Direct chemical method for preparing 2,3-epoxyamides using sodium chlorite

Article abstract of DOI:10.1021/jo300542d

A direct method for preparing 2,3-epoxyamides from tertiary allylamines via a tandem C-H oxidation/double bond epoxidation using sodium chlorite is reported. Apparently, the reaction course consists of two steps: (i) allylic oxidation of the starting allylamine to corresponding unsaturated allylamide with sodium chlorite followed by (ii) epoxidation of the allylamide to the 2,3-epoxyamide mediated by hypochlorite ion, which is formed in situ by reduction of sodium chlorite. The reaction conditions tolerate the presence of free hydroxyl groups and typical functional groups such as TBS, aryl, alkyl, allyl, acetyl, and benzyl groups; however, when an activated aromatic ring (e.g., sesamol) is present in the substrate, the use of a scavenger is necessary.

Full text of DOI:10.1021/jo300542d

Article
pubs.acs.org/joc
Direct Chemical Method for Preparing 2,3-Epoxyamides Using
Sodium Chlorite
Lilia Fuentes,† Urbano Osorio,† Leticia Quintero,† Herbert Hopfl,‡ Nixache Vazquez-Cabrera,†
́
̈
and Fernando Sartillo-Piscil*,†
†Centro de Investigacion
‡Centro de Investigaciones Químicas, Universidad Auton
Mexico
́
de la Facultad de Ciencias Químicas, BUAP, 14 Sur Esq. San Claudio, San Manuel, 72570, Puebla, Mex
́
ico
́
oma del Estado de Morelos, Av. Universidad 1001, 62209, Cuernavaca,
́
S
* Supporting Information
ABSTRACT: A direct method for preparing 2,3-epoxyamides from tertiary allylamines
via a tandem C−H oxidation/double bond epoxidation using sodium chlorite is
reported. Apparently, the reaction course consists of two steps: (i) allylic oxidation of
the starting allylamine to corresponding unsaturated allylamide with sodium chlorite
followed by (ii) epoxidation of the allylamide to the 2,3-epoxyamide mediated by
hypochlorite ion, which is formed in situ by reduction of sodium chlorite. The reaction
conditions tolerate the presence of free hydroxyl groups and typical functional groups
such as TBS, aryl, alkyl, allyl, acetyl, and benzyl groups; however, when an activated
aromatic ring (e.g., sesamol) is present in the substrate, the use of a scavenger is necessary.
to 2,3-epoxyamides via C−H oxidation of A followed by
epoxidation of the double bond in intermediate B. If both
reactions could be performed in a sequential or “one-pot”
fashion, then a more direct chemical method for preparing 2,3-
epoxyamides (C) will be achieved (Scheme 2).
INTRODUCTION
■
2,3-Epoxyamides (also known as glycidic amides) are very
important organic compounds that are found in nature1 or
prepared in the laboratory for eventually being used as versatile
and useful building blocks in organic synthesis.2 In spite of the
importance of these compounds, there still are no direct
synthetic methods for their preparation. Generally, 2,3-
epoxyamides are synthetized either by Darzen condensation
of α-haloacetamides,3 α-sulphoniumacetamides,4 α-diazoaceta-
mides5 ammoniumacetamides6 with carbonyl compounds, or
by means of epoxidation of α,β-unsaturated amides.7 In both
procedures, the amide group is first prepared, then the epoxide
group (Scheme 1).
Scheme 2. Sequential Double Oxidation Strategy of
Allylamines to 2,3-Epoxyamides
Scheme 1. Known Strategies for the Synthesis of 2,3-
Epoxyamides
In order to prove our strategy and with the expectation to
obtain optically pure epoxyamides, we chose chiral (S)-
diallylamine 1 as model of study. Although there is a number
of methods for the C−H oxidation of amines to their
corresponding amides, most of them operate in the presence
of transition metals and represent therefore a nonenvironmen-
tal process.8
Searching in the literature, mild chemical methods for allylic
oxidation of olefins can be found,9 such as the oxidation of
steroid 2 to the corresponding α,β-unsaturated ketone 3 with
sodium chlorite, which was reported by Salvador and
To overcome this backlog, we considered it necessary to
introduce into the organic chemistry scenario a more direct
method for the preparation of glycidic amides from simple
substrates and chemical reagents.
RESULTS AND DISCUSSION
■
For this purpose, we wondered about the possibility of
developing a selective double oxidation process of allylamines
Received: March 19, 2012
Published: June 4, 2012
© 2012 American Chemical Society
5515
dx.doi.org/10.1021/jo300542d | J. Org. Chem. 2012, 77, 5515−5524

The Journal of Organic Chemistry
Article
Silvestre.9a Unfortunately, the allylic oxidation of the model
compound (S)-1 did not proceed under these reaction
conditions (Scheme 3).
entries 7−10). Another interesting result is that only one allyl
group was oxidized, which suggests that the allylamines and not
the allylamides undergo C−H oxidation with NaClO2 in acidic
media. To prove this, the allylamide (S)-6 was treated under
the same conditions as amine (S)-1, and there was no evidence
for the formation of an oxidation product within 20 h; the
starting material remained unchanged. Further, the lack of
reactivity of amide (S)-6 offers insights in the reaction course.
Apparently, the amine functionality is needed for the C−H
oxidation, and the epoxidation of the deactivated double bond
does not proceed with NaClO2. A rational reaction course
might be as follows: first, C−H oxidation of the allylamine (S)-
1 by sodium chlorite to the unsaturated allylamide (S)-6, via
the formation of intermediate D, which might be initiated by
ClO2 radical;9a,13 second, epoxidation of the deactivated double
bond of (S)-6 by hypochlorite ion, which is formed in situ by
the reduction of sodium chlorite,14 to give 2,3-epoxyamide (S/
R)-4; and finally, ketoamide (S)-5 formed through acid-
catalyzed isomerization of epoxyamide (S/R)-4 (Scheme 4).
The conversion of 6 to 4 was corroborated using hypochlorite
from Clorox.
Scheme 3. Allylic Oxidation with NaClO2 (2 → 3) Tested for
Chiral Diallylamine (S)-1
Having in mind that the use of NaClO2 as oxidizing agent is a
good choice (especially for being an environmentally friendly
reagent), we explored variation in the reaction conditions. It is
well-known that the effectiveness of sodium chlorite as
oxidative agent in the transformation of aldehydes to carboxylic
acids is improved in slightly acidic solutions (pH within 3−
6).10,11 Therefore, monosodium phosphate, hydrochloric acid,
or acetic acid were employed, in the presence or absence of a
chlorine scavenger agent such as 2-methyl-2-butene.10 Further
details for the condition reactions are listed in Table 1.
As expected, screening investigation showed that allylamine
(S)-1 underwent allylic oxidation under acidic conditions
(compounds 4−6, see all the entries in Table 1). Furthermore,
an unexpected and gratifying result was observed: the
epoxidation step proceeded in a tandem fashion to give
epoxyamide (S/R)-4 (see Table 1, entries 1−6). 2,3-
Epoxyamide (S,R/S)-4 (as an inseparable mixture of diaster-
eoisomers) and ketoamide (S)-5 were obtained in almost
equimolar amounts (Table 1, entries 1−6). The formation of
ketoamide (S)-5 can be explained by the well-known
isomerization process of epoxides to keto or aldehyde
compounds under acidic conditions.12
Scheme 4. Proposed Reaction Course for the Tandem
Synthesis of Epoxyamide (S)-4, Ketoamide (S)-5 and Amide
(S)-6 from Allylamine (S)-1
The fact that epoxyamide 4 is not formed when stronger
acids are used proves this assumption to be correct (Table 1,
Under this scenario, this tandem oxidation reaction does not
require the use of a scavenger, because most of the hypochlorite
a b
,
Table 1. Developing the Selective Oxidation of Allylamine (S)-1
entry NaClO2 (equiv)
acid (equiv/mL)
solvents scavenger
temp (°C) t (h) 4 (%) 5 (%) 6 (%)
1
2
3
4
5
6
7
8
9
10
21
10
5
NaH2PO4
t-BuOH/H2O/THF (7:3:3) 2-methyl-2-butene (100 equiv)
t-BuOH/H2O/THF (7:3:3) 2-methyl-2-butene (100 equiv)
t-BuOH/H2O/THF (7:3:3) 2-methyl-2-butene (100 equiv)
t-BuOH/H2O/THF (7:3:3) 2-methyl-2-butene (100 equiv)
t-BuOH/H2O/THF (7:3:3) none
20
21
0
12
21
12
12
29
5
42
38
42
10
29
30
40
39
38
12
29
28
34
40
40
45
5
traces
7
NaH2PO4
NaH2PO4
c
c
NaH2PO4
20
0
5
NaH2PO4
10
10
10
40
10
NaH2PO4
t-BuOH/H2O/THF (7:3:3) none
20
20
0
traces
HC1 IN (0.6)
HC1 IN (0.3)
CH3COOH (0.6)
CH3COOH (0.3)
t-BuOH/THF (7:3) 2-methyl-2-butene (100 equiv)
t-BuOH/THF (7:3) none
1
8
9
8
8
1
t-BuOH/THF (7:3) none
0
1
10
t-BuOH/THF (7:3) none
0
3
a
b
c
Substrate concentration was 0.1 M in each case. Yields after purification by column chromatography. Approximately 50% of the starting material
remained unchanged.
5516
dx.doi.org/10.1021/jo300542d | J. Org. Chem. 2012, 77, 5515−5524

The Journal of Organic Chemistry
Article
formed, which is normally considered an unwanted byproduct
in other oxidation reactions,10,11 is consumed during the
epoxidation reaction.15 Therefore, in this case the hypochlorite
represents a key side-product for the success of the reaction.
Furthermore, an alternative mechanistic course for the reaction
might involve the iminium intermediate E, as in the case for α-
oxidations of amines with transition metals,16 then nucleophilic
attack by water would provide carbinolamine F, which
undergoes oxidation to amide 6, followed by the above-
described oxidation of double bond with hypochlorite to give
epoxyamide 4 (Scheme 5). This alternative proposal forced us
In order to extend the scope of this new reaction, we
prepared a series of allylamines [(S)-7−(S)-11)]. Diallylic
amine (S)-7, which is structurally related to amine (S)-1, was
prepared to confirm that the oxidation occurs selectively only
on one of the allyl groups. Additionally, a series of
allylpiperidines (S)-8−(S)-11 was designed, not only for
examining the stability of the N-heterocyclic ring and the
compatibility of common functional groups under this oxidizing
condition reactions, but also for preparing advanced chiral
intermediaries that can eventually be utilized for the synthesis
of alkaloids (Scheme 6).
Chiral diallylamine (S)-7 was prepared from amine (S)-12 in
the presence of 3,3-dimethylallyl bromide and Na2CO3 in dry
acetonitrile at room temperature. Under the same reaction
conditions, but using 2-(2-bromoethyl)-1,3-dioxolane instead
3,3-dimethylallyl bromide, the piperidine precursor (S)-13 was
also obtained in good yield. Treatment of (S)-13 with aqueous
HCl (5 N) gave aldehyde (S)-11 in quantitative yield via
hydrolysis followed by intramolecular aldol closure. Allylpiper-
idine (S)-8 bearing a free hydroxyl group was prepared by
treating (S)-11 with NaBH4 in ethanol. Allylpiperidines bearing
a OTBS group (S)-9 and a highly electron-donating aryl group
(S)-10 were obtained using TBSCl/imidazole and sesamol
under Mitsunobu conditions,17 respectively (Scheme 6).
Happily, we found that all the allylamines (S)-7−(S)-11 were
converted exclusively into their corresponding 2,3-epoxyamides
[(S,R/S)-12, (S)-13a and (S)-13b, (S)-14a and (S)-14b, (S)-
15a and (S)-15b, (S)-16a and (S)-16b, (S)-17a and (S)-17b]
in modest to high yields (Table 2, entries 1−10), even when
reducing the quantity of NaClO2 from 10 to 8 equiv and in the
absence of 2-methyl-2-butene. Despite the fact that diallylamine
(S)-7 gave a modest yield of epoxyamide (S,R/S)-12 (as an
inseparable mixture of diastereoisomer), again only one allyl
group was oxidized (Table 2, entry 1), even in the absence of a
scavenger (Table 2, entry 2).
Scheme 5. Alternative Proposed Reaction Course and 18O-
Labeling Experiment
to carry out a 18O-labeling experiment using 18O-enriched water
(98% purity) in order to examine whether the amide oxygen
atom is provided from water16a,b or if NaClO2 is the source of
all oxygen atoms. The mass spectra of compounds 4−6
evidenced that no incorporation of 18O occurred in any of the
products 4−6, revealing thus that the mechanistic pathway
given in Scheme 4 is more likely.
Interestingly, allylpiperidine (S)-8, which contains a free
hydroxyl group that could be oxidized, afforded 2,3-
epoxyamides (S)-13a and (S)-13b in high yield with a ratio
of 38:62, respectively (Table 2, entries 3 and 4). A similar result
was observed for allylpiperidine (S)-9, which gave the cyclic
Scheme 6. Preparation of Diallylamine (S)-7 and Allylpiperidines (S)-8−(S)-11
5517
dx.doi.org/10.1021/jo300542d | J. Org. Chem. 2012, 77, 5515−5524

The Journal of Organic Chemistry
Article
a b
,
Table 2. Developing the First Direct Synthesis of 2,3-Epoxyamides
a
b
c
Substrate concentration was 0.1 M in each case. Yields after purification by column chromatography. As an inseparable mixture of
diastereoisomers.
2,3-epoxyamides (S)-14a and (S)-14b in 83% yield and 40:60
ratio, respectively (Table 2, entries 5 and 6). Interestingly, but
not surprisingly, 2,3-epoxyamides (S)-15a and (S)-15b were
obtained in high yield when a scavenger was used (Table 2,
entry 7); however, in its absence, chlorination on the sesamol
moiety was observed (epoxyamides (S)-16a and (S)-16b; Table
2, entry 8). Allylpiperidine (S)-11 was the most challenging
case for this new tandem oxidation reaction because it was quite
expectable that the aldehyde group might inhibit the tandem
oxidation under this reaction condition because of oxidation to
the corresponding carboxylic acid.10,11 However, not only was
the 2,3-epoxyamide moiety formed successfully, but also the
aldehyde group was oxidized to the carboxylic acid group,
which was isolated in form of the corresponding ester by
adding TMS-CHN2 (Table 2, entries 9 and 10). It is important
to note that, with exception of the epoxyamides (S,R/S)-4 and
(S,R/S)-12, all of the epoxyamides [(S)-13a and (S)-13b, (S)-
14a and (S)-14b, (S)-15a and (S)-15b, (S)-16a and (S)-16b,
5518
dx.doi.org/10.1021/jo300542d | J. Org. Chem. 2012, 77, 5515−5524

The Journal of Organic Chemistry
Article
(S)-17a and (S)-17b] were separated by column chromatog-
raphy.
Treatment of piperidine 19 under reaction conditions shown
in Table 2 (either in presence or absence of a scavenger)
afforded amide 2619 in good yield, indicating that the benzyl
group acts similar to the allyl group; however, when
allylbenzylamine (S)-20 was submitted to the same reaction
conditions, epoxyamides (S,S*)-27 and (S,R*)-28 were
obtained in modest yield (Chart 1). This establishes that allylic
In order to determine the absolute configuration of the two
chiral centers formed for the epoxyamides, X-ray crystallo-
graphic study was performed for representative epoxyamide. To
this end, epoxyamide (S)-13b was converted to its tosylate
derivative (1′S,3R,4R)-18, which provided single crystals
suitable for X-ray diffraction analysis (Scheme 7).18
a
Chart 1. Further Oxidation Products
Scheme 7. Derivatization of Epoxyamide (S)-13b to
(1′S,3R,4R)-18 for X-ray Crystallographic Diffraction
Analysis18
In order to extend even more the scope of this
unprecedented reaction, we considered it necessary to examine
different functional groups looking for diversity, stereo-
selectivity, and mechanistic insights. To this end, tertiary
amines (19−23) were prepared according to Scheme 8 (which
is similar to Scheme 6). Piperidine benzylated 19 was selected
to test benzylic C−H oxidation; allylbenzylamine (S)-20 was
prepared to examine the reactivity of both groups, allyl versus
benzyl; similarly, with the allylamine (S)-21 we wish to
compare the reactivity between C−H acidic protons and allylic
C−H hydrogen atoms. Finally, chiral piperidines (R)-22 and
(R)-23 derived from (R)-2-phenylglycinol 24 were prepared to
increase the stereoselectivity in the epoxidation step.
a
Yields after purification by column chromatography *Absolute
stereochemistry was not determined.
Scheme 8. Preparation of Tertiary Amines 19, (S)-21, (S)-22, (R)-22 and (R)-23
5519
dx.doi.org/10.1021/jo300542d | J. Org. Chem. 2012, 77, 5515−5524

The Journal of Organic Chemistry
Article
C−H bond is more reactive than benzylic C−H bond. On the
other hand, amino ester (S)-21 did not afford the expected
epoxyamide (not shown), but an amide ester (S)-29 was
obtained in moderated yield, and deallylated product (S)-30 as
byproduct.20 Therefore, it can be established that sodium
chlorite selectively oxidizes C−H bond in the following order:
RNCH2CO2R > RNCH2CCHR > RNCH2Ph.
CONCLUSIONS
■
In summary, we have developed a direct protocol for the
synthesis of 2,3-epoxyamides (glycidic amides) from tertiary
allylamines under mild, nonexpensive, and environmentally
friendly conditions. Further accounts describing the epoxida-
tion step in a stereoselective fashion, mechanistic studies for the
C−H oxidation step, and applications of this tandem oxidation
in total synthesis of biologically important alkaloids will be
reported in due course.
Piperidines derived from (R)-2-phenylglycinol, (R)-22 and
(R)-23, which were designed to improve the stereoselectivity
for the epoxidation step, did not provide the expected results;
actually, this chiral auxiliary resulted to be less effective than the
(S)-(−)-α-methylbenzylamine (S)-12. In this case, the
diastereomer ratio of epoxyamides (1′R,3R,4R)-31/
(1′R,3S,4S)-32 and (1′R,3R,4R)-33/(1′R,3S,4S)-34 is 50:50
(Chart 1); however, each one of the epoxyamides could be
separated by column chromatography. Although there are
examples of asymmetric epoxidation of unsaturated amides with
good enantiomeric excess,21 the use of both chiral auxiliary (S)-
12 and (R)-24 allows the easy separation of each of the
epoxyamides (piperidine derivatives) by column chromatog-
raphy and therefore enables the preparation of epoxyamides in
enantiomerically pure form.
EXPERIMENTAL SECTION
■
General Information. All reagents purchased commercially were
used without purification. The solvents were used as technical grade
1
and freshly distilled prior use unless otherwise noted. H NMR and
13C NMR spectra were recorded at 400 and 100 MHz spectrometers,
respectively. 1H NMR and 13C NMR spectra were recorded in CDCl3
and are reported in ppm relative to tetramethylsilane (TMS). Data for
1H NMR are reported as follows: chemical shift (δ ppm), multiplicity
(s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br =
broad), coupling constant (Hz), and integration. Data for 13C NMR
are reported in terms of chemical shift. Optical rotations, [α]D values,
are reported in 10−1 dg cm2 g−1; concentration (c) is in g/100 mL.
Procedure for N-Alkylation of (S)-(−)-α-Methylbenzylamine
and (R)-2-Phenylglycinol. To a stirred suspension of Na2CO3 (3.14
g, 29.7 mmol) in 40 mL of CH3CN at room temperature was added
(S)-(−)-α-methylbenzylamine (1.5 g, 12.3 mmol); the reaction
mixture was stirred for 15 min before the corresponding alkyl halide
(29.7 mmol) dissolved in 5 mL of acetonitrile was added. The reaction
mixture was stirred at room temperature until the starting materials
were completely consumed. Then, the mixture was filtered off, and the
solvent was removed under reduced pressure. The residue was purified
by column chromatography on silica gel to give the corresponding
product.
It is noteworthy to mention that C−H oxidation of
compound (S)-21 to amide ester (S)-29 excludes the formation
of iminium intermediate G (which is similar to intermediate E
shown in Scheme 5), because of instability caused by the
electron-withdrawing substituent (carbonyl group). Addition-
ally, the oxidation of piperidine (R)-22 would afford bicyclic
compound 36 by nucleophilic addition of free hydroxyl group
to iminium intermediate H; however, after detailed NMR
analysis and exhaustive purification process, this putative
compound (35) was not observed (Scheme 9).
(S)-N-Allyl-N-(1-phenylethyl)prop-2-en-1-amine-1.22 Ob-
20
tained 2.2 g (90%) as a yellow pale oil: [α]D = −43.4 (c = 1.0,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.35 (d, J = 6.8 Hz, 3H), 3.02
(dd, J = 14.4, 6.4 Hz, 2H), 3.14 (dd, J = 14.4, 6.4 Hz, 2H), 3.89 (q, J =
6.8, 1H), 5.13 (m, 4H); 5.84 (ddt, J = 17.2, 10.4, 6.4 Hz, 2H), 7.20 (m,
5H); 13C NMR (100 MHz, CDCl3) δ 17.0, 52.5, 58.2, 116.8, 126.6,
127.6, 128.0, 136.5, 143.9.
Therefore, the mechanistic course for (S)-21 to amide ester
(S)-29 occurs via the formation of intermediate I, which is
similar to intermediate D shown in Scheme 4.
Scheme 9. Experimental Evidence against the Formation of
an Iminium Intermediate
(S)-3-Methyl-N-(3-methylbut-2-enyl)-N-(1-phenylethyl)but-
20
2-en-1-amine-7. Obtained 2.5 g (80%) as a yellow pale oil: [α]D
=
−50.16 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.35 (d, J =
6.8 Hz, 3H), 1.56 (s, 6H), 1.70 (s, 6H), 2.96 (dd, J = 14.4, 6.8 Hz,
2H), 3.09 (dd, J = 14.4, 6.8 Hz, 2H), 3.87 (q, J = 6.8 Hz, 1H), 5.26 (t,
J = 6.8 Hz, 2H), 7.20 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 17.3,
17.9, 25.9, 47.1, 58.5, 122.41, 122.5, 126.4, 127.7, 127.9, 133.7, 144.5;
HRMS-FAB (m/z) [M + H]+ 258.2245 (calcd. 258.2222 for
C18H28N).
(S)-N-Benzyl-3-methyl-N-(1-phenylethyl)but-2-en-1-amine-
20. Obtained 1.85 g (82%) as a colorless oil: [α]D20 = −49.23 (c = 1.2,
1
CH2Cl2); H NMR (400 MHz, CDCl3) δ 1.37 (d, J = 6.8 Hz, 3H),
1.52 (s, 3H), 1.69 (s, 3H), 2.90 (dd, J = 14.4, 6.4 Hz, 1H), 3.12 (dd, J
= 14.4, 6.8 Hz, 1H), 3.46 (d, J = 14.0 Hz, 1H), 3.55 (d, J = 14.0 Hz,
1H), 3.93 (q, J = 6.8 Hz, 1H), 5.28 (m, 1H), 7.30 (m, 10H); 13C NMR
(100 MHz, CDCl3) δ 15.6, 18.0, 25.9, 46.9, 53.7, 57.5, 122.4, 126.4,
126.5, 127.8, 127.9, 128.0, 128.5, 134.1, 140.9, 144.1; HRMS-FAB m/z
[M + H]+ 280.2073 (calcd. 280.2065 for C20H26N).
(S)-Ethyl 2-(Allyl(1-phenylethyl)amino)ethanoate-21. Ob-
20
tained 1.31 g (65%) as a colorless oil: [α]D = −115.22, (c = 1.00,
1
CH2Cl2); H NMR (400 MHz, CDCl3) δ 1.25 (t, J = 7.2 Hz, 3H),
1.36 (d, J = 6.8 Hz, 3H), 3.22 (d, J = 6.8 Hz, 2H), 3.28 (d, J = 17.2 Hz,
1H), 3.44 (d, J = 17.2 Hz, 1H), 4.06 (q, J = 6.8 Hz, 1H), 4.13 (q, J =
7.2 Hz, 2H), 5.15 (m, 2H), 5.82 (ddt, J = 17.2 10.4, 6.4 Hz, 1H), 7.30
(m, 5H); 13C NMR (100 MHz, CDCl3) δ 14.2, 19.4, 50.9, 54.2, 60.1,
117.4, 126.9, 127.5, 128.2, 136.1, 144.3, 172.1; HRMS-FAB m/z [M +
H]+ 248.1659 (calcd. 248.1651 for C15H22NO2).
5520
dx.doi.org/10.1021/jo300542d | J. Org. Chem. 2012, 77, 5515−5524

The Journal of Organic Chemistry
Article
(S)-N,N-Bis(2-(1,3-dioxolan-2-yl)ethyl)-1-phenylethanamine-
13. To a stirred suspension of K2CO3 (8.55 g, 61.9 mmol) in 20 mL of
CH3CN at room temperature were added (S)-(−)-α-methylbenzyl-
amine (3.0 g, 24.8 mmol) and 2-(2-bromoethyl)-[1.3]dioxolane (11.2
g, 61.9 mmol). The resulting mixture was refluxed for 12 h, and then
the reaction mixture was cooled to room temperature. The solids were
filtered off, and the solvent was removed under reduced pressure. The
49.3, 60.9, 65.2, 69.8, 121.3, 127.9, 128.2, 128.9, 135.9, 136.4; HRMS-
FAB m/z [M + H]+ 234.1505 (calcd for 234.1494 for C14H20NO2).
(S)-5-((t-Butyldimethylsilyloxy)methyl)-1-(1-phenylethyl)-
1,2,3,6-tetrahydropyridine-9. To a flask containing a solution of 8
(0.660 g, 3.04 mmol) and imidazole (0.414 g, 6.08 mmol) in 20 mL of
CH2Cl2 at 0 °C was added dropwise t-Bu(CH3)2SiCl (0.686 g, 4.54
mmol) dissolved in 4 mL of CH2Cl2. The reaction was stirred for 1.5
h, and then water (4 mL) was added. The phases were separated, and
the aqueous phase was extracted with EtOAc (2 × 15 mL). The
combined organic phases were dried over Na2SO4, and the solvent was
removed under reduced pressure. Flash chromatography on silica gel
gave 0.96 g (95%) of desired product 9 as a yellow oil: [α]D20 = −0.83
residue was purified by column chromatography (SiO2, hexanes/
20
EtOAc, 4:1) yielding 7.14 g (90%) of 13 as a colorless oil: [α]D
=
1
3.86 (c = 1.53, CH3Cl); H NMR (400 MHz, CDCl3) δ 1.34 (d, J =
6.8, 3H), 1. 78 (td, J = 7.6, 4.8 Hz, 4H), 2.52 (m, 2H), 2.64 (m, 2H),
3.78 (m, 4H), 3.82 (q, J = 7.2 Hz, 1H), 3.90 (m, 4H), 4.82 (t, J = 5.2
Hz, 2H), 7.28 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 16.6, 32.1,
45.0, 59.1, 64.5, 64.6, 103.3, 126.4, 127.5, 127.8, 143.9; HRMS-FAB
(m/z) [M + H]+ 322.2006 (calcd. 322.2018 for C18H28NO4).
(R)-2-(Bis(2-(1,3-dioxolan-2-yl)ethyl)amino)-2-phenyletha-
nol. Obtained 6.6 g (90%) as a colorless oil: [α]D20 = −37.7 (c = 1.0,
CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 1.81 (m, 2H), 1.92 (m, 2H),
2.36 (m, 2H), 2.83 (dt, J = 13.2, 7.6 Hz, 2H), 3.60 (dd, J = 10.4, 4.4
Hz, 1H), 3.92 (m, 11H), 4.93 (t, J = 4.8 Hz, 2H), 7.26 (m, 5H); 13C
NMR (100 MHz, CDCl3) δ 32.1, 44.6, 60.8, 64.7, 64.8, 64.9, 103.4,
127.6, 128.2, 128.8, 136.2; HRMS-FAB m/z [M + H]+ 338.1970
(calcd. 338.1967 for C18H28NO5).
1
(c = 1.0, CHCl3); H NMR (400 MHz, CDCl3) δ 0.05 (s, 6H), 0.90
(s, 9H), 1.43 (d, J = 6.8 Hz, 3H), 2.12 (m, 2H), 2.40 (ddd, J = 12.8,
7.6, 5.2 Hz, 1H), 2.58 (dt, J = 10.8, 5.2 Hz, 1H), 2.85 (d, J = 16.0 Hz,
1H), 3.10 (d, J = 16.0 Hz, 1H), 3.45 (q, J = 6.8 Hz, 1H), 4.03
(apparent s, 2H), 5.70 (apparent s, 1H) 7.30 (m, 5H); 13C NMR (100
MHz, CDCl3) δ −5.4, 18.3, 20.2, 25.8, 25.8, 47.4, 50.7, 64.8, 65.6,
119.8, 126.8, 127.5, 128.1, 136.1, 144.1; HRMS-FAB (m/z) [M + H]+
332.2431 (calcd 332.2410 for C20H34NOSi).
(R)-(1-(2-(t-Butyldimethylsilyloxy)-1-phenylethyl)-1,2,5,6-
tetrahydropyridin-3-yl)methanol-23. To a flask containing a
solution of 25 (0.685 g, 2.96 mmol) and imidazole (0.403 g, 5.92
mmol) in 20 mL of CH2Cl2 at 0 °C was added dropwise t-
Bu(CH3)2SiCl (0.892 g, 2.27 mmol) dissolved in 5 mL of CH2Cl2.
The reaction was stirred for 2.0 h, and then water (5 mL) was added.
The phases were separated, and the aqueous phase was extracted with
EtOAc (2 × 10 mL) and dried over Na2SO4, and the solvent was
removed under reduced pressure at 0 °C. The residue was dissolved in
MeOH (20 mL) and a solution of NaBH4 (0.168 g, 4.44 mmol) in
MeOH (5 mL) was added dropwise. After it was stirred at room
temperature for 30 min, water (15 mL) was added. The mixture was
evaporated under reduced pressure, and then the aqueous mixture was
extracted with EtOAc (3 × 15 mL). The organic layer was dried over
Na2SO4, and the solvent was evaporated under reduced pressure. Flash
chromatography on silica gel gave the desired product 23 as yellow oil
(0.770 g, 75% yield): [α]D20 = 5.05 (c = 1.0, CH2Cl2); 1H NMR (400
MHz, CDCl3) δ −0.09 (s, 3H), −0.04 (s, 3H), 0.82 (s, 9H), 2.12 (m,
2H), 2.50 (ddd, J = 11.4, 7.2, 4.8 Hz, 1H), 2.66 (dt, J = 10.8, 5.2 Hz,
1H), 3.02 (d, J = 16.0 Hz, 1H), 3.27 (d, J = 16.0 Hz, 1H), 3.49 (t, J =
5.6 Hz, 1H), 3.87 (dd, J = 10.4, 6.0 Hz, 1H), 3.96 (s, 2H), 4.11 (dd, J
= 10.4, 6.0 Hz, 1H), 5.70 (s, 1H) 7.28 (m, 5H); 13C NMR (100 MHz,
CDCl3) δ - 5.6, −5.6, 18.1, 25.67 48.0, 51.6, 65.4, 65.7, 71.8, 121.2,
127.1, 128.0, 128.6, 136.6, 140.4; HRMS-FAB m/z [M + H]+
348.2359 (calcd. 348.2359 for C20H34NO2Si).
(S)-5-((Benzo[d][1,3]dioxol-5-yloxy)methyl)-1-(1-phenyleth-
yl)-1,2,3,6-tetrahydropyridine-10. To a flask containing 9 (1.26 g,
5.8 mmol), PPh3 (3.04 g, 11.6 mmol), and sesamol (1.04 g, 7.53
mmol) in 40 mL of dry benzene at 0 °C was added dropwise DIAD
(2.11 g, 10.4 mmol). The reaction mixture was allowed to stir
vigorously for 3 h and then concentrated under reduced pressure.
Flash chromatography on silica gel (hexanes/EtOAc 4:1) gave 1.76 g
of 10 as a yellow oil (90%): [α]D20 = 3.39, (c = 1.0, CH2Cl2); 1H NMR
(400 MHz, CDCl3) δ 1.43 (d, J = 6.8 Hz, 3H), 2.15 (m, 2H), 2.36
(ddd, J = 12.0, 7.2, 5.2 Hz, 1H), 2.62 (dt, J = 11.2, 5.2 Hz, 1H), 2.94
(d, J = 15.6 Hz, 1H), 3.24 (d, J = 15.6 Hz, 1H), 3.48 (q, J = 6.8 Hz,
1H), 4.29 (s, 2H), 5.83 (s, 1H), 5.87 (s, 2H), 6.30 (dd, J = 8.4, 2.4 Hz,
1H), 6.48 (d, J = 5.6 Hz, 1H), 6.67 (d, J = 8.4 Hz, 1H), 7.27 (m, 5H);
13C NMR (100 MHz, CDCl3) δ 20.0, 25.8, 46.8, 50.8, 64.5, 71.6, 98.2,
(S)-1-(1-Phenylethyl)-1,2,5,6-tetrahydropyridine-3-carbalde-
hyde-11. To a flask containing a solution of 13 (1.0 g, 3.31 mmol) in
1,4-dioxane (1.0 mL) was added 1 mL of HCl (5 M solution in water)
at room temperature. The resulting mixture was stirred under reflux
until the total consumption of starting materials. The reaction was
quenched with the addition of NaOH until reaching a pH = 8. The
biphasic mixture was extracted with EtOAc (3 × 15 mL) and dried
with Na2SO4. The solvent was evaporated under reduced pressure.
The desired product was obtained in quantitative yield as brown oil:
[α]D20 = 30.13 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.45
(d, J = 6.8 Hz, 3H), 2.40 (m, 3H), 2.66 (m, 1H), 3.05 (d, J = 16.0 Hz,
1H), 3.46 (d, 16.0 Hz, 1H), 3.57 (q, J = 6.8 Hz, 1H), 6.84 (s, 1H), 7.3
(m, 5H), 9.41 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 19.6, 27.6,
46.5, 46.6, 64.4, 127.1, 127.5, 128.3, 140.3, 143.0, 148.9, 192.5; HRMS-
EI (m/z) 215.1297 (calcd. 215.1310 for C14H17NO).
(R)-1-(2-Hydroxy-1-phenylethyl)-1,2,5,6-tetrahydropyridine-
3-carbaldehyde-35. Obtained in quantitative yield as an orange oil:
20
1
[α]D = −17.7 (c = 1.0, CH2Cl2); H NMR (400 MHz, CDCl3) δ
2.40 (m, 1H), 2.48 (m, 2H), 2.82 (dt, J = 10.4, 4.8 Hz, 1H), 2.92 (br,
1H), 3.24 (m, 2H) 3.73 (dd, J = 10.4, 5.2 Hz, 1H), 3.81 (dd, J = 10.4,
5.2 Hz, 1H), 4.06 (t, J = 9.2 Hz 1H), 6.81 (s, 1H), 7.3 (m, 5H), 9.38
(s, 1H); 13C NMR (100 MHz, CDCl3) δ 27.5, 45.4, 60.6, 69.6, 128.0,
128.3, 128.8, 135.3, 140.1, 148.3, 192.1; HRMS-FAB (m/z) [M + H]+
232.1318 (calcd. 232.1338 for C14H18NO2).
(S)-(1-(1-Phenylethyl)-1,2,5,6-tetrahydropyridin-3-yl)-
methanol-8. To a solution of 11 (1.0 g, 4.64 mmol) in 25 mL of
MeOH at 0 °C was added dropwise a solution of NaBH4 (0.263 g,
6.95 mmol) in MeOH (5 mL). The reaction mixture was stirred for 30
min at room temperature before 15 mL of water was added. The
biphasic mixture was evaporated under reduced pressure, and then the
aqueous mixture was extracted with EtOAc (3 × 15 mL). The organic
phase was dried over Na2SO4, and the solvent was evaporated under
20
reduced pressure to give quantitatively 8 as pale yellow oil: [α]D
=
7.39 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.44 (d, J = 6.8
Hz, 3H), 2.12 (m, 2H), 2.34 (ddd, J = 11.2, 7.6, 5.2 Hz, 1H), 2.60 (dt,
J = 11.2, 5.2 Hz, 1H), 2.89 (d, J = 16 Hz, 1H), 3.21 (d, J = 16 Hz, 1H),
3.49 (q, J = 6.8 Hz, 1H), 3.96 (s, 2H), 5.71 (m, 1H), 7.3 (m, 5H); 13C
NMR (100 MHz, CDCl3) δ 19.8, 25.7, 47.2, 50.5, 64.4, 65.09, 120.9,
126.9, 127.6, 128.1, 136.5, 143.0; HRMS-FAB (m/z) [M + H]+
218.1541 (calcd. 218.1545 for C14H20NO).
100.9, 105.7, 107.7, 124.1, 126.9, 127.5, 128.1, 132.5, 141.5, 143.7,
148.0, 154.2; HRMS-FAB (m/z) [M + H]+ 338.1731 (calcd. 338.1756
for C21H24NO3).
General Procedure for Tandem Oxidation. Allylamine (1.0
mmol) and NaH2PO4 (1.37 g, 10 mmol) were dissolved in 13 mL of a
mixture of t-BuOH/THF/H2O (7:3:3), and the reaction mixture was
vigorously stirred at room temperature for 15 min. Then, the reaction
mixture was cooled to 0 °C followed by addition of 2-methyl-2-butene
(optional) and sequential addition of NaClO2 (0.722 g, 8.0 mmol)
dissolved in 1.5 mL of H2O. The reaction mixture was stirred until the
starting material was consumed (see Table 1 in manuscript for selected
(R)-2-(3-(Hydroxymethyl)-5,6-dihydropyridin-1(2H)-yl)-2-
20
phenylethanol-22. Obtained 0.620 g (90%) as a yellow oil: [α]D
=
1
−8.97 (c = 1.0, CH2Cl2); H NMR (400 MHz, CDCl3) δ 2.15 (m,
2H), 2.31 (dt, J = 11.2, 5.6 Hz, 1H), 2.74 (dt, J = 11.2, 5.6 Hz, 1H),
2.92 (br, 2H), 3.06 (m, 2H), 3.74 (m, 2H), 3.96 (s, 2H), 4.04 (m, 1H),
5.67 (s, 1H), 7.3 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 25.8, 45.9,
5521
dx.doi.org/10.1021/jo300542d | J. Org. Chem. 2012, 77, 5515−5524

The Journal of Organic Chemistry
Article
entry). The phases were separated, and the aqueous phase was
extracted with EtOAc (3 × 15 mL). The combined organic phases
were dried over Na2SO4, and the solvent was removed under reduced
pressure. The residue was purified by column chromatography on
silica gel to give the corresponding product.
1.47 (d, J = 7.2 Hz, 3H), 1.88 (m, 1H), 2.22 (apparent dq, J = 14.4, 2.8
Hz, 1H), 2.80 (m, 1H), 3.13 (m, 1H), 3.72 (d, J = 3.2 Hz, 1H), 4.20
(d, J = 12.8 Hz, 1H), 4.33 (d, J = 12.8 Hz, 1H), 5.95 (q, J = 7.2 Hz,
1H), 7.28 (m, 5H); 13C NMR (100 MHz, CDCl3) δ −5.5, 5.4, 15.4,
18.3, 23.9, 25.8, 36.0, 50.2, 54.3, 57.5, 58.6, 127.2, 127.3, 128.4, 139.4,
167.1; HRMS-FAB (m/z) [M + H]+ 362.2180 (calcd. 362.2151 for
C20H32NO3Si).
(S)-N-Allyl-N-(1-phenylethyl)oxirane-2-carboxamide-4. Ob-
tained 0.096 g (42%) as a colorless oil: NMR data are reported for
1
the mixture of diastereoisomers and E/Z rotamers; H NMR (400
2,3-Epoxyamide (1′S,3R,4R)-14b. Obtained 0.179 g (50%) as a
20
1
MHz, CDCl3) δ 1.51 (d, J = 7.2 Hz), 1.52 (d, J = 7.2 Hz), 1.69 (d, J =
7.2 Hz), 2.90 (m), 3.03 (m), 3.57 (m), 3.83 (m), 5.02 (m), 5.14 (m),
5.43 (q, J = 6.8 Hz), 5.67 (m), 6.00 (m), 6.06 (q, J = 7.2 Hz), 6.07 (q, J
= 7.2 Hz), 7.3 (m); 13C NMR (100 MHz, CDCl3) δ 16.4, 45.1, 45.3,
46.5, 46.7, 47.3, 47.5, 51.7, 116.7, 116.9, 127.5, 127.6, 127.6, 128.4,
128.7, 134.0, 134.6, 134.8, 139.9, 140.0, 168.2; HRMS-FAB (m/z) [M
+ H]+ 232.1341 (calcd. 232.1338 for C14H18NO2).
(S)-N-Allyl-2-oxo-N-(1-phenylethyl)propanamide-5. Obtained
0.09 g (40%) as a colorless oil: [α]D20 = −130.68 (c = 1.0, CH3Cl); 1H
NMR (400 MHz, CDCl3) δ 1.58 (d, J = 6.8 Hz, 3H), 1.65 (d, 6.8 Hz,
3H), 2.35 (s, 3H), 2.39 (s, 3H), 3.52 (dd, J = 15.6, 6.4 Hz, 1H), 3.64
(dd, J = 16.8, 6.0 Hz, 1H), 3.84 (dd, J = 16.8, 6.0 Hz, 1H), 4.04 (dd, J
= 15.6, 5.2 Hz, 1H), 4.95 (m, 1H), 4.99 (m, 1H), 5.05 (m, 1H), 5.07
(m, 2H), 5.54 (ddt, J = 17.2, 10.0, 6.0 Hz, 1H), 5.72 (dddd, J = 17.2,
10.4, 5.6, 5.2 Hz, 1H), 5.92 (q, J = 6.8 Hz, 1H), 7.3 (m, 10H); 13C
NMR (100 MHz, CDCl3) δ 16.3, 18.2, 27.4, 27.6, 44.8, 45.6, 51.3,
55.7, 117.2, 118.0, 127.3, 127.5, 127.7, 127.9, 128.5, 128.6, 133.2,
134.8, 139.2, 139.4, 167.4, 167.5, 198.3, 198.8; HRMS-FAB (m/z) [M
+ H]+ 232.1337 (calcd. 232.1338 for C14H18NO2).
yellow oil: [α]D = −86.17 (c = 1.0, CHCl3); H NMR (400 MHz,
CDCl3) δ 0.08 (s, 3H), 0.09 (s, 3H), 0.89 (s, 9H), 1.48 (d, J = 6.8 Hz,
3H), 1.66 (ddd, J = 14.8, 12.8, 6.0 Hz, 1H), 2.16 (d, J = 14.8 Hz, 1H),
2.72 (dd, J = 12.4, 5.6 Hz, 1H), 3.22 (td, J = 12.8, 4.4 Hz, 1H), 3.70 (d,
J = 3.2 Hz, 1H), 4.19 (d, J = 12.8 Hz, 1H), 4.36 (d, J = 13.2 Hz, 1H),
5.98 (q, J = 6.8 Hz, 1H), 7.29 (m, 5H); 13C NMR (100 MHz, CDCl3)
δ −5.4, −5.3, 15.5, 18.3, 23.6, 25.8, 35.0, 50.1, 54.2, 57.4, 58.6, 127.0,
127.3, 128.4, 140.1, 167.2; HRMS-FAB (m/z) [M + H]+ 362.2180
(calcd. 362.2151 for C20H32NO3Si).
2,3-Epoxyamide (1′S,3S,4S)-15a. Obtained 0.123 g (33.5%) as a
pale yellow solid: mp 105−107 °C; [α]D20 = −88.3 (c = 1.0, CH2Cl2);
1H NMR (400 MHz, CDCl3) δ 1.49 (d, J = 7.2 Hz, 3H), 1.87 (m,
1H), 2.25 (dq, J = 14.4, 2.8 Hz, 1H), 2.83 (dd, J = 9.6, 2.8 Hz, 2H),
3.83 (d, J = 2.8 Hz, 1H), 4.41 (d, J = 12.0 Hz, 1H), 4.69 (d, J = 12.0
Hz, 1H), 5.89 (s, 2H), 5.98 (q, J = 7.2 Hz, 1H), 6.39 (dd, J = 8.4, 2.4
Hz, 1H), 6.54 (d, J = 2.4 Hz, 1H), 6.69 (d, J = 8.4 Hz, 1H), 7.28 (m,
5H); 13C NMR (100 MHz, CDCl3) δ 15.4, 23.9, 35.9, 50.5, 55.6, 56.2,
65.2, 98.4, 101.1, 106.0, 107.8, 127.2, 127.4, 128.4, 139.1, 141.8, 148.0,
153.9, 166.2; HRMS-EI (m/z) 367.1389 (calcd. 367.1420 for
C21H21NO5).
2,3-Epoxyamide (1′S,3R,4R)-15b. Obtained 0.185 g (50.5%) as a
pale yellow oil: [α]D20= −85.1 (c = 1.0, CHCl3); 1H NMR (400 MHz,
CDCl3) δ 1.50 (d, J = 7.2 Hz, 3H), 1.72 (ddd, J = 14.4, 12.8, 6.0 Hz,
1H), 2.19 (d, J = 13.6 Hz, 1H), 2.76 (dd, J = 12.4 Hz, 5.6, 1H), 3.25
(td, J = 12.8, 4.4 Hz, 1H), 3.83 (d, J = 2.5 Hz, 1H), 4.44 (d, J = 12.0
Hz, 1H), 4.69 (d, J = 12.0 Hz, 1H), 5.90 (s, 2H), 6.01 (q, J = 7.2 Hz,
1H), 6.40 (dd, J = 8.4, 2.4 Hz, 1H), 6.54 (d, J = 2.4 Hz, 1H), 6.69 (d, J
= 8.4 Hz, 1H), 7.3 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 15.6,
23.7, 35.0, 50.5, 55.6, 56.1, 65.2, 98.4, 101.1, 106.1,107.8, 127.0, 127.5,
128.5, 139.9, 1419, 148.1, 154.0, 166.4; HRMS-EI (m/z) 367.1411
(calcd. 367.1420 for C21H21NO5).
2,3-Epoxyamide (1′S,3S,4S)-16a. Obtained 0.10 g (27%) as a
pale yellow oil: [α]D20= −36.6 (c = 0.5, CH2Cl2); 1H NMR (400 MHz,
CDCl3) δ 1.50 (d, J = 7.2 Hz, 3H), 1.97 (m, 1H), 2.29 (apparent dq, J
= 10.4, 3.2 Hz, 1H), 2.81 (dd, J = 10.4, 3.2 Hz, 2H), 4.01 (d, J = 2.8
Hz, 1H), 4.48 (d, J = 12.0 Hz, 1H), 4.78 (d, J = 12.0 Hz, 1H), 5.94 (s,
2H), 5.99 (q, J = 7.2 Hz, 1H), 6.71 (s, 1H), 6.81 (s, 1H), 7.30 (m,
5H); 13C NMR (100 MHz, CDCl3) δ 15.5, 24.1, 36.0, 50.6, 55.7, 56.3,
66.6, 94.4, 98.4, 101.8, 109.8, 114.7, 127.3, 127.5, 128.6, 139.3, 142.2,
146.9, 149.2, 166.3; HRMS-FAB m/z [M + H]+ 402.1117 (calcd.
402.1108 for C21H21NO5Cl).
(S)-N-Allyl-N-(1-phenylethyl)prop-2-enamide-6. Obtained
20
0.019 g (9%) as a colorless oil: [α]D = −198.12 (c = 1.0, CHCl3);
1
NMR data are reported for the mixture of E/Z rotamers; H NMR
(400 MHz, CDCl3) δ 1.52 (d, J = 7.2 Hz), 1.64 (d, J = 6.8 Hz), 3.64
(d, J = 17.2 Hz), 3.80 (d, J = 17.2 Hz), 5.08 (m), 5.24 (m), 5.61 (m),
5.70 (m), 5.8 (m), 6.16 (q, J = 7.2 Hz), 6.5 (m), 6.64 (m), 7.3 (m);
13C NMR (100 MHz, CDCl3) δ 16.5, 18.7, 45.6, 45.7, 51.1, 51.2,
116.4, 116.6, 126.5, 126.6, 127.6, 127.3, 127.4, 127.4, 127.9, 128.3,
128.5, 131.0, 134.5, 134.9, 140.4, 140.5, 160.7; HRMS-FAB (m/z) [M
+ H]+ 216.1387 (calcd. 216.1388 for C14H18NO2).
(S)-3,3-Dimethyl-N-(3-methylbut-2-enyl)-N-(1-phenylethyl)-
oxirane-2-carboxamide-12. Obtained 0.17 g (54%) as a pale yellow
oil: NMR data is reported as a mixture of diastereoisomers and E/Z
1
rotamers; H NMR (400 MHz, CDCl3) δ 1.32−1.72 (m), 3.38 (s,
1H), 3.03 (m), 3.16 (m), 3.31−3.72 (m), 3.89 (m), 4.03 (dd, J = 14.8,
6.8 Hz), 4.10 (dd, J = 14.8, 6.8 Hz), 4.84 (m), 4.96 (m), 5.50 (m), 5.16
(m), 5.28 (q, J = 7.2 Hz), 5.38 (q, J = 7.2 Hz), 6.03 (q, J = 7.2 Hz),
6.10 (q, J = 7.2 Hz), 7.29 (m); 13C NMR (100 MHz, CDCl3) δ 16.4,
16.5, 17.6, 17.7, 17.9, 18.6, 23.9, 24.0, 25.6, 25.9, 41.0, 41.1, 47.1, 50.8,
51.3, 54.2, 54.8, 59.6, 59.9, 60.9, 61.3, 121.2, 122.0, 122.2, 126.7, 126.8,
127.4, 127.5, 127.6, 127.8, 128.3, 128.6, 128.7, 133.6, 133.9, 140.1,
140.5, 167.3, 167.4; HRMS-FAB (m/z) [M + H]+ 288.1976 (calcd.
288.1964 for C18H26NO2).
2,3-Epoxyamide (1′S,3R,4R)-16b. Obtained 0.16 g (41%) as a
2,3-Epoxyamide (1′S,3S,4S)-13a. Obtained 0.079 g (31%) as a
pale yellow oil: [α]D20= −70.87 (c = 1.0, CH2Cl2); H NMR (400
1
20
1
pale yellow oil: [α]D = −118.6 (c = 1.0, CHCl3); H NMR (400
MHz, CDCl3) δ 1.49 (d, J = 7.2 Hz, 3H), 1.94 (m, 1H), 2.21
(apparent dq, J = 14.4, 2.8, Hz, 1H), 2.81 (dd, J = 9.6, 2.8 Hz, 2H),
3.27 (br, 1H), 3.54 (d, J = 2.8 Hz, 1H), 3.96 (s, 2H), 5.93 (q, J = 7.2
Hz, 1H), 7.28 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 15.3, 24.0,
35.9, 50.5, 56.7, 56.8, 62.2, 127.1, 127.4, 128.4, 138.9, 167.4; HRMS-
FAB (m/z) [M + H]+ 248.1281 (calcd. 248.1287 for C14H18NO3).
2,3-Epoxyamide (1′S,3R,4R)-13b. Obtained 0.120 g (49%) as a
MHz, CDCl3) δ 1.50 (d, J = 7.2 Hz, 3H), 1.74 (ddd, J = 14.4, 12.8, 6.0
Hz, 1H), 2.20 (d, J = 14.8 Hz, 1H), 2.76 (dd, J = 12.4, 6.0 Hz, 1H),
3.25 (td, J = 12.4, 4.0 Hz, 1H), 3.99 (d, J = 2.8 Hz, 1H), 4.49 (d, J =
12.0 Hz, 1H), 4.78 (d, J = 12.0 Hz, 1H), 5.93 (s, 2H), 6.00 (q, J = 7.2
Hz, 1H), 6.71 (s, 1H), 6.80 (s, 1H), 7.31 (m, 5H); 13C NMR (100
MHz, CDCl3) δ 15.6, 20.2, 23.6, 34.9, 50.4, 55.5, 56.1, 66.3, 98.2,
101.7, 109.7, 114.5, 127.0, 127.4, 128.4, 139.8, 142.0, 146.8, 149.1,
166.3; HRMS-FAB (m/z) [M + H]+ 402.1110 (calcd. 402.1108 for
C21H21NO5Cl).
pale yellow oil: [α]D20= −113.2 (c = 1.0, CHCl3); H NMR (400
1
MHz, CDCl3) δ 1.50 (d, J = 7.2 Hz, 3H), 1.71 (ddd, J = 14.4, 12.8, 6.0
Hz, 1H), 2.17 (d, J = 14.4 Hz, 1H), 2.76 (dd, J = 12.4, 5.6 Hz, 1H),
3.22 (td, J = 12.8, 4.4 Hz, 1H), 3.54 (d, J = 3.2 Hz, 1H), 3.99 (s, 2H),
5.99 (q, J = 7.2 Hz, 1H), 7.3 (m, 5H); 13C NMR (100 MHz, CDCl3) δ
15.5, 23.8, 34.9, 50.4, 56.6, 56.8, 62.6, 126.9, 127.5, 128.4, 139.6, 167.6;
HRMS-FAB (m/z) [M + H]+ 248.1295 (calcd 248.1287 for
C14H18NO3).
2,3-Epoxyamide (1′S,3S,4S)-17a. Obtained 0.067 g (24%) as a
pale yellow oil: [α]D20= −113.1 (c = 1.0, CH2Cl2); H NMR (400
1
MHz, CDCl3) δ 1.50 (d, J = 7.2 Hz, 3H), 2.05 (ddd J = 14.8, 12.4, 6.0
Hz, 1H), 2.27 (m, 1H), 2.76 (td, J = 12.8, 4.0 Hz, 1H), 2.88 (dd, J =
12.8, 6.0 Hz, 1H), 3.73 (d, J = 2.5 Hz, 1H), 3.88 (s, 3H), 5.99 (q, J =
7.2 Hz, 1H), 7.29 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 15.3, 23.8,
35.6, 50.7, 52.8, 56.9, 57.6, 127.2, 127.5, 128.5, 138.8, 162.9, 166.0;
HRMS-FAB (m/z) [M + H]+ 276.1265 (calcd. 276.1236 for
C15H18NO4).
2,3-Epoxyamide (1′S,3S,4S)-14a. Obtained 0.120 g (33%) as a
20
1
yellow solid: mp 73−75 °C; [α]D = −91.17 (c = 1.0, CHCl3); H
NMR (400 MHz, CDCl3) δ 0.07 (s, 3H), 0.08 (s, 3H), 0.90 (s, 9H),
5522
dx.doi.org/10.1021/jo300542d | J. Org. Chem. 2012, 77, 5515−5524

The Journal of Organic Chemistry
Article
2,3-Epoxyamide (1′S,3R,4R)-17b. Obtained 0.10 g (36%) as a
pale yellow solid: mp 97−100 °C; [α]D20= −128.30 (c = 1.0, CH2Cl2);
1H NMR (400 MHz, CDCl3) δ 1.49 (d, J = 7.2 Hz, 3H), 1.82 (ddd, J
= 14.8, 12.4, 6.0 Hz, 1H), 2.20 (m, 1H), 2.77 (dd, J = 12.4, 6.0 Hz,
1H), 3.18 (td, J = 12.4, 4.4 Hz, 1H), 3.71 (d, J = 2.1 Hz, 1H), 3.89 (s,
3H), 5.98 (q, J = 7.2 Hz, 1H), 7.32 (m, 5H); 13C NMR (100 MHz,
CDCl3) δ 15.4, 23.6, 34.7, 50.9, 52.8, 56.9, 57.5, 127.2, 127.6, 128.5,
139.4, 163.1, 166.1. HRMS-FAB (m/z) [M + H]+ 276.1211 (calcd.
276.1236 for C15H18NO4).
127.1, 128.5, 144.5, 172.5; HRMS-FAB m/z [M + H]+ 208.1346
(calcd. 208.1338 for C12H18NO2).
2,3-Epoxyamide (1′R,3R,4R)-31. Obtained 0.07 g (31%) as a
white solid: mp 124−127 °C; [α]D20 = −94.65 (c = 1.0, CH2Cl2); 1H
NMR (400 MHz, CDCl3) δ 1.77 (ddd, J = 14.4, 12.8, 6.0 Hz, 1H),
2.20 (d, J = 14.8 Hz, 1H), 2.90 (dd, J = 12.4, 5.2 Hz, 1H), 3.34 (td, J =
12.8, 4.4 Hz, 1H), 3.59 (d, J = 2.8 Hz, 1H), 3.94 (d, J = 12.4 Hz, 1H),
4.03 (d, J = 12.4 Hz, 1H), 4.14 (dd, J = 11.6, 5.6 Hz, 1H), 5.80 (dd, J =
8.8, 5.6 Hz, 1H), 7.29 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 23.8,
36.4, 56.7, 56.9, 58.1, 61.1, 62.2, 127.4, 127.9, 128.7, 136.4, 168.9;
HRMS-FAB m/z [M + H]+ 264.1237 (calcd. 264.1236 for
C14H18NO4).
2,3-Epoxyamide (1′S,3R,4R)-18. To a flask containing a solution
of 8 (0.070 g, 0.28 mmol) and TsCl (0.064 g, 0.34 mmol) in 5 mL of
CH2Cl2 was added NEt3 (0.057 g, 0.568 mmol). The reaction was
stirred for 3 h, and then water (2 mL) was added. The phases were
separated, and the aqueous phase was extracted with EtOAc (2 × 10
mL). The combined organic phases were dried over Na2SO4, and the
solvent was removed under reduced pressure. Flash chromatography
on silica gel gave 0.107 g (95%) of the desired product 18 as a white
2,3-Epoxyamide (1′R,3S,4S)-32. Obtained 0.050 g (22%) as a
20
1
yellow pale oil: [α]D = −57.1 (c = 1.0, CH2Cl2). H NMR (400
MHz, CDCl3) δ 2.10 (m, 1H), 2.21 (apparent dq, J = 14.8, 2.8 Hz,
1H), 2.96 (m, 2H), 3.23 (br, 1H), 3.60 (d, J = 2.8 Hz, 1H), 3.90 (d, J =
12.6 Hz, 1H), 4.05 (d, J = 12.6 Hz, 1H), 4.15 (m, 2H), 5.74 (dd, J =
8.8, 4.8 Hz, 1H), 7.33 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 23.9,
37.9, 57.1, 57.3, 58.7, 61.2, 62.6, 127.7, 128.1, 128.8, 135.8, 169.4;
HRMS-FAB m/z [M + H]+ 264.1233 (calcd. 264.1236 for
C14H18NO4).
1
solid: mp 133−136 °C; H NMR (400 MHz, CDCl3) δ 1.45 (d, J =
7.2 Hz, 3H), 1.68 (ddd, J = 14.4, 12.8, 6.0 Hz, 1H), 2.15 (d, J = 14.8
Hz, 1H), 2.45 (s, 3H), 2.72 (dd, J = 12.4 Hz, 5.6, 1H), 3.17 (td, J =
12.4, 4.4 Hz, 1H), 3.75 (d, J = 3.2 Hz, 1H), 4.38 (d, J = 12.0 Hz, 1H),
4.83(d, J = 12.0 Hz, 1H), 5.92 (q, J = 7.2 Hz, 1H), 7.30 (m, 7H), 7.82
(d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 14.1, 15.5, 21.6,
23.5, 34.8, 50.6, 55.0, 66.2, 127.0, 127.6, 128.0, 128.5, 129.9, 132.4,
139.6, 145.0, 167.3.
2,3-Epoxyamide (1′R,3R,4R)-33. Obtained 0.048 g (36%) as a
colorless oil: [α]D20 = −62.13 (c = 1.0, CH2Cl2); 1H NMR (400 MHz,
CDCl3) δ 0.09 (s, 6H), 0.89 (s, 9H), 1.78 (ddd, J = 14.4, 12.8, 6.0 Hz,
1H), 2.19 (d, J = 14.8 Hz, 1H), 2.93 (dd, J = 12.4, 5.6 Hz, 1H), 3. 08
(br, 1H), 3.34 (td, J = 12.4, 4.0 Hz, 1H), 3.55 (d, J = 2.4 Hz, 1H), 3.
96 (s, 2H), 4.04 (dd, J = 10.8, 7.6 Hz, 1H), 4.10 (dd, J = 10.8, 5.6 Hz,
1H), 5.81 (apparent t, J = 5.6 Hz, 1H), 7.31 (m, 5H); 13C NMR (100
MHz, CDCl3) δ-5.6, −5.5, 18.0, 24.1, 25.7, 36.5, 56.7, 56.8, 57.0, 61.7,
62.9, 127.6, 127.7, 128.6, 137.1, 168.5; HRMS-FAB m/z [M + H]+
378.2103 (calcd. 378.2101 for C20H32NO4Si).
(*R)-N-Benzyl-3,3-dimethyl-N-((S)-1-phenylethyl)oxirane-2-
carboxamide-27. Obtained 0.057 g (36%) as a white solid: mp 104−
107 °C; [α]D20 = −32.21 (c = 0.81, CH2Cl2); NMR data is reported as
1
a mixture of E/Z rotamers; H NMR (400 MHz, CDCl3) δ 0.88 (s,
3H), 1.23 (s, 3H), 1.33 (s, 3H), 1.39 (s, 3H), 1.54 (d, J = 7.2 Hz, 3H),
1.60 (d, J = 7.2 Hz, 3H), 3.21 (s, 1H), 3.56 (s, 1H), 4.00 (d, J = 15.2
Hz, 1H), 4.27 (d, J = 17.6 Hz, 1H), 4.46 (d, J = 17.6 Hz, 1H), 4.92 (d,
J = 15.2 Hz, 1H), 5.47 (q, J = 7.2 Hz, 1H), 6.17 (q, J = 7.2 Hz, 1H),
7.27 (m, 20H); 13C NMR (100 MHz, CDCl3) δ 16.8, 18.3, 19.1, 19.6,
23.6, 24.0, 46.2, 47.0, 52.0, 55.5, 60.5, 61.0, 61.4, 126.1, 126.8, 126.8,
127.4, 127.5, 127.6, 127.7, 128.2, 128.5, 128.5, 128.7, 128.8, 138.3,
140.3, 168.0, 168.2; HRMS-FAB m/z [M + H]+ 310.1820 (calcd.
310.1807 for C20H24NO2).
2,3-Epoxyamide (1′R,3S,4S)-34. Obtained 0.048 g (36%) as a
colorless oil: [α]D20 = −28.9 (c = 1.0, CH2Cl2); H NMR (400 MHz,
1
CDCl3) δ 0.09 (s, 3H), 0.10 (s, 3H), 0.89 (s, 9H), 2.03 (ddd, J = 14. 4,
12.8, 6.0 Hz, 1H), 2.23 (d, J = 14.4 Hz, 1H), 3.02 (td, J = 12.8, 4.0 Hz,
1H), 3.14 (dd, J = 12.8, 6.0 Hz, 1H), 3.58 (d, J = 2.8 Hz, 1H), 3.95 (s,
2H), 4.04 (dd, J = 10.8, 5.2 Hz, 1H), 4.11(dd, J = 10.8, 6.8 Hz, 1H),
5.70 (apparent t, J = 6.0 Hz, 1H), 7.3 (m, 5H); 13C NMR (100 MHz,
CDCl3) δ −5.6, −5.4, 18.0, 24.1, 25.7, 38.1, 57.1, 57.1, 57.4, 61.8, 62.9,
127.7, 127.9, 128.5, 136.8, 168.3; HRMS-FAB m/z [M + H]+
378.2100 (calcd. 378.2101 for C20H32NO4Si).
(*S)-N-Benzyl-3,3-dimethyl-N-((S)-1-phenylethyl)oxirane-2-
carboxamide-28. Obtained 0.051 g (32%) as a white solid: mp 131−
134 °C; [α]D20 = −115.27 (c = 0.5, CH2Cl2); NMR data is reported as
1
a mixture of E/Z rotamers; H NMR (400 MHz, CDCl3) δ 1.08 (s,
3H), 1.24 (s, 3H), 1.33 (s, 3H), 1.39 (s, 3H), 1.46 (d, J = 7.2 Hz, 3H),
1.52 (d, J = 7.2 Hz, 3H), 3.24 (s, 1H), 3.48 (s, 1H), 4.06 (d, J = 15.6
Hz, 1H), 4.29 (d, J = 17.6 Hz, 1H), 4.43 (d, J = 17.6 Hz, 1H), 4.94 (d,
J = 15.6 Hz, 1H), 5.36 (q, J = 7.2 Hz, 1H), 6.24 (q, J = 7.2 Hz, 1H),
7.23 (m, 20H); 13C NMR (100 MHz, CDCl3) δ 16.7, 18.4, 19.2, 19.4,
23.7, 23.8, 46.4, 46.6, 51.6, 54.9, 59.9, 61.0, 61.3, 126.1, 126.8, 126.9,
127.4, 127.7, 127.8, 128.2, 128.5, 128.6, 128.7, 128.8, 137.7, 138.8,
140.4, 168.2; HRMS-FAB m/z [M + H]+ 310.1825 (calcd. 310.1807
for C20H24NO2).
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 1H and 13C NMR spectra and CIF file for
epoxyamide (1′S,3R,4R)-18. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*Tel.: +52 222 2955500 ext 7391. Fax: +52 222 2454972. E-
mail: fernando.sartillo@correo.buap.mx.
(S)-Ethyl 2-(Allyl(1-phenylethyl)amino)-2-oxoacetate-29. Ob-
20
tained 0.046 g (44%) as a colorless oil: [α]D = −115.21 (c = 1.0,
1
CH2Cl2); NMR data is reported as a mixture of E/Z rotamers; H
NMR (400 MHz, CDCl3) δ 1.34 (t, J = 7.6 Hz, 3H), 1.37 (t, J = 7.2
Hz, 3H), 1.57 (d, J = 7.2, 3H), 1.65 (d, J = 7.2 Hz, 3H), 3.44 (dd, J =
15.2, 6.4 Hz, 1H), 3.63 (dd, J = 16.8, 6.4 Hz, 1H), 3.79 (dd, J = 16.8,
5.2 Hz, 1H), 3.94 (dd, J = 15.6, 5.2 Hz, 1H), 4.28 (q, J = 7.2 Hz, 2H),
4.36 (q, J = 7.2 Hz, 2H), 4.95 (q, J = 7.2 Hz, 1H), 5. 02 (m, 4H), 5.63
(m, 2H), 5.89 (q, J = 7.2 Hz, 1H), 7.3 (m, 10H); 13C NMR (100
MHz, CDCl3) δ 13.9, 14.0, 16.5, 17.8, 44.1, 46.4, 51.4, 56.4, 61.9, 62.1,
117.1, 117.6, 127.3, 127.7, 127.8, 128.1, 128.5, 128.6, 133.0, 134.5,
138.5, 139.1, 162.0, 162.3, 162.9, 163.4; HRMS-FAB m/z [M + H]+
262.1468 (calcd. 262.1443 for C15H20NO3).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from CONACyT
and Benemer
́
ita Universidad Auton
́
oma de Puebla (BUAP-
VIEP). We also thank Mr. Vladimir Carranza-Tellez for
technical assistance in mass spectroscopy.
(S)-Ethyl 2-(1-Phenylethylamino)acetate-30. Obtained 0.033 g
(28%) as a colorless oil: [α]D20 = −68.80 (c = 1.0, CH2Cl2). 1H NMR
(400 MHz, CDCl3) δ 1.24 (t, J = 7.6 Hz, 3H), 1.38 (d, J = 6.8 Hz,
3H), 2.01 (br, 1H), 3.22 (d, J = 17.6 Hz, 1H), 3.29 (d, J = 17.6 Hz,
1H), 3.79 (q, J = 6.8 Hz, 1H), 4.15 (q, J = 7.2 Hz, 2H), 7.3 (m, 5H);
13C NMR (100 MHz, CDCl3) δ 14.2, 24.2, 48.8, 57.7, 60.7, 126.7,
REFERENCES
■
(1) (a) Hanakada, K.; Tamai, M.; Yamaguishi, M.; Ohmura, S.;
Sawada, J.; Tanaka, I. Agric. Biol. Chem. 1978, 42, 523. (b) Milner, P.
H.; Coates, N. J.; Gilpin, M. L.; Spear, S. R. J. Nat. Prod. 1996, 59, 400.
(c) Riemer, B.; Hofer, O.; Greger, H. Phytochemistry 1997, 45, 337.
5523
dx.doi.org/10.1021/jo300542d | J. Org. Chem. 2012, 77, 5515−5524

The Journal of Organic Chemistry
Article
(2) Recent and impressive synthetic applications of 2,3-epoxyamides:
(a) Sarabia, F.; Vivar-García, C.; García-Ruíz, C.; Martín-Ortíz, L.;
Romero-Carrasco, A. J. Org. Chem. 2012, 77, 1328. (b) Sarabia, F.;
Vivar-García, C.; García-Castro, M.; Martín-Ortiz, J. J. Org. Chem.
2010, 76, 3139. (c) Wei-Jun, L.; Bing-Da, Lv.; Liu-Zhu, G. Angew.
= 100 K, 2θmax = 50.00, 9379 reflections measured, 3399 unique (Rint =
0.063), R1 = 0.0497 for 2611 reflections with I > 2σ(I) and wR2 =
0.1243 for all data, 255 parameters, GOF = 1.007. Crystallographic
data for the crystal structure have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no.
CCDC-870304. Copies of the data can be obtained free of charge
on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, U.K.
Fax: (+44)1223-336-033. E-mail: deposit@ccdc.cam.ac.uk. Web:
http://www.ccdc.cam.ac.uk.
Chem. Int. Ed. 2009, 48, 6503. (d) Aparicio, D. M.; Teran
Gnecco, D.; Galindo, A.; Juarez, J. R.; Orea, M. L.; Mendoza, A.
Tetrahedron: Asymmetry 2009, 20, 2764.
́
, J. L.;
́
(3) (a) Rosen, T. In Comprehensive Organic Synthesis; Trost, B. M.,
Feming, I., Heathcock, C. H., Eds.; Pergamon: Oxford, 1991; Vol. 2, p
409. (b) Tung, C. C.; Speziale, A. J.; Frazier, H. W. J. Org. Chem. 1963,
28, 1514.
(4) Representative examples: (a) Illa, O.; Arshad, M.; Ros, A.;
McGarrigle, E. M.; Aggarwal, V. K. J. Am. Chem. Soc. 2010, 132, 1828.
(b) McGarrigle, E. M.; Myers, E. L.; Illa, O.; Shaw, M. A.; Riches, S. L.;
Aggarwal, V. K. Chem. Rev. 2007, 107, 5841. (c) Aggarwal, V. K.;
Hynd, G.; Picoul, W.; Vasse, J. L. J. Am. Chem. Soc. 2002, 124, 9964.
(d) Zhou, Y.-G.; Hou, X.-L.; Dai, L.-X.; Xia, L. J.; Tang, M.-H. J. Chem.
Soc., Perkin Trans. I 1999, 77.
(19) Das, S.; Addismpm, D.; Zhou, S.; Junge, K.; Beller, M. J. Am.
Chem. Soc. 2010, 132, 1770.
(20) It has been reported that ClO2 promotes oxidative dealkylation
of tertiary amines: Hull, L. A.; Davis, G. T.; Rosenblatt, D. H.;
Williams, H. K. R.; Weglein, R. C. J. Am. Chem. Soc. 1967, 89, 1163.
(21) Imashiro, R.; Seki, M. J. Org. Chem. 2004, 69, 4216.
(22) Ingrassia, L.; Mulliez, M. Bull. Soc. Chim. 1995, 135, 1157.
(5) (a) He, L.; Liu, W. J.; Ren, L.; Lei, T.; Gong, L. Z. Adv. Synth.
Catal. 2010, 352, 1123. (b) Doyle, M. P.; Mckervey, M. A.; Ye, T.
Modern Catalytic Methods for Organic Synthesis with Diazo Compounds;
Wiley: New York, 1998. (c) Lop
́
ez-Herrera, F. J.; Sarabia-García, F.;
Pino-Gonzalez, M. S. Tetrahedron Lett. 1994, 35, 2933.
́
(6) (a) Waser, M.; Herchi, R.; Muller, N. Chem. Commun. 2011, 47,
̈
2170. (b) Herchl, R.; Stiftinger, M.; Waser, M. Org. Biomol. Chem.
2011, 9, 7021.
́
́
(7) (a) Díez, D.; Nunez, M. G.; Anton, A. B.; García, P.; Moro, R. F.;
̃
Garrido, N. M.; Marcos, I. S. Curr. Org, Synth. 2008, 5, 189.
(b) Nemoto, T.; Kakei, H.; Gnanadesikda, V.; Tosaki, S.-Y.; Ohshima,
T.; Shibasaki, M. J. Am. Chem. Soc. 2002, 124, 14544.
(8) Representative examples: (a) Wang, Y.; Kobayashi, H.;
Yamaguchi, K.; Mizuno, N. Chem. Commun. 2012, 48, 2642. (b) So,
M. H.; Liu, Y.; Ho, C.-M.; Che, C.-M. Chem.Asian J. 2009, 4, 1551.
(c) Kim, J. W.; Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed.
2008, 47, 9249. (d) Klitgaard, S. K.; Egeblad, K.; Mentzel, U. V.;
Popov, A. G.; Jensen, T.; Taarning, E.; Nielsen, I. S.; Christensen, C.
H. Green Chem. 2008, 10, 419. (f) Sharma, N. K.; Ganesh, K. N.
Tetrahedron. Lett. 2004, 45, 1403.
(9) (a) Silvestre, S. M.; Salvador, J. A. R. Tetrahedron 2007, 63, 2439.
(b) Crich, D.; Zou, Y. Org. Lett. 2004, 6, 775. (c) Yu, J.-Q.; Corey, E. J.
J. Am. Chem. Soc. 2003, 125, 3232. (d) Umbreit, M. A.; Sharpless, K. B.
J. Am. Chem. Soc. 1977, 99, 5526. Excellent reviews: (e) Ley, S. V. In
Organoselenium Chemistry; Liotta, D., Ed.; Wiley: New York, 1987; p
163. (f) Eames, J.; Watkinson, M. Angew. Chem., Int. Ed. 2001, 40,
3567.
(10) Lindgren, B. O.; Nilsson, T. Acta Chem. Scand. 1973, 27, 888.
(11) Bal, B. S.; Childers, W. E.; Pinnick, H. W. Tetrahedron 1981, 37,
2091.
(12) (a) Rickborn, B. In Comprehensive Organic Synthesis; Trost, B.
M., Ed.; Pergamon: Oxford, 1991; Vol. 3, Chapter 3.3, p 733.
(b) Maruoka, K.; Murase, N; Bureau, R.; Ooi, T.; Yamamoto, H.
Tetrahedron 1994, 50, 3663. (c) Ranu, B. C.; Jana, U. J. Org. Chem.
1998, 63, 8212.
(13) Geng and coworkers demonstrated that radical ClO2 can be
prepared from sodium chlorite. See: Geng, X.-L.; Wang, Z.; Li, X.-Q.;
Zhang, C. J. Org. Chem. 2005, 70, 9610.
(14) Taylor, M. C.; White, J. F.; Vincent, G. P.; Cunningham, G. L.
Ind. Eng. Chem. 1940, 32, 899.
(15) It is well-known that hypochlorite oxidizes α,β-unsaturated
compounds; see: Thierry, S.; Lilian, A.; Charle, M. Synlett 1996, 571.
(16) (a) Kim, J. W.; Yamaguchi, K.; Mizuno, N. Angew. Chem., Int.
Ed. 2008, 47, 9249. (b) Liu, Y.; Yao, B.; Deng, C.-L.; Tang, R.-Y.;
Zhang, X.-Y.; Li, J.-H. Org. Lett. 2011, 13, 2184. (c) Soule, J.-F.;
́
Miyamura, H.; Kobayashi, S. J. Am. Chem. Soc. 2011, 133, 18550.
(17) Mitsunobu, O. Synthesis 1981, 1.
(18) Crystal data for C21H23NO5S: Mr = 401.46, 0.08 × 0.18 × 0.32
mm3, monoclinic, space group P21, a = 8.521(3), b = 8.286(2), c =
14.091(4) Å, β = 102.858(5)°, V = 969.9(5) Å3, Z = 2, ρcalcd = 1.375, T
5524
dx.doi.org/10.1021/jo300542d | J. Org. Chem. 2012, 77, 5515−5524