Direct synthesis of oxazolines from olefins and amides using t-BuOI

Article abstract of DOI:10.1039/b706572h

A new and simple method for the synthesis of oxazolines from readily accessible olefins and amides using tert-butyl hypoiodite is described; aromatic/aliphatic olefins and amides can be used in the reaction to give a variety of oxazolines. The Royal Socie

Full text of DOI:10.1039/b706572h

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Direct synthesis of oxazolines from olefins and amides using t-BuOI{
Satoshi Minakata,* Yoshinobu Morino, Toshihiro Ide, Yoji Oderaotoshi and Mitsuo Komatsu
Received (in Cambridge, UK) 1st May 2007, Accepted 25th May 2007
First published as an Advance Article on the web 7th June 2007
DOI: 10.1039/b706572h
N-benzoylaziridine. When the effect of other representative
iodinating agents, such as iodine, N-iodosuccinimide (NIS) and
bis(pyridine)iodine tetrafluoroborate (IPy2BF4),10 on the reaction
was investigated under the same conditions, iodine and IPy2BF4
did not give the desired oxazoline, and the yield of 1 was rather
low (28%) in the case of NIS. In a study of the role of t-BuOX
halogen atoms in the reaction, when t-BuOCl was used, a small
amount of N-(2-chloro-2-phenylethyl)benzamide was produced.11
When the reaction was conducted with a combination of t-BuOCl
and NaBr, oxazoline 1 was obtained in 16% yield without the
formation of the adduct, as in the case when only t-BuOCl was
used. These results show that t-BuOI represents an ideal reagent
for the direct synthesis of oxazolines. Although the reaction was
conducted in the dark, as a precaution, the efficiency of the
aziridination8 using t-BuOI in interior light was found to bear
comparison with results in the dark.
A new and simple method for the synthesis of oxazolines from
readily accessible olefins and amides using tert-butyl hypoiodite
is described; aromatic/aliphatic olefins and amides can be used
in the reaction to give a variety of oxazolines.
A great number of oxazoline-containing natural products and
biologically active compounds are present in marine organisms.1
Moreover, enantiomerically pure oxazolines act as efficient chiral
sources or ligands for asymmetric transformations,2 and achiral
oxazolines are also valuable intermediates in organic synthesis.3
Thus, the development of a practical and convenient method for
the construction of an oxazoline ring is an important goal. A
general route to oxazolines is the reaction of hydroxyamides,
prepared from b-aminoalcohols and acid chlorides, with thionyl
chloride via cyclization.4 Oxazolines are also directly formed by the
reaction of b-aminoalcohols with nitriles, acid chlorides, esters or
carboxylic acids.4 We recently reported on the direct synthesis of
oxazolines from olefins using a nitridomanganese complex and
acid chlorides,5 which was accomplished by changing the activator
of the complex.6 Although the method is crucial for the asym-
metric synthesis of a variety of chiral oxazolines, a stoichiometric
amount of a metal nitride complex is required for a successful
reaction. It would be desirable to develop a method for the
synthesis of oxazolines from readily accessible resources such as
olefins and amides, but to our knowledge, there are no examples of
this type of procedure to date.7 Quite recently, we reported8 on the
novel aziridination of olefins with readily available sulfonamides
using tert-butyl hypoiodite (t-BuOI).9 The potential of this reagent
prompted us to further investigate alternative unprecedented
organic transformations. Based on this background, we report
here the direct synthesis of oxazolines from unfunctionalized
olefins and simple amides using t-BuOI.
ð1Þ
Some other amides were examined for their potential for
oxazoline synthesis from styrene (Table 1). The reaction of styrene
with para-methoxybenzamide using t-BuOI under the above
conditions afforded oxazoline 2a in 37% yield. An electron-
deficient amide, para-nitrobenzamide, was found to be reactive,
giving oxazoline 2b in 67% yield along with the regioisomer 3b in
11% yield, which are readily separable by silica gel chromato-
graphy. Although the efficiency needs to be improved, an aliphatic
amide also functioned as a component of an oxazoline.
Since para-nitrobenzamide was found to act as a good
component for the synthesis of oxazolines, some unfunctionalized
olefins were subjected to the reaction using the amides and t-BuOI
(Table 2). a-Methylstyrene was smoothly converted to oxazoline
2d as one regioisomer by the reaction with para-nitrobenzamide.
When trans-b-methylstyrene was employed, two regioisomers were
produced in 72% yield, while the reaction gave trans-oxazolines
To explore the possibility of the proposed [3 + 2] type synthesis
of oxazolines, a model reaction between styrene and benzamide
was performed in the presence of t-BuOI, prepared in situ from
t-BuOCl and NaI.8 By optimizing the solvent, reaction tempera-
ture and amount of the reagents, the conditions shown in eqn (1)
were found to be suitable, successfully leading to the production
of 2,5-diphenyl-2-oxazoline (1) without the formation of an
Table 1 Oxazoline synthesis from styrene with amide derivatives
R
Time/h Yield (%)
2 : 3
Recovery of amide (%)
Department of Applied Chemistry, Graduate School of Engineering,
Osaka University, Yamadaoka 2-1, Suita, Osaka 565-0871, Japan.
E-mail: minakata@chem.eng.osaka-u.ac.jp; Fax: +81 6-6879-7402
{ Electronic supplementary information (ESI) available: Procedure of
synthesis and experimental data of oxazolines. See DOI: 10.1039/b706572h
p-MeOC6H4
p-NO2C6H4 12
n-Bu
5
37
78
28
100 : 0 63
86 : 14 21
86 : 14 53
5
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Table 2 Synthesis of oxazolines from olefins with para-nitrobenza-
midea
Olefin
Time/h Yield (%)
Product [ratio]
5
79
12
72
Scheme 1 A plausible reaction pathway.
Our proposed pathway for the synthesis of oxazolines is shown
in Scheme 1, using 3-hexene as the specific case. Two equivalents
of t-BuOI, generated in situ, initially react with the amide, not the
olefin, to give diiodinated amide 4. This occurs because a Lewis
acid or UV light is known9b to be required for olefins to react with
t-BuOI. When benzamide in CD3CN was treated with t-BuOCl
12
55
1
and NaI, the H NMR spectrum showed a signal corresponding
to the active hydrogens on the amide nitrogen that smoothly
disappeared and a signal corresponding to the tert-butyl group of
t-BuOH that appeared within one hour.13 From the NMR study,
the generation of 414 might be suggested but there is no clear
evidence at present. The active species 4 might function as an
iodonium source, which reacts with 3-hexene to generate the cyclic
iodonium intermediate 5, followed by the addition of the counter
amide anion, yielding adduct 6.
24
50
In fact, after the reaction of para-nitrobenzamide with t-BuOI,
the addition of trans-3-hexene led to the production of oxazoline
1
2h in almost the same yield (70% by H NMR) as the reaction
96
71
shown in Table 2. More recently, Corey’s group reported an
elegant haloamidation of olefins using N-bromoacetamide and a
Lewis acid catalyst.15 Although the nitrogen source in the reaction
is the solvent, CH3CN, iodoamides formed by the addition of
CH3CN to the iodonium intermediate 5 were not observed in our
case.
96
68
In summary, a simple synthetic method is described for the
direct formation of oxazolines from unfunctionalized olefins and
readily accessible amides. In addition, the utility of t-BuOI, besides
aziridination,8 could be demonstrated for the unprecedented ring
construction of oxazolines. Although the efficiency needs to be
improved to be a more practical transformation, and toleration
toward functional groups should be addressed, this is the first
example of the synthesis of valuable oxazolines. Further applica-
tions of t-BuOI in other transformations are currently under
investigation.
a
Reaction conditions: olefin (1 mmol), para-nitrobenzamide
(ArCONH2, 0.5 mmol), t-BuOCl (1.5 mmol), NaI (1.5 mmol),
MeCN (3 mL), rt.
exclusively with retention of the stereochemistry of the starting
olefin. The reaction of 1,2-dihydronaphthalene with para-nitro-
benzamide proceeded to afford the corresponding oxazoline 2f as
the sole product. Mono and disubstituted aliphatic olefins were
also applicable to the reaction and, in the reactions of trans- and
cis-3-hexene, complete stereoselectivity was observed, indicating
that a cyclic iodonium intermediate might be involved in the
reaction path. From another synthetic viewpoint, the present
method can be regarded as an aminohydroxylation of olefins,
because oxazolines are easily converted to the corresponding
b-aminoalcohols.5b,12
This work was partially supported by a Grant-in-Aid for
Scientific Research from the Japan Society for the Promotion of
Science.
Notes and references
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3280 | Chem. Commun., 2007, 3279–3281
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