neat) 2984,1810,1649,1488,1322,1287,
1038, 1009, 933, 803, 691. HRMS (ESI): m/z: calcd for C19H17BrNO2þ
[MþH]þ 370.0443, found 370.0445.
NMR (600 MHz, CDCl3)
d
1.37 (s, 3H), 4.73 (d, J¼8.4 Hz, 1H), 5.09 (d,
J¼10.2 Hz, 1H), 5.27 (d, J¼16.8 Hz, 1H), 6.05 (ddd, J¼8.4, 10.2,
16.8 Hz,1H), 7.46e7.51 (m, 3H), 7.53e7.60 (m, 3H), 7.79 (d, J¼8.2 Hz,
1H), 7.86 (d, J¼8.2 Hz, 1H), 7.99 (d, J¼7.8 Hz, 2H), 8.07 (d, J¼5.7 Hz,
1H), 8.28 (d, J¼8.0 Hz, 1H). 13C NMR (151 MHz, CDCl3)
d 22.3, 50.5,
4.2.18. (E)-2-(3-(4-Bromophenyl)allyl)-4-methyl-2-phenyloxazol-
74.4, 119.1, 123.1, 125.6, 125.6, 125.9, 126.3, 126.5, 127.9, 128.1, 128.8,
129.2, 132.3, 132.8, 134.0, 134.6, 136.0, 159.9, 181.1. IR (neat) 3061,
2931, 1814, 1655, 1451, 1291, 1155, 1005, 927, 878, 782, 692. HRMS
(ESI): m/z: calcd for C23H20NOþ2 [MþH]þ 342.1494, found 342.1484.
5(2H)-one ((5e)). White solid. Mp 158e162 ꢀC. 1H NMR (600 MHz,
CDCl3)
d
2.27 (s, 3H), 2.96 (ddd, J¼1.1, 7.4, 14.2 Hz, 1H), 3.05 (ddd,
J¼1.1, 7.4, 14.2 Hz, 1H), 5.89 (dt, J¼7.4, 15.8 Hz, 1H), 6.32 (d,
J¼15.8 Hz, 1H), 7.12 (d, J¼8.4 Hz, 2H), 7.36e7.41 (m, 5H), 7.57 (d,
J¼7.0 Hz, 2H). 13C NMR (151 MHz, CDCl3)
d 14.0, 44.7, 107.1, 121.5,
4.2.24. (E)-4-Methyl-2-(3-(naphthalen-1-yl)allyl)-2-phenyloxazol-
121.6, 125.9, 127.8,128.6, 129.0, 131.7, 135.2,135.7,138.3,160.4, 165.1.
IR (neat) 3063, 2939, 1787, 1655, 1488, 1451, 1307, 1224, 1071, 804,
611. HRMS (ESI): m/z: calcd for C19H17BrNOþ2 [MþH]þ 370.0443,
found 370.0445.
5(2H)-one (5h). Yellow oil. 1H NMR (600 MHz, CDCl3)
d 2.29 (s, 3H),
3.11 (dd, J¼7.2, 14.4 Hz, 1H), 3.18 (dd, J¼7.2, 14.4 Hz, 1H), 5.92 (dt,
J¼7.2, 15.6 Hz, 1H), 7.11 (d, J¼15.6 Hz, 1H), 7.37e7.43 (m, 5H), 7.48 (t,
J¼3.8 Hz, 2H), 7.63 (d, J¼7.6 Hz, 2H), 7.76 (t, J¼4.7 Hz, 1H), 7.83 (d,
J¼9.4 Hz, 1H), 7.91 (d, J¼9.4 Hz, 1H). 13C NMR (151 MHz, CDCl3)
4.2.19. (S*)-4-((R*)-1-(2-Methoxyphenyl)allyl)-4-methyl-2-
d
14.1, 45.0, 107.3, 123.9, 123.9, 124.0, 125.7, 125.9, 126.0, 126.1, 128.1,
phenyloxazol-5(4H)-one (3f-B1). White solid. Mp 116e118 ꢀC. 1H
128.5, 128.7, 129.0, 131.1, 133.5, 134.3, 134.7, 138.5, 160.5, 165.3. IR
(neat) 3060, 1781, 1736, 1655, 1449, 1325, 1148, 967, 778, 701. HRMS
(ESI): m/z: calcd for C23H20NOþ2 [MþH]þ 342.1494, found 342.1488.
NMR (600 MHz, CDCl3)
d
1.35 (s, 3H), 3.85 (s, 3H), 4.48 (d, J¼9.6 Hz,
1H), 5.05 (dd, J¼1.8, 10.2 Hz, 1H), 5.20 (ddd, J¼1.8, 16.8 Hz, 1H), 5.91
(ddd, J¼16.8, 9.6, 10.2 Hz, 1H), 6.88 (ddd, J¼9.6, 10.2, 16.8 Hz, 1H),
7.00 (ddd, J¼1.0, 7.6, 7.6 Hz, 1H), 7.24 (dd, J¼1.0, 7.6, 7.6 Hz, 1H), 7.49
(t, J¼7.4 Hz, 2H), 7.57 (t, J¼7.4 Hz, 1H). 13C NMR (151 MHz, CDCl3)
4.2.25. (S*)-4-Methyl-4-((R*)-1-(naphthalen-2-yl)allyl)-2-
phenyloxazol-5(4H)-one (3i-B1). White solid. Mp 150e153 ꢀC. 1H
d
21.9, 50.0, 55.5, 73.8, 110.7, 118.9, 120.8, 126.1, 126.8, 128.0, 128.2,
NMR (600 MHz, CDCl3)
d
1.37 (s, 3H), 3.88 (d, J¼9.0 Hz, 1H), 5.11 (d,
128.8, 129.7, 132.6, 135.6, 157.3, 159.6, 180.9. IR (neat) 3033, 3006,
2836, 1806, 1640, 1461, 1300, 1242, 1099, 1076, 919, 879, 749, 678.
HRMS (ESI): m/z: calcd for C20H20NOþ3 [MþH]þ 322.1443, found
322.1434.
J¼10.2 Hz, 1H), 5.23 (d, J¼16.8 Hz, 1H), 6.08 (ddd, J¼9.0, 10.2,
16.8 Hz, 1H), 7.44e7.51 (m, 4H), 7.58 (t, J¼7.4 Hz, 1H), 7.68 (d,
J¼8.5 Hz, 1H), 7.83 (q, J¼8.7 Hz, 3H), 7.88 (s, 1H), 8.04 (d, J¼7.9 Hz,
2H). 13C NMR (151 MHz, CDCl3)
d 22.7, 57.7, 73.7, 77.4, 119.1, 126.0,
126.2, 127.2, 127.7, 128.0, 128.1, 128.3, 128.3, 128.9, 132.8, 132.8,
133.5, 135.7, 136.1, 160.0, 180.8. IR (neat) 3064, 2979, 1810, 1649,
1448, 1287, 1152, 996, 919, 745, 713. HRMS (ESI): m/z: calcd for
C23H20NOþ2 [MþH]þ 342.1494, found 342.1487.
4.2.20. (E)-2-(3-(2-Methoxyphenyl)allyl)-4-methyl-2-phenyloxazol-
5(2H)-one (5f). Yellow oil. 1H NMR (600 MHz, CDCl3)
d 2.27 (s, 3H),
3.01 (dd, J¼7.4, 14.2 Hz, 1H), 3.08 (dd, J¼7.4, 14.2 Hz, 1H), 3.80 (s,
3H), 5.89 (dt, J¼7.4, 16.0 Hz, 1H), 6.69 (d, J¼16.0 Hz, 1H), 6.83 (d,
J¼8.2 Hz, 1H), 6.88 (t, J¼7.5 Hz, 1H), 7.2 (t, J¼7.5 Hz, 1H), 7.26 (d,
J¼7.5 Hz, 1H), 7.35e7.41 (m, 3H), 7.59 (d, J¼7.7 Hz, 2H). 13C NMR
4.2.26. (E)-4-Methyl-2-(3-(naphthalen-2-yl)allyl)-2-phenyloxazol-
5(2H)-one (5i). White solid. Mp 176e179 ꢀC (decomp.). 1H NMR
(600 MHz, CDCl3)
d
2.28 (s, 3H), 3.06 (dd, J¼1.2, 7.4 Hz, 1H), 3.11 (dd,
(151 MHz, CDCl3)
d 13.9, 45.1, 55.4, 77.4, 107.3, 110.9, 120.7, 121.2,
J¼1.2, 7.4 Hz,1H), 6.04 (dt, J¼7.4,15.8 Hz,1H), 6.55 (d, J¼15.8 Hz,1H),
7.36e7.48 (m, 6H), 7.60 (d, J¼7.1 Hz, 2H), 7.63 (s, 1H), 7.75 (d,
J¼8.6 Hz, 1H), 7.78 (d, J¼6.7 Hz, 2H). 13C NMR (151 MHz, CDCl3)
125.9, 127.0, 128.6, 128.8, 128.9, 131.5, 138.6, 156.7, 160.3, 165.3. IR
(neat) 3031, 2938, 2837, 1780, 1598, 1580, 1489, 1148, 974, 753, 700.
HRMS (ESI): m/z: calcd for C20H20NOþ3 [MþH]þ 322.1443, found
322.1433.
d
14.0, 44.9,107.2,120.8,123.4,125.9,126.0,126.3,126.3,127.7,128.0,
128.3, 128.6, 128.9, 133.0, 133.5, 134.1, 136.5, 138.4, 160.4, 165.2. IR
(neat) 3057, 2915, 1781, 1655, 1141, 1077, 988, 819, 745, 699. HRMS
(ESI): m/z: calcd for C23H20NOþ2 [MþH]þ 342.1494, found 342.1484.
4.2.21. (S*)-4-((R*)-1-(2-Chlorophenyl)allyl)-4-methyl-2-
phenyloxazol-5(4H)-one (3g-B1). Colorless oil. 1H NMR (600 MHz,
CDCl3)
d
1.37 (s, 3H), 4.53 (d, J¼9.0 Hz, 1H), 5.09 (d, J¼10.2 Hz, 1H),
4.2.27. (S*)-4-Methyl-2-phenyl-4-((S*)-5-phenylpent-1-en-3-yl)ox-
5.24 (d, J¼16.8 Hz, 1H), 5.81 (ddd, J¼9.0, 10.2, 16.8 Hz, 1H), 7.20 (t,
J¼7.6 Hz, 1H), 7.32 (t, J¼7.6, 1H), 7.39 (d, J¼8.0 Hz, 1H), 7.49 (t,
J¼7.8 Hz, 2H), 7.58 (t, J¼7.8 Hz, 1H), 7.90 (d, J¼7.6 Hz, 1H), 8.04 (d,
azol-5(4H)-one (3j-B1). Colorless oil. 1H NMR (600 MHz, CDCl3)
d
1.45 (s, 3H), 1.54e1.60 (m, 2H), 2.41e2.49 (m, 2H), 2.67 (ddd,
J¼5.3, 10.1, 14.4 Hz, 1H), 5.23 (d, J¼17.0 Hz, 1H), 5.36 (d, J¼10.1 Hz,
1H), 5.78 (ddd, J¼10.1, 17.0 Hz, 1H), 7.10 (d, J¼7.6 Hz, 2H), 7.15 (t,
J¼7.4 Hz, 1H), 7.24 (t, J¼7.4 Hz, 2H), 7.47 (t, J¼7.7 Hz, 2H), 7.56 (t,
J¼7.7 Hz, 1H), 7.98 (d, J¼7.7 Hz, 2H). 13C NMR (151 MHz, CDCl3)
J¼7.6 Hz, 2H). 13C NMR (151 MHz, CDCl3)
d 21.8, 51.8, 73.8, 119.9,
125.9, 127.1, 128.1, 128.5, 128.8, 129.7, 130.3, 132.8, 134.7, 134.8, 136.1,
160.0, 180.4. IR (neat) 3069, 1817, 1651, 1580, 1451, 1293, 1159, 1005,
929, 877, 700. HRMS (ESI): m/z: calcd for C19H17ClNOþ2 [MþH]þ
326.0948, found 326.0938.
d
22.8, 31.0, 33.5, 51.2, 72.1, 120.3, 125.9, 125.9, 128.0, 128.4, 128.5,
128.8, 132.7, 135.9, 141.5, 160.0, 181.0. IR (neat) 2931, 1818, 1655,
1496, 1452, 1321, 1291, 1164, 999, 861, 694. HRMS (ESI): m/z: calcd
for C21H22NOþ2 [MþH]þ 320.1651, found 320.1640.
4.2.22. (E)-2-(3-(2-Chlorophenyl)allyl)-4-methyl-2-phenyloxazol-
5(2H)-one ((5g)). Yellow oil. 1H NMR (600 MHz, CDCl3)
d 2.29 (s,
3H), 3.04 (ddd, J¼1.2, 7.2, 14.4 Hz, 1H), 3.11 (ddd, J¼1.2, 7.2, 14.4 Hz,
1H), 5.89 (dt, J¼7.2, 15.6 Hz, 1H) 6.75 (d, J¼15.6 Hz,1H), 7.17 (m, 2H),
7.30e7.42 (m, 5H), 7.59 (d, J¼7.7 Hz, 2H). 13C NMR (151 MHz, CDCl3)
4.2.28. (R*)-4-Methyl-2-phenyl-4-((S*)-5-phenylpent-1-en-3-yl)ox-
azol-5(4H)-one (3j-B2). Colorless oil. 1H NMR (600 MHz, CDCl3)
d
1.48 (s, 3H) 1.67 (m,1H),1.92e1.97 (m,1H), 2.40e2.49 (m, 2H), 2.72
d
14.0, 44.7,107.0,123.6,125.9,126.9,127.0,128.6,128.8,129.0,129.7,
(ddd, J¼4.2, 10.2, 14.4 Hz, 1H), 5.20 (dd, J¼1.1, 17.0 Hz, 1H), 5.25 (dd,
132.8, 132.9, 135.0, 138.3, 160.4, 165.1. IR (neat) 3062, 1783, 1655,
J¼1.5, 10.2 Hz, 1H), 5.67 (ddd, J¼10.2, 17.0 Hz, 1H), 7.15 (d, J¼9.5 Hz,

M. Kawatsura et al. / Tetrahedron 67 (2011) 7686e7691
7691
2H), 7.18 (t, J¼7.4 Hz,1H), 7.26 (t, J¼7.4 Hz, 2H), 7.48 (t, J¼7.4 Hz, 2H),
References and notes
7.57 (t, J¼7.4 Hz, 1H), 7.99 (d, J¼7.4 Hz, 2H). 13C NMR (151 MHz,
1. (a) Mosey, R. A.; Fisk, J. S.; Tepe, J. J. Tetrahedron: Asymmetry 2008, 19,
2755e2762; (b) Mukerjee, A. K. Heterocycles 1987, 26, 1077e1097.
2. (a) Trost, B. M.; Dogra, K. J. Am. Chem. Soc. 2002, 124, 7256e7257; (b) Trost, B.
M.; Lee, C. J. Am. Chem. Soc. 2001, 123, 12191e12201; (c) Trost, B. M.; Ariza, X. J.
Am. Chem. Soc. 1999, 121, 10727e10737; (d) Trost, B. M.; Heinemann, C.; Ariza,
X.; Weigand, S. J. Am. Chem. Soc. 1999, 121, 8667e8668; (e) Trost, B. M.; Lee, C. B.
J. Am. Chem. Soc. 1998, 120, 6818e6819; (f) Trost, B. M.; Ariza, X. Angew. Chem.,
Int. Ed. 1997, 36, 2635e2637.
CDCl3)
d 25.6, 33.1, 36.6, 54.0, 75.5, 123.4, 129.1, 129.2, 131.2, 131.6,
131.7, 132.0, 135.9, 138.8, 144.9, 163.3, 183.4. IR (neat) 2933, 1820,
1653, 1496, 1451, 1321, 1292, 1159, 1003, 926, 879, 694. HRMS (ESI):
m/z: calcd for C21H22NOþ2 [MþH]þ 320.1651, found 320.1642.
4.2.29. (S)-4-((R)-1-(4-Fluorophenyl)allyl)-4-methyl-2-
phenyloxazol-5(4H)-one ((4S,10R)-3k-B1). Colorless oil. 1H NMR
ꢀ
3. (a) Frebault, F.; Luparia, M.; Oliveria, M. T.; Goddard, R.; Maulide, N. Angew.
Chem., Int. Ed. 2010, 49, 5672e5676; (b) Weber, M.; Jautze, S.; Frey, W.; Peters, R.
J. Am. Chem. Soc. 2010, 132, 12222e12225; (c) Kawatsura, M.; Ikeda, D.; Ishii, T.;
Komatsu, Y.; Uenishi, J. Synlett 2006, 2435e2438.
4. For reviews, see: (a) Takeuchi, R.; Kezuka, S. Synthesis 2006, 3349e3366; (b)
Takeuchi, R. Synlett 2002, 1954e1965.
(600 MHz, CDCl3)
d
1.34 (s, 3H), 3.69 (d, J¼9.6 Hz, 1H), 5.11 (dd,
J¼1.1,10.2 Hz,1H), 5.18 (dd, J¼1.1,16.8 Hz,1H), 5.96 (ddd, J¼9.6,10.2,
16.8 Hz, 1H), 7.03 (t, J¼8.6 Hz, 2H), 7.42 (d, J¼8.6 Hz, 1H), 7.43 (d,
J¼8.6 Hz, 1H), 7.49 (d, J¼7.5 Hz, 1H), 7.50 (d, J¼7.5 Hz, 1H), 7.59 (t,
J¼7.5 Hz, 1H), 8.01 (d, J¼8.3 Hz, 2H). 13C NMR (151 MHz, CDCl3)
5. Recent examples of iridium-catalyzed allylic alkylation, see: (a) Wu, Q.-F.; He,
H.; Liu, W.-B.; You, S.-L. J. Am. Chem. Soc. 2010, 132, 11418e11419; (b) Giacomina,
F.; Riat, D.; Alexakis, A. Org. Lett. 2010, 12, 1156e1159; (c) Liu, W.-B.; Zheng,
S.-C.; He, H.; Zhao, X.-M.; Dai, L.-X.; You, S.-L. Chem. Commun. 2009,
6604e6606; (d) Onodera, G.; Watabe, K.; Matsubara, M.; Oda, K.; Kezuka, S.;
Takeuchi, R. Adv. Synth. Catal. 2008, 350, 2725e2732; (e) Liu, W.-B.; He, H.; Dai,
L.-X.; You, S.-L. Org. Lett. 2008, 10, 1815e1818; (f) He, H.; Zheng, X.-J.; Li, Y.; Dai,
L.-X.; You, S.-L. Org. Lett. 2007, 9, 4339e4341; (g) Nemoto, T.; Sakamoto, T.;
Fukuyama, T.; Hamada, Y. Tetrahedron Lett. 2007, 48, 4977e4981; (h) Gnamm,
d
22.4, 56.7, 73.4, 115.4 (JCeF¼78.8 Hz), 119.1, 125.8, 128.0, 128.8,
130.7 (JCeF¼31.6 Hz), 132.8, 134.2, 135.4, 162.1 (JCeF¼245 Hz), 162.9,
180.5. 19F NMR (565 MHz, CDCl3)
d
46.5 (sep, J¼4.0 Hz). IR (neat)
2981, 1817, 1654, 1509, 1451, 1294, 1226, 1161, 927, 1004, 915, 702.
HRMS (ESI): m/z: calcd for C19H17FNOþ2 [MþH]þ 310.1243, found
310.1234. ½a 2D4
ꢃ29.0 (c 3.2, CHCl3) (93% ee). Enantiomer ratio was
ꢂ
€
€
C.; Forster, S.; Miller, N.; Brodner, K.; Helmchen, G. Synlett 2007, 790e794; (i)
€
determined by HPLC using a Daicel CHIRALPAK AD-H (hexane/2-
propanol¼200/1, flow: 0.2 mL/min, 254 nm, 35 ꢀC, tR 33.1 min
(major); tR 37.2 min (minor)).
Schelwies, M.; Dubon, P.; Helmchen, G. Angew. Chem., Int. Ed. 2006, 45,
2466e2469; (j) Alexakis, A.; Polet, D. Org. Lett. 2004, 6, 3529e3532; (k) Lip-
owsky, G.; Miller, N.; Helmchen, G. Angew. Chem., Int. Ed. 2004, 43, 4595e4597;
(l) Kinoshita, N.; Marx, K. H.; Tanaka, K.; Tsubaki, K.; Kawabata, T.; Yoshikai, N.;
Nakamura, E.; Fuji, K. J. Org. Chem. 2004, 69, 7960e7964; (m) García-Yebra, C.;
Janssen, J. P.; Rominger, F.; Helmchen, G. Organometallics 2004, 23, 5459e5470;
(n) Bartels, B.; García-Yebra, C.; Helmchen, G. Eur. J. Org. Chem. 2003,
1097e1103; (o) Stanley, L. M.; Bai, C.; Ueda, M.; Hartwig, J. F. J. Am. Chem. Soc.
2010, 132, 8918e8920.
6. Reaction by IrCl3, Ir(acac)3, Ir4(CO)12, Ir(cod)(acac) or [IrCp*Cl2]2 resulted in no
reaction.
7. Relative stereochemistry was determined by comparison with reported NMR
data in Ref. 2a.
4.2.30. (S,E)-2-(3-(4-Fluorophenyl)allyl)-4-methyl-2-phenyloxazol-
5(2H)-one ((S)-5k). Yellow oil. 1H NMR (600 MHz, CDCl3)
d 2.28 (s,
3H), 2.97 (ddd, J¼1.1, 7.5, 14.3 Hz, 1H), 3.05 (ddd, J¼1.1, 7.5, 14.3 Hz, 1H),
5.81 (dt, J¼7.5, 15.8 Hz, 1H), 6.35 (d, J¼15.8 Hz, 1H), 6.97 (t, J¼8.7 Hz,
2H), 7.23 (q, J¼5.3 Hz, 2H), 7.35e7.42 (m, 3H), 7.58 (d, J¼6.8 Hz, 2H).
13C NMR (151 MHz, CDCl3)
d
14.0, 44.7, 107.1, 115.5 (JCeF¼22.7 Hz),
8. Olefin geometry was determined to be E by X-ray crystallographic analysis of
5lb; see also Ref. 10.
120.2, 125.9, 127.8 (JCeF¼52.7 Hz), 128.6, 129.0, 132.9 (JCeF¼3.3 Hz),
135.2, 138.3, 160.4, 162.4 (JCeF¼246 Hz), 165.2. 19F NMR (565 MHz,
CDCl3)
d
47.5 (sep, J¼4.5 Hz). IR (neat) 3064, 2943, 1779, 1662, 1600.
1519, 1425, 1318, 1228, 1143, 1013, 843, 704. HRMS (ESI): m/z: calcd for
C19H17FNOþ2 [MþH]þ 310.1243, found 310.1234. ½a 2D4
ꢃ5.8 (c 1.9,
ꢂ
CHCl3) (88% ee). Enantiomer ratio was determined by HPLC using
a Daicel CHIRALPAK AD-H (hexane/2-propanol¼99/1, flow: 1.0 mL/
min, 254 nm, 35 ꢀC, tR 14.3 min (major); tR 17.6 min (minor)).
4.2.31. (S,E)-2-(3-(4-Bromophenyl)allyl)-2-(4-chlorophenyl)-4-
methyloxazol-5(2H)-one ((S)-5lb). White solid. Mp 214e216 ꢀC. 1H
9. The reaction using NaHMDS exhibited a lower yield, although the almost same
product ratio was obtained.
NMR (600 MHz, CDCl3)
d
2.28 (s, 3H), 2.92 (dd, J¼7.2, 14.4 Hz, 1H),
3.00 (dd, J¼7.2, 14.4 Hz, 1H), 5.88 (dt, J¼7.2, 16.2 Hz, 1H), 6.31 (d,
J¼16.2 Hz, 1H), 7.13 (d, J¼8.5 Hz, 2H), 7.37 (d, J¼8.5 Hz, 2H), 7.41 (d,
J¼8.5 Hz, 2H), 7.50 (t, J¼8.6 Hz, 2H). 13C NMR (151 MHz, CDCl3)
10. Recent examples of aza-Cope rearrangement, see: (a) Lukowski, M.; Jacobs, K.;
Hsueh, P.; Lindsay, H. A.; Milletti, M. C. Tetrahedron 2009, 65, 10311e10316; (b)
Rueping, M.; Antonchick, A. P. Angew. Chem., Int. Ed. 2008, 47, 10090e10093; (c)
ꢀ
Gloria, P. M. C.; Prabhakar, S.; Lobo, A. M. Tetrahedron Lett. 2008, 49,
d
14.0, 44.8, 106.5, 121.0, 121.7, 127.3, 127.8, 128.8, 131.7, 135.0, 135.4,
7355e7357; (d) Stas, S.; Tehrani, K. A.; Laus, G. Tetrahedron 2008, 64,
3457e3463; (e) Weston, M. H.; Nakajima, K.; Back, T. G. J. Org. Chem. 2008, 73,
135.4, 136.7, 160.6, 164.8. IR (neat) 3036, 2923, 1773, 1657, 1488,
ꢀ
4630e4637; (f) Gonzalez, I.; Bellas, I.; Souto, A.; Rodríguez, R.; Cruces, J. Tet-
1401, 1150, 971, 806. HRMS (ESI): m/z: calcd for C19H10BrClNO2þ
rahedron Lett. 2008, 49, 2002e2004; (g) Merino, P.; Tejero, T.; Mannucci, V.
Tetrahedron Lett. 2007, 48, 3385e3388.
[MþH]þ 404.0053, found 404.0045. ½a 2D4
ꢃ2.0 (c 0.30, CHCl3) (99%
ꢂ
11. Absolute configuration of oxazolinone derivatives was determined by X-ray
crystallographic analysis of (S)-5lb. Detailed X-ray crystallographic data are
available from the CCDC, 12 Union Road, Cambridge CB2, 1EZ, UK (www.ccdc.
cam.ac.uk) (CCDC 820985; see also Supplementary data).
ee). Enantiomer ratio was determined by HPLC using a Daicel
CHIRALPAK AD-H (hexane/2-propanol¼19/1, flow: 0.5 mL/min,
254 nm, 35 ꢀC, tR 19.1 min (major); tR 21.4 min (minor)). Re-
crystallization from dichloromethane/hexane at 5 ꢀC gave a suitable
colorless crystal for X-ray study (CCDC 820985).
12. The aza-Cope rearrangement of diastereomerically pure (4S10S)-3c-B2 (95% ee)
in toluene at 60 ꢀC gave a 93% ee of (S)-5c.
13. Kawatsura, M.; Ata, F.; Wada, S.; Hayase, S.; Uno, H.; Itoh, T. Chem. Commun.
2007, 298e300.
14. Lehmann, J.; Lloyd-Jones, G. C. Tetrahedron 1995, 51, 8863e8874.
Supplementary data
ꢁ
ꢀ
ꢁ
ꢀ
15. Stambasky, J.; Malkov, A. V.; Kocovsky, P. J. Org. Chem. 2008, 73, 9148e9150.
16. Kadnikova, E. N.; Thakor, V. A. Tetrahedron: Asymmetry 2008, 19, 1053e1058.
17. Marion, N.; Gealageas, R.; Nolan, S. P. Org. Lett. 2007, 9, 2653e2656.
18. Liu, X.; Hartwig, J. F. Org. Lett. 2003, 11, 1915e1918.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.08.016.