FeCl3·6H2O, a catalyst for the diastereoselective synthesis of cis-isoxazolidines from N-protected δ-hydroxylamino allylic acetates

Article abstract of DOI:10.1021/jo401627p

An ecofriendly and diastereoselective synthesis of cis-3,5-disubstituted isoxazolidines through the FeCl₃·6H₂O-catalyzed cyclization of δ-hydroxylamino allylic acetates is described. The synthetic potential of these products is highlighted by the preparation of several functionalized 1,3-amino alcohol precursors.

Full text of DOI:10.1021/jo401627p

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Article
FeCl3.6H2O, a catalyst for the diastereoselective synthesis of cis-
isoxazolidines from N-protected delta-hydroxylamino allylic acetates
Johan Cornil, Amandine Guerinot, Sébastien Reymond, and Janine Cossy
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo401627p • Publication Date (Web): 12 Sep 2013
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FeCl3ó6H2O, a catalyst for the diastereoselective synthesis of cis-isoxazolidines from
N-protected δ-hydroxylamino allylic acetates
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Johan Cornil, Amandine Guérinot, Sébastien Reymond* and Janine Cossy*
Laboratoire de Chimie Organique, ESPCI ParisTech, UMR CNRS 7084, 10 rue Vauquelin,
75231 Paris Cedex 05, France.
janine.cossy@espci.fr; sebastien.reymond@espci.fr
tel: +33 140794429; fax: +33 140794660
Abstract
An eco-friendly and diastereoselective synthesis of cis-3,5-disubstituted isoxazolidines
through the FeCl3ó6H2O-catalyzed cyclization of δ-hydroxylamino allylic acetates is
described. The synthetic potential of these products is highlighted by the preparation of
several functionalized 1,3-amino alcohol precursors.
Introduction
Nitrogen- and oxygen-containing heterocyclic frameworks are ubiquitous subunits in
biologically active products, and among them, isoxazolidines represent an interesting class of
heterocycles bearing both an oxygen and a nitrogen atom embedded in a five-membered ring.
Isoxazolidines can be encountered in natural products such as dactylicapnosine and
pyrinodemin A,1 and they can be precursors of various 1,3-amino alcohols when the N-O
bond is reductively cleaved.2 Although convenient methods for the construction of substituted
isoxazolidines exist, the development of highly stereoselective and eco-friendly reactions to
access these heterocycles remains a challenge. Among the existing methods to synthesize
3 , 4 , 5
isoxazolidines,
metal-catalyzed cyclizations of δ-hydroxylamino alkenes and
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δ-hydroxylamino allenes using palladium,6 copper,7 silver8 or gold complexes9 are attractive
methods.10,11 Recently, we have reported a highly diastereoselective synthesis of cis-2,6-
disubstituted piperidines through the cyclization of N-protected ζ-amino allylic acetates under
thermodynamic conditions.12 Herein, we wish to report that FeCl3ó6H2O is able to catalyze
the cyclization of δ-hydroxylamino allylic alcohol derivatives of type A to produce
substituted isoxazolidines B with good diastereoselectivities (Scheme 1).
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Scheme 1. Objective of the study
Results and discussion
Synthesis of isoxazolidines
In order to tune up the conditions allowing the cyclization of A to B, substrate 1a was treated
with various Brønsted and Lewis acids (Table 1). When N-tosyl δ-hydroxylamino allylic
acetate 1a was treated with 10 mol % of HCl, HBr/AcOH, CF3CO2H, or H2SO4·SiO2 in
CH2Cl2 for 24 h at 50 °C, no reaction occurred and 1a was recovered (Table 1, entries 1-4). In
the presence of PTSA•H2O or TfOH, the conversion of 1a was incomplete even after 24 h
(Table 1, entries 5-6). When Lewis acids such as ZnBr2, Cu(OTf)2, Zn(OTf)2, La(OTf)3, or
InCl3 were used, isoxazolidine 2a was formed, however with incomplete conversion of 1a
(Table 1, entries 7-11), whereas the use of AgOTf led to almost full conversion of 1a
providing 2a as a 90/10 cis/trans diastereomeric mixture (Table 1, entry 12).13 The best
results were obtained by using TiCl4, Bi(OTf)3, and FeCl3•6H2O14 as 2a was isolated in
excellent yields with a 90/10 cis/trans ratio (Table 1, entries 13-15).15,16 As FeCl3•6H2O is
cheap, easy-to-handle and environmentally benign, it was selected to determine the scope and
limitations of the δ-hydroxylamino allylic acetates cyclization.
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Table 1. Evaluation of various Brønsted and Lewis acids
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cis/trans
ratioa
-
entry
catalyst
yield (conversion)a
1
2
HCl aq. (2N)
HBr / AcOH
TFA
0%
0%
-
3
0%
-
4
H2SO4•SiO2
PTSA•H2O
TfOH
0%
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5
(21%)
(59%)
(50%)
(80%)
(77%)
(67%)
(33%)
(96%)
(95%)
93% (100%)
94% (100%)
nd
6
85/15
nd
7
ZnBr2
8
Cu(OTf)2
Zn(OTf)2
La(OTf)3
InCl3
nd
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nd
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nd
nd
AgOTf
90/10
90/10
90/10
90/10
TiCl4
Bi(OTf)3
FeCl3•6H2O
a Ratio determined by 1H NMR on the crude reaction mixture.
To study the influence of the nature of the leaving group on the cyclization, N-tosyl δ-
hydroxylamino allylic alcohol 1a’ was prepared and treated with 10 mol % of FeCl3•6H2O
(Scheme 2). Cyclization of this δ-hydroxylamino allylic alcohol proceeded with a lower yield
of 73% compared to the cyclization of the corresponding δ-hydroxylamino allylic acetate
(94%) (Table 1, entry 15). As a consequence, we decided to use allylic acetates for further
studies.
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Scheme 2. Influence of the leaving group
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The influence of the N-protecting groups in 1 (R1 group) and of the allylic substituent (R2
group) on the cyclization was examined and the results are summarized in Table 2. The
replacement of the N-tosyl group by a N-nosyl group resulted in similar results as 2b was
isolated in 95% yield and with a 89/11 cis/trans ratio (Table 2, entry 1). The presence of a N-
carbamate group in 1c (N-Cbz) and 1d (N-Alloc) provided the expected isoxazolidines 2c and
2d in 63% and 95% yield respectively, with a 85/15 cis/trans ratio (Table 2, entries 2-3).
However, when a N-Boc or a N-Ac group was present in 1 such as in 1e and 1f, no conversion
of these latter was observed (Table 2, entries 4-5). In addition, with 1g and 1h bearing an
allylic phenyl substituent (R2 = Ph), the corresponding isoxazolidines were isolated in good
yield and diastereoselectivity (78% and 86% yields respectively with a 80/20 cis/trans ratio)
(Table 2, entries 6-7). Noteworthy, contrary to 1f, 1h possessing a N-Boc protecting group
and a phenyl R2 substituent cyclized when treated with FeCl3•6H2O (Table 2, entry 7).
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Table 2. Influence of the N-protecting group and of the allylic substituent on the
cyclization
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entry
R1
Ns
R2
H
2 (yield %) cis/trans ratioa
1
1
2b (95%)
2c (63%)
2d (95%)
0%
89/11
85/15
85/15
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1c
1d
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Alloc
Ac
H
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H
4
H
5
Boc
Ts
H
0%
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7
Ph
Ph
2g (78%)
2h (86%)
80/20
60/40
1g
1h
Boc
a Determined by 1H NMR.
The reaction conditions were applied to an array of N-tosyl δ-hydroxylamino allylic acetates
1i-1o to form the corresponding isoxazolidines 2i-2o, the results are reported in Table 3 and in
Scheme 3. In the absence of any R3 substituent (R3 = H) and with a R2 ethyl substituent (1i,
R2 = Et), isoxazolidine 2i was isolated with an excellent yield of 96% (Table 3, entry 1).
Different R3 alkyl groups (R3 = Cy, Me) were introduced and the corresponding
isoxazolidines 2j-2k were isolated in good yields. When 1j (R2 = H, R3 = Cy) was treated
with FeCl3•6H2O, the corresponding isoxazolidine 2j was obtained with good yield and
diastereoselectivity (Table 3, entry 2). In the absence of any allylic substitutent (R2 = H), a
good cis/trans ratio was observed even when a R3 methyl group was present (Table 3, entry
3). When R3 is a phenyl group, and in the absence of any allylic substituent (R2 = H), an
excellent yield of 95% in isoxazolidine 2l was obtained and the cis/trans ratio was 86/14
(Table 3, entry 4). In presence of an ester substituent as in 1m (R3 = CO2Et), no conversion of
the starting material was observed (Table 3, entry 5).17
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Table 3. Synthesis of 3,5-disubstituted isoxazolidines
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entry
R2
Et
H
R3
H
2a (yield %) cis/trans ratiob
1
1i
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5
2i (96%)
2j (83%)
2k (83%)
2l (92%)
2m (0%)
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83/17
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H
Me
Ph
1k
1l
H
H
CO2Et
1m
a Only the (E)-isomer was observed by 1H NMR. bDetermined by 1H NMR.
In addition, allylic acetate 1n bearing a methyl group at the γ position was synthesized and
treated with 10 mol % of FeCl3•6H2O (Scheme 3, eq 1). The expected isoxazolidine 2n was
isolated with a good yield of 90% but with low diastereoselectivity (dr = 60/40). Interestingly,
the presence of a trisubstituted double bond as in 1o was tolerated as the corresponding
isoxazolidine 2o possessing a quaternary center was formed in 95% yield with a
diastereomeric ratio of 75/25 (Scheme 3, eq 2).
Scheme 3. Synthesis of 3,4-disubstituted and 3,3,5-trisubstituted isoxazolidines
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It is worth noting that a six-membered ring was formed through the FeCl3•6H2O-catalyzed
cyclization of N-tosyl ε-hydroxylamino allylic acetate 1p (Scheme 4). The reaction proceeded
in good yield (85%) but with poor diastereoselectivity (dr = 53/47).
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Scheme 4. Synthesis of a six-membered ring
Mechanistic studies
Recently, we have reported that the FeCl3•6H2O catalyzed cyclization of N-protected ζ-amino
allylic acetates could proceed via an allylic carbocation intermediate.12 Furthermore, a
FeCl3•6H2O induced re-opening of the 2,6-disubstituted piperidines was observed thus
leading to the more stable cis-isomers under thermodynamic control. In order to check if a
similar mechanism was operating for the formation of isoxazolidines, the enantio-enriched
acetate (R)-1i (ee = 86%) was prepared and treated with 10 mol % of FeCl3•6H2O. After 24 h
at 50 °C, the corresponding isoxazolidine 2i was obtained as a racemate thus confirming the
hypothesis of a carbocation intermediate (Scheme 5).
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Scheme 5. Evidence for a carbocation intermediate
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The ability of FeCl3•6H2O to induce the epimerization of isoxazolidines was then studied and
two compounds were examined. In the absence of any allylic substituent (R2 = H), when the
1:1 mixture of cis/trans-isoxazolidines 2a was treated with 1 equiv of FeCl3•6H2O, after 24 h
at 50 °C, no evolution of the diastereomeric ratio was observed. In contrast, for 2g (R2 = Ph),
an epimerization was observed upon treatment with only 0.1 equiv of FeCl3•6H2O and the
diastereomeric ratio was increased from 50/50 to 80/20 in favour of the more stable cis-
isomer (Scheme 6). Thus, depending on the R2 substituent, the reaction is under either kinetic
or thermodynamic control. When R2 = H, no epimerization of the obtained isoxazolidines
occurs, the reaction proceed under kinetic control and the diastereoselectivity observed (Table
1, entry 15) could be explained by the minimization of steric interactions in the transition state
(TS I versus TS II). When R2 = Ph, FeCl3•6H2O is able to epimerize the obtained
isoxazolidines leading, under thermodynamic control, to the more stable cis-isomers as the
major products (Scheme 6).
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Scheme 6. Evaluation of the FeCl3-induced epimerization of 3,5-disubstituted
isoxazolidines and hypothetic mechanistic pathways depending on the nature of the R2
group
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Surprisingly, when N-tosyl β-hydroxylamino allylic acetates 1q (dr = 50/50) and 1r (dr =
50/50) were reacted with 0.1 equiv of FeCl3•6H2O, the corresponding isoxazolidines were
isolated in 88% yield and 95% yield respectively but without any diastereoselectivity
(Scheme 7). These results are in contrast with the reactivity of N-tosyl δ-hydroxylamino
allylic acetates suggesting that in the case of β-hydroxylamino allylic acetates, a SN2 type
mechanism may occur instead of a carbocationic pathway.
Scheme 7. Cyclisation of β-hydroxylamino allylic acetates derivatives
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Synthetic valorization of isoxazolidines
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Isoxazolidines bearing an insaturation are valuable compounds as they can be considered as
highly functionalizable 1,3-amino alcohol precursors. In order to illustrate the great synthetic
potential of the obtained isoxazolidines, isoxazolidine 2a was used as a model substrate and
involved in several transformations (Scheme 8). At first, the N-O bond was reductively
cleaved upon treatment of 2a with Zn in a AcOH/H2O mixture to give the corresponding
amino-alcohol 3 in quantitative yield.2 The double bond was oxidatively cleaved (OsO4,
NMO then NaIO4) and aldehyde 4 was isolated in 89% yield. An oxidation of the double
bond in the presence of RuCl3•xH2O and NaIO4 furnished the carboxylic acid 5 (quant.).
Hydroboration using 9-BBN followed by oxidative treatment (NaOH, H2O2) led to alcohol 6
in quantitative yield. A cross-metathesis with crotonaldehyde in presence of the 2nd generation
Grubbs-Hoveyda catalyst (G-H) was performed and 7 was isolated in 79% yield. Finally, a
palladium-catalyzed Heck reaction with 3-bromopyridine delivered alkene 8 in 81% yield.
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Scheme 8. Synthesis of amino-alcohol and functionalized isoxazolidines
In addition, isoxazolidine 6 was efficiently transformed into lactone 9 upon reductive
cleavage and subsequent oxidation of the primary alcohol (TEMPO, BAIB). Reduction of this
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lactone followed by addition of allyltrimethylsilane in presence of BF3•OEt2 led to the
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corresponding amido-tetrahydropyran 10 in quantitative yield (Scheme 9).
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Scheme 9. Formation of tetrahydropyran 10
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Conclusion
In summary, we have developed an eco-friendly and diastereoselective method for the
synthesis of cis-3,5-disubstituted isoxazolidines. The mild conditions are compatible with
various N-protecting groups and a wide range of di- and trisubstituted isoxazolidines has been
prepared. These compounds can allow the access to functionalized 1,3-amino alcohols as
illustrated by the synthesis of various precursors. According to the nature of the allylic
substituent, kinetic or thermodynamic control could be invoked to account for the
diastereoselectivities observed.
Experimental section
General experimental methods. All reactions were carried out in dry solvents under argon
atmosphere unless otherwise noted. THF and CH2Cl2 were dried using a solvent purification
system. All commercially obtained chemicals were used as received without further
purification. TLC was performed on silica gel plates visualized either with a UV lamp (254
nm) or using a staining solution (p-anisaldehyde, KMnO4 or ninhydrin solutions). Purification
was performed on silica gel (230-400 mesh). NMR spectra were recorded on 400 MHz (400
MHz for 1H NMR and 100 MHz for 13C NMR) spectrometer. The carbon NMR spectra were
recorded proton decoupled (13C{1H}). Proton chemical shifts are reported relative to residual
solvent peak (CDCl3 at 7.26 ppm, C6D6 at 7.16 ppm, DMSO-d6 at 2.50 ppm). Carbon
chemical shifts are reported relative to residual solvent peaks (CDCl3 at 77.3 ppm, C6D6 at
128.1 ppm, DMSO- d6 at 39.5 ppm). Infrared (IR) spectra (IRFT), wave numbers are
indicated in cm-1. Mass spectra with electronic impact (MS-EI) were recorded on a GC/MS
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(70 eV). High-resolution mass spectra (HRMS) were performed using Electrospray Ionization
(ESI) with Orbitrap mass analysis.
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General procedure A for the allylation of aldehydes and subsequent Mitsunobu reaction
with N-hydroxyphtalimide. To a solution of aldehyde (1 equiv) in THF (0.2M) at -78 °C
was added allylmagnesium chloride (2M/THF, 1.5 equiv). After 2-4 h at -78 °C, the reaction
medium was warmed to room temperature and a saturated aqueous solution of NH4Cl was
added. The two phases were separated, the aqueous layer was extracted twice with Et2O and
the combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The
crude product was filtered through silica gel to obtain the desired alcohol. To a solution of the
previously synthesized alcohol (1 equiv) in THF (0.1M) were added PPh3 (1.3 equiv) and N-
hydroxyphtalimide (1.3 equiv). The resulting mixture was cooled to 0 °C before DIAD (1.3
equiv) was added dropwise. After 30 min at 0 °C, the reaction medium was allowed to reach
room temperature. After 4-10 h, the solvent was removed under reduced pressure and the
residue was purified by flash chromatography on silica gel to afford the desired product.
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General procedure B for the cross-metathesis. To a solution of alkene (1 equiv) in CH2Cl2
(0.1M) were added allylic acetate (2 equiv if the partner is symmetric, otherwise 3 equiv) and
Hoveyda-Grubbs II catalyst (2.5 mol %) in a sealed tube. The reaction medium was warmed
to 50 °C for 12 h before adding another portion of Hoveyda-Grubbs catalyst (2.5 mol %).
After 12 hours at 50 °C, the solvent was evaporated under reduced pressure. A flash
chromatography on silica gel yielded the expected olefin.
Genaral procedure C for the Ing-Manske phtalimide cleavage. To a solution of phtalimide
derivative (1 equiv) in THF (0.2M) was added hydrazine hydrate (67% in water, 5 equiv).
After 1-3 h, water and EtOAc were added. The aqueous layer was extracted with EtOAc and
the combined organic layers were dried over Na2SO4, filtered and concentrated under reduced
pressure. The residue was purified by flash chromatography on silica gel to afford the
hydroxylamine ether.
General procedure D for the N-tosylation of hydroxylamine ethers. To a solution of
hydroxylamine ether (1 equiv) in CH2Cl2 (0.1M) were added at -78 °C pyridine (2 equiv),
DMAP (0.1 equiv) and TsCl (1.1 equiv). After 4 h at -78 °C, the reaction medium was
allowed to reach room temperature. After 5-10 h at rt, the reaction medium was quenched by
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addition of a saturated aqueous solution of CuSO4. The aqueous layer was extracted with
CH2Cl2 and the combined organic layers were dried over Na2SO4, filtered and concentrated
under reduced pressure. A flash chromatography on silica gel afforded the corresponding N-
tosylhydroxylamine ether.
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General procedure E for the FeCl3.6H2O catalyzed cyclization of N-protected δ-
hydroxylamino allylic acetates 1a-1r into isoxazolidines 2a-2r. To a solution of N-
protected hydroxylamine ether (1 equiv) in CH2Cl2 (0.1M) was added FeCl3.6H2O (0.1 equiv)
in a sealed vial. The reaction medium was warmed to 50 °C for 24 h. After cooling down to
room temperature, the reaction mixture was filtered on a pad of basic alumina and eluted with
CH2Cl2. The obtained products do not require further purification, unless specified.
[(E)-5-(p-tolylsulfonylamino)oxytetradec-2-enyl] acetate (1a). General procedure A was
applied to decanal (1.8 g, 12 mmol). Purification by flash chromatography silica gel (PE/Et2O
98/2 to 90/10) yielded 2-(1-allyldecoxy)isoindoline-1,3-dione as a yellow liquid (3.67 g, 10.7
1
mmol, 89%). H NMR (400 MHz, CDCl3) δ 7.86 – 7.79 (m, 2H), 7.77 – 7.71 (m, 2H), 5.91
(ddt, J = 17.2, 10.2, 7.0 Hz, 1H), 5.13 (dq, J = 17.1, 1.5 Hz, 1H), 5.08 (ddt, J = 10.2, 2.1, 1.2
Hz, 1H), 4.31 (quint, J = 5.9 Hz, 1H), 2.47 (ddt, J = 7.0, 5.9, 1.3 Hz, 2H), 1.76 – 1.60 (m,
2H), 1.55 – 1.47 (m, 2H), 1.37 – 1.19 (m, 12H), 0.87 (t, J = 6.9 Hz, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 164.3, 134.4, 133.5, 129.1, 123.4, 117.6, 87.3, 37.2, 32.3, 31.9, 29.6, 29.5,
29.5, 29.3, 25.0, 22.7, 14.1; IR (neat, ν/cm-1) : 2924, 2854, 1790, 1731, 1467, 1372, 1188,
1121, 1082, 1015; MS (EI, m/z) 302 (1, [M-CH2CH=CH2]+), 180 (10, [M-PhtNOH]+), 164
(41), 163 (19, [PhtNOH]+·), 125 (12), 111 (26), 104 (25), 97 (55), 96 (23), 25 (15), 90 (14), 83
(69), 82 (25), 81 (27), 76 (21), 71 (15); HRMS (ESI) Calcd for C21H29NO3 [M+Na]+ :
366.2040, Found : 366.2040. General procedure
B
was applied to 2-(1-
allyldecoxy)isoindoline-1,3-dione (3 g, 8.7 mmol). Purification by flash chromatography on
silica gel (PE/Et2O 90/10 to 80/20) yielded [(E)-5-(1,3-dioxoisoindoline-2-yl)oxytetradec-2-
1
enyl] as a yellow oil (2.65 g, 6.4 mmol, 74%, E/Z = 82/18). H NMR (400 MHz, CDCl3) δ
7.85 – 7.80 (m, 2H), 7.79 – 7.71 (m, 2H), 5.95 – 5.86 (m, 1H), 5.73 – 5.63 (m, 1H), 4.50 (dapp,
J = 6.2 Hz, 2H), 4.29 (quintapp, J = 5.9 Hz, 1H), 2.56 – 2.45 (m, 2H), 2.04 (s, 3H), 1.77 – 1.61
13
(m, 2H), 1.54 – 1.45 (m, 2H), 1.38 – 1.23 (m, 12H), 0.87 (t, J = 6.8 Hz, 3H); C{1H} NMR
(100 MHz, CDCl3) δ 170.8, 164.2, 134.4, 130.5, 129.0, 127.0, 123.4, 87.1, 64.8, 35.7, 32.4,
31.9, 29.6, 29.5, 29.5, 29.3, 25.0, 22.7, 21.0, 14.1; IR (neat, ν/cm-1) : 2926, 2855, 1790, 1735,
1467, 1374, 1235, 1188, 1083, 1025; MS (EI, m/z) 253 (13, [M-PhtNOH]+), 163 (14,
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[PhtNOH]+·), 123 (25), 111 (18), 109 (52), 104 (35), 97 (31), 95 (91), 90 (21), 83 (48), 81
(100), 80 (29), 79 (42), 77 (20), 76 (37), 71 (15), 70 (16), 69 (64), 67 (90), 57 (40), 55 (92);
HRMS (ESI) Calcd for C24H33NO5 [M+Na]+ : 438.2251, Found : 438.2256. General
procedure C was applied to [(E)-5-(1,3-dioxoisoindoline-2-yl)oxytetradec-2-enyl] (1.7 g, 4.1
mmol). Purification by flash chromatography on silica gel (PE/Et2O 80/20 to 65/35) yielded
[(E)-5-aminooxytetradec-2-enyl] acetate as a colorless oil (1.07 g, 3.75 mmol, 91%, E/Z =
83/17). 1H NMR (400 MHz, CDCl3) δ 5.84 – 5.73 (m, 1H), 5.70 – 5.60 (m, 1H), 4.53 (dd, J =
6.3, 0.9 Hz, 2H), 3.61 (quintapp, J = 5.94 Hz, 1H), 2.45 – 2.26 (m, 2H), 2.06 (s, 3H), 1.60 –
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1.17 (m, 16H), 0.88 (t, J = 6.8 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 170.9, 132.3,
126.2, 83.3, 65.1, 35.6, 32.4, 31.9, 29.7, 29.6, 29.6, 29.3, 25.4, 22.7, 21.0, 14.1; IR (neat,
ν/cm-1) : 2925, 2854, 1741, 1594, 1463, 1378, 1232, 1025; MS (EI, m/z) 227 (1), 226 (5, [M-
OAc]+), 172 (4), 155 (12), 123 (3), 109 (8), 97 (7), 96 (9), 95 (22), 85 (5), 84 (3), 83 (18), 82
(6), 81 (28), 80 (4), 79 (7), 72 (5), 71 (15), 70 (8), 69 (23), 68 (6), 67 (23), 57 (25), 56 (10), 54
(100); HRMS (ESI) Calcd for C16H31NO3 [M+Na]+ : 308.2196, Found : 308.2197. General
procedure D was applied to [(E)-5-aminooxytetradec-2-enyl] acetate (864 mg, 3 mmol).
Purification by flash chromatography on silica gel (PE/Et2O 90/10 to 80/20) yielded 1a as a
pale yellow oil (1.2 g, 2.7 mmol, 91%). 1H NMR (400 MHz, C6D6) δ 7.90 – 7.83 (m, 2H),
6.86 – 6.81 (m, 2H), 6.63 (brs, 1H), 5.66 – 5.56 (m, 1H), 5.53 – 5.41 (m, 1H), 4.40 (dd, J =
6.2, 0.8 Hz, 2H), 4.21 – 4.09 (m, 1H), 2.26 – 2.09 (m, 2H), 1.88 (s, 3H), 1.69 (s, 3H), 1.53 –
1.12 (m, 16H), 0.93 (t, J = 6.9 Hz, 3H); 13C{1H} NMR (100 MHz, C6D6) δ 170.2, 144.2,
135.4, 131.3, 129.6, 129.0, 127.3, 85.7, 64.9, 36.0, 32.8, 32.4, 31.0, 30.1, 30.0, 29.8, 25.7,
23.1, 21.2, 20.6, 14.4; IR (neat, ν/cm-1) : 3216, 2925, 2854, 1739, 1598, 1458, 1379, 1339,
1231, 1167, 1092, 1022; MS (EI, m/z) 171 (18, [TsNH2]+·), 155 (17), 108 (15), 107 (34), 96
(14), 91 (100), 89 (14), 81 (17), 77 (13), 65 (52), 63 (23), 53 (17), 51 (15); HRMS
(ESI) Calcd for C23H37NO5S [M+Na]+ : 462.2285, Found : 462.2289
N-[1-[(E)-4-hydroxybut-2-enyl]decoxy]-4-methyl-benzenesulfonamide (1a’). To a solution
of 1a (90 mg, 0.2 mmol, 1 equiv) in MeOH (2 mL) was added NaOH (0.8 mL, 1M/water, 5
equiv). The reaction medium was stirred at room temperature for 4 hours before quenching
the reaction with water and diluting with EtOAc. The phases were separated and the aqueous
phase was extracted twice with EtOAc. The combined organic phases were washed with
brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was
purified by flash chromatography on silica gel (PE/Et2O 70/30) to obtain 1a’ as a yellow oil
1
(50 mg, 0.13 mmol, 63%). H NMR (400 MHz, C6D6) δ 7.98 (dapp, J = 7.8 Hz, 2H), 7.94 (s,
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1H), 6.91 (dapp, J = 8.0 Hz, 2H), 5.78 – 5.45 (m, 2H), 4.22 – 4.18 (m, 1H), 4.04 – 3.98 (m,
2H), 2.66 (brs, 1H), 2.47 – 2.33 (m, 1H), 2.29 – 2.15 (m, 1H), 1.93 (s, 3H), 1.73 – 1.29 (m,
16H), 0.92 (t, J = 6.8 Hz, 3H); 13C{1H} NMR (100 MHz, C6D6) δ 144.3, 135.0, 132.1, 129.7,
129.0, 128.1, 85.8, 63.4, 35.9, 32.8, 32.3, 30.0, 30.0, 30.0, 29.8, 25.8, 23.1, 21.4, 14.4; IR
(neat, ν/cm-1) : 3514, 3220, 2925, 2854, 1598, 1465, 1337, 1186, 1167, 1092; MS (EI, m/z)
171 (15), 155 (17), 108 (18), 107 (40), 91 (100), 89 (18), 80 (5), 77 (5), 65 (51), 63 (23), 51
(12); HRMS (ESI) Calcd for C21H35NO4S [M+Na]+ : 420.2179, Found : 420.2178.
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(E)-5-[(2-nitrophenyl)sulfonylamino)oxytetradec-2-enyl] acetate (1b). To a solution of
[(E)-5-aminooxytetradec-2-enyl] acetate (150 mg, 0.53 mmol, 1 equiv) in CH2Cl2 (3 mL) was
added at 0 °C NsCl (111 mg, 0.95 equiv), Et3N (0.15 mL, 2 equiv) and DMAP (6.5 mg, 0.1
equiv). The reaction medium was stirred for 60 h before quenching the reaction with brine.
The phases were separated and the aqueous layer was extracted twice with CH2Cl2. The
combined organic layers were washed with brine, dried over Na2SO4, filtered and
concentrated under reduced pressure. The residue was purified by flash chromatography on
silica gel (PE/ EtOAc 90/10) to obtain 1b as a yellow oil (170 mg, 0.4 mmol, 72%, E/Z >
1
90/10). H NMR (400 MHz, CDCl3) δ 8.23 – 8.17 (m, 1H), 7.85 – 7.75 (m, 2H), 7.85 – 7.75
(m, 2H), 5.80 – 5.69 (m, 1H), 5.68 – 5.58 (m, 1H), 4.53 (dapp, J = 6.0 Hz, 2H), 4.18 (quintapp,
J = 5.8 Hz, 1H), 2.50 – 2.33 (m, 2H), 2.07 (s, 3H), 1.57 – 1.41 (m, 2H), 1.39 – 1.21 (m, 14H),
0.88 (t, J = 6.8 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.8, 148.5, 134.7, 133.7,
132.7, 131.0, 130.6, 126.9, 125.6, 86.0, 64.8, 35.4, 32.1, 31.9, 29.6, 29.5, 29.5, 29.3, 25.2,
22.7, 21.0, 14.1; IR (neat, ν/cm-1) : 3273, 2925, 2855, 1736, 1593, 1542, 1441, 1396, 1361,
1304, 1231, 1178, 1125, 1022; MS (EI, m/z) 253 (1, [M-ONHNs]+), 252 (7), 203 (4), 144
(12), 143 (100), 142 (6), 129 (7), 128 (26), 117 (5), 115 (9), 105 (14), 104 (15), 91 (13), 90
(8), 77 (14), 76 (11), 51 (4); HRMS (ESI) Calcd for C22H34N2O7S [M+Na]+ : 493.1979,
Found : 493.1978.
[(E)-5-(benzyloxycarbonylaminooxy)tetradec-2-enyl] acetate (1c). To a solution of [(E)-5-
aminooxytetradec-2-enyl] acetate (50 mg, 0.175 mmol, 1 equiv) in a 1/1 mixture of
CH2Cl2/water (1 mL) at -20 °C was added CbzCl (33 mg, 1.1 equiv) and Na2CO3 (20 mg,
1.05 equiv). After 20 h at rt, the reaction medium was quenched with water and diluted with
CH2Cl2. The layers were separated and the aqueous layer was extracted with CH2Cl2 twice.
The combined organic extracts were washed with brine, dried over Na2SO4 and concentrated
under reduced pressure. The residue was purified on silica gel (PE/Et2O 70/30) to obtain 1c as
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a colorless oil (70 mg, 0.17 mmol, 96%, E/Z = 80/20). 1H NMR (400 MHz, CDCl3) δ 7.39 –
7.31 (m, 5H), 7.23 (brs, 1H), 5.88 – 5.72 (m, 1H), 5.63 (dt, J = 15.3, 6.2 Hz, 1H), 5.17 (s,
2H), 4.49 (dapp, J = 6.1 Hz, 2H), 3.81 (quintapp, J = 5.7 Hz, 1H), 2.37 (tapp, J = 6.6 Hz, 2H),
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2.05 (s, 3H), 1.59 – 1.37 (m, 2H), 1.37 – 1.20 (m, 14H), 0.88 (t, J = 6.9 Hz, 3H); C{1H}
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NMR (100 MHz, CDCl3) δ 170.9, 157.7, 135.6, 131.6, 128.6, 128.4, 128.3, 126.6, 85.2, 67.5,
65.0, 35.5, 32.2, 31.9, 29.7, 29.6, 29.5, 29.3, 25.3, 22.7, 21.0, 14.1; IR (neat, ν/cm-1) : 3288,
2924, 2854, 1738, 1456, 1377, 1338, 1230, 1105, 1026; HRMS (ESI) Calcd for C24H37NO5
[M+Na]+ : 442.2564, Found : 442.2569.
(E)-5-((((allyloxy)carbonyl)amino)oxy)tetradec-2-en-1-yl acetate (1d). To a solution of
(E)-5-aminooxytetradec-2-enyl] acetate (250 mg, 0.88 mmol, 1 equiv) in CH2Cl2 (10 mL) at
-78 °C were added AllocCl (106 µL, 1.1 equiv), pyridine (139 µL, 2 equiv) and DMAP (11
mg, 0.1 equiv). After 2 h at -78 °C and 48 h at room temperature, the reaction medium was
quenched by addition of aq. CuSO4 and diluted with CH2Cl2. The layers were separated and
the aqueous layer was extracted twice with CH2Cl2. The combined organic layers were
washed with brine, dried over MgSO4 and concentrated under reduced pressure. The residue
was purified by flash chromatography on silica gel (PE/Et2O 90/10) to obtain 1d as a
1
colorless oil (302 mg, 0.81 mmol, 92%). H NMR (400 MHz, CDCl3) δ 7.20 (s, 1H), 5.92
(ddt, J = 17.2, 10.5, 5.8 Hz, 1H), 5.86 – 5.75 (m, 1H), 5.65 (dt, J = 13.8, 6.3 Hz, 1H), 5.34
(dd, J = 17.2, 1.3 Hz, 1H), 5.25 (dd, J = 10.5, 1.2 Hz, 1H), 4.63 (d, J = 5.8 Hz, 2H), 4.52 (d, J
= 6.3 Hz, 2H), 3.91 – 3.74 (m, 1H), 2.36 (tapp, J = 6.4 Hz, 2H), 2.06 (s, 1H), 1.58 – 1.21 (m,
16H), 0.88 (t, J = 6.8 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.9, 157.6, 132.0,
131.6, 126.6, 118.6, 85.2, 66.4, 65.0, 35.5, 32.2, 31.9, 29.7, 29.6, 29.6, 29.3, 25.3, 22.7, 21.0,
14.1; IR (neat, ν/cm-1) : 3296, 2925, 2855, 1739, 1650, 1459, 1378, 1325, 1230, 1107, 1026;
MS (EI, m/z) 253 (1), 224 (3), 155 (12), 123 (15), 109 (25), 97 (19), 96 (19), 95 (55), 83 (29),
82 (14), 81 (60), 71 (20), 69 (42), 67 (47), 57 (54), 55 (67), 54 (100); HRMS (ESI) Calcd for
C20H35NO5 [M+Na]+ : 392.2407, Found : 392.2411.
(E)-5-(acetamidooxy)tetradec-2-en-1-yl acetate (1e). To
a
solution of (E)-5-
aminooxytetradec-2-enyl] acetate (250 mg, 0.88 mmol, 1 equiv) in CH2Cl2 (10 mL) at -78 °C
were added AcCl (69 µL, 1.1 equiv) and pyridine (139 µL, 2 equiv). After 24 h at rt, the
reaction medium was quenched by addition of aq. CuSO4 and diluted with CH2Cl2. The layers
were separated and the aqueous layer was extracted with CH2Cl2 twice. The combined
organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under
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reduced pressure. The residue was purified by flash chromatography on silica gel (PE/Et2O
70/30 to 50/50) to obtain 1e as a colorless oil (250 mg, 0.77 mmol, 87%, E/Z = 81/19). 1H
NMR (400 MHz, DMSO) δ 10.66 (s, 1H), 5.80 – 5.75 (m, 1H), 5.67 – 5.53 (m, 1H), 4.46 (d, J
= 6.2 Hz, 2H), 3.75 – 3.64 (m, 1H), 2.28 – 2.23 (m, 2H), 2.00 (s, 3H), 1.71 (s, 3H), 1.53 –
13
1.16 (m, 16H), 0.85 (t, J = 6.8 Hz, 3H); C{1H} NMR (100 MHz, DMSO) δ 170.0, 166.4,
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131.1, 126.4, 83.1, 64.2, 34.7, 31.5, 31.3, 29.0, 28.9, 28.9, 28.7, 24.5, 22.1, 20.6, 19.6, 13.9;
IR (neat, ν/cm-1) : 3196, 2924, 2854, 1741, 1664, 1520, 1459, 1367, 1228, 1082, 1024; MS
(EI, m/z) 208 (2), 155 (49), 124 (5), 109 (6), 97 (10), 96 (95), 95 (41), 85 (38), 81 (96), 71
(70), 69 (19), 67 (17), 57 (70), 55 (41), 54 (100); HRMS (ESI) Calcd for C18H33NO4 [M+Na]+
: 350.2302, Found : 350.2300.
[(E)-5-(tert-butoxycarbonylamino)oxytetradec-2-enyl] acetate (1f). To a solution of [(E)-
5-aminooxytetradec-2-enyl] acetate (150 mg, 0.53 mmol, 1 equiv) in 1,4-dioxane (5 mL) was
added at 0 °C Boc2O (186 mg, 1.6 equiv). After 12 h at rt, the reaction was diluted with water
and EtOAc. The phases were separated and the aqueous layer was extracted twice with
EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and
concentrated under reduced pressure. The residue was purified by flash chromatography on
silica gel (PE/Et2O 70/30) to obtain 1f as a pale yellow oil (171 mg, 0.45 mmol, 84%, E/Z =
1
80/20). H NMR (400 MHz, CDCl3) δ 6.96 (brs, 1H), 5.89 – 5.75 (m, 1H), 5.71 – 5.59 (m,
1H), 4.52 (dd, J = 6.4, 0.9 Hz, 2H), 3.77 (quintapp, J = 5.7 Hz, 1H), 2.44 – 2.30 (m, 2H), 2.06
(s, 3H), 1.49 (s, 9H), 1.70 – 1.40 (m, 2H), 1.39 – 1.18 (m, 14H), 0.87 (t, J = 6.9 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 170.9, 157.1, 131.8, 126.4, 84.9, 81.6, 65.0, 35.5, 32.1,
31.9, 29.7, 29.6, 29.5, 29.3, 28.2, 25.3, 22.7, 21.0, 14.1; IR (neat, ν/cm-1) : 3304, 2925, 2855,
1741, 1457, 1367, 1234, 1165, 1103, 1022; HRMS (ESI) Calcd for C21H39NO5 [M+Na]+ :
408.2720, Found : 408.2720.
Acetic acid (E)-5-aminooxy-1-phenyl-tetradec-2-enyl ester (1g). General procedure B was
applied to 2-(1-allyldecoxy)isoindoline-1,3-dione (343 mg, 1 mmol). Purification on silica gel
(PE/Et2O 90/10 to 80/20) yielded acetic acid (E)-5-(1,3-dioxo-1,3-dihydro-isoindol-2-yloxy)-
1-phenyl-tetradec-2-enyl ester as a dark pink oil (230 mg, 0.47 mmol, 47%, 50/50 mixture of
diastereoisomers α and β). 1H NMR (400 MHz, CDCl3) δ 7.86 – 7.78 (m, 2H), 7.77 – 7.70 (m,
2H), 7.38 – 7.26 (m, 5H), 6.21 (brd, J = 6.1 Hz, 1H), 5.91 – 5.69 (m, 2H), 4.27 (sextapp, J =
6.0 Hz, 1H), 2.51 – 2.44 (m, 2H), 2.08 (s, 1.5H), 2.08 (s, 1.5H), 1.77 – 1.11 (m, 16H), 0.90 –
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0.85 (m, 3H); C{1H} NMR (100 MHz, CDCl3) δ 170.0, 164.2, 139.5, 134.4, 131.4, 129.0,
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129.0, 128.5, 128.5, 128.0, 126.9, 123.5, 87.2, 87.1, 75.8, 35.7, 35.6, 32.3, 32.0, 29.5, 29.5,
29.5, 29.3, 24.9, 22.7, 21.3, 14.1; IR (neat, ν/cm-1) : 2924, 2854, 1790, 1731, 1494, 1467,
1370, 1232, 1188, 1122, 1082, 1016; MS (EI, m/z) 268 (25), 169 (11), 156 (22), 155 (77), 154
(16), 142 (14), 141 (38), 130 (45), 129 (22), 128 (26), 115 (24), 92 (11), 91 (100), 79 (15);
HRMS (ESI) Calcd for C30H37NO5 [M+Na]+ : 514.2564, Found : 514.2561. General
procedure C was applied to acetic acid (E)-5-(1,3-dioxo-1,3-dihydro-isoindol-2-yloxy)-1-
phenyl-tetradec-2-enyl ester (225 mg, 0.47 mmol). Purification on silica gel (PE/Et2O 80/20
to 50/50) yielded acetic acid (E)-5-aminooxy-1-phenyl-tetradec-2-enyl ester as a colorless oil
(130 mg, 0.36 mmol, 77%, 50/50 mixture of diastereoisomers). 1H NMR (400 MHz, CDCl3) δ
7.38 – 7.24 (m, 5H), 6.23 (brd, J = 6.3 Hz, 1H), 5.82 – 5.66 (m, 2H), 5.19 (brs, 2H), 3.60 –
3.51 (m, 1H), 2.33 – 2.29 (m, 2H), 2.10 (s, 1.5H), 2.09 (s, 1.5H), 1.54 – 1.43 (m, 2H), 1.35 –
1.19 (m, 14H), 0.92 – 0.84 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.1, 139.7, 130.8,
130.5, 128.6, 128.0, 126.9, 83.3, 76.3, 35.8, 32.6, 32.0, 29.8, 29.7, 29.6, 29.4, 25.5, 22.8, 21.4,
14.2; IR (neat, ν/cm-1) : 2924, 2854, 1736, 1587, 1494, 1456, 1370, 1232, 1072, 1018; MS
(EI, m/z) 130 (85), 71 (18), 70 (50), 68 (21), 67 (24), 57 (96), 56 (18), 55 (100); HRMS
(ESI) Calcd for C20H33NO2 [M+Na-Ac]+: 342.2791, Found : 342.2793. General procedure D
was applied to acetic acid (E)-5-aminooxy-1-phenyl-tetradec-2-enyl ester (125 mg, 0.35
mmol). Purification on silica gel (PE/Et2O 80/20 to 50/50) yielded 1g as a pale yellow oil
(147 mg, 0.29 mmol, 82%, 50/50 mixture of diastereoisomers). 1H NMR (400 MHz, C6D6) δ
7.90 – 7.82 (m, 2H), 7.66 (d, J = 10.8 Hz, 2H), 7.20 – 7.14 (m, 2H), 7.10 – 7.04 (m, 1H), 6.86
– 6.79 (m, 2H), 6.42 (d, J = 6.8 Hz, 0.5H), 6.39 (d, J = 6.8 Hz, 0.5H), 5.86 – 5.74 (m, 2H),
4.18 – 4.09 (m, 1H), 2.29 – 2.10 (m, 2H), 1.88 (s, 1.5H), 1.87 (s, 1.5H), 1.73 (s, 1.5H), 1.69
(s, 1.5H), 1.37 – 1.21 (m, 16H), 0.95 – 0.90 (m, 3H); 13C{1H} NMR (100 MHz, C6D6) δ
169.8, 144.2, 140.2, 131.7, 130.3, 129.9, 129.7, 129.7, 129.0, 128.9, 128.4, 128.3, 127.5,
127.4, 85.9, 76.7, 76.3, 36.5, 33.1, 32.9, 32.4, 30.1, 30.1, 29.9, 25.7, 23.2, 21.3, 20.9, 14.5 ;
IR (neat, ν/cm-1) : 3216, 2924, 2854, 1736, 1598, 1494, 1456, 1372, 1340, 1306, 1234, 1167,
1092, 1019; HRMS (ESI) Calcd for C29H41NO5S [M+Na]+ : 538.2598, Found : 538.2597.
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(E)-5-(((tert-butoxycarbonyl)amino)oxy)-1-phenyltetradec-2-en-1-yl acetate (1h). General
procedure C was applied to 2-(1-allyldecoxy)isoindoline-1,3-dione (4 g, 11.7 mmol).
Purification by flash chromatography on silica gel (PE/Et2O 95/5 to 90/10) yielded O-(tridec-
1-en-4-yl)hydroxylamine as a pale yellow oil (2.25 g, 10.5 mmol, 90%). 1H NMR (400 MHz,
CDCl3) δ 5.82 (ddt, J = 17.2, 10.2, 7.2 Hz, 1H), 5.21 (s, 2H), 5.14 – 5.00 (m, 2H), 3.62 – 3.52
(pent, J = 5.8 Hz, 1H), 2.39 – 2.18 (m, 2H), 1.56 – 1.18 (m, 16H), 0.87 (t, J = 6.8 Hz, 3H);
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13C{1H} NMR (100 MHz, CDCl3) δ 135.2, 116.6, 83.3, 37.3, 32.3, 31.9, 29.8, 29.6, 29.6,
29.3, 25.5, 22.7, 14.1; IR (neat, ν/cm-1) : 3317, 3077, 2923, 2854, 1641, 1586, 1466, 1350,
1183, 1128; HRMS (ESI) Calcd for C13H27NO [M+H]+ : 214.2165, Found : 214.2166. To a
solution of O-(tridec-1-en-4-yl)hydroxylamine (200 mg, 0.94 mmol, 1 equiv) in 1,4-dioxane
(10 mL) was added at 0 °C Boc2O (327 mg, 1.6 equiv). The reaction medium was stirred for
12 h at room temperature before quenching the reaction with water and diluting with EtOAc.
The phases were separated and the aqueous layer was extracted twice with EtOAc. The
combined organic layers were washed with brine, dried over Na2SO4, filtered and
concentrated under reduced pressure. The residue was purified by flash chromatography on
silica gel (PE/Et2O 98/2 to 95/5) to obtain the expected hydroxylamine as a colorless oil (282
mg, 96%).The previously synthesized hydroxylamine (270 mg, 0.86 mmol) was subjected to
procedure B (using 4 equiv of phenylallyl acetate as the partner). Purification by flash
chromatography on silica gel (PE/Et2O 90/10) yielded 1h as a brown oil (250 mg, 0.54 mmol,
63%, 55/45 mixture of diastereoisomers). 1H NMR (400 MHz, CDCl3) δ 7.38 – 7.28 (m, 5H),
6.32 – 6.28 (m, 1H), 6.23 (d, J = 6.0 Hz, 0.5H), 5.92 – 5.89 (m, 1H), 5.73 – 5.70 (m, 0.5H),
3.93 – 3.85 (m, 1H), 2.40 – 2.32 (m, 1H), 2.10 – 2.07 (m, 4H), 1.59 – 1.46 (m, 11H), 1.32 –
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0.99 (m, 14H), 0.88 (t, J = 6.3 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 169.9, 163.5,
131.1, 130.7, 128.6, 128.3, 127.2, 126.9, 83.7, 81.0, 75.0, 31.9, 29.9, 29.8, 29.7, 29.5, 29.5,
29.3, 28.1, 25.0, 22.7, 21.3, 14.1; IR (neat, ν/cm-1) : 2926, 2855, 1741, 1495, 1456, 1393,
1369, 1337, 1272, 1230, 1150, 1113, 1020; HRMS (ESI) Calcd for C27H43NO5 [M+Na]+ :
484.3033, Found : 484.3036.
(E)-7-((4-methylphenylsulfonamido)oxy)hept-4-en-3-yl acetate (1i). To a solution of
penten-3-ol (500 mg, 7 mmol, 1 equiv) in THF (70 mL) were added PPh3 (2.4 g, 1.3 equiv)
and N-hydroxyphtalimide (1.5 g, 1.3 equiv). The resulting mixture was cooled to 0 °C before
DIAD (1.8 mL, 1.3 equiv) was added dropwise. After 30 min at 0 °C, the reaction medium
was allowed to warm to rt. After 2 h, the solvent was removed under reduced pressure and the
residue was purified by flash chromatography on silica gel (PE/Et2O 80/20) to afford 2-(but-
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3-en-1-yloxy)isoindoline-1,3-dione as a colorless oil (1.56 g, 7 mmol, quant.). H NMR (400
MHz, CDCl3) δ 7.86 – 7.81 (m, 2H), 7.78 – 7.71 (m, 2H), 5.89 (ddt, J = 17.0, 10.3, 6.6 Hz,
1H), 5.21 (dq, J = 17.2, 1.6 Hz, 1H), 5.12 (ddd, J = 10.3, 2.6, 1.3 Hz, 1H), 4.26 (t, J = 6.9 Hz,
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2H), 2.57 (qt, J = 6.7, 1.3 Hz, 2H); C{1H} NMR (100 MHz, CDCl3) δ 163.6, 134.5, 133.1,
128.9, 123.5, 117.6, 77.3, 32.5; IR (neat, ν/cm-1) : 2954, 1788, 1727, 1642, 1611, 1467, 1391,
1372, 1290, 1245, 1186, 1127, 1082, 1018; MS (EI, m/z) 217 (0.1, [M]+·), 187 (2), 164 (3),
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163 (29, [PhtNOH]+·) 148 (3), 147 (3), 146 (5), 133 (8), 130 (3), 105 (9), 104 (19), 90 (14), 77
(6), 76 (23), 75 (4), 55 (100, [M-PhtNO]+); HRMS (ESI) Calcd for C12H11NO3 [M+Na]+ :
240.0631, Found : 240.0632. To a solution of 2-(but-3-en-1-yloxy)isoindoline-1,3-dione (50
mg, 0.23 mmol, 1 equiv) in CH2Cl2 (2 mL) were added ethyl crotonate (53 µL, 2 equiv) and
Hoveyda-Grubbs II catalyst (3.6 mg, 2.5 mol %). After 24 h at rt, the solvent was evaporated
under reduced pressure and flash chromatography on silica gel of the residue (PE/Et2O 70/30
to 50/50) yielded (E)-2-((5-oxohept-3-en-1-yl)oxy)isoindoline-1,3-dione as a brown oil (45
mg, 0.16 mmol, 71%, E/Z > 95/5). 1H NMR (400 MHz, CDCl3) δ 7.86 (ddd, J = 7.1, 5.4, 3.1
Hz, 2H), 7.82 – 7.73 (m, 2H), 6.95 (dt, J = 16.0, 6.7 Hz, 1H), 6.33 (dt, J = 16.0, 1.5 Hz, 1H),
4.37 (t, J = 6.4 Hz, 2H), 2.74 (qd, J = 6.5, 1.5 Hz, 2H), 2.63 (q, J = 7.3 Hz, 2H), 1.13 (t, J =
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7.3 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 200.9, 163.5, 140.9, 134.6, 132.1, 128.8,
123.6, 76.2, 33.4, 31.2, 8.0; IR (neat, ν/cm-1) : 2976, 1788, 1725, 1672, 1631, 1467, 1373,
1290, 1186, 1128, 1082, 1017; HRMS (ESI) Calcd for C15H15NO4 [M+Na]+ : 296.0893,
Found : 296.0895. To a solution of (E)-2-((5-oxohept-3-en-1-yl)oxy)isoindoline-1,3-dione
(245 mg, 0.89 mmol, 1 equiv) in a 1/1 mixture of MeOH and CH2Cl2 (10 mL) was added at
0 °C CeCl3.7H2O (400 mg, 1.2 equiv). After stirring 5 minutes at 0 °C, NaBH4 (44 mg, 1.5
equiv) was added portionwise. The mixture was stirred 2 h at 0 °C before quenching carefully
with aq. NH4Cl. The aqueous layer was extracted with CH2Cl2 and the combined organic
layers were dried over MgSO4, filtered and concentrated under reduced pressure. Purification
by flash chromatography on silica gel (PE/EtOAc 50/50) afforded (E)-2-((5-hydroxyhept-3-
en-1-yl)oxy)isoindoline-1,3-dione as a colorless oil (170 mg, 0.62 mmol, 70%, E/Z > 95/5).
1H NMR (400 MHz, CDCl3) δ 7.83 – 7.80 (m, 2H), 7.74 – 7.72 (m, 2H), 5.77 – 5.59 (m, 2H),
4.29 – 4.17 (m, 2H), 3.99 (q, J = 6.5 Hz, 1H), 2.53 (q, J = 6.5 Hz, 2H), 1.55 – 1.51 (m, 2H),
0.89 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.6, 136.0, 134.5, 128.9,
126.1, 123.6, 77.5, 74.2, 31.1, 30.0, 9.7; IR (neat, ν/cm-1) : 3503, 2962, 2930, 1790, 1731,
1467, 1374, 1292, 1187, 1130, 1082, 1017; MS (EI, m/z) 283 (8), 257 (6, [M-H2O]+), 213
(30), 183 (46), 145 (94), 135 (73), 113 (40, [M-PhtNO]+), 111 (20), 91 (38), 89 (100), 85
(85), 73 (79); HRMS (ESI) Calcd for C15H17NO4 [M+Na]+ : 298.1050, Found : 298.1053. To
a solution of (E)-2-((5-hydroxyhept-3-en-1-yl)oxy)isoindoline-1,3-dione (160 mg, 0.58 mmol,
1 equiv) in CH2Cl2 (10 mL) was added at 0 °C Ac2O (0.11 mL, 2 equiv), pyridine (0.18 mL, 4
equiv) and DMAP (7 mg, 0.1 equiv). The reaction medium was stirred for 4 h at rt before
quenching the reaction with an aqueous solution of CuSO4. The phases were separated and
the aqueous layer was extracted twice with CH2Cl2. The combined organic layers were
washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The
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residue was purified by flash chromatography on silica gel (PE/Et2O 80/20 to 50/50) to obtain
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(E)-7-((1,3-dioxoisoindolin-2-yl)oxy)hept-4-en-3-yl acetate as a colorless oil (160 mg, 0.5
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mmol, 87%). H NMR (400 MHz, CDCl3) δ 7.86 – 7.81 (m, 2H), 7.77 – 7.72 (m, 2H), 5.75
(dtd, J = 15.4, 6.6, 0.8 Hz, 1H), 5.58 (ddt, J = 15.6, 6.9, 1.1 Hz, 1H), 5.14 (q, J = 6.6 Hz, 1H),
4.23 (t, J = 6.9 Hz, 2H), 2.55 (q, J = 6.7 Hz, 2H), 2.04 (s, 3H), 1.71 – 1.53 (m, 2H), 0.88 (t, J
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= 7.4 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 170.4, 163.6, 134.5, 131.3, 128.9, 127.9,
123.5, 77.2, 75.6, 31.0, 27.3, 21.3, 9.4; IR (neat, ν/cm-1) : 2969, 1789, 1726, 1467, 1371,
1237, 1186, 1127, 1082, 1017; MS (EI, m/z) 274 (3, [M-Ac]+), 164 (11), 111 (12), 104 (23),
95 (100), 94 (99), 90 (19), 83 (31), 79 (90), 77 (16), 76 (30), 67 (45), 57 (39), 55 (33); HRMS
(ESI) Calcd for C17H19NO5 [M+Na]+ : 340.1155, Found : 340.1153. General procedure C was
applied to (E)-7-((1,3-dioxoisoindolin-2-yl)oxy)hept-4-en-3-yl acetate (145 mg, 0.46 mmol).
Purification by flash chromatography on silica gel (PE/Et2O 50/50) yielded (E)-7-
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(aminooxy)hept-4-en-3-yl acetate as a colorless oil (76 mg, 0.4 mmol, 88%, E/Z = 93/7). H
NMR (400 MHz, CDCl3) δ 5.68 (dtd, J = 15.4, 6.8, 0.8 Hz, 1H), 5.47 (ddt, J = 15.5, 7.1, 1.4
Hz, 1H), 5.35 – 4.75 (m, 2H), 5.12 (q, J = 6.7 Hz, 1H), 3.72 (t, J = 6.7 Hz, 2H), 2.34 (qd, J =
6.5, 1.2 Hz, 2H), 2.04 (s, 3H), 1.61 (qdd, J = 13.8, 7.4, 6.6 Hz, 2H), 0.87 (t, J = 7.4 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 170.5, 130.3, 130.0, 76.0, 61.67, 31.5, 27.4, 21.4, 9.5; IR
(neat, ν/cm-1) : 3320, 2969, 2936, 2879, 1727, 1673, 1591, 1458, 1371, 1238, 1074, 1018; MS
(EI, m/z) 129 (12), 112 (30), 101 (33), 83 (100), 82 (79), 81 (59), 79 (51), 67 (93), 57 (48), 55
(53), 53 (34); HRMS (ESI) Calcd for C9H17NO3 [M+Na]+ : 210.1101, Found : 210.1100.
General procedure D was applied to (E)-7-(aminooxy)hept-4-en-3-yl acetate (165 mg, 0.88
mmol). Purification by flash chromatography on silica gel (PE/ EtOAc 90/10 to 80/20)
yielded 1i as a colorless oil (281 mg, 0.82 mmol, 93%).1H NMR (400 MHz, CDCl3) δ 7.84 –
7.77 (m, 2H), 7.34 (dd, J = 8.6, 0.6 Hz, 2H), 7.02 (d, J = 3.7 Hz, 1H), 5.69 – 5.58 (m, 1H),
5.45 (ddt, J = 15.5, 7.0, 1.4 Hz, 1H), 5.08 (q, J = 6.7 Hz, 1H), 4.03 (t, J = 6.6 Hz, 2H), 2.44 (s,
3H), 2.34 (qd, J = 6.7, 1.0 Hz, 2H), 2.03 (s, 3H), 1.62 – 1.57 (m, 2H), 0.86 (t, J = 7.4 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 170.7, 144.9, 133.7, 130.8, 129.7, 129.2, 128.6, 76.3,
75.9, 31.3, 27.4, 21.7, 21.4, 9.5; IR (neat, ν/cm-1) : 3213, 2967, 2938, 2880, 1730, 1712, 1598,
1403, 1372, 1339, 1307, 1291, 1240, 1165, 1120, 1092, 1074, 1019; MS (EI, m/z) 281 (6, [M-
AcOH]+), 155 (11, [M-ONHTs]+), 126 (100), 91 (74), 84 (11), 82 (15), 81 (19), 72 (11), 67
(11), 65 (31), 56 (11), 55 (33), 54 (27); HRMS (ESI) Calcd for C16H23NO5S [M+Na]+ :
364.1223, Found : 364.1190.
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[(E)-5- cyclohexyl-5-(p-tolylsulfonylamino)oxy-pent-2-enyl] acetate (1j). General
procedure A was applied to cyclohexanecarboxaldehyde (800 mg, 7.14 mmol). Purification
by flash chromatography on silica gel (PE/Et2O 96/4) yielded 2-(1-cyclohexylbut-3-
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enoxy)isoindoline-1,3-dione as a yellow oil (1.3 g, 3.1 mmol, 43% for the two steps). H
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NMR (400 MHz, CDCl3) δ 7.81 (dd, J = 5.4, 3.1 Hz, 2H), 7.73 (dd, J = 5.5, 3.1 Hz, 2H), 5.99
(ddt, J = 17.2, 10.2, 6.9 Hz, 1H), 5.11 (dq, J = 17.2, 1.6 Hz, 1H), 5.04 (dq, J = 10.2 Hz, 1.6
Hz, 1H), 4.13 (q, J = 6.4 Hz, 1H), 2.51 – 2.37 (m, 2H), 1.99 – 1.91 (m, 1H), 1.90 – 1.83 (m,
1H), 1.83 – 1.76 (m, 2H), 1.73 – 1.63 (m, 2H), 1.30 – 1.14 (m, 5H); 13C{1H} NMR (100
MHz, CDCl3) δ 164.3, 134.4, 134.4, 129.1, 123.4, 117.0, 91.0, 39.8, 34.1, 28.2, 28.0, 26.5,
26.2, 26.2; IR (neat, ν/cm-1) : 2925, 2853, 1790, 1729, 1641, 1467, 1449, 1372, 1187, 1122,
1081, 1025; MS (EI, m/z) 164 (9), 137 (14), 136 (26), 104 (29), 96 (8), 95 (100), 94 (9), 93
(8), 90 (16), 83 (16), 82 (10), 81 (85), 79 (17), 77 (13), 76 (30), 69 (20), 67 (50), 55 (79);
HRMS (ESI) Calcd for C18H21NO3 [M+Na]+ : 322.1414, Found : 322.1416. General
procedure B was applied to 2-(1-cyclohexylbut-3-enoxy)isoindoline-1,3-dione (220 mg, 0.74
mmol). Purification by flash chromatography on silica gel (PE/Et2O 90/10) yielded [(E)-5-
cyclohexyl-5-(1,3-dioxoisoindolin-2-yl)oxy-pent-2-enyl] acetate as an oil (192 mg, 0.52
mmol, 70%, E/Z = 75/25). 1H NMR (400 MHz, CDCl3) δ 7.82 (dd, J = 5.5, 3.0 Hz, 2H), 7.74
(dd, J = 5.4, 3.1 Hz, 2H), 6.01 – 5.89 (m, 1H), 5.72 – 5.61 (m, 1H), 4.48 (dd, J = 6.3 Hz, 0.9
Hz, 2H), 4.12 (qapp, J = 5.2 Hz, 1H), 2.56 – 2.37 (m, 2H), 2.03 (s, 3H), 1.99 – 1.91 (m, 1H),
1.90 – 1.84 (m, 1H), 1.83 – 1.74 (m, 2H), 1.74 – 1.63 (m, 2H), 1.32 – 1.11 (m, 5H); 13C{1H}
NMR (100 MHz, CDCl3) δ 170.8, 164.2, 134.4, 131.4, 129.0, 126.4, 123.4, 90.9, 64.8, 40.0,
32.6, 28.4, 27.8, 26.4, 26.2, 26.1, 20.9; IR (neat, ν/cm-1) : 2927, 2853, 1790, 1732, 1467,
1450, 1373, 1232, 1188, 1124, 1082, 1017; MS (EI, m/z) 209 (4), 149 (44), 148 (12), 107
(16), 105 (13), 104 (30), 95 (52), 93 (22), 91 (18), 90 (15), 83 (19), 81 (39), 79 (28), 77 (17),
76 (31), 67 (100), 55 (62), 54 (16), 53 (20); HRMS (ESI) Calcd for C21H25NO5 [M+Na]+ :
394.1625, Found : 394.1628. General procedure C was applied to [(E)-5-cyclohexyl-5-(1,3-
dioxoisoindolin-2-yl)oxy-pent-2-enyl] acetate (190 mg, 0.52 mmol). Purification by flash
chromatography on silica gel (PE/Et2O 70/30) yielded [(E)-5-aminooxy-5-cyclohexyl-pent-2-
enyl] acetate as a colorless oil (76 mg, 0.32 mmol, 61%, E/Z = 80/20). 1H NMR (400 MHz,
CDCl3) δ 5.88 – 5.70 (m, 1H), 5.69 – 5.59 (m, 1H), 4.53 (dapp, J = 6.4 Hz, 2H), 3.36 (qapp, J =
5.7 Hz, 1H), 2.39 – 2.20 (m, 2H), 2.05 (s, 3H), 1.81 – 1.48 (m, 6H), 1.29 – 0.93 (m, 5H);
13C{1H} NMR (100 MHz, CDCl3) δ 170.9, 133.2, 125.7, 87.9, 65.2, 39.8, 32.8, 28.9, 28.6,
26.6, 26.3, 26.2, 21.0; IR (neat, ν/cm-1) : 3319, 2924, 2852, 1736, 1590, 1449, 1365, 1229,
1148, 1024; MS (EI, m/z) 149 (4), 111 (16), 95 (27), 83 (55), 81 (23), 79 (19), 68 (11), 67
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(47), 56 (10), 55 (100), 54 (93); HRMS (ESI) Calcd for C13H23NO3 [M+H]+ : 242.1751,
Found : 242.1753. General procedure D was applied to [(E)-5-aminooxy-5-cyclohexyl-pent-
2-enyl] acetate (60 mg, 0.25 mmol). Purification by flash chromatography on silica gel
(Benzene/Et2O 90/10) yielded 1j as an oil (147 mg, 0.18 mmol, 71%, E/Z = 90/10). 1H NMR
(400 MHz, CDCl3) δ 7.80 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 6.99 (s, 1H), 5.85 –
5.73 (m, 1H), 5.71 – 5.52 (m, 1H), 4.52 (dd, J = 6.4, 1.1 Hz, 2H), 3.89 (qapp, J = 5.6 Hz, 1H),
2.44 (s, 3H), 2.43 – 2.36 (m, 1H), 2.31 – 2.20 (m, 1H), 2.06 (s, 3H), 1.80 – 1.53 (m, 6H), 1.32
– 0.81 (m, 5H); 13C{1H} NMR (100 MHz, CDCl3) δ 171.0, 144.7, 134.0, 132.0, 129.6, 128.6,
126.3, 89.8, 65.0, 39.4, 32.5, 28.7, 28.2, 26.4, 26.3, 26.1, 21.6, 21.0; IR (neat, ν/cm-1) : 3213,
2925, 2852, 2360, 1737, 1598, 1494, 1449, 1338, 1233, 1185, 1166, 1092, 1021; MS (EI, m/z)
335 (8), 226 (11), 181 (11), 180 (83), 155 (21), 96 (27), 95 (31), 93 (15), 92 (13), 91 (100), 83
(25), 82 (11), 81 (42), 79 (22), 77 (10), 69 (12), 68 (22), 67 (54), 65 (34), 55 (62); HRMS
(ESI) Calcd for C20H29NO5S [M+Na]+ : 418.1659, Found : 418.1656.
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[(E)-5-(p-tolylsulfonylamino)oxyhex-2-enyl] acetate (1k). To a solution of pent-4-en-2-ol
(1.05 g, 17.5 mmol, 1 equiv) in THF (100 mL) was added PPh3 (8.3 g, 1.8 equiv) and N-
hydroxyphtalimide (5.1 g, 1.8 equiv). The mixture was cooled to 0 °C and DIAD (5.2 mL, 1.5
equiv) was added dropwise. After 3 h, the reaction medium was concentrated and the residue
was purified by flash chromatography on silica gel (PE/Et2O 90/10) to afford 2-(1-methylbut-
3-enoxy)isoindoline-1,3-dione as a white solid (3.95 g, 17 mmol, 97%). Mp : 54 °C; 1H NMR
(400 MHz, CDCl3) δ 7.86 – 7.79 (m, 2H, HAr), 7.78 – 7.71 (m, 2H, HAr), 5.88 (ddt, J = 17.1,
10.1, 7.0 Hz, 1H, H4), 5.16 (dq, J = 17.1, 1.8 Hz, 1H, H5), 5.10 (dq, J = 10.4, 1.6 Hz, 1H, H5’),
4.44 (sextapp, J = 6.4 Hz, 1H, H2), 2.62 – 2.35 (m, 2H, H3), 1.35 (d, J = 6.0 Hz, 3H, H1);
13C{1H} NMR (100 MHz, CDCl3) δ 164.2, 134.4, 133.3, 128.9, 123.5, 117.9, 83.4, 39.3, 18.3;
IR (neat, ν/cm-1) : 2983, 2925, 1783, 1737, 1639, 1610, 1465, 1416, 1380, 1362, 1287, 1245,
1184, 1156, 1137, 1121, 1082, 1053, 1012; MS (EI, m/z) 190 (2, [M-CH2CH=CH2]+), 164
(16), 163 (14, [PhtNOH]+·), 133 (9), 105 (13), 104 (42), 90 (30), 77 (12), 76 (64), 75 (11), 69
(100), 68 (95), 67 (32), 53 (14); HRMS (ESI) Calcd for C13H13NO3 [M+Na]+ : 254.0788,
Found : 254.0789. General procedure B was applied to 2-(1-methylbut-3-enoxy)isoindoline-
1,3-dione (300 mg, 1.3 mmol). Purification by flash chromatography on silica gel (PE/Et2O
70/30) yielded [(E)-5-(1,3-dioxoisoindolin-2-yl)oxyhex-2-enyl] acetate as an orange oil (250
mg, 0.82 mmol, 63%, E/Z = 83/17). 1H NMR (400 MHz, CDCl3) δ 7.86 – 7.80 (m, 2H), 7.78
– 7.70 (m, 2H), 5.89 – 5.75 (m, 1H), 5.73 – 5.55 (m, 1H), 4.51 (dd, J = 6.2, 1.0 Hz, 2H), 4.11
(sextapp, J = 5.9 Hz, 1H), 2.67 – 2.37 (m, 2H), 2.05 (s, 3H), 1.34 (d, J = 6.0 Hz, 3H); 13C{1H}
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NMR (100 MHz, CDCl3) δ 170.8, 164.2, 134.5, 130.2, 129.0, 127.3, 123.5, 83.3, 64.8, 37.7,
21.0, 18.4; IR (neat, ν/cm-1) : 2935, 1789, 1727, 1611, 1467, 1365, 1229, 1187, 1121, 1082,
1063, 1016; MS (EI, m/z) 244 (1, [M-OAc]+), 141 (48, [M-PhtNO]+), 130 (7), 104 (17), 99
(14), 90 (20), 82 (7), 81 (100), 79 (15), 76 (22), 55(7), 54 (7), 53 (10); HRMS (ESI) Calcd for
C16H17NO5 [M+Na]+ : 326.0999, Found : 326.1003. General procedure C was applied to [(E)-
5-(1,3-dioxoisoindolin-2-yl)oxyhex-2-enyl] acetate (400 mg, 1.3 mmol). Purification by flash
chromatography on silica gel (PE/Et2O 50/50) provided [(E)-5-aminooxyhex-2-enyl] acetate
as a yellow oil (1.07 g, 0.81 mmol, 62%, E/Z = 83/17). 1H NMR (400 MHz, CDCl3) δ 5.81 –
5.70 (m, 1H), 5.70 – 5.59 (m, 1H), 4.52 (dd, J = 6.4, 0.8 Hz, 2H), 3.70 (sextapp, J = 6.1 Hz,
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1H), 2.45 – 2.15 (m, 2H), 2.05 (s, 3H), 1.14 (d, J = 6.4 Hz, 3H); C{1H} NMR (100 MHz,
CDCl3) δ 170.9, 132.1, 126.2, 79.2, 65.1, 37.8, 21.1, 18.4; IR (neat, ν/cm-1) : 3222, 2970,
2929, 1735; 1592, 1446, 1367, 1229, 1126, 1067, 1025; HRMS (ESI) Calcd for C8H15NO3
[M+Na]+ : 196.0944, Found : 196.0940. General procedure D was applied to [(E)-5-
aminooxyhex-2-enyl] acetate (30 mg, 0.17 mmol). Purification by flash chromatography on
silica gel (PE/Et2O 60/40) yielded 1k as a colorless oil (43 mg, 0.13 mmol, 78%, E/Z >
90/10). 1H NMR (400 MHz, CDCl3) δ 7.80 (dapp, J = 8.0 Hz, 2H), 7.33 (dapp, J = 8.0 Hz, 2H),
6.91 (s, 1H), 5.77 – 5.56 (m, 2H), 4.52 (dapp, J = 6.0 Hz, 2H), 3.70 (sextapp, J = 6.2 Hz, 1H),
2.44 (s, 3H), 2.40 – 2.20 (m, 2H), 2.06 (s, 3H), 1.18 (d, J = 6.4 Hz, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 170.9, 144.8, 133.8, 131.0, 129.6, 128.5, 126.8, 81.7, 64.9, 37.7, 21.6, 20.9,
18.4; IR (neat) : 3213, 2976, 2933, 1736, 1716, 1598, 1446, 1379, 1341, 1307, 1232, 1165,
1120, 1091, 1067, 1023; MS (EI, m/z) 171 (19, [TsNH2]+·), 155 (16, [Ts]+), 108 (15), 107
(31), 91 (100), 89 (15), 77 (13), 65 (53), 64 (11), 63 (21), 51 (14); HRMS (ESI) Calcd for
C15H21NO5S [M+Na]+ : 350.1033, Found : 350.1024.
[(E)-5-phenyl-5-(p-tolylsulfonamino)oxy-pent-2-enyl] acetate (1l). General procedure A
was applied to benzaldehyde (1.6 g, 15 mmol). Purification by flash chromatography on silica
gel (PE/Et2O 90/10) yielded 2-(1-phenylbut-3-enoxy)isoindoline-1,3-dione as a white solid
1
(4.2 g, 14.3 mmol, 95%). Mp : 80 °C; H NMR (400 MHz, CDCl3) δ 7.75 – 7.70 (m, 2H),
7.70 – 7.65 (m, 2H), 7.49 – 7.45 (m, 2H), 7.36 – 7.28 (m, 3H), 5.79 (ddt, J = 17.1, 10.2, 6.9
Hz, 1H), 5.39 (t, J = 7.1 Hz, 1H), 5.15 (dq, J = 17.1, 1.5 Hz, 1H), 5.07 (ddt, J = 10.2, 1.8, 1.2
Hz, 1H), 2.95 (dtt, J = 14.3, 7.1, 1.3 Hz, 1H), 2.77 – 2.68 (dtt, J = 14.3, 7.1, 1.3 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 163.7, 137.5, 134.3, 133.0, 129.1, 128.8, 128.3, 128.2,
123.4, 118.1, 88.3, 39.2; IR (neat, ν/cm-1) : 3064, 1788, 1727, 1641, 1610, 1494, 1466, 1455,
1366, 1335, 1290, 1247, 1187, 1155, 1116, 1082, 1016; MS (EI, m/z) 252 (2, [M-
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CH2CH=CH2]+), 132 (13), 131 (100, [M-PhtNO]+), 130 (42), 129 (26), 128 (10), 116 (14),
115 (17), 105 (12), 104 (21), 91 (60), 90 (11), 77 (28), 76 (28); HRMS (ESI) Calcd for
C18H15NO3 [M+Na]+ : 316.0944, Found : 316.0944. General procedure B was applied to 2-(1-
phenylbut-3-enoxy)isoindoline-1,3-dione (300 mg, 1.02 mmol). Purification by flash
chromatography on silica gel (PE/Et2O 70/30) yielded [(E)-5-(1,3-dioxoisoindolin-2-yl)oxy-
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5-phenyl-pent-2-enyl] acetate as a brown oil (270 mg, 0.74 mmol, 73%, E/Z > 90/10). H
NMR (400 MHz, CDCl3) δ 7.76 – 7.70 (m, 2H), 7.69 – 7.65 (m, 2H), 7.49 – 7.43 (m, 2H),
7.37 – 7.27 (m, 3H), 5.80 – 5.62 (m, 2H), 5.38 (t, J = 7.0 Hz, 1H), 4.49 – 4.46 (m, 2H), 3.03 –
2.92 (m, 1H), 2.80 – 2.68 (m, 1H), 2.03 (s, 3H); C{1H} NMR (100 MHz, CDCl3) δ 170.7,
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163.6, 137.3, 134.3, 129.9, 129.2, 128.8, 128.3, 128.1, 127.4, 123.4, 88.1, 64.7, 37.8, 20.9; IR
(neat, ν/cm-1) : 2930, 1789, 1728, 1610, 1496, 1467, 1456, 1364, 1289, 1187, 1125, 1082,
1016; MS (EI, m/z) 252 (7), 203 (4, [M-PhtNO]+), 143 (100), 129 (7), 128 (25), 115 (9), 105
(12), 104 (13), 91 (13), 90 (8), 77 (12), 76 (9); HRMS (ESI) Calcd for C21H19NO5 [M+Na]+ :
388.1155, Found : 388.1155. General procedure C was applied to (E)-5-(1,3-dioxoisoindolin-
2-yl)oxy-5-phenyl-pent-2-enyl] acetate (250 mg, 0.68 mmol). Purification by flash
chromatography on silica gel (PE/Et2O 60/40) yielded [(E)-5-aminooxy-5-phenyl-pent-2-
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enyl] acetate as a colorless oil (117 mg, 0.5 mmol, 73%, E/Z > 95/5). H NMR (400 MHz,
CDCl3) δ 7.41 – 7.27 (m, 5H), 5.73 (dt, J = 15.1, 6.9 Hz, 1H), 5.65 – 5.56 (m, 1H), 4.81 (brs,
2H), 4.55 (dd, J = 7.7, 5.8 Hz, 1H), 4.52 – 4.46 (m, 2H), 2.71 – 2.54 (m, 1H), 2.47 – 2.36 (m,
1H), 2.05 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.8, 140.9, 131.5, 128.6, 128.0,
126.7, 126.5, 86.4, 64.9, 39.0, 21.0; IR (neat, ν/cm-1) : 3321, 3030, 2935, 1734, 1586, 1494,
1454, 1364, 1228, 1073, 1024; MS (EI, m/z) 202 (0.4, [M-NH2OH]+·), 144 (9), 143 (72), 129
(9), 128 (32), 122 (24), 1225 (13), 107 (37), 106 (18), 105 (100), 91 (17), 79 (45), 78 (12), 77
(68), 54 (95); HRMS (ESI) Calcd for C13H17NO3 [M+Na]+ : 258.1101, Found : 258.1102.
General procedure D applied to [(E)-5-aminooxy-5-phenyl-pent-2-enyl] acetate (113 mg, 0.25
mmol) (additional 0.1 equiv of DMAP after 12 h). Purification by flash chromatography on
silica gel (PE/Et2O 70/30) yielded 1l as a colorless oil (150 mg, 0.21 mmol, 83%, E/Z > 95/5).
1H NMR (400 MHz, CDCl3) δ 7.81 – 7.77 (m, 2H), 7.37 – 7.22 (m, 7H), 6.79 (brs, 1H), 5.78
– 5.68 (m, 1H), 5.66 – 5.58 (m, 1H), 5.02 (dd, J = 8.1, 5.8 Hz, 1H), 4.52 (dapp, J = 6.2 Hz,
2H), 2.68 – 2.58 (m, 1H), 2.50 – 2.41 (m, 1H), 2.45 (s, 3H), 2.06 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 170.8, 144.8, 139.4, 133.7, 130.7, 129.6, 128.6, 128.5, 128.3, 127.0, 126.9,
87.8, 64.7, 38.1, 21.7, 21.0; IR (neat, ν/cm-1) : 3210, 2925, 2854, 1736, 1598, 1495, 1455,
1343, 1307, 1233, 1186, 1166, 1091, 1024; MS (EI, m/z) 174 (19), 155 (34), 144 (41), 143
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(39), 129 (76), 128 (25), 105 (18), 104 (36), 91 (100), 77 (29), 70 (15), 66 (32), 65 (38), 51
(18); HRMS (ESI) Calcd for C20H23NO5S [M+Na]+ : 412.1189, Found : 412.1189.
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(E)-Ethyl 6-acetoxy-2-((4-methylphenylsulfonamido)oxy)hex-4-enoate (1m). To a solution
of ethyl glyoxylate (2,86 mL, 15 mmol, 50% in toluene, 1 equiv) in water (100 mL) at rt were
added allyl bromide (1.43 mL, 1.1 equiv) and indium powder (1.74 g, 1 equiv). After 24 h at
rt, the reaction medium was quenched with 1N HCl aqueous solution and EtOAc was added.
A white precipitate was formed and the mixture was stirred for 1.5 h. The two phases were
separated, the aqueous layer was extracted twice with EtOAc and the combined organic layers
were dried over MgSO4, filtered and concentrated in vacuo to deliver 2-hydroxypent-4-enoic
acid ethyl ester as a crude yellow oil (1.61 g). To a solution of the previously obtained alcohol
(1.6 g, 11.1 mmol, 1 equiv) in THF (60 mL) were added PPh3 (3.78 g, 1.3 equiv) and N-
hydroxyphtalimide (2.35 g, 1.3 equiv). The resulting mixture was cooled to 0 °C before
DIAD (2.8 mL, 1.3 equiv) was added dropwise. After 30 min at 0 °C, the reaction medium
was warmed to room temperature. After 3 h, the solvent was removed under reduced pressure
and the residue was purified by flash chromatography on silica gel (PE/Et2O 70/30) to afford
ethyl 2-((1,3-dioxoisoindolin-2-yl)oxy)pent-4-enoate as a yellow oil (1.8 g, 6.15 mmol, 41%
over two steps). 1H NMR (400 MHz, CDCl3) δ 7.88 – 7.79 (m, 2H), 7.79 – 7.72 (m, 2H), 5.94
(ddt, J = 17.1, 10.2, 6.9 Hz, 1H), 5.24 (dq, J = 17.1, 1.5 Hz, 1H), 5.18 (dd, J = 10.2, 1.1 Hz,
1H), 4.79 (t, J = 6.6 Hz, 1H), 4.32 – 4.18 (m, 2H), 2.87 – 2.69 (m, 2H), 1.28 (t, J = 7.1 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 168.7, 163.1, 134.6, 131.2, 128.8, 123.6, 119.0,
84.5, 61.7, 35.1, 14.0; IR (neat, ν/cm-1) : 2983, 1793, 1731, 1643, 1647, 1371, 1292, 1186,
1127, 1081, 1017; MS (EI, m/z) 216 (2), 163 (11), 133 (12), 132 (13), 130 (29), 127 (100),
105 (29), 104 (65), 103 (11), 99 (73), 90 (55), 85 (25), 81 (20), 77 (22), 76 (88), 75 (14), 71
(19), 69 (19), 64 (11), 63 (13), 55 (37); HRMS (ESI) Calcd for C15H15NO5 [M+Na]+ :
312.0842, Found : 312.0842. General procedure B was applied to ethyl 2-((1,3-
dioxoisoindolin-2-yl)oxy)pent-4-enoate (300 mg, 1.04 mmol). Purification on silica gel
(PE/Et2O 60/40) yielded (E)-ethyl 6-acetoxy-2-((1,3-dioxoisoindolin-2-yl)oxy)hex-4-enoate
as an orange oil (260 mg, 0.72 mmol, 69%, E/Z = 70/30). 1H NMR (400 MHz, CDCl3) δ 7.86
– 7.81 (m, 2H), 7.78 – 7.73 (m, 2H), 5.97 – 5.84 (m, 1H), 5.83 – 5.71 (m, 1H), 4.81 – 4.75 (m,
1H), 4.66 (d, J = 6.2 Hz, 0.6H), 4.54 (d, J = 5.9 Hz, 1.4H), 4.29 – 4.19 (m, 2H), 2.92 – 2.71
(m, 2H), 2.06 (s, 3H), 1.31 – 1.23 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.7, 168.6,
163.1, 134.6, 128.8, 128.5, 127.9, 127.5, 127.1, 123.7, 84.3, 64.5, 61.9, 61.8, 60.1, 33.7, 29.1,
20.9, 14.0, 14.0; IR (neat, ν/cm-1) : 2982, 1793, 1730, 1611, 1467, 1445, 1367, 1228, 1186,
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1123, 1081, 1019; MS (EI, m/z) 302 (1), 199 (12), 148 (31), 147 (10), 139 (91), 130 (19), 111
(100), 105 (18), 104 (38), 99 (11), 93 (16), 90 (30), 83 (44), 81 (57), 77 (11), 76 (45), 67 (59),
55 (30); HRMS (ESI) Calcd for C18H19NO7 [M+Na]+ : 384.1054, Found : 384.1058. General
procedure C was applied to (E)-ethyl 6-acetoxy-2-((1,3-dioxoisoindolin-2-yl)oxy)hex-4-
enoate (200 mg, 0.55 mmol). Purification on silica gel (PE/Et2O 50/50) yielded (E)-ethyl 6-
acetoxy-2-(aminooxy)hex-4-enoate as a colorless oil (95 mg, 0.41 mmol, 75%, E/Z = 90/10).
1H NMR (400 MHz, CDCl3) δ 5.80 – 5.61 (m, 4H), 4.51 (dd, J = 6.0, 0.9 Hz, 2H), 4.28 – 4.17
(m, 3H), 2.58 – 2.41 (m, 2H), 2.05 (s, 3H), 1.29 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 171.9, 170.7, 129.8, 127.3, 82.3, 64.7, 60.9, 34.1, 21.0, 14.3; IR (neat, ν/cm-1) :
3330, 2925, 1733, 1586, 1446, 1368, 1228, 1190, 1128, 1025; HRMS (ESI) Calcd for
C10H17NO5 [M+Na]+ : 254.0999, Found : 254.1002. General procedure D was applied to (E)-
ethyl 6-acetoxy-2-(aminooxy)hex-4-enoate (30 mg, 0.13 mmol). Purification by
chromatography on silica gel (PE/Et2O 60/40) yielded 1m as a waxy oil (45 mg, 0.12 mmol,
89%, E/Z > 90/10). 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.3 Hz, 2H), 7.63 (s, 1H), 7.32
(d, J = 8.1 Hz, 2H), 5.76 – 5.61 (m, 2H), 4.63 (dd, J = 8.3, 4.5 Hz, 1H), 4.53 (d, J = 5.6 Hz,
2H), 4.19 (q, J = 7.1 Hz, 2H), 2.59 – 5.51 (m, 1H), 2.43 (s, 3H), 2.46 – 2.36 (m, 1H), 2.06 (s,
3H), 1.26 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.7, 170.5, 145.0, 133.4,
129.6, 128.9, 128.6, 127.7, 83.5, 64.4, 61.4, 33.8, 21.6, 20.9, 14.1; IR (neat, ν/cm-1) : 3205,
2982, 1735, 1598, 1446, 1372, 1344, 1228, 1198, 1166, 1090, 1022; HRMS (ESI) Calcd for
C17H23NO7S [M+Na]+ : 408.1087, Found : 408.1086.
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(E)-4-methyl-5-((4-methylphenylsulfonamido)oxy)pent-2-en-1-yl acetate (1n). To a
solution of 2-methyl-but-3-en-1-ol (1.45 g, 17 mmol, 1 equiv) in THF (80 mL) was added
PPh3 (5.8 g, 1.3 equiv) and N-hydroxyphtalimide (3.6 g, 1.3 equiv). The mixture was cooled
down to 0 °C and DIAD (4.4 mL, 1.3 equiv) was added dropwise. After 2 h, the reaction
medium was concentrated and the residue was purified by flash chromatography on silica gel
(PE/Et2O 90/10 to 80/20) to afford 2-((2-methylbut-3-en-1-yl)oxy)isoindoline-1,3-dione as a
yellow oil (3.5 g, 15,1 mmol, 89%). 1H NMR (400 MHz, CDCl3) δ 7.85 – 7.82 (m, 2H), 7.77
– 7.73 (m, 2H), 5.86 (ddd, J = 17.3, 10.5, 6.8 Hz, 1H), 5.18 (dt, J = 17.3, 1.4 Hz, 1H), 5.09
(dt, J = 10.5, 1.3 Hz, 1H), 4.15 (dd, J = 8.7, 6.5 Hz, 1H), 4.02 (dd, J = 8.7, 7.1 Hz, 1H), 2.80 –
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2.66 (m, 1H), 1.20 (d, J = 6.8 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 163.5, 139.3,
134.5, 129.0, 123.5, 115.3, 82.3, 36.6, 16.3; IR (neat, ν/cm-1) : 3506, 3081, 2968, 2882, 1789,
1728, 1641, 1610, 1467, 1417, 1391, 1374, 1290, 1245, 1187, 1159, 1126, 1082, 1017; MS
(EI, m/z) 186 (0.3), 164 (13), 163 (14, [PhtNOH]+·), 104 (17), 90 (13), 76 (22), 69 (100, [M-
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PhtNO]+), 68 (66), 67 (19); HRMS (ESI) Calcd for C13H13NO3 [M+Na]+ : 254.0787, Found :
254.0791. General procedure B was applied to 2-((2-methylbut-3-en-1-yl)oxy)isoindoline-
1,3-dione (500 mg, 2.17 mmol). Purification by flash chromatography on silica gel (PE/Et2O
90/10 to 80/20) yielded (E)-5-((1,3-dioxoisoindolin-2-yl)oxy)-4-methylpent-2-en-1-yl acetate
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as a brown oil (418 mg, 1.4 mmol, 64%, E/Z > 95/5). H NMR (400 MHz, CDCl3) δ 7.85 –
7.81 (m, 2H), 7.76 – 7.72 (m, 2H), 5.85 – 5.78 (dd, J = 15.7, 6.5 Hz, 1H), 5.75 – 5.70 (m,
1H), 4.53 (dapp, J = 5.8 Hz, 2H), 4.13 (dd, J = 8.8, 6.6 Hz, 1H), 4.02 (dd, J = 8.8, 7.0 Hz, 1H),
2.75 (septapp, J = 6.8 Hz, 1H), 2.06 (s, 3H), 1.20 (d, J = 6.8 Hz, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 170.8, 163.5, 136.0, 134.5, 128.9, 124.8, 123.5, 82.1, 64.9, 35.5, 21.0, 16.4;
IR (neat, ν/cm-1) : 2966, 1789, 1726, 1467, 1365, 1229, 1187, 1128, 1082, 1017; MS (EI, m/z)
202 (3), 141 (24), 104 (20), 99 (9), 90 (21), 81 (100), 79 (14), 76 (28), 67 (16), 55 (11), 53
(14), 50 (13); HRMS (ESI) Calcd for C16H17NO5 [M+Na]+ : 326.0999, Found : 326.1002.
General procedure C was applied to (E)-5-((1,3-dioxoisoindolin-2-yl)oxy)-4-methylpent-2-
en-1-yl acetate (385 mg, 1.3 mmol). Purification by flash chromatography on silica gel
(PE/Et2O 80/20 to 60/40) provided (E)-5-(aminooxy)-4-methylpent-2-en-1-yl acetate as a
1
yellow oil (145 mg, 0.84 mmol, 65%, E/Z > 95/5). H NMR (400 MHz, CDCl3) δ 5.75 – 5.67
(m, 1H), 5.61 (dtd, J = 15.5, 6.0, 0.9 Hz, 1H), 5.38 (brs, 2H), 4.52 (d, J = 6.2 Hz, 2H), 3.56
(dd, J = 8.4, 5.6 Hz, 1H), 3.52 (dd, J = 8.4, 5.0 Hz, 1H), 2.57 (sept, 6.9 Hz, 1H), 2.06 (s, 3H),
1.00 (d, J = 6.9 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.9, 138.2, 123.8, 80.3, 65.2,
35.5, 21.0, 16.5; IR (neat, ν/cm-1) : 3319, 2961, 1734, 1591, 1456, 1380, 1365, 1229, 1023;
HRMS (ESI) Calcd for C8H15NO3 [M+Na]+ : 196.0944, Found : 196.0944. General procedure
D was applied to (E)-5-(aminooxy)-4-methylpent-2-en-1-yl acetate (110 mg, 0.6 mmol).
Purification by flash chromatography on silica gel (PE/Et2O 80/20 to 60/40) yielded acetate
1n as a pale yellow oil (150 mg, 0.43 mmol, 72%, E/Z > 90/10). 1H NMR (400 MHz, CDCl3)
δ 7.83 – 7.78 (m, 2H), 7.34 (dd, J = 8.6, 0.6 Hz, 2H), 7.01 – 6.95 (m, 1H), 5.66 (dd, J = 15.5,
6.7 Hz, 1H), 5.62 – 5.54 (m, 1H), 4.51 (d, J = 5.5 Hz, 2H), 3.89 (d, J = 6.8 Hz, 2H), 2.57
(sept, J = 6.7 Hz, 1H), 2.45 (s, 3H), 2.06 (s, 3H), 0.99 (d, J = 6.9 Hz, 3H); C{1H} NMR
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(100 MHz, CDCl3) δ 170.9, 144.9, 137.2, 133.7, 129.7, 128.6, 124.4, 81.3, 65.0, 35.4, 21.7,
21.0, 16.5; IR (neat) : 3212, 2963, 1736, 1598, 1455, 1381, 1364, 1338, 1306, 1234, 1186,
1165, 1092, 1026; HRMS (ESI) Calcd for C15H21NO5S [M+Na]+ : 350.1033, Found :
350.1035
(Z)-3-methyl-5-((4-methylphenylsulfonamido)oxy)tetradec-2-en-1-yl acetate (1o). To a
solution of decanal (3.6 mL, 19.2 mmol, 1 equiv) in THF (130 mL) at -78 °C was added 2-
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methallylmagnesium chloride (50 mL, 0.5M/THF, 1.3 equiv). After 4 h at -78 °C, the reaction
medium was warmed to rt and a saturated aqueous solution of NH4Cl was added. The two
phases were separated, the aqueous layer was extracted twice with Et2O and the combined
organic layers were dried over MgSO4, filtered and concentrated in vacuo. The crude product
was filtered on silica gel (PE/Et2O 90/10) to provide the corresponding alcohol. To a solution
of this alcohol (1 equiv) in CH2Cl2 (120 mL) were added DIPEA (7 mL, 3.5 equiv) and
acryloyl chloride (2.8 mL, 3 equiv) at 0 °C. After 1 h at 0 °C, the reaction medium was
allowed to reach rt. After 1 h, a saturated aqueous solution of NaHCO3 was added. The two
phases were separated, the aqueous layer was extracted twice with CH2Cl2 and the combined
organic layers were dried over MgSO4, filtered and concentrated in vacuo. The crude product
was purified by flash chromatography on silica gel (PE/Et2O 97/3 to 95/5 to 90/10) to obtain
2-methyltridec-1-en-4-yl acrylate as a colorless oil (3 g, 11.3 mmol, 59% over two steps). 1H
NMR (400 MHz, CDCl3) δ 6.37 (dd, J = 17.3, 1.6 Hz, 1H), 6.09 (dd, J = 17.3, 10.4 Hz, 1H),
5.79 (dd, J = 10.4, 1.6 Hz, 1H), 5.11 (pentapp, J = 6.2 Hz, 1H), 4.77 (dq, J = 2.9, 1.4 Hz, 1H),
4.71 (dt, J = 3.0, 0.9 Hz, 1H), 2.33 (ddd, J = 13.9, 7.6, 0.7 Hz, 1H), 2.23 (ddd, J = 14.0, 5.4,
0.5 Hz, 1H), 1.77 – 1.73 (t, J = 0.9 Hz, 3H), 1.61 – 1.53 (m, 2H), 1.37 – 1.19 (m, 14H), 0.87
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(t, J = 6.9 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 165.9, 141.8, 130.2, 128.9, 113.3,
72.5, 42.9, 34.1, 31.9, 29.5, 29.5, 29.5, 29.3, 25.3, 22.7, 22.5, 14.1; IR (neat, ν/cm-1) : 3076,
2956, 2926, 2855, 1725, 1638, 1458, 1405, 1378, 1296, 1270, 1193, 1047; MS (EI, m/z) 195
(0.3, [M-OCOCH=CH2]+), 138 (5), 110 (4), 96 (6), 95 (10), 83 (8), 82 (16), 81 (10), 69 (5),
68 (8), 67 (9), 57 (5), 56 (5), 55 (100); HRMS (ESI) Calcd for C17H30O2 [M+Na]+ : 289.2138,
Found : 289.2139. To a solution of 2-methyltridec-1-en-4-yl acrylate (2.9 g, 11 mmol, 1
equiv) in CH2Cl2 (70 mL) was added Hoveyda-Grubbs catalyst (93 mg, 1 mol %). The
reaction medium was warmed to 50 °C for 24 h before another portion of Hoveyda-Grubbs
catalyst (2 mol %) was added. After 48 hours at rt, the solvent was evaporated under reduced
pressure. A flash chromatography on silica gel (PE/EtOAc 95/5 to 90/10) yielded 4-methyl-6-
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nonyl-5,6-dihydro-2H-pyran-2-one as a brown oil (1.8 g, 7.6 mmol, 69%). H NMR (400
MHz, CDCl3) δ 5.82 – 5.78 (m, 1H), 4.36 (dddd, J = 11.6, 7.5, 5.2, 4.0 Hz, 1H), 2.31 (ddq, J
= 17.8, 11.7, 1.1 Hz, 1H), 2.18 (dd, J = 17.8, 4.0 Hz, 1H), 1.97 (t, J = 1.1 Hz, 3H), 1.78 (dddd,
J = 13.5, 10.1, 7.4, 4.9 Hz, 1H), 1.62 (ddt, J = 13.5, 10.4, 5.2 Hz, 1H), 1.56 – 1.34 (m, 2H),
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1.34 – 1.20 (m, 12H), 0.88 (t, J = 6.9 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ 165.5,
157.1, 116.5, 77.3, 34.8, 34.7, 31.9, 29.5, 29.5, 29.4, 29.3, 24.9, 23.0, 22.7, 14.1; IR (neat,
ν/cm-1) : 2923, 2854, 1718, 1648, 1466, 1435, 1390, 1286, 1248, 1156, 1133, 1049, 1016; MS
(EI, m/z) 238 (1, [M]+), 125 (2), 112 (7), 111 (100), 100 (3), 95 (4), 83 (15), 82 (29), 69 (4),
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