Photochemical Transformation of O-(β-Arylethyl) Arylimidates into 2,4-Diaryl-5-iodoxazoles with 1,3-Diiodo-5,5-dimethylhydantoin

Article abstract of DOI:10.1002/ejoc.202000383

Treatment of O-(β-arylethyl) arylimidates with 1,3-diiodo-5,5-dimethylhydantoin (DIH) under irradiation with a tungsten lamp in 1,2-dichloroethane gave the corresponding 2,4-diaryl-5-iodoxazoles and 2,4-diaryloxazoles in good to moderate yields, respectively, depending on the aryl group. It was proposed that the reactions proceeded through the formation of N-iodoimidates by the reaction of O-(β-arylethyl) arylimidates with DIH, followed by the formation of iminyl radicals via homolytic N–I bond cleavage, the 1,5-H shift by the iminyl radicals, the C–I bond formation of the formed carbon-centered radicals with iodine, the nucleophilic cyclization by the imino groups to form 2,4-diaryloxazolines, the oxidation of the formed 2,4-diaryloxazolines to 2,4-diaryloxazoles, and the iodination of the formed 2,4-diaryloxazoles to 2,4-diaryl-5-iodoxazoles with DIH.

Full text of DOI:10.1002/ejoc.202000383

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Photochemistry | Very Important Paper |
Photochemical Transformation of O-(ꢀ-Arylethyl) Arylimidates
into 2,4-Diaryl-5-iodoxazoles with 1,3-Diiodo-5,5-dimethyl-
hydantoin
Aya Saito[a] and Hideo Togo*[a]
Abstract: Treatment of O-(ꢀ-arylethyl) arylimidates with 1,3-di- lytic N–I bond cleavage, the 1,5-H shift by the iminyl radicals,
iodo-5,5-dimethylhydantoin (DIH) under irradiation with a tung- the C–I bond formation of the formed carbon-centered radicals
sten lamp in 1,2-dichloroethane gave the corresponding 2,4- with iodine, the nucleophilic cyclization by the imino groups to
diaryl-5-iodoxazoles and 2,4-diaryloxazoles in good to moder- form 2,4-diaryloxazolines, the oxidation of the formed
ate yields, respectively, depending on the aryl group. It was 2,4-diaryloxazolines to 2,4-diaryloxazoles, and the iodination of
proposed that the reactions proceeded through the formation the formed 2,4-diaryloxazoles to 2,4-diaryl-5-iodoxazoles with
of N-iodoimidates by the reaction of O-(ꢀ-arylethyl) arylimidates DIH.
with DIH, followed by the formation of iminyl radicals via homo-
Introduction
amides for the formation of 2-substituted oxazoles are known.
Recent reports for the preparation of oxazoles with transition
metals are as follows:[3] the preparation of 2,4,5-triaryloxazoles
with O-aroyl cyanohydrins in the presence of Pd(TFA)2 and
bpy;[3a] the preparation of 4,5-disubstituted 2-(trifluoromethyl)-
oxazoles with oximes, arenethiol, trifluoroacetic anhydride, NIS,
and K2S2O8 in the presence of Cu(OTf)2;[3b] the preparation of
4-substituted 2,5-diaryloxazoles with trans-2-aryl-3-nitrocyclo-
propane-1,1-dicarboxylates and aromatic nitriles in the pres-
ence of SnCl4;[3c] the preparation of 2,5-diaryloxazoles with N-
aroyl enamines in the presence of CuCl2 and N-methylimid-
azole;[3d] the preparation of 2-aryl-5-methyloxazoles with aroyl
chlorides and propargylamines via propargyl amides in the
presence of FeCl3;[3e] the preparation of 2-aryloxazole-4-
carboxylates with aromatic amides and α-bromoketones in the
presence of AgSbF6;[3f] and others.[3g,3h] Moreover, recent re-
ports for the preparation of oxazoles under transition-metal-
free conditions are as follow:[4] the preparation of 2,5-diaryl-
oxazoles with α-bromoacetophenones and benzylamines in the
presence of Eosin Y under blue LED irradiation;[4a] the prepara-
tion of 4,5-disubstituted 2-methyloxazoles with N-acetyl en-
amines, fluorobenziodoxole, and BF3·Et2O;[4b] the electrochemi-
cal preparation of 2-aryl-5-(fluoromethyl)oxazoles with N-
propargylamides in the presence of p-iodotoluene;[4c] the prep-
aration of 2,4,5-triaryloxazoles with 2H-azirines and aromatic al-
dehydes in the presence of 9-mesityl-10-methylacridinium per-
chlorate under blue LED irradiation;[4d] the preparation of 2,4-
disubstituted 5-aryloxazoles with alkyl aryl ketones, I2, Oxone®,
and CF3SO3H in nitriles;[4e] the preparation of 2,5-diaryloxazoles
with α-bromoacetophenones, benzylamines, I2, and K2CO3;[4f]
the preparation of 2,4,5-trisubstituted oxazoles with N-acyl
enamines, PhI(OAc)2, and BF3·Et2O;[4g] the preparation of 4-sub-
stituted 2,5-diaryloxazoles with vinyliminophosphoranes and
aroyl chlorides;[4h] and others.[4i,4j]
Oxazoles are one of the most important heteroaromatics be-
cause an oxazole unit is contained in many natural products,
such as plants and marine products, and some of those natural
products show potent biological activities.[1] In particular, 2-
aryloxazoles have attracted much attention due to their potent
biological activities, such as antibacterial and antifungal activi-
ties, as shown in Figure 1.[1a,1b]
Figure 1. Biologically active 2-aryloxazoles.
Synthetic studies of the oxazole unit have been carried out
extensively.[2] As typical conventional methods for the prepara-
tion of oxazoles, the Robinson-Gabriel synthesis with α-(acylam-
ino)ketones and the Van Leusen reaction with aldehydes and
α-(tosyl)methyl isocyanide for the formation of 2-unsubstituted
oxazoles, the Fisher oxazole synthesis with cyanohydrins and
aldehydes, and the Bredereck reaction with α-haloketones and
[a] A. Saito, Prof. Dr. H. Togo
Graduate School of Science, Chiba University,
Yayoi-cho 1-33, Inage-ku, Chiba 263-8522 Japan
Fax: 81-43-290-2792
E-mail: togo@faculty.chiba-u.jp
http://reaction-2.chem.chiba-u.jp/index.html
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.202000383.
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On the other hand, the synthetic uses of imino-nitrogen- herein the preparation of 2,4-diaryl-5-iodoxazoles from O-
centered radical (iminyl radicals) for the preparation of nitrogen- (ꢀ-arylethyl) arylimidates with DIH (1,3-diiodo-5,5-dimethyl-
containing heterocycles, such as dihydropyrroles and phen- hydantoin) under irradiation with a tungsten lamp.
anthridines, have attracted much attention recently.[5] Recent
synthetic studies of iminyl radicals for the preparation of nitro-
gen-containing heterocycles are as follows:[6] the preparation of
pyrrolines (dihydropyrroles) from O-methyl oximes of aryl 3-
butenyl ketones and SmI2;[6a] the preparation of pyrrolines from
O-benzoyl oximes of aryl 3-butenyl ketones and diethyl phos-
phite in the presence of AgNO3;[6b] the preparation of cyclo-
penta[b]quinoxalines from O-aroyl oximes of cyclobutanones
and aromatic isocyanides in the presence of fac-Ir(ppy)3 under
irradiation with LED lamp;[6c] the preparation of dihydronaphth-
alenones from O-benzoyl oximes of aryl isopentyl ketones in the
presence of Fe(acac)3;[6d] the preparation of spiropyrrolines from
O-aroyl oximes of alkyl o-biaryl ketones in the presence of
DBU under irradiation with a visible light;[6e] the preparation of
5-alkoxy-2-aryl-4-iodopyrrolines from O-alkyl imidates, NaI, and
PhI(OAc)2 under blue LED irradiation;[6f] and the preparation of
quinazolinones from N-(3-butenyl),N-cyanobenzamides, arene-
sulfinic acids, and tBuOOH in the presence of Na2Eosin Y under
green LED irradiation, or N-(3-butenyl),N-cyanobenzamides and
arenesulfonyl chlorides in the presence of Ru(bpy)3Cl2 under
blue LED irradiation.[6g] Those reactions proceed through the
formation of iminyl radicals at first, followed by the cyclization
onto olefinic groups by iminyl radicals, the cyclization onto aro-
matic rings by iminyl radicals, or the 1,5-H shift by iminyl radicals
and then cyclization. As regards synthetic studies of iminyl radi-
cals for the preparation of nitrogen-containing heteroaromatics,
we also reported the preparation of 6-aryl- or 6-alkylphen-
anthridines from the reactions of o-cyanobiaryls and aryllithiums
or alkyllithiums, followed by the reaction with water and then
with I2 at 60 °C;[7a] the preparation of 6-arylphenanthridines
from the reaction of aryl o-biaryl ketones, TMS2NH, and Sc(OTf)3,
followed by the reaction with I2 at 60 °C;[7b] and the preparation
of 2-arylquinolines from the reactions of ꢀ-arylpropionitriles and
aryllithiums, followed by the reaction with water and then with
NIS (N-iodosuccinimide) under irradiation with a tungsten
lamp.[7c] All those reactions proceed through the formation of
N-iodoimines, their homolytic N–I bond cleavage to form iminyl
radicals, and their cyclization on the aromatic rings.
Results and Discussion
First, treatment of triflate salt 1Aa (1.0 mmol) with NaH
(1.5 equiv.) in THF (4.0 mL) gave free O-(ꢀ-phenylethyl) p-tolyl-
imidate (1st step). After removal of the solvent, treatment of
generated O-(ꢀ-phenylethyl) p-tolylimidate with NIS (4.0 equiv.,
5.0 equiv., and 6.0 equiv.) in the presence of K2CO3 (3.0 equiv.)
in 1,2-dichloroethane (DCE, 5.0 mL) under irradiation with a
300 W tungsten lamp for 6 h in the range of 35–38 °C (2nd step)
gave 5-iodo-4-phenyl-2-p-tolyloxazole 4Aa in 68 %, 54 %, and
65 % yields, together with 4-phenyl-2-p-tolyloxazoline 2Aa in
15 %, 35 %, and 27 % yields, and 4-phenyl-2-p-tolyloxazole 3Aa
in 10 %, 11 %, and 0 % yields, respectively, as shown in Table 1
(entries 1–3). Under the same procedure and conditions, treat-
ment of O-(ꢀ-phenylethyl) p-tolylimidate with 1,3-diiodo-5,5-
dimethylhydantoin (DIH, 2.0 equiv., 2.5 equiv., and 3.0 equiv.),
which has two N–I groups, gave 4Aa in 42 %, 61 %, and 79 %
Table 1. Optimization for reaction conditions of 5-iodo-2-p-tolyl-4-phenylox-
azole 4Aa.
Entry
Reagent
[equiv.]
Condition
Time
[h]
Yield
[%]
1
2
3
4
5
6
7
NIS (4.0)
NIS (5.0)
NIS (6.0)
DIH (2.0)
DIH (2.5)
DIH (3.0)
DIH (3.0)
DIH (3.0)
DIH (3.0)
DIH (3.0)
DIH (3.0)
DIH (3.0)
I2 (3.0)
300 W W-hν
300 W W-hν
300 W W-hν
300 W W-hν
300 W W-hν
300 W W-hν
300 W W-hν
300 W W-hν
300 W W-hν
40 W W-hν
White LED
6
6
6
6
6
6
8
8
8
8
8
8
6
8
8
68 (15)[a] (10)[b]
54 (35)[a] (11)[b]
65 (27)[a]
42 (34)[a] (14)[b]
61 (17)[a]
79 (17)[a]
87 (8)[a]
8[c]
9[d]
10
11
12
13
14[f]
15[g]
19 (16)[a]
0 (74)[a] (20)[b]
20 (56)[a]
0 (14)[a]
Recently, Nagib et al. reported interesting methods for the
preparation of ꢀ-amino alcohols through the reactions of (tri-
chloromethyl)imidates prepared from alcohols and trichloro-
acetonitrile, with NaI and PhI(OAc)2 under visible-light irradia-
tion, via the formation of iminyl radicals, their 1,5-H shift, their
cyclization to form oxazolines, and their hydrolysis,[8a] and the
preparation of γ-functionalized ꢀ-amino alcohols from alcohols
through the reactions of (trichloromethyl)imidates with NaI and
PhI(OAc)2 under visible light irradiation via the formation of
amidyl radicals, their 1,5-H shift, formation of olefinic group,
iodocyclization, and their hydrolysis.[8b] He et al. also reported
the preparation of ꢀ-amino alcohols from (trichloromethyl)-
imidates, and 2-aryloxazolines from arylimidates with NIS or
with NIS and Ag2O at 110 °C.[8c]
70 °C
0
300 W W-hν
300 W W-hν
300 W W-hν
6 (26)[a] (54)[e]
0
DIH (3.0)
DIH (3.0)
0
[a] Yield of compound 2Aa. [b] Yield of compound 3Aa. [c] Reaction was
carried out without K2CO3. [d] In 2nd step, THF was used instead of DCE.
[e] Yield of recovered O-(ꢀ-phenylethyl) p-tolylimidate. [f] In 2nd step, BHT
(1.5 equiv.) was added. [g] In 2nd step, TEMPO (1.5 equiv.) was added.
As part of our synthetic studies of nitrogen-containing
heteroaromatics using iminyl radicals,[7] we would like to report
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yields, together with 2Aa in 34 %, 17 %, and 17 % yields, and oxazolines 2 and oxazoles 3 depending on the substituent, as
3Aa in 14 %, 0 %, and 0 % yields, respectively (entries 4–6). shown in Scheme 1. Treatment of triflate salts 1Da–1Dd and
Thus, DIH was a better choice than NIS for the formation of 5- 1Ea–1Ed of O-(ꢀ-arylethyl) p-methoxyphenylimidates and O-(ꢀ-
iodo-4-phenyl-2-p-tolyloxazole 4Aa in 79 % yield (entry 6).
Moreover, when the reaction time in the 2nd step was pro-
longed to 8 h under the same conditions, the yield of 5-iodo-
4-phenyl-2-p-tolyloxazole 4Aa was improved to 87 % (entry 7).
On the other hand, when the reaction was carried out without
K2CO3 under the same conditions in the 2nd step, the yield of
4Aa was dramatically decreased to 19 %, and 2Aa was formed
as well in 16 % yield (entry 8). When THF was used instead of
DCE in the 2nd reaction step, 4Aa was not obtained at all, and
2Aa and 3Aa were generated in 74 % and 20 % yields, respec-
tively (entry 9).
arylethyl) naphthalen-2-ylimidates bearing phenyl (a), p-tolyl
(b), p-fluorophenyl (c), and p-chlorophenyl (d) groups under the
same procedure and conditions gave also 4-aryl-5-iodo-2-
p-methoxyphenyloxazoles 4Da–4Dd and 4-aryl-5-iodo-2-
(naphthalen-2′-yl)oxazoles 4Ea–4Ed in moderate to good
yields, respectively, together with oxazolines 2 depending on
the substituent of the aromatics.
Here, 5-iodo-2-p-methoxyphenyl-4-p-tolyloxazole 4Db was
formed in 40 % yield together with p-iodoanisole in 41 % yield,
which would be generated through the electrophilic ipso-sub-
stitution of the p-methoxyphenylimidate group by an iodonium
species in the reaction of O-ꢀ-(p-tolyl)ethyl p-methoxyphenyl-
imidate with DIH. In addition, 4-p-fluorophenyl-5-iodo-2-p-
methoxyphenyloxazole 4Dc was produced in 54 % yield to-
gether with p-methoxybenzonitrile in 16 % yield, the latter of
which would be formed via a radical ꢀ-cleavage reaction of the
formed iminyl radical. Treatment of triflate salt 1Fa of
O-(ꢀ-phenylethyl) benzothiophen-2-ylimidate under the same
procedure and conditions gave 2-(benzothiophen-2′-yl)-5-iodo-
4-phenyloxazole 4Fa in 56 % yield, together with oxazoline 2Fa
in 36 % yield, whereas the same treatment of triflate salt of
O-(ꢀ-phenylethyl) benzofuran-2-ylimidate under the same
procedure and conditions gave 2-(benzofuran-2′-yl)-5-iodo-4-
phenyloxazole in low yield (ca. 10 %). The same treatment of
O-(ꢀ-p-nitrophenylethyl) arylimidate salts 1Ae, 1Be, 1Ce, 1Ee,
and 1Ge gave 2-aryl-4-p-nitrophenyloxazoles 3Ae, 3Be, 3Ce,
3Ee, and 3Ge in good to moderate yields, together with their
oxazolines 2 in 12 %, 19 %, 24 %, 33 %, and 33 % yields, respec-
tively. Thus, the results suggest that the iodination of formed
2-aryl-4-p-nitrophenyloxazoles at 5-position does not proceed
smoothly because of the electron-withdrawing p-nitrophenyl
group at 4-position. On the other hand, when O-(ꢀ-arylethyl) p-
chlorophenylimidates derived from 1Ga, 1Gb, and 1Gc bearing
an electron-withdrawing group, i.e., a p-chlorophenyl group, at
2-position were treated with DIH under the same irradiation
conditions in the range of 35–38 °C, p-chlorobenzonitrile was
obtained in 64 %, 72 %, and 74 % yields, respectively, probably
via the radical ꢀ-elimination of the formed iminyl radicals, with-
out the formation of oxazolines and oxazoles. However, when
the same irradiation reactions of O-(ꢀ-arylethyl) p-chlorophenyl-
imidates were carried out at 10 °C, corresponding oxazolines
2Ga, 2Gb, and 2Gc were obtained in 77 %, 75 %, and 74 %
yields, together with their 5-iodoxazoles in low yields, respec-
tively, although the reaction mixtures were further warmed at
40 °C for 5 h after the irradiation. Treatment of O-ꢀ-(p-nitro-
phenyl)ethyl p-methoxyphenylimidate salt 1De that has an
electron-withdrawing group, i.e., a p-nitrophenyl group, under
the same procedure and conditions gave also oxazolines 2De
in 66 % yield, together with 5-iodooxazole 4De in low yield.
Moreover, treatment of O-propyl p-tolylimidate salt 1Af and
Instead of a 300 W tungsten lamp, when the reaction of O-
(ꢀ-phenylethyl) p-tolylimidate with DIH was carried out under
irradiation with a 40 W tungsten lamp and a white LED lamp
(13.6 W) in the 2nd step, the yields of 4Aa were 20 % and 0 %,
and those of 2Aa were in 56 % and 14 %, respectively (entries
10, 11). Furthermore, when the 2nd reaction step was conducted
under warming conditions at 70 °C instead of irradiation with a
300 W tungsten lamp, 5-iodooxazole 4Aa was not formed at all
(entry 12). When molecular iodine (3.0 equiv.) instead of DIH
was used in the 2nd reaction step, 5-iodoxazole 4Aa was ob-
tained in only 6 % yield, together with oxazoline 2Aa and start-
ing O-(ꢀ-phenylethyl) p-tolylimidate in 26 % and 54 % yields,
respectively (entry 13).
From those results, treatment of O-(ꢀ-phenylethyl) p-tolylimi-
date (1.0 mmol) with DIH (3.0 equiv.) and K2CO3 (3.0 equiv.) in
DCE (5.0 mL) under irradiation with a 300 W tungsten lamp for
8 h in the 2nd reaction step gave 5-iodo-4-phenyl-2-p-tolylox-
azole 4Aa in the best yield (entry 7). As a gram-sale experiment,
treatment of salt 1Aa (5.0 mmol) under the same procedure
and conditions as those of entry 7 gave 5-iodo-4-phenyl-2-p-
tolyloxazole 4Aa in 70 % yield, as shown in Scheme 1. To under-
stand the reaction mechanism, the reactions of O-(ꢀ-phenyl-
ethyl) p-tolylimidate with DIH and K2CO3 in DCE in the 2nd step
were carried out in the presence of 2,6-di-tert-butyl-p-cresol
(BHT, 1.5 equiv.) and 2,2,6,6-tetramethylpiperidine 1-oxyl
(TEMPO, 1.5 equiv.) under the same conditions as those of entry
7. However, 5-iodo-4-phenyl-2-p-tolyloxazole 4Aa and related
compounds 2Aa and 3Aa were not formed at all in both reac-
tions (entries 14, 15). Thus, the results suggest that the 2nd step
is a radical-mediated reaction.
Based on those results, triflate salts 1Ab–1Ad, 1Ba–1Bd, and
1Ca–1Cd of O-(ꢀ-arylethyl) p-tolylimidates, O-(ꢀ-arylethyl)
phenylimidates, and O-(ꢀ-arylethyl) 3,5-dimethylphenylimidates
(1.0 mmol) bearing phenyl (a), p-tolyl (b), p-fluorophenyl (c),
and p-chlorophenyl (d) groups were treated with NaH
(1.5 equiv.) in THF (5.0 mL) at room temperature for 15 min.
(1st step), followed by removal of the solvent and subsequent
treatment with DIH (3.0 equiv.) and K2CO3 (3.0 equiv.) in DCE
(5.0 mL) under irradiation with a 300 W tungsten lamp for 8 h
(2nd step) to give 4-aryl-5-iodo-2-p-tolyloxazoles 4Ab–4Ad, O-butyl p-tolylimidate salt 1Ag under the same procedure and
4-aryl-5-iodo-2-phenyloxazoles 4Ba–4Bd, and 4-aryl-2-(3′,5′- conditions also gave 4-methyl-2-p-tolyloxazoline 2Af and 4-
dimethylphenyl)-5-iodoxazoles 4Ca–4Cd in good to moderate ethyl-2-p-tolyloxazoline 2Ag in 63 % and 68 % yields, respec-
yields, respectively, except 4Ba, together with small amounts of tively, although the reaction mixtures were further warmed at
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Scheme 1. Transformation of arylimidates 1 to 5-iodooxazoles 4.
40 °C for 24 h after the irradiation. Thus, oxidation of formed corresponding oxazoles 3 did not proceed smoothly under the
oxazolines 2 bearing electron-withdrawing groups, such as a present reaction conditions. Moreover, when the triflate salt of
p-nitrophenyl group, and an alkyl group at 4-position to the O-(ꢀ-phenylethyl) p-(trifluoromethyl)phenylimidate was treated
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under the same procedure and conditions, the reaction did not K2CO3 in DMF, and with ethynylbenzene and Cu in Et3N in the
proceed at all, i.e., N-iodonation did not occur due to the pres- presence of PdCl2(Ph3P)2 under warming conditions gave 4,5-
ence of a powerful electron-withdrawing group, such as a p- diphenyl-2-p-tolyloxazole 5Aa, 4-phenyl-5-styryl-2-p-tolylox-
(trifluoromethyl)phenyl group. Taken together, treatment of O- azole 6Aa, and 4-phenyl-5-phenylethynyl-2-p-tolyloxazole 7Aa
(ꢀ-arylethyl) arylimidates bearing p-tolyl (A), phenyl (B), 3,5- in good yields, respectively. 4-Phenyl-5-p-toluenesulfenyl-2-p-
dimethylphenyl(C),p-methoxyphenyl(D),naphthalen-2-yl(E),and tolyloxazole 8Aa could be also obtained by the treatment of
benzothiophen-2-yl (F) groups in the arylimidate part, and 4Aa with p-toluenethiol and K2CO3 in the presence of CuI in
bearing phenyl (a), p-tolyl (b), p-fluorophenyl (c), and p-chloro- iPrOH in moderate yield.
phenyl (d) groups in the ꢀ-arylethyl part, gave mainly the corre-
sponding 2,4-diaryl-5-iodoxazoles. On the other hand, treat-
ment of O-(ꢀ-arylethyl) arylimidates bearing a p-chlorophenyl
group in the arylimidate part, and bearing an alkyl group in-
stead of a ꢀ-arylethyl group gave oxazolines 2. Thus, the oxid-
ation of formed oxazolines 2 to oxazoles 3 and the iodination
of oxazoles 3 to 5-iodoxazoles 4 bearing electron-withdrawing
aryl groups or alkyl groups with DIH did not proceed smoothly.
A plausible reaction mechanism is shown in Scheme 3. O-(ꢀ-
Arylethyl) arylimidate generated from the reaction of triflate salt
1 and NaH reacts with DIH to form N-iodoimidate In-1. Once
N-iodoimidate In-1 is formed, homolytic bond cleavage of its
N–I bond occurs to produce iminyl radical In-2 and an iodine
atom. The 1,5-hydrogen atom shift (1,5-H shift)[9] from benzylic
hydrogen atom via a six-membered transition state by iminyl
radical In-2 occurs to form benzylic carbon-centred radical In-
Once 2,4-diaryl-5-iodoxazoles were obtained, they could be 3, which smoothly reacts with molecular iodine to form ꢀ-iodo-
smoothly converted into various 2,4-diaryloxazole derivatives. ethyl arylimidate In-4. Intramolecular nucleophilic cyclization of
Warming treatment of 5-iodo-4-phenyl-2-p-tolyloxazole 4Aa In-4 occurs in the 5-exo-tet mode to give 2,4-diaryloxazoline 2.
with Zn in ethanol gave 4-phenyl-2-p-tolyloxazole 3Aa in 96 % 2,4-Diaryloxazoline 2 further reacts with DIH to generate 2,4-
yield, as shown in Scheme 2. Treatment of 4Aa with PhB(OH)2 diaryloxazole 3 through intermediates In-5, In-6, and In-7.
and K2CO3 in a mixture of DMF and water, with styrene and Iodination of oxazole 3 finally occurs to form 2,4-diaryl-5-iodo-
oxazole 4, without electron-withdrawing groups, such as p-
chlorophenyl and p-nitrophenyl groups at 2- or 4-position, or
bearing an alkyl group at 4-position. Practically, the treatment
of 4-phenyl-2-p-tolyloxazoline 2Aa and 4-phenyl-2-p-tolylox-
azole 3Aa with DIH (2.0 equiv.) and K2CO3 (1.5 equiv.) in DCE
(5.0 mL) for 8 h under irradiation with a tungsten lamp gave
Scheme 2. Derivatization of 2Aa.
Eur. J. Org. Chem. 0000, 0–0
Scheme 3. Plausible reaction mechanism.
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O-(ꢀ-Phenylethyl) p-tolylimidate·TfOH salt (1Aa): white solid;
5-iodo-4-phenyl-2-p-tolyloxazole 4Aa in 53 % and 55 % yields,
respectively.
Finally, quite recently, Nagib et al. reported the preparation
of 2,4-diaryloxazoles from O-(ꢀ-arylethyl) arylimidates with CsI
and PhI(OAc)2 in toluene under 23 W fluorescent lighting, that
was exceedingly related to the present study.[10]
mp: 172–173 °C; IR (neat): ν = 3065, 1610, 1449, 1238, 1026, 736,
˜
630 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.44 (s, 3H), 3.26 (t, 2H, J =
5.9 Hz), 4.88 (t, 2H, J = 6.1 Hz), 7.27–7.37 (m, 7H), 7.87 (d, 2H, J =
8.3 Hz), 10.1 (s, 1H), 10.6 (s, 1H); 13C-NMR (100 MHz, [D6]DMSO): δ =
21.8, 39.5, 73.6, 121.2 (q, JC-F = 322.3 Hz), 123.4, 127.4, 129.1 (2C),
129.4 (2C), 129.6 (2C), 130.4 (2C), 137.1, 147.2, 171.7; HRMS (ESI):
Calcd for C16H18ON [M]+ = 240.1383, Found = 240.1378.
O-[ꢀ-(p-Toyl)ethyl] p-tolylimidate·TfOH salt (1Ab): white solid;
Conclusions
mp: 164–166 °C; IR (neat): ν = 3073, 1609, 1449, 1224, 1024, 742,
˜
628 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.33 (s, 3H), 2.44 (s, 3H),
3.21 (t, 2H, J = 5.9 Hz), 4.86 (t, 2H, J = 6.1 Hz), 7.14 (d, 2H, J =
7.9 Hz), 7.19 (d, 2H, J = 8.2 Hz), 7.33 (d, 2H, J = 7.9 Hz), 7.88 (d, 2H,
J = 8.4 Hz), 10.1 (s, 1H), 10.6 (s, 1H); 13C-NMR (100 MHz, [D6]DMSO):
δ = 20.7, 21.4, 33.3, 73.4, 120.9 (q, JC-F = 322.3 Hz), 123.0, 129.0 (2C),
129.1 (2C), 129.3 (2C), 130.0 (2C), 133.6, 136.1, 146.8, 171.3; HRMS
(ESI): Calcd for C17H20ON [M]+ = 254.1539, Found = 254.1532.
O-(ꢀ-Arylethyl) arylimidates, which can be prepared easily as
solids of triflate salts by the reaction of aromatic nitriles and
ꢀ-arylethyl alclohols in the presence of TfOH, react with DIH
under irradiation with a tungsten lamp to form the correspond-
ing 2,4-diaryl-5-iodoxazoles in good to moderate yields,
through the formation of N-iodoimidates, the homolytic bond
cleavage of their N–I bonds, the 1,5-H shift by iminyl radicals,
the nucleophilic cyclization in the 5-exo-tet mode to form oxaz-
olines, the oxidation of the oxazolines to oxazoles, and the
iodination of the oxazoles at 5-position. Thus, the present
method is a multi-step one-pot transition-metal-free reaction
for the preparation of 2,4-diaryl-5-iodoxazoles and 2.4-diarylox-
azoles from O-(ꢀ-arylethyl) arylimidates. It should be note that
O-[ꢀ-(p-Fluorophenyl)ethyl] p-tolylimidate·TfOH salt (1Ac):
white solid; mp: 167–169 °C; IR (neat): ν = 3056, 1610, 1467, 1223,
˜
1
1024, 828, 630 cm–1; H-NMR (400 MHz, CDCl3): δ = 2.45 (s, 3H),
3.24 (t, 2H, J = 5.9 Hz), 4.86 (t, 2H, J = 6.1 Hz), 7.04 (t, 2H, J = 8.6 Hz),
7.25–7.29 (m, 2H), 7.34 (d, 2H, J = 8.2 Hz), 7.87 (d, 2H, J = 8.4 Hz);
13C-NMR (100 MHz, CDCl3): δ = 21.3, 39.1, 73.1, 115.3 (d, 2C, JC-F
=
20.7 Hz), 120.8 (q, JC-F = 321.3 Hz), 123.0, 129.0 (2C), 130.0 (2C),
electron-withdrawing aryl groups, such as the p-nitrophenyl 131.1 (d, 2C, JC-F = 7.5 Hz), 132.9, 146.7, 161.4 (d, JC-F = 242.4 Hz),
171.2; HRMS (ESI): Calcd for C16H17ONF [M]+ = 258.1289, Found =
258.1280.
group, in the imidates retarded the reaction. We believe the
present method would be useful because it provides a straight-
forward procedure for the preparation of 2,4-diaryloxazoles
from O-(ꢀ-arylethyl) arylimidates under transition-metal-free
conditions.
O-[ꢀ-(p-Chlorophenyl)ethyl] p-tolylimidate·TfOH salt (1Ad):
white solid; mp: 166–168 °C; IR (neat): ν = 3071, 1609, 1449, 1224,
˜
1024, 628 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.45 (s, 3H), 3.23(t,
2H, J = 5.9 Hz), 4.86 (t, 2H, J = 6.1 Hz), 7.24 (d, 2H, J = 8.4 Hz), 7.31–
7.35 (m, 4H), 7.86 (d, 2H, J = 8.4 Hz); 13C-NMR (100 MHz, [D6]DMSO):
δ = 21.4, 39.1, 72.9, 120.9 (q, JC-F = 322.3 Hz), 123.0, 128.6 (2C),
129.0 (2C), 130.0 (2C), 131.1 (2C), 131.8, 135.9, 146.8, 171.3; HRMS
(ESI): Calcd for C16H17ON35Cl [M]+ = 274.0993, Found = 274.0984.
Experimental Section
1
General. H NMR spectra were measured on 400 MHz spectrome-
ters. Chemical shifts were recorded as follows: chemical shift in ppm
from internal tetramethylsilane on the δ scale, multiplicity (s =
singlet; d = doublet; t = triplet; q = quartet; sext = sextet; m =
multiplet; br = broad), coupling constant (Hz), integration, and as-
signment. 13C NMR spectra were measured on 100 MHz spectrome-
ters. Chemical shifts were recorded in ppm from the solvent reso-
nance employed as the internal standard (CDCl3 at 77.0 ppm, or
[D6]DMSO at 39.5 ppm). Characteristic peaks in the infrared (IR)
spectra were recorded in wave number, cm–1 on a JASCO FT/IR-
4100 spectrometer. Melting points were determined using a Yamato
Melting Point Apparatus Model MP-21. High-resolution mass spec-
tra (HRMS) were recorded by Thermo Fisher Scientific Exactive Orbi-
O-[ꢀ-(p-Nitrophenyl)ethyl] p-tolylimidate·TfOH salt (1Ae): white
solid; mp: 164–165 °C; IR (neat): ν = 3054, 1607, 1520, 1235, 1023,
˜
630 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.45 (s, 3H), 3.39 (t, 2H, J =
5.9 Hz), 4.94 (t, 2H, J = 6.1 Hz), 7.35 (d, 2H, J = 8.2 Hz), 7.50 (d, 2H,
J = 8.6 Hz), 7.86 (d, 2H, J = 8.6 Hz), 8.22 (d, 2H, J = 8.8 Hz), 10.1 (s,
1H), 10.7 (s, 1H); 13C-NMR (100 MHz, [D6]DMSO): δ = 21.3, 39.1, 72.4,
120.8 (q, JC-F = 322.3 Hz), 122.9, 123.6 (2C), 129.0 (2C), 130.0 (2C),
130.6 (2C), 145.3, 146.6, 146.8, 171.2; HRMS (ESI): Calcd for
C
16H17O3N2 [M]+ = 285.1234, Found = 285.1230.
O-Propyl p-tolylimidate·TfOH salt (1Af): white solid; mp: 108–
110 °C; IR (neat): ν = 3079, 1611, 1461, 1222, 1163, 1024, 628 cm–1
;
˜
trap mass spectrometers. Melting points were uncorrected. Thin- 1H-NMR (400 MHz, CDCl3): δ = 1.13 (t, 3H, J = 7.4 Hz), 2.00 (sext,
layer chromatography (TLC) was performed using 0.25 mm silica
2H, J = 7.4 Hz), 2.46 (s, 3H), 4.61 (t, 2H, J = 6.3 Hz), 7.37 (d, 2H, J =
gel plates (60F254). The products were purified by column chroma- 8.1 Hz), 8.00 (d, 2H, J = 8.5 Hz); 13C-NMR (100 MHz, [D6]DMSO): δ =
tography on neutral silica gel 60N (63–200 mesh).
10.0, 21.2, 21.4, 74.5, 120.9 (q, JC-F = 322.3 Hz), 123.2, 129.1 (2C),
130.0 (2C), 146.7, 171.5; HRMS (ESI): Calcd for C11H16ON [M]+
178.1226, Found = 178.1225.
=
Typical Procedure for Preparation of O-(ꢀ-arylethyl) Arylimid-
ate·TfOH Salts 1: Triflate salts 1 were prepared based on the litera-
ture[8a] with aromatic nitriles and ꢀ-arylethanols with TfOH. To a
solution of 2-phenylethyl alcohol (20.0 mmol, 2443.0 mg) and p-
O-Butyl p-tolylimidate·TfOH salt (1Ag): white solid; mp: 114–
115 °C; IR (neat): ν = 3032, 1608, 1454, 1224, 1160, 1028, 631 cm–1
;
˜
tolunitrile (24.0 mmol, 2812.0 mg) in CH2Cl2 (40.0 mL) was added 1H-NMR (400 MHz, CDCl3): δ = 1.02 (t, 3H, J = 7.5 Hz), 1.56 (sext,
TfOH (24.0 mmol, 2.1 mL) at room temperature. The obtained mix- 2H, J = 7.7 Hz), 1.95 (quin, 2H, J = 7.0 Hz), 2.46 (s, 3H), 4.65 (t, 2H,
ture was stirred for 24 h at 60 °C under argon atmosphere, and
then evaporated under reduced pressure. Diethyl ether was added
to the mixture at 0 °C until precipitation occurred. The salt was
filtered, and washed with diethyl ether to give O-(ꢀ-phenylethyl) p-
tolylimidate·TfOH salt (1Aa, 444.8 mg, 57 %).
J = 6.1 Hz), 7.37 (d, 2H, J = 8.4 Hz), 7.99 (d, 2H, J = 8.4 Hz), 10.1 (s,
1H), 10.7 (s, 1H); 13C-NMR (100 MHz, [D6]DMSO): δ = 13.5, 18.5, 21.4,
29.5, 72.9, 120.9 (q, JC-F = 322.3 Hz), 123.2, 129.0 (2C), 130.0 (2C),
146.7, 171.5; HRMS (ESI): Calcd for C12H18ON [M]+ = 192.1383,
Found = 192.1378.
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O-(ꢀ-Phenylethyl) phenylimidate·TfOH salt (1Ba): white solid;
mp: 124–126 °C; IR (neat): ν = 3081, 1602, 1456, 1238, 1023, 698 cm–1
(2C), 133.0, 136.8, 137.8, 139.4 (2C), 172.8; HRMS (ESI): Calcd for
C18H22ON [M]+ = 268.1696, Found = 268.1692.
;
˜
1H-NMR (400 MHz, CDCl3): δ = 3.27 (t, 2H, J = 5.9 Hz), 4.92 (t, 2H,
J = 6.1 Hz), 7.28–7.38 (m, 5H), 7.54 (t, 2H, J = 8.2 Hz), 7.72 (t, 1H,
J = 7.7 Hz), 7.97 (dd, 2H, J = 8.6, 1.1 Hz); 13C-NMR (100 MHz,
[D6]DMSO): δ = 33.7, 73.5, 121.0 (q, JC-F = 322.3 Hz), 126.1, 127.1,
128.8 (2C), 129.1 (2C), 129.3 (2C), 129.4 (2C), 135.6, 136.8, 171.6;
HRMS (ESI): Calcd for C15H16ON [M]+ = 226.1226, Found = 226.1223.
O-[ꢀ-(p-Fluorophenyl)ethyl] 3,5-dimethylphenylimidate·TfOH
salt (1Cc): white solid; mp: 128–130 °C; IR (neat): ν = 3048, 1602,
˜
1508, 1223, 1027, 835, 631 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.37
(s, 6H), 3.24 (t, 2H, J = 6.1 Hz), 4.85 (t, 2H, J = 6.1 Hz), 7.04 (t, 2H,
J = 8.8 Hz), 7.27–7.30 (m, 2H), 7.34 (s, 1H), 7.55 (s, 2H), 10.1 (s, 1H),
10.7 (s, 1H); 13C-NMR (100 MHz, CDCl3): δ = 20.9 (2C), 33.4, 73.8,
115.6 (d, JC-F = 20.1 Hz), 120.1 (q, JC-F = 318.5 Hz), 124.5, 126.7 (2C),
130.5 (d, JC-F = 8.5 Hz), 131.7 (d, JC-F = 3.8 Hz), 137.8, 139.4 (2C),
162.0 (d, JC-F = 245.2 Hz), 172.7; HRMS (ESI): Calcd for C17H19ONF
[M]+ = 272.1445, Found = 272.1441.
O-[ꢀ-(p-Tolyl)ethyl] phenylimidate·TfOH salt (1Bb): white solid;
mp: 125–127 °C; IR (neat): ν = 3102, 1602, 1381, 1243, 1025,
˜
628 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.33 (s, 3H), 3.23 (t, 2H, J =
6.1 Hz), 4.88 (t, 2H, J = 6.1 Hz), 7.16 (d, 2H, J = 7.9 Hz), 7.20 (d, 2H,
J = 8.3 Hz), 7.55 (t, 2H, J = 7.9 Hz), 7.73 (t, 1H, J = 7.6 Hz), 7.98 (dd,
2H, J = 8.6, 1.4 Hz), 10.3 (s, 1H), 10.8 (s, 1H); 13C-NMR (100 MHz,
[D6]DMSO): δ = 20.7, 33.2, 73.5, 120.8 (q, JC-F = 322.3 Hz), 126.0,
129.0 (2C), 129.1 (2C), 129.2 (2C), 129.4 (2C), 133.5, 135.6, 136.0,
171.5; HRMS (ESI): Calcd for C16H18ON [M]+ = 240.1383, Found =
240.1378.
O-[ꢀ-(p-Chlorophenyl)ethyl] 3,5-dimethylphenylimidate·TfOH
salt (1Cd): white solid; mp: 140–141 °C; IR (neat): ν = 3039, 1600,
˜
1226, 1024, 628 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.37 (s, 6H),
3.24 (t, 2H, J = 6.1 Hz), 4.86 (t, 2H, J = 6.1 Hz), 7.25 (d, 2H, J =
6.3 Hz), 7.33 (d, 2H, J = 8.6 Hz), 7.34 (s, 1H), 7.54 (s, 2H), 10.1 (s, 1H),
10.7 (s, 1H); 13C-NMR (100 MHz, CDCl3): δ = 20.9 (2C), 33.5, 73.6,
120.1 (q, JC-F = 319.5 Hz), 124.5, 126.7 (2C), 128.8 (2C), 130.3 (2C),
133.0, 134.5, 137.9, 139.5 (2C), 172.7; HRMS (ESI): Calcd for
O-[ꢀ-(p-Fluorophenyl)ethyl] phenylimidate·TfOH salt (1Bc):
white solid; mp: 100–102 °C; IR (neat): ν = 3080, 1601, 1511, 1223,
˜
C
17H19ONCl [M]+ = 288.1150, Found = 288.1146.
1024, 626 cm–1
;
1H-NMR (400 MHz, CDCl3): δ = 3.25 (t, 2H, J =
6.1 Hz), 4.88 (t, 2H, J = 6.1 Hz), 7.04 (t, 2H, J = 8.6 Hz), 7.28–7.30 (m,
2H), 7.55 (t, 2H, J = 7.7 Hz), 7.74 (t, 1H, J = 7.5 Hz), 7.97 (d, 2H, J =
7.5 Hz); 13C-NMR (100 MHz, [D6]DMSO): δ = 32.8, 73.4, 115.4 (d,
JC-F = 20.7 Hz), 120.9 (q, JC-F = 322.3 Hz), 126.0, 129.1 (2C), 129.4
(2C), 131.2 (d, JC-F = 8.5 Hz), 132.9 (d, JC-F = 2.8 Hz), 135.6, 161.5 (d,
O-[ꢀ-(p-Nitrophenyl)ethyl] 3,5-dimethylphenylimidate·TfOH
salt (1Ce): white solid; mp: 169–170 °C; IR (neat): ν = 3078, 1606,
˜
1517, 1246, 1028, 634 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.37 (s,
6H), 3.39 (t, 2H, J = 6.1 Hz), 4.93 (t, 2H, J = 6.1 Hz), 7.36 (s, 1H), 7.51
(d, 2H, J = 8.8 Hz), 7.55 (s, 2H), 8.23 (d, 2H, J = 8.8 Hz), 10.2 (s, 1H),
10.7 (s, 1H); 13C-NMR (100 MHz, [D6]DMSO): δ = 20.7 (2C), 39.1, 72.5,
120.8 (q, JC-F = 322.3 Hz), 123.6 (2C), 125.8, 126.5 (2C), 130.6 (2C),
137.0, 138.9 (2C), 145.2, 146.6, 171.6; HRMS (ESI): Calcd for
JC-F = 246.4 Hz), 171.6; HRMS (ESI): Calcd for C15H15ONF [M]+
=
244.1132, Found = 244.1127.
O-[ꢀ-(p-Chlorophenyl)ethyl] phenylimidate·TfOH salt (1Bd):
C
17H19O3N2 [M]+ = 299.1390, Found = 299.1385.
white solid; mp: 130–132 °C; IR (neat): ν = 3091, 1602, 1382, 1242,
˜
1
1025, 627 cm–1; H-NMR (400 MHz, CDCl3): δ = 3. 25 (t, 2H, J =
O-(ꢀ-Phenylethyl) p-methoxyphenylimidate·TfOH salt (1Da):
5.9 Hz), 4.89 (t, 2H, 5.9 Hz), 7.24–7.28 (m, 2H), 7.33 (d, 2H, J = 8.6 Hz),
7.56 (t, 2H, J = 7.7 Hz), 7.74 (t, 1H, J = 7.5 Hz), 7.97 (dd, 2H, J = 8.6,
1.4 Hz); 13C-NMR (100 MHz, [D6]DMSO): δ = 32.9, 73.1, 120.9 (q,
JC-F = 322.3 Hz), 126.0, 128.6 (2C), 129.0 (2C), 129.4 (2C), 131.1 (2C),
131.8, 135.6, 135.8, 171.5; HRMS (ESI): Calcd for C15H15ON35Cl [M]+ =
260.0837, Found = 260.0833.
yellow solid; mp: 155–157 °C; IR (neat): ν = 3067, 1601, 1456, 1241,
˜
1225, 1021, 750 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 3.25 (t, 2H, J =
6.1 Hz), 3.89 (s, 3H), 4.86 (t, 2H, J = 6.1 Hz), 6.99 (d, 2H, J = 9.0 Hz),
7.27–7.37 (m, 5H), 7.96 (d, 2H, J = 9.2 Hz); 13C-NMR (100 MHz,
CDCl3): δ = 34.3, 55.8, 73.7, 114.8 (2C), 116.3, 120.2 (q, JC-F
=
318.5 Hz), 127.1, 128.8 (2C), 128.9 (2C), 131.7 (2C), 136.2, 165.9,
171.5; HRMS (ESI): Calcd for C16H18O2N [M]+ = 256.1332, Found =
256.1330.
O-[ꢀ-(p-Nitrophenyl)ethyl] phenylimidate·TfOH salt (1Be): white
solid; mp: 134–136 °C; IR (neat): ν = 3064, 1600, 1523, 1240, 1023,
˜
1
697 cm–1; H-NMR (400 MHz, CDCl3): δ = 3.41 (t, 2H, J = 6.1 Hz),
O-[ꢀ-(p-Tolyl)ethyl] p-methoxyphenylimidate·TfOH salt (1Db):
4.97 (t, 2H, J = 6.3 Hz), 7.52 (d, 2H, J = 8.4 Hz), 7.58 (t, 2H, J =
7.9 Hz), 7.77 (t, 1H, J = 7.9 Hz), 7.97 (d, 2H, J = 7.9 Hz), 8.24 (d, 2H,
J = 8.4 Hz), 10.4 (s, 1H), 10.9 (s, 1H); 13C-NMR (100 MHz, [D6]DMSO:
δ = 33.3, 72.6, 120.9 (q, JC-F = 322.3 Hz), 123.7 (2C), 125.9, 129.0
(2C), 129.4 (2C), 130.6 (2C), 135.6, 145.3, 146.6, 171.5; HRMS (ESI):
Calcd for C15H15O3N2 [M]+ = 285.1234, Found = 285.1230.
yellow solid; mp: 135–137 °C; IR (neat): ν = 2987, 1605, 1463, 1233,
˜
1160, 1020, 632 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.33 (s, 3H),
3.21 (t, 2H, J = 5.9 Hz), 3.90 (s, 3H), 4.83 (t, 2H, J = 5.9 Hz), 7.00 (d,
2H, J = 9.1 Hz), 7.12–7.20 (m, 4H), 7.97 (d, 2H, J = 9.1 Hz), 9.91 (s,
1H), 10.4 (s, 1H); 13C-NMR (100 MHz, CDCl3): δ = 21.0, 33.9, 55.8,
73.9, 114.8 (2C), 116.4, 120.2 (q, JC-F = 318.5 Hz), 128.7 (2C), 129.4
(2C), 131.7 (2C), 133.1, 136.7, 165.9, 171.5; HRMS (ESI): Calcd for
O-(ꢀ-Phenylethyl) 3,5-dimethylphenylimidate·TfOH salt (1Ca):
C
17H20O2N [M]+ = 270.1489, Found = 270.1486.
white solid; mp: 127–129 °C; IR (neat): ν = 3049, 1600, 1241, 1026,
˜
630 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.36 (s, 6H), 3.26 (t, 2H, J =
5.9 Hz), 4.88 (t, 2H, J = 5.9 Hz), 7.27–7.37 (m, 6H), 7.54 (s, 2H), 10.1
(s, 1H), 10.7 (s, 1H); 13C-NMR (100 MHz, CDCl3): δ = 20.9 (2C), 34.2,
73.9, 120.1 (q, JC-F = 319.5 Hz), 124.6, 126.7 (2C), 127.1, 128.7 (2C),
128.9 (2C), 136.1, 137.8, 139.4 (2C), 172.7; HRMS (ESI): Calcd for
C17H20ON [M]+ = 254.1539, Found = 254.1538.
O-[ꢀ-(p-Fluorophenyl)ethyl] p-methoxyphenylimidate·TfOH salt
(1Dc): yellow solid; mp: 149–150 °C; IR (neat): ν = 2988, 1602, 1466,
˜
1235, 1024, 629 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 3.23 (t, 2H, J =
5.9 Hz), 3.90 (s, 3H), 4.84 (t, 2H, J = 5.9 Hz), 7.00 (d, 2H, J = 9.3 Hz),
7.04 (t 2H, J = 8.6 Hz), 7.25–7.29 (m, 2H), 7.97 (d, 2H, J = 9.1 Hz),
9.91 (s, 1H), 10.5 (s, 1H); 13C-NMR (100 MHz, [D6]DMSO): δ = 32.8,
56.0, 72.9, 114.9 (2C), 115.4 (d, JC-F = 20.7 Hz), 117.3, 120.9 (q, JC-F
=
O-[ꢀ-(p-Tolyl)ethyl] 3,5-dimethylphenylimidate·TfOH salt (1Cb):
322.3 Hz), 131.1 (d, 2C, JC-F = 8.5 Hz), 131.5 (2C), 133.0, 161.4 (d,
JC-F = 242.4 Hz), 165.2, 170.6; HRMS (ESI): Calcd for C16H17O2NF
[M]+ = 274.1238, Found = 274.1234.
white solid; mp: 151–153 °C; IR (neat): ν = 3039, 1601, 1226, 1158,
˜
1025, 631 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.34 (s, 3H), 2.36 (s,
6H), 3.22 (t, 2H, J = 6.1 Hz), 4.85 (t, 2H, J = 6.1 Hz), 7.16 (d, 2H, J =
7.9 Hz), 7.20 (d, 2H, J = 8.2 Hz), 7.33 (s, 1H), 7.54 (s, 2H), 10.1 (s, 1H),
10.6 (s, 1H); 13C-NMR (100 MHz, CDCl3): δ = 20.9 (2C), 21.0, 33.9,
74.2, 120.1 (q, JC-F = 318.5 Hz), 124.6, 126.8 (2C), 128.8 (2C), 129.4
O-[ꢀ-(p-Chlorophenyl)ethyl] p-methoxyphenylimidate·TfOH salt
(1Dd): yellow solid; mp: 150–152 °C; IR (neat): ν = 3086, 1601, 1441,
˜
1240, 1023, 628 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 3.23 (t, 2H, J =
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5.9 Hz), 3.90 (s, 3H), 4.84 (t, 2H, J = 6.1 Hz), 7.00 (d, 2H, J = 8.8 Hz),
1165, 1028, 634 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 3.45 (t, 2H, J =
7.24 (d, 2H, J = 8.6 Hz), 7.32 (d, 2H, J = 8.4 Hz), 7.96 (d, 2H, J = 5.9 Hz), 5.02 (t, 2H, J = 5.9 Hz), 7.55 (d, 2H, J = 8.6 Hz), 7.64 (t, 1H,
9.1 Hz), 9.92 (s, 1H), 10.5 (s, 1H); 13C-NMR (100 MHz, CDCl3): δ =
33.6, 55.8, 73.3, 114.8 (2C), 116.2, 120.1 (q, JC-F = 318.5 Hz), 128.9
(2C), 130.2 (2C), 131.6 (2C), 133.0, 134.6, 166.0, 171.5; HRMS (ESI):
Calcd for C16H17O2N35Cl [M]+ = 290.0942, Found = 290.0939.
J = 7.7 Hz), 7.72 (t, 1H, J = 7.7 Hz), 7.84 (dd, 1H, J = 8.8, 2.0 Hz),
7.90 (d, 1H, J = 8.6 Hz), 7.97 (d, 1H, J = 8.8 Hz), 8.03 (d, 1H, J =
8.2 Hz), 8.25 (d, 2H, J = 8.6 Hz), 8.66 (s, 1H), 10.4 (s, 1H), 11.0 (s, 1H);
13C-NMR (100 MHz, [D6]DMSO): δ = 33.4, 72.7, 120.9 (q, JC-F
=
321.3 Hz), 123.1, 123.4, 123.7 (2C), 128.0, 128.0, 129.2, 129.7, 130.1,
130.6 (2C), 131.5, 131.7, 135.9, 145.3, 146.7, 171.5; HRMS (ESI): Calcd
for C19H17O3N2 [M]+ = 321.1234, Found = 321.1231.
O-[ꢀ-(p-Nitrophenyl)ethyl] p-methoxyphenylimidate·TfOH salt
(1De): yellow solid; mp: 149–151 °C; IR (neat): ν = 3057, 1602, 1520,
˜
1230, 1023, 631 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 3.38 (t, 2H, J =
5.9 Hz), 3.91 (s, 3H), 4.93 (t, 2H, J = 5.9 Hz), 7.01 (d, 2H, J = 8.8 Hz),
7.50 (d, 2H, J = 8.4 Hz), 7.96 (d, 2H, J = 8.8 Hz), 8.23 (d, 2H, J =
O-(ꢀ-Phenylethyl) benzothiophen-2-ylimidate·TfOH salt (1Fa):
yellow solid; mp: 163–165 °C; IR (neat): ν = 3003, 1525, 1365, 1239,
˜
8.4 Hz), 9.96 (s, 1H), 10.5 (s, 1H); 13C-NMR (100 MHz, [D6]DMSO): δ = 1164, 1025, 632 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 3.26 (t, 2H, J =
33.5, 56.1, 72.3, 115.0 (2C), 117.3, 120.9 (q, JC-F = 321.3 Hz), 123.7
(2C), 130.6 (2C), 131.6 (2C), 145.4, 146.7, 165.3, 170.7; HRMS (ESI):
Calcd for C16H17O4N2 [M]+ = 301.1183, Found = 301.1180.
5.8 Hz), 4.90 (t, 2H, J = 5.8 Hz), 7.28–7.39 (m, 5H), 7.47 (td, 1H, J =
7.5, 1.1 Hz), 7.56 (td, 1H, J = 8.3, 1.1 Hz), 7.88 (dd, 1H, J = 8.3, 0.9 Hz),
8.00 (d, 1H, J = 7.9 Hz), 8.72 (s, 1H), 10.2 (s, 1H), 10.9 (s, 1H);
13C-NMR (100 MHz, [D6]DMSO): δ = 33.8, 73.9, 121.0 (q, JC-F
=
O-(ꢀ-Phenylethyl) naphthalen-2-ylimidate·TfOH salt (1Ea): yel-
322.3 Hz), 123.3, 126.1, 126.7, 127.1, 127.9, 128.8 (2C), 129.0, 129.4
(2C), 133.6, 136.7, 138.1, 142.3, 166.7; HRMS (ESI): Calcd for
C17H16ONS [M]+ = 282.0947, Found = 282.0947.
low solid; mp: 163–165 °C; IR (neat): ν = 3061, 1487, 1237, 1166,
˜
1027, 633 cm–1
;
1H-NMR (400 MHz, CDCl3): δ = 3.33 (t, 2H, J =
6.1 Hz), 4.97 (t, 2H, J = 6.1 Hz), 7.28–7.40 (m, 5H), 7.61 (t, 1H, J =
7.0 Hz), 7.69 (dd, 1H, J = 8.3, 1.4 Hz), 7.86–7.90 (m, 2H), 7.94 (d, 1H,
J = 8.8 Hz), 8.03 (d, 1H, J = 8.1 Hz), 8.65 (s, 1H), 10.3 (s, 1H), 10.9 (s,
O-(ꢀ-Phenylethyl) p-chlorophenylimidate·TfOH salt (1Ga): white
solid; mp: 129–131 °C; IR (neat): ν = 3033, 1595, 1447, 1227, 1024,
˜
1H); 13C-NMR (100 MHz, [D6]DMSO): δ = 33.7, 73.5, 120.9 (q, JC-F
=
633 cm–1; H-NMR (400 MHz, CDCl3): δ = 3.26 (t, 2H, J = 5.9 Hz),
1
322.3 Hz), 123.1, 123.4, 127.0, 128.0, 128.0, 128.7 (2C), 129.1, 129.3 4.90 (t, 2H, J = 6.1 Hz),7.27–7.30 (m, 3H), 7.35 (t, 2H, J = 8.2 Hz),
(2C), 129.7, 130.1, 131.5, 131.6, 135.8, 136.7, 171.4; HRMS (ESI): Calcd 7.50 (d, 2H, J = 8.6 Hz), 7.91(d, 2H, J = 8.8 Hz), 10.3 (s, 1H), 10.9 (s,
for C19H18ON [M]+ = 276.1383, Found = 267.1379.
1H); 13C-NMR (100 MHz, CDCl3): δ = 34.2, 74.5, 120.0 (q, JC-F
=
318.5 Hz), 123.1, 127.3 (2C), 128.8 (3C), 129.8 (2C), 130.5 (2C), 135.8,
143.0, 171.6; HRMS (ESI): Calcd for C15H15ON35Cl [M]+ = 260.0837,
Found = 260.0838.
O-[ꢀ-(p-Tolyl)ethyl] naphthalen-2-ylimidate·TfOH salt (1Eb): yel-
low solid; mp: 159–160 °C; IR (neat): ν = 3092, 1486, 1240, 1167,
˜
1028, 634 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.34 (s, 3H), 3.28 (t,
2H, J = 5.8 Hz), 4.94 (t, 2H, J = 5.8 Hz), 7.18 (d, 2H, J = 7.6 Hz), 7.24
(d, 2H, J = 8.3 Hz), 7.61 (t, 1H, J = 6.8 Hz), 7.69 (t, 1H, J = 6.8 Hz),
7.88–7.90 (m, 2H), 7.95 (d, 1H, J = 8.8 Hz), 8.04 (d, 1H, J = 7.9 Hz),
8.67 (s, 1H), 10.3 (s, 1H), 10.9 (s, 1H); 13C-NMR (100 MHz, [D6]DMSO):
O-[ꢀ-(p-Tolyl)ethyl] p-chlorophenylimidate·TfOH salt (1Gb):
white solid; mp: 145–147 °C; IR (neat): ν = 3033, 1591, 1447, 1227,
˜
1023, 649 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.33 (s, 3H), 3.22 (t,
2H, J = 5.9 Hz), 4.87 (t, 2H, J = 5.9 Hz), 7.11–7.19 (m, 4H), 7.51 (d,
δ = 20.7, 39.1, 73.6, 120.9 (q, JC-F = 322.3 Hz), 123.1, 123.4, 128.0, 2H, J = 8.8 Hz), 7.93 (d, 2H, J = 8.8 Hz), 10.3 (s, 1H), 10.9 (s, 1H); 13C-
128.0, 129.2 (2C), 129.3 (2C), 129.7 (2C), 130.1, 131.5, 131.7, 133.6, NMR (100 MHz, CDCl3): δ = 21.0, 33.8, 74.7, 120.0 (q, JC-F = 319.5 Hz),
135.8, 136.1, 171.4; HRMS (ESI): Calcd for C20H20ON [M]+ = 290.1539,
Found = 290.1537.
123.2, 128.7 (2C), 129.5 (2C), 129.8 (2C), 130.5 (2C), 132.7, 136.9,
143.1, 171.7; HRMS (ESI): Calcd for C16H17ON35Cl [M]+ = 274.0993,
Found = 274.0995.
O-[ꢀ-(p-Fluorophenyl)ethyl] naphthalen-2-ylimidate·TfOH salt
(1Ec): yellow solid; mp: 167–169 °C; IR (neat): ν = 3062, 1487, 1238,
O-[ꢀ-(p-Fluorophenyl)ethyl] p-chlorophenylimidate·TfOH salt
˜
1166, 1026, 634 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 3.30 (t, 2H, J = (1Gc): white solid; mp: 129–130 °C; IR (neat): ν = 3033, 1594, 1448,
˜
5.9 Hz), 4.94 (t, 2H, J = 6.1 Hz), 7.07 (t, 2H, J = 8.6 Hz), 7.31–7.34 (m,
2H), 7.63 (t, 1H, J = 7.9 Hz), 7.70 (t, 1H, J = 7.3 Hz), 7.86 (dd, 1H, J =
8.7, 1.8 Hz), 7.90 (d, 1H, J = 8.2 Hz), 7.96 (d, 1H, J = 8.8 Hz), 8.03 (d,
1225, 1021, 628 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 3.24 (t, 2H, J =
6.1 Hz), 4.87 (t, 2H, J = 6.1 Hz), 7.04 (tt, 2H, J = 8.6, 2.0 Hz), 7.24–
7.29 (m, 2H), 7.53 (d, 2H, J = 8.6 Hz), 7.92 (d, 2H, J = 8.6 Hz); 13C-
1H, J = 7.9 Hz), 8.66 (s, 1H), 10.3 (s, 1H), 10.9 (s, 1H); 13C-NMR NMR (100 MHz, CDCl3): δ = 33.4, 74.4, 115.7 (d, JC-F = 21.6 Hz), 120.0
(100 MHz, [D6]DMSO): δ = 32.8, 73.4, 115.4 (d, JC-F = 21.6 Hz), 120.8
(q, JC-F = 318.5 Hz), 123.1, 129.8 (2C), 130.4 (d, JC-F = 7.5 Hz), 130.5
(q, JC-F = 322.3 Hz), 123.1, 123.4, 128.0, 128.0, 129.2, 129.7, 130.1, (2C), 131.4 (d, JC-F = 2.8 Hz), 143.2, 162.0 (d, JC-F = 245.2 Hz), 171.6;
131.2 (d, JC-F = 8.5 Hz), 131.5, 131.6, 132.9, 135.8, 161.4 (d, JC-F
=
HRMS (ESI): Calcd for C15H14ON35ClF [M]+ = 278.0742, Found =
242.4 Hz), 171.4; HRMS (ESI): Calcd for C19H17ONF [M]+ = 294.1289, 278.0742.
Found = 294.1285.
O-[ꢀ-(p-Nitrophenyl)ethyl] p-chlorophenylimidate·TfOH salt
O-[ꢀ-(p-Chlorophenyl)ethyl] naphthalen-2-ylimidate·TfOH salt
(1Ge): white solid; mp: 151–153 °C; IR (neat): ν = 3032, 1592, 1524,
˜
(1Ed): yellow solid; mp: 167–169 °C; IR (neat): ν = 3088, 1488, 1239,
1227, 1021, 630 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 3.39 (t, 2H, J =
5.9 Hz), 4.96 (t, 2H, J = 6.1 Hz), 7.94 (d, 2H, J = 8.6 Hz), 7.54 (d, 2H,
J = 8.6 Hz), 7.92 (d, 2H, J = 8.6 Hz), 8.23 (d, 2H, J = 8.6 Hz); 13C-NMR
(100 MHz, CDCl3): δ = 33.6, 73.6, 120.9 (q, JC-F = 322.3 Hz), 125.0,
127.0, 128.7 (2C), 129.2 (2C), 129.6 (2C), 130.9 (2C), 136.6, 140.7,
170.6; HRMS (ESI): Calcd for C15H14O3N235Cl [M]+ = 305.0687,
Found = 305.0688.
˜
1028, 632 cm–1
;
1H-NMR (400 MHz, CDCl3): δ = 3.29 (t, 2H, J =
6.1 Hz), 4.94 (t, 2H, J = 6.1 Hz), 7.29 (d, 2H, J = 8.6 Hz), 7.35 (d, 2H,
J = 8.6 Hz), 7.61 (t, 1H, J = 7.0 Hz), 7.69 (t, 1H, J = 8.2 Hz), 7.85 (dd,
1H, J = 8.7, 1.8 Hz), 7.88 (d, 1H, J = 8.2 Hz), 7.94 (d, 1H, J = 8.6 Hz),
8.02 (d, 1H, J = 8.2 Hz), 8.64 (d, 1H, J = 1.6 Hz), 10.3 (s, 1H), 10.9 (s,
1H); 13C-NMR (100 MHz, [D6]DMSO): δ = 33.0, 73.2, 120.9 (q, JC-F
=
322.3 Hz), 123.1, 123.4, 127.9, 128.0, 128.6 (2C), 129.2, 129.7, 130.1,
131.2 (2C), 131.5, 131.6, 131.7, 135.8, 135.9, 171.4; HRMS (ESI): Calcd
for C19H17ON35Cl [M]+ = 310.0993, Found = 310.0991.
Typical Procedure for Transformation of O-(ꢀ-Arylethyl) Aryl-
imidate·TfOH Salts 1 into 2,4-Diaryl-5-iodoxazoles 4: To a solu-
tion of O-(ꢀ-phenylethyl) p-tolylimidate·TfOH salt (1Aa, 1.0 mmol,
389.4 mg) in THF (4.0 mL) was added NaH (1.5 mmol, 65.0 mg) at
O-[ꢀ-(p-Nitrophenyl)ethyl] naphthalen-2-ylimidate·TfOH salt
(1Ee): yellow solid; mp: 152–154 °C; IR (neat): ν = 3058, 1515, 1247, room temperature. The obtained mixture was stirred for 15 min. at
˜
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room temperature under argon atmosphere. After removal of the
8.7 Hz), 7.47–7.49 (m, 3H), 8.01–8.11 (m, 4H); 13C-NMR (100 MHz,
solvent, 1,2-dichloroethane (5.0 mL), K2CO3 (3.0 mmol, 414.6 mg), CDCl3): δ = 82.6, 115.5 (d, 2C, JC-F = 21.6 Hz), 126.3 (2C), 126.5,
and DIH (3.0 mmol, 1140.0 mg) were added to the residue. The 126.6, 128.8 (2C), 128.8 (d, 2C, JC-F = 8.5 Hz), 130.9, 144.3, 162.8 (d,
obtained mixture was stirred for 8 h in the range of 35–38 °C under
irradiation with a 300 W tungsten lamp. Sat. Na2SO3 aq. solution
(15.0 mL) was added to the reaction mixture and the product was
extracted with CHCl3 (15.0 mL × 3). The organic layer was dried with
Na2SO4 and filtered. After removal of the solvent, the residue was
purified by silica-gel column chromatography (eluent: n-hexane/
J
C-F = 248.1 Hz), 165.9; HRMS (ESI): Calcd for C15H10ONFI [M + H]+ =
365.9786, Found = 365.9780.
4-p-Chlorophenyl-5-iodo-2-phenyloxazole (4Bd): Yield: 194.0 mg
(51 %); white solid; mp: 123–124 °C; IR (neat): ν = 2987, 1477, 1092,
˜
961, 830 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 7.44 (d, 2H, J = 8.6 Hz),
7.47–7.50 (m, 3H), 8.01 (d, 2H, J = 8.6 Hz), 8.07–8.09 (m, 2H);
13C-NMR (100 MHz, CDCl3): δ = 83.0, 126.4 (2C), 126.5, 128.1 (2C),
128.7 (2C), 128.8 (2C), 129.0, 130.9, 134.3, 144.1, 166.0; HRMS (ESI):
Calcd for C15H10ON35ClI [M + H]+ = 381.9490, Found = 381.9486.
EtOAc
= 9:1) to give 5-iodo-4-phenyl-2-p-tolyloxazole (4Aa,
314.8 mg, 87 %).
5-Iodo-4-phenyl-2-p-tolyloxazole (4Aa): Yield: 314.8 mg (87 %);
white solid; mp: 90–92 °C; IR (neat): ν = 2915, 1558, 1500, 1093,
˜
2-(3′,5′-Dimethylphenyl)-5-iodo-4-phenyloxazole (4Ca): Yield:
725, 689 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.42 (s, 3H), 7.28 (d,
2H, J = 8.1 Hz), 7.38 (t, 1H, J = 7.4 Hz), 7.47 (t, 2H, J = 7.4 Hz), 7.98
(d, 2H, J = 8.3 Hz), 8.04 (d, 2H, J = 7.0 Hz); 13C-NMR (100 MHz,
CDCl3): δ = 21.9, 34.3, 74.0, 121.8, 127.2, 128.8 (2C), 128.9 (2C), 129.2
(2C), 130.2 (2C), 136.1, 147.8, 172.3; HRMS (ESI): Calcd for C16H13ONI
[M + H]+ = 362.0036, Found = 362.0031.
310.7 mg (83 %); white solid; mp: 151–153 °C; IR (neat): ν = 2969,
˜
1540, 1442, 1229, 1097, 694 cm–1; 1H-NMR (400 MHz, CDCl3): δ =
2.39 (s, 6H), 7.11 (s, 1H), 7.38 (t, 1H, J = 7.5 Hz), 7.47 (t, 2H, J =
7.5 Hz), 7.71 (s, 2H), 8.04 (d, 2H, J = 7.0 Hz); 13C-NMR (100 MHz,
CDCl3): δ = 21.2 (2C), 82.6, 124.1 (2C), 126.4, 126.9 (2C), 128.4 (2C),
130.5, 132.5 (2C), 138.4 (2C), 144.9, 166.2; HRMS (ESI): Calcd for
5-Iodo-2,4-di-p-tolyloxazole (4Ab): Yield: 283.8 mg (76 %); white C17H15ONI [M + H]+ = 376.0193, Found = 376.0194.
solid; mp: 125–126 °C; IR (neat): ν = 2973, 1501, 1086, 960, 826,
˜
2-(3′,5′-Dimethylphenyl)-5-iodo-4-p-tolyloxazole (4Cb): Yield:
728 cm–1
;
1H-NMR (400 MHz, CDCl3): δ = 2.40 (s, 3H), 2.41 (s, 3H),
248.7 mg (64 %); white solid; mp: 111–113 °C; IR (neat): ν = 2915,
˜
7.26–7.28 (m, 4H), 7.93 (d, 2H, J = 8.2 Hz), 7.97 (d, 2H, J = 8.2 Hz);
13C-NMR (100 MHz, CDCl3): δ = 21.4, 21.6, 81.9, 124.1, 126.3 (2C),
126.8 (2C), 127.7, 129.1 (2C), 129.4 (2C), 138.3, 141.1, 145.0, 166.0;
HRMS (ESI): Calcd for C17H15ONI [M + H]+ = 376.0193, Found =
376.0188.
1557, 1495, 1224, 1087, 957, 732 cm–1; 1H-NMR (400 MHz, CDCl3):
δ = 2.39 (s, 6H), 2.40 (s, 3H), 7.10 (s, 1H), 7.27 (d, 2H, J = 8.2 Hz),
7.71 (s, 2H), 7.93 (d, 2H, J = 8.2 Hz); 13C-NMR (100 MHz, CDCl3): δ =
21.2 (2C), 21.4, 82.1, 124.1 (2C), 126.5, 126.8 (2C), 127.7, 129.1 (2C),
132.5, 138.3, 138.4 (2C), 145.0, 166.1; HRMS (ESI): Calcd for
4-p-Fluorophenyl-5-iodo-2-p-tolyloxazole (4Ac): Yield: 304.2 mg
C
18H17ONI [M + H]+ = 390.0349, Found = 390.0348.
(80 %); white solid; mp: 122–124 °C; IR (neat): ν = 2987, 1500, 1222,
˜
4-p-Fluorophenyl-2-(3′,5′-dimethylphenyl)-5-iodoxazole (4Cc):
1087, 962, 827, 730 cm–1
;
1H-NMR (400 MHz, CDCl3): δ = 2.42 (s,
Yield: 203.3 mg (52 %); white solid; mp: 142–143 °C; IR (neat):
3H), 7.15 (t, 2H, J = 8.6 Hz), 7.29 (d, 2H, J = 7.9 Hz), 7.97 (d, 2H, J =
1
ν = 2971, 1558, 1491, 1293, 1102, 835 cm–1; H-NMR (400 MHz,
˜
8.4 Hz), 8.00–8.05 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ = 21.6, 82.1,
CDCl3): δ = 2.39 (s, 6H), 7.11 (s, 1H), 7.15 (tt, 2H, J = 8.8, 1.8 Hz),
115.4 (d, JC-F = 21.6 Hz), 123.9, 126.3 (2C), 126.7, 128.8 (d, JC-F
=
7.70 (s, 2H), 8.01–8.04 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ = 21.2
8.5 Hz), 129.5 (2C), 141.3, 144.2, 162.8 (d, JC-F = 248.1 Hz), 166.1;
HRMS (ESI): Calcd for C16H12ONFI [M + H]+ = 379.9942, Found =
379.9938.
(2C), 82.3, 115.4 (d, JC-F = 21.6 Hz), 124.0 (2C), 126.3, 126.7 (d, JC-F
=
2.8 Hz), 128.7 (d, JC-F = 8.5 Hz), 132.6 (2C), 138.4 (2C), 144.1, 162.7
(d, JC-F = 248.1 Hz), 166.2; HRMS (ESI): Calcd for C17H14ONFI [M +
4-p-Chlorophenyl-5-iodo-2-p-tolyloxazole (4Ad): Yield: 300.0 mg H]+ = 394.0099, Found = 394.0099.
(76 %); white solid; mp: 136–138 °C; IR (neat): ν = 2987, 1498, 1089,
˜
4-p-Chlorophenyl-2-(3′,5′-dimethylphenyl)-5-iodoxazole (4Cd):
961, 827, 729 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.42 (s, 3H), 7.28
(d, 2H, J = 8.4 Hz), 7.43 (d, 2H, J = 8.6 Hz), 7.96 (d, 2H, J = 8.1 Hz),
8.00 (d, 2H, J = 8.4 Hz); 13C-NMR (100 MHz, CDCl3): δ = 21.6, 82.6,
123.9, 126.3 (2C), 128.1 (2C), 128.6 (2C), 129.1, 129.5 (2C), 134.3,
Yield: 329.4 mg (80 %); white solid; mp: 131–133 °C; IR (neat): ν =
˜
2910, 1557, 1479, 1227, 1085, 733 cm–1; 1H-NMR (400 MHz, CDCl3):
δ = 2.39 (s, 6H), 7.11 (s, 1H), 7.44 (d, 2H, J = 8.2 Hz), 7.70 (s, 2H),
8.00 (d, 2H, J = 8.2 Hz); 13C-NMR (100 MHz, CDCl3): δ = 21.2 (2C),
82.8, 124.1 (2C), 126.3, 128.1 (2C), 128.6 (2C), 129.1, 132.7, 134.3,
138.5 (2C), 144.0, 166.3; HRMS (ESI): Calcd for C17H14ON35ClI [M +
H]+ = 409.9803, Found = 409.9804.
141.3, 144.0, 166.2; HRMS (ESI): Calcd for C16H12ONClI [M + H]+
395.9647, Found = 395.9643.
=
2,4-Diphenyl-5-iodoxazole (4Ba): Yield: 134.7 mg (39 %); white
solid; mp: 92–93 °C; IR (neat): ν = 3054, 1557, 1447, 1287, 1090,
˜
5-Iodo-2-p-methoxyphenyl-4-phenyloxazole
217.5 mg (58 %); yellow solid; mp: 92–93 °C; IR (neat): ν = 2973,
(4Da):
Yield:
704cm–1; 1H-NMR (400 MHz, CDCl3): δ = 7.39 (tt, 1H, J = 7.3, 1.4 Hz),
7.45–7.50 (m, 5H), 8.05 (d, 2H, J = 7.0 Hz), 8.08–8.11 (m, 2H); 13C-
NMR (100 MHz, CDCl3): δ = 82.9, 126.4 (2C), 126.7, 126.9 (2C), 128.4
(2C), 128.5, 128.8 (2C), 130.5, 130.8, 145.1, 165.9; HRMS (ESI): Calcd
for C15H11ONI [M + H]+ = 347.9880, Found = 347.9875.
˜
1615, 1498, 1246, 1021, 826 cm–1; 1H-NMR (400 MHz, CDCl3): δ =
3.88 (s, 3H), 6.98 (t, 2H, J = 9.0 Hz), 7.38 (t, 1H, J = 7.6 Hz), 7.47 (t,
2H, J = 7.6 Hz), 8.01–8.05 (m, 4H); 13C-NMR (100 MHz, CDCl3): δ =
55.4, 81.9, 114.1 (2C), 119.5, 126.8 (2C), 128.0 (2C), 128.4, 128.4 (2C),
130.6, 144.8, 161.6, 165.9; HRMS (ESI): Calcd for C16H13O2NI [M +
H]+ = 377.9985, Found = 377.9980.
5-Iodo-2-phenyl-4-p-tolyloxazole (4Bb): Yield: 295.9 mg (82 %);
white solid; mp: 101–103 °C; IR (neat): ν = 2987, 1495, 1086, 960,
˜
1
818, 687 cm–1; H-NMR (400 MHz, CDCl3): δ = 2.41 (s, 3H), 7.28 (d,
5-Iodo-2-p-methoxyphenyl-4-p-tolyloxazole
(4Db):
Yield:
2H, J = 8.4 Hz), 7.46–7.49 (m, 3H), 7.94 (d, 2H, J = 8.2 Hz), 8.07–8.10
(m, 2H); 13C-NMR (100 MHz, CDCl3): δ = 21.4, 82.4, 126.3 (2C), 126.8
(3C), 127.6, 128.8 (2C), 129.2 (2C), 130.7, 138.4, 145.2, 165.8; HRMS
(ESI): Calcd for C16H13ONI [M + H]+ = 362.0036, Found = 362.0031.
154.9 mg (40 %); white solid; mp: 125–127 °C; IR (neat): ν = 2968,
˜
1501, 1251, 1023, 825 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.40 (s,
3H), 3.88 (s, 3H), 6.98 (d, 2H, J = 8.8 Hz), 7.27 (d, 2H, J = 8.2 Hz),
7.92 (d, 2H, J = 8.2 Hz), 8.02 (d, 2H, J = 9.0 Hz); 13C-NMR (100 MHz,
CDCl3): δ = 21.3, 55.4, 81.3, 114.1 (2C), 119.6, 126.8 (2C), 127.8, 128.0
4-p-Fluorophenyl-5-iodo-2-phenyloxazole (4Bc): Yield: 266.0 mg
(73 %); white solid; mp: 118–119 °C; IR (neat): ν = 2987, 1494, 1231, (2C), 129.1 (2C), 138.3, 144.9, 161.6, 165.8; HRMS (ESI): Calcd for
˜
1
1093, 836, 684 cm–1; H-NMR (400 MHz, CDCl3): δ = 7.16 (t, 2H, J = C17H15O2NI [M + H]+ = 392.0142, Found = 392.0138.
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4-p-Fluorophenyl-5-iodo-2-p-methoxyphenyloxazole
(4Dc):
4-p-Nitrophenyl-2-p-tolyloxazole (3Ae): Yield: 202.2 mg (72 %);
Yield: 214.4 mg (54 %); yellow solid; mp: 136–138 °C; IR (neat):
yellow solid; mp: 194–197 °C; IR (neat): ν = 1605, 1504, 1330, 1105,
˜
1
ν = 1613, 1499, 1245, 1023, 827 cm–1; H-NMR (400 MHz, CDCl3): 852, 728 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.44 (s, 3H), 7.31 (d,
˜
δ = 3.88 (s, 3H), 6.98 (d, 2H, J = 9.1 Hz), 7.15 (t, 2H, J = 8.6 Hz), 7.99–
2H, J = 8.2 Hz), 7.97–8.02 (m, 4H), 8.10 (s, 1H), 8.30 (d, 2H, J =
9.1 Hz); 13C-NMR (100 MHz, CDCl3): δ = 21.6, 124.2 (2C), 126.0 (2C),
126.6 (2C), 129.6 (2C), 135.1, 137.5, 140.0 (2C), 141.3, 147.2, 162.8;
HRMS (ESI): Calcd for C16H13O3N2 [M + H]+ = 281.0921, Found =
281.0923.
8.04 (m, 4H); 13C-NMR (100 MHz, CDCl3): δ = 55.4, 81.5, 114.2 (2C),
115.4 (d, JC-F = 21.6 Hz), 119.4, 126.8, 128.1 (2C), 128.7 (d, JC-F
=
8.5 Hz), 144.1, 161.4, 162.7 (d, JC-F = 249.0 Hz), 165.9; HRMS (ESI):
Calcd for C16H12O2NFI [M + H]+ = 395.9891, Found = 395.9886.
4-p-Nitrophenyl-2-phenyloxazole (3Be): Yield: 120.2 mg (45 %);
4-p-Chlorophenyl-5-iodo-2-p-methoxyphenyloxazole
(4Dd):
yellow solid; mp: 176–178 °C; IR (neat): ν = 1603, 1515, 1330, 1107,
˜
Yield: 221.9 mg (54 %); white solid; mp: 136–137 °C; IR (neat):
1
856, 714 cm–1; H-NMR (400 MHz, CDCl3): δ = 7.49–7.53 (m, 3H),
ν = 1503, 1251, 1023, 834 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 3.88
˜
8.00 (d, 2H, J = 9.0 Hz), 8.11–8.16 (m, 3H), 8.30 (d, 2H, J = 9.0 Hz);
13C-NMR (100 MHz, CDCl3): δ = 124.2 (2C), 126.1 (2C), 126.6 (2C),
126.9, 128.9 (2C), 130.9, 135.4, 137.4, 140.1, 147.2, 162.6; HRMS (ESI):
Calcd for C15H11O3N2 [M + H]+ = 267.0764, Found = 267.0767.
(s, 3H), 6.99 (d, 2H, J = 9.1 Hz), 7.43 (d, 2H, J = 8.8 Hz), 7.98–8.03
(m, 4H); 13C-NMR (100 MHz, CDCl3): δ = 55.4, 82.0, 114.2 (2C), 119.3,
128.1 (4C), 128.6 (2C), 129.1, 134.2, 143.9, 161.7, 166.0; HRMS (ESI):
Calcd for C16H12O2NClI [M + H]+ = 411.9596, Found = 411.9591.
4-p-Nitrophenyl-2-(3′,5′-dimethylphenyl)oxazole (3Ce): Yield:
5-Iodo-2-(naphthalen-2′-yl)-4-phenyloxazole
249.2 mg (63 %); white solid; mp: 111–113 °C; IR (neat): ν = 1549,
(4Ea):
Yield:
154.3 mg (52 %); yellow solid; mp: 174–176 °C; IR (neat): ν = 1608,
˜
˜
1513, 1333, 1112, 851, 733 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.41
(s, 6H), 7.14 (s, 1H), 7.75 (s, 2H), 7.99 (d, 2H, J = 9.0 Hz), 8.11 (s, 1H),
8.30 (d, 2H, J = 9.0 Hz); 13C-NMR (100 MHz, CDCl3): δ = 21.2 (2C),
124.1 (2C), 124.3 (2C), 126.0 (2C), 126.6, 132.6, 135.2, 137.5, 138.5
(2C), 140.0, 147.1, 162.9; HRMS (ESI): Calcd for C17H15O3N2 [M +
H]+ = 295.1077, Found = 295.1077.
1444, 1291, 1093, 822, 753 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 7.41
(tt, 1H, J = 7.4, 2.0 Hz), 7.50 (t, 2H, J = 7.4 Hz), 7.53–7.58 (m, 2H),
7.87–7.90 (m, 1H), 7.93–7.98 (m, 2H), 8.09 (d, 2H, J = 7.0 Hz), 8.19
(dd, 1H, J = 8.5, 1.8 Hz), 8.60 (s, 1H); 13C-NMR (100 MHz, CDCl3): δ =
83.1, 123.1, 123.9, 126.4, 126.8, 126.9 (2C), 127.4, 127.8, 128.5 (2C),
128.5, 128.6, 128.8, 130.5, 132.9, 134.3, 145.2, 166.0; HRMS (ESI):
Calcd for C19H13ONI [M + H]+ = 398.0036, Found = 398.0032.
2-(Naphthalen-2′-yl)-4-p-nitrophenyloxazole
(3Ee):
Yield:
316.3 mg (45 %); yellow solid; mp: 196–198 °C; IR (neat): ν = 1598,
˜
5-Iodo-2-(naphthalen-2′-yl)-4-p-tolyloxazole
271.3 mg (66 %); white solid; mp: 130–131 °C; IR (neat): ν = 1547,
(4Eb):
Yield:
1
1507, 1305, 1105, 829, 749 cm–1; H-NMR (400 MHz, CDCl3): δ =
˜
7.55–7.60 (m, 2H), 7.88–7.91 (m, 1H), 7.96–7.98 (m, 2H), 8.03 (d, 2H,
J = 8.8 Hz), 8.17 (s, 1H), 8.21 (dd, 1H, J = 8.6, 1.6 Hz), 8.31 (d, 2H,
J = 8.6 Hz), 8.62 (s, 1H); 13C-NMR (100 MHz, CDCl3): δ = 123.3, 124.1,
124.2 (2C), 126.1 (2C), 126.8, 126.9, 127.6, 127.9, 128.8 (2C), 132.9,
134.4, 135.6, 137.4, 140.3, 147.3, 162.8; HRMS (ESI): Calcd for
1493, 1290, 1086, 818, 751 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.42
(s, 3H), 7.30 (d, 2H, J = 7.6 Hz), 7.53–7.57 (m, 2H), 7.86–7.89 (m, 1H),
7.92–7.98 (m, 4H), 8.18 (dd, 1H, J = 8.6, 1.8 Hz), 8.58 (s, 1H); 13C-
NMR (100 MHz, CDCl3): δ = 21.4, 82.6, 123.1, 124.0, 126.4, 126.8,
126.8 (2C), 127.4, 127.6, 127.8, 128.6, 128.8, 129.2 (2C), 132.9, 134.3,
C
19H13O3N2 [M + H]+ = 317.0921, Found = 317.0918.
138.4, 145.3, 165.9; HRMS (ESI): Calcd for C20H15ONI [M + H]+
412.0193, Found = 412.0187.
=
2-p-Chlorophenyl-4-p-nitrophenyloxazole (3Ge): Yield: 190.2 mg
(63 %); yellow solid; mp: 184–186 °C; IR (neat): ν = 1607, 1513, 1342,
˜
1088, 851, 732 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 7.49 (td, 2H, J =
8.8, 2.0 Hz), 7.99 (td, 2H, J = 9.0, 2.0 Hz), 8.07 (td, 2H, J = 8.8, 2.0 Hz),
8.13 (s, 1H), 8.31 (td, 2H, J = 9.0, 2.0 Hz); 13C-NMR (100 MHz, CDCl3):
δ = 124.2 (2C), 125.3, 126.1 (2C), 127.9 (2C), 129.2 (2C), 135.6, 137.1,
137.2, 140.3, 147.3, 161.6; HRMS (ESI): Calcd for C15H10O3N2Cl [M +
H]+ = 303.0347, Found = 303.0347.
4-p-Fluorophenyl-5-iodo-2-(naphthalen-2′-yl)oxazole
Yield: 303.7 mg (73 %); white solid; mp: 144–146 °C; IR (neat): ν =
(4Ec):
˜
1547, 1491, 1214, 1095, 835, 753 cm–1; 1H-NMR (400 MHz, CDCl3):
δ = 7.18 (t, 2H, J = 8.8 Hz), 7.54–7.59 (m, 2H), 7.87–7.90 (m, 1H),
7.93–7.97 (m, 2H), 8.05–8.10 (m, 2H), 8.17 (dd, 1H, J = 8.6, 1.8 Hz),
8.58 (s, 1H); 13C-NMR (100 MHz, CDCl3): δ = 82.8, 115.5 (d, 2C,
JC-F = 21.6 Hz), 123.0, 123.8, 126.4, 126.6 (2C), 126.8, 127.5, 127.9,
128.7, 128.8 (d, 2C, JC-F = 8.5 Hz), 132.9, 134.3, 144.5, 162.8 (d,
2-p-Chlorophenyl-4-phenyloxazoline (2Ga): Yield: 197.9 mg
(77 %); white solid; mp: 86–87 °C; IR (neat): ν = 1641, 1488, 1258,
˜
J
C-F = 249.0 Hz), 166.0; HRMS (ESI): Calcd for C19H12ONFI [M + H]+ =
1069, 696 cm–1
;
1H-NMR (400 MHz, CDCl3): δ = 4.28 (t, 1H, J =
415.9942, Found = 415.9938.
8.3 Hz), 4.80 (dd, 1H, J = 10.1, 8.5 Hz), 5.38 (dd, 1H, J = 10.1, 8.1 Hz),
7.27–7.31 (m, 3H), 7.35–7.38 (m, 2H), 7.42 (d, 2H, J = 8.5 Hz), 7.98
(d, 2H, J = 8.5 Hz); 13C-NMR (100 MHz, CDCl3): δ = 70.2, 75.0, 126.0,
126.7 (2C), 127.7, 128.7 (2C), 128.8 (2C), 129.8 (2C), 137.7, 142.1,
163.8; HRMS (ESI): Calcd for C15H13ON35Cl [M + H]+ = 258.0680,
Found = 258.0684.
4-p-Chlorophenyl-5-iodo-2-(naphthalen-2′-yl)oxazole
Yield: 273.0 mg (63 %); white solid; mp: 140–142 °C; IR (neat): ν =
(4Ed):
˜
1549, 1479, 1282, 1090, 828, 751 cm–1; 1H-NMR (400 MHz, CDCl3):
δ = 7.46 (d, 2H, J = 8.8, Hz), 7.53–7.59 (m, 2H), 7.86–7.90 (m, 1H),
7.92–7.97 (m, 2H), 8.04 (d, 2H, J = 8.8 Hz), 8.16 (dd, 1H, J = 8.6,
1.8 Hz), 8.56 (s, 1H); 13C-NMR (100 MHz, CDCl3): δ = 83.3, 123.0,
123.7, 126.5, 126.8, 127.5, 127.8, 128.1 (2C), 128.7 (2C), 128.8, 129.0
(2C), 132.9, 134.3 (2C), 144.2, 166.0; HRMS (ESI): Calcd for
C19H12ON35ClI [M + H]+ = 431.9647, Found = 431.9642.
2-p-Chlorophenyl-4-p-tolyloxazoline (2Gb): Yield: 203.6 mg
(75 %); white solid; mp: 100–101 °C; IR (neat): ν = 1643, 1489, 1269,
˜
1
1074, 954, 810 cm–1; H-NMR (400 MHz, CDCl3): δ = 2.34 (s, 3H),
4.27 (t, 1H, J = 8.3 Hz), 4.78 (dd, 1H, J = 10.2, 8.3 Hz), 5.35 (dd, 1H,
J = 10.1, 8.3Hz), 7.15–7.20 (m, 4H), 7.41 (d, 2H, J = 8.8 Hz), 7.97 (d,
2H, J = 8.8 Hz); 13C-NMR (100 MHz, CDCl3): δ = 21.1, 69.9, 75.0,
126.1, 126.6 (2C), 128.6 (2C), 129.4 (2C), 129.8 (2C), 137.4, 137.6,
2-(Benzothiophen-2′-yl)-5-iodo-4-phenyloxazole (4Fa): Yield:
203.7 mg (56 %); yellow solid; mp: 162–164 °C; IR (neat): ν = 1600,
˜
1
1445, 1293, 1074, 962, 746 cm–1; H-NMR (400 MHz, CDCl3): δ =
139.1, 163.6; HRMS (ESI): Calcd for C16H15ON35Cl [M + H]+
272.0837, Found = 272.0840.
=
7.38–7.45 (m, 3H), 7.46–7.50 (m, 2H), 7.84–7.90 (m, 2H), 7.97 (s, 1H),
8.03–8.06 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ = 83.2, 122.5, 124.7,
125.0, 125.0, 126.1, 127.0 (2C), 128.5 (2C), 128.6, 128.7, 130.1, 139.3,
2-p-Chlorophenyl-4-p-fluorophenyloxazoline
(2Gc):
Yield:
140.7, 145.4, 161.9; HRMS (ESI): Calcd for C17H11ONIS [M + H]+
403.9601, Found = 403.9601.
=
205.0 mg (74 %); white solid; mp: 98–100 °C; IR (neat): ν = 1637,
˜
1507, 1223, 1094, 832 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 4.24 (t,
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1H, J = 8.3 Hz), 4.80 (dd, 1H, J = 10.1, 8.5 Hz), 5.37 (dd, 1H, 10.1,
8.1 Hz), 7.05 (tt, 2H, J = 8.5, 2.0 Hz), 7.24–7.29 (m, 2H), 7.42 (d, 2H,
J = 8.8 Hz), 7.97 (d, 2H, J = 8.8 Hz); 13C-NMR (100 MHz, CDCl3): δ =
69.4, 74.9, 115.6 (d, JC-F = 21.6 Hz), 125.8, 128.3 (d, JC-F = 8.5 Hz),
umn chromatography (eluent: n-hexane/EtOAc = 9:1) to give 4,5-
diphenyl-2-p-tolyloxazole (5Aa, 141.1 mg, 91 %).
4,5-Diphenyl-2-p-tolyloxazole (5Aa): Yield: 141.1 mg (91 %); white
solid; mp: 126–128 °C; IR (neat): ν = 2987, 1496, 1021, 964, 762,
˜
128.7 (2C), 129.8 (2C), 137.8, 137.9 (d, JC-F = 2.8 Hz), 162.2 (d, JC-F
245.2 Hz), 163.9; HRMS (ESI): Calcd for C15H12ON35ClF [M + H]+
276.0586, Found = 276.0588.
=
=
685 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.43 (s, 3H), 7.29 (d, 2H,
J = 7.9 Hz), 7.34 –7.43 (m, 6H), 7.68 (d, 2H, J = 6.7 Hz), 7.73 (d, 2H,
J = 6.7 Hz), 8.05 (d, 2H, J = 8.1 Hz); 13C-NMR (100 MHz, CDCl3): δ =
21.5, 124.6, 126.4 (2C), 126.4 (2C), 128.1 (3C), 128.4, 128.5 (2C), 128.6
2-p-Methoxyphenyl-4-p-nitrophenyloxazoline
(2De):
Yield:
197.9 mg (66 %); yellow solid; mp: 100–102 °C; IR (neat): ν = 2955, (2C), 129.0, 129.4 (2C), 132.6, 136.6, 140.6, 145.2, 160.3; HRMS (ESI):
˜
1650, 1421, 1337, 1247, 1074, 739 cm–1; 1H-NMR (400 MHz, CDCl3): Calcd for C22H18ON [M + H]+ = 312.1383, Found = 312.1384.
δ = 3.88 (s, 3H), 4.21 (t, 1H, J = 8.3 Hz), 4.84 (dd, 1H, J = 10.1, 8.5 Hz),
Transformation of 5-Iodo-4-phenyl-2-p-tolyloxazole 4Aa into 4-
5.48 (dd, 1H, J = 10.1, 8.1 Hz), 6.97 (d, 2H, J = 8.8 Hz), 7.49 (d, 2H,
Phenyl-(E)-5-styryl-2-p-tolyloxazole 6Aa: To a mixture of 5-iodo-
J = 8.5 Hz), 7.98 (d, 2H, J = 9.0 Hz), 8.22 (d, 2H, J = 9.0 Hz); 13C-NMR
4-phenyl-2-p-tolyloxazole (4Aa, 0.5 mmol, 180.6 mg), K2CO3
(100 MHz, CDCl3): δ = 55.4, 69.3, 74.2, 113.8 (2C), 119.3, 123.9 (2C),
(1.0 mmol, 138.2 mg), and PdCl2(PPh3)2 (0.010 mmol, 7.0 mg) in
DMF (5.0 mL) was added styrene (1.0 mmol, 57 μL) under argon
atmosphere. The obtained mixture was stirred for 3 h at 60 °C. Sat.
NaHCO3 aq. solution (5.0 mL) was added to the reaction mixture,
and the product was extracted with EtOAc (15.0 mL × 3) and
127.6 (2C), 130.3 (2C), 147.3, 149.9, 162.5, 165.5; HRMS (ESI): Calcd
C
16H15O4N2 for [M + H]+ = 299.1026, Found = 299.1024.
4-Methyl-2-p-tolyloxazoline (2Af): Yield: 110.1 mg (63 %); yellow
oil; IR (neat): ν = 2966, 1644, 1512, 1259, 1059, 727 cm–1; 1H-NMR
˜
(400 MHz, CDCl3): δ = 1.36 (d, 3H, J = 6.6 Hz), 2.39 (s, 3H), 3.94 (t, washed with brine (15.0 mL). The organic layer was dried with
2H, J = 7.9 Hz), 4.32–4.41 (m, 1H), 4.51 (dd, 1H, J = 9.3, 7.9 Hz), 7.21
(d, 2H, J = 7.9 Hz), 7.83 (d, 2H, J = 8.2 Hz); 13C-NMR (100 MHz,
CDCl3): δ = 21.4, 21.5, 61.8, 73.9, 125.0, 128.1 (2C), 129.0 (2C), 141.5,
163.5; HRMS (ESI): Calcd for C11H14ON [M + H]+ = 176.1070, Found =
176.1071.
Na2SO4. After removal of the solvent under reduced pressure, the
residue was purified by silica-gel column chromatography (eluent:
n-hexane/EtOAc = 9:1) to give 4-phenyl-(E)-5-styryl-2-p-tolyloxazole
(6Aa, 126.9 mg, 75 %).
4-Phenyl-(E)-5-styryl-2-p-tolyloxazole (6Aa): Yield: 126.9 mg
4-Ethyl-2-p-tolyloxazoline (2Ag): Yield: 128.1 mg (68 %); yellow
(75 %); yellow solid; mp: 136–138 °C; IR (neat): ν = 1652, 1498, 1080,
˜
oil; IR (neat): ν = 2963, 1646, 1352, 1064, 827, 727 cm–1; H-NMR
953, 705 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.44 (s, 3H), 7.21 (d,
1H, J = 16.1 Hz), 7.27–7.32 (m, 4H), 7.37–7.42 (m, 3H), 7.50 (t, 2H,
J = 7.7 Hz), 7.53 (d, 2H, J = 7.3 Hz), 7.80 (d, 2H, J = 7.0 Hz), 8.08 (d,
2H, J = 8.4 Hz); 13C-NMR (100 MHz, CDCl3): δ = 21.6, 113.4, 124.5,
126.6 (3C), 127.7 (2C), 128.0 (3C), 128.8 (3C), 129.5 (2C), 129.7 (2C),
132.2, 136.7, 138.6, 140.8, 144.9, 160.3; HRMS (ESI): Calcd for
C24H20ON [M + H]+ = 338.1539, Found = 338.1541.
1
˜
(400 MHz, CDCl3): δ = 0.99 (t, 3H, J = 7.4 Hz), 1.55–1.66 (m, 1H),
1.72–1.83 (m, 1H), 2.39 (s, 3H), 4.04 (t, 1H, J = 7.9 Hz), 4.19–4.27 (m,
1H), 4.46 (dd, 1H, J = 9.3, 8.3 Hz), 7.21 (d, 2H, J = 8.5 Hz), 7.83 (d,
2H, J = 8.3 Hz); 13C-NMR (100 MHz, CDCl3): δ = 9.92, 21.5, 28.6, 67.8,
72.0, 125.0, 128.1 (2C), 128.9 (2C), 141.5, 163.5; HRMS (ESI): Calcd
for C12H16ON [M + H]+ = 190.1226, Found = 190.1223.
Transformation of 5-Iodo-4-phenyl-2-p-tolyloxazole 4Aa into 4-
Phenyl-2-p-tolyloxazole 3Aa: To a mixture of 5-iodo-4-phenyl-2-p-
tolyloxazole (4Aa, 0.5 mmol, 180.6 mg) in EtOH (7.5 mL) was added
Zn powder (5.0 mmol, 363.3 mg) under argon atmosphere. The
obtained mixture was stirred for 16 h at refluxing temperature. The
cooled mixture was filtered through celite, and then the filtrate was
concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (eluent: n-hexane/AcOEt =
9:1) to afford 4-phenyl-2-p-tolyloxazole (3Aa, 113.4 mg, 96 %).
Transformation of 5-Iodo-4-phenyl-2-p-tolyloxazole 4Aa into 4-
Phenyl-5-phenylethynyl-2-p-tolyloxazole 7Aa: To a mixture of 5-
iodo-4-phenyl-2-p-tolyloxazole (4Aa, 0.5 mmol, 180.6 mg), CuI
(0.010 mmol, 1.9 mg), and PdCl2(PPh3)2 (0.010 mmol, 7.0 mg) in
Et3N (2.5 mL) was added ethynylbenzene (0.6 mmol, 66 μL) under
argon atmosphere. The obtained mixture was stirred for 3 h at
60 °C. H2O (2.5 mL) was added to the reaction mixture, and the
product was extracted with EtOAc (15.0 mL × 3) and washed with
brine (15.0 mL). The organic layer was dried with Na2SO4. After
removal of the solvent under reduced pressure, the residue was
purified by silica-gel column chromatography (eluent: n-hexane/
EtOAc = 9:1) to give 4-phenyl-5-phenylethynyl-2-p-tolyloxazole
(7Aa, 161.3 mg, 96 %).
4-Phenyl-2-p-tolyloxazole (3Aa): Yield: 113.4 mg (96 %); white
solid; mp: 109–110 °C; IR (neat): ν = 1498, 1117, 1075, 929, 732 cm–1
;
˜
1H-NMR (400 MHz, CDCl3): δ = 2.42 (s, 3H), 7.27–7.35 (m, 3H), 7.43
(t, 2H, J = 7.9 Hz), 7.82 (d, 2H, J = 8.1 Hz), 7.94 (s, 1H), 8.01 (d, 2H,
J = 7.9 Hz); 13C-NMR (100 MHz, CDCl3): δ = 21.5, 124.8, 125.6 (2C),
4-Phenyl-5-phenylethynyl-2-p-tolyloxazole
(7Aa):
Yield:
126.4 (2C), 128.0, 128.7 (2C), 129.4 (2C), 131.2, 133.1, 140.6, 141.8, 161.3 mg (96 %); yellow solid; mp: 112–114 °C; IR (neat): ν = 2987,
˜
162.1; HRMS (ESI): Calcd for C16H14ON [M + H]+ = 236.1070, Found =
236.1067.
2198, 1499, 1248, 1078 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.43 (s,
3H), 7.30 (d, 2H, J = 8.1 Hz), 7.38 (tt, 1H, J = 7.4, 2.0 Hz), 7.41–7.43
(m, 3H), 7.48 (t, 2H, J = 7.4 Hz), 7.60–7.63 (m, 2H), 8.06 (d, 2H, J =
8.1 Hz), 8.23 (d, 2H, J = 7.2 Hz); 13C-NMR (100 MHz, CDCl3): δ = 21.6,
78.4, 100.1, 122.0, 124.2, 126.4 (2C), 126.8 (2C), 128.6 (4C), 129.0,
129.1, 129.5 (2C), 131.0 (2C), 131.4 (2C), 141.2, 143.6, 161.1; HRMS
(ESI): Calcd for C24H18ON [M + H]+ = 336.1383, Found = 336.1383.
Transformation of 5-Iodo-4-phenyl-2-p-tolyloxazole 4Aa into
4,5-Diphenyl-2-p-tolyloxazole 5Aa: To a mixture of 5-iodo-4-
phenyl-2-p-tolyloxazole (4Aa, 0.5 mmol, 180.6 mg) and PhB(OH)2
(1.0 mmol, 121.9 mg) in DMF (10.0 mL) was added PdCl2(PPh3)2
(0.025 mmol, 17.5 mg) under argon atmosphere. The obtained mix-
ture was stirred for 30 min at room temperature. Then, K2CO3
(1.0 mmol, 138.2 mg) in H2O (2.0 mL) was added to the mixture,
and the obtained mixture was stirred for 6 h at 60 °C. Water (5.0 mL)
was added to the reaction mixture, and the product was extracted
with CH2Cl2 (15.0 mL × 3) and washed with brine (15.0 mL × 2). The
organic layer was dried with Na2SO4. After removal of the solvent
under reduced pressure, the residue was purified by silica-gel col-
Transformation of 5-Iodo-4-phenyl-2-p-tolyloxazole 4Aa into 4-
Phenyl-5-p-toluenesulfenyl-2-p-tolyloxazole 8Aa: To a mixture of
5-iodo-4-phenyl-2-p-tolyloxazole (4Aa, 0.5 mmol, 180.6 mg), CuI
(0.025 mmol, 4.8 mg), K2CO3 (0.1 mmol, 138.2 mg), and p-toluene-
thiol (0.55 mmol, 68.4 mg) in iPrOH (5.0 mL) was added ethylene
glycol (1.0 mmol, 56 μL) under argon atmosphere. The obtained
mixture was stirred for 72 h at 90 °C. H2O (5.0 mL) was added to
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4-Phenyl-5-p-toluenesulfenyl-2-p-tolyloxazole
(8Aa):
Yield:
161.5 mg (45 %); white solid; mp: 101–103 °C; IR (neat): ν = 2971,
˜
1498, 1180, 1073, 803, 731 cm–1; 1H-NMR (400 MHz, CDCl3): δ = 2.29
(s, 3H), 2.41 (s, 3H), 7.09 (d, 2H, J = 8.3 Hz), 7.20 (d, 2H, J = 8.1 Hz),
7.28 (d, 2H, J = 8.1 Hz), 7.36 (tt, 1H, J = 7.2, 2.0 Hz), 7.44 (t, 2H, J =
7.2 Hz), 8.02 (d, 2H, J = 8.3 Hz), 8.18 (d, 2H, J = 7.0 Hz); 13C-NMR
(100 MHz, CDCl3): δ = 21.0, 21.6, 124.3, 126.7 (2C), 127.3 (2C), 128.0
(2C), 128.4 (2C), 128.6, 129.5 (2C), 130.1 (2C), 130.9, 131.2, 136.0,
136.9, 141.3, 145.9, 163.6; HRMS (ESI): Calcd for C23H20ONS [M +
H]+ = 358.1260, Found = 358.1262.
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and derivatives 3Aa–8Aa, including 2,5-diaryloxazolines 2Ga, 2Gb,
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Acknowledgments
This work was supported by JSPS KAKENHI Grant Number
JP18K05118 in Japan.
Keywords: Oxazole · Iminyl Radical · Imidate · DIH · 1,5-H
shift
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Received: March 23, 2020
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Photochemistry
2,4-Diaryl-5-iodoxazoles could be ob-
tained by the treatment of O-(ꢀ-aryl-
ethyl) arylimidates with 1,3-diiodo-5,5-
dimethylhydantoin (DIH) under irradia-
tion with a tungsten lamp. This reac-
tion proceeds through multiple stets,
i.e., formation of N-iodoimidate, iminyl
radical, 1,5-H shift, 5-exo-tet cyclization
to oxazoline, oxidation to oxazole, and
iodination to 5-iodoxazole.
A. Saito, H. Togo* ............................ 1–13
Photochemical Transformation of
O-(ꢀ-Arylethyl) Arylimidates into
2,4-Diaryl-5-iodoxazoles with 1,3-
Diiodo-5,5-dimethylhydantoin
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