Asymmetric α-2-tosylethenylation of N,N-dialkyl-l-amino acid esters via the formation of non-racemic ammonium enolates

Article abstract of DOI:10.1039/c1ob06074k

Asymmetric α-2-tosylethenylation of (S)-2-(pyrrolidin-1-yl)propanoic acid esters was shown to produce good yields with high enantioselectivities. The reaction proceeds via the formation of a non-racemic ammonium enolate without an external source of chirality.

Full text of DOI:10.1039/c1ob06074k

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PAPER
Asymmetric a-2-tosylethenylation of N,N-dialkyl-L-amino acid esters via the
formation of non-racemic ammonium enolates†
Eiji Tayama,* Tomohito Igarashi, Hajime Iwamoto and Eietsu Hasegawa
Received 4th July 2011, Accepted 26th September 2011
DOI: 10.1039/c1ob06074k
Asymmetric a-2-tosylethenylation of (S)-2-(pyrrolidin-1-yl)propanoic acid esters was shown to
produce good yields with high enantioselectivities. The reaction proceeds via the formation of a
non-racemic ammonium enolate without an external source of chirality.
Introduction
Ethynyl tolyl sulfone (1) is a highly reactive Michael acceptor
and reacts with various nucleophiles to produce 2-tosylethenyl
derivatives under mild conditions.1 Conjugate addition of tertiary
amines to 1 generates the corresponding zwitterionic interme-
diates, which serve as unique synthetic intermediates.2 Weston
et al. applied this reaction to the synthesis of medium- and
large-ring cyclic amines using a 3-aza-Cope rearrangement of
the zwitterionic intermediates.3 Recently, we reported the asym-
metric a-2-tosylethenylation of N-alkyl-L-proline esters with 1
via the formation of the zwitterionic intermediate (Scheme 1).4
Scheme 2 a-2-Tosylethenylation of N,N-dialkyl acyclic amino acid ester
2 with 1.
Because this method worked for N-alkyl-L-proline esters, we have
attempted to extend the reaction protocol to N,N-dialkyl acyclic
amino acid esters 2 to obtain the corresponding a-(2-tosylethenyl)
derivatives 3 (Scheme 2). The proposed reaction would proceed via
the formation of a zwitterionic intermediate A, proton transfer to
an ammonium ylide B, conjugate addition of B to 1, and the
elimination of an N-(2-tosylethenyl) substituent from nitrogen.
(2b), 2-(dibenzylamino) (2c), and 2-(diallylamino) (2d) derivatives
with 1 gave similar results (entries 2–4).5 This lack of reactivity
could be explained by the steric repulsion of the tertiary amines
inhibiting the initial conjugate addition of 2a–d to 1. Thus,
we prepared the 2-(dimethylamino) derivative 2e and performed
the reaction (entry 5). The a-adduct 3e was obtained in 26%
yield. Unexpectedly, 3e was obtained in an enantio-enriched form
(4% ee), even though the expected reaction intermediate is the
achiral ammonium ylide B depicted in Scheme 2. Prompted by this
unexpected observation, we investigated the reaction using other
types of N,N-dialkyl amino acid esters with 1. Next, we prepared
the 2-piperidinyl derivatives (2f, 2g) and examined their reactivity
(entries 6, 7). The ee values of the corresponding a-adducts 3
were dramatically improved (3f: 17%, 75% ee; 3g: 36%, 77% ee).
Surprisingly, when the reactions of the 2-pyrrolidinyl derivatives
(2h, 2i) were performed under the same conditions (entries 8, 9),
the a-adducts 3h or 3i were obtained in reasonable yields with high
enantioselectivities (3h: 69%, 92% ee; 3i: 81%, 91% ee). Use of the
tert-butyl ester derivatives (2g, 2i) resulted in improved yields of 3.
The configuration of 3i was determined to be S after conversion
to 5 by reductive desulfonylation and hydrogenation (Scheme 3).
The specific rotation value of 5 was compared to that of an au-
thentic S sample prepared from (S)-a-ethylalanine tert-butyl ester
[(S)-6].6
Scheme 1 Asymmetric a-2-tosylethenylation of N-alkyl-L-proline esters.
Results and discussion
We examined the reaction of (S)-cyclohexyl 2-(benzyl(methyl)-
amino)propanoate (2a) with 2.0 equivalents of 1 in DMF at 0 ◦C
for 4 h (Table 1, entry 1). Unreacted 1 was quenched by the
addition of methylamine to prevent further reactions. None of the
a-adduct 3a was detected. The reactions of 2-(allyl(benzyl)amino)
Department of Chemistry, Faculty of Science, Niigata University, Niigata,
950-2181, Japan. E-mail: tayama@chem.sc.niigata-u.ac.jp; Fax: +81 25 262
7741
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c1ob06074k
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Table 1 Effects of substituents on the asymmetric a-2-tosylethenylation
of N,N-dialkyl acyclic amino acid esters 2
afforded 3i in the quantitative yield. Alcoholic solvents, such as
isopropanol or ethanol, could also be used (entries 5, 6), but
the use of methanol resulted in a lower ee (entry 7, 78% ee).
The addition of water to THF or methanol did not negatively
affect the reaction (entries 8, 9). The yield was decreased when
a more acidic solvent, such as 2,2,2-trifluoroethanol, was used
(entry 10, 29%, 81% ee). Next, we investigated the effects of
reaction temperature and concentration. The yield was lowered
at room temperature because of the formation of by-product7
(entry 11, 71%, 90% ee). The enantioselectivity was improved at
lower reaction temperature (-40 ◦C) (entry 12, 86%, 96% ee). The
reaction under lower concentration (0.01 M) did not show the
remarkable effects (entry 13, 92%, 91% ee); however, the yield was
lowered under higher concentration (0.2 M) because of formation
of the same by-product7 described above (entry 14, 77%, 93% ee).
To define the scope and limitation of the present asymmetric
a-2-tosylethenylation, we prepared a series of substrates derived
from acyclic L-amino acids and examined their reactions with
1 (Table 3). The use of primary esters, such as n-butyl (2j) or
benzyl (2k) as substrates, resulted in lower yields because of
the undesired side reactions8 (entry 1, 40%, 88% ee; entry 2,
11%, 90% ee). Other a-amino acid derivatives prepared from
phenylalanine (2l) or leucine (2m) reacted smoothly with the same
levels of enantioselectivity (entry 3, 99%, 81% ee; entry 4, 80%,
92% ee), but the valine derivative 2n was less reactive (entry 5).
The corresponding a-adduct 3n was obtained in only 27% yield
with 95% ee. The yield was improved to 54% after 48 h of stirring
(entry 6). The reaction of the 2-phenylglycine derivative 2o (85%
ee) gave 3o with a lower enantioselectivity (entry 7, 40% ee). The
N,N-diethylamide derivative 2p did not react at all (entry 8). It is
worth noting that the reaction of the acyclic amino acid derivative
2i proceeded without adding 1 in excess (entries 9, 10).
Entry R1
R2
R3
Yield (%)a ee (%)b
1
2
3
4
5
6
7
8
9
CH2Ph
CH2Ph
CH2Ph
Me
cHex
a
b
c
d
e
f
g
h
i
0c
—
—
—
—
4
75
77
92
CH2CH CH2 cHex
0c
CH2Ph
cHex
0c
CH2CH CH2 CH2CH CH2 cHex
0c
Me
Me
cHex
cHex
tBu
26
17
36
69
81
–(CH2)5–
–(CH2)5–
–(CH2)4–
–(CH2)4–
cHex
tBu
91 (S)
a Isolated yield. b Determined by HPLC analysis. c Recovered 2a–d in 75–
99% yield. See also ref. 5.
Scheme 3 Determination of the absolute configuration of 3i. Reagents
and conditions: (i) Mg, THF–MeOH, 50 ◦C, (ii) H2, Pd–C, EtOAc, rt, (iii)
1,4-butanediol di-p-toluenesulfonate, KHCO3, MeCN, reflux.
To improve the chemical yield and enantioselectivity of the
asymmetric a-2-tosylethenylation, we tested this reaction in
various conditions (Table 2). The reaction proceeded with the same
levels of enantioselectivity in dichloromethane, toluene, THF, and
ethyl acetate (entries 1–4, 88–94% ee). The use of ethyl acetate
Although its exact origin is unclear, the high stereoselectivity
might be rationalized as a result of the formation of the non-
racemic ammonium enolate (memory of chirality)9,10 (Scheme 4).
Conjugate addition of 2i to 1 generates the zwitterionic interme-
diate A. Intermediate A is converted to the ammonium ylide B by
Table 2 Asymmetric a-2-tosylethenylation of 2i in various conditions
Table 3 Asymmetric a-2-tosylethenylation of acyclic L-amino acid
derivatives 2
Entry Solvent
Temp./◦C Conc./M Yield (%)a ee (%)b
1
2
3
4
5
6
7
8
CH2Cl2
Toluene
THF
0
0
0
0
0
0
0
0
0
0
rt
-40
0
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.01
0.2
97
92
91
99
92
85
81
91
74
29
71c
86
92
77c
90
88
94
90
93
88
78
93
83
81
90
96
91
93
Entry Equiv. of 1 R1
R2
Yield (%)b
ee (%)c
EtOAc
1
2
3
4
5
6
7
8
9
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.5
1.0
Me
Me
OnBu
j
k
l
40
11
99
80
27
54d
90
0
88
90
81
92
95
95
40e
—
93
91
iPrOH
OCH2Ph
EtOH
MeOH
THF–H2O (2 : 1)
MeOH–H2O (2 : 1)
CF3CH2OH
EtOAc
EtOAc
EtOAc
EtOAc
CH2Ph OtBu
iBu
iPr
iPr
Ph
Me
Me
Me
OtBu
OtBu
OtBu
OcHex
NEt2
OtBu
OtBu
m
n
n
o
p
i
9
10
11
12
13
14
90
86
10
i
0
a The absolute configurations of 3j–o were assigned tentatively by analogy
with (S)-3i. b Isolated yield. c Determined by HPLC analysis. d Stirred for
48 h at 0 ◦C. e The enantio-purity of 2o was 85% ee.
a Isolated yield. b Determined by HPLC analysis. c Small amount of
by-product was obtained (entry 11, 14%; entry 14, 11%). Details: see
ref. 7.
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Scheme 6 Reaction of non-racemic substrate (S)-2i at different % ee.
Scheme 7 [1,2] Stevens rearrangement of (S)-N-benzyl-2-(pyrrolidin-
1-yl)propanoic acid ester-derived ammonium salt 7.
proceed via the formation of a similar ammonium ylide B or
enolate B¢; the rearrangement product 8 was not obtained in an
enantio-enriched form (69%, 0% ee).
Scheme 4 Proposed mechanism for the asymmetric a-2-tosylethenylation
of 2i.
intramolecular deprotonation of the more acidic a-proton. Ylide B
serves as a non-racemic ammonium enolate B¢, which undergoes
conjugate addition with 1 diastereoselectively to afford the (S)-
zwitterion C. Elimination of the N-2-tosylethenyl substituent
from nitrogen by the reaction with a nucleophile such as 2i
affords a-adduct 3i with high enantioselectively and regenerate
the intermediate A.
To rule out the effect of the intermediates or products for the
asymmetric induction, we examined the reaction of a 1 : 1 mixture
of (S)-2i and (rac)-2l with 1 under the same conditions (Scheme 5).
The a-adducts 3i and 3l were obtained, respectively; however, no
remarkable changes to the product ee were observed (3i: 93% ee,
3l: 0% ee).
Conclusions
In conclusion, we have reported that the asymmetric a-2-
tosylethenylation of (S)-2-(pyrrolidin-1-yl)propanoic acid esters
2 using ethynyl tolyl sulfone 1 as an electrophile13 produces a
good yield with high enantioselectivity without the addition of
any bases. The reaction would proceed via the formation of a non-
racemic ammonium enolate without an external source of chirality
(memory of chirality).
Experimental section
General
1H and 13C NMR spectra were measured on a Varian 400 MHz
(1H: 400 MHz, 13C: 100 MHz) spectrometer. Splitting patterns are
indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet;
m, multiplet; br, broad peak. Infrared spectra were recorded
on a Perkin Elmer Spectrum GX FT-IR spectrometer. Specific
rotations were recorded on a JASCO Polarimeter P-1010. High-
resolution mass spectra were measured on a Thermofisher Scien-
tific LC/FT-MS spectrometer. Elemental analyses were recorded
on a J-Science Lab Micro Corder JM10. HPLC analyses were
performed using a JASCO HPLC pump PU-2080 and a UV/VIS
detector UV-2075. Reactions were conducted in a round-bottomed
flask with a magnetic stirring bar under an argon atmosphere. For
thin layer chromatography (TLC) analysis throughout this work,
Merck TLC plates (silica gel 60 F254) were used. The products
were purified by preparative column chromatography on silica gel
(silica gel 60 N, spherical neutral, KANTO Chemical Co., Inc.,
Japan).
Scheme 5 a-2-Tosylethenylation of 1 : 1 mixture of (S)-2i and (rac)-2l.
Next, we carried out the reaction of non-racemic substrate (S)-
2i at different% ee (25% ee, 51% ee, and 75% ee) and obtained the
results against the % ee of the product 3i. The non-linear effects
were not observed (Scheme 6).
To eliminate the asymmetric [1,2] vinylic Stevens rearrange-
ment11,12 of the non-racemic ammonium enolate B¢ as a possible
pathway, we examined a base-induced [1,2] Stevens rearrangement
of the N-benzyl ammonium salt 7 (Scheme 7). The reaction would
Representative procedure for the asymmetric a-tosylethenylation of
N,N-dialkyl L-amino acid ester 2i
A solution of ethynyl tolyl sulfone (1) (72 mg, 0.40 mmol) in ethyl
acetate (1.3 mL) was added to a solution of 2i (40 mg, 0.20 mmol)
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in ethyl acetate (2.7 mL) at 0 ◦C under an argon atmosphere.
After stirring for 4 h at the same temperature, the excess amount
of 1 was quenched by addition of 40% methylamine solution in
methanol (46 mL, 0.45 mmol). The resulting mixture was stirred
for 15 min at 0 ◦C, diluted with water, and extracted with ethyl
acetate. The combined extracts were washed with brine, dried
over sodium sulfate, and concentrated. Purification of the residue
by chromatography on silica gel (n-hexane/ethyl acetate = 2/1
as eluent) gave (S,E)-tert-butyl 2-methyl-2-(pyrrolidin-1-yl)-4-(p-
toluenesulfonyl)but-3-enoate (3i) (75 mg, 99% yield) as a white
solid.
tR = 34.1 min for the minor enantiomer and 37.8 min for the
major enantiomer]; nmax(film)/cm-1 2975, 2935, 2854, 2816, 1723,
1628, 1597, 1455, 1393, 1369, 1319, 1286, 1253, 1148, 1123, 1087,
1049, 961, 885, 840, 812, 770, 675; dH (400 MHz, CDCl3, Me4Si)
7.76 (2H, d, J = 8.2 Hz, ArH), 7.32 (2H, d, J = 8.2 Hz, ArH),
7.14 (1H, d, J = 15.4 Hz, TsCH CH), 6.59 (1H, d, J = 15.4
Hz, TsCH = CH), 2.49 (4H, t, J = 4.8 Hz, NCH2), 2.43 (3H, s,
ArCH3), 1.54–1.38 (6H, m, piperidinyl-CH2), 1.44 (9H, s, t-Bu),
1.31 (3H, s, 2-CH3); dC (100 MHz, CDCl3, CHCl3) 170.5, 148.8,
144.2, 137.6, 130.6, 129.8, 127.6, 82.1, 68.1, 48.5, 28.1, 26.7, 24.7,
21.6, 20.8; HRMS-ESI (m/z): [M + H]+ calc. for C21H32NO4S,
394.2047; found, 394.2032.
(E)-Cyclohexyl 2-(N,N-dimethylamino)-2-methyl-4-(p-
toluenesulfonyl)but-3-enoate (3e)
(S,E)-Cyclohexyl 2-methyl-2-(pyrrolidin-1-yl)-4-(p-toluene-
sulfonyl)but-3-enoate (3h)
Yellow oil (Found: C, 63.0; H, 7.7; N, 3.4. Calc. for C20H29NO4S:
24
C, 63.3; H, 7.7; N, 3.7%); [a] -1.5 (c 1.00 in EtOH); 4% ee
Yellow oil (Found: C, 64.9; H, 7.7; N, 3.6. Calc. for C22H31NO4S:
C, 65.15; H, 7.7; N, 3.45%); [a] -27.2 (c 1.00 in EtOH); 92% ee
589
25
589
[determined by HPLC analysis: Daicel Chiralpak AD-H column,
n-hexane/ethanol = 92/8 as eluent, flow rate = 0.50 mL min-1, tR =
24.7 min for the major enantiomer and 29.0 min for the minor
enantiomer]; nmax(film)/cm-1 3059, 2938, 2861, 2793, 1721, 1634,
1597, 1452, 1403, 1369, 1320, 1235, 1147, 1086, 1037, 1013, 972,
912, 813, 736, 683; dH (400 MHz, CDCl3, Me4Si) 7.76 (2H, d, J =
8.2 Hz, ArH), 7.33 (2H, d, J = 8.2 Hz, ArH), 7.13 (1H, d, J = 15.2
Hz, TsCH CH), 6.58 (1H, d, J = 15.2 Hz, TsCH = CH), 4.83
(1H, tt, J = 8.8, 4.0 Hz, OCH), 2.43 (3H, s, ArCH3), 2.28 (6H,
s, N(CH3)2), 1.93–1.64 (4H, m, c-Hex), 1.58–1.22 (6H, m, c-Hex),
1.38 (3H, s, 2-CH3); dC (100 MHz, CDCl3, CHCl3) 170.7, 146.9,
144.3, 137.4, 131.6, 129.9, 127.7, 73.9, 67.2, 39.7, 31.48, 31.46,
25.2, 23.51, 23.50, 21.6, 20.6; HRMS-ESI (m/z): [M + H]+ calc.
for C20H30NO4S, 380.1890; found, 380.1876.
[determined by HPLC analysis: Daicel Chiralpak AD-H column,
n-hexane/ethanol = 95/5 as eluent, flow rate = 0.50 mL min-1, tR =
21.5 min for (S)-3h and 25.5 min for (R)-3h]; nmax(film)/cm-1 3059,
2938, 2860, 1722, 1631, 1597, 1452, 1370, 1320, 1302, 1289, 1250,
1193, 1147, 1085, 1035, 1013, 973, 912, 835, 812, 736, 706; dH (400
MHz, CDCl3, Me4Si) 7.76 (2H, d, J = 8.2 Hz, ArH), 7.33 (2H, d,
J = 8.2 Hz, ArH), 7.18 (1H, d, J = 15.4 Hz, TsCH CH), 6.56
(1H, d, J = 15.4 Hz, TsCH = CH), 4.83 (1H, tt, J = 8.6, 3.8 Hz,
OCH), 2.82–2.74 (2H, m, NCH2), 2.71–2.62 (2H, m, NCH2), 2.44
(3H, s, ArCH3), 1.84–1.63 (8H, m, NCH2CH2 and c-Hex), 1.56–
1.24 (6H, m, c-Hex), 1.45 (3H, s, 2-CH3); dC (100 MHz, CDCl3,
CHCl3) 171.0, 146.6, 144.2, 137.4, 131.1, 129.8, 127.6, 73.6, 65.4,
47.3, 31.4, 25.2, 24.1, 23.4, 23.1, 21.5; HRMS-ESI (m/z): [M +
H]+ calc. for C22H32NO4S, 406.2047; found, 406.2033.
(E)-Cyclohexyl 2-methyl-2-(piperidin-1-yl)-4-(p-toluenesulfonyl)-
but-3-enoate (3f)
(S,E)-tert-Butyl 2-methyl-2-(pyrrolidin-1-yl)-4-(p-toluenesul-
fonyl)but-3-enoate (3i)
Colorless oil (Found: C, 66.0; H, 8.1; N, 3.6. Calc. for C23H33NO4S:
25
C, 65.8; H, 7.9; N, 3.3%); [a] -16.2 (c 1.00 in EtOH); 75% ee
White solid (Found: C, 63.4; H, 7.9; N, 3.6. Calc. for C20H29NO4S:
C, 63.3; H, 7.7; N, 3.7%); [a]
589
25
589
[determined by HPLC analysis: Daicel Chiralpak AD-H column,
n-hexane/ethanol = 95/5 as eluent, flow rate = 0.50 mL min-1, tR =
17.0 min for the major enantiomer and 20.8 min for the minor
enantiomer]; nmax(film)/cm-1 3058, 2937, 2858, 1723, 1632, 1597,
1452, 1371, 1320, 1240, 1179, 1147, 1120, 1087, 1034, 1013, 961,
908, 864, 835, 812, 737, 704, 685; dH (400 MHz, CDCl3, Me4Si)
7.76 (2H, d, J = 8.2 Hz, ArH), 7.33 (2H, d, J = 8.2 Hz, ArH),
7.16 (1H, d, J = 15.2 Hz, TsCH CH), 6.61 (1H, d, J = 15.2 Hz,
TsCH = CH), 4.82 (1H, tt, J = 8.6, 3.6 Hz, OCH), 2.48 (4H, t, J =
5.0 Hz, NCH2), 2.43 (3H, s, ArCH3), 1.83–1.63 (4H, m, c-Hex),
1.56–1.24 (12H, m, piperidinyl-CH2 and c-Hex), 1.35 (3H, s, 2-
CH3); dC (100 MHz, CDCl3, CHCl3) 170.7, 148.3, 144.2, 137.5,
130.9, 129.8, 127.5, 73.5, 67.7, 48.4, 31.5, 31.4, 26.6, 25.2, 24.6,
23.4, 23.3, 22.6, 21.5, 20.7, 14.0; HRMS-ESI (m/z): [M + H]+
calc. for C23H34NO4S, 420.2203; found, 420.2188.
-30.5 (c 1.00 in EtOH);
91% ee [determined by HPLC analysis: Daicel Chiralpak AS-
H column, n-hexane/isopropanol = 90/10 as eluent, flow rate =
0.50 mL min-1, tR = 23.1 min for (R)-3i and 31.6 min for (S)-
3i]; nmax(film)/cm-1 3062, 2972, 2875, 2828, 1729, 1596, 1475,
1456, 1392, 1368, 1303, 1269, 1146, 1088, 1039, 990, 930, 877,
844, 815, 740, 699; dH (400 MHz, CDCl3, Me4Si) 7.76 (2H, d,
J = 8.0 Hz, ArH), 7.33 (2H, d, J = 8.0 Hz, ArH), 7.16 (1H, d,
J = 15.2 Hz, TsCH CH), 6.53 (1H, d, J = 15.2 Hz, TsCH =
CH), 2.81–2.73 (2H, m, NCH2), 2.71–2.63 (2H, m, NCH2), 2.43
(3H, s, ArCH3), 1.76–1.68 (4H, m, NCH2CH2), 1.45 (9H, s, t-Bu),
1.42 (3H, s, 2-CH3); dC (100 MHz, CDCl3, CHCl3) 170.8, 147.0,
144.2, 137.5, 130.8, 129.8, 127.5, 82.1, 65.6, 47.2, 28.0, 24.1, 23.1,
21.5; HRMS-ESI (m/z): [M + H]+ calc. for C20H30NO4S, 380.1890;
found, 380.1878.
(E)-tert-Butyl 2-methyl-2-(piperidin-1-yl)-4-(p-toluenesulfonyl)-
(S,E)-n-Butyl 2-methyl-2-(pyrrolidin-1-yl)-4-(p-toluenesulfonyl)-
but-3-enoate (3g)
but-3-enoate (3j)
Colorless oil (Found: C, 63.9; H, 8.0; N, 3.8. Calc. for C21H31NO4S:
Yellow oil (Found: C, 63.1; H, 7.9; N, 3.9. Calc. for C20H29NO4S:
24
22
C, 64.1; H, 7.9; N, 3.6%); [a] -21.1 (c 1.00 in EtOH); 77% ee
C, 63.3; H, 7.7; N, 3.7%); [a]
-26.0 (c 1.00 in EtOH);
589
589
[determined by HPLC analysis: Daicel Chiralcel OJ-H column,
n-hexane/ethanol = 99/1 as eluent, flow rate = 0.50 mL min-1,
88% ee [determined by HPLC analysis: Daicel Chiralpak
AS-H column, n-hexane/isopropanol = 90/10 as eluent, flow
342 | Org. Biomol. Chem., 2012, 10, 339–345
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rate = 0.50 mL min-1, tR = 30.9 min for (R)-3j and 36.9 min for (S)-
3j]; nmax(film)/cm-1 3058, 2962, 2873, 1727, 1630, 1597, 1459, 1378,
1321, 1302, 1289, 1246, 1196, 1147, 1085, 1018, 968, 836, 812, 708;
dH (400 MHz, CDCl3, Me4Si) 7.76 (2H, d, J = 8.2 Hz, ArH), 7.33
(2H, d, J = 8.2 Hz, ArH), 7.18 (1H, d, J = 15.2 Hz, TsCH CH),
6.56 (1H, d, J = 15.2 Hz, TsCH = CH), 4.15 (1H, dt, J = 12.4,
6.8 Hz, OCH2CH2CH2CH3), 4.12 (1H, dt, J = 12.4, 6.8 Hz,
OCH2CH2CH2CH3), 2.81–2.70 (2H, m, NCH2), 2.69–2.59 (2H,
m, NCH2), 2.44 (3H, s, ArCH3), 1.78–1.69 (4H, m, NCH2CH2),
1.61 (2H, tt, J = 7.4, 6.8 Hz, OCH2CH2CH2CH3), 1.46 (3H,
s, 2-CH3), 1.35 (2H, tq, J = 7.4, 7.4 Hz, OCH2CH2CH2CH3),
0.93 (3H, t, J = 7.4 Hz, OCH2CH2CH2CH3); dC (100 MHz,
CDCl3, CHCl3) 171.7, 146.3, 144.3, 137.4, 131.2, 129.9, 127.7,
65.5, 65.0, 47.4, 30.6, 24.1, 23.1, 21.6, 19.1, 13.6; HRMS-
ESI (m/z): [M + H]+ calc. for C20H30NO4S, 380.1890; found,
380.1872.
(S,E)-tert-Butyl 4-methyl-2-(pyrrolidin-1-yl)-2-(2¢-p-tosylvinyl)-
pentanoate (3m)
Yellow solid (Found: C, 65.4; H, 8.4; N, 3.4. Calc. for C23H35NO4S:
25
589
C, 65.5; H, 8.4; N, 3.3%); [a] -39.9 (c 1.00 in EtOH); 92% ee
[determined by HPLC analysis: Daicel Chiralpak AS-H column,
n-hexane/isopropanol = 95/5 as eluent, flow rate = 0.50 mL min-1,
tR = 24.8 min for (R)-3m and 33.2 min for (S)-3m]; nmax(film)/cm-1
3059, 2964, 2872, 1717, 1628, 1597, 1457, 1392, 1368, 1320, 1300,
1241, 1146, 1087, 1039, 1017, 977, 921, 841, 811, 707, 686; dH (400
MHz, CDCl3, Me4Si) 7.77 (2H, d, J = 8.0 Hz, ArH), 7.32 (2H,
d, J = 8.0 Hz, ArH), 7.20 (1H, d, J = 15.2 Hz, TsCH CH),
6.65 (1H, d, J = 15.2 Hz, TsCH = CH), 2.80–2.71 (2H, m,
NCH2), 2.61–2.52 (2H, m, NCH2), 2.43 (3H, s, ArCH3), 2.00–
1.91 (1H, m, CH2CH(CH3)2), 1.71–1.56 (6H, m, CH2CH(CH3)2
and NCH2CH2), 1.47 (9H, s, t-Bu), 0.853 (3H, d, J = 6.4 Hz,
CH2CH(CH3)2), 0.850 (3H, d, J = 6.4 Hz, CH2CH(CH3)2); dC
(100 MHz, CDCl3, CHCl3) 170.3, 147.2, 144.1, 137.8, 131.0, 129.8,
127.6, 82.2, 68.6, 47.4, 46.8, 28.2, 24.5, 24.3, 23.7, 23.5, 21.6;
HRMS-ESI (m/z): [M + H]+ calc. for C23H36NO4S, 422.2360;
found, 422.2344.
(S,E)-Benzyl 2-methyl-2-(pyrrolidin-1-yl)-4-(p-toluenesulfonyl)-
but-3-enoate (3k)
Yellow oil (Found: C, 66.6; H, 6.6; N, 3.6. Calc. for C23H27NO4S:
25
589
C, 66.8; H, 6.6; N, 3.4%); [a] -19.1 (c 1.00 in EtOH); 90% ee
(S,E)-tert-Butyl 2-isopropyl-2-(pyrrolidin-1-yl)-4-(p-toluenesul-
fonyl)but-3-enoate (3n)
[determined by HPLC analysis: Daicel Chiralpak AS-H column,
n-hexane/isopropanol = 90/10 as eluent, flow rate = 0.50 mL
min-1, tR = 22.0 min for (S)-3k and 30.5 min for (R)-3k];
White solid (Found: C, 64.65; H, 8.2; N, 3.6. Calc. for C22H33NO4S:
n
max(film)/cm-1 3059, 3034, 2964, 2872, 1728, 1630, 1596, 1495,
26
589
C, 64.8; H, 8.2; N, 3.4%); [a] -51.5 (c 1.00 in EtOH); 95% ee
1455, 1376, 1320, 1300, 1289, 1186, 1146, 1084, 1017, 968, 911,
812, 752, 699; dH (400 MHz, CDCl3, Me4Si) 7.72 (2H, d, J =
8.0 Hz, ArH), 7.39–7.26 (7H, m, ArH), 7.18 (1H, d, J = 15.2
Hz, TsCH CH), 6.53 (1H, d, J = 15.2 Hz, TsCH = CH), 5.18
(1H, d, J = 12.4 Hz, CH2Ph), 5.15 (1H, d, J = 12.4 Hz, CH2Ph),
2.78–2.68 (2H, m, NCH2), 2.67–2.58 (2H, m, NCH2), 2.43 (3H,
s, ArCH3), 1.74–1.63 (4H, m, NCH2CH2), 1.47 (3H, s, 2-CH3);
dC (100 MHz, CDCl3, CHCl3) 171.4, 146.0, 144.3, 137.2, 135.3,
131.4, 129.8, 128.5, 128.4, 128.2, 127.6, 66.8, 65.5, 47.3, 24.0, 23.0,
21.6; HRMS-ESI (m/z): [M + H]+ calc. for C23H28NO4S, 414.1734;
found, 414.1725.
[determined by HPLC analysis: Daicel Chiralpak AS-H column,
n-hexane/isopropanol = 97/3 as eluent, flow rate = 0.50 mL min-1,
tR = 42.3 min for (R)-3n and 48.3 min for (S)-3n]; nmax(film)/cm-1
3059, 2971, 2930, 2875, 1716, 1633, 1597, 1456, 1392, 1369, 1320,
1297, 1289, 1252, 1147, 1087, 1017, 976, 928, 878, 841, 815, 734,
709; dH (400 MHz, CDCl3, Me4Si) 7.78 (2H, d, J = 8.2 Hz,
ArH), 7.32 (2H, d, J = 8.2 Hz, ArH), 7.07 (1H, d, J = 15.2 Hz,
TsCH CH), 6.58 (1H, d, J = 15.2 Hz, TsCH = CH), 2.84–2.73
(2H, m, NCH2), 2.53–2.45 (2H, m, NCH2), 2.43 (3H, s, ArCH3),
2.37 (1H, qq, J = 6.8, 6.8 Hz, CH(CH3)2), 1.70–1.57 (4H, m,
NCH2CH2), 1.48 (9H, s, t-Bu), 0.84 (3H, d, J = 6.8 Hz, CH(CH3)2),
0.74 (3H, d, J = 6.8 Hz, CH(CH3)2); dC (100 MHz, CDCl3, CHCl3)
170.4, 144.1, 144.0, 138.0, 132.9, 129.8, 127.6, 82.1, 72.5, 46.7, 33.5,
28.3, 23.6, 21.6, 18.5, 16.4; HRMS-ESI (m/z): [M + H]+ calc. for
C22H34NO4S, 408.2203; found, 408.2189.
(S,E)-tert-Butyl 2-benzyl-2-(pyrrolidin-1-yl)-4-(p-toluene-
sulfonyl)but-3-enoate (3l)
Colorless oil (Found: C, 68.4; H, 7.5; N, 3.0. Calc. for C26H33NO4S:
27
589
C, 68.5; H, 7.3; N, 3.1%); [a]
+15.8 (c 1.00 in EtOH);
(R,E)-Cyclohexyl 2-phenyl-2-(pyrrolidin-1-yl)-4-(p-toluenesul-
fonyl)but-3-enoate (3o)
81% ee [determined by HPLC analysis: Daicel Chiralpak AS-
H column, n-hexane/isopropanol = 90/10 as eluent, flow rate =
0.50 mL min-1, tR = 22.5 min for (R)-3l and 27.8 min for (S)-3l];
Colorless oil (Found: C, 69.4; H, 7.4; N, 3.1. Calc. for C27H33NO4S:
22
589
n
max(film)/cm-1 3062, 3032, 2974, 2934, 2873, 1718, 1597, 1495,
C, 69.35; H, 7.1; N, 3.0%); [a] +15.3 (c 1.00 in EtOH); 40% ee
1454, 1393, 1369, 1319, 1302, 1264, 1147, 1086, 1021, 973, 841,
813, 737, 702; dH (400 MHz, CDCl3, Me4Si) 7.70 (2H, d, J = 8.4
Hz, ArH), 7.32 (2H, d, J = 8.4 Hz, ArH), 7.21–7.14 (3H, m, Ph),
7.01–6.94 (2H, m, Ph), 6.79 (1H, d, J = 15.2 Hz, TsCH CH),
6.62 (1H, d, J = 15.2 Hz, TsCH = CH), 3.49 (1H, d, J = 13.0
Hz, CH2Ph), 2.95–2.86 (2H, m, NCH2), 2.80 (1H, d, J = 13.0 Hz,
CH2Ph), 2.73–2.64 (2H, m, NCH2), 2.44 (3H, s, ArCH3), 1.79–1.67
(4H, m, NCH2CH2), 1.43 (9H, s, t-Bu); dC (100 MHz, CDCl3,
CHCl3) 169.5, 147.2, 144.1, 137.6, 135.0, 131.4, 130.4, 129.7,
128.1, 127.7, 127.0, 82.6, 69.6, 47.1, 44.8, 28.2, 23.7, 21.5; HRMS-
ESI (m/z): [M + H]+ calc. for C26H34NO4S, 456.2203; found,
456.2186.
[determined by HPLC analysis: Daicel Chiralpak AS-H column,
n-hexane/isopropanol = 92/8 as eluent, flow rate = 0.50 mL min-1,
tR = 42.6 min for (R)-3o and 50.6 min for (S)-3o]; nmax(film)/cm-1
3061, 2937, 2860, 1722, 1625, 1597, 1492, 1449, 1400, 1319, 1232,
1196, 1145, 1086, 1033, 1010, 987, 907, 835, 813, 761, 736, 700; dH
(400 MHz, CDCl3, Me4Si) 7.70 (2H, d, J = 8.4 Hz, ArH), 7.33–
7.22 (8H, m, ArH and TsCH CH), 6.61 (1H, d, J = 15.2 Hz,
TsCH = CH), 4.96 (1H, tt, J = 8.6, 4.0 Hz, OCH), 2.87–2.78 (2H,
m, NCH2), 2.58–2.49 (2H, m, NCH2), 2.44 (3H, s, ArCH3), 1.90–
1.77 (2H, m, c-Hex), 1.77–1.60 (6H, m, NCH2CH2 and c-Hex),
1.60–1.21 (6H, m, c-Hex); dC (100 MHz, CDCl3, CHCl3) 170.1,
145.5, 144.2, 138.0, 137.6, 131.0, 129.8, 128.3, 128.1, 127.9, 127.6,
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74.1, 73.8, 48.3, 31.51, 31.48, 25.2, 24.5, 23.4, 21.6; HRMS-ESI
1367, 1300, 1248, 1173, 1134, 1121, 1075, 1045, 1026, 1002, 984,
908, 848, 809, 749; dH (400 MHz, CDCl3, Me4Si) 2.90–2.82 (2H,
m, NCH2), 2.76–2.68 (2H, m, NCH2), 1.84 (1H, dq, J = 13.6, 7.6
Hz, CH2CH3), 1.77–1.70 (4H, m, NCH2CH2), 1.63 (1H, dq, J =
13.6, 7.6 Hz, CH2CH3), 1.46 (9H, s, t-Bu), 1.24 (3H, s, 2-CH3), 0.88
(3H, t, J = 7.6 Hz, CH2CH3); dC (100 MHz, CDCl3, CHCl3) 173.8,
80.3, 64.9, 46.7, 30.7, 28.3, 24.2, 20.1, 8.6; HRMS-ESI (m/z): [M
+ H]+ calc. for C13H26NO2, 228.1958; found, 228.1947.
(m/z): [M + H]+ calc. for C27H34NO4S, 468.2203; found, 468.2183.
(S,E)-Cyclohexyl 2-[allyl(2¢-tosylpenta-1¢,4¢-dienyl)amino]-
propanoate (9)5
Colorless oil (Found: C, 66.6; H, 7.8; N, 3.15. Calc. for
C24H33NO4S: C, 66.8; H, 7.7; N, 3.25%); [a]25869 -90.1 (c 1.00 in
EtOH); nmax(film)/cm-1 3081, 2938, 2860, 1732, 1622, 1494, 1451,
1419, 1281, 1198, 1170, 1138, 1085, 1031, 1015, 917, 814, 761,
707; dH (400 MHz, CDCl3, Me4Si) 7.69 (2H, d, J = 8.2 Hz, ArH),
7.63 (1H, s, 1¢-H), 7.24 (2H, d, J = 8.2 Hz, ArH), 5.84–5.65 (2H,
m, CH2CH = CH2), 5.24–5.13 (2H, m, CH2CH CH2), 4.97–4.85
(2H, m, CH2CH CH2), 4.81 (1H, tt, J = 8.8, 3.2 Hz, OCH), 4.09
(1H, q, J = 7.2 Hz, NCHCO), 3.91–3.77 (2H, m, CH2CH CH2),
3.09–2.94 (2H, m, CH2CH CH2), 2.39 (3H, s, ArCH3), 1.93–1.60
(4H, m, c-Hex), 1.60–1.20 (6H, m, c-Hex), 1.49 (3H, d, J = 7.2 Hz,
2-CH3); dC (100 MHz, CDCl3, CHCl3) 171.1, 145.5, 142.3, 139.7,
136.7, 134.4, 129.3, 127.4, 117.0, 115.6, 103.0, 73.9, 61.2, 51.6,
31.4, 29.1, 25.2, 23.5, 21.4, 16.7; HRMS-ESI (m/z): [M + H]+
calc. for C24H34NO4S, 432.2203; found, 432.2182.
Preparation of the authentic sample (S)-5
A mixture of (S)-66 (68 mg, 0.39 mmol, 98% ee), 1,4-butanediol
di-p-toluenesulfonate14 (163 mg, 0.41 mmol), and potassium
hydrogen carbonate (0.12 g, 1.2 mmol) in acetonitrile (2 mL)
was refluxed for 6 h. The resulting mixture was cooled to room
temperature and concentrated. The residue was purified twice by
chromatography on silica gel (1st: dichloromethane/methanol =
20/1 to 10/1 as eluent; 2nd: n-hexane/ethyl acetate = 3/1 to 1.5/1
23
589
as eluent) to obtain (S)-5 (26 mg, 29% yield). Colorless oil; [a]
+8.7 (c 1.00 in CHCl3).
[1,2] Stevens rearrangement of (S)-N-benzyl-2-(pyrrolidin-1-yl)-
propanoic acid ester-derived ammonium salt 7
(S,3E,5E)-tert-Butyl 2-methyl-2-(pyrrolidin-1-yl)-4,6-ditosylhexa-
3,5-dienoate (10)7
A solution of 7 (73 mg, 0.19 mmol) in THF (4 mL) was
treated with potassium tert-butoxide (26 mg, 0.23 mmol) at 0 ◦C
and stirred for 4 h. The resulting mixture was quenched with
saturated aqueous ammonium chloride and extracted with ethyl
acetate. The combined extracts were washed with brine, dried
over sodium sulfate, and concentrated. The residue was purified
by chromatography on silica gel (n-hexane/ethyl acetate = 2/1
as eluent) to afford tert-butyl 2-methyl-3-phenyl-2-(pyrrolidin-1-
yl)propanoate (8) (38 mg, 69% yield). Colorless oil (Found: C, 74.4;
H, 9.3; N, 4.7. Calc. for C18H27NO2: C, 74.7; H, 9.4; N, 4.8%). 0% ee
[determined by HPLC analysis: Daicel Chiralcel OD-H column,
n-hexane/ethanol/diethylamine = 99.5/0.5/0.05 as eluent, flow
rate = 0.50 mL min-1, tR = 8.2 and 9.3 min]; nmax(film)/cm-1 3063,
2972, 2873, 1715, 1604, 1495, 1455, 1391, 1368, 1251, 1163, 1098,
1033, 1011, 964, 939, 912, 849, 737, 701; dH (400 MHz, CDCl3,
Me4Si) 7.27–7.17 (5H, m, Ph), 3.32 (1H, d, J = 13.0 Hz, CH2Ph),
2.97-2.89 (2H, m, NCH2), 2.88–2.80 (2H, m, NCH2), 2.82 (1H, d,
J = 13.0 Hz, CH2Ph), 1.83–1.74 (4H, m, NCH2CH2), 1.46 (9H, s,
t-Bu), 1.16 (3H, s, 2-CH3); dC (100 MHz, CDCl3, CHCl3) 172.6,
137.8, 130.6, 127.8, 126.2, 80.9, 65.3, 46.9, 43.4, 28.3, 24.0, 21.0;
HRMS-ESI (m/z): [M + H]+ calc. for C18H28NO2, 290.2115; found,
290.2103.
Yellow solid (Found: C, 62.2; H, 6.9; N, 2.4. Calc. for C29H37NO6S2:
24
C, 62.2; H, 6.7; N, 2.5%); [a]
n
+96.0 (c 1.00 in EtOH);
589
max(film)/cm-1 3056, 2974, 2927, 2874, 1724, 1628, 1597, 1455,
1370, 1322, 1240, 1149, 1085, 1041, 993, 837, 812, 764, 708; dH
(400 MHz, CDCl3, Me4Si) 7.75 (2H, d, J = 8.4 Hz, ArH), 7.70
(2H, d, J = 8.4 Hz, ArH), 7.36 (2H, d, J = 8.4 Hz, ArH), 7.33
(2H, d, J = 8.4 Hz, ArH), 7.10 (1H, d, J = 15.8 Hz, 5-H), 6.81
(1H, s, 3-H), 6.41 (1H, d, J = 15.8 Hz, 6-H), 2.57–2.35 (4H, m,
NCH2), 2.46 (3H, s, ArCH3), 2.45 (3H, s, ArCH3), 1.67–1.54 (4H,
m, NCH2CH2), 1.41 (9H, s, t-Bu), 1.40 (3H, s, 2-CH3); dC (100
MHz, CDCl3, CHCl3) 161.1, 145.7, 144.72, 144.66, 144.3, 137.1,
136.4, 131.5, 130.1, 129.9, 129.7, 128.4, 127.7, 83.8, 60.7, 46.5,
27.7, 23.4, 21.7, 21.6, 19.9; HRMS-ESI (m/z): [M + H]+ calc. for
C29H38NO6S2, 560.2135; found, 560.2119.
Preparation of tert-butyl 2-methyl-2-(pyrrolidin-1-yl)butanoate (5)
from 3i
(Step 1) A solution of 3i (296 mg, 0.780 mmol) in THF
(7.8 mL) was added to a suspention of magnesium powder
(193 mg, 7.94 mmol) in dry methanol (7.8 mL) at 50 ◦C. The
mixture was stirred for 2 h at the same temperature◦and quenched
with saturated aqueous ammonium chlolride at 0 C. Extractive
workup and purification by chromatography on silica gel (n-
hexane/ethyl acetate = 2/1 as eluent) gave tert-butyl 2-methyl-2-
(pyrrolidin-1-yl)but-3-enoate (4) (73 mg, 42% yield) as a colorless
oil. (Step 2) A mixture of 4 (63 mg, 0.28 mmol) and palladium
on carbon (loading: 10 wt%, 5 mg) in ethyl acetate (2.8 mL)
was stirred for 1 h under a hydrogen atmosphere. The resulting
mixture was filtered through a pad of Celite and the filtrate was
concentrated. The residue was purified by chromatography on
silica gel (dichloromethane/methanol = 10/1 as eluent) to give
5 (52 mg, 82% yield). Colorless oil (Found: C, 68.4; H, 11.1; N,
6.1. Calc. for C13H25NO2: C, 68.7; H, 11.1; N, 6.2%); [a]25849 +8.0
(c 1.00 in CHCl3); nmax(film)/cm-1 2973, 2876, 1719, 1457, 1391,
Acknowledgements
This work was supported by the Grant for the Promotion of
Niigata University Research Projects (23C018), the Foundation
for Japanese Chemical Research, and the Uchida Energy Science
Promotion Foundation.
Notes and references
1 (a) T. G. Back, K. N. Clary and D. Gao, Chem. Rev., 2010, 110, 4498–
4553; (b) T. G. Back, Tetrahedron, 2001, 57, 5263–5301; (c) L. Waykole
and L. A. Paquette, Org. Syn., 1989, 67, 149–156.
2 Previous examples of reactions of ethynyl tolyl sulfone with tertiary
amines: (a) B. Drouillat, F. Couty and V. Razafimahale´o, Synlett, 2009,
344 | Org. Biomol. Chem., 2012, 10, 339–345
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3182–3186; (b) L. G. Voskressensky, A. V. Listratova, T. N. Borisova, S.
A. Kovaleva, R. S. Borisov and A. V. Varlamov, Tetrahedron, 2008, 64,
10443–10452; (c) L. G. Voskressensky, A. V. Listratova, T. N. Borisova,
G. G. Alexandrov and A. V. Varlamov, Eur. J. Org. Chem., 2007, 6106–
6117; (d) L. G. Voskressensky, S. V. Akbulatov, T. N. Borisova, A. V.
Kleimenov and A. V. Varlamov, Russ. Chem. Bull., Int. Ed., 2007, 56,
2323–2329; (e) L. G. Voskressensky, T. N. Borisova, A. V. Listratova, L.
N. Kulikova, A. A. Titov and A. V. Varlamov, Tetrahedron Lett., 2006,
47, 4585–4589.
3 (a) M. H. Weston, M. Parvez and T. G. Back, J. Org. Chem., 2010,
75, 5402–5405; (b) M. H. Weston, K. Nakajima and T. G. Back, J.
Org. Chem., 2008, 73, 4630–4637; (c) M. H. Weston, K. Nakajima, M.
Parvez and T. G. Back, Chem. Commun., 2006, 3903–3905.
4 T. Igarashi, E. Tayama, H. Iwamoto and E. Hasegawa, Tetrahedron
Lett., 2011, 52, 1819–1821.
5 The starting materials 2a–d were recovered in 75–99% yield. When
the reaction of the 2-(diallylamino) derivative 2d was performed at
room temperature for 2 days, the 3-aza-Cope rearrangement proceeded
to give the corresponding product 9 in 71% yield; however, the [2,3]
Stevens rearrangement product (a-allyl derivaive) was not obtained.
The compound data of 9 were summarized in the Experimental
section.
8 Similar results were obtained in our previous work, see ref. 4. The
reactions afforded unidentifiable products and the substrate 2j or 2k
were not recovered.
9 For reviews: (a) J. Eames and M. J. Suggate, Angew. Chem., Int. Ed.,
2005, 44, 186–189; (b) H. Zhao, D. C. Hsu and P. R. Carlier, Synthesis,
2005, 1–16; (c) K. Fuji and T. Kawabata, Chem.-Eur. J., 1998, 4, 373–
376.
10 Examples of asymmetric intermolecular a-substitution via memory of
chirality, see: (a) M. Branca, S. Pena, R. Guillot, D. Gori, V. Alezra and
C. Kouklovsky, J. Am. Chem. Soc., 2009, 131, 10711–10718; (b) M. K.
Ghorai, K. Ghosh and A. K. Yadav, Tetrahedron Lett., 2009, 50, 476–
479; (c) M. Branca, D. Gori, R. Guillot, V. Alezra and C. Kouklovsky,
J. Am. Chem. Soc., 2008, 130, 5864–5865; (d) S. MacQuarrie-Hunter
and P. R. Carlier, Org. Lett., 2005, 7, 5305–5308; (e) P. R. Carlier, P.
C.-H. Lam, J. C. DeGuzman and H. Zhao, Tetrahedron: Asymmetry,
2005, 16, 2998–3002; (f) T. Kawabata, J. Chen, H. Suzuki and K. Fuji,
Synthesis, 2005, 1368–1377; (g) P. R. Carlier, H. Zhao, J. DeGuzman
and P. C.-H. Lam, J. Am. Chem. Soc., 2003, 125, 11482–11483; (h) T.
Kawabata, S. Kawakami, S. Shimada and K. Fuji, Tetrahedron, 2003,
59, 965–974; (i) T. Kawabata, S. Kawakami and K. Fuji, Tetrahedron
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11 An example of [1,2] vinyl Stevens rearrangement: S. H. Pine, J. Cheney,
B. Catto and J. D. Petersen, J. Org. Chem., 1974, 39, 130–133.
12 Voskressensky et al. reported the [1,2] vinylic Stevens rearrangement of
ammonium ylides generated by the reaction of tertiary amine with
electron-deficient acetylene, such as ethyl propiolate, see: (a) L. G.
Voskressensky, L. N. Kulikova, A. V. Kleimenov, N. I. Guranova, A. V.
Listratova and A. V. Varlamov, Chem. Heterocycl. Compd., 2010, 46,
625–626; (b) L. G. Voskressensky, L. N. Kulikova, A. Kleimenov, N.
Guranova, T. N. Borisova and A. V. Varlamov, Tetrahedron Lett., 2009,
50, 4851–4853.
6 Prepared by the literature using (R,R)-3,4,5-trifluorophenyl-NAS bro-
mide, see: T. Ooi, M. Takeuchi, M. Kameda and K. Maruoka, J. Am.
Chem. Soc., 2000, 122, 5228–5229.
7 The sturucture of by-product was 10 which would be derived
by tosylethenylation of intermediate
The compound data of 10 was summarized in the Experimental
C depicted in Scheme 4.
section.
13 We attempted reactions using other types of electron-deficient terminal
acetylenes, such as ethyl propiolate. The reaction proceeded; however,
the yield and ee of the corresponding a-adduct was lower (EtOAc,
0 ◦C, 4 h, 11%, 78% ee).
14 A. R. Abreu, M. M. Pereira and J. C. Bayo´n, Tetrahedron, 2010, 66,
743–749.
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