Synthesis of α-Substituted Enoximes with Nucleophiles via Nitrosoallenes

Article abstract of DOI:10.1021/acs.joc.5b02364

This paper reports nitrosoallene-mediated synthesis of α-substituted enoximes. Nucleophilic substitution of nitrosoallenes, a novel chemical species prepared from allenyl N-hydroxysulfonamides, afforded α-functionalized enoximes. Introduction of various nucleophiles proceeded smoothly to form C-N, C-O, C-S, C-F, and C-C bonds in the presence of azodicarboxylates.

Full text of DOI:10.1021/acs.joc.5b02364

Article
pubs.acs.org/joc
Synthesis of α‑Substituted Enoximes with Nucleophiles
via Nitrosoallenes
Hiroki Tanimoto,* Keiichi Yokoyama, Yusuke Mizutani, Takashi Shitaoka, Tsumoru Morimoto,
Yasuhiro Nishiyama, and Kiyomi Kakiuchi
Graduate School of Materials Science, Nara Institute of Science and Technology (NAIST), 8916-5 Takayamacho, Ikoma,
Nara 630-0192, Japan
S
* Supporting Information
ABSTRACT: This paper reports nitrosoallene-mediated syn-
thesis of α-substituted enoximes. Nucleophilic substitution of
nitrosoallenes, a novel chemical species prepared from allenyl
N-hydroxysulfonamides, afforded α-functionalized enoximes.
Introduction of various nucleophiles proceeded smoothly to form
C−N, C−O, C−S, C−F, and C−C bonds in the presence of
azodicarboxylates.
Scheme 1. New Approach to α-Functionalized Enoximes
Using Nitrosoallenes
INTRODUCTION
■
α,β-Unsaturated carbonyl compounds, and especially their imine
derivatives (i.e., enimines and enoximes), have found recent
attention as highly useful synthons serving as Michael acceptors,
Diels−Alder dienophiles, and heterocycle precursors toward
bioactive molecules (Figure 1).1 Moreover, enimine structures are
nucleophiles to 1 would proceed to afford α-functionalized
enoximes. The nitroso group is a well-known strong electron-
withdrawing substituent, and applications of nitrosoalkenes have
been extensively documented.6,7 However, to the best of our
knowledge, no synthetic report of compounds 1 is found,
and their chemical reactivity should be explored.8,9 Additionally,
enoximes are efficient precursors for construction of various
amino compounds through cascade reactions and for the assembly
of functionalized heterocycle cores like pyridines and isoxazolines
in agrochemicals and anticancer agents.10 We herein describe the
study of novel chemical species nitrosoallenes and the nucleophilic
addition reaction affording α-functionalized enoximes.
Figure 1. Unsaturated imines.
also found in bioactive natural products.2 In this context, develop-
ing new functionalized enimine and enoxime syntheses is required.
Among these syntheses, introducing methods of polar substituents
like amines and sulfones to the α-positions of enimines or enoximes
could provide the basis for achievement of highly efficient organic
syntheses while β-functionalization can be achieved by 1,4-addition.
It is apparent in previous studies that allenamine deriv-
atives could produce enamines substituted with nucleophiles at
α-positions in low yields.3,4 Inspired by these umpolung reac-
tions, we envisioned that nitrosoallenes 1 could be efficient
intermediates producing α-functionalized enoximes in a similar
manner (Scheme 1).5 Thus, we anticipated that 1,4-additions of
RESULTS AND DISCUSSION
Because of the instability of nitroso groups, we selected
N-sulfonyl hydroxylamines, which easily dissociate to generate
■
Received: October 16, 2015
© XXXX American Chemical Society
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DOI: 10.1021/acs.joc.5b02364
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Table 1. Optimization of Reaction Conditions
a
entry
conditions
yield [%]
73
1
CsF, CH3CN, rt
2
CsF, THF, rt
0
3
TBAF, CH3CN, rt
TBAF, THF, rt
TBAF, THF, 0 °C
TBAF, AcOH, THF, 0 °C
TBAF, AcOH, THF, rt
42
72
64
94
88
88
81
85
89
74
77
88
4
5
6
7
8
TBAF, AcOH, CH3CN, 0 °C
TBAF, AcOH, Et2O, 0 °C
TBAF, AcOH, CPME, 0 °C
TBAF, AcOH, 4-MTHP, 0 °C
TBAF, AcOH, 1,4-dioxane, rt
TBAF, AcOH, DMF, 0 °C
TBAF (2.5 equiv), AcOH, CHCl3, 0 °C
TBAF, AcOH, toluene, 0 °C to rt
AgF, CH3CN, rt
9
10
11
12
13
14
15
16
17
b
b
54 (6: 11%)
0 (6: 48%)
0 (7: 63%)
c
16
,
TfOH (2 equiv), CH2Cl2−CH3CN (1:1), 0 °C
a
b
c
Isolated yield. Performed in 3 h. Performed in 1 h. CPME: cyclopentyl methyl ether. 4-MTHP: 4-methyltetrahydropyran.
the corresponding nitroso compounds.11 Thus, N-allenyl-N-
siloxysulfonamides 2, which have not been reported as well as
nitrosoallenes, were prepared from propargyl alcohols 3 and
Fukuyama’s reagent12 or its analogues 4 by applying a modified
procedure of Lu’s and Wang’s protocol (Scheme 1).3,13a At this
point, although other procedures (isomerization of N-siloxyl
propargylamides with base or SN2′-type additions)13d were
unsuccessful and R3−4 positions (Scheme 1) are limited to
aromatic rings, it was clear that the unknown reactivity of
nitrosoallenes should be revealed. From the outset, we examined
the transfer of the sulfone moiety of 2a to afford α-sulfonyl
enoxime 5a, a series of useful vinyl sulfones,14 via 1,4-addition of
sulfinates15 to nitrosoallene 1a (Table 1).
and nitrosoketenes9 showcase the unique reactivity of these
novel chemical species. The structures of 5a′, prepared from 5a,
and 6, were determined by X-ray crystallographic analyses
(see the Supporting Information).
With reaction conditions optimized (Table 1, entry 6), and
before examination of the various nucleophiles to be installed,
the focus was shifted to the exploration of the substrate scope
(Table 2). Electron-donating as well as electron-withdrawing
groups on the sulfone moiety were well-tolerated, and the
sulfones were successfully transferred to the α-position of the
enoximes in excellent yields (entries 1−5). The sterically
hindered mesitylenesulfonyl group also afforded 5g in moderate
yield (entry 6). When all substituents on the allenylamides were
aryl groups, the 2-isoxazolines 8h−i were afforded as major
products derived from the cyclocondensation of initially generated
vinylsulfones 5h−i probably due to their steric bulkiness. Thus,
overall yields of the sulfone-transfer reactions (entries 7−8) were
nearly 80%. Moreover, aldoxime 5j and functionalized alkyl
ketoximes 5k−m were successfully accessed (entries 9−12).
Electron-withdrawing as well as electron-rich aromatic substituents
of R3 and R4 gave 5n−o in excellent yields (entries 13−14).
Unsymmetrical allene 2p delivered 5p in excellent yield (entry 15).
Since no isomerization of (E)- or (Z)-5p under the same reaction
conditions occurred, the excellent (Z)-selectivity is presumably
attributed to the steric repulsion between the o-tolyl group and
the BuC(NO) moiety at the late transition state of 1,4-addition.
The structure of (Z)-5p was unambiguously determined by X-ray
crystallographic analysis (see the Supporting Information).
Cesium fluoride12 in acetonitrile successfully gave the desired
5a in good yield, whereas the reaction in THF did not because
of the insolubility in THF (entries 1−2). Tetrabutylammonium
fluoride (TBAF) in acetonitrile afforded 5a in moderate yield
(entry 3). Use of TBAF in THF improved the product yield
(entries 4−5), and the conversion to 5a was significantly
improved using acetic acid (AcOH) as an additive (entries 6−7).
This finding can be attributed to the reactivity of the sulfinic
acids under acidic conditions. TBAF with a large excess of AcOH
gave exclusively desilylated product. Reactions in other solvents
afforded 5a in similar yields, whereas dioxane and dimethyl-
formamide gave 5a in slightly lower yields (entries 8−13).
Although chloroform was applicable in this reaction, it required
2.5 equiv of TBAF and longer reaction time (entry 14). Reaction
in toluene yielded 5a in 54% along with 11% of isoxazoline 6
(entry 15). Silver fluoride gave cyclocondensation product 6
exclusively (entry 16).13b Trifluoromethanesulfonic acid16
afforded 2-isoxazoline 7, probably derived from 6 after the
removal of the toluenesulfonyl group. It is noteworthy that the
reaction (entry 6) was completed within 10 min. The rapid
conversions of nitrosoallenes compared to that of nitrosoalkenes7,8
Following our mechanistic rationale (Table 1), we speculated
that other nucleophiles could be installed and thus examined
the α-functionalizations of enoximes with various nucleophilic
reagents. However, because of the strong nucleophilicity of
the in situ generated sulfinates,17 formation of undesired vinyl
sulfones was inevitable even in the presence of a large excess of
B
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Table 2. Scope of Substrates and Sulfones
ab
,
entry
R1
R2
R3
R4
yield [%]
1
2
3
4
5
Ph
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
94 (5b)
96 (5c)
96 (5d)
88 (5e)
91 (5f)
63 (5g)
26 (5h)
51 (8h)
22 (5i)
53 (8i)
60 (5j)
96 (5k)
85 (5l)
4-Cl-C6H4
4-F-C6H4
4-MeO-C6H4
Me
c
6
Mes
7
8
4-tol
4-tol
4-Br-C6H4
Ph
Ph
9
10
11
12
13
14
15
4-tol
4-tol
4-tol
4-tol
4-tol
4-tol
4-tol
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
c-Hex
PhOCH2
TIPSCC-(CH2)5
n-Bu
84 (5m)
98 (5n)
91 (5o)
4-Cl-C6H4
4-Cl-C6H4
n-Bu
4-MeO-C6H4
2-Me-C6H5
4-MeO-C6H4
d
n-Bu
Ph
92 (5p)
a
b
c
d
1
Isolated yield. Obtained as a single isomer on oxime. Performed at rt. E/Z ratio = 1:19 determined by H NMR.
the additional nucleophiles. After extensive examination of
trapping reagents18 of sulfinates and oxidizers to sulfonates19
(MeI, acrylates, propiolates, DCC, NBS, iodine, oxone, etc.),
we were pleased to discover azodicarboxylates20 as power-
ful and selective scavenging reagents. In the absence of
azodicarboxylates, 1.5 equiv of diethylamine did not give the
adduct 9a (Scheme 2). Excess use of amine could afford the
be detected in the absence of the scavenger because of rapid
sulfonylation.
We next turned to the α-substitution reaction with additional
nucleophiles (Scheme 3).23 When reactive nucleophiles with
the scavengers were used, the trapping step was performed
at low temperature prior to the addition of the nucleophile.
Under these conditions and nucleophiles, addition of acetic
acid was unnecessary. Acyclic as well as cyclic amino groups
were successfully introduced to obtain α-amino enoximes 9a−e
in good to excellent yields. TsNH2 could be introduced in
moderate yield, whereas vinyl imides 9g−h and nitroolefin 9i
were obtained in high yields. Efficient synthon vinyl azide 9j24
was afforded in excellent yield as an inseparable mixture with
2H-azirine 9j′. Vinyl azide 9j was an unstable compound and
was slowly converted to azirine 9j′ even under refrigeration.
9j′ could also be selectively prepared in a one-pot reaction in 62%
yield. The crystalline 9i and 9j′ were subjected to X-ray crystal-
lographic analysis (see the Supporting Information). Nitro-
soallenes allowed nucleophilic fluorination to give 9k simply using
commercially available weak fluorinating agent TBAF. Although
methanol gave 9l in low yield, the acetoxy moiety was efficiently
installed, and a thiol nucleophile produced 9n in 86% yield.
Moreover, introduction of the scavenger facilitates complete
transfer of the additional sulfinate to afford 5b from tosylamide
2a. The carbon nucleophile cyanide was also successfully
installed in excellent yield to give 9o, which could be applicable
in the synthetic derivatives of entacapone for Parkinson’s
disease and antitumor CC-5079.25 The absence of isonitriles is
probably due to the same as 1,4-addition to enones.26 Upon
completion of the reactions in the presence of azodicarbox-
ylates, formation of sulfonylhydrazides 10a−b27 was observed.
It should be noted that 9d, 9f, and 9k−m could not be obtained
without the addition of scavengers.
Scheme 2. Addition of Azodicarboxylate as a Scavenger of
Sulfinates
desired compound, but only in moderate to fair yields even
with diethylamine as a solvent. However, in the presence of the
discovered scavenger, the desired 9a was successfully afforded
in excellent yield without the undesired tosyl adduct 5a. The
poorly electrophilic 1,1′-(azodicarbonyl)dipiperidine21 was not
successful, whereas the reaction in the presence of diethyl
(DEAD), diisopropyl (DIAD), or dimethoxyethyl azodicarbox-
ylate (DMEAD) as sulfinate traps could be performed at
0 °C as well as at lower temperature. At −60 to −78 °C, the
peppermint green color of the solution, analogous to that of
nitrosoalkynes6a,22 (see the Supporting Information) and
probably emitted by the nitrosoallenes, was maintained for
more than 3 h, and the following substitution with additional
nucleophiles proceeded successfully. No greenish color could
After identification of a suitable sulfinate scavenger allowing
reactive nitrosoallenes to remain in the flask, low temperature
IR spectra of reaction mixtures were tested for spectroscopic
C
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Scheme 3. α-Functionalizations with Additional
Nucleophiles
EXPERIMENTAL SECTION
■
General Information. NMR spectra were recorded at 500 MHz
for H NMR, 126 MHz for 13C NMR, and 471 MHz for 19F NMR.
1
Chemical shifts are reported as δ values in ppm and calibrated by
1
residual solvent peaks (CDCl3, δ 7.26 for H NMR, δ 77.00 for 13C
NMR; DMSO-d6, δ 2.50 for 1H NMR, δ 39.52 for 13C NMR),
tetramethylsilane (δ 0 for 1H NMR), or hexafluorobenzene (δ −162.0
for 19F NMR). Abbreviations are as follows: s (singlet), d (doublet),
t (triplet), q (quartet), br (broad peak), m (complex multiplet). Mass
spectra were by EI (70 eV), CI, FAB, or ESI using a double-focusing
mass spectrometer. Low temperature IR spectra were measured with
a cryostat (CaF2 windows). The purification of materials which
were hard to purify with silica gel was performed using a preparative
high-performance liquid chromatography (HPLC) or recycling gel-
permeation chromatography (GPC).
Preparation of Propargyl Alcohols (3a, 3h−p). 1,1-Diphenyl-
2-hexyn-1-ol (3a).
Prepared in accordance with our previous report.3a,b
1,1,2-Triphenyl-2-propyn-1-ol (3h).
Prepared in accordance with our previous report.3a,b
3-(4-Bromophenyl)-1,1-diphenylprop-2-yn-1-ol (3i).
To a stirred solution of 1-bromo-4-ethynylbenzene (481 mg, 2.66 mmol)
in THF (25 mL) was added lithium hexamethyldisilazide (1.0 M in
THF, 3.8 mL, 3.8 mmol) at 0 °C under a nitrogen atmosphere. After 1 h,
benzophenone (456 mg, 2.50 mmol) was added to the mixture in one
portion, and the reaction mixture was stirred overnight at room tem-
perature. The reaction was quenched with saturated ammonium chloride
aqueous solution. The mixture was extracted with ethyl acetate and was
washed with water and brine. The combined organic layers were dried
over sodium sulfate and were concentrated in vacuo. The residue was
purified by flash silica gel column chromatography (hexane/ethyl acetate =
50/1 to 20/1 to 10/1) to afford propargyl alcohol 3i (902.1 mg, 99%).
Pale yellow oil; Rf value 0.15 (hexane/ethyl acetate = 10/1); IR (NaCl,
neat) νmax 3428, 3059, 3028, 1486, 1449, 1334, 1011, 823, 751,
698 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.64 (d, 4H, J = 7.5 Hz), 7.45
(d, 2H, J = 8.5 Hz), 7.36−7.33 (m, 6H), 7.27 (t, 2H, J = 7.5 Hz), 2.92
(s, 1H); 13C NMR (126 MHz, CDCl3) δ 144.6, 133.2, 131.6, 128.3,
127.8, 126.0, 122.9, 121.2, 92.7, 86.1, 74.8; HRMS (ESI) calcd for
C21H1579BrNaO [M + Na]+ 385.02040, found 385.02063.
a
−78 or −60 °C for 5 min; then the nucleophile was added and the
b
1
mixture was stirred at 0 °C for 10 min. Determined by H NMR.
c
d
2.7 equiv of TBAF was used. 0 °C for 10 min, then reflux for 15 min.
4.0 equiv of TBAF was used.
e
1,1-Diphenyl-2-propyn-1-ol (3j).
evidence of nitrosoallenes (see the Supporting Information).
The spectra showed a new absorption at 1925 cm−1, probably
derived from allene stretch (1940 cm−1 for 2a). Unfortunately,
the absorption from a nitroso group of 1a is not clear because
of overlap with the absorption peaks from THF, substituents
of nitrosoallene, and other reagents at the expected region
(1500−1400 cm−1).6a,9c,28
Prepared in accordance with our previous report.3a,b
1,1-Diphenyl-2-cyclohexyl-2-propyn-1-ol (3k).
In conclusion, we have developed a synthesis of α-functionalized
enoximes via novel nitrosoallenes. Various nucleophiles, including
carbon nucleophiles, were successfully attached to the α-position of
enoximes. We believe that the field of synthetic organic chemistry
will find utility for these novel reactive species.29 Further investiga-
tions on developing preparation methods of allenylsulfonamides,
the reactivity and physical properties of nitrosoallenes under
modified conditions, and their applications are currently in progress.
Prepared in accordance with our previous report.3a,b
1,1-Diphenyl-4-phenoxy-2-butyn-1-ol (3l).
Prepared in accordance with our previous report.3a,b
D
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1,1-Diphenyl-10-(triisopropylsilyl)deca-2,9-diyn-1-ol (3m).
7.0 Hz), 1.43 (tq, 2H, J = 7.5, 7.5 Hz), 0.92 (t, 3H, J = 7.5 Hz); 13C NMR
(126 MHz, CDCl3) δ 144.4, 142.1, 136.2, 131.9, 128.1, 127.7, 127.6,
126.4, 125.8, 125.3, 88.4, 81.9, 73.9, 30.6, 22.0, 20.9, 18.6, 13.6; HRMS
(ESI) calcd for C20H22ONa [M + Na]+ 301.15683, found 301.15625.
Preparation of Siloxysulfonamides (4a−g). N-((tert-Butyl-
dimethylsilyl)oxy)-4-toluenesulfonamide (4a).
To a stirred solution of 1,8-nonadiyne (602.7 mg, 5.00 mmol) in
THF (65 mL) under a nitrogen atmosphere was added n-butyllithium
(1.63 M in hexane, 5.1 mL, 8.3 mmol) at −78 °C, and the mixture
was stirred for 1 h. After warming up to 0 °C, benzophenone (911 mg,
5.00 mmol) was added, and the mixture was stirred at ambient
temperature for 3 h. After cooling back to −78 °C, additional
n-butyllithium (1.63 M in hexane, 5.1 mL, 8.3 mmol) was added and
triisopropylsilyl chloride (1.18 mL, 5.50 mmol) was added at 0 °C.
Stirred overnight at ambient temperature, reaction mixture was
extracted with ether, and the organic layer was washed with water
and brine. The combined organic layers were dried over sodium sulfate
and concentrated in vacuo. The resulting residue was purified by flash
silica gel column chromatography (hexane/ethyl acetate = 99/1 to
90/10), followed by recycling HPLC separation to afford propargyl
alcohol 3m (817.0 mg, 35%). Colorless oil; Rf = 0.32 (hexane/ethyl
acetate = 10/1); IR (NaCl, neat) νmax 3462, 3060, 2940, 2864, 2170,
Prepared in accordance with Fukuyama’s report.12
N-((tert-Butyldimethylsilyl)oxy) Benzenesulfonamide (4b).
To a stirred solution of O-tert-butyldimethylsilylhydroxylamine
(362.5 mg, 2.46 mmol)30 in THF (8.5 mL) were added pyridine
(0.4 mL, 4.92 mmol) and benzenesulfonyl chloride (0.31 mL,
2.46 mmol) at room temperature. After 24 h, the reaction was quenched
with saturated ammonium chloride aqueous solution. The reaction
mixture was extracted with ether and was washed with water and brine.
The combined organic layers were dried over sodium sulfate and were
concentrated in vacuo. The resulting residual solid was purified by silica
gel column chromatography (hexane/ethyl acetate = 8/1 to 6/1) to
afford benzenesulfonamide 4b (464.2 mg, 66%). White solid; Rf value
0.30 (hexane/ethyl acetate = 7/1); mp 58−60 °C; IR (NaCl, neat) νmax
1
1449, 1329, 1204, 1139, 996 cm−1; H NMR (500 MHz, CDCl3)
δ 7.60 (d, 4H, J = 7.0 Hz), 7.31 (dd, 4H, J = 7.5 Hz, J = 7.0 Hz), 7.24
(t, 2H, J = 7.5 Hz), 2.71 (s, 1H), 2.34 (t, 2H, J = 7.0 Hz), 2.25 (t, 2H,
J = 7.0 Hz), 1.62 (tt, 2H, J = 7.0, 6.5 Hz), 1.58−1.52 (m, 4H), 1.11−
0.98 (m, 21H); 13C NMR (126 MHz, CDCl3) δ 145.4, 128.1, 127.5,
126.0, 108.9, 88.1, 83.1, 80.2, 74.4, 28.3, 28.13, 28.11, 19.7, 18.9, 18.6,
11.3; HRMS (ESI) calcd for C31H42OSiNa [M + Na]+ 481.29026,
found 481.29001.
1
3188, 2929, 1254, 1167, 834, 787, 741 cm−1; H NMR (500 MHz,
CDCl3) δ 7.92 (dd, 2H, J = 7.5, 1.0 Hz), 7.65 (dd, 1H, J = 7.5, 1.0 Hz),
7.55 (dd, 2H, J = 7.5, 7.5 Hz), 6.55 (s, 1H), 0.88 (s, 9H), 0.17 (s, 6H);
13C NMR (126 MHz, CDCl3) δ 136.0, 133.8, 128.8, 25.8, 17.9, −5.5;
1,1-Di(4-chlorophenyl)-2-hexyn-1-ol (3n).
HRMS (FAB) calcd for C12H22NO3SSi [M + H]+ 288.1089, found
288.1090.
N-((tert-Butyldimethylsilyl)oxy)-4-chlorobenzenesulfonamide
(4c).
Prepared in accordance with our previous report.3a,b
1,1-Di(4-methoxyphenyl)-2-hexyn-1-ol (3o).
4c (685.5 mg, 63%) was obtained from O-tert-butyldimethylsilylhy-
droxylamine (500 mg, 3.39 mmol), pyridine (0.5 mL, 6.78 mmol), and
4-chlorobenzenesulfonyl chloride (716.5 mg, 3.39 mmol) after silica
gel column chromatography (hexane/ethyl acetate = 8/1 to 6/1).
White solid; Rf value 0.28 (hexane/ethyl acetate = 7/1); mp 98−
99 °C; IR (NaCl, neat) νmax 3199, 2929, 1337, 1169, 1092, 831,
767 cm−1; H NMR (500 MHz, CDCl3) δ 7.85 (d, 2H, J = 8.5 Hz),
1
7.53 (d, 2H, J = 8.5 Hz), 6.50 (s, 1H), 0.89 (s, 9H), 0.19 (s, 6H); 13
C
Prepared in accordance with our previous report.3a,b
1-Phenyl-1-(o-tolyl)hept-2-yn-1-ol (3p).
NMR(125 MHz, CDCl3) δ 140.5 134.5, 130.3, 129.2, 25.8, 17.9, −5.5;
HRMS (FAB) calcd for C12H21ClNO3SSi [M + H]+ 322.0700, found
322.0694.
N-((tert-Butyldimethylsilyl)oxy)-4-fluorobenzenesulfonamide
(4d).
To a stirred solution of 1-hexyne (1.48 mL, 13.0 mmol) in THF
(20 mL) a under nitrogen atmosphere was added n-butyllithium
(1.63 M in hexane, 7.36 mL, 12.0 mmol) at 0 °C. After 1 h,
2-methylbenzophenone (1.81 mL, 10.0 mmol) was added to the
mixture, which was stirred overnight at room temperature. The
reaction mixture was extracted with ether and was washed with water
and brine. The combined organic layers were dried over sodium sulfate
and concentrated in vacuo. The resulting residue was purified by flash
silica gel column chromatography (hexane/ethyl acetate = 100/1 to
50/1 to 20/1) to afford propargyl alcohol 3p (2.68 g, 97%). Pale
yellow oil; Rf = 0.35 (hexane/ethyl acetate = 10/1); IR (NaCl, neat)
νmax 3545, 3458, 3060, 2957, 2931, 2871, 2228, 1601, 1484, 1448,
1328, 999 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.95 (d, 1H, J = 8.0 Hz),
7.49 (d, 2H, J = 6.5 Hz), 7.32−7.21 (m, 5H), 7.10 (d, 1H, J = 7.0 Hz),
2.61 (s, 1H), 2.32 (t, 2H, J = 7.0 Hz), 2.08 (s, 3H), 1.56 (tt, 2H, J = 7.5,
4d (1.38 g, 65%) was obtained from O-tert-butyldimethylsilyl-
hydroxylamine (1.03 g, 6.99 mmol), pyridine (1.1 mL, 14 mmol), and
4-fluorobenzenesulfonyl chloride (1.36 g, 6.99 mmol) after silica gel
column chromatography (hexane/ethyl acetate = 5/1) to afford
sulfonamide. White solid; Rf value 0.73 (hexane/ethyl acetate = 2/1);
mp 106−107 °C; IR (NaCl, neat) νmax 3189, 2929, 1590, 1337, 1166,
1
837, 729 cm−1; H NMR (500 MHz, CDCl3) δ 7.95−7.92 (m, 2H),
7.26−7.21 (m, 2H), 6.52 (s, 1H), 0.88 (s, 9H), 0.18 (s, 6H); 13C NMR
(126 MHz, CDCl3) δ; 165.9 (d, JC‑F = 256 Hz), 132.0 (d, JC‑F = 2.5 Hz),
131.7 (d, JC‑F = 9.7 Hz), 116.2 (d, JC‑F = 22.8 Hz), 25.8, 17.9, −5.5;
19F NMR (471 MHz, CDCl3) δ −103.6; HRMS (ESI) calcd for
C12H20FNO3SSiNa [M + Na]+ 328.08149, found 328.08029.
E
DOI: 10.1021/acs.joc.5b02364
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
N-((tert-Butyldimethylsilyl)oxy)-4-methoxybenzenesulfonamide
(4e).
N-((tert-Butyldimethylsilyl)oxy)-N-(1,1-diphenylhepta-1,2-dien-3-yl)-
4-methylbenzenesulfonamide (2a).
To a stirred solution of hydroxylamine hydrochloride (69.5 mg,
1.00 mmol) and tert-butyldimethylsilyl chloride (151 mg, 1.00 mmol)
in dimethylformamide was added triethylamine (0.65 mL, 4.5 mmol)
dropwise at 0 °C. The mixture was warmed up to room temperature
and was stirred for 30 min. After cooling the mixture again to 0 °C,
4-methoxybenzenesulfonyl chloride (198 mg, 0.95 mmol) was added;
then the mixture was stirred overnight at room temperature. The
mixture was extracted with ether and was washed with water, 20%
citric acid aqueous solution, and brine. The combined organic layers
were dried over sodium sulfate and were concentrated in vacuo. The
resulting residual solid was purified by recrystallization (hexane/ethyl
acetate = 10/1) to afford methoxybenzenesulfonamide 4e (229.8 mg,
75%). White solid; Rf value 0.22 (hexane/ethyl acetate = 4/1); mp
101−103 °C; IR (NaCl, neat) νmax 3193, 2930, 2859, 1598, 1499,
1067 mg (65%) of product 2a was obtained from propargyl alcohol 3a
(3.0 mmol, 793.1 mg) with sulfonamide 4a (904.4 mg, 3.0 mmol),
activated molecular sieves 4A (1200 mg), and trimethylsilyl trifluoro-
methanesulfonate (54 μL, 0.3 mmol) (silica gel column chromatog-
raphy: hexane/diethyl ether = 40/1 to 20/1), followed by recrystalli-
zation (hexane). Pale yellow solid; Rf value 0.45 (hexane/ethyl acetate =
9/1); mp 94−96 °C; IR (NaCl, neat) νmax 3058, 3030, 2956, 2929,
2858, 1940, 1598, 1363, 1173, 829 cm−1; 1H NMR (500 MHz, CDCl3)
δ 7.72 (d, 2H, J = 8.5 Hz), 7.27−7.17 (m, 8H), 6.97 (br, 4H), 2.58
(dd, 2H, J = 8.0 Hz), 2.45 (s, 3H), 1.62 (tt, 2H, J = 8.0, 7.0 Hz), 1.38
(tq, 2H, J = 7.5, 7.0 Hz), 0.91 (t, 3H, J = 7.0 Hz), 0.79 (s, 9H), 0.07
(br, 6H); 13C NMR (125 MHz, CDCl3) δ 200.6, 144.3, 136.7, 130.1,
130.0, 129.2, 128.8, 127.9, 127.5, 119.4, 117.9, 32.3, 29.8, 25.8,
22.6, 21.8, 17.8, 13.9, −4.8; HRMS (ESI) calcd for C32H41NO3SSiNa
[M + Na]+ 570.24741, found 570.24791.
1
1329, 1259, 1160, 1093, 1018 cm−1; H NMR (500 MHz, CDCl3) δ
7.84 (d, 2H, J = 8.5 Hz), 7.00 (d, 2H, J = 8.5 Hz), 6.47 (br, 1H), 3.89
(s, 3H), 0.88 (s, 9H), 0.17 (s, 6H); 13C NMR (126 MHz, CDCl3) δ
163.8, 131.0, 127.5, 114.0, 55.7, 25.8, 17.9, −5.5; HRMS (ESI) calcd
for C13H23NNaO4SSi [M + Na]+ 340.10147, found 340.10054.
N-((tert-Butyldimethylsilyl)oxy)methanesulfonamide (4f).
N-((tert-Butyldimethylsilyl)oxy)-N-(1,1-diphenylhepta-1,2-dien-3-yl)-
benzenesulfonamide (2b).
238.8 mg (40%) of product 2b was obtained from propargyl alcohol
3a (295 mg, 1.11 mmol), sulfonamide 4b (319.1 mg, 1.11 mmol),
activated molecular sieves 4A (350 mg), and trimethylsilyl trifluoro-
methanesulfonate (20 μL, 0.111 mmol) (silica gel column chroma-
tography: hexane/diethyl ether = 25/1). Pale yellow oil; Rf value 0.53
(hexane/ethyl acetate = 8/1); IR (NaCl, neat) νmax 2957, 1937, 1447,
1362, 1253, 1183, 830, 578 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.88
(dd, 2H, J = 7.0, 1.5 Hz), 7.64 (td, 1H, J = 7.5, 1.5 Hz), 7.42 (t, 1H, J =
7.5 Hz), 7.28−7.22 (m, 7H), 6.97 (br, 4H), 2.59 (t, 2H, J = 7.5 Hz),
1.65 (tt, 2H, J = 7.5, 7.5 Hz), 1.40 (tq, 2H, J = 7.5, 7.5 Hz), 0.93
(t, 3H, J = 7.5 Hz), 0.81 (s, 9H), 0.10 (s, 6H); 13C NMR (126 MHz,
CDCl3) δ 200.6, 136.6, 133.6, 133.2, 130.0, 128.8, 128.5, 128.0, 127.6,
119.2, 118.1, 32.2, 29.7, 25.8, 22.6, 17.8, 13.9, −4.9; HRMS (ESI)
calcd for C31H39NO3SSiNa [M + Na]+ 556.23176, found 556.23184.
N-((tert-Butyldimethylsilyl)oxy)-4-chloro-N-(1,1-diphenylhepta-
1,2-dien-3-yl)benzenesulfonamide (2c).
4f (892.9 mg, 66%) was obtained from hydroxylamine hydrochloride
(417.1 mg, 6.0 mmol), tert-butyldimethylsilyl chloride (904.3 mg,
6.0 mmol), triethylamine (4.2 mL, 30 mmol), and methanesulfonyl
chloride (0.47 mL, 6.0 mmol) after silica gel column chromatography
(hexane/ethyl acetate = 3/1). White solid; Rf value 0.40 (hexane/ethyl
acetate = 3/1); mp 31−32 °C; IR (NaCl, neat) νmax 3210, 2931, 1330,
1
1254, 1168, 833, 788 cm−1; H NMR (500 MHz, CDCl3) δ 6.85
(s, 1H), 3.03 (s, 3H), 0.93 (s, 9H), 0.20 (s, 6H); 13C NMR (126 MHz,
CDCl3) δ 35.6, 25.8, 17.9, −5.5; Anal. Calcd for C7H19NOSSi: C.
37.30%; H. 8.50%; N: 6.21%, found: C. 37.31%; H. 8.79%; N: 6.22%.
N-((tert-Butyldimethylsilyl)oxy)-2,4,6-trimethylbenzenesulfon-
amide (4g).
4g (800.6 mg, 49%) was obtained from O-tert-butyldimethylsilylhy-
droxylamine (736.5 mg, 5.0 mmol), pyridine (0.8 mL, 10 mmol), and
mesitylsulfonyl chloride (1.09 g, 5.0 mmol) after silica gel column
chromatography (hexane/ethyl acetate = 15/1 to 10/1). White solid;
Rf value 0.43 (hexane/ethyl acetate = 7/1); mp 99−101 °C; IR (NaCl,
1
neat) νmax 3168, 2930, 1603, 1333, 1254, 1165, 831 cm−1; H NMR
(500 MHz, CDCl3) δ 6.98 (s, 2H), 6.51 (s, 1H), 2.65 (s, 6H), 2.32
(s, 3H), 0.84 (s, 9H), −0.02 (s, 6H); 13C NMR (126 MHz, CDCl3) δ
143.5, 141.2, 131.9, 130.0, 25.8, 23.2, 21.0, 17.9, −5.8; HRMS (ESI)
calcd for C15H27NO3SSiNa [M + Na]+ 352.13786, found 352.13748.
Preparation of Allenamides (2a−p). Allenamides were prepared
by modified conditions of Lu and Wang’s procedure.13 To a stirred
solution of propargyl alcohol, sulfonamide (1 equiv), and activated mole-
cular sieves 4A (400 g/mol to propargyl alcohol) in dichloromethane
(0.1 M) was added trimethylsilyl trifluoromethanesulfonate (0.1 equiv)
slowly at −78 °C. The mixture was stirred overnight with gradual
warming up to room temperature. The mixture was filtrated by
short plug silica gel column chromatography,followed by concentration
in vacuo. The obtained residue was purified by silica gel column
chromatography to afford allenamides.
199.4 mg (40%) of product 2c was obtained from propargyl alcohol 3a
(227.4 mg, 0.86 mmol), sulfonamide 4c (277.9 mg, 0.86 mmol),
activated molecular sieves 4A (344 mg), and trimethylsilyl trifluoro-
methanesulfonate (16 μL, 0.086 mmol) (silica gel column chromatog-
raphy: hexane/diethyl ether = 25/1). Pale yellow oil; Rf value 0.44
(hexane/ethyl acetate = 7/1); IR (NaCl, neat) νmax 2956, 2929, 1938,
1367, 1182, 1091, 829, 756 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.73
(d, 2H, J = 8.5 Hz), 7.24−7.29 (m, 8H), 6.96 (br, 4H), 2.61 (t, 2H, J =
8.0 Hz), 1.63 (tt, 2H, J = 8.0, 7.5 Hz), 1.39 (qt, 2H, J = 7.5, 7.5 Hz),
0.93 (t, 3H, J = 7.5 Hz), 0.81 (s, 9H), 0.12 (s, 6H); 13C NMR
(126 MHz, CDCl3) δ 200.5, 140.3, 136.5, 131.33, 131.28, 128.8, 128.7,
128.1, 127.8, 119.2, 118.4, 32.7, 29.7, 25.8, 22.6, 17.8, 13.9, −4.74;
HRMS (FAB) calcd for C31H39ClNO3SSi [M + H]+ 568.2108, found
568.2107.
F
DOI: 10.1021/acs.joc.5b02364
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
N-((tert-Butyldimethylsilyl)oxy)-N-(1,1-diphenylhepta-1,2-dien-3-yl)-
N-((tert-Butyldimethylsilyl)oxy)-N-(1,1-diphenylhepta-1,2-dien-3-yl)-
4-fluorobenzenesulfonamide (2d).
2,4,6-trimethylbenzenesulfonamide (2g).
153.9 mg (28%) of product 2d was obtained from propargyl alcohol
3a (264 mg, 1.00 mmol), sulfonamide 4d (305 mg, 1.00 mmol),
activated molecular sieves 4A (400 mg), and trimethylsilyl trifluoro-
methanesulfonate (18 μL, 0.10 mmol) (silica gel column chromatog-
raphy: hexane/ethyl acetate = 99/1 to 95/5, followed by recycling
HPLC separation). Colorless oil; Rf = 0.59 (hexane/ethyl acetate =
10/1); IR (NaCl, neat) νmax 3060, 3027, 2957, 2930, 2859, 1937, 1592,
1493, 1367, 1253, 1238, 1181, 1155, 1089 cm−1; 1H NMR (500 MHz,
CDCl3) δ 7.79 (dd, 2H, J = 9.0, 5.0 Hz), 7.28−7.22 (m, 6H), 7.00−
6.95 (m, 6H), 2.59 (t, 2H, J = 7.5 Hz), 1.62 (tt, 2H, J = 7.5, 7.5 Hz),
1.38 (tq, 2H, J = 7.5, 7.5 Hz), 0.91 (t, 3H, J = 7.5 Hz), 0.79 (s, 9H),
53.7 mg (16%) of product 2g was obtained from propargyl alcohol 3a
(152.5 mg, 0.576 mmol), sulfonamide 4g (190.1 mg, 0.576 mmol),
molecular sieves 4A (230 mg), and trimethylsilyl trifluoromethanesul-
fonate (10 μL, 0.0576 mmol) (silica gel column chromatography:
hexane/diethyl ether = 25/1). pale yellow oil; Rf value 0.52 (hexane/
ethyl acetate = 8/1); IR (NaCl, neat) νmax 2956, 2929, 1942, 1341,
1
1256, 1166, 830, 697 cm−1; H NMR (500 MHz, CDCl3) δ 7.45
(d, 4H, J = 7.0 Hz), 7.36−7.29 (m, 6H), 6.92 (s, 2H), 2.69 (s, 6H),
2.67 (t, 2H, J = 8.0 Hz), 2.30 (s, 3H), 1.60 (tt, 2H, J = 8.0, 7.5 Hz),
1.41 (tq, 2H, J = 7.5, 7.5 Hz), 0.91 (t, 3H, J = 7.5 Hz), 0.65 (s, 9H),
−0.44 (s, 6H); 13C NMR (126 MHz, CDCl3) δ 203.6, 143.4, 142.1,
136.1, 131.8, 130.7, 129.0, 128.2, 127.7, 117.1, 116.9, 30.0, 29.3, 25.6,
23.3, 22.5, 21.0, 17.6, 14.0, −5.8; HRMS (ESI) calcd for
C34H45NO3SSiNa [M + Na]+ 598.27871, found 598.27887.
0.10 (br, 6H); 13C NMR (126 MHz, CDCl3) δ 200.5, 165.8 (d, JC‑F
=
256 Hz), 136.5, 132.7 (d, JC‑F = 9.6 Hz), 128.8, 128.7, 128.0, 127.8,
119.3, 118.3, 115.8 (d, JC‑F = 22.8 Hz), 32.6, 29.7, 25.8, 22.6, 17.8,
13.9, −4.7; 19F NMR (471 MHz, CDCl3) δ −103.9; HRMS (ESI)
calcd for C31H38FNNaO3SSi [M + Na]+ 574.22234, found 574.22245.
N-((tert-Butyldimethylsilyl)oxy)-N-(1,1-diphenylhepta-1,2-dien-3-yl)-
4-methoxybenzenesulfonamide (2e).
N-((tert-Butyldimethylsilyl)oxy)-4-methyl-N-(1,3,3-triphenyl-
propa-1,2-dien-1-yl)benzenesulfonamide (2h).
129.9 mg (46%) of product 2h was obtained from propargyl alcohol
3h (142 mg, 0.500 mmol), sulfonamide 4a (151 mg, 0.500 mmol),
activated molecular sieves 4A (201 mg), and trimethylsilyl trifluoro-
methanesulfonate (9 μL, 0.05 mmol) (silica gel column chromatog-
raphy: hexane/ethyl acetate = 200/1 to 100/1 to 50/1). Pale yellow
solid; Rf value 0.46 (hexane/ethyl acetate = 10/1); mp 54−57 °C; IR
(NaCl, neat) νmax 3057, 2928, 2857, 1912, 1362, 1172 cm−1; 1H NMR
(500 MHz, CDCl3) δ 7.72 (d, 2H, J = 7.0 Hz), 7.68 (d, 2H, J =
8.0 Hz), 7.42 (t, 2H, J = 8.5 Hz), 7.30−7.36 (m, 3H), 7.25 (dd, 4H, J =
8.5, 8.5 Hz), 7.08 (d, 2H, J = 8.0 Hz), 7.00 (d, 4H, J = 7.5 Hz), 2.42
(s, 3H), 0.89 (s, 9H), 0.18 (s, 6H); 13C NMR (125 MHz, CDCl3)
δ 205.1, 144.3, 135.7, 134.3, 130.2, 129.7, 129.0, 128.9, 128.4, 128.1,
128.0, 126.3, 120.7, 120.2, 25.8, 21.8, 17.8, −4.7; HRMS (ESI) calcd
for C34H37NNaO3SSi [M + Na]+ 590.2161, found 590.2153.
374.4 mg (65%) of product 2e was obtained from propargyl alcohol 3a
(264 mg, 1.00 mmol), sulfonamide 4e (317 mg, 1.00 mmol), activated
molecular sieves 4A (400 mg), and trimethylsilyl trifluoromethanesul-
fonate (18 μL, 0.10 mmol) (silica gel column chromatography: hexane/
ethyl acetate = 99/1 to 4/1). Pale yellow oil; Rf = 0.35 (hexane/ethyl
acetate = 10/1); IR (NaCl, neat) νmax 3060, 2954, 2928, 2854, 1937,
1
1596, 1496, 1362, 1260, 1167, 1092, 1027 cm−1; H NMR (500 MHz,
CDCl3) δ 7.75 (d, 2H, J = 8.5 Hz), 7.26−7.19 (m, 6H), 6.93 (br, 4H),
6.85 (d, 2H, J = 8.5 Hz), 3.86 (s, 3H), 2.60 (t, 2H, J = 8.0 Hz), 1.63
(tt, 2H, J = 8.0, 7.5 Hz), 1.39 (tq, 2H, J = 7.5, 7.0 Hz), 0.92 (t, 3H, J =
7.0 Hz), 0.77 (s, 9H), 0.05 (s, 6H); 13C NMR (126 MHz, CDCl3) δ
200.6, 163.7, 136.8, 132.1, 128.8, 127.9, 127.5, 124.4, 119.6, 117.9, 113.8,
55.5, 32.4, 29.8, 25.8, 22.6, 17.8, 13.9, −4.8; HRMS (ESI) calcd for
C32H41NO4SSiNa [M + Na]+ 586.2423, found 586.2412.
N-(1-(4-Bromophenyl)-3,3-diphenylpropa-1,2-dien-1-yl)-N-((tert-
butyldimethylsilyl)oxy)-4-methylbenzenesulfonamide (2i).
N-((tert-Butyldimethylsilyl)oxy)-N-(1,1-diphenylhepta-1,2-dien-3-yl)-
methanesulfonamide (2f).
95.7 mg (29%) of product 2i was obtained from propargyl alcohol 3i
(182 mg, 0.500 mmol), sulfonamide 4a, activated molecular sieves
4A (203 mg), and trimethylsilyl trifluoromethanesulfonate (9 μL,
0.05 mmol) (silica gel column chromatography: hexane/ethyl acetate =
100/1 to 50/1 to 20/1). Pale yellow solid; Rf value 0.46 (hexane/ethyl
acetate = 10/1); mp 56−58 °C; IR (NaCl, neat) νmax 3058, 2955, 2928,
1910, 1597, 1485, 1362, 1254, 1171 cm−1; 1H NMR (500 MHz,
CDCl3) δ 7.66 (d, 2H, J = 8.0 Hz), 7.51 (d, 2H, J = 8.5 Hz), 7.48
(d, 2H, J = 8.5 Hz), 7.30 (t, 2H, J = 7.5 Hz), 7.22 (dd, 4H, J = 7.5, 7.5 Hz),
7.06 (d, 2H, J = 8.0 Hz), 6.92 (d, 4H, J = 7.5 Hz), 2.40 (s, 3H),
0.83 (s, 9H), 0.10 (s, 6H); 13C NMR (126 MHz, CDCl3) δ 205.0,
144.5, 135.5, 133.5, 131.6, 130.2, 129.6, 129.1, 128.9, 128.3, 128.2,
127.8, 122.0, 121.2, 119.6, 25.8, 21.8, 17.8, −4.7; HRMS (ESI) calcd
for C34H3679BrNaNO3SSi [M + Na]+ 668.1266, found 668.1268.
62.2 mg (13%) of product 2f was obtained from propargyl alcohol 3a
(396.6 mg, 1.5 mmol), sulfonamide 4f (338.1 mg, 1.5 mmol), activated
molecular sieves 4A (600 mg), and trimethylsilyl trifluoromethanesulfonate
(27 μL, 0.15 mmol) (silica gel column chromatography: hexane/
diethyl ether = 25/1). Pale yellow oil; Rf value 0.58 (hexane/ethyl
acetate = 8/1); IR (NaCl, neat) νmax 2956, 2929, 1939, 1358, 1171,
954, 830, 697 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.37−7.32
(m, 10H), 2.79 (s, 3H), 2.58 (t, 2H, J = 8.0 Hz), 1.59 (tt, 2H, J = 8.0,
7.0 Hz), 1.37 (qt, 2H, J = 8.0, 7.0 Hz), 1.80 (t, 3H, J = 7.0 Hz), 0.90
(s, 9H), 0.16 (s, 6H); 13C NMR (126 MHz, CDCl3) δ 200.6, 135.8,
128.6, 128.4, 128.1, 120.3, 119.0, 33.0, 31.0, 29.3, 25.8, 22.4, 17.8, 13.9,
−4.7; HRMS (ESI) calcd for C26H37NO3SSiNa [M + Na]+ 494.21611,
found 494.21589.
G
DOI: 10.1021/acs.joc.5b02364
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
N-((tert-Butyldimethylsilyl)oxy)-N-(3,3-diphenylpropa-1,2-dien-1-yl)-
86.8 mg (24%) of product 2m was obtained from propargyl alcohol
3m (226 mg, 0.492 mmol), sulfonamide 4a (148 mg, 0.492 mmol),
activated molecular sieves 4A (197 mg), and trimethylsilyl trifluoro-
methanesulfonate (9 μL, 0.049 mmol) (silica gel column chromatog-
raphy: hexane/ethyl acetate = 19/1). Colorless oil; Rf = 0.52 (hexane/
ethyl acetate = 10/1); IR (NaCl, neat) νmax 3060, 2939, 2862, 2170,
1936, 1598, 1462, 1364, 1253, 1173 cm−1; 1H NMR (500 MHz,
CDCl3) δ 7.70 (d, 2H, J = 8.0 Hz), 7.25 (t, 2H, J = 7.5 Hz), 7.20
(dd, 4H, J = 7.5, 7.0 Hz), 7.16 (d, 2H, J = 8.0 Hz), 6.96 (br, 4H), 2.56
(t, 2H, J = 7.5 Hz), 2.44 (s, 3H), 2.17 (t, 2H, J = 7.0 Hz), 1.63 (tt, 2H,
J = 7.5, 7.5 Hz), 1.53−1.41 (m, 4H), 1.09−0.98 (m, 21H), 0.79
(s, 9H), 0.06 (s, 6H); 13C NMR (126 MHz, CDCl3) δ 200.7, 144.3,
136.6, 130.2, 130.0, 129.2, 128.8, 128.0, 127.6, 119.2, 118.0, 109.0,
80.0, 32.4, 28.7, 28.6, 27.0, 25.9, 21.8, 19.7, 18.6, 17.8, 11.3, −4.8;
HRMS (ESI) calcd for C44H63NO3SSi2Na [M + Na]+ 764.39649,
found 764.39688.
4-methylbenzenesulfonamide (2j).
61.0 mg (12%) of product 2j was obtained from propargyl alcohol 3j
(208 mg, 1.00 mmol), sulfonamide 4a (301 mg, 1.00 mmol), activated
molecular sieves 4A (400 mg), and trimethylsilyl trifluoromethanesul-
fonate (18 μL, 0.10 mmol) (silica gel column chromatography: hexane/
ethyl acetate = 98/2 to 85/15). Yellow oil; Rf value 0.35 (hexane/ethyl
acetate = 10/1); IR (NaCl, neat) νmax 3031, 2955, 2928, 2857, 1950,
1
1365, 1173 cm−1; H NMR (500 MHz, CDCl3) δ 7.79 (d, 2H, J =
8.0 Hz), 7.36 (d, 2H, J = 8.0 Hz), 7.26 (t, 2H, J = 7.5 Hz), 7.17 (br, 4H),
7.11 (s, 1H), 6.96 (br, 4H), 2.56 (s, 3H), 0.74 (s, 9H), −0.03 (br, 6H);
13C NMR (126 MHz, CDCl3) δ 198.5, 144.7, 135.7, 130.2, 129.3, 129.2,
128.8, 128.0, 127.8, 120.6, 106.6, 25.7, 21.9, 17.7, −5.3; HRMS (ESI)
calcd for C28H33NNaO3SSi [M + Na]+ 514.1848, found 514.1847.
N-((tert-Butyldimethylsilyl)oxy)-N-(1-cyclohexyl-3,3-diphenyl-
propa-1,2-dien-1-yl)-4-methylbenzenesulfonamide (2k).
N-(1,1-Bis(4-chlorophenyl)hepta-1,2-dien-3-yl)-N-((tert-butyl-
dimethylsilyl)oxy)-4-methylbenzenesulfonamide (2n).
64.9 mg (14%) of product 2k was obtained from propargyl alcohol 3k
(232 mg, 0.800 mmol), sulfonamide 4a (241 mg, 0.800 mmol),
activated molecular sieves 4A (320 mg), and trimethylsilyl trifluoro-
methanesulfonate (15 μL, 0.080 mmol) (silica gel column chromatog-
raphy: hexane elution to hexane/ethyl acetate = 95/5). White solid;
Rf = 0.33 (hexane/ethyl acetate = 20/1); mp 41−42 °C; IR (NaCl,
neat) νmax 3058, 2928, 2854, 1935, 1598, 1492, 1448, 1362, 1258,
187.3 mg (61%) of product 2n was obtained from propargyl alcohol
3n (167 mg, 0.500 mmol), sulfonamide 4a (151 mg, 0.500 mmol),
activated molecular sieves 4A (200 mg), and trimethylsilyl trifluoro-
methanesulfonate (9 μL, 0.05 mmol) (silica gel column chromatog-
raphy: hexane/ethyl acetate = 200/1 to 100/1). Pale yellow solid;
Rf value 0.51 (hexane/ethyl acetate = 10/1); mp 106−109 °C; IR
1
1173, 1087 cm−1; H NMR (500 MHz, CDCl3) δ 7.67 (d, 2H, J =
1
(NaCl, neat) νmax 3032, 2929, 1934, 1489, 1363, 1174, 830 cm−1; H
8.5 Hz), 7.22 (t, 2H, J = 7.5 Hz), 7.17 (dd, 4H, J = 7.5, 7.0 Hz), 7.12
(d, 2H, J = 8.5 Hz), 6.91 (d, 4H, J = 7.0 Hz), 2.88 (tt, 1H, J = 11.5,
3.0 Hz), 2.42 (s, 3H), 2.13 (br, 2H), 1.80 (br, 2H), 1.73 (br, 1H),
1.39(qt, 4H, J = 12.5, 3.0 Hz), 1.28−1.17 (m, 3H), 0.75(s, 9H), 0.07
(s, 6H); 13C NMR (126 MHz, CDCl3) δ 199.6, 144.2, 136.8, 130.1,
130.0, 129.2, 128.6, 127.9, 127.3, 125.1, 118.7, 40.9, 32.6, 26.43,
26.38, 25.6, 21.8, 17.8, −4.6; HRMS (ESI) calcd for C34H43NNaO3SSi
[M + Na]+ 596.2631, found 596.2634.
NMR (500 MHz, CDCl3) δ 7.71 (d, 2H, J = 8.0 Hz), 7.22 (d, 2H, J =
8.0 Hz), 7.18 (d, 4H, J = 9.0 Hz), 6.88 (br, 4H), 2.58 (t, 2H, J =
7.5 Hz), 2.48 (s, 3H), 1.60 (tt, 2H, J = 7.5, 7.5 Hz), 1.38 (tq, 2H,
J = 7.5, 7.5 Hz), 0.91 (t, 3H, J = 7.5 Hz), 0.80 (s, 9H), 0.09 (s, 6H);
13C NMR(126 MHz, CDCl3) δ 200.7, 144.6, 134.8, 133.5, 130.1,
129.94, 129.88, 129.2, 128.3, 120.3, 115.8, 31.9, 29.8, 25.8, 22.5,
21.7, 17.7, 13.9, −4.8; HRMS (ESI) calcd for C32H39Cl2NaNO3SSi
[M + Na]+ 638.1695, found 638.1693.
N-((tert-Butyldimethylsilyl)oxy)-4-methyl-N-(1-phenoxy-4,4-
diphenylbuta-2,3-dien-2-yl)benzenesulfonamide (2l).
N-(1,1-Bis(4-methoxyphenyl)hepta-1,2-dien-3-yl)-N-((tert-butyl-
dimethylsilyl)oxy)-4-methylbenzenesulfonamide (2o).
66.3 mg (6%) of product 2l was obtained from propargyl alcohol 3l
(629 mg, 2.00 mmol) and sulfonamide 4a (603 mg, 2.00 mmol),
activated molecular sieves 4A (800 mg), and trimethylsilyl trifluoro-
methanesulfonate (36 μL, 0.20 mmol) (silica gel column chromatog-
raphy: hexane/ethyl acetate = 98/2 to 90/10, followed by recycling
HPLC). Colorless sticky oil; Rf = 0.44 (hexane/ethyl acetate = 1/10);
IR (NaCl, neat) νm1ax 3060, 2927, 2856, 1943, 1599, 1493, 1461, 1362,
1253, 1173 cm−1; H NMR (500 MHz, CDCl3) δ 7.72 (d, 2H, J =
8.0 Hz), 7.25 (t, 2H, J = 7.5 Hz), 7.20−7.14 (m, 8H), 6.95−6.87
(m, 7H), 4.97 (s, 2H), 2.44 (s, 3H), 0.78 (s, 9H), 0.09 (s, 6H);
13C NMR (126 MHz, CDCl3) δ 201.6, 158.2, 144.7, 135.8, 130.3, 129.5,
129.34, 129.29, 129.1, 127.94, 127.92, 121.0, 120.9, 115.4, 114.7,
66.6, 25.8, 21.8, 17.8, −4.9; HRMS (ESI) calcd for C35H39NO4SSiNa
[M + Na]+ 620.2267, found 620.2262.
100.1 mg (33%) of product 2o was obtained from propargyl alcohol
3o (121.3 mg, 0.50 mmol), sulfonamide 4a (151.1 mg, 0.500 mmol),
activated molecular sieves 4A (200 mg), and trimethylsilyl trifluoro-
methanesulfonate (9 μL, 0.05 mmol) (silica gel column chromatog-
raphy: hexane/ethyl acetate = 100/1 to 50/1 to 25/1). Pale yellow oil;
Rf value 0.43 (hexane/ethyl acetate = 10/1); IR (NaCl, neat) νmax
3036, 2929, 1931, 1605, 1509, 1248, 1173 cm−1; 1H NMR (500 MHz,
CDCl3) δ 7.73 (d, 2H, J = 8.0 Hz), 7.21 (d, 2H, J = 8.0 Hz), 6.90
(br, 4H), 6.75 (d, 4H, J = 8.5 Hz), 3.82 (s, 6H), 2.54 (t, 2H, J = 8.0
Hz), 2.47 (s, 3H), 1.60 (tt, 2H, J = 8.0, 7.5 Hz), 1.37 (tq, 2H, J = 7.5,
7.5 Hz), 0.90 (t, 2H, J = 7.5 Hz), 0.82 (s, 9H), 0.09 (s, 6H); 13C NMR
(126 MHz, CDCl3) δ 199.7, 159.0, 144.2, 130.4, 130.0, 129.9, 129.2,
129.1, 118.6, 117.1, 113.3, 55.2, 32.2, 29.8, 25.8, 22.5, 21.8, 17.8, 13.9,
−4.8; HRMS (ESI) calcd for C34H45NaNO5SSi [M + Na]+ 630.2685,
found 630.2684.
N-((tert-Butyldimethylsilyl)oxy)-N-(1,1-diphenyl-10-(triisopropylsilyl)-
deca-1,2-dien-9-yn-3-yl)-4-methylbenzenesulfonamide (2m).
H
DOI: 10.1021/acs.joc.5b02364
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The Journal of Organic Chemistry
Article
N-((tert-Butyldimethylsilyl)oxy)-4-methyl-N-(1-phenyl-1-(o-tolyl)-
After quenching the reaction with saturated sodium bicarbonate
aqueous solution, the mixture was extracted with ethyl acetate and was
washed with water and brine. The combined organic layers were dried
over magnesium sulfate and were concentrated in vacuo. The resulting
residual solid was purified by decantation (hexane/ethyl acetate = 6:1)
to afford bromobenzoate 5a′ (33.5 mg, 74%). White solid; Rf value
0.50 (hexane/ethyl acetate = 3/1); mp 168−169 °C (recrystallized
from ether); IR (NaCl, neat) νmax 2959, 1749, 1590, 1320, 1251, 1149,
1059, 748, 702 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.93 (d, 2H, J =
9.0 Hz), 7.64 (d, 2H, J = 9.0 Hz), 7.43 (d, 2H, J = 8.5 Hz), 7.35−7.30
(m, 3H), 7.22−7.27 (m, 5H), 7.14 (d, 2H, J = 8.0 Hz), 7.09 (d, 2H, J =
6.5 Hz), 2.54 (t, 2H, J = 7.5 Hz), 2.37 (s, 3H), 1.43 (tt, 2H, J = 7.5,
7.5 Hz), 1.19 (tq, 2H, J = 7.5, 7.5 Hz), 0.80 (t, 3H, J = 7.5 Hz); 13C
NMR (126 MHz, CDCl3) δ 165.7, 162.6, 155.8, 144.2, 138.9, 138.0,
137.7, 137.3, 132.0, 131.1, 129.5, 129.11, 129.08, 129.04, 128.62, 128.56,
128.4, 128.1, 127.8, 127.6, 32.0, 27.2, 22.7, 21.6, 13.7; HRMS (ESI) calcd
for C33H30BrNO4SNa [M + Na]+ 638.09766, found 638.09757.
hepta-1,2-dien-3-yl)benzenesulfonamide (2p).
235.8 mg (17%) of product 2p was obtained from propargyl alcohol
3p (696 mg, 2.50 mmol), sulfonamide 4a (754 mg, 250 mmol),
activated molecular sieves 4A (1.0 g), and trimethylsilyl trifluoro-
methanesulfonate (45 μL, 0.25 mmol) (silica gel column chromatog-
raphy: hexane/ethyl acetate = 99/1 to 91/9, followed by recycling
HPLC). Pale yellow oil; Rf = 0.47 (hexane/ethyl acetate = 10/1); IR
(NaCl, neat) νmax 3060, 2928, 1943, 1598, 1462, 1362, 1252, 1173,
1089 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.56 (d, 2H, J = 8.0 Hz),
7.24−7.15 (m, 4H), 7.10−7.07 (m, 2H), 6.97−6.94 (m, 4H), 6.87
(d, 1H, J = 7.5 Hz), 2.59−2.48 (m, 2H), 2.33 (s, 3H), 1.82 (s, 3H),
1.65−1.54 (m, 2H), 1.38 (tq, 2H, J = 7.5, 7.5 Hz), 0.91 (t, 3H, J =
7.5 Hz), 0.80 (s, 9H), 0.20 (br, 3H), 0.15 (s, 3H); 13C NMR (126
MHz, CDCl3) δ 199.8, 144.1, 136.5, 136.0, 135.7, 130.0, 129.91,
129.85, 129.6, 128.9, 128.1, 127.4, 127.2, 125.6, 118.8, 116.6, 32.2,
29.8, 25.8, 22.6, 21.7, 19.9, 17.8, 13.9, −4.5, −4.8; HRMS (ESI) calcd
for C33H43NNaO3SSi [M + Na]+ 584.26306, found 584.26241.
General Procedure of α-Sulfonyl Enoximes (Vinyl Sulfones)
Synthesis. To a stirred solution of allenylsulfonamide (1 equiv) and
acetic acid (1.5 equiv) in THF (0.1 M) was added tetrabutylammo-
nium fluoride (1.2 equiv) at 0 °C. After 10 min, the reaction was
quenched with saturated sodium bicarbonate aqueous solution. The
reaction mixture was extracted with ethyl acetate and was washed with
water and brine. The combined organic layers were dried over sodium
sulfate or magnesium sulfate and were concentrated in vacuo. The
resulting residue was purified by flash silica gel column chromatog-
raphy to afford α-sulfonyl enoximes. E/Z chemistry of oximes is not
determined except for 5a, but all were obtained as single isomers.
(E)-1,1-Diphenyl-2-tosylhept-1-en-3-one Oxime (5a).
1,1-Diphenyl-2-(phenylsulfonyl)hept-1-en-3-one Oxime (5b).
30.6 mg (94%) of product 5b was obtained from allenamide 2b (40.0 mg,
0.075 mmol), acetic acid (6.5 μL, 0.113 mmol), and tetrabutyl-
ammonium fluoride (90 μL, 1.0 M in THF, 0.09 mmol) (silica gel
column chromatography: hexane/ethyl acetate = 7/1 to 3/1). Colorless
oil; Rf value 0.20 (hexane/ethyl acetate = 3/1); IR (NaCl, neat) νmax
3492, 2958, 1445, 1307, 1147, 701 cm−1; 1H NMR (500 MHz, CDCl3) δ
8.88 (br, 1H), 7.54 (dd, 2H, J = 7.0, 1.0 Hz), 7.46 (td, 1H, J = 7.5,
1.0 Hz), 7.30−7.19 (m, 10H), 7.09 (d, 2H, J = 7.5 Hz), 2.32 (t, 2H, J =
8.5 Hz), 1.40 (tt, H, J = 8.5, 7.5 Hz), 1.22 (tq, 2H, J = 7.5, 7.5 Hz), 0.83
(t, 3H, J = 7.5 Hz); 13C NMR (126 MHz, CDCl3) δ 156.3, 155.1, 141.2,
139.6, 138.6, 137.8, 132.7, 129.2, 129.1, 128.8, 128.3, 128.2, 128.1, 128.0,
127.6, 29.7, 27.0, 22.8, 13.7; HRMS (ESI) calcd for C25H25NO3SNa
[M + Na]+ 442.14528, found 442.14592.
2-((4-Chlorophenyl)sulfonyl)-1,1-diphenylhept-1-en-3-one Oxime
(5c).
30.6 mg (94%) of product 5a was obtained from allenamide 2a
(41.1 mg, 0.075 mmol), acetic acid (6.5 μL, 0.113 mmol), and
tetrabutylammonium fluoride (90 μL, 1.0 M in THF, 0.09 mmol)
(silica gel column chromatography: hexane/ethyl acetate = 10/1 to 3/1).
Colorless solid; Rf value 0.25 (hexane/ethyl acetate = 3/1); mp 144−
145 °C; IR (NaCl, neat) νmax 3424, 3192, 2958, 2929, 2871, 1596, 1444,
32.1 mg (96%) of product 5c was obtained from allenamide 2c
(42.0 mg, 0.074 mmol), acetic acid (6.3 μL, 0.11 mmol), and
tetrabutylammonium fluoride (89 μL, 1.0 M in THF, 0.089 mmol)
(hexane/ethyl acetate = 10/1 to 3/1). Colorless oil; Rf value 0.42
(hexane/ethyl acetate = 3/1); IR (NaCl, neat) νmax 3442, 3194, 2959,
1
1579, 1317, 1148, 754 cm−1; H NMR (500 MHz, CDCl3) δ 9.01
1
1315, 1146, 703 cm−1; H NMR (500 MHz, CDCl3) δ 8.95 (s, 1H),
(s, 1H), 7.43 (d, 2H, J = 9.0 Hz), 7.32−7.19 (m, 10H), 7.08 (d, 2H,
J = 7.5 Hz), 2.33 (t, 2H, J = 8.0 Hz), 1.42 (tt, 2H, J = 8.0, 7.5 Hz),
1.24 (tq, 2H, J = 7.5, 7.5 Hz), 0.84 (t, 3H, J = 7.5 Hz); 13C NMR
(126 MHz, CDCl3) δ 156.4, 155.5, 139.6, 139.43, 139.35, 138.3, 137.7,
129.5, 129.2, 129.1, 129.0, 128.6, 128.5, 128.1, 127.7, 29.7, 27.0, 22.8,
13.7; HRMS (ESI) calcd for C25H24ClNO3SNa [M + Na]+ 476.10631,
found 476.10649.
7.40 (d, 2H, J = 8.0 Hz), 7.31−7.20 (m, 8H), 7.12−7.07 (m, 4H), 2.35
(s, 3H), 2.32 (t, 2H, J = 8.0 Hz), 1.39 (tt, 2H, J = 8.0, 7.0 Hz), 1.22
(tq, 2H, J = 7.5, 7.0 Hz), 0.83 (t, 3H, J = 7.5 Hz); 13C NMR (126 MHz,
CDCl3) δ 156.3, 154.8, 143.6, 139.7, 138.6, 138.1, 138.0, 129.09, 129.07,
129.01, 128.7, 128.20, 128.16, 128.0, 127.6, 29.8, 26.9, 22.8, 21.5, 13.7;
HRMS (ESI) calcd for C26H27NO3SNa [M + Na]+ 456.16093, found
456.16097.
2-((4-Fluorophenyl)sulfonyl)-1,1-diphenylhept-1-en-3-one Oxime
(5d).
(E)-1,1-Diphenyl-2-tosylhept-1-en-3-one O-(4-Bromobenzoyl)
Oxime (5a′, CCDC 1056831).
41.9 mg (96%) of product 5d was obtained from allenamide 2d (55.2 mg,
0.100 mmol), acetic acid (9 μL, 0.15 mmol), and tetrabutylammonium
fluoride (120 μL, 1.0 M in THF, 0.12 mmol) (silica gel column
chromatography: hexane/ethyl acetate = 95/5 to 70/30). White solid;
Rf = 0.39 (hexane/ethyl acetate = 2/1); mp 37−39 °C; IR (NaCl,
neat) νmax 3427, 3188, 3056, 2959, 2931, 2871, 1590, 1492, 1317,
1290, 1236, 1146 cm−1; 1H NMR (500 MHz, CDCl3) δ 8.94 (br, 1H),
To a stirred solution of oxime 5a (31.6 mg, 0.073 mmol) in dichloro-
methane (2.0 mL) were added triethylamine (30 μL, 0.219 mmol),
N,N-dimethyl-4-aminopyridine (1.8 mg, 0.015 mmol), and
p-bromobenzoyl chloride (19.2 mg, 0.089 mmol) at room temperature
under a nitrogen atmosphere, and the mixture was stirred for 15 h.
I
DOI: 10.1021/acs.joc.5b02364
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The Journal of Organic Chemistry
Article
7.50 (dd, 2H, J = 8.5, 5.0 Hz), 7.29 (m, 1H), 7.26−7.19 (m, 7H), 7.08
(d, 2H, J = 6.5 Hz), 6.93 (dd, 2H, J = 8.5, 8.5 Hz), 2.32 (t, 2H, J =
8.0 Hz), 1.41 (tt, 2H, J = 8.0, 7.5 Hz), 1.23 (tq, 2H, J = 7.5, 7.0 Hz),
0.83 (t, 3H, J = 7.0 Hz); 13C NMR (126 MHz, CDCl3) δ 165.1
1,3,3-Triphenyl-2-tosylprop-2-en-1-one Oxime (5h).
(d, JC‑F = 256 Hz), 156.5, 155.3, 139.5, 138.5, 137.7, 137.1 (d, JC‑F
=
3.7 Hz), 130.9 (d, JC‑F = 9.6 Hz), 129.2, 129.1, 129.0, 128.4, 128.1,
127.7, 115.6 (d, JC‑F = 22.8 Hz), 29.7, 27.0, 22.8, 13.7; 19F NMR
(471 MHz, CDCl3) δ −105.0; HRMS (ESI) calcd for C25H24FNNaO3S
[M + Na]+ 460.13586, found 460.13584.
2-((4-Methoxyphenyl)sulfonyl)-1,1-diphenylhept-1-en-3-one
Oxime (5e).
11.2 mg (25%) of oxime 5h, and 25.5 mg (57%) of dihydroisoxazole
8h were obtained from allenamide 2h (56.7 mg, 0.1 mmol), acetic acid
(9 μL, 0.15 mmol), and tetrabutylammonium fluoride (120 μL, 1.0 M
in THF, 0.120 mmol) (silica gel column chromatography: hexane/
ethyl acetate = 50/1 to 10/1 to 5/1). Colorless oil; Rf value 0.29
(hexane/ethyl acetate = 2/1); IR (NaCl, neat) νmax 3404, 3156, 3057,
1
3025, 2854, 1595, 1443, 1314, 1146, 1081, 763, 702 cm−1; H NMR
(500 MHz, CDCl3) δ 8.49 (br, 1H), 7.49−7.47 (m, 2H), 7.43 (d, 2H,
J = 9.0 Hz), 7.30−7.21 (m, 6H), 7.18−7.11 (m, 5H), 7.08 (t, 4H, J =
8.0 Hz), 2.35 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 156.5, 151.9,
143.7, 139.8, 139.4, 138.2, 137.9, 132.4, 129.2, 129.1, 129.03, 128.96,
128.8, 128.5, 128.4, 128.3, 127.9, 127.7, 127.6, 21.6; HRMS (ESI)
calcd for C28H23NNaO3S [M + Na]+ 476.12963, found 476.12940.
3,5,5-Triphenyl-4-tosyl-4,5-dihydroisoxazole (8h).
39.4 mg (88%) of product 5e was obtained from allenamide 2e
(56.4 mg, 0.1 mmol), acetic acid (9 μL, 0.15 mmol), and tetrabutyl-
ammonium fluoride (120 μL, 1.0 M in THF, 0.12 mmol) (silica gel
column chromatography: hexane/ethyl acetate = 92/8 to 1/1). White
solid; Rf = 0.21 (hexane/ethyl acetate = 2/1); mp 40−42 °C; IR
(NaCl, neat) νmax 3427, 3192, 3058, 2959, 2871, 1594, 1496, 1444,
1
1317, 1298, 1261, 1144 cm−1; H NMR (500 MHz, CDCl3) δ 9.08
White solid; Rf = 0.37 (hexane/ethyl acetate = 4/1); mp 234−235 °C;
IR (NaCl, neat) νm1ax 3060, 3029, 2978, 2920, 2596, 1494, 1447, 1326,
1149, 1085 cm−1; H NMR (500 MHz, CDCl3) δ 7.70 (d, 2H, J =
7.0 Hz), 7.59 (d, 2H, J = 8.0 Hz), 7.44 (d, 2H, J = 8.0 Hz), 7.38−7.20
(m, 9H), 7.07 (d, 2H, J = 7.5 Hz), 7.01 (d, 2H, J = 7.5 Hz), 5.77
(s, 1H), 2.35 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 155.8, 145.1,
143.5, 135.5, 134.4, 130.3, 129.2, 129.1, 128.7, 128.6, 128.5, 128.3,
128.2, 128.0, 127.7, 127.5, 124.8, 94.0, 76.4, 21.6; HRMS (ESI) calcd
for C28H23NO3SNa [M + Na]+ 476.12963, found 476.13009.
1-(4-Bromophenyl)-3,3-diphenyl-2-tosylprop-2-en-1-one Oxime
(5i).
(br, 1H), 7.43 (d, 2H, J = 9.5 Hz), 7.30−7.19 (m, 8H), 7.12 (d, 2H,
J = 6.5 Hz), 6.75 (d, 2H, J = 9.5 Hz), 3.79 (s, 3H), 2.32 (t, 2H, J =
8.0 Hz), 1.39 (tt, 2H, J = 8.0, 7.5 Hz), 1.21 (tq, 2H, J = 7.5, 7.0 Hz),
0.82 (t, 3H, J = 7.0 Hz); 13C NMR (126 MHz, CDCl3) δ 163.1, 156.5,
154.4, 139.8, 138.9, 138.0, 132.6, 130.4, 129.09, 129.06, 128.7, 128.2,
128.0, 127.6, 113.6, 55.5, 29.8, 26.9, 22.9, 13.7; HRMS (ESI) calcd for
C26H27NO4SNa [M + Na]+ 472.15585, found 472.15593.
2-(Methylsulfonyl)-1,1-diphenylhept-1-en-3-one Oxime (5f).
22.4 mg (91%) of product 5f was obtained from allenamide 2f
(32.4 mg, 0.069 mmol), acetic acid (5.9 μL, 0.103 mmol), and tetrabutyl-
ammonium fluoride (83 μL, 1.0 M in THF, 0.083 mmol) (silica gel
column chromatography: hexane/ethyl acetate = 10/1 to 3/1). Colorless
oil; Rf value 0.10 (hexane/ethyl acetate = 3/1); IR (NaCl, neat) νmax
3407, 2959, 1309, 1139, 964, 702 cm−1; 1H NMR (500 MHz, CDCl3) δ
7.39−7.34 (m, 5H), 7.30−7.25 (m, 5H), 2.88 (s, 3H), 2.24 (t, 2H, J =
8.0 Hz), 1.37 (m, 2H), 1.19 (tq, 2H, J = 7.5, 7.5 Hz), 0.80 (t, 3H, J =
7.5 Hz); 13C NMR (126 MHz, CDCl3) δ 157.5, 155.0, 139.5, 138.1,
136.9, 129.3, 129.1, 129.0, 128.8, 128.2, 127.9, 43.7, 29.6, 26.9, 22.8, 13.7;
HRMS (ESI) calcd for C20H23NO3SNa [M + Na]+ 380.12963, found
380.12953.
11.6 mg (22%) of oxime 5i and 28.3 mg (53%) of dihydroisoxazole 8i
were obtained from allenamide 2i (64.7 mg, 0.100 mmol), acetic acid
(9 μL, 0.15 mmol), and tetrabutylammonium fluoride (120 μL, 1.0 M
in THF, 0.12 mmol) (silica gel column chromatography: hexane/ethyl
acetate = 10/1 to 5/1 to 2/1). Colorless oil; Rf value 0.24 (hexane/
ethyl acetate = 2/1); IR (NaCl, neat) νmax 3398, 3160, 3028, 2864,
1
1587, 1487, 1314, 1146 cm−1; H NMR (500 MHz, CDCl3) δ 8.39
(br, 1H), 7.43 (d, 2H, J = 8.5 Hz), 7.37 (d, 2H, J = 8.5 Hz), 7.32
(d, 2H, J = 8.5 Hz), 7.29 (t, 1H, J = 7.0 Hz), 7.23 (dd, 2H, J = 7.5, 7.0
Hz), 7.17 (t, 1H, J = 7.5 Hz), 7.14 (dd, 2H, J = 7.5, 6.5 Hz), 7.10−7.09
(m, 4H), 7.04 (d, 2H, J = 6.5 Hz), 2.36 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 156.9, 151.1, 143.9, 139.6, 138.9, 138.0, 137.7, 131.3, 130.9,
130.6, 129.1, 128.9, 128.8, 128.7, 128.4, 128.0, 127.6, 123.5, 21.6;
HRMS (ESI) calcd for C28H2279BrNaNO3S [M + Na]+ 554.0402,
found 554.0418.
2-(Mesitylsulfonyl)-1,1-diphenylhept-1-en-3-one Oxime (5g).
3-(4-Bromophenyl)-5,5-diphenyl-4-tosyl-4,5-dihydroisoxazole
At room temperature, 17.0 mg (63%) of product 5g was obtained
from allenamide 2g (33.9 mg, 0.059 mmol), acetic acid (5.0 μL,
0.088 mmol), and tetrabutylammonium fluoride (70 μL, 1.0 M in
THF, 0.070 mmol) (silica gel column chromatography: hexane/ethyl
acetate = 10/1 to 3/1). Pale yellow oil; Rf value 0.31 (hexane/ethyl
acetate = 3/1); IR (NaCl, neat) νmax 3419, 2958, 1603, 1444, 1303,
1138, 701 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.79 (br, 1H), 7.25−
7.12 (m, 10H), 6.72 (s, 2H), 2.52 (s, 6H), 2.35 (t, 2H, J = 8.0 Hz),
2.20 (s, 3H), 1.34 (m, 2H), 1.14 (qt, 2H, J = 7.5, 7.5 Hz), 0.78 (t, 3H,
J = 7.5 Hz); 13C NMR (126 MHz, CDCl3) δ 156.0, 151.7, 142.4,
140.0, 139.7, 138.6, 138.2, 134.6, 131.6, 129.7, 128.80, 128.76, 128.2,
127.9, 127.5, 30.1, 26.9, 22.8, 22.5, 20.9, 13.7; HRMS (ESI) calcd for
C28H31NO3SNa [M + Na]+ 484.19223, found 484.19215.
(8i).
White solid; Rf = 0.41 (hexane/ethyl acetate = 2/1); mp 90−91 °C; IR
(NaCl, neat) νmax 3060, 2981, 1593, 1492, 1448, 1397, 1329, 1149 cm−1;
1H NMR (500 MHz, CDCl3) δ 7.50 (dd, 4H, J = 8.5, 7.5 Hz), 7.39
(d, 2H, J = 8.5 Hz), 7.35 (d, 2H, J = 7.0 Hz), 7.24−7.14 (m, 7H), 6.97
(br, 4H), 5.64 (s, 1H), 2.30 (s, 3H); 13C NMR (126 MHz, CDCl3)
J
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δ 155.0, 145.4, 143.3, 135.2, 134.2, 131.7, 129.2, 129.1, 128.7, 128.5,
128.2, 128.1, 127.6, 124.9, 124.8, 94.3, 76.3, 21.7; HRMS (ESI) calcd
for C28H2279BrNNaO3S [M + Na]+ 554.04015, found 554.03949.
3,3-Diphenyl-2-tosylacrylaldehyde Oxime (5j).
column chromatography: hexane/ethyl acetate = 98/2 to 70/30).
colorless oil; Rf = 0.47 (hexane/ethyl acetate = 2/1); IR (NaCl, neat)
νmax 3431, 3190, 3058, 2940, 2864, 2170, 1596, 1463, 1317,
1
1148 cm−1; H NMR (500 MHz, CDCl3) δ 8.72 (br, 1H), 7.39 (d,
2H, J = 8.0 Hz), 7.29 (t, 1H, J = 7.0 Hz), 7.26−7.18 (m, 7H), 7.10−
7.08 (m, 4H), 2.35 (s, 3H), 2.29 (t, 2H, J = 7.5 Hz), 2.16 (t, 2H, J =
7.5 Hz), 1.44 (tt, 2H, J = 7.5, 7.0 Hz), 1.40−1.28 (m, 4H), 1.08−0.98
(m, 21H); 13C NMR (126 MHz, CDCl3) δ 156.2, 154.8, 143.7, 139.7,
138.6, 138.1, 137.9, 129.1, 129.0, 128.8, 128.24, 128.20, 128.1, 127.6,
109.0, 80.0, 29.9, 28.7, 28.4, 24.2, 21.6, 19.6, 18.6, 11.2; HRMS (ESI)
calcd for C38H49NO3SSiNa [M + Na]+ 650.31001, found 650.31007.
1,1-Bis(4-chlorophenyl)-2-tosylhept-1-en-3-one Oxime (5n).
23.1 mg (60%) of product 5j was obtained from allenamide 2j (49.2 mg,
0.100 mmol), acetic acid (9 μL, 0.15 mmol), and tetrabutylammonium
fluoride (120 μL, 1.0 M in THF, 0.12 mmol) (silica gel column
chromatography: hexane/ethyl acetate = 92/8 to 50/50). White solid;
Rf = 0.32 (hexane/ethyl acetate = 2/1); mp 234−235 °C; IR (NaCl,
neat) νmax 3312, 3055, 3027, 1598, 1563, 1489, 1444, 1312, 1137,
1
993 cm−1; H NMR (500 MHz, DMSO-d6) δ 11.44 (s, 1H), 7.81
(s, 1H), 7.51 (d, 2H, J = 8.0 Hz), 7.34−7.26 (m, 8H), 7.10 (d, 2H, J =
7.5 Hz), 7.01 (d, 2H, J = 7.0 Hz), 2.36 (s, 3H); 13C NMR (126 MHz,
DMSO-d6) δ 156.0, 144.0, 143.8, 140.4, 138.8, 138.2, 134.1, 129.4,
129.3, 128.93, 128.90, 128.6, 128.5, 127.7, 127.5, 21.1; HRMS (ESI)
calcd for C22H19NNaO3S [M + Na]+ 400.09833, found 400.09826.
1-Cyclohexyl-3,3-diphenyl-2-tosylprop-2-en-1-one Oxime (5k).
49.2 mg (98%) of product 5n was obtained from allenamide 2n (61.8,
0.100 mmol), acetic acid (9 μL, 0.15 mmol), and tetrabutylammonium
fluoride (120 μL, 1.0 M in THF, 0.12 mmol) (silica gel column
chromatography: hexane/ethyl acetate = 50/1 to 10/1 to 5/1). White
solid; Rf value 0.13 (hexane/ethyl acetate = 4/1); mp 62−66 °C; IR
(NaCl, neat) νmax 3423, 2958, 1594, 1489, 1146, 1090, 1014, 814
cm−1; 1H NMR (500 MHz, CDCl3) δ 8.52 (br, 1H, OH), 7.40 (d, 2H,
J = 8.0 Hz), 7.213 (d, 2H, J = 9.0 Hz), 7.211 (d, 2H, J = 8.5 Hz), 7.13
(d, 2H, J = 9.0 Hz), 7.11 (d, 2H, J = 8.5 Hz), 7.01 (d, 2H, J = 8.0 Hz),
2.38 (s, 2H), 2.32 (t, 3H, J = 8.0 Hz), 1.36 (tt, 2H, J = 8.0, 7.0 Hz),
1.22 (tq, 2H, J = 7.5, 7.0 Hz), 0.83 (t, 3H, J = 7.5 Hz); 13C NMR
(126 MHz, CDCl3) δ 156.3, 151.9, 144.2, 139.8, 137.8, 137.7, 135.9,
135.3, 134.8, 130.7, 129.1, 128.4, 128.2, 128.0, 29.7, 27.0, 22.8, 21.6,
13.7; HRMS (ESI) calcd for C26H25Cl2NaNO3S [M + Na]+ 524.0830,
found 524.0823.
43.3 mg (96%) of product 5k was obtained from allenamide 2k
(57.4 mg, 0.100 mmol), acetic acid (9 μL, 0.15 mmol), and tetrabutyl-
ammonium fluoride (120 μL, 1.0 M in THF, 0.12 mmol) (silica gel
column chromatography: hexane/ethyl acetate = 95/5 to 70/30).
White solid; Rf = 0.40 (hexane/ethyl acetate = 2/1); mp 72−75 °C; IR
(NaCl, neat) νmax 3435, 3185, 3028, 2927, 2852, 1596, 1445, 1302,
1146, 1086 cm−1; 1H NMR (500 MHz, CDCl3) δ 8.93 (br, 1H), 7.33
(d, 2H, J = 8.5 Hz), 7.28−7.21 (m, 6H), 7.18 (dd, 2H, J = 8.0, 7.5 Hz),
7.05−7.01 (m, 4H), 2.95 (tt, 1H, J = 12.0, 3.0 Hz), 2.32 (s, 3H),
1.65 (br, 7H), 1.27−1.20 (m, 2H), 1.11−1.03 (m, 1H); 13C NMR
(126 MHz, CDCl3) δ 159.2, 154.9, 143.3, 140.2, 138.6, 138.3, 138.0,
129.9, 129.6, 128.9, 128.8, 128.2, 128.1, 127.9, 127.5, 39.7, 28.5, 26.3,
25.9, 21.5; HRMS (ESI) calcd for C28H29NNaO3S [M + Na]+
482.17658, found 482.17700.
1,1-Bis(4-methoxyphenyl)-2-tosylhept-1-en-3-one Oxime (5o).
44.8 mg (91%) of product 5o was obtained from allenamide 2o
(60.8 mg, 0.100 mmol), acetic acid (9 μL, 0.15 mmol), and tetrabutyl-
ammonium fluoride (120 μL, 1.0 M in THF, 0.120 mmol) (silica gel
column chromatography: hexane/ethyl acetate = 50/1 to 10/1 to 5/1).
Pale yellow oil; Rf value 0.32 (hexane/ethyl acetate = 2/1); IR (NaCl,
neat) νmax 3502, 2929, 1603, 1509, 1254, 1175 cm−1; 1H NMR
(500 MHz, CDCl3) δ 9.05 (br, 1H), 7.43 (d, 2H, J = 8.5 Hz), 7.12
(d, 2H, J = 9.0 Hz), 7.08 (d, 2H, J = 8.5 Hz), 7.01 (d, 2H, J = 9.0 Hz),
6.76−6.73 (m, 4H), 3.82 (s, 3H), 3.72 (s, 3H), 2.34 (s, 3H), 2.31
(t, 2H, J = 8.0 Hz), 1.40 (tt, 2H, J = 8.0, 7.5 Hz), 1.23 (tq, 2H, J = 7.5,
7.5 Hz), 0.83 (t, 3H, J = 7.5 Hz); 13C NMR (126 MHz, CDCl3) δ
160.1, 159.7, 156.7, 154.4, 143.3, 138.5, 136.8, 132.6, 131.34, 131.30,
130.7, 128.9, 128.1, 113.3, 112.8, 55.2, 55.1, 29.7, 27.0, 22.8, 21.5, 13.7;
HRMS (ESI) calcd for C28H31NNaO5S [M + Na]+ 516.18206, found
516.18142.
1-Phenoxy-4,4-diphenyl-3-tosylbut-3-en-2-one Oxime (5l).
41.2 mg (85%) of product 5l was obtained from allenamide 2l
(59.8 mg, 0.1 mmol), acetic acid (9 μL, 0.15 mmol), and tetrabutyl-
ammonium fluoride (120 μL, 1.0 M in THF, 0.12 mmol) (silica gel
column chromatography: hexane/ethyl acetate = 20/1 to 10/1 to 4/1
to 2/1). White solid; Rf = 0.29 (hexane/ethyl acetate = 2/1); mp 47−
48 °C; IR (NaCl, neat) νmax 3400, 3193, 3060, 2876, 1597, 1495, 1444,
1
1303, 1242, 1146, 1086 cm−1; H NMR (500 MHz, CDCl3) δ 9.18
(br, 1H), 7.40−7.35 (m, 4H), 7.27 (t, 1H, J = 7.5 Hz), 7.21−7.16
(m, 7H), 7.08 (d, 2H, J = 7.0 Hz), 7.05 (t, 1H, J = 7.0 Hz), 7.01−6.99
(m, 4H), 4.91 (s, 2H), 2.31 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
157.7, 157.0, 154.4, 143.6, 140.1, 138.0, 137.6, 136.5, 129.6, 129.2,
128.8, 128.7, 128.4, 128.27, 128.25, 128.18, 127.7, 121.5, 114.7, 64.4,
21.5; HRMS (ESI) calcd for C29H25NNaO4S 506.14020 [M + Na]+,
found 506.14008.
(1Z,3E)-1-Phenyl-1-(o-tolyl)-2-tosylhept-1-en-3-one Oxime ((Z)-5p,
CCDC 1056832).
1,1-Diphenyl-2-tosyl-10-(triisopropylsilyl)dec-1-en-9-yn-3-one
Oxime (5m).
1
155.0 mg (87%, (Z)-5p/(E)-5p = 19/1 determined by H NMR)
of products as a mixture was obtained from allenamide 2p (225 mg,
0.400 mmol), acetic acid (34 μL, 0.60 mmol), and tetrabutyl-
ammonium fluoride (480 μL, 1.0 M in THF, 0.480 mmol) (silica gel
column chromatography: hexane/ethyl acetate = 95/5 to 60/40).
52.8 mg (84%) of product 5m was obtained from allenamide 2m
(74.2 mg, 0.100 mmol), acetic acid (9 μL, 0.15 mmol), and tetrabutyl-
ammonium fluoride (120 μL, 1.0 M in THF, 0.12 mmol) (silica gel
K
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Separation of (Z)-5p and (E)-5p was performed with HPLC
(Column: Kaseisorb LC ODS 2000) (methanol/water = 75/25) to
afford purified (Z)-5p (132.0 mg) and (E)-5p (4.3 mg). White solid;
Rf = 0.41 (hexane/ethyl acetate = 2/1); mp 122−124 °C; IR (NaCl,
neat) νmax 3433, 3178, 3061, 3023, 2958, 2929, 2871, 1596, 1455,
1316, 1147, 1085 cm−1; 1H NMR (500 MHz, CDCl3) δ 9.27 (br, 1H),
7.39−7.21 (m, 10H), 7.09 (d, 2H, J = 8.0 Hz), 6.95 (br, 1H), 2.50
(ddd, 1H, J = 14.5, 10.5, 5.5 Hz), 2.36 (s, 3H), 2.19 (br, 1H), 1.69
(br, 3H), 1.39 (br, 2H), 1.30−1.14 (m, 2H), 0.81 (t, 3H, J = 7.5 Hz);
13C NMR (126 MHz, CDCl3) δ 156.7, 154.2, 143.8, 139.1, 138.2,
137.9, 136.8, 135.9, 130.1, 129.9, 129.4, 128.9, 128.8, 128.6, 128.5,
127.9, 124.9, 30.0, 27.0, 22.9, 21.5, 19.6, 13.7; HRMS (ESI) calcd for
C27H29NNaO3S [M + Na]+ 470.17658, found 470.17690.
7.5 Hz), 0.88 (t, 3H, J = 7.5 Hz); 13C NMR (126 MHz, CDCl3) δ
159.0, 144.3, 128.3, 127.4, 126.0, 90.6, 50.1, 28.3, 27.6, 22.2, 13.7;
HRMS (ESI) calcd for C19H21NONa [M + Na]+ 302.15208, found
302.15242.
General Experimental Procedure of Sulfinate-Trapping
Substitutions To Afford α-Sulfonyl Enoximes. (Procedure A)
To a stirred solution of allenamide, azodicarboxylate (1.5 equiv), and
nucleophile reagent (1.5 equiv in general) in THF (0.05 M) was added
tetrabutylammonium fluoride THF solution (1.2 equiv in general) at
0 °C under a nitrogen atmosphere. After 10 min, the mixture was
extracted with ether and was washed with water and brine. The
combined organic layers were dried over magnesium sulfate and were
concentrated in vacuo. The resulting residual solid was purified by
silica gel column chromatography to afford the desired α-substituted
enoxime. (Procedure B) To a stirred solution of allenamide and
azodicarboxylate (1.5 equiv) was added tetrabutylammonium fluoride
THF solution (2 equiv in general) at −78 or −60 °C under a nitrogen
atmosphere. After 5 min, nucleophile reagent (equivalent depending
on used reagent; see below) was added at the same temperature, and
the mixture was warmed up to 0 °C. After 10 min, the reaction mixture
was treated in the same manner of procedure A to obtain the desired
α-substituted enoxime. When the Rf values of the products on TLC
were equal or similar to that of DIAD or tosylhydorazides, we used
DMEAD instead of DIAD for purifications. E/Z chemistry of oximes is
not determined except for 9g and 9h′, but all were obtained as single
isomers.
(1E)-1-Phenyl-1-(o-tolyl)-2-tosylhept-1-en-3-one Oxime ((E)-5p).
White solid; Rf value 0.41 (hexane/ethyl acetate = 2/1); mp 152−
154 °C; IR (NaCl, neat) νmax 3433, 3060, 2958, 2927, 2871, 1596,
1
1456, 1315, 1146, 1085 cm−1; H NMR (500 MHz, CDCl3) δ 7.38
(d, 2H, J = 8.5 Hz), 7.26−7.06 (m, 11H), 2.36 (s, 3H), 2.23 (t, 2H, J =
8.0 Hz), 2.17 (s, 3H), 1.43 (br, 2H), 1.26 (m, 2H), 0.87 (t, 3H, J = 7.5
Hz); 13C NMR (126 MHz, CDCl3) δ 156.4, 155.0, 143.5, 140.3, 139.1,
138.3, 136.7, 135.2, 130.6, 129.3, 128.9, 128.6, 128.4, 128.3, 128.1,
127.4, 125.2, 30.0, 26.9, 23.1, 21.6, 20.2, 13.8; HRMS (ESI) calcd for
C27H29NNaO3S [M + Na]+ 470.17658, found 470.17659.
2-(Diethylamino)-1,1-diphenylhept-1-en-3-one Oxime (9a).
Synthesis of Isoxazoline Byproducts. 3-Butyl-5,5-diphenyl-2-
tosyl-2,5-dihydroisoxazole (6, CCDC 1056830).
(Procedure A) 25.8 mg (98%) of product 9a was obtained from
allenamide 2a (41.1 mg, 0.075 mmol), diisopropyl azodicarboxylate
(0.113 mmol, 22 μL), diethylamine (12 μL, 0.113 mmol), and tetra-
butylammonium fluoride (90 μL, 1.0 M in THF, 0.09 mmol) (silica gel
column chromatography: hexane/diethyl ether = 35/1 to 10/1).
Yellow oil; Rf value 0.57 (hexane/ethyl acetate = 3/1); IR (NaCl, neat)
To a stirred solution of allenamide 2a (110 mg, 0.20 mmol) in
acetonitrile (4.0 mL) was added silver fluoride (30.6 mg, 0.241 mmol)
at room temperature, and the reaction mixture was stirred overnight.
Concentration of the mixture in vacuo, followed by silica gel column
chromatography (hexane/ethyl acetate = 98/2 to 85/15), gave
dihydroisoxazole 6 (42.1, mg, 48%). White solid; Rf = 0.23 (hexane/
ethyl acetate = 10/1); mp 126−127 °C; IR (NaCl, neat) νmax 3059,
2957, 2871, 1664, 1596, 1362, 1172 cm−1; 1H NMR (500 MHz,
CDCl3) δ 7.36 (d, 2H, J = 8.0 Hz), 7.21−7.14 (m, 6H), 7.96 (dd, 4H,
J = 6.5, 2.0 Hz), 7.83 (d, 2H, J = 8.0 Hz), 5.36 (s, 1H), 2.60 (t, 2H, J =
8.0 Hz), 2.30 (s, 3H), 1.64 (tt, 2H, J = 8.0, 7.0 Hz), 1.37 (tq, 2H, J =
7.0, 7.5 Hz), 0.92 (t, 3H, J = 7.5 Hz); 13C NMR (126 MHz, CDCl3) δ
144.5, 144.2, 141.1, 129.5, 128.95, 128.88, 127.9, 127.2, 126.5. 114.6,
94.5, 29.8, 27.5, 22.2, 21.6, 13.8; LRMS (EI) m/z 433 (9%, M+), 278
(35), 167 (43), 105 (100); HRMS (EI) calcd for C26H27NO3S (M+)
433.1712, found 433.1717.
1
νmax 3175, 2962, 2929, 1550, 1442, 1071, 765, 699 cm−1; H NMR
(500 MHz, CDCl3) δ 7.25 (t, 2H, J = 7.0 Hz), 7.15 (m, 5H), 7.09
(tt, 1H, J = 7.5, 2.0 Hz), 7.03 (d, 2H, J = 7.0 Hz), 2.72 (q, 4H, J =
7.0 Hz), 2.09 (t, 2H, J = 8.0 Hz), 1.47 (tt, 2H, J = 8.0, 7.0 Hz), 1.26
(qt, 2H, J = 7.0, 7.5 Hz), 0.98 (t, 6H, J = 7.0 Hz), 0.85 (t, 3H, J =
7.5 Hz); 13C NMR (126 MHz, CDCl3) δ 160.7, 143.8, 143.7, 141.7,
130.8, 130.5, 127.7, 127.6, 125.7, 125.5, 123.2, 45.0, 28.9, 27.7, 23.3,
13.8, 13.3; HRMS (ESI) calcd for C23H31N2O [M + H]+ 351.24364,
found 351.24321.
1,1-Diphenyl-2-(pyrrolidin-1-yl)hept-1-en-3-one Oxime (9b).
3-Butyl-5,5-diphenyl-4,5-dihydroisoxazole (7).
(Procedure B) 25.9 mg (99%) of product 9b was obtained from
allenamide 2a (41.1 mg, 0.075 mmol), bis(2-methoxyethyl)
azodicarboxylate (26.3 mg, 0.113 mmol), tetrabutylammonium
fluoride (150 μL, 1.0 M in THF, 0.15 mmol), and then pyrrolidine
(12.5 μL, 0.15 mmol) by a reaction at −60 to 0 °C (silica gel column
chromatography: hexane/diethyl ether = 13:1). Yellow oil; Rf value
0.48 (hexane/ethyl acetate = 3/1); IR (NaCl, neat) νmax 3168, 2959,
2858, 1554, 1442, 1377, 764, 699 cm−1; 1H NMR (500 MHz, CDCl3)
δ 8.35 (br, 1H), 7.27−7.24(m, 2H), 7.18−7.08 (m, 8H), 2.86 (s, 4H),
2.06 (br, 2H), 1.70 (dd, 4H, J = 10.0, 3.0 Hz), 1.44 (tt, 2H, J = 8.5,
7.0 Hz), 1.27 (qt, 2H, J = 7.5, 7.0 Hz), 0.85 (t, 3H, J = 7.5 Hz);
13C NMR (126 MHz, CDCl3) δ 159.9, 143.6, 143.4, 140.2, 131.0,
130.9, 127.6, 127.5, 125.3, 125.2, 119.3, 50.0, 28.5, 27.8, 25.1, 23.1,
13.8; HRMS (ESI) calcd for C23H29N2O [M + H]+ 349.22799, found
349.22641.
To a stirred solution of allenamide 2a (0.075 mmol, 41.1 mg) in
dichloromethane (0.7 mL) was added trifluoromethanesulfonic acid
(13 μL, 0.15 mmol) at 0 °C. After 1 h, the reaction was quenched with
saturated sodium bicarbonate aqueous solution. The mixture was
extracted with ether and was washed with water and brine. The com-
bined organic layers were dried over sodium sulfate and were con-
centrated in vacuo. The resulting residue was purified by flash silica gel
column chromatography (hexane/diethyl ether = 10/1) to afford
isoxazoline 7 (25.8 mg, 63%). White solid; Rf value 0.60 (hexane/ethyl
acetate = 3/1); mp 55−56 °C; IR (NaCl, neat) νmax 2957, 1492, 1447,
889, 754, 699 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.42−7.40
(m, 4H), 7.34−7.31 (m, 4H), 7.27−7.24 (m, 2H), 3.54 (s, 2H), 2.35
(t, 2H, J = 8.0 Hz), 1.54 (tt, 2H, J = 8.0, 7.5 Hz), 1.29 (tq, 2H, J = 7.5,
L
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1,1-Diphenyl-2-(piperidin-1-yl)hept-1-en-3-one Oxime (9c).
(35.0 mg, 0.15 mmol), p-toluenesulfonamide (0.30 mmol, 51.0 μL),
and tetrabutylammonium fluoride (200 μL, 1.0 M in THF, 0.20 mmol)
(silica gel column chromatography: hexane/diethyl ether = 2/1). White
solid; Rf value 0.12 (hexane/ethyl acetate = 2/1); mp 158−159 °C; IR
(NaCl, neat) νmax 3270, 3059, 2958, 1738, 1598, 1322, 1167, 701 cm−1;
1H NMR (500 MHz, CDCl3) δ 8.03 (br, 1H), 7.64 (d, 2H, J = 8.0 Hz),
(Procedure A) 25.1 mg (92%) of product 9c was obtained from
allenamide 2a (41.1 mg, 0.075 mmol), diisopropyl azodicarboxylate
(22 μL, 0.113 mmol), piperidine (11 μL, 0.113 mmol), and tetrabutyl-
ammonium fluoride (90 μL, 1.0 M in THF, 0.09 mmol) (silica gel
column chromatography: hexane/diethyl ether = 35/1 to 10/1).
Yellow oil; Rf value 0.48 (hexane/ethyl acetate = 3/1); IR (NaCl, neat)
νmax 3171, 2931, 1442, 1386, 978, 765, 699 cm−1; 1H NMR (500 MHz,
CDCl3) δ 9.50 (br, 1H), 7.29 (t, 2H, J = 7.5 Hz), 7.19−7.15 (m, 3H),
7.12−7.09 (m, 1H), 7.05 (d, 4H, J = 7.5 Hz), 2.59 (br, 4H), 2.10
(t, 2H, J = 7.0 Hz), 1.50−1.43 (m, 8H, J = 7.0, 7.5 Hz), 1.27 (qt, 2H,
J = 7.0, 7.5 Hz), 0.85 (t, 3H, J = 7.5 Hz); 13C NMR (126 MHz,
CDCl3) δ 160.8, 144.6, 143.64, 143.62, 130.7, 130.6, 127.7, 127.6,
125.8, 125.7, 123.5, 52.0, 28.4, 27.8, 26.3, 24.2, 23.2, 13.8; HRMS
(ESI) calcd for C24H31N2O [M + H]+ 363.24364, found 363.24339.
2-Morpholino-1,1-diphenylhept-1-en-3-one Oxime (9d).
7.34 (d, 2H, J = 8.0 Hz), 7.26−7.13 (m, 6H), 7.00 (dd, 2H, J = 7.0,
1.0 Hz), 6.58 (dd, 2H, J = 7.0, 1.0 Hz), 5.95 (s, 1H), 2.52 (m, 5H), 1.63
(m, 2H), 1.37 (tq, 2H, J = 7.5, 7.5 Hz), 0.95 (t, 3H, J = 7.5 Hz);
13C NMR (126 MHz, CDCl3) δ 156.9, 144.1, 139.5, 138.3, 135.6, 134.9,
129.7, 129.2, 129.0, 128.8, 128.6, 128.1, 127.9, 127.8, 127.2, 28.5, 27.2,
23.3, 21.7, 13.9; HRMS (ESI) calcd for C26H28N2O3SNa [M + Na]+
471.17183, found 471.17138.
2-(3-(Hydroxyimino)-1,1-diphenylhept-1-en-2-yl)isoindoline-1,3-
dione (9g).
(Procedure B) 33.1 mg (73%) of product 9g was obtained from
allenamide 2a (54.8 mg, 0.10 mmol), bis(2-methoxy ethyl)-
azodicarboxylate (35.1 mg, 0.15 mmol), tetrabutylammonium fluoride
(420 μL, 0.42 mmol, 1.0 M in THF), and then phthalimide (44.1 mg,
0.30 mmol) by a reaction at −60 to 0 °C (silica gel column chroma-
tography: hexane/ethyl acetate = 4/1 with 1% MeOH, followed by
GPC purification). White solid; Rf value 0.48 (hexane/ethyl acetate =
2/1); mp 189−190 °C; IR (NaCl, neat) νmax 3404, 2958, 1720, 1377,
(Procedure A) 19.2 mg (70%) of product 9d was obtained from
allenamide 2a (41.1 mg, 0.075 mmol), diisopropyl azodicarboxylate
(22 μL, 0.113 mmol), morpholine (10 μL, 0.113 mmol), and tetra-
butylammonium fluoride (90 μL, 1.0 M in THF, 0.09 mmol) (silica gel
column chromatography: toluene/ethyl acetate = 20/1). Yellow solid;
Rf value 0.28 (hexane/ethyl acetate = 3/1); mp 158−160 °C; IR
(NaCl, neat) νmax 3172, 2958, 1442, 1263, 1116, 983, 757, 700 cm−1;
1H NMR (500 MHz, CDCl3) δ 9.55 (br, 1H), 7.32−7.29 (m, 2H),
7.23−7.05 (m, 8H), 3.55 (t, 4H, J = 4.5 Hz), 2.68 (t, 4H, J = 4.5 Hz),
2.10 (t, 2H, J = 8.0 Hz), 1.45 (tt, 2H, J = 8.5, 8.0 Hz), 1.27 (tq, 2H, J =
7.5, 7.0 Hz), 0.86 (t, 3H, J = 7.0 Hz); 13C NMR (126 MHz, CDCl3) δ
160.4, 143.3, 143.1, 142.9, 130.7, 130.6, 128.0, 127.8, 126.4, 126.2,
125.3, 67.1, 50.9, 28.5, 27.9, 23.2, 13.8; HRMS (ESI) calcd for
C23H28N2O2Na [M + Na]+ 387.20485, found 387.20477.
Methyl (3-(Hydroxyimino)-1,1-diphenylhept-1-en-2-yl)-L-prolinate
(9e).
1
1115, 887 cm−1; H NMR (500 MHz, CDCl3) δ 7.77 (s, 1H), 7.74−
7.72 (m, 2H), 7.64−7.62 (m, 2H), 7.36−7.28 (m, 5H), 7.16−7.12
(m, 5H), 1.99−1.96 (m, 2H), 1.50−1.44 (m, 2H), 1.11 (tq, 2H, J =
7.5, 7.5 Hz), 0.76 (t, 3H, J = 7.5 Hz); 13C NMR (126 MHz, CDCl3) δ
166.9, 159.4, 148.3, 140.7, 139.6, 133.9, 131.8, 130.2, 128.8, 128.7,
128.3, 128.2, 128.0, 123.5, 122.8, 28.0, 27.4, 23.0, 13.6; HRMS (ESI)
calcd for C27H24N2O3Na [M + Na]+ 447.16846, found 447.16805.
1-(3-(Hydroxyimino)-1,1-diphenylhept-1-en-2-yl)pyrrolidine-2,5-
dione (9h).
(Procedure B) 29.7 mg (79%) of product 9h was obtained from
allenamide 2a (54.8 mg, 0.10 mmol), bis(2-methoxy ethyl)-
azodicarboxylate (35.1 mg, 0.15 mmol), tetrabutylammonium fluoride
(420 μL, 0.42 mmol, 1.0 M in THF), and then succinimide (29.7 mg,
0.30 mmol) by a reaction at −60 to 0 °C (silica gel column chroma-
tography: hexane/ethyl acetate = 3/2 to 1/1, followed by GPC
purification). White solid; Rf value 0.40 (hexane/ethyl acetate = 1/1);
mp 130−131 °C; IR (NaCl, neat) νmax 3366, 2957, 1714, 1380, 1189,
988 cm−1; 1H NMR (500 MHz, CDCl3) δ 8.78 (br-s, 1H), 7.37−7.31
(m, 3H), 7.28−7.24 (m, 5H), 7.15−7.12 (m, 2H), 2.63 (m, 2H), 2.34
(m, 2H), 1.99 (m, 2H), 1.46 (m, 2H), 1.11 (tq, 2H, J = 7.5, 7.5 Hz),
0.75 (t, 3H, J = 7.5 Hz); 13C NMR (126 MHz, CDCl3) δ 175.8, 158.8,
148.2 140.4, 139.1, 130.1, 128.9, 128.35, 128.32, 128.29, 128.1, 123.3,
28.2, 27.9, 27.5, 22.9, 13.6,; HRMS (ESI) calcd for C23H24N2O3Na
[M + Na]+ 399.16846, found 399.16808.
(Procedure B) 22.6 mg (74%) of product 9e was obtained from
allenamide 2a (41.1 mg, 0.075 mmol), bis(2-methoxyethyl)
azodicarboxylate (26.3 mg, 0.113 mmol), tetrabutylammonium
fluoride (1.0 M in THF, 150 μL, 0.15 mmol), and then methyl
L-prolinate hydrochloride (37.3 mg, 0.225 mmol) by a reaction at −60
to 0 °C (silica gel column chromatography: hexane/diethyl ether = 5/1).
Yellow oil ; Rf value 0.37 (hexane/ethyl acetate = 3/1); [α]2D0 + 841.7
(CHCl3, c = 1.0); IR (NaCl, neat) νmax 3187, 2956, 1745, 1560, 1442,
1372, 1172, 763, 700 cm−1; 1H NMR(500 MHz, CDCl3) δ 9.42
(br, 1H), 7.31−7.08 (m, 10H), 3.99 (t, 1H, J = 6.5 Hz), 3.69 (s, 3H),
3.07 (q, 1H, J = 8.5 Hz), 2.79−2.75 (m, 1H), 2.41−2.35 (m, 1H), 2.12−
2.05 (m, 1H), 1.83−1.64 (m, 4H), 1.34−1.14 (m, 4H), 0.81 (t, 3H, J =
7.5 Hz); 13C NMR (126 MHz, CDCl3) δ 174.8, 158.8, 143.1, 143.0,
139.0, 131.1, 130.8, 127.7, 127.6, 125.9, 125.8, 122.8, 60.2, 52.2, 51.8,
30.4, 28.9, 27.5, 24.6, 23.1, 13.8; HRMS (ESI) calcd for C25H30N2O3Na
[M + Na]+ 429.21541, found 429.21467.
(E)-2-Nitro-1,1-diphenylhept-1-en-3-one Oxime (9i, CCDC
1056829).
N-(3-(Hydroxyimino)-1,1-diphenylhept-1-en-2-yl)-4-methyl-
benzenesulfonamide (9f).
(Procedure B) 21.8 mg (90%) of product 9i was obtained from
allenamide 2a (41.1 mg, 0.075 mmol), diisopropyl azodicarboxylate
(22 μL, 0.113 mmol), tetrabutylammonium fluoride (150 μL, 1.0 M
in THF, 0.15 mmol), and then dicyclohexylamine nitrite (51 mg,
0.225 mmol) by a reaction at −78 to 0 °C (silica gel column chroma-
tography: hexane/diethyl ether = 20/1 to 13/1). Yellow solid; Rf value
0.42 (hexane/ethyl acetate = 3/1); mp 110−111 °C; IR (NaCl, neat)
(Procedure A) 21.9 mg (49%) of product 9f was obtained from
allenamide 2a (54.8 mg, 0.10 mmol), bis(2-methoxyethyl) azodicarboxylate
M
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The Journal of Organic Chemistry
Article
νmax 3303, 2958, 1528, 1342, 976, 759, 697 cm−1; 1H NMR (500 MHz,
CDCl3) δ 8.58 (s, 1H), 7.41−7.33 (m, 6H), 7.23−7.19 (m, 4H), 4.26
(t, 2H, J = 8.0 Hz), 1.50 (m, 2H), 1.27 (tq, 2H, J = 7.5, 7.5 Hz), 0.84
(t, 3H, J = 7.5 Hz); 13C NMR (126 MHz, CDCl3) δ 155.8, 144.6,
143.5, 137.6, 137.1, 130.1, 129.8, 129.6, 128.7, 128.6, 128.5, 27.6, 27.0,
22.6, 13.6; HRMS (ESI) calcd for C19H20N2O3Na [M + Na]+
347.13716, found 347.13687.
(tt, 2H, J = 8.0, 7.5 Hz), 1.27 (tq, 2H, J = 7.5, 7.5 Hz), 0.87 (t, 3H, J =
7.5 Hz); 13C NMR (126 MHz, CDCl3) δ 154.9 (d, JC‑F = 29 Hz),
149.9 (d, JC‑F = 255 Hz), 137.7 (d, JC‑F = 6.0 Hz), 137.2, 130.2 (d,
JC‑F = 4.0 Hz), 129.9 (d, JC‑F = 5.0 Hz), 128.3, 128.0, 127.8, 127.7,
125.6 (d, JC‑F = 16 Hz), 27.8, 25.9, 22.7, 13.7; 19F NMR (471 MHz,
CDCl3, hexafluorobenzene δ −162.0) δ −109.9; HRMS (CI) calcd for
C19H21FNO [M + H]+ 298.1607, found 298.1603.
2-Azido-1,1-diphenylhept-1-en-3-one Oxime (9j) (as an Insepa-
rable Mixture with Azirine 9j′).
2-Methoxy-1,1-diphenylhept-1-en-3-one Oxime (9l).
(Procedure A) 3.5 mg (15%) of product 9l was obtained from
allenamide 2a (41.1 mg, 0.075 mmol), diisopropyl azodicarboxylate
(29 μL, 0.15 mmol), methanol (15 μL, 0.375 mmol), and tetrabutyl-
ammonium fluoride (150 μL, 1.0 M in THF, 0.15 mmol) (silica gel
column chromatography: hexane/ethyl acetate = 35/1 to 10/1).
Colorless oil; Rf value 0.46 (hexane/ethyl acetate = 3/1); IR (NaCl,
neat) νmax 3195, 2957, 1596, 1443, 1211, 698 cm−1; 1H NMR
(500 MHz, CDCl3) δ 7.31−7.12 (m, 10H), 3.57 (s, 3H), 2.28 (t, 2H,
J = 8.0 Hz), 1.54 (m, 2H), 1.31 (qt, 2H, J = 7.5, 7.5 Hz), 0.89 (t, 3H,
J = 7.5 Hz); 13C NMR (126 MHz, CDCl3) δ 157.9, 140.2, 139.8,
130.3, 129.7, 128.1, 127.91, 127.89, 126.9, 126.8, 58.0, 27.6, 27.4, 23.1,
13.8; HRMS (ESI) calcd for C20H23NO2Na [M + Na]+ 332.16265,
found 332.16272.
(Procedure B) 45.2 mg (6.7:1 determined by 1H NMR; azide 9j 83%,
azirine 9j′ 12%) of product 9j as an inseparable mixture with azirine
9j′ was obtained from allenamide 2a (82.2 mg, 0.15 mmol), bis-
(2-methoxyethyl) azodicarboxylate (52.7 mg, 0.225 mmol), tetrabu-
tylammonium fluoride (480 μL, 1.0 M in THF, 0.48 mmol), and then
azidotrimethylsilane (40 μL, 0.30 mmol) by a reaction at −60 to 0 °C
(silica gel column chromatography: hexane/ethyl acetate = 10/1). 9j
was an unstable compound, and it was gradually converted to 9j′ even
in a refrigerator. Pale yellow oil; Rf value 0.55 (hexane/ethyl acetate =
3/1); IR (NaCl, neat) νmax 3263, 2959, 2105, 1444, 1298, 751,
1
698 cm−1; H NMR (500 MHz, CDCl3) δ 8.85 (s, 1H), 7.36−7.24
(m, 8H), 7.16−7.14 (m, 2H), 2.08 (t, 2H, J = 8.0 Hz), 1.46−1.38
(m, 2H), 1.25 (tq, 2H, J = 7.5, 7.5 Hz), 0.85 (t, 3H, J = 7.5 Hz); 13C
NMR (126 MHz, CDCl3) δ 158.0, 139.6, 139.3, 132.3, 130.3, 130.2,
129.1, 128.2, 128.0, 127.8, 127.7, 27.7, 27.6, 22.6, 13.7; LRMS (EI)
m/z 320 (M+, 0.2%), 275 (26), 182 (76), 165 (60); HRMS (EI) calcd
for C19H20N4O (M+) 320.1637, found 320.1620.
3-(Hydroxyimino)-1,1-diphenylhept-1-en-2-yl Acetate (9m).
One-Pot Conversion from Allenamide 2a to Pure 1-(2,2-
Diphenyl-2H-azirin-3-yl)pentan-1-one Oxime (9j′, CCDC 1056828)
via Vinyl Azide 9j.
(Procedure A) 17.6 mg (52%) of product 9m was obtained from
allenamide 2a (54.8 mg, 0.10 mmol), bis(2-methoxyethyl) azodicar-
boxylate (35 mg, 0.15 mmol), acetic acid (29 μL, 0.50 mmol), and
tetrabutylammonium fluoride (1.0 M in THF, 400 μL, 0.40 mmol)
(silica gel column chromatography: hexane/ethyl acetate = 10/1 to 3/1).
Colorless oil; Rf value 0.31 (hexane/ethyl acetate = 3/1); IR (NaCl, neat)
νmax 3255, 2958, 1764, 1444, 1212, 766, 699 cm−1; 1H NMR (500 MHz,
CDCl3) δ 8.66 (br, 1H), 7.32−7.16 (m, 10H), 2.05 (t, 2H, J = 8.0 Hz),
2.04 (s, 3H), 1.44 (tt, 2H, J = 8.0, 7.5 Hz), 1.14 (tq, 2H, J = 7.5, 7.0 Hz),
0.78 (t, 3H, J = 7.0 Hz); 13C NMR (126 MHz, CDCl3) δ 169.6, 157.9,
139.5, 139.2, 138.7, 135.4, 130.2, 129.1, 128.3, 128.10, 128.07, 127.7, 27.7,
27.3, 22.9, 20.7, 13.6; HRMS (ESI) calcd for C21H23NO3Na [M + Na]+
360.15756, found 360.15721.
To stirred mixture of allenamide 2a (54.8 mg, 0.10 mmol), diisopropyl
azodicarboxylate (29 μL, 0.15 mmol), and azidotrimethylsilane (20 μL,
0.15 mmol) in THF (2.0 mL) was added tetrabutylammonium
fluoride (270 μL, 1.0 M in THF, 0.15 mmol) at 0 °C. After 10 min, the
mixture was heated under reflux condition for 15 min. The reaction
mixture was extracted with ether and washed with water and brine.
The combined organic layers were dried over sodium sulfate and were
concentrated in vacuo. The resulting residual solid was purified by silica
gel column chromatography (hexane/ethyl acetate = 13/1) to afford
azirine 9j′ (18.1 mg, 62%). White solid; Rf value 0.55 (hexane/ethyl
acetate = 3/1); mp 105−106 °C; IR (NaCl, neat) νmax 3244, 2959,
2-(Naphthalen-2-ylthio)-1,1-diphenylhept-1-en-3-one Oxime
(9n).
1
1731, 1447, 1003, 697 cm−1; H NMR (500 MHz, CDCl3) δ 9.34
(s, 1H), 7.31−7.25 (m, 10H), 2.80 (t, 2H, J = 8.0 Hz), 1.68 (tt, 2H, J =
8.0, 7.5 Hz), 1.37 (tq, 2H, J = 7.5, 7.5 Hz), 0.92 (t, 3H, J = 7.5 Hz);
13C NMR (126 MHz, CDCl3) δ 166.5, 151.2, 140.8, 128.3, 128.1,
127.4, 46.4, 27.7, 25.5, 22.7, 13.7; LRMS (EI) m/z 292 (M+, 23%),
275 (53), 166 (47), 165 (100); HRMS (EI) calcd for C19H20N2O
(M+) 292.1576, found 292.1563.
(Procedure B) 27.4 mg (83%) of product 9n was obtained from
allenamide 2a (0.075 mmol, 41.1 mg), diisopropyl azodicarboxylate
(22 μL, 0.113 mmol), tetrabutylammonium fluoride (150 μL, 1.0 M in
THF, 0.15 mmol), and then 2-naphthalenethiol (0.113 mmol, 18 mg)
by a reaction at −78 to 0 °C (silica gel column chromatography:
hexane/toluene = 1/1 to 1/3). Pale yellow solid; Rf value 0.43
(hexane/ethyl acetate = 3/1); mp 90−91 °C; IR (NaCl, neat) νmax
3191, 2957, 1442, 944, 758, 698 cm−1; 1H NMR (500 MHz, CDCl3) δ
8.32 (br, 1H), 7.73−7.63 (m, 4H), 7.42−7.37 (m, 3H), 7.32−7.14
(m, 10H), 2.29 (t, 2H, J = 8.0 Hz), 1.37 (tt, 2H, J = 8.0, 7.5 Hz), 1.21
(qt, 2H, J = 7.5, 7.0 Hz), 0.80 (t, 3H, J = 7.0 Hz); 13C NMR
(126 MHz, CDCl3) δ 158.9, 150.2, 142.1, 141.7, 133.6, 132.6, 131.8,
129.5, 129.4, 129.0, 128.3, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6,
127.4, 127.3, 126.3, 125.7, 28.9, 27.7, 23.1, 13.7; LRMS (EI) m/z 437
(M+, 53%), 420 (53), 210 (100); HRMS (EI) calcd for C29H27NOS
(M+) 437.1813, found 437.1815.
2-Fluoro-1,1-diphenylhept-1-en-3-one Oxime (9k).
(Procedure B) 25.6 mg (43%) of product 9k was obtained from
allenamide 2a (109.6 mg, 0.20 mmol), bis(2-methoxyethyl)
azodicarboxylate (70.3 mg, 0.30 mmol), and tetrabutylammonium
fluoride (2.0 mL, 1.0 M in THF, 2.0 mmol, used without dehydration)
by a reaction at −78 to 0 °C (silica gel column chromatography:
hexane/ethyl acetate = 10/1). Colorless oil; Rf value 0.57 (hexane/
ethyl acetate = 3/1); IR (NaCl, neat) νmax 3232, 2958, 1444, 1186,
1,1-Diphenyl-2-(phenylsulfonyl)hept-1-en-3-one Oxime (5b)
from Allenyl Tosylamide (2a). (Procedure B) 41.4 mg (99%) of
product 5b was obtained from tosyl allenamide 2a (54.8 mg,
0.10 mmol), bis(2-methoxyethyl) azodicarboxylate (35 mg, 0.15 mmol),
1
963, 367, 697 cm−1; H NMR (500 MHz, CDCl3) δ 8.80 (br, 1H),
7.33−7.25 (m, 8H), 7.16−7.14 (m, 2H), 2.25 (t, 2H, J = 8.0 Hz), 1.48
N
DOI: 10.1021/acs.joc.5b02364
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The Journal of Organic Chemistry
Article
tetrabutylammonium fluoride (200 μL, 1.0 M in THF, 0.20 mmol),
and then sodium benzenesulfinate (60 mg, 0.30 mmol) dissolved in
methanol (1.0 mL) by a reaction at −60 to 0 °C (silica gel column
chromatography: hexane/ethyl acetate = 7/1 to 3/1).
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: tanimoto@ms.naist.jp.
2-(Diphenylmethylene)-3-(hydroxyimino)heptanenitrile (9o).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(Procedure A) 22.1 mg (94%) of product 9o was obtained from
allenamide 2a (41.1 mg, 0.075 mmol), diisopropyl azodicarboxylate
(22 μL, 0.113 mmol), trimethylsilyl cyanide (14 μL, 0.113 mmol), and
tetrabutylammonium fluoride (200 μL, 1.0 M in THF, 0.20 mmol)
(silica gel column chromatography: hexane/diethyl ether = 35/1 to
10/1). No-odor white solid; Rf value 0.33 (hexane/ethyl acetate = 3/1);
mp 170−172 °C; IR (NaCl, neat) νmax 3278, 2954, 2208, 1555, 1444,
966, 700 cm−1; 1H NMR (500 MHz, CDCl3) δ 8.31 (br, 1H), 7.46−7.34
(m, 8H), 7.18−7.16 (m, 2H), 2.13 (t, 2H, J = 8.0 Hz), 1.45 (tt, 2H, J =
8.0, 7.5 Hz), 1.25 (qt, 2H, J = 7.5, 7.5 Hz), 0.84 (t, 3H, J = 7.5 Hz); 13C
NMR (126 MHz, CDCl3) δ 161.0, 157.4, 139.2, 138.6, 130.3, 130.04,
129.96, 128.5, 118.5, 107.3, 27.9, 27.2, 22.6, 13.7; HRMS (ESI) calcd for
C20H20N2ONa [M + Na]+ 327.14733, found 327.14716.
This work was supported in part by Grants-in-Aid of MEXT for
Young Scientists (B) (15K17856). We acknowledge the
fellowship of the Japan Chemical Industry Association, and
the presidential special research support fellowship of NAIST
for Y.M. We also thank Ms. Yuriko Nishiyama, Ms. Yoshiko
Nishikawa, Mr. Kazuo Fukuda (MS), Mr. Fumio Asanoma
(elemental analysis), and Mr. Shohei Katao (X-ray analysis) of
NAIST. We acknowledge Kuraray Co., Ltd., for the gift of 4-
Me-THP, and UNISOKU, Co., Ltd., for use of cell and cryostat
on low temperature IR experiments).
Analytical Data of 1-Tosylhydrazine-1,2-dicarboxylates. Yields
of obtained hydrazides 10a−b were not calculated, but 10a−b was easily
obtained by a general procedure of sulfinate-trapping substitutions.
Diisopropyl 1-Tosylhydrazine-1,2-dicarboxylate (10a).
REFERENCES
■
(1) For a review, see: (a) Groenendaal, B.; Ruijter, E.; Orru, R. V. A.
Chem. Commun. 2008, 5474. For other recent works, see: (b) Tanaka,
K.; Siwu, E. R. O.; Hirosaki, S.; Iwata, T.; Matsumoto, R.; Kitagawa, Y.;
Pradipta, A. R.; Okumura, M.; Fukase, K. Tetrahedron Lett. 2012, 53,
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S.; Kudo, K.; Ito, A.; Honjo, T.; Yata, M.; Otani, T.; Kutsumura, N.;
Colorless crystal; Rf value 0.31 (hexane/ethyl acetate = 3/1); mp
93−95 °C; IR (NaCl, neat) νmax 3331, 2984, 1743, 1375, 1241, 1175,
1103 cm−1; 1H NMR (500 MHz, CDCl3) δ 8.00 (d, 2H, J = 8.5 Hz),
7.33 (d, 2H, J = 8.5 Hz), 7.00 (s, 1H), 5.00−4.90 (m, 2H), 2.44
(s, 3H), 1.33−1.14 (m, 12H); 13C NMR (126 MHz, CDCl3) δ 154.4,
150.9,145.2, 135.0, 129.5, 129.2, 72.9, 70.9, 21.9, 21.7, 21.6; HRMS
(ESI) calcd for C15H22N2NaO6S [M + Na]+ 381.10963, found
381.11054.
́
Saito, T.; Berree, F.; Romain, E.; Tripoteau, F.; Carboni, B. Eur. J. Org.
Chem. 2015, 2015, 4367. (i) Phillips, E. M.; Mesganaw, T.; Patel, A.;
Duttwyler, S.; Mercado, B. Q.; Houk, K. N.; Ellman, J. A. Angew.
Chem., Int. Ed. 2015, 54, 12044.
Bis(methoxyethyl) 1-Tosylhydrazine-1,2-dicarboxylate (10b).
(2) For our previous works on the synthesis of unsaturated imines
and its application to natural product synthesis, see: (a) Hayashi, K.;
Tanimoto, H.; Zhang, H.; Morimoto, T.; Nishiyama, Y.; Kakiuchi, K.
Org. Lett. 2012, 14, 5728. (b) Tanimoto, H.; Kakiuchi, K. Nat. Prod.
Commun. 2013, 8, 1021. (c) Zhang, H.; Hayashi, K.; Tanimoto, H.;
Morimoto, T.; Nishiyama, Y.; Kakiuchi, K. Tetrahedron 2014, 70, 8600.
Other examples of enimine alkaloid synthesis; see: (d) Cuthbertson, J.
D.; Taylor, R. J. K. Angew. Chem., Int. Ed. 2013, 52, 1490. (e) Baran, P.
S.; Shenvi, R. A. J. Am. Chem. Soc. 2006, 128, 14028.
(3) (a) Zhang, H.; Tanimoto, H.; Morimoto, T.; Nishiyama, Y.;
Kakiuchi, K. Org. Lett. 2013, 15, 5222. (b) Zhang, H.; Tanimoto, H.;
Morimoto, T.; Nishiyama, Y.; Kakiuchi, K. Tetrahedron 2014, 70, 9828.
For our works on the synthesis of α-amino acids by umpolung
functionalizations, see: (c) Mizutani, Y.; Tanimoto, H.; Morimoto, T.;
Nishiyama, Y.; Kakiuchi, K. Tetrahedron Lett. 2012, 53, 5903.
(4) For similar reactions of allenols, see: Gronnier, C.; Kramer, S.;
Odabachian, Y.; Gagosz, F. J. Am. Chem. Soc. 2012, 134, 828.
(5) Phosphine-catalyzed synthesis of α-substituted enonates from
alkynoates has been developed by Trost et al. See: (a) Trost, B. M.;
Dake, G. R. J. Am. Chem. Soc. 1997, 119, 7595. (b) Lu, C.; Lu, X. Org.
White solid; Rf value 0.25 (hexane/ethyl acetate = 1/1); mp 93 °C;
IR (NaCl, neat) νmax 3675, 3331, 2929, 1746, 1523, 1377, 1233,
1068 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.99 (d, 2H, J = 8.0 Hz),
7.66 (s, 1H), 7.32 (d, 2H, J = 8.0 Hz), 4.34−4.20 (m, 4H), 3.63 (t, 2H,
J = 4.0 Hz), 3.51 (t, 2H, J = 4.0 Hz), 3.40 (s, 3H), 3.31 (s, 3H), 2.43
(s, 3H); 13C NMR (126 MHz, CDCl3) δ 154.8, 151.4, 145.3, 134.7,
129.6, 129.2, 70.4, 69.8, 66.8, 65.5, 59.0, 58.8, 21.7; HRMS (ESI) calcd
for C15H22N2NaO8S [M + Na]+ 413.09946, found 413.09919.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b02364.
■
S
The results of low temperature IR, and 1H and 13C NMR
spectra (PDF)
Crystallographic data of new compound (CCDC number
́
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Yoshida, M.; Doi, T. Chem. Lett. 2015, 44, 141.
1056828) 9j′ (CIF)
Crystallographic data of new compound (CCDC number
1056829) 9i (CIF)
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1056830) 6 (CIF)
Crystallographic data of new compound (CCDC number
1056831) 5a′ (CIF)
Crystallographic data of new compound (CCDC number
1056832) (Z)-5p (CIF)
O
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