A convenient synthesis of γ-amino-ynamides via additions of lithiated ynamides to aryl imines; Observation of an aza-meyer-schuster rearrangement

Article abstract of DOI:10.1055/s-0033-1338476

Efforts in developing an expeditious and convenient method for synthesizing γ-amino-ynamides via nucleophilic addition of lithiated ynamides to aryl imines are described. This work also features an aza-variant of a Meyer-Schuster rearrangement of γ-amino-ynamides and their synthetic utility in intramolecular ketenimine [2+2] cycloadditions. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0033-1338476

PAPER
▌1749
paper
A Convenient Synthesis of γ-Amino-Ynamides via Additions of Lithiated Ynamides
to Aryl Imines; Observation of an Aza-Meyer–Schuster Rearrangement
Synthesis of γ-Amino-Ynamides
Rui Qi,a Xiao-Na Wang,b Kyle A. DeKorver,*c Yu Tang,*a Chao-Chao Wang,a Qian Li,a Hui Li,a Ming-Can Lv,a
Qing Yu,a Richard P. Hsung*b
a
School of Pharmaceutical Science and Technology, and Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, Tianjin
University, Tianjin 300072, P. R. of China
E-mail: tangyu114@gmail.com
b
Department of Chemistry and Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin–Madison, Madison,
WI 53705, USA
E-mail: rhsung@wisc.edu
c
Dow AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 46268, USA
Fax +1(608)2625345; E-mail: kadekorver@dow.com
Received: 25.03.2013; Accepted after revision: 14.04.2013
With the deepest respect and admiration, we dedicate this paper to Professor Scott E. Denmark on the very special occasion of his 60th
birthday.
zing ynamides3 and their structural relatives5,6 have con-
Abstract: Efforts in developing an expeditious and convenient
tinued to appear in the literature.3e Recently, when we
method for synthesizing γ-amino-ynamides via nucleophilic addi-
employed γ-amino-ynamides 1 (see Scheme 1) to develop
tion of lithiated ynamides to aryl imines are described. This work
also features an aza-variant of a Meyer–Schuster rearrangement of
N-tethered intramolecular transformations for construct-
γ-amino-ynamides and their synthetic utility in intramolecular ing N-heterocycles,7 we recognized that this class of yn-
ketenimine [2+2] cycloadditions.
amides was not trivial to make.
The existing copper-catalyzed protocols,1,2,5 albeit attrac-
tive, may not be suitable to couple directly amides with N-
Key words: lithiated ynamides, γ-amino-ynamides, aryl imines,
azetene, aza-Meyer–Schuster rearrangement
unprotected propargyl amines 3 (see retrosynthetic cleav-
age a).8 On the other hand, with N-protected propargyl
We have been involved with the chemistry of ynamides
for the last 17 years, and this burgeoning field has attract-
ed significant attention from the synthetic community.1–4
Consequently, new and improved protocols for synthesi-
amines 5, it would constitute an encumbered process, in
addition to the fact that the penultimate deprotection step
could still pose problems to the stability of the ynamides.
The most direct access would be retrosynthetic pathway b,
R3
H
Cu(II)
H
a
EWG
EWG
R
N
R2
EWG
R
N
R2
N
R2
+
NH
X
N
N
γ
γ
R
R1
R1
R1
N-unprotected
1: γ-amino-ynamides
2
3: X = H or Br
removing "PG" with
ynamide surviving
PG
H
PG
EWG
R
Cu(II)
N-protection
EWG
R
N
R2
R2
N
R2
N
+
NH
N
X
γ
R1
R1
R1
4: PG = protecting group
5: X = H or Br
6: propargyl amines
N-heterocycle syn
fn1
H
fn2
b
R2
EWG
N
EWG
R
N
R2
N
M
H
γ
R1
N
R1
EWG
N
R
N
2
7: M = metal
R
R1
Scheme 1 Possible approaches to γ-amino-ynamides; fn = functional group
SYNTHESIS 2013, 45, 1749–1758
Advanced online publication: 15.05.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338476; Art ID: SS-2013-C0233-OP
© Georg Thieme Verlag Stuttgart · New York

1750
R. Qi et al.
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in which the metallated ynamide 7 could be added to a ni- What intrigued us was that some of these γ-amino-
trogen source in the form of an imine. While metallated ynamides were not overtly stable to silica gel column
ynamides have been added to a number of electrophiles,9 chromatography, and appeared to rearrange cleanly into
to the best of our knowledge, their addition to imines re- another compound, especially in the presence of acid.
mains unreported.1 Inspired by Poisson’s recent account10 Upon further examination, we found that ynamide 12a un-
on additions of lithiated ynol ethers to imines,11 we derwent rearrangement into α,β-unsaturated amidine 16
explored this potentially expeditious method. We report when treated with triflimide (HNTf2) (5 mol%) at room
here a general and convenient protocol for synthesizing temperature (Scheme 3). The assignment of amidine 16
γ-amino-ynamides.
was confirmed through its single crystal X-ray structure
(Figure 1). Two possible mechanistic pathways can be
proposed to account for this rearrangement. Pathway ‘a’
features an acid-promoted γ-elimination followed by reas-
sociation of the departing amide with the allenylidine im-
inium ion 17. Pathway ‘b’ favors an intramolecular non-
dissociative possibility through pericyclic ring-opening of
azetene intermediate 19.13
Deprotonation of ynamides 8 with lithium hexamethyl-
disilazide (LHMDS) (1.5 equiv) in tetrahydrofuran at
–50 °C, followed by the addition of various imines, turned
out to be a highly efficient protocol. A diverse array of N-
sulfonyl or N-carbamoyl-γ-amino-ynamides 9–15 could
be accessed in good yields through this simple method
(Scheme 2). Examples of the ynamide precursors includ-
ed: oxazolidinone-substituted (9a–d, 10 and 11), sulfo- To further delineate these two possibilities, we carried out
nyl-substituted (12a–e, 13 and 14), or even phosphoryl- the following crossover experiments (Scheme 4). After
substituted12 (15). Ketimines were also suitable substrates treating a mixture of γ-amino-ynamides 12a and 12f in a
(10 and 13), while aldimines were represented by elec- ratio of either 4:1 (reaction A), or 1:4 (reaction B) with N-
tron-withdrawing (12d) or -donating (9d and 12e) sulfo- phenyl-bis(trifluoromethanesulfonimide) (5 mol%), we
nyl systems.
examined closely the crude reaction mixture and all the
H
EWG
R
LHMDS (1.5 equiv), THF, –50 °C
EWG
R
N
EWG
N
H
N
N
EWG
–50 °C, 1 h
Ar
H
8
9–15
(1.5 equiv)
Ar
O
O
Ts
O
N
Ts
Ts
NH
NH
NH
O
O
O
N
N
O
N
9a: 68%a
9b: 80%
9c: 81%
Boc
O
Ts
O
N
O
PMBS
Cbz
NH
Ph
Ph
NH
NH
O
O
O
N
N
9d: 72%b
10: 73%
11: 61%
Ts
Bn
Ts
Bn
Ts
Bn
N
Ts
Bn
N
N
N
Ts
Ns
Ts
Ts
N
H
N
N
H
N
H
H
N
O
Boc
12c: 79%
12a: 84%
Ts
Bn
12b: 67%
12d: 78%
O
O
O
Ts
Ts
Bn
N
P
N
N
N
Ph
Ph
Ts
Ts
PMBS
Ts
N
N
H
N
N
H
H
H
12e: 70%
13: 65%
14: 74%
15: 48%
Scheme 2 Addition of lithiated ynamides to aryl imines. Yields are those of isolated products. PMBS = p-methoxybenzenesulfonyl.
Synthesis 2013, 45, 1749–1758
© Georg Thieme Verlag Stuttgart · New York

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Synthesis of γ-Amino-Ynamides
1751
Ts
Bn
Ts
Bn
N
N
N
b
HNTf2 (5 mol%), CH2Cl2, r.t., 10 min
an acid-promoted rearrangement
Ts
a
H
Ts
N
H
H
12a
16: 78%
pericyclic ring-opening
Ts
pathway a
Ts
pathway b
Ts
N
Bn
Bn
H
Bn
N
N
H
N
•
H
N
•
N
Ts
H
Ts
•
H
Ts
17: allenylidine iminium ion
18
19: azetene
Scheme 3 Acid-promoted rearrangement of ynamide 12a
fractions resulting from purification of both reactions. We
did not find possible crossover products 16af and 16fa in
1
either reaction using H NMR spectroscopy, and yn-
amides 12a and 12f, in both reactions, appeared to yield
only their respective rearranged products 16a and 16f.
The presence of products 16af and 16fa would have im-
plied pathway a being operative.
To be more precise, we scanned the crude mixtures from
incomplete reactions using LC–MS, and impressively, we
did not find fractions with a mass that would correlate to
either 16af or 16fa (see red arrows in Figure 2, which in-
dicate where 16af and 16fa would be respectively, when
co-injected with the crude mixtures from reactions A and
B). It is noteworthy that rearrangement of ynamide 12a
appears to be much faster than that of 12f. These results
suggest the rearrangement occurs via pathway b involving
the formation of azetene 19 and pericyclic ring-opening.
Related ring-openings through oxetenes14,15 are quite well
Figure 1 X-ray crystal structure of vinyl amidine 16 (ORTEP repre-
sentation; CCDC 937489)
known, and the current rearrangement essentially consti-
tutes an aza-variant of the Meyer–Schuster rearrange-
ment.16
Ts
Bn
Ts
Bn
Ts
Bn
N
N
N
PMBS
PMBS
N
N
PMBS
N
H
16af: m/z [M + H]+ 561.1
12f: m/z [M + H]+ 611.2
16f: m/z [M + H]+ 611.2
[M + Na]+ 633.1
[M + Na]+ 633.2
not seen
[M + K]+ 649.1
HNTf2 (5 mol%)
CH2Cl2, r.t.
and
Ts
Bn
Ts
Bn
Ts
Bn
N
N
N
Ts
Ts
N
N
Ts
N
H
16fa: m/z [M + H]+ 595.2
12a: m/z [M + H]+ 545.2
16a: m/z [M + H]+ 545.2
[M + Na]+ 567.1
[M + Na]+ 567.2
not seen
[M + K]+ 583.1
Scheme 4 A crossover experiment
© Georg Thieme Verlag Stuttgart · New York
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R. Qi et al.
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Ph
O
Ts
Ph
OH
NH
O
O
N
NTs
Ph
O
DIAD, Ph3P, THF, 15 h
N
9a
20: 60%
O
O
O
Ts
Bn
Ts
N
P
N
N
Ph
Ph
N
N
N
Ts
Ts
Ts
21: 37% from 12a
22: 44% from 14
23: 57% from 15
Scheme 5 N-Allylations of γ-amino-ynamides
While this rearrangement is of interest both synthetically
and mechanistically, and that this has become an ongoing
project of another focus, we demonstrate here how these
γ-amino-ynamides can be utilized in further transforma-
tions. As shown in Scheme 5, the γ-amino group in 9a
could be readily N-allylated using Mitsunobu conditions,
leading to ynamide 20 in 60% yield. This N-allylation
proved to be quite general for a number of γ-amino-yn-
amides such as 12a, 14, and 15 to give N-allylated prod-
ucts 21–23, respectively. An immediate application of
these products is in a palladium(0)-catalyzed aza-Claisen
rearrangement17–19 in tandem with ketenimine [2+2] cy-
cloaddition,20–23 leading to either a rare crossed cycload-
duct 24 from ynamide 22, or fused cycloadduct 25 derived
from ynamide 23 in a highly stereoselective manner
(Scheme 6).7
In conclusion, we have described herein our efforts in de-
veloping an expeditious and convenient method for syn-
thesizing γ-amino-ynamides via nucleophilic addition of
lithiated ynamides to aryl imines. In this study, we also
uncovered an aza-variant of a Meyer–Schuster rearrange-
Figure 2 LC–MS traces from crossover experiments A and B
Ts
Ts
N
Ph
N
Ts
N
Ph
Ph
•
Pd(PPh3)4 (5 mol%)
Ln
Ts
N
Ts
toluene, 70 °C, 2 h
N
PdII
H
Ph
Ph
N
H
Ts
Ph
24: 95%; single isomer
22
crossed-[2+2]
O
O
Ph
O
P
PdII
Ln
O
O
O
N
Ts
same as
above
P
N
N
H
•
N
O
O
P
N
Ts
O
Ph
N
Ts
25: 85%; dr = 9:1
23
fused-[2+2]
Scheme 6 Application of γ-amino-ynamides in [2+2] cycloadditions
Synthesis 2013, 45, 1749–1758
© Georg Thieme Verlag Stuttgart · New York

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Synthesis of γ-Amino-Ynamides
1753
13C NMR (100 MHz, DMSO-d6): δ = 21.5, 43.7, 46.4, 63.1, 66.5,
75.3, 108.6, 110.5, 127.4, 129.5, 137.4, 143.1, 143.5, 149.2, 155.6.
MS (ESI): m/z (%) = 743 (100) [2 M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C17H16N2O5SNa: 383.0672;
ment of γ-amino-ynamides and demonstrated the useful-
ness of these γ-amino-ynamides in designing
intramolecular transformations.
found: 383.0675.
1H and 13C NMR spectra were recorded on a Bruker Avance 600
MHz spectrometer at 25 °C. Chemical shift values are given in ppm
and referenced to SiMe4 as the internal standard (0.00 ppm). The
peak patterns are indicated as follows: s, singlet; d, doublet; t, trip-
let; q, quartet; qui, quintet; m, multiplet and dd, doublet of doublets.
The coupling constants, J, are reported in hertz (Hz). IR spectra
were recorded on a Bio Rad FTS-185 Fourier Transform infrared
spectrophotometer. Mass spectra were obtained on an Agilent 6310
ion trap and HP5989A mass spectrometer. High-resolution mass
spectrometry (HRMS) was conducted on a Bruker Micro Q-TOF
spectrometer. Melting points were determined with a National Micro
Melting point apparatus without corrections. Organic solutions
were concentrated by rotary evaporation below 40 °C under vacu-
um. TLC plates were visualized by exposure to ultraviolet light.
3-[1-(4-Methylphenylsulfonamido)-3-(2-oxooxazolidin-3-
yl)prop-2-yn-1-yl]-1-tert-butoxycarbonyl-1H-indole (9c)
Yield: 0.26 g (81%); white solid; mp 199–201 °C; Rf = 0.33 (hex-
anes–EtOAc, 2:3).
IR (KBr): 1367 (s), 1408 (m), 1435 (w), 1454 (m), 1478 (m), 1566
(w), 1598 (w), 1731 (s), 1782 (s), 2270 (w), 2355 (w), 2914 (w),
2986 (w), 3246 (br, s) cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.66 (s, 9 H), 2.42 (s, 3 H), 3.59–
3.71 (ddd, J = 8.4, 16.4, 24.4 Hz, 2 H), 4.38 (t, J = 8.0 Hz, 2 H),
4.93 (d, J = 8.8 Hz, 1 H), 5.59 (d, J = 8.8 Hz, 1 H), 7.21–7.24 (m, 3
H), 7.30–7.33 (t, J = 8.0 Hz, 1 H), 7.68 (d, J = 8.0 Hz, 1 H), 7.71 (s,
1 H), 7.80 (d, J = 8.0 Hz, 2 H), 8.10 (d, J = 8.0 Hz, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 21.4, 28.1, 42.0, 46.5, 64.1,
67.5, 76.0, 84.5, 115.2, 118.4, 120.5, 123.2, 125.0, 125.2, 127.4,
128.0, 129.7, 135.7, 138.6, 143.1, 149.3, 156.3.
Reagents and solvents were purchased as reagent grade and were
used without further purification. Flash column chromatography
was performed over silica gel 100–200 mesh and the eluent was a
mixture of ethyl acetate and petroleum ether (PE).
MS (ESI): m/z (%) = 1041 (100) [2 M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C26H27N3O6SNa: 532.1513;
found: 532.1516.
γ-Amino-Ynamides; General Procedure
To a soln of the ynamide (0.1 M in freshly distilled THF) at –50 °C
was added dropwise LHMDS (1.5 equiv, 1.0 M soln in THF) via a
syringe. The mixture was allowed to stir at –50 °C for 1 h to ensure
complete deprotonation. Next, a soln of the imine (1.5 equiv, 1.5 M
in freshly distilled THF) was added over 10 min. After 1 h, H2O (5
mL) was added and the mixture was allowed to warm to r.t., and
then diluted with EtOAc. The organic phase was separated and the
aq phase extracted twice with EtOAc. The combined organic phase
was washed with sat. aq NaCl soln, dried over Na2SO4, and concen-
trated in vacuo. The crude residue was purified by silica gel flash
column chromatography (gradient elution: EtOAc in PE) to give the
corresponding γ-amino-ynamide.
4-Methoxy-N-[3-(2-oxooxazolidin-3-yl)-1-phenylprop-2-yn-1-
yl]benzenesulfonamide (9d)
Yield: 0.18 g (72%); white solid; mp 148–150 °C; Rf = 0.26 (hex-
anes–EtOAc, 2:3).
IR (KBr): 1421 (m), 1477 (m), 1499 (m), 1579 (m), 1596 (m), 1757
(s), 2260 (m), 2848 (w), 2916 (w), 2974 (w), 3010 (w), 3032 (w),
3080 (w), 3292 (br, s) cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.66–3.70 (ddd, J = 9.2, 16.4, 24.8
Hz, 2 H), 3.88 (s, 3 H), 4.38 (t, J = 8.0 Hz, 2 H), 4.98 (d, J = 8.8 Hz,
1 H), 5.46 (d, J = 6.8 Hz, 1 H), 6.99 (d, J = 8.8 Hz, 2 H), 7.29–7.34
(m, 3 H), 7.48 (d, J = 8.0 Hz, 2 H), 7.85 (d, J = 8.8 Hz, 2 H).
13C NMR (100 MHz, DMSO-d6): δ = 46.5, 48.9, 56.1, 64.0, 68.4,
77.0, 114.5, 127.6, 128.3, 128.8, 129.4, 133.4, 138.9, 156.0, 162.6.
MS (ESI): m/z (%) = 795 (100) [2 M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C19H18N2O5SNa: 409.0829;
4-Methyl-N-[3-(2-oxooxazolidin-3-yl)-1-phenylprop-2-yn-1-
yl]benzenesulfonamide (9a)
Yield: 0.16 g (68%); white solid; mp 147–149 °C; Rf = 0.46 (hex-
anes–EtOAc, 2:3).
IR (KBr): 1415 (m), 1475 (m), 1492 (w), 1597 (w), 1761 (s), 1928
(w), 2268 (m), 2912 (w), 2972 (w), 3062 (w), 3086 (w), 3263 (br, s)
cm–1.
found: 409.0828.
1H NMR (400 MHz, CDCl3): δ = 2.43 (s, 3 H), 3.64–3.73 (ddd,
J = 8.4, 16.3, 22.7 Hz, 2 H), 4.39 (t, J = 8.0 Hz, 2 H), 4.92 (d,
J = 8.4 Hz, 1 H), 5.48 (d, J = 8.4 Hz, 1 H), 7.29–7.34 (m, 5 H), 7.47
(d, J = 6.8 Hz, 2 H), 7.80 (d, J = 8.4 Hz, 2 H).
4-Methyl-N-[3-(2-oxooxazolidin-3-yl)-1,1-diphenylprop-2-yn-
1-yl]benzenesulfonamide (10)
Yield: 0.15 g (73%); white solid; mp 183–185 °C; Rf = 0.30 (hex-
anes–EtOAc, 7:3).
13C NMR (100 MHz, DMSO-d6): δ = 21.4, 46.7, 48.9, 64.0, 68.2,
77.0, 127.3, 127.6, 128.4, 128.9, 129.8, 138.80, 138.82, 143.1,
156.1.
IR (KBr): 1421 (m), 1449 (w), 1479 (w), 1599 (w), 1632 (w), 1767
(s), 2266 (m), 2320 (w), 2378 (w), 2878 (w), 2920 (w), 2938 (w),
3059 (w), 3165 (s), 3440 (br, s) cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.41 (s, 3 H), 3.78 (t, J = 8.0 Hz,
2 H), 4.40 (t, J = 8.0 Hz, 2 H), 5.38 (s, 1 H), 7.19 (d, J = 4.0 Hz, 2
H), 7.24–7.33 (m, 6 H), 7.50 (d, J = 8.0 Hz, 4 H), 7.61 (d, J = 8.0
Hz, 2 H).
MS (ESI): m/z (%) = 763 (100) [2 M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C19H18N2O4SNa: 393.0879;
found: 393.0880.
13C NMR (100 MHz, DMSO-d6): δ = 21.4, 46.4, 62.7, 64.1, 70.5,
79.9, 127.2, 127.4, 127.8, 128.4, 129.3, 140.4, 142.6, 143.8, 156.1.
MS (ESI): m/z (%) = 915 (100) [2 M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C25H22N2O4SNa: 469.1192;
N-[1-(Furan-2-yl)-3-(2-oxooxazolidin-3-yl)prop-2-yn-1-yl]-4-
methylbenzenesulfonamide (9b)
Yield: 0.18 g (80%); light yellow solid; mp 155–157 °C; Rf = 0.41
(hexanes–EtOAc, 2:3).
IR (KBr): 1373 (w), 1386 (w), 1423 (s), 1445 (w), 1477 (m), 1497
(w), 1597 (w), 1747 (s), 1984 (w), 2274 (m), 2860 (w), 2910 (w),
3205 (br, s) cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.42 (s, 3 H), 3.73 (t, J = 8.0 Hz,
2 H), 4.39 (t, J = 8.0 Hz, 2 H), 5.16 (d, J = 8.0 Hz, 1 H), 5.52 (d,
J = 8.0 Hz, 1 H), 6.26 (d, J = 3.2 Hz, 1 H), 6.36 (d, J = 3.2 Hz, 1 H),
7.28 (s, 1 H), 7.30 (d, J = 6.8 Hz, 2 H), 7.77 (d, J = 8.4 Hz, 2 H).
found: 469.1192.
Benzyl 3-(2-Oxooxazolidin-3-yl)-1-phenylprop-2-yn-1-ylcarba-
mate (11)
Yield: 0.26 g (61%); white solid; mp 102–104 °C; Rf = 0.56 (hex-
anes–EtOAc, 2:3).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1749–1758

1754
R. Qi et al.
PAPER
IR (KBr): 1377 (w), 1421 (m), 1454 (w), 1475 (w), 1493 (w), 1526
(s), 1687 (s), 1773 (s), 2262 (m), 2330 (w), 2360 (w), 2920 (w),
3033 (w), 3057 (w), 3309 (br, s) cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.91 (t, J = 8.0 Hz, 2 H), 4.44 (t,
J = 8.0 Hz, 2 H), 5.14 (dd, J = 12.0, 16.0 Hz, 2 H), 5.30 (d, J = 8.8
Hz, 1 H), 5.85 (d, J = 8.8 Hz, 1 H), 7.29–7.38 (m, 6 H), 7.52 (d,
J = 7.2 Hz, 2 H).
13C NMR (100 MHz, DMSO-d6): δ = 46.5, 46.9, 64.1, 66.2, 69.6,
75.6, 127.3, 128.2, 128.27, 128.34, 128.8, 128.9, 137.3, 140.0,
155.9, 156.5.
13C NMR (100 MHz, CDCl3): δ = 21.4, 21.6, 28.1, 42.7, 55.1, 67.7,
79.0, 84.0, 115.1, 117.5, 119.7, 122.8, 124.7, 124.9, 127.2, 127.4,
127.5, 128.3, 128.4, 128.5, 129.3, 129.7, 134.2, 134.6, 135.9, 137.2,
143.3, 144.7, 149.3.
MS (ESI): m/z (%) = 1389 (100) [2 M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C37H37N3O6S2Na: 706.2016;
found: 706.2016.
N-Benzyl-4-methyl-N-[3-(4-nitrophenylsulfonamido)-3-phenyl-
prop-1-yn-1-yl]benzenesulfonamide (12d)
Yield: 0.16 g (78%); white solid; mp 141–143 °C; Rf = 0.38 (hex-
anes–EtOAc, 7:3).
MS (ESI): m/z (%) = 723 (38) [2 M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C20H18N2O4Na: 373.1159;
IR (KBr): 1167 (s), 1348 (s), 1529 (s), 1597 (w), 2248 (m), 3275 (s)
cm–1.
found: 373.1159.
1H NMR (400 MHz, CDCl3): δ = 2.45 (s, 3 H), 4.32 (s, 2 H), 5.33
(d, J = 8.0 Hz, 1 H), 5.47 (d, J = 8.0 Hz, 1 H), 7.15 (d, J = 6.8 Hz, 2
H), 7.20–7.27 (m, 6 H), 7.29–7.33 (m, 4 H), 7.64 (d, J = 8.4 Hz, 2
H), 7.90 (d, J = 8.8 Hz, 2 H), 8.15 (d, J = 8.8 Hz, 2 H).
N-Benzyl-4-methyl-N-[3-(4-methylphenylsulfonamido)-3-
phenylprop-1-yn-1-yl]benzenesulfonamide (12a)
Yield: 0.61 g (84%); white solid; mp 158–160 °C; Rf = 0.28 (hex-
anes–EtOAc, 2:3).
IR (KBr): 1362 (s), 1400 (w), 1427 (m), 1450 (m), 1492 (m), 1597
(m), 1917 (w), 1964 (w), 2249 (m), 2367 (w), 2837 (w), 2871 (w),
2922 (w), 3070 (w), 3275 (br, s) cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.37 (s, 3 H), 2.43 (s, 3 H), 4.29
(dd, J = 13.6, 20.8 Hz, 2 H), 4.72 (d, J = 8.4 Hz, 1 H), 5.34 (d,
J = 8.4 Hz, 1 H), 7.12 (d, J = 6.8 Hz, 2 H), 7.18–7.20 (m, 5 H),
7.22–7.26 (m, 4 H), 7.29–7.33 (m, 3 H), 7.60 (d, J = 8.4 Hz, 2 H),
7.68 (d, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, DMSO-d6): δ = 21.6, 49.8, 55.0, 68.0, 80.4,
124.1, 127.2, 127.5, 128.2, 128.5, 128.6, 128.7, 129.9, 133.9, 134.3,
137.1, 145.0, 146.1, 149.8 (2 carbon signals missing due to over-
lap).
MS (ESI): m/z (%) = 1173 (100) [2 M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C29H25N3O6S2Na: 598.1077;
found: 598.1057.
13C NMR (100 MHz, DMSO-d6): δ = 21.4, 21.6, 48.8, 55.2, 68.7,
79.4, 127.1, 127.6, 127.9, 128.3, 128.6, 128.73, 128.74, 128.9,
129.7, 130.5, 134.4, 135.2, 138.9, 139.2, 142.8, 145.4.
MS (ESI): m/z (%) = 1111 (100) [2 M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C30H28N2O4S2Na: 567.1383;
N-Benzyl-N-[3-(4-methoxyphenylsulfonamido)-3-phenylprop-
1-yn-1-yl]-4-methylbenzenesulfonamide (12e)
Yield: 0.12 g (70%); white solid; mp 150–152 °C; Rf = 0.30 (hex-
anes–EtOAc, 7:3).
IR (KBr): 1367 (s), 1404 (w), 1435 (m), 1495 (s), 1579 (s), 1597 (s),
1801 (w), 1895 (w), 1951 (w), 1969 (w), 2032 (w), 2250 (s), 2585
(w), 2844 (w), 2947 (w), 3014 (w), 3032 (w), 3105 (w), 3226 (br, s)
cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.45 (s, 3 H), 3.83 (s, 3 H), 4.34
(dd, J = 13.6, 24.4 Hz, 2 H), 4.85 (d, J = 8.4 Hz, 1 H), 5.35 (d,
J = 8.4 Hz, 1 H), 6.89 (d, J = 8.8 Hz, 2 H), 7.15 (d, J = 6.4 Hz, 2 H),
7.20–7.33 (m, 10 H), 7.63 (d, J = 8.0 Hz, 2 H), 7.75 (d, J = 8.8 Hz,
2 H).
13C NMR (100 MHz, CDCl3): δ = 21.6, 49.4, 55.1, 55.5, 68.5, 79.9,
114.1, 127.1, 127.6, 128.2, 128.4, 128.56, 128.58, 128.7, 129.3,
129.7, 131.9, 134.1, 134.5, 137.7, 144.8, 162.8.
MS (ESI): m/z (%) = 583 (100) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C30H28N2O5S2Na: 583.1332;
found: 567.1382.
N-Benzyl-N-[3-(furan-2-yl)-3-(4-methylphenylsulfonami-
do)prop-1-yn-1-yl]-4-methylbenzenesulfonamide (12b)
Yield: 0.35 g (67%); white solid; mp 116–117 °C; Rf = 0.20 (hex-
anes–EtOAc, 7:3).
IR (KBr): 1367 (s), 1420 (w), 1440 (m), 1498 (m), 1529 (w), 1660
(w), 1732 (w), 1801 (w), 1917 (w), 2247 (m), 2368 (w), 2723 (w),
2877 (w), 3032 (w), 3120 (br, s) cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.35 (s, 3 H), 2.42 (s, 3 H), 4.30
(dd, J = 14.0, 21.6 Hz, 2 H), 5.06 (d, J = 8.5 Hz, 1 H), 5.38 (d,
J = 8.5 Hz, 1 H), 6.09 (d, J = 3.2 Hz, 1 H), 6.20 (t, J = 2.9 Hz, 1 H),
7.16 (m, 4 H), 7.26 (m, 6 H), 7.63 (d, J = 8.2 Hz, 2 H), 7.67 (d,
J = 8.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 21.5, 21.7, 43.7, 55.2, 66.7, 78.9,
108.3, 110.4, 127.2, 127.7, 128.4, 128.6, 128.7, 129.6, 129.8, 134.1,
134.5, 137.4, 142.9, 143.5, 144.9, 149.8.
MS (ESI): m/z (%) = 1091 (100) [2 M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C28H26N2O5S2Na: 557.1175;
found: 583.1336.
N-Benzyl-N-[3-(4-methoxyphenylsulfonamido)-3-(naphthalen-
2-yl)prop-1-yn-1-yl]-4-methylbenzenesulfonamide (12f)
Yield: 0.12 g (76%); white solid; mp 152–154 °C; Rf = 0.24 (hex-
anes–EtOAc, 7:3).
IR (KBr): 1360 (s), 1463 (w), 1496 (m), 1556 (s), 1576 (s), 1610 (s),
2830 (w), 3021 (w), 3445 (br, s) cm–1.
found: 557.1175.
1H NMR (600 MHz, CDCl3): δ = 2.37 (s, 3 H), 3.73 (s, 3 H), 4.35
(dd, J = 14.4, 36.6 Hz, 2 H), 5.00 (d, J = 8.0 Hz, 1 H), 5.48 (d, J =
8.1 Hz, 1 H), 6.77 (d, J = 5.6 Hz, 2 H), 7.14 (d, J = 4.4 Hz, 2 H),
7.17 (d, J = 5.2 Hz, 2 H), 7.24–7.30 (m, 4 H), 7.47 (s, 2 H), 7.60 (d,
J = 5.2 Hz, 2 H), 7.69 (m, 5 H), 7.78 (d, J = 4.0 Hz, 1 H).
3-[3-(N-Benzyl-4-methylphenylsulfonamido)-1-(4-methylphe-
nylsulfonamido)prop-2-yn-1-yl]-1-tert-butoxycarbonyl-1H-in-
dole (12c)
Yield: 0.19 g (79%); white solid; mp 143–145 °C; Rf = 0.27 (hex-
anes–EtOAc, 4:1).
13C NMR (100 MHz, CDCl3): δ = 21.6, 49.7, 55.2, 55.5, 68.6, 80.3,
114.1, 125.0, 126.2, 126.3, 126.4, 127.6, 127.6, 128.2, 128.4, 128.5,
128.6, 128.7, 129.4, 129.8, 131.9, 132.96, 133.02, 134.2, 134.5,
135.1, 144.8, 162.8.
IR (KBr): 1082 (m), 1159 (s), 1370 (s), 1454 (m), 1597 (w), 1735
(s), 2254 (m), 2981 (w), 3252 (s) cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.66 (s, 9 H), 2.30 (s, 3 H), 2.41
(s, 3 H), 4.17 (d, J = 14.4 Hz, 1 H), 4.37 (d, J = 14.4 Hz, 1 H), 5.03
(d, J = 8.8 Hz, 1 H), 5.60 (d, J = 8.4 Hz, 1 H), 7.06–7.11 (m, 4 H),
7.15–7.21 (m, 3 H), 7.23–7.27 (m, 3 H), 7.29–7.34 (m, 2 H), 7.55
(d, J = 4.4 Hz, 1 H), 7.60 (d, J = 8.0 Hz, 2 H), 7.64–7.66 (m, 3 H).
MS (ESI): m/z (%) = 611 (100) [M + H]+.
Synthesis 2013, 45, 1749–1758
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of γ-Amino-Ynamides
1755
HRMS (ESI): m/z [M + Na]+ calcd for C34H30N2O5S2Na: 633.1488;
found: 633.1487.
at r.t. and the reaction progress was monitored using TLC analysis.
When the starting material had been consumed completely, the mix-
ture was quenched with Et3N. Removal of the solvent in vacuo led
to a crude residue that was purified using silica gel flash column
chromatography (gradient elution: EtOAc in hexane).
N-Benzyl-4-methyl-N-[3-(4-methylphenylsulfonamido)-3,3-di-
phenylprop-1-yn-1-yl]benzenesulfonamide (13)
Yield: 0.13 g (65%); white solid; mp 147–149 °C; Rf = 0.25 (hex-
anes–EtOAc, 10:3).
(1Z,2E)-N-benzyl-N,N′-ditosylcinnamimidamide (16a)
Yield: 0.14 g (78%); white solid; mp 156–157 °C; Rf = 0.59 (hex-
anes–EtOAc, 7:3).
IR (KBr): 1367 (s), 1400 (m), 1438 (m), 1452 (s), 1493 (m), 1594
(m), 1649 (w), 1762 (w), 1803 (w), 1818 (w), 1936 (w), 2256 (s),
2322 (w), 2956 (w), 3034 (w), 3089 (w), 3208 (br, s) cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.41 (s, 3 H), 2.44 (s, 3 H), 4.35
(s, 2 H), 5.14 (s, 1 H), 7.09 (d, J = 8.0 Hz, 2 H), 7.15–7.30 (m, 17
H), 7.39 (d, J = 8.0 Hz, 2 H), 7.71 (d, J = 8.0 Hz, 2 H).
13C NMR (100 MHz, DMSO-d6): δ = 21.4, 21.5, 54.8, 62.7, 71.3,
82.2, 127.0, 127.2, 127.7, 127.9, 128.2, 128.6, 128.8, 128.9, 129.2,
130.5, 134.5, 135.0, 140.4, 142.3, 143.6, 145.4.
IR (KBr): 1346 (m), 1380 (w), 1399 (w), 1446 (w), 1495 (w), 1512
(w), 1558 (m), 1576 (m), 1612 (m), 1705 (m), 1747 (w), 2928 (w),
2964 (w), 3030 (w), 3064 (w), 3443 (br, s) cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.39 (s, 6 H), 4.93 (s, 2 H), 7.03–
7.16 (m, 5 H), 7.18–7.24 (m, 6 H), 7.38–7.43 (m, 5 H), 7.46 (d,
J = 8.4 Hz, 2 H), 7.51 (d, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, DMSO-d6): δ = 21.5, 21.6, 52.0, 119.4, 127.0,
127.8, 128.2, 128.3, 128.4, 128.6, 128.9, 129.2, 129.6, 130.6, 134.3,
135.4, 135.7, 138.5, 143.1, 144.7, 145.0, 164.1.
MS (ESI): m/z (%) = 1263 (100) [2 M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C36H32N2O4S2Na: 643.1696;
MS (APCI): m/z (%) = 545 (100) [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C30H28N2O4S2Na: 567.1383;
found: 643.1710.
N-Allyl-4-methyl-N-[3-(4-methylphenylsulfonamido)-3-phenyl-
prop-1-yn-1-yl]benzenesulfonamide (14)
found: 567.1384.
Yield: 0.31 g (74%); white solid; mp 123–124 °C; Rf = 0.22 (hex-
anes–EtOAc, 3:1).
(1Z,2E)-N-Benzyl-N'-[(4-methoxyphenyl)sulfonyl)-3-(naphtha-
len-2-yl]-N-tosylacrylimidamide (16f)
Yield: 0.060 g (65%); yellow solid; mp 139–140 °C; Rf = 0.33 (hex-
anes–EtOAc, 7:3).
IR (film): 1365 (s), 1597 (m), 1738 (m), 2248 (m), 2922 (m), 2961
(m) cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.39 (s, 3 H), 2.43 (s, 3 H), 3.72
(ddt, J = 1.2, 6.4, 14.8 Hz, 1 H), 3.78 (ddt, J = 1.2, 6.4, 14.8 Hz, 1
H), 4.98 (d, J = 8.4 Hz, 1 H), 5.10 (dq, J = 1.2, 16.8 Hz, 1 H), 5.12
(dq, J = 1.2, 10.4 Hz, 1 H), 5.41 (d, J = 8.4 Hz, 1 H), 5.52 (ddt,
J = 6.4, 10.4, 16.8 Hz, 1 H), 7.22 (dd, J = 0.8, 8.4 Hz, 2 H), 7.26
(dd, J = 0.8, 8.4 Hz, 2 H), 7.28–7.34 (m, 3 H), 7.39–7.41 (m, 2 H),
7.63 (d, J = 8.4 Hz, 2 H), 7.71 (d, J = 8.4 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 21.6, 21.8, 49.6, 54.0, 68.1, 79.7,
120.1, 127.37, 127.39, 127.8, 128.4, 128.7, 129.7, 129.9, 130.7,
134.6, 137.7, 137.9, 143.5, 145.0.
IR (KBr): 1364 (s), 1429 (m), 1454 (m), 1496 (s), 1557 (m), 1596
(s), 2252 (m), 2843 (w), 2914 (w), 3062 (w), 3219 (s) cm–1.
1H NMR (600 MHz, CDCl3): δ = 2.39 (s, 3 H), 3.80 (s, 3 H), 4.95
(s, 2 H), 6.81 (d, J = 12.0 Hz, 2 H), 7.14 (d, J = 12.0 Hz, 2 H), 7.20–
7.26 (m, 7 H), 7.49–7.58 (m, 7 H), 7.80 (s, 1 H), 7.84 (t, J = 6.0 Hz,
3 H).
13C NMR (150 MHz, CDCl3): δ = 21.6, 52.1, 55.6, 100.0, 113.7,
119.5, 123.6, 126.8, 127.5, 127.8, 128.2, 128.4, 128.6, 128.7, 128.8,
129.1, 129.6, 130.5, 131.8, 133.2, 133.3, 134.4, 135.3, 135.8,
145.01, 145.02, 162.7, 164.0.
MS (ESI): m/z (%) = 495 (100) [M + H]+.
MS (ESI): m/z (%) = 611 (100) [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C26H27N2O4S2: 495.1407;
found: 495.1427.
HRMS (ESI): m/z [M + Na]+ calcd for C34H30N2O5S2Na: 633.1488;
found: 633.1490.
N-{3-[Allyl(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-
yl)amino]-1-phenylprop-2-yn-1-yl}-4-methylbenzenesulfon-
amide (15)
Yield: 0.65 g (48%); white solid; mp 137–138 °C; Rf = 0.23 (hex-
anes–EtOAc, 1:1).
(1Z,2E)-N-Benzyl-N'-[(4-methoxyphenyl)sulfonyl]-N-tosylcin-
namimidamide (16af)
Yield: 0.24 g (72%); yellow solid; mp 149–151 °C; Rf = 0.39 (hex-
anes–EtOAc, 7:3).
IR (KBr): 1322 (m), 1361 (s), 1496 (m), 1556 (s), 1577 (s), 1595 (s),
1610 (s), 2841 (w), 2935 (w), 2960 (w), 3033 (w), 3062 (w) cm–1.
1H NMR (600 MHz, CDCl3): δ = 2.39 (s, 3 H), 3.82 (s, 3 H), 4.95
(s, 2 H), 6.81 (d, J = 8.5 Hz, 2 H), 7.02 (d, J = 16.2 Hz, 1 H), 7.11–
7.14 (m, 3 H), 7.18–7.25 (m, 5 H), 7.38 (m, 5 H), 7.48 (d, J = 7.8
Hz, 2 H), 7.56 (d, J = 8.4 Hz, 2 H).
13C NMR (150 MHz, CDCl3): δ = 21.6, 52.0, 55.6, 113.7, 119.4,
127.8, 128.2, 128.29, 128.30, 128.6, 128.9, 129.1, 129.6, 130.6,
133.2, 134.3, 135.3, 135.7, 144.6, 145.0, 162.7, 164.0.
IR (film): 1273 (s), 1325 (s), 1454 (m), 2251 (m), 2888 (m), 2934
(m), 2968 (m), 3143 (br, m) cm–1.
1H NMR (500 MHz, CDCl3): δ = 0.84 (s, 3 H), 1.01 (s, 3 H), 2.38
(s, 3 H), 3.60–3.69 (m, 2 H), 3.94–4.02 (m, 4 H), 5.15 (d, J = 9.5
Hz, 1 H), 5.18 (d, J = 16.0 Hz, 1 H), 5.35 (s, 1 H), 5.67–5.75 (m, 1
H), 6.22 (br s, 1 H), 7.20–7.26 (m, 5 H), 7.38–7.40 (m, 2 H), 7.73
(d, J = 8.5 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 20.4, 20.9, 21.2, 31.7 (d, J = 6.8
Hz), 49.1, 52.8 (d, J = 5.8 Hz), 62.6 (d, J = 5.8 Hz), 78.0 (d, J = 6.8
Hz), 81.5 (d, J = 4.8 Hz), 118.5, 126.0, 126.8 (d, J = 4.9 Hz), 127.7,
128.1, 129.1, 131.9, 137.6, 138.2, 142.8.
MS (ESI): m/z (%) = 561 (100) [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C30H28N2O5S2Na: 583.1332;
found: 583.1332.
31P NMR (202 MHz, CDCl3): δ = –1.31.
MS (ESI): m/z (%) = 489 (100) [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C24H30N2O5PS: 489.1608;
(1Z,2E)-N-Benzyl-3-(naphthalen-2-yl)-N,N′-ditosylacrylimid-
amide (16fa)
Yield: 0.19 g (57%); yellow solid; mp 178–179 °C; Rf = 0.54 (hex-
anes–EtOAc, 7:3).
found: 489.1600.
γ-Amino-Ynamide Rearrangement; General Procedure
To a soln of the γ-amino-ynamide (0.05 M in anhyd CH2Cl2) was
added HNTf2 (0.05 equiv) at r.t. The resulting mixture was stirred
IR (KBr): 1361 (s), 1454 (w), 1496 (w), 1593 (m), 3028 (w), 3260
(w) cm–1.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1749–1758

1756
R. Qi et al.
PAPER
1H NMR (600 MHz, CDCl3): δ = 2.38 (s, 6 H), 4.95 (s, 2 H), 7.14
(d, J = 7.8 Hz, 2 H), 7.16 (d, J = 7.2 Hz, 2 H), 7.21–7.26 (m, 7 H),
7.48 (d, J = 8.4 Hz, 2 H), 7.52 (d, J = 7.8 Hz, 4 H), 7.57 (d, J = 8.4
Hz, 1 H), 7.80 (s, 1 H), 7.85 (m, 3 H).
MS (APCI): m/z (%) = 661 (100) [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C39H36N2O4S2Na: 683.2009;
found: 683.2008.
13C NMR (150 MHz, CDCl3): δ = 21.5, 21.6, 52.1, 119.5, 123.6,
125.6, 126.8, 127.0, 127.5, 127.8, 128.2, 128.4, 128.6, 128.7, 128.8,
129.2, 129.6, 130.5, 131.8, 133.2, 134.4, 135.3, 135.7, 138.5, 143.1,
145.0, 145.2, 164.2.
(E)-N-Allyl-N-[3-(N-cinnamyl-4-methylphenylsulfonamido)-3-
phenylprop-1-yn-1-yl]-4-methylbenzenesulfonamide (22)
Yield: 0.070 g (44%); white solid; mp 80–81 °C; Rf = 0.38 (hex-
anes–EtOAc, 2:1).
IR (film): 1365 (s), 1597 (m), 1738 (m), 2248 (m), 2922 (m), 2961
(m) cm–1.
MS (ESI): m/z (%) = 595 (100) [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C34H30N2O4S2Na: 617.1539;
1H NMR (500 MHz, CDCl3): δ = 2.38 (s, 6 H), 3.77 (ddd, J = 1.0,
8.0, 15.5 Hz, 1 H), 3.82 (ddt, J = 1.5, 3.0, 6.0 Hz, 2 H), 3.88 (ddd,
J = 1.0, 6.0, 15.5 Hz, 1 H), 5.108 (dq, J = 1.0, 11.0 Hz, 1 H), 5.115
(dq, J = 1.0, 17.5 Hz, 1 H), 5.53 (ddt, J = 6.0, 11.0, 17.5 Hz, 1 H),
5.60 (ddd, J = 6.0, 8.0, 16.0 Hz, 1 H), 6.13 (d, J = 16.0 Hz, 1 H),
6.26 (s, 1 H), 6.94 (dd, J = 1.5, 7.5 Hz, 2 H), 7.14–7.20 (m, 2 H),
7.22–7.30 (m, 7 H), 7.54 (dd, J = 1.0, 7.0 Hz, 2 H), 7.68 (d, J = 8.5
Hz, 2 H), 7.78 (d, J = 8.5 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 21.7, 21.8, 47.7, 53.7, 54.1, 65.9,
81.4, 120.0, 125.7, 126.5, 127.6, 127.8, 127.9, 128.28, 128.34,
128.4, 128.5, 129.8, 130.0, 130.9, 132.7, 134.9, 136.7, 137.1, 137.2,
143.5, 145.1.
found: 617.1535.
N-Allylation; Typical Procedure
A flame-dried, screw-cap vial was charged with γ-amino-ynamide
14 (125.0 mg, 0.25 mmol), cinnamyl alcohol (36.9 mg, 0.275
mmol), PPh3 (72.1 mg, 0.275 mmol) and THF (0.8 mL). The soln
was stirred for 5 min at r.t., cooled to 0 °C and treated with diiso-
propyl azodicarboxylate (DIAD) (51.0 μL, 0.275 mmol) dropwise.
The cooling bath was removed and the mixture was allowed to
warm to r.t. The reaction progress was monitored using TLC, and
when the starting material had been consumed (after 15 h), the sol-
vent was removed in vacuo. The crude residue was purified by silica
gel flash column chromatography [isocratic elution: hexanes–
EtOAc, 4:1 containing 2% Et3N (to buffer the silica gel)] to afford
ynamide 22 as a mixture with DIAD-H2 being the byproduct. Yn-
amide 22 (67.0 mg, 0.11 mmol, 44%) was recrystallized cleanly
from the mixture using benzene–hexane.
MS (ESI): m/z (%) = 495 (60), 611 (30) [M + H]+.24
N-{3-[Allyl(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-
yl)amino]-1-phenylprop-2-yn-1-yl}-4-methyl-N-(2-methylal-
lyl)benzenesulfonamide (23)
Yield: 0.31 g (57%); colorless oil; Rf = 0.32 (Et2O).
N-Cinnamyl-4-methyl-N-[3-(2-oxooxazolidin-3-yl)-1-phenyl-
prop-2-yn-1-yl]benzenesulfonamide (20)
Yield: 0.18 g (60%); white solid; mp 129–130 °C; Rf = 0.22 (hex-
anes–EtOAc, 7:3).
IR (film): 1281 (s), 1331 (s), 1453 (m), 2249 (m), 2891 (m), 2974
(m) cm–1.
1H NMR (500 MHz, CDCl3): δ = 1.04 (s, 3 H), 1.08 (s, 3 H), 1.31
(s, 3 H), 2.44 (s, 3 H), 3.57–3.79 (m, 4 H), 4.01–4.09 (m, 2 H), 4.12–
4.19 (m, 2 H), 4.57 (d, J = 47.0 Hz, 2 H), 5.20 (d, J = 10.0 Hz, 1 H),
5.21 (d, J = 17.0 Hz, 1 H), 5.72–5.78 (m, 1 H), 6.19 (d, J = 3.0 Hz,
1 H), 7.26–7.34 (m, 5 H), 7.52–7.54 (m, 2 H), 7.77 (d, J = 8.0 Hz, 2
H).
13C NMR (125 MHz, CDCl3): δ = 19.4, 21.1 (d, J = 2.4 Hz), 21.4,
32.1 (d, J = 6.8 Hz), 51.2, 53.0 (d, J = 5.8 Hz), 54.1 (d, J = 1.4 Hz),
59.5 (d, J = 5.8 Hz), 77.8 (d, J = 7.2 Hz), 77.9 (d, J = 6.7 Hz), 83.7
(d, J = 5.3 Hz), 113.8, 118.7, 127.7, 127.8, 127.9, 128.5, 129.4,
132.2 (d, J = 2.0 Hz), 136.1, 137.0 (d, J = 1.0 Hz), 140.9, 143.3.
IR (film): 1368 (w), 1417 (m), 1424 (m), 1441 (w), 1473 (m), 1493
(m), 1599 (w), 1789 (s), 2250 (m), 2924 (w), 2986 (w), 3038 (w),
3432 (br, s) cm–1.
1H NMR (600 MHz, CDCl3): δ = 2.42 (s, 3 H), 3.56 (dq, J = 8.4,
26.4 Hz, 2 H), 3.81 (d, J = 6.6 Hz, 2 H), 4.29–4.33 (m, 2 H), 5.70
(dt, J = 6.6, 22.8 Hz, 1 H), 6.14 (d, J = 15.6 Hz, 1 H), 6.29 (s, 1 H),
7.02 (d, J = 7.2 Hz, 2 H), 7.15 (t, J = 7.2 Hz, 1 H), 7.20 (t, J = 7.2
Hz, 2 H), 7.24–7.26 (m, 1 H), 7.30–7.32 (m, 4 H), 7.59 (d, J = 7.8
Hz, 2 H), 7.85 (d, J = 8.4 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 21.5, 46.4, 47.4, 53.4, 63.0, 66.5,
78.4, 125.7, 126.3, 127.4, 127.9, 128.2, 128.3, 128.5, 129.6, 132.7,
136.2, 136.6, 136.9, 143.4, 155.7 (1 carbon signal missing due to
overlap).
31P NMR (202 MHz, CDCl3): δ = –0.75.
MS (APCI): m/z (%) = 543 (57) [M + H]+.
HRMS (ESI): m/z [M + NH4]+ calcd for C28H39N3O5PS: 560.2343;
MS (APCI): m/z (%) = 487 (100) [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C28H26N2O4SNa: 509.1505;
found: 560.2337.
[2+2] Cycloaddition; Typical Procedure
found: 509.1506.
To a flame-dried, screw-cap vial were added ynamide 23 [54.4 mg,
0.10 mmol, 0.1 M in toluene (1 mL)] and Pd(PPh3)4 (5.80 mg,
0.0050 mmol). The vial was sealed under N2 and heated to 70 °C.
After 2 h, TLC analysis showed complete consumption of the start-
ing ynamide and the solvent was removed in vacuo. The crude res-
idue was purified through silica gel flash column chromatography
(isocratic elution: hexanes–EtOAc, 1:1) to afford cycloadduct 25
(46.3 mg, 0.085 mmol) in 85% yield.
(E)-N-Benzyl-N-[3-(N-cinnamyl-4-methylphenylsulfonamido)-
3-phenylprop-1-yn-1-yl]-4-methylbenzenesulfonamide (21)
Yield: 0.17 g (37%); white solid; mp 125–126 °C; Rf = 0.54 (hex-
anes–EtOAc, 7:3).
IR (film): 1363 (m), 1399 (w), 1427 (w), 1454 (m), 1490 (m), 1592
(m), 2245 (m), 2857 (w), 2921 (w), 3028 (w), 3064 (w), 3438 (br,
s) cm–1.
1H NMR (600 MHz, CDCl3): δ = 2.33 (s, 3 H), 2.38 (s, 3 H), 3.56
(dd, J = 7.2, 15.0 Hz, 1 H), 3.72 (dd, J = 5.4, 15.0 Hz, 1 H), 4.36
(dd, J = 14.4, 39.0 Hz, 2 H), 5.51–5.56 (m, 1 H), 5.98 (d, J = 15.6
Hz, 1 H), 6.22 (s, 1 H), 6.90 (d, J = 6.0 Hz, 2 H), 7.10 (d, J = 7.2
Hz, 2 H), 7.16–7.23 (m, 12 H), 7.26–7.29 (m, 3 H), 7.64 (d, J = 8.4
Hz, 2 H), 7.75 (d, J = 7.2 Hz, 2 H).
(E)-N-[(1R,2R,5S)-1-Allyl-2,7-diphenyl-3-tosyl-3-azabicyc-
lo[3.1.1]heptan-6-ylidene]-4-methylbenzenesulfonamide (24)
Yield: 0.060 g (95%); white solid; mp 114–115 °C; Rf = 0.40 (hex-
anes–EtOAc, 2:1).
IR (film): 1327 (s), 1453 (m), 1597 (m), 1660 (s), 1727 (m), 2852
(m), 2930 (m), 3032 (w) cm–1.
13C NMR (125 MHz, CDCl3): δ = 21.5, 21.6, 47.4, 53.6, 55.2, 66.3,
81.6, 125.6, 126.4, 127.4, 127.7, 127.8, 128.0, 128.1, 128.3, 128.4,
128.5, 128.7, 129.7, 129.9, 132.4, 134.3, 134.7, 136.6, 136.96,
136.97, 143.4, 144.9 (1 carbon signal missing due to overlap).
1H NMR (500 MHz, CDCl3): δ = 1.76 (dd, J = 9.0, 15.5 Hz, 1 H),
1.84 (ddt, J = 2.0, 5.0, 15.5 Hz, 1 H), 2.37 (s, 3 H), 2.45 (s, 3 H),
3.62 (s, 1 H), 4.206 (s, 1 H), 4.212 (d, J = 15.5 Hz, 1 H), 4.62 (dd,
Synthesis 2013, 45, 1749–1758
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of γ-Amino-Ynamides
1757
J = 5.5, 11.0 Hz, 1 H), 4.76 (dd, J = 1.0, 17.0 Hz, 1 H), 5.07 (d,
J = 10.0 Hz, 1 H), 5.48 (dddd, J = 5.0, 9.0, 10.0, 17.0 Hz, 1 H), 5.72
(s, 1 H), 6.88 (d, J = 7.0 Hz, 2 H), 7.03 (t, J = 8.0 Hz, 2 H), 7.07–
7.09 (m, 4 H), 7.16 (t, J = 7.5 Hz, 1 H), 7.21–7.23 (m, 5 H), 7.33 (d,
J = 8.0 Hz, 2 H), 7.83 (d, J = 8.0 Hz, 2 H).
Synthesis, Houben-Weyl Methods of Molecular
Transformations; Weinreb, S. M., Ed.; Thieme: Stuttgart,
2005, Chap. 21.4. (d) Evano, G.; Blanchard, N.; Toumi, M.
Chem. Rev. 2008, 108, 3054. (e) Evano, G.; Jouvinb, K.;
Coste, A. Synthesis 2013, 45, 17.
13C NMR (100 MHz, CDCl3): δ = 21.6, 21.8, 30.7, 45.9, 53.1, 54.0,
66.1, 72.2, 120.1, 127.0, 127.7, 127.8, 127.9, 128.1, 128.5, 128.6,
128.9, 129.5, 129.8, 130.8, 136.2, 136.4, 136.6, 137.0, 143.3, 144.7,
193.5.
MS (ESI): m/z (%) = 611 (100) [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C35H35N2O4S2: 611.2038;
(4) For ynamide chemistry published since September 2012,
see: (a) Karmakar, R.; Mamidipalli, P.; Yun, S. Y.; Lee, D.
Org. Lett. 2013, 15, 1938. (b) Brioche, J.; Meyer, C.; Cossy,
J. Org. Lett. 2013, 15, 1626. (c) Yun, S. Y.; Wang, K.-P.;
Lee, N.-K.; Mamidipalli, P.; Lee, D. J. Am. Chem. Soc.
2013, 135, 4668. (d) Heffernan, S. J.; Beddoes, J. M.;
Mahon, M. F.; Hennessy, A. J.; Carbery, D. R. Chem.
Commun. 2013, 49, 2314. (e) Kong, Y.; Jiang, K.; Cao, J.;
Fu, L.; Yu, L.; Lai, G.; Cui, Y.; Hu, Z.; Wang, G. Org. Lett.
2013, 15, 422. (f) Yavari, I.; Nematpour, M.; Sodagar, E.
Synlett 2013, 24, 161. (g) Yavari, I.; Nematpour, M. Synlett
2013, 24, 165. (h) Bhunia, S.; Chang, C.-J.; Liu, R.-S. Org.
Lett. 2012, 14, 5522. (i) Minko, Y.; Pasco, M.; Lercher, L.;
Botoshansky, M.; Marek, I. Nature 2012, 490, 522. (j) Hoye,
T. R.; Baire, B.; Niu, D.; Willoughby, P. H.; Woods, B. P.
Nature 2012, 490, 208. (k) Cao, J.; Kong, Y.; Deng, Y.; Lai,
G.; Cui, Y.; Hu, Z.; Wang, G. Org. Biomol. Chem. 2012, 10,
9556. (l) Greenaway, R. L.; Campbell, C. D.; Chapman, H.
A.; Anderson, E. A. Adv. Synth. Catal. 2012, 354, 3187.
(m) Jiang, Z.; Lu, P.; Wang, Y. Org. Lett. 2012, 14, 6266.
(n) Gati, W.; Rammah, M. M.; Rammah, M. B.; Evano, G.
Beilstein J. Org. Chem. 2012, 8, 2214. (o) Smith, D. L.;
Chidipudi, S. R.; Goundry, W. R.; Lam, H. W. Org. Lett.
2012, 14, 4934. (p) Heffernan, S. J.; Carbery, D. R.
Tetrahedron Lett. 2012, 53, 5180.
found: 611.2047.
2-{(E)-[(1R,4R,5S)-5-Allyl-1-methyl-4-phenyl-3-tosyl-3-azabi-
cyclo[3.2.0]heptan-6-ylidene]amino}-5,5-dimethyl-1,3,2-dioxa-
phosphinane 2-Oxide (25)
Yield: 0.050 g (85%); colorless oil; Rf = 0.15 (hexanes–EtOAc,
1:1).
IR (film): 1287 (s), 1340 (s), 1702 (s), 2879 (m), 2933 (m), 2966 (m)
cm–1.
1H NMR (500 MHz, CDCl3): δ = 0.95 (s, 3 H), 1.37 (s, 3 H), 1.45
(s, 3 H), 2.02–2.06 (m, 1 H), 2.13–2.18 (m, 1 H), 2.29 (s, 3 H), 3.28
(t, J = 2.5 Hz, 2 H), 3.38 (d, J = 10.5 Hz, 1 H), 3.83 (d, J = 10.5 Hz,
1 H), 3.98 (dd, J = 10.5, 21.0 Hz, 2 H), 4.39 (dd, J = 4.0, 10.0 Hz, 2
H), 4.59 (dd, J = 1.5, 17.0 Hz, 1 H), 4.90 (dd, J = 1.0, 10.0 Hz, 1 H),
5.24 (s, 1 H), 5.65–5.73 (m, 1 H), 6.95 (t, J = 8.0 Hz, 4 H), 7.10–
7.15 (m, 4 H), 7.21 (d, J = 7.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 19.8, 20.3, 21.4, 22.2, 32.4 (d,
J = 6.2 Hz), 32.5, 43.6, 53.2 (d, J = 16.2 Hz), 59.8, 70.4 (d, J = 27.4
Hz), 71.6 (d, J = 2.4 Hz), 77.8 (d, J = 7.2 Hz), 78.2 (d, J = 6.7 Hz),
118.7, 126.8, 128.0, 128.3, 128.8, 129.0, 131.7, 135.4, 135.7, 142.7,
200.4 (d, J = 9.6 Hz).
(5) For accounts on syntheses of ynamides published since
2012, see: (a) Jin, X.; Yamaguchi, K.; Mizuno, N. Chem.
Lett. 2012, 41, 866. (b) Jin, X.; Yamaguchi, K.; Mizuno, N.
Chem. Commun. 2012, 48, 4974. (c) Jouvin, K.;
31P NMR (202 MHz, CDCl3): δ = –3.02.
MS (APCI): m/z (%) = 543 (100) [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C28H36N2O5PS: 543.2078;
Heimburger, J.; Evano, G. Chem. Sci. 2012, 3, 756.
(d) Jouvin, K.; Coste, A.; Bayle, A.; Legrand, F.;
Karthikeyan, G.; Tadiparthi, K.; Evano, G. Organometallics
2012, 31, 7933. (e) Tong, X.; Ni, G.; Deng, X.; Xia, C.
Synlett 2012, 23, 2497. (f) Wang, M.-G.; Wu, J.; Shang, Z.-
C. Synlett 2012, 23, 589. (g) Laouiti, A.; Jouvin, K.;
Bourdreux, F.; Rammah, M. M.; Rammah, M. B.; Evano, G.
Synthesis 2012, 44, 1491.
found: 543.2062.
Acknowledgment
R.P.H. thanks NIH (GM066055) for funding. K.A.D. is grateful to
the American Chemical Society for a Division of Medical Chemi-
stry Pre-Doctoral Fellowship. Y.T. thanks the Natural Science
Foundation of China for generous funding (No. 21172169 and No.
21172168). The Instrumentation Center at the School of Phar-
maceutical Science and Technology of Tianjin University is greatly
appreciated for providing analytical services.
(6) For syntheses of novel structural analogues of ynamides,
see: Yne-sulfoxyimines: (a) Wang, L.; Huang, H.;
Priebbenow, D. L.; Pan, F.-F.; Bolm, C. Angew. Chem. Int.
Ed. 2013, 52, 3478. (b) Yne-hydrazides: Beveridge, R. E.;
Batey, R. A. Org. Lett. 2012, 14, 540. Yne-imines:
(c) Laouiti, A.; Rammah, M. M.; Rammah, M. B.; Marrot,
J.; Couty, F.; Evano, G. Org. Lett. 2012, 14, 6. (d) Ynimides:
Souto, J. A.; Becker, P.; Iglesias, Á.; Muñiz, K. J. Am. Chem.
Soc. 2012, 134, 15505. (e) Sueda, T.; Oshima, A.; Teno, N.
Org. Lett. 2011, 13, 3996. (f) Sueda, T.; Kawada, A.; Urash,
Y.; Teno, N. Org. Lett. 2013, 15, 1563. Diamino-acetylenes:
(g) Petrov, A. R.; Daniliuc, C. G.; Jones, P. G.; Tamm, M.
Chem. Eur. J. 2010, 16, 11804. Amidinyl-ynamides: (h) Li,
J.; Neuville, L. Org. Lett. 2013, 15, 1752.
(7) DeKorver, K. A.; Hsung, R. P.; Song, W.-Z.; Walton, M. C.;
Wang, X.-N. Org. Lett. 2012, 14, 3214.
(8) Hashmi, A. S. K.; Schuster, A. M.; Zimmer, M.; Rominger,
F. Chem. Eur. J. 2011, 17, 5511.
(9) (a) Frederick, M. O.; Mulder, J. A.; Tracey, M. R.; Hsung, R.
P.; Huang, J.; Kurtz, K. C. M.; Shen, L.; Douglas, C. J.
J. Am. Chem. Soc. 2003, 125, 2368. (b) Rodriguez, D.;
Martinez-Esperon, M. F.; Castedo, L.; Saá, C. Synlett 2007,
1963. (c) See reference 6b.
References
(1) For current leading reviews on ynamides, see: (a) DeKorver,
K. A.; Li, H.; Lohse, A. G.; Hayashi, R.; Lu, Z.; Zhang, Y.;
Hsung, R. P. Chem. Rev. 2010, 110, 5064. (b) Evano, G.;
Coste, A.; Jouvin, K. Angew. Chem. Int. Ed. 2010, 49, 2840.
(2) For reviews accounting partially the chemistry of ynamides,
see: (a) Ackermann, L.; Potukuchi, H. K. Org. Biomol.
Chem. 2010, 8, 4503. (b) Domínguez, G.; Perez-Castells, J.
Chem. Soc. Rev. 2011, 40, 3430. (c) Weding, N.; Hapke, M.
Chem. Soc. Rev. 2011, 40, 4525. (d) Madelaine, C.; Valerio,
V.; Maulide, N. Chem. Asian J. 2011, 6, 2224.
(3) For reviews on syntheses of ynamides, see: (a) Mulder, J. A.;
Kurtz, K. C. M.; Hsung, R. P. Synlett 2003, 1379. (b) Dehli,
J. R.; Legros, J.; Bolm, C. Chem. Commun. 2005, 43, 973.
(c) Tracey, M. R.; Hsung, R. P.; Antoline, J. A.; Kurtz, K. C.
M.; Shen, L.; Slafer, B. W.; Zhang, Y. In Science of
(10) Verrier, C.; Carret, S.; Poisson, J.-F. Org. Lett. 2012, 14,
5122.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1749–1758

1758
R. Qi et al.
PAPER
Yudin, A. K. Org. Lett. 2009, 11, 1281. (c) Cant, A. A.;
(11) (a) Mak, X. Y.; Ciccolini, R. P.; Robinson, J. M.; Tester, J.
W.; Danheiser, R. L. J. Org. Chem. 2009, 74, 9381.
(b) Hashmi, A. S. K.; Rudolph, M.; Huck, J.; Frey, W.; Bats,
J. W.; Hamzic, M. Angew. Chem. Int. Ed. 2009, 48, 5848.
(12) DeKorver, K. A.; Walton, M. C.; North, T. D.; Hsung, R. P.
Org. Lett. 2011, 13, 4862.
(13) For recent studies involving azetenes, see: (a) Shindoh, N.;
Takemoto, Y.; Takasu, K. Chem. Eur. J. 2009, 15, 7026.
(b) Shindoh, N.; Kitaura, K.; Takemoto, Y.; Takasu, K.
J. Am. Chem. Soc. 2011, 133, 8470. (c) Shindoh, N.;
Takemoto, Y.; Takasu, K. Heterocycles 2011, 82, 1133.
(d) Saito, A.; Konishi, T.; Hanzawa, Y. Org. Lett. 2010, 12,
372.
Bertrand, G. H. V.; Henderson, J. L.; Roberts, L.; Greaney,
M. F. Angew. Chem. Int. Ed. 2009, 48, 5199. (d) Yasui, H.;
Yorimitsu, H.; Oshima, K. Chem. Lett. 2008, 37, 40.
(e) Walters, M. A. J. Am. Chem. Soc. 1994, 116, 11618.
(19) For our work in this area, see: (a) Zhang, Y.; DeKorver, K.
A.; Lohse, A. G.; Zhang, Y.-S.; Huang, J.; Hsung, R. P. Org.
Lett. 2009, 11, 899. (b) DeKorver, K. A.; Hsung, R. P.;
Lohse, A. G.; Zhang, Y. Org. Lett. 2010, 12, 1840.
(c) DeKorver, K. A.; Johnson, W. L.; Zhang, Y.-S.; Zhang,
Y.; Lohse, A. G.; Hsung, R. P. J. Org. Chem. 2011, 76, 5092.
(d) DeKorver, K. A.; Wang, X.-N.; Walton, M. C.; Hsung,
R. P. Org. Lett. 2012, 14, 1768.
(14) For a review on related oxetenes, see: Shindo, M. Synthesis
2003, 2275.
(20) For leading reviews on the chemistry of ketenimines, see:
(a) Krow, G. R. Angew. Chem., Int. Ed. Engl. 1971, 10, 435.
(b) Barker, M. W.; McHenry, W. E. In The Chemistry of
Ketenes, Allenes and Related Compounds, Part 2; Patai, S.,
Ed.; Wiley-Interscience: Chichester, 1980, 701–720.
(c) Alajarin, M.; Vidal, A.; Tovar, F. Targets Heterocycl.
Syst. 2000, 4, 293.
(21) For reviews, see: (a) Snider, B. B. Chem. Rev. 1988, 88, 793.
(b) Tidwell, T. T. Ketenes; Wiley: New York, 1995, 486–
502.
(22) For leading references on fused ketene [2+2] cycloadditions,
see: (a) Snider, B. B.; Hui, R. A. H. F.; Kulkarni, Y. S. J. Am.
Chem. Soc. 1985, 107, 2194. (b) Brady, W. T.; Giang, Y. F.
J. Org. Chem. 1985, 50, 5177. (c) Marko, I.; Ronsmans, B.;
Hesbain-Frisque, A.-M.; Dumas, S.; Ghosez, L. J. Am.
Chem. Soc. 1985, 107, 2192. (d) Lee, S. Y.; Kulkarni, Y. S.;
Burbaum, B. W.; Johnston, M. I.; Snider, B. B. J. Org.
Chem. 1988, 53, 1848. (e) Zhang, W.; Collins, M. R.;
Mahmood, L.; Dowd, P. Tetrahedron Lett. 1995, 36, 2729.
(f) Tran, V.; Minehan, T. Org. Lett. 2011, 13, 6588.
(23) For a closely related study, see: (a) Li, B.-S.; Yang, B.-M.;
Wang, S.-H.; Zhang, Y.-Q.; Cao, X.-P.; Tu, Y.-Q. Chem.
Sci. 2012, 3, 1975. See also: (b) McCaleb, K. L.; Halcomb,
R. L. Org. Lett. 2000, 2, 2631. (c) Bélanger, B.; Léevesque,
F.; Pâquet, J.; Barbe, G. J. Org. Chem. 2005, 70, 291.
(24) HRMS (ESI) was attempted, but the sample was not stable
enough.
(15) For recent examples associated with oxetenes, see:
(a) Cheng, D.; Ling, F.; Li, Z.; Yao, W.; Ma, C. Org. Lett.
2012, 14, 3146. (b) Aikawa, K.; Hioki, Y.; Shimizu, N.;
Mikami, K. J. Am. Chem. Soc. 2011, 133, 20092. (c) Saito,
A.; Kasai, J.; Odaira, Y.; Fukaya, H.; Hanzawa, Y. J. Org.
Chem. 2009, 74, 5644. (d) Saito, A.; Umakoshi, M.; Yagyu,
N.; Hanzawa, Y. Org. Lett. 2008, 10, 1783. (e) You, L.; Al-
Rashid, Z. F.; Figueroa, R.; Ghosh, S. K.; Li, G.; Lu, T.;
Hsung, R. P. Synlett 2007, 1656. (f) Kurtz, K. C. M.; Hsung,
R. P.; Zhang, Y. Org. Lett. 2006, 8, 231. (g) Mori, S.;
Shindo, M. Org. Lett. 2004, 6, 3945. (h) Shindo, M.; Sato,
Y.; Yoshikawa, T.; Koretsune, R.; Shishido, K. J. Org.
Chem. 2004, 69, 3912. (i) Shindo, M.; Matsumoto, K.; Mori,
S.; Shishido, K. J. Am. Chem. Soc. 2002, 124, 6840.
(16) For leading references, see: (a) Dudley, G.; Engel, D. A.;
Lopez, S. S. Synlett 2007, 949. (b) Engel, D. A.; Dudley, G.
Org. Lett. 2006, 8, 4027. (c) For a review, see:
Swaminathan, S.; Narayanan, K. V. Chem. Rev. 1971, 71,
429.
(17) For leading reviews on aza-Claisen rearrangements, see:
(a) Majumdar, K. C.; Bhattacharyya, T.; Chattopadhyay, B.;
Nandi, R. K. Synthesis 2009, 2117. (b) Nubbemeyer, U. Top.
Curr. Chem. 2005, 244, 149.
(18) For some examples of aza-Claisen rearrangements, see:
(a) Majumdar, K. C.; Samanta, S.; Chattopadhyay, B.;
Nandi, R. K. Synthesis 2010, 863. (b) Cheung, L. L. W.;
Synthesis 2013, 45, 1749–1758
© Georg Thieme Verlag Stuttgart · New York