Stereoselective synthesis of chiral amino allenes by organocopper- mediated anti-S(N)2'-substitution reaction of chiral ethynylaziridines

Article abstract of DOI:10.1016/S0040-4020(00)00136-8

Chiral N-protected amino allenes have been synthesized from 3-alkyl-2- ethynylaziridines via organocopper-mediated reactions. Treatment of enantiomerically pure (2R,3S)-2,3-trans-3-alkyl-2-ethynylaziridines with RCu(CN)M (M=Li or MgX) in THF at -78°C affords exclusively the expected (S,S)-amino allenes in high yields in a regio- and stereoselective manner. On the other hand, (2S,3S)-2,3,cis-3-alkyl-2-ethynylaziridines give stereoisomeric (S,R)-amino allenes in comparable high yields. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00136-8

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2811±2820
Stereoselective Synthesis of Chiral Amino Allenes by
Organocopper-Mediated anti-SN20-Substitution Reaction of
Chiral Ethynylaziridines
b
b
b
a
Hiroaki Ohno,a, Ayako Toda, Nobutaka Fujii, Yoshiji Takemoto, Tetsuaki Tanaka
*
and Toshiro Ibukab,²
aGraduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
bGraduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
Received 21 September 1999; revised 6 January 2000; accepted 13 January 2000
AbstractÐChiral N-protected amino allenes have been synthesized from 3-alkyl-2-ethynylaziridines via organocopper-mediated reactions.
Treatment of enantiomerically pure (2R,3S)-2,3-trans-3-alkyl-2-ethynylaziridines with RCu(CN)M (MˆLi or MgX) in THF at 2788C
affords exclusively the expected (S,S)-amino allenes in high yields in a regio- and stereoselective manner. On the other hand, (2S,3S)-
2,3-cis-3-alkyl-2-ethynylaziridines give stereoisomeric (S,R)-amino allenes in comparable high yields. q 2000 Elsevier Science Ltd. All
rights reserved.
The stereochemical course of organocopper-mediated SN20
substitution of propargylic compounds has been well docu-
mented.1,2 Propargylic ethers,3a thio ethers,3b esters,4 and
sulfonates5 usually undergo highly stereoselective anti-
facial reactions; i.e. the SN20 displacement generally
proceeds anti to the leaving group (anti-SN20 reactions).
The organocopper-mediated ring-opening reaction of
propargylic epoxides also affords the corresponding
hydroxy allenes in a highly regio- and anti-SN20-selective
manner.6 The hydroxy allenes have been used as key inter-
mediates in various subsequent chemical transformations.7
Recently, Marshall and co-workers elegantly demonstrated
that the hydroxy allenes could be cyclized to 2,5-dihydro-
or syn products, depending on the reaction conditions or
copper reagents used.3,11
On the other hand, amino allenes, the aza-analogs of
hydroxy allenes, are also an important class of molecules
with highly reactive chemical properties due to their
cumulated double bonds.12 Allenic compounds bearing a
nitrogen functionality separated from the allenic carbon
atom by one,13 three,14 and four15 carbon atoms are attrac-
tive substrates for constructing ®ve- and six-membered aza-
heterocycles.13d,14a±e,15,16
Recently, highly strained compounds like azacyclo-
propanes17 and azacyclobutanes14d,18,19 have been success-
fully synthesized from amino allenes via palladium-
catalyzed cyclization reactions. However, except for a few
cases,13g,i a scan of the literature has revealed a surprising
paucity of methods that facilitate the synthesis of chiral
8
furans, important structural units of poly ether antibiotics
and various polyene mycotoxins,9 in a highly regio- and
stereo-selective manner (Scheme 1).10 Interestingly, it has
been reported by Alexakis et al. that the SN20 displacement
of the propargylic epoxides or ethers can lead to either anti
Scheme 1.
Keywords: allenes; aziridines; regiocontrol; stereoselection.
* Corresponding author. Tel.: 181-6-6879-8212; fax: 181-6-6879-8214; e-mail: hohno@phs.osaka-u.ac.jp
Deceased 20 January 2000.
²
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00136-8

2812
H. Ohno et al. / Tetrahedron 56 (2000) 2811±2820
Scheme 2. Synthesis of amino allenes via an organocopper-mediated reaction; abbreviations: MˆLi or MgBr; R1ˆalkyl; R2ˆarylsulfonyl; R3ˆalkyl or tri-n-
butylstannyl.
internal allenes bearing a nitrogen functionality separated
from the allenic carbon atom only by one carbon atom.
mixture of 9 (an anti-SN20 product), 10 (a syn-SN20 product),
and 11 (a reduction product) in favor of the unexpected
product 11 (entry 1, Table 1). In a similar manner, exposure
of 8 to Me2CuLi´LiCN´2LiBr´2LiCl23 yielded a mixture of
9, 10, and the dimethylated compound 12 (entry 2, Table 1).
In connection with a program directed towards the reaction
of chiral amino allenes, we required a reliable procedure for
the synthesis of internal amino allenes like 5 and 7 with high
optical purity (Scheme 2). It is of considerable interest to
determine whether chiral ethynylaziridines can be trans-
formed diastereoselectively into chiral amino allenes. We
wish to report a highly ef®cient ring-opening reaction of
chiral 2,3-trans- and 2,3-cis-ethynylaziridines 4 and 620
affording the corresponding (S,S)- and (S,R)-amino allenes
5 and 7 in both excellent isolated yields and high dia-
stereoisomeric purities as illustrated in Scheme 2.21
Claeson and Olsson had previously reported that certain
allenes were racemized by treatment with organocuprates.24
However, this was not to be the present case since exposure
of the chiral allene 9 or 10 to Me2CuLi´LiCN´2LiCl com-
pletely recovered the starting allene 9 or 10 unchanged. In
the reactions of certain propargylic epoxides11 with organo-
copper reagents, it has been frequently documented that
small changes in the reaction conditions (solvents and
organocopper reagents) and substrate structure can alter
the course of reactions. Although it was not surprising that
the reaction of 8 with Me2CuLi´3LiI yielded a large amount
of a reduction product 11 as the major product, the
occurrence of the dimethylated product 12 by the reaction
of 8 with Me2CuLi´LiCN´2LiBr´2LiCl is an unprecedented
striking example. For reasons we cannot explain, classical
Gilman-type organocuprates and R2CuLi´LiCN´2LiCl gave
mixtures containing little, if any, of the expected product 9
(Scheme 3).
Results and Discussion
The requisite N-arylsulfonylated 2,3-trans- and 2,3-cis-3-
alkyl-2-ethynylaziridines 8, 16, 20±25, ent-8, ent-16, 34±
37 with high optical purities for the present study were
prepared in
a straightforward manner from natural
a-amino acids following our recently published pro-
cedures.20 It is well known that the reactivity of NH-aziri-
dines towards nucleophilic reagents is relatively low: hence,
activation by the introduction of a strong electron-
withdrawing protective group on the nitrogen atom of the
aziridine is required. 2,4,6-Trimethylbenzenesulfonyl (Mts)
or 4-methoxy-2,3,6-trimethylbenzenesulfonyl (Mtr) serves
as an effective activating group. In addition, the Mts or Mtr
group can withstand a wide range of chemical manipu-
lations and yet be removed by the use of Yajima's
protocol.22
After considerable experimentation, it was found that
organocyanocuprates, RCu(CN)M´nLiX (MˆLi or MgBr,
XˆCl or Br), are the reagent of choice for the ring-opening
reactions, giving excellent isolated yields of the corre-
sponding anti-SN20 products (Scheme 4). Typically,
reaction of the aziridine 8 with MeCu(CN)Li´LiBr´2LiCl
in THF at 2788C for 3 h yielded the expected dia-
stereomerically pure amino allene 9 (an anti-SN20 product)
as the single isomer in 93% isolated yield (entry 3, Table 1).
While we cannot conclusively rule out the presence of trace
quantities of isomeric- or reduction-products, the (S,R)
product 9 was the only one detected by HPLC analysis.
Similarly, exposure of 8 to i-PrCu(CN)MgBr´2LiCl,
n-BuCu(CN)Li´2LiCl, and n-Bu3SnCu(CN)Li´2LiCl yields
the corresponding ring-opened products 13, 14, and 15 in
high yields (entries 4±6, Table 1). The 2,3-trans-isomer 16
also gave exclusively the anti-SN20 products 10, 17, 18, and
19 (Scheme 4 and entries 7±10, Table 1).
Except for a few exceptional cases,11 it has been well-
documented that treatment of propargylic oxiranes with
Gilman-type reagents afford the expected allenyl alcohols
via an anti-SN20 pathway.6b,7,10b,c Accordingly, we initiated
our study to determine the scope of the organocopper-
mediated ring-opening reaction using 2,3-cis-2-ethynyl-
aziridine 8 with some organocopper reagents as shown in
Scheme 3 and Table 1. The reaction of 8 in THF with
Gilman-type reagent, Me2CuLi´3LiI, afforded a separable
Scheme 3. Reagents and abbreviations: aˆMe2CuLi´3Lil; bˆMe2CuLiCN´2LiBr´2LiCl; Mtsˆ2,4,6-trimethylbenzenesulfonyl.

H. Ohno et al. / Tetrahedron 56 (2000) 2811±2820
2813
Table 1. Reactions of some 2-ethynylaziridines with organocopper reagents (all reactions were carried out in THF at 2788C using 4 equiv. of the organocopper
reagent)
a
Entry
Substrate
Reagent
Me2CuLi´3LiI
Reaction time (h)
Product(s)
Abs. con®g.
[a]D
Ratiob
Yield (%)c
1
2
3
4
5
6
7
8
8
8
8
8
8
8
16
16
16
16
20
0.5
0.5
3.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
2
9110111
9:10:11ˆ25:2:73
9:10:12 45:18:37
9ˆ100
78
72
93
99
97
90
98
98
99
92
96
99
99
97
99
98
88
89
90
97
Me2CuLi´LiCN´2LiBr´2LiCl
MeCu(CN)Li´LiBr´2LiCl
i-PrCu(CN)MgCl´2LiCl
n-BuCu(CN)Li´2LiCl
Bu3SnCu(CN)Li´2LiCl
MeCu(CN)Li´LiBr´2LiCl
i-PrCu(CN)MgCl´2LiCl
n-BuCu(CN)Li´2LiCl
Bu3SnCu(CN)Li´2LiCl
MeCu(CN)Li´LiBr´2LiCl
MeCu(CN)Li´2LiCl
9110112
9
13
(S,R)
(S,R)
(S,R)
(S,R)
(S,S)
(S,S)
(S,S)
(S,S)
(S,R)
(S,R)
(S,S)
(S,S)
(R,R)
(R,S)
(R,S)
(R,S)
(R,R)
(R,R)
273
2102
2108
2236
136
186
177
1183
263
273
125
19
241
127
177
199
238
264
13ˆ100
14
15
10
17
18
19
26
27
28
29
30
31
ent-9
32
ent-10
33
14ˆ100
15ˆ100
10ˆ100
17ˆ100
9
18ˆ100
10
11
12
13
14
15
16
17
18
19
20
19ˆ100
26ˆ100
21
22
23
24
6
0.5
27ˆ100
MeCu(CN)Li´LiBr´2LiCl
MeCu(CN)Li´2LiCl
MeCu(CN)Li´2LiCl
28ˆ100
0.5
29ˆ100
d
30ˆ100
25
MeCu(CN)Li´2LiCl
0.5
1.2
0.7
0.5
0.7
31ˆ100
ent-8
ent-8
ent-16
ent-16
MeCu(CN)Li´LiBr´2LiCl
EtCu(CN)MgBr´2LiCl
MeCu(CN)Li´2LiCl
ent-9ˆ100
32ˆ100
ent-10ˆ100
33ˆ100
EtCu(CN)MgBr´2LiCl
a Optical rotations were measured in chloroform.
b Ratios were determined by isolation or HPLC.
c Isolated yields.
d 2788C (1 h) then 2788C to 2208C (1 h).
As shown in Scheme 4 and Table 1 (entries 11±16), the
2,3-cis- and trans-aziridines (20 and 21) and (22 and 23)
prepared from (S)-phenylalanine as well as 2,3-cis- and
trans-aziridines 24 and 25 synthesized from (S)-serine
also gave the corresponding amino allenes in good yields
by treatment with methylcyanocuprate. Thus, the described
methodology involving the organocyanocuprate-mediated
reaction clearly has several advantages over other methods
in terms of mildness, selectivity, ef®ciency and con-
venience.
with a net anti-SN20 substitution reaction. As can be seen
from Fig. 1, in the solid-state, the phenyl ring of the benzyl
group was folded over the allenic group. Such folding has
also been reported for various compounds involving a
benzyl group and a carbon±carbon double bond26 and it
has been suggested that the folded conformation would be
stabilized by intramolecular dipole±dipole interactions
generally referred to as p-stacking.
Mitochondrial monoamine oxidase (MAO) is a ¯avin-
linked enzyme that is responsible for the oxidative inacti-
vation of the transmitter amines.27 An allenic amine 34 is a
typical known irreversible inhibitor of MAO.28 For the
purpose of synthesis of bioactive compounds, the amino
allenes ent-9, ent-10, 32, and 33 have also been synthesized
in high yields and diastereoisomeric purities from the
Although the absolute con®guration listed in Table 1 of all
the amino allenes synthesized could be deduced from the
well-established organocyanocuprate-mediated anti-SN20
pathway, the unambiguous structure assignment for 28
rested on X-ray analysis.25 The X-ray data are consistent
Scheme 4. Abbreviations: Mtsˆ2,4,6-trimethylbenzenesulfonyl; Mtrˆ4-methoxy-2,4,6-trimethylbenzenesulfonyl. For organocopper reagents, see Table 1.

2814
H. Ohno et al. / Tetrahedron 56 (2000) 2811±2820
Next, we examined the ring-opening reaction of alkynyl-
aziridines 34±37 bearing a methoxycarbonyl or trimethyl-
silyl functionality on the terminal sp carbon atom (Schemes
7 and 8). Considerable difference was observed between the
reactions of 2,3-cis- and 2,3-trans-aziridines with methyl-
cyanocuprate.
Thus, whereas treatment of 2,3-cis-aziridine 34 bearing a
methoxycarbonyl group with MeCu(CN)Li gave a mixture
of three products 38 (an anti-SN20 product), 39 (a syn-SN20
product), and 40 in variable ratios, exposure of 2,3-cis-aziri-
dine 35 having a trimethylsilyl group to MeCu(CN)Li
afforded a mixture of two products 41 and 42 (Scheme 7).
It should be clearly noted that the reaction of 35 with
methylcyanocuprate was very slow at 2788C and did not
proceed to completion. Consequently, the reaction mixture
was allowed to warm to 08C and stirred for 1.5 h.
Figure 1. Solid-state conformation of 28.
corresponding ethynylaziridines ent-8 and ent-16 (Scheme
5; entries 17±20, Table 1).
It has been shown by Alexakis, Normant and co-workers
that some propargylic epoxides react with copper(I)-
catalyzed Grignard reagents to afford a-allenic alcohols.
The reaction has been reported to be highly diastereoselec-
tive and its stereochemical outcome (syn- or anti-isomer)
has been fully controlled. In an attempt to study those
factors which in¯uence the product distribution, we brie¯y
examined the effects of reaction condition parameters on the
composition of products. The reaction of two aziridines 8
and 16 with n-BuMgCl was investigated under otherwise
identical conditions to those reported by Alexakis11b
(Scheme 6). The two reactions shown in Scheme 6 yielded
in each case a mixture of two SN20 products in favor of the
anti-SN20 product. In view of the low syn-SN20 diastereo-
selectivity, this aspect of the study was not pursued further
(Scheme 6).
On the other hand, as shown in Scheme 8, 2,3-trans-aziri-
dines 36 and 37 afford exclusively the anti-SN20 products 39
and 43, respectively, in high yields and high diastereomeric
purities. Reaction time of 30 min at 278 to 2208C was
suf®cient for complete conversion of the 2,3-trans-alkynyl-
aziridine 37 into the amino allene 43.
Finally, we examined ring-opening reactions of ethynyl
azacyclobutanes 44 and 45 under a number of different
conditions and with a number of organocopper reagents in
hopes of synthesizing amino allenes. In both cases, we
obtained substantial amounts of the unchanged starting
materials; however, there was no sign in any of these experi-
ments of any quantities of the expected amino allenes. There
Scheme 5.
Scheme 6.

H. Ohno et al. / Tetrahedron 56 (2000) 2811±2820
2815
Scheme 7.
Scheme 8.
Scheme 9.
is, therefore, little hope of using N-protected ethynyl aza-
cyclobutanes for amino allene formation (Scheme 9).
DIP-360 digital polarimeter. For ¯ash chromatography,
silica gel 60 H (silica gel for thin-layer chromatography,
Merck) or silica gel 60 (®ner than 230 mesh, Merck) was
employed. For HPLC, m-bondasphere-C18 (3.9£150 mm,
Merck) was employed.
In summary, chiral amino allenes with high optical purity
have been synthesized from (2R,3S)-2,3-cis- or (2S,3S)-
2,3-trans-2-ethynylaziridines via organocopper-mediated
reactions. Work on synthetic transformations of amino
allenes thus obtained is in progress and will be reported
elsewhere in due course.
General procedure for RCu(CN)Li´nLiX-mediated ring-
opening reaction of 3-alkyl-2-ethynylaziridines (Table 1,
entry 3±20). Synthesis of (5S,aR)-6-methyl-5-[N-(2,4,6-
trimethylbenzenesulfonyl)amino]-2,3-heptadiene (9) (Table
1, entry 3) from the aziridine (8). To a stirred solution of
CuCN (71.6 mg, 0.8 mmol) and LiCl (67.7 mg, 1.6 mmol)
in dry THF (1 mL) under argon was added by syringe
MeLi´LiBr (1.5 M solution in Et2O; 0.53 mL, 0.8 mmol)
at 2788C, and the mixture was stirred for 10 min with
warming to 08C. The aziridine 8 (58.3 mg, 0.2 mmol) in
dry THF (0.5 mL) was added to the above stirred reagent
at 2788C, and the stirring was continued for 3 h followed by
quenching with a solution of 1:1 saturated NH4Cl±28%
NH4OH (2 mL). The mixture was extracted with Et2O and
the extract was washed with water and dried over MgSO4.
Usual workup followed by ¯ash chromatography over silica
gel with n-hexane/EtOAc (5:1) gave the title compound 9
(57 mg, 93% yield) as colorless crystals from n-hexane. Mp
638C. [a]2D2ˆ273.4 (cˆ0.638, CHCl3); 1H NMR (270 MHz,
CDCl3) d 0.81 (d, Jˆ6.5 Hz, 3H), 0.86 (d, Jˆ7.0 Hz, 3H),
Experimental
General methods
All reactions were carried out under a positive pressure of
argon, and glassware and syringes were dried in an electric
oven at 1008C prior to use. Melting points are uncorrected.
Nominal (LRMS) and exact mass (HRMS) spectra were
recorded on a JEOL JMS-01SG-2 or JMS-HX/HX 110A
1
mass spectrometer. H NMR spectra (270 or 300 MHz)
were recorded in CDCl3 unless otherwise speci®ed. Chemi-
cal shifts are reported in parts per million down®eld from
internal Me4Si (sˆsinglet, dˆdoublet, dd ˆdouble doublet,
dddˆdoublet of double doublet, tˆtriplet, mˆmultiplet).
Optical rotations were measured in CHCl3 with a JASCO

2816
H. Ohno et al. / Tetrahedron 56 (2000) 2811±2820
1.56 (dd, Jˆ7.0, 3.0 Hz, 3H), 1.75±1.87 (m, 1H), 2.29 (s,
3H), 2.64 (s, 6H), 3.53±3.62 (m, 1H), 4.55 (d, Jˆ8.1 Hz,
1H), 4.83±4.91 (m, 1H), 5.02±5.13 (m, 1H), 6.93 (s, 2H).
13C NMR (67.8 MHz, CDCl3) d 14.3, 18.1, 18.3, 21.1, 23.3,
33.2, 58.0, 89.4, 90.2, 132.1, 135.0, 139.1, 142.1, 203.9.
LRMS (FAB) m/z, 308 (MH1), 306, 264, 254, 200,
183, 167, 119 (base peak), 109, 91. HRMS (FAB) m/
z, calcd for C17H26NO2S (MH1) 308.1684; found:
308.1679.
was added by syringe MeLi´LiBr (1.5 M solution in Et2O;
1.6 mL, 2.4 mmol) at 2788C, and the mixture was stirred
for 10 min with warming to 08C. The aziridine 8 (87.4 mg,
0.3 mmol) in dry THF (0.5 mL) was added dropwise to the
above stirred reagent at 2788C, and the stirring was con-
tinued for 30 min followed by quenching with a solution of
1:1 saturated NH4Cl±28% NH4OH (2 mL). The mixture
was extracted with Et2O and the extract was washed with
water and dried over MgSO4. Usual workup followed by ¯ash
chromatography over silica gel with n-hexane/EtOAc (8:1)
gave a mixture of amino allenes 9, 10, and 12 (66 mg, 72%
combined yield; 9:10:12ˆ45:18:37, HPLC). Further puri®ca-
tion by ¯ash chromatography over silica gel with n-hexane/
EtOAc (15:1) gave the title compound 12 (24 mg) in a pure
form. Compound 12: colorless oil. [a]3D3ˆ235.0 (cˆ0.078,
CHCl3); 1H NMR (270 MHz, CDCl3) d 0.81 (d, Jˆ6.8 Hz,
3H), 0.85 (d, Jˆ7.0 Hz, 3H), 1.61 (d, Jˆ3.0 Hz, 6H), 1.80±
1.88 (m, 1H), 2.29 (s, 3H), 2.64 (s, 6H), 3.53 (ddd, Jˆ7.8,
5.7, 4.6 Hz, 1H), 4.54 (d, Jˆ7.8 Hz, 1H), 4.80±4.85 (m,
1H), 6.93 (s, 2H). LRMS (FAB) m/z, 322 (MH1), 321,
278, 254, 183, 138, 123, 119 (base peak), 69, 55, 43, 41.
HRMS (FAB) m/z, calcd for C18H28NO2S (MH1) 322.1841;
found: 322.1835.
(5S,aS)-6-Methyl-5-[N-(2,4,6-trimethylbenzenesulfonyl)-
amino]-2,3-heptadiene (10) (Table 1, entry 7). By a pro-
cedure identical with that described for the preparation of
the amino allene 9 from 8, the aziridine 16 (1.02 g,
3.5 mmol) was converted into the title compound 10
(1.05 g, 98% yield) by treatment with MeCu(CN)-
Li´LiBr´2LiCl at 2788C for 30 min. Compound 10: color-
less crystals from cold n-hexane. Mp 368C. [a]2D3ˆ135.8
1
(cˆ1.68, CHCl3); H NMR (270 MHz, CDCl3) d 0.84 (d,
Jˆ6.8 Hz, 3H), 0.86 (d, Jˆ7.0 Hz, 3H), 1.56 (dd, Jˆ6.8,
3.2 Hz, 3H), 1.75±1.89 (m, 1H), 2.29 (s, 3H), 2.64 (s, 6H),
3.54±3.61 (m, 1H), 4.59 (d, Jˆ8.4 Hz, 1H), 4.87±4.96 (m,
1H), 5.02±5.14 (m, 1H), 6.93 (s, 2H). 13C NMR (67.8 MHz,
CDCl3) d 14.4, 18.0, 18.2, 21.1, 23.4, 33.3, 57.5, 89.9, 90.3,
132.1, 135.0, 139.0, 142.1, 203.5. LRMS (FAB) m/z, 308
(MH1), 306, 264, 254, 200, 183, 167, 119 (base peak), 109,
91. HRMS (FAB) m/z, calcd for C17H26NO2S (MH1)
308.1684; found: 308.1687.
(6S,aR)-2,7-Dimethyl-6-[N-(2,4,6-trimethylbenzenesul-
fonyl)amino]-3,4-octadiene (13) (Table 1, entry 4). By a
procedure similar to that described for the preparation of the
amino allene 9 from 8, the aziridine 8 (87.4 mg, 0.3 mmol)
was converted into the title compound 13 (100 mg, 99%
yield) by treatment with i-PrCu(CN)MgCl´2LiCl at 2788C
for 30 min. Compound 13: colorless oil; [a]3D0ˆ2102
Reaction of 2-ethynylaziridine (8) with Me2CuLi´3LiI
(Table 1, entry 1). (4S)-5-Methyl-4-[N-(2,4,6-trimethyl-
benzenesulfonyl)amino]-1,2-hexadiene (11). To a stirred
suspension of CuI (152 mg, 0.8 mmol) in dry THF (1 mL)
under argon was added by syringe MeLi´LiI (0.90 M solu-
tion in Et2O; 1.78 mL, 1.6 mmol) at 2788C, and the mixture
was stirred for 10 min with warming to 08C. The aziridine 8
(58.3 mg, 0.2 mmol) in THF (0.5 mL) was added to the
above stirred reagent at 2788C, and the stirring was con-
tinued for 30 min followed by quenching with a solution of
1:1 saturated NH4Cl±28% NH4OH (2 mL). The mixture
was extracted with Et2O and the extract was washed with
water and dried over MgSO4. Usual workup followed by
¯ash chromatography over silica gel with n-hexane/EtOAc
(8:1) gave a mixture of amino allenes 9, 10, and 11 (48 mg,
78% combined yield; 9:10:11ˆ25:2:73, HPLC). Further
puri®cation by ¯ash chromatography over silica gel with
n-hexane/EtOAc (15:1) gave the title compound 11
(35 mg) in a pure form. Compound 11: colorless crystals
from n-hexane. Mp 618C. [a]3D0ˆ23.44 (cˆ0.524, CHCl3);
1H NMR (270 MHz, CDCl3) d 0.84 (d, Jˆ6.8 Hz, 3H), 0.88
(d, Jˆ7.0 Hz, 3H), 1.75±1.87 (m, 1H), 2.30 (s, 3H), 2.63 (s,
6H), 3.56±3.66 (m, 1H), 4.57 (d, Jˆ8.6 Hz, 1H), 4.63 (dd,
Jˆ6.8, 2.7 Hz, 2H), 4.93 (dt, Jˆ6.8, 6.8 Hz, 1H), 6.94 (s,
2H). 13C NMR (67.8 MHz, CDCl3) d 18.2, 18.3, 21.1, 23.4,
33.4, 57.6, 78.1, 90.1, 132.1, 135.0, 139.1, 142.2, 207.4.
Anal. Calcd for C16H23NO2S: C, 65.49; H, 7.90; N, 4.77.
Found: C, 65.27; H, 7.84; N, 4.69.
1
(cˆ1.04, CHCl3); H NMR (270 MHz, CDCl3) d 0.84 (d,
Jˆ6.8 Hz, 3H), 0.87 (d, Jˆ7.0 Hz, 3H), 0.957 (d, Jˆ7.0 Hz,
3H), 0.961 (d, Jˆ6.5 Hz, 3H), 1.78±1.95 (m, 1H), 2.14±
2.28 (m, 1H), 2.29 (s, 3H), 2.63 (s, 6H), 3.57±3.65 (m,
1H), 4.58 (d, Jˆ7.8 Hz, 1H), 5.05 (ddd, Jˆ6.2, 5.4,
3.0 Hz, 1H), 5.12 (ddd, Jˆ6.2, 6.2, 3.2 Hz, 1H), 6.93 (s,
2H). 13C NMR (67.8 MHz, CDCl3) d 18.0, 18.3, 21.1,
22.69, 22.73, 23.5, 28.3, 33.4, 57.2, 91.2, 103.3, 132.1,
135.0, 139.0, 142.0, 200.7. LRMS (FAB) m/z, 336 (MH1),
334, 292, 254, 200, 183, 152, 137, 119 (base peak), 95.
HRMS (FAB) m/z, calcd for C19H30NO2S (MH1)
336.1997; found: 336.1991.
(3S,aR)-2-Methyl-3-[N-(2,4,6-trimethylbenzenesulfonyl)-
amino]-4,5-decadiene (14) (Table 1, entry 5). By a pro-
cedure similar to that described for the preparation of the
amino allene 9 from 8, the aziridine 8 (291 mg, 1 mmol) was
converted into the title compound 14 (338 mg, 97% yield)
by treatment with n-BuCu(CN)Li´2LiCl at 2788C for
30 min. Compound 14: colorless oil; [a]32Dˆ2108
1
(cˆ0.871, CHCl3); H NMR (270 MHz, CDCl3) d 0.83 (d,
Jˆ7.0 Hz, 3H), 0.86 (d, Jˆ7.0 Hz, 3H), 0.89 (t, Jˆ7.0 Hz,
3H), 1.27±1.38 (m, 4H), 1.76±1.88 (m, 1H), 1.86±1.95
(m, 2H), 2.29 (s, 3H), 2.63 (s, 6H), 3.56±3.63 (m, 1H),
4.60 (d, Jˆ8.4 Hz, 1H), 4.92±4.99 (m, 1H), 5.10 (tdd,
Jˆ6.8, 6.8, 3.0 Hz, 1H), 6.93 (s, 2H). 13C NMR
(67.8 MHz, CDCl3) d 14.1, 18.0, 18.2, 21.1, 22.4, 23.4,
28.7, 31.6, 33.3, 57.3, 90.8, 95.6, 132.1, 135.0, 139.0,
142.0, 202.4. LRMS (FAB) m/z, 350 (MH1), 348, 306,
254, 200, 183, 151, 119 (base peak), 95, 69. HRMS
(FAB) m/z, calcd for C20H32NO2S (MH1) 350.2154;
found: 350.2160.
Reaction of 2-ethynylaziridine (8) with Me2Cu(CN)-
Li2´2LiBr´2LiCl (Table 1, entry 2). (5S)-2,6-Dimethyl-5-
[N-(2,4,6-trimethylbenzenesulfonyl)amino]-2,3-heptadiene
(12). To a stirred solution of CuCN (107 mg, 1.2 mmol) and
LiCl (102 mg, 2.4 mmol) in dry THF (1 mL) under argon

H. Ohno et al. / Tetrahedron 56 (2000) 2811±2820
2817
Reaction of 2-ethynylaziridine (8) with n-Bu3SuCu(CN)-
Li´2LiCl (Table 1, entry 6). (4S,aR)-5-Methyl-1-tributyl-
stannyl-4-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-1,2-
hexadiene (15). To a stirred solution of n-Bu3SnH
(0.323 mL, 1.2 mmol) in dry THF (1 mL) under argon
was added LDA [0.5 M solution in n-hexane/THF (2:1);
2.4 mL, 1.2 mmol] at 2788C, and the mixture was stirred
for 20 min at 08C. A solution of CuCN (107 mg, 1.2 mmol)
and LiCl (102 mg, 2.4 mmol) in dry THF (1.5 mL) was
added dropwise to the above mixture at 2788C, and the
mixture was stirred for 5 min with warming to 08C. To the
resulting dark red reagent, the aziridine 8 (87.3 mg,
0.3 mmol) in dry THF (0.5 mL) was added at 2788C with
stirring, and the stirring was continued for 30 min followed
by quenching with a solution of 1:1 saturated NH4Cl±28%
NH4OH (5 mL). The mixture was extracted with Et2O and
the extract was washed with water and dried over MgSO4.
Usual workup followed by ¯ash chromatography over silica
gel with n-hexane/EtOAc (7:1) gave the title compound 15
(157 mg, 90% yield) as a colorless oil. [a]2D6ˆ2236
Jˆ7.8 Hz, 1H), 4.84±4.92 (m, 1H), 5.01 (tdd, Jˆ7.0, 7.0,
2.4 Hz, 1H), 6.93 (s, 2H). 13C NMR (67.8 MHz, CDCl3) d
14.0, 18.1, 18.5, 21.1, 22.3, 23.3, 28.5, 31.4, 33.3, 58.4,
90.3, 94.4, 132.0, 135.1, 139.0, 142.0, 203.1. LRMS
(FAB) m/z, 350 (MH1), 348, 306, 254, 200, 183, 166,
151, 119 (base peak), 95, 69. HRMS (FAB) m/z, calcd
for C20H32NO2S (MH1) 350.2154; found: 350.2150.
(4S,aS)-5-Methyl-1-tributylstannyl-4-[N-(2,4,6-trimethyl-
benzenesulfonyl)amino]-1,2-hexadiene (19) (Table 1,
entry 10). By a procedure identical with that described
for the preparation of the amino allene 15 from 8, the aziri-
dine 16 (87.3 mg, 0.3 mmol) was converted into the title
compound 19 (160 mg, 92% yield) by treatment with
n-Bu3SnCu(CN)Li´2LiCl atˆ2788C for 30 min. Compound
19: colorless oil; [a]2D8ˆ1183 (cˆ0.552, CHCl3); 1H NMR
(270 MHz, CDCl3) d 0.77±0.97 (m, 21H), 1.21±1.52 (m,
12H), 1.69±1.83 (m, 1H), 2.29 (s, 3H), 2.63 (s, 6H), 3.48±
3.59 (m, 1H), 4.25±4.42 (m, 1H), 4.44 (d, Jˆ8.4 Hz, 1H),
4.67±4.76 (m, 1H), 6.92 (s, 2H). 13C NMR (67.8 MHz,
CDCl3) d 10.6, 13.9, 18.3, 18.7, 21.1, 23.3, 27.4, 29.1,
33.6, 59.6, 77.9, 78.9, 132.0, 135.3, 139.1, 141.9, 206.3.
LRMS (FAB) m/z, 582 (M2H)2, 580, 578, 292, 290,
252, 248, 199, 198 (base peak), 183, 153, 64. HRMS
(FAB) m/z, calcd for C28H48NO2SSn (M2H)2 582.2427;
found: 582.2423.
1
(cˆ0.868, CHCl3); H NMR (270 MHz, CDCl3) d 0.79±
0.98 (m, 21H), 1.23±1.60 (m, 12H), 1.78±1.90 (m, 1H),
2.29 (s, 3H), 2.64 (s, 6H), 3.56±3.66 (m, 1H), 4.46±4.57
(m, 2H), 5.05±5.15 (m, 1H), 6.93 (s, 2H). 13C NMR
(67.8 MHz, CDCl3) d 10.7, 13.9, 18.2, 18.4, 21.1, 23.5,
27.4, 29.1, 33.3, 56.6, 80.8, 81.3, 132.1, 135.2, 139.0,
142.0, 205.4. LRMS (FAB) m/z, 582 (M2H)2, 580, 578,
292, 290, 252, 248, 199 (base peak), 198, 183, 153, 64.
HRMS (FAB) m/z, calcd for C28H48NO2SSn (M2H)2
582.2427; found: 582.2430.
(5S,aR)-5-[N-(2,4,6-Trimethylbenzenesulfonyl)amino]-6-
phenyl-2,3-hexadiene (26) (Table 1, entry 11). By a pro-
cedure identical with that described for the preparation of
the amino allene 9 from 8, the aziridine 20 (1.1 g,
3.24 mmol) was converted into the title compound 26
(1.1 g, 96% yield) by treatment with MeCu(CN)-
Li´LiBr´2LiCl at 2788C for 2 h. Compound 26: colorless
(6S,aS)-2,7-Dimethyl-6-[N-(2,4,6-trimethylbenzenesulfo-
nyl)amino]-3,4-octadiene (17) (Table 1, entry 8). By a
procedure similar to that described for the preparation of
the amino allene 9 from 8, the aziridine 16 (87.4 mg,
0.3 mmol) was converted into the title compound 17
(99 mg, 98% yield) by treatment with i-PrCu(CN)MgCl´2LiCl
at 2788C for 30 min. Compound 17: colorless crystals from
cold n-hexane. Mp 478C. [a]3D3ˆ185.8 (cˆ0.613, CHCl3);
1H NMR (270 MHz, CDCl3) d 0.79 (d, Jˆ7.0 Hz, 3H), 0.88
(d, Jˆ7.0 Hz, 3H), 0.93 (d, Jˆ7.0 Hz, 3H), 0.96 (d,
Jˆ6.8 Hz, 3H), 1.69±1.86 (m, 1H), 2.16±2.27 (m, 1H),
2.30 (s, 3H), 2.63 (s, 6H), 3.54±3.62 (m, 1H), 4.53 (d,
Jˆ8.1 Hz, 1H), 4.95 (ddd, Jˆ6.2, 6.2, 3.0 Hz, 1H), 5.01
(ddd, Jˆ6.2, 6.2, 3.0 Hz, 1H), 6.93 (s, 2H). 13C NMR
(67.8 MHz, CDCl3) d 18.3, 18.5, 21.1, 22.6, 23.3, 28.2,
33.3, 58.7, 91.7, 101.7, 132.1, 135.2, 139.0, 142.0,
201.7. LRMS (FAB) m/z, 336 (MH1), 334, 292, 254,
200, 183, 152, 137, 119 (base peak), 95. HRMS (FAB)
m/z, calcd for C19H30NO2S (MH1) 336.1997; found:
336.2003.
1
oil. [a]2D8ˆ263.2 (cˆ0.155, CHCl3); H NMR (270 MHz,
CDCl3) d 1.51 (dd, Jˆ7.0, 3.5 Hz, 3H), 2.28 (s, 3H), 2.55 (s,
6H), 2.84±2.87 (m, 2H), 3.87±3.98 (m, 1H), 4.57 (d,
Jˆ7.3 Hz, 1H), 5.00±5.17 (m, 2H), 6.89 (s, 2H), 7.04±
7.12 (m, 2H), 7.15±7.25 (m, 3H). 13C NMR (67.8 MHz,
CDCl3) d 14.2, 21.1, 23.2, 42.5, 53.1, 90.4, 92.3, 126.8,
128.6, 129.8, 132.1, 134.3, 136.9, 139.2, 142.2, 203.2.
LRMS (FAB) m/z, 356 (MH1), 302, 264, 200, 183, 157,
129, 119 (base peak), 91. HRMS (FAB) m/z, calcd for
C21H26NO2S (MH1) 356.1684; found: 356.1689.
(5S,aR)-5-[N-(4-Methoxy-2,3,6-trimethylbenzenesulfonyl)-
amino]-6-phenyl-2,3-hexadiene (27) (Table 1, entry 12).
By a procedure identical with that described for the prepara-
tion of the amino allene 9 from 8, the aziridine 21 (739 mg,
2 mmol) was converted into the title compound 27 (766 mg,
99% yield) by treatment with MeCu(CN)Li´2LiCl at 2788C
for 6 h. Compound 27: colorless needles from n-hexane/
1
(3S,aS)-2-Methyl-3-[N-(2,4,6-trimethylbenzenesulfonyl)-
amino]-4,5-decadiene (18) (Table 1, entry 9). By a pro-
cedure similar to that described for the preparation of the
amino allene 9 from 8, the aziridine 16 (437 mg, 1.5 mmol)
was converted into the title compound 18 (521 mg, 99%
yield) by treatment with n-BuCu(CN)Li´2LiCl at 2788C
for 30 min. Compound 18: colorless oil; [a]3D1ˆ176.6
Et2O (4:1). mp 928C; [a]2D6ˆ273.0 (cˆ1.34, CHCl3); H
NMR (270 MHz, CDCl3) d 1.53 (dd, Jˆ7.0, 3.2 Hz, 3H),
2.08 (s, 3H), 2.37 (s, 3H), 2.65 (s, 3H), 2.82 (dd, Jˆ13.5,
6.5 Hz, 1H), 2.86 (dd, Jˆ13.5, 6.5 Hz, 1H), 3.84 (s, 3H),
3.85±3.96 (m, 1H), 4.55 (d, Jˆ7.0 Hz, 1H), 5.03±5.19 (m,
2H), 6.54 (s, 1H), 7.02±7.09 (m, 2H), 7.12±7.22 (m, 3H).
13C NMR (67.8 MHz, CDCl3) d 12.2, 14.2, 18.1, 24.7, 42.4,
53.2, 55.7, 90.2, 92.6, 112.1, 125.3, 126.8, 128.5, 129.4,
129.7, 137.0, 138.9, 139.1, 159.4, 203.3. Anal. Calcd for
C22H27NO3S: C, 68.54; H, 7.06; N, 3.63. Found: C, 68.33;
H, 7.00; N, 3.60.
1
(cˆ1.13, CHCl3); H NMR (270 MHz, CDCl3) d 0.82 (d,
Jˆ6.5 Hz, 3H), 0.84±0.88 (m, 3H), 0.88 (d, Jˆ7.0 Hz, 3H),
1.25±1.32 (m, 4H), 1.73±1.87 (m, 1H), 1.85±1.95 (m, 2H),
2.29 (s, 3H), 2.63 (s, 6H), 3.52±3.61 (m, 1H), 4.58 (d,

2818
H. Ohno et al. / Tetrahedron 56 (2000) 2811±2820
(5S,aS)-5-[N-(2,4,6-Trimethylbenzenesulfonyl)amino]-6-
phenyl-2,3-hexadiene (28) (Table 1, entry 13). By a pro-
cedure identical with that described for the preparation of
the amino allene 9 from 8, the aziridine 22 (1.02 g, 3 mmol)
was converted into the title compound 28 (1.06 g, 99%
yield) by treatment with MeCu(CN)Li´LiBr´2LiCl at
2788C for 30 min. Compound 28: colorless needles from
n-hexane/Et2O (1:1). Mp 968C; [a]2D6ˆ124.8 (cˆ0.895,
compound 31 (80 mg, 98% yield) by treatment with
MeCu(CN)Li´2LiCl at 2788C for 30 min. Compound 31:
1
colorless oil. [a]2D4ˆ127.1 (cˆ0.784, CHCl3); H NMR
(270 MHz, CDCl3) d 0.03 (s, 6H), 0.87 (s, 9H), 1.57 (dd,
Jˆ6.8, 3.2 Hz, 1H), 2.29 (s, 3H), 2.63 (s, 6H), 3.55 (dd,
Jˆ9.7, 5.1 Hz, 1H), 3.58 (dd, Jˆ9.7, 5.1 Hz, 1H), 3.66±
3.75 (m, 1H), 4.95±5.03 (m, 1H), 5.05 (d, Jˆ6.5 Hz, 1H),
5.06±5.17 (m, 1H), 6.93 (s, 2H). 13C NMR (67.8 MHz,
CDCl3) d 25.34, 25.30, 14.3, 18.5, 21.1, 23.2, 26.0,
54.2, 66.1, 89.1, 89.8, 132.1, 134.6, 139.2, 142.2, 204.0.
LRMS (FAB) m/z, 410 (MH1), 408, 352, 314, 298, 264,
256, 211 (base peak), 119, 79, 75, 73. HRMS (FAB) m/z,
calcd for C21H36NO3SSi (MH1) 410.2185; found: 410.2177.
1
CHCl3); H NMR (270 MHz, CDCl3) d 1.52 (dd, Jˆ7.3,
3.2 Hz, 3H), 2.28 (s, 3H), 2.55 (s, 6H), 2.82 (dd, Jˆ13.5,
7.3 Hz, 1H), 2.86 (dd, Jˆ13.5, 6.2 Hz, 1H), 3.87±3.98 (m,
1H), 4.57 (d, Jˆ7.3 Hz, 1H), 4.96±5.01 (m, 1H), 5.13 (qdd,
Jˆ7.3, 7.3, 2.7 Hz, 1H), 6.88 (s, 2H), 7.04±7.09 (m, 2H),
7.15±7.25 (m, 3H). 13C NMR (67.8 MHz, CDCl3) d 14.2,
21.1, 23.2, 42.7, 53.6, 90.2, 92.3, 126.9, 128.6, 129.7, 132.1,
134.3, 137.0, 139.2, 142.2, 203.3. Anal. Calcd for
C21H25NO2S: C, 70.95; H, 7.09; N, 3.94. Found: C, 70.69;
H, 7.07; N, 3.80.
(6R,aS)-7-Methyl-6-[N-(2,4,6-trimethylbenzenesulfonyl)-
amino]-3,4-octadiene (32) (Table 1, entry 18). By a pro-
cedure similar to that described for the preparation of the
amino allene 9 from 8, the aziridine ent-8 (100 mg,
0.34 mmol) was converted into the title compound 32
(98 mg, 89% yield) by treatment with EtCu(CN)MgBr´2LiCl
at 2788C for 42 min. Compound 32: colorless oil. [a]2D5ˆ
(5S,aS)-5-[N-(4-Methoxy-2,3,6-trimethylbenzenesulfonyl)-
amino]-6-phenyl-2,3-hexadiene (29) (Table 1, entry 14).
By a procedure identical with that described for the prepara-
tion of the amino allene 9 from 8, the aziridine 23 (924 mg,
2.5 mmol) was converted into the title compound 29
(933 mg, 97% yield) by treatment with MeCu(CN)Li´2LiCl
at 2788C for 30 min. Compound 29: colorless oil.
[a]2D7ˆ19.43 (cˆ1.08, CHCl3); 1H NMR (270 MHz,
CDCl3) d 1.54 (dd, Jˆ7.0, 3.5 Hz, 3H), 2.08 (s, 3H), 2.38
(s, 3H), 2.64 (s, 3H), 2.76±2.88 (m, 2H), 3.84 (s, 3H), 3.85±
3.96 (m, 1H), 4.55 (d, Jˆ6.8 Hz, 1H), 5.01±5.10 (m, 1H),
5.14 (qdd, Jˆ7.0, 7.0, 2.7 Hz, 1H), 6.54 (s, 1H), 7.02±7.09
(m, 2H), 7.12±7.22 (m, 3H). 13C NMR (67.8 MHz, CDCl3)
d 12.2, 14.2, 18.0, 24.7, 42.6, 53.6, 55.7, 90.0, 92.5, 112.1,
125.2, 126.8, 128.5, 129.4, 129.6, 137.1, 139.0, 139.1,
159.4, 203.4. LRMS (FAB) m/z, 386 (MH1), 332, 294
(base peak), 230, 213, 197, 157, 149, 119, 91. HRMS
(FAB) m/z, calcd for C22H28NO3S (MH1) 386.1790;
found: 386.1796.
1
198.5 (cˆ0.644, CHCl3); H NMR (270 MHz, CDCl3) d
0.84 (d, Jˆ6.8 Hz, 3H), 0.87 (d, Jˆ6.8 Hz, 3H), 0.95 (t,
Jˆ7.3 Hz, 3H), 1.79±1.99 (m, 3H), 2.29 (s, 3H), 2.63 (s,
6H), 3.56±3.64 (m, 1H), 4.57 (d, Jˆ8.1 Hz, 1H), 4.97±5.04
(m, 1H), 5.12±5.21 (m, 1H), 6.93 (s, 2H). 13C NMR
(67.8 MHz, CDCl3) d 13.6, 17.9, 18.2, 21.0, 22.0, 23.4,
33.3, 57.2, 91.5, 95.0, 132.0, 134.9, 138.9, 142.0, 202.0.
LRMS (FAB) m/z, 322 (MH1), 278, 254, 123, 119 (base
peak). HRMS (FAB) m/z, calcd for C18H28NO2S (MH1)
322.1841; found: 322.1843.
(6R,aR)-7-Methyl-6-[N-(2,4,6-trimethylbenzenesulfonyl)-
amino]-3,4-octadiene (33) (Table 1, entry 20). By a pro-
cedure similar to that described for the preparation of the
amino allene 9 from 8, the aziridine ent-16 (100 mg,
0.34 mmol) was converted into the title compound 33
(107 mg, 97% yield) by treatment with EtCu(CN)MgBr´2LiCl
at 2788C for 42 min. Compound 33: colorless oil.
[a]2D5ˆ263.9 (cˆ0.545, CHCl3); 1H NMR (270 MHz,
CDCl3) d 0.81 (d, Jˆ6.8 Hz, 3H), 0.87 (d, Jˆ6.8 Hz, 3H),
0.93 (t, Jˆ7.3 Hz, 3H), 1.74±1.86 (m, 1H), 1.87±1.99 (m,
2H), 2.29 (s, 3H), 2.64 (s, 6H), 3.54±3.62 (m, 1H), 4.60 (d,
Jˆ8.1 Hz, 1H), 4.89±4.96 (m, 1H), 5.06±5.14 (m, 1H), 6.93
(s, 2H). 13C NMR (67.8 MHz, CDCl3) d 13.5, 18.1, 18.4,
21.1, 21.9, 23.3, 33.2, 58.3, 91.2, 96.2, 132.0, 135.0, 139.0,
142.0, 202.7. LRMS (FAB) m/z, 322 (MH1), 278, 254, 123
(base peak), 119. HRMS (FAB) m/z, calcd for C18H28NO2S
(MH1) 322.1841; found: 322.1837.
(5R,aR)-6-(tert-Butyldimethylsiloxy)-5-[N-(2,4,6-trimethyl-
benzenesulfonyl)amino]-2,3-hexadiene (30) (Table 1,
entry 15). By a procedure identical with that described
for the preparation of the amino allene 9 from 8, the aziri-
dine 24 (78.7 mg, 0.2 mmol) was converted into the title
compound 30 (81 mg, 99% yield) by treatment with
MeCu(CN)Li´2LiCl at 2788C for 1 h and an additional
1 h with warming to 2208C. Compound 30: colorless oil.
[a]2D6ˆ240.7 (cˆ0.961, CHCl3); 1H NMR (270 MHz,
CDCl3) d 0.02 (s, 6H), 0.87 (s, 9H), 1.57 (dd, Jˆ7.0,
3.2 Hz, 3H), 2.29 (s, 3H), 2.64 (s, 6H), 3.51±3.60 (m,
2H), 3.66±3.76 (m, 1H), 4.97±5.13 (m, 3H), 6.94 (s, 2H).
13C NMR (67.8 MHz, CDCl3) d 25.3, 14.1 18.5, 21.1, 23.2,
26.0, 54.1, 65.9, 89.2, 90.1, 132.1, 134.6, 139.1, 142.2,
203.9. LRMS (FAB) m/z, 410 (MH1), 408, 352, 314, 298,
264, 256, 211, 119, 79, 75, 73 (base peak). HRMS (FAB)
m/z, calcd for C21H36NO3SSi (MH1) 410.2185; found:
410.2186.
Methyl (5S,aS)-2,6-Dimethyl-5-[N-(2,4,6-trimethylben-
zenesulfonyl)amino]-2,3-heptadienoate (38), its (5S,aR)
isomer (39), and methyl (5S,3Z)-3,6-dimethyl-5-[N-
(2,4,6-trimethylbenzenesulfonyl)amino]-3-heptenoate (40)
from the aziridine (34). By a procedure identical with that
described for the preparation of the amino allene 9 from 8,
the aziridine 34 (70 mg, 0.2 mmol) was converted into the
title compound 38 (28 mg, 38% yield), 39 (2 mg, 3% yield),
and 40 (20 mg, 27% yield) by treatment with MeCu(CN)-
Li´2LiCl at 2788C for 30 min. Compound 38: colorless oil.
[a]2D5ˆ120.5 (cˆ2.22, CHCl3); 1H NMR (270 MHz,
CDCl3) d 0.88 (d, Jˆ7.0 Hz, 3H), 0.92 (d, Jˆ6.8 Hz, 3H),
1.72 (d, Jˆ3.0 Hz, 3H), 1.79±1.97 (m, 1H), 2.29 (s, 3H),
(5R,aS)-6-(tert-Butyldimethylsiloxy)-5-[N-(2,4,6-trimethyl-
benzenesulfonyl)amino]-2,3-hexadiene (31) (Table 1,
entry 16). By a procedure identical with that described
for the preparation of the amino allene 9 from 8, the aziri-
dine 25 (78.7 mg, 0.2 mmol) was converted into the title

H. Ohno et al. / Tetrahedron 56 (2000) 2811±2820
2819
2.64 (s, 6H), 3.64 (ddd, Jˆ8.4, 7.6, 5.4 Hz, 1H), 3.67 (s,
3H), 4.73 (d, Jˆ8.4 Hz, 1H), 5.27 (dq, Jˆ7.6, 3.0 Hz, 1H),
6.95 (s, 2H). 13C NMR (67.8 MHz, CDCl3) d 14.8, 18.2,
18.5, 21.1, 23.3, 33.4, 52.3, 58.1, 93.9, 97.8, 132.2, 134.6,
139.1, 142.4, 167.7, 209.4. LRMS (FAB) m/z, 366 (MH1),
334, 322, 254, 183, 167 (base peak), 147, 119, 107, 73.
HRMS (FAB) m/z, calcd for C19H28NO4S (MH1)
366.1739; found: 366.1736. Compound 39: colorless oil.
[a]2D3ˆ2150 (cˆ0.136, CHCl3); 1H NMR (270 MHz,
CDCl3) d 0.83 (d, Jˆ7.0 Hz, 3H), 0.88 (d, Jˆ7.0 Hz, 3H),
1.76 (d, Jˆ3.0 Hz, 3H), 1.81±1.93 (m, 1H), 2.29 (s, 3H),
2.63 (s, 6H), 3.72 (d, Jˆ0.5 Hz, 3H), 3.72±3.81 (m, 1H),
4.57±4.64 (m, 1H), 5.43 (dq, Jˆ4.6, 3.0 Hz, 1H), 6.94 (s,
2H). 13C NMR (67.8 MHz, CDCl3) d 14.9, 17.8, 18.2, 21.1,
23.3, 33.3, 52.4, 57.0, 95.4, 99.6, 132.1, 134.7, 139.0, 142.3,
167.8, 209.1. LRMS (FAB) m/z, 366 (MH1), 334, 322, 254,
183, 167 (base peak), 135, 119, 107, 91, 73. HRMS (FAB)
m/z, calcd for C19H28NO4S (MH1) 366.1739; found:
366.1742. Compound 40: colorless oil. [a]2D4ˆ185.0
for 30 min (278 to 2208C). Compound 43: colorless oil.
[a]2D1ˆ2124 (cˆ0.953, CHCl3); 1H NMR (270 MHz,
CDCl3) d 0.07 (s, 9H), 0.79 (d, Jˆ7.0 Hz, 3H), 0.84 (d,
Jˆ7.0 Hz, 3H), 1.60 (d, Jˆ3.0 Hz, 3H), 1.78±1.90 (m,
1H), 2.29 (s, 3H), 2.64 (s, 6H), 3.64 (ddd, Jˆ8.1, 5.1,
4.6 Hz, 1H), 4.44 (d, Jˆ8.1 Hz, 1H), 4.71 (dq, Jˆ5.1,
3.0 Hz, 1H), 6.93 (s, 2H). LRMS (FAB) m/z, 380 (MH1),
364, 344, 272, 256, 196, 154, 119, 73 (base peak). HRMS
(FAB) m/z, calcd for C20H34NO2SSi (MH1) 380.2079;
found: 380.2080.
(2S,4R)-2-Ethynyl-4-isopropyl-N-(2,4,6-trimethylbenzene-
sulfonyl)azetidine (44). Colorless needles from n-hexane/
1
Et2O (4:1). Mp 1018C; [a]3D0ˆ223.4 (cˆ1.32, CHCl3); H
NMR (270 MHz, CDCl3) d 0.73 (d, Jˆ7.0 Hz, 3H), 0.83 (d,
Jˆ7.0 Hz, 3H), 1.66±1.75 (m, 1H), 2.08 (ddd, Jˆ11.0, 8.0,
8.0 Hz, 1H), 2.30 (s, 3H), 2.31 (d, Jˆ2.0 Hz, 1H), 2.42 (ddd,
Jˆ11.0, 9.0, 9.0 Hz, 1H), 2.69 (s, 6H), 4.17 (ddd, Jˆ9.0,
8.0, 5.0 Hz, 1H), 4.67 (ddd, Jˆ9.0, 8.0, 2.0 Hz, 1H), 6.92±
6.93 (m, 2H). Anal. Calcd for C17H23NO2S: C, 66.85; H,
7.59; N, 4.59. Found: C, 66.84; H, 7.43; N, 4.38.
1
(cˆ0.528, CHCl3); H NMR (300 MHz, CDCl3) d 0.82 (d,
Jˆ6.8 Hz, 3H), 0.85 (d, Jˆ6.8 Hz, 3H), 1.57 (d, Jˆ1.4 Hz,
3H), 1.63±1.77 (m, 1H), 2.29 (s, 3H), 2.55 (d, Jˆ15.2 Hz,
1H), 2.61 (s, 6H), 3.04 (d, Jˆ15.2 Hz, 1H), 3.63 (s, 3H),
3.76 (ddd, Jˆ9.8, 6.8, 5.6 Hz, 1H), 4.43 (d, Jˆ6.8 Hz, 1H),
4.97 (dq, Jˆ9.8, 1.4 Hz, 1H), 6.92 (s, 2H). LRMS (FAB) m/
z, 368 (MH1), 324, 169 (base peak), 137, 119, 109, 95.
HRMS (FAB) m/z, calcd for C19H30NO4S (MH1)
368.1895; found: 368.1890.
(2R,4R)-2-Ethynyl-4-isopropyl-N-(2,4,6-trimethylbenzene-
sulfonyl)azetidine (45). Colorless crystals from n-hexane/
Et2O (5:1). Mp 92±948C; [a]2D8ˆ1109 (cˆ1.02, CHCl3); 1H
NMR (500 MHz, CDCl3) d 0.64 (d, Jˆ6.5 Hz, 3H), 0.68 (d,
Jˆ6.5 Hz, 3H), 1.59±1.67 (m, 1H), 2.07 (ddd, Jˆ10.5, 8.0,
3.5 Hz, 1H), 2.29 (s, 3H), 2.35 (ddd, Jˆ10.5, 8.0, 8.0 Hz,
1H), 2.60 (d, Jˆ2.0 Hz, 1H), 2.64 (s, 6H), 4.58±4.63 (m,
2H), 6.91 (s, 2H). Anal. Calcd for C17H23NO2S: C, 66.85; H,
7.59; N, 4.59. Found: C, 66.75; H, 7.38; N, 4.39.
(5S,aS)-6-Methyl-2-trimethylsilyl-5-[N-(2,4,6-trimethyl-
benzenesulfonyl)amino]-2,3-heptadiene (41) and (4S,3S)-
3,5-dimethyl-1-trimethylsilyl-4-[N-(2,4,6-trimethylbenzene-
sulfonyl)amino]-1-hexyne (42) from the aziridine (35).
By a procedure identical with that described for the prepar-
ation of the amino allene 9 from 8, the aziridine 35 (51 mg,
0.14 mmol) was converted into the title compound 41
(46 mg, 87% yield) and 42 (6 mg, 11% yield), by treatment
with MeCu(CN)Li´2LiCl for 1.5 h (278 to 08C). Compound
41: colorless oil. [a]D26ˆ152.5 (cˆ0.976, CHCl3); 1H NMR
(270 MHz, CDCl3) d 0.07 (s, 9H), 0.77 (d, Jˆ7.0 Hz, 3H),
0.84 (d, Jˆ6.8 Hz, 3H), 1.56 (d, Jˆ2.7 Hz, 3H), 1.68±1.84
(m, 1H), 2.28 (s, 3H), 2.64 (s, 6H), 3.59 (ddd, Jˆ7.8, 6.5,
4.6 Hz, 1H), 4.43 (d, Jˆ7.8 Hz, 1H), 4.65 (dq, Jˆ6.5,
2.7 Hz, 1H), 6.93 (s, 2H). LRMS (FAB) m/z, 380 (MH1),
364, 344, 272, 256, 197, 196, 119, 73 (base peak). HRMS
(FAB) m/z, calcd for C20H34NO2SSi (MH1) 380.2079;
found: 380.2068. Compound 42: colorless crystals from n-
Acknowledgements
This work was supported by Japan Health Sciences Foun-
dation and Grant-in-aid for Scienti®c Research from the
Ministry of Education, Science, Sports and Culture of
Japan. H. O. is grateful to Research Fellowships of the
Japan Society for the Promotion of Science for Young
Scientists. The authors thank Prof. T. Taga and Dr Y.
Miwa, Kyoto University, for determining the X-ray crystal
structure of compound 28.
References
1
hexane. Mp 1178C; [a]2D2ˆ267.6 (cˆ 0.352, CHCl3); H
1. Lipshutz, B. H.; Sengupta, S. In Organic Reactions, Paquette
et al., Eds.; Wiley: New York, 1992; Vol. 42, p 135.
NMR (300 MHz, CDCl3) d 0.13 (s, 9H), 0.75 (d,
Jˆ6.8 Hz, 3H), 0.90 (d, Jˆ6.8 Hz, 3H), 1.08 (d,
Jˆ7.1 Hz, 3H), 2.03±2.13 (m, 1H), 2.29 (s, 3H), 2.48 (qd,
Jˆ7.1, 6.9 Hz, 1H), 2.66 (s, 6H), 3.08 (ddd, Jˆ9.8, 6.9,
2.8 Hz, 1H), 4.68 (d, Jˆ9.8 Hz, 1H), 6.94 (s, 2H). LRMS
(FAB) m/z, 380 (MH1), 364, 292, 254 (base peak), 183, 119,
73. HRMS (FAB) m/z, calcd for C20H34NO2SSi (MH1)
380.2079; found: 380.2074.
2. Ibuka, T.; Yamamoto, Y. Organocopper Reagents; Taylor,
R. J. K., Ed.; Oxford University Press: London, 1994, pp 143±158.
3. (a) Marek, I.; Mangeney, P.; Alexakis, A.; Normant, J. F.
Tetrahedron Lett. 1986, 27, 5499. (b) Tseng, H.-R.; Luh, T.-Y. J.
Org. Chem. 1997, 62, 4568.
4. Sahlberg, C.; Claesson, A. J. Org. Chem. 1984, 49, 4120. Reich,
H. J.; Eisenhart, E. K.; Whipple, W. L.; Kelly, M. J. J. Am. Chem.
Soc. 1988, 110, 6432. Kang, S.-K.; Kim, S.-G.; Cho, D.-G.
Tetrahedron: Asymmetry 1992, 3, 1509. Spino, C.; Thibault, C.;
Gingras, S. J. Org. Chem. 1998, 63, 5283.
(5S,aR)-6-Methyl-2-trimethylsilyl-5-[N-(2,4,6-trimethyl-
benzenesulfonyl)amino]-2,3-heptadiene (43). By a pro-
cedure identical with that described for the preparation of
the amino allene 9 from 8, the aziridine 37 (55 mg,
0.15 mmol) was converted into the title compound 43
(56 mg, 98% yield), by treatment with MeCu(CN)Li´2LiCl
5. (a) Macdonald, T. L.; Reagan, D. R.; Brinkmeyer, R. S. J. Org.
Chem. 1980, 45, 4740. (b) Elsevier, C. J.; Vermeer, P. J. Org.
Chem. 1989, 54, 3726. (c) Marshall, J. A.; Wang, X.-J. J. Org.
Chem. 1992, 57, 3387. (d) Buckle, M. J. C.; Fleming, I.

2820
H. Ohno et al. / Tetrahedron 56 (2000) 2811±2820
Tetrahedron Lett. 1993, 34, 2383. (e) D'Aniello, F.; Mann, A.;
Taddei, M.; Wermuth, C.-G. Tetrahedron Lett. 1994, 35, 7775.
6. (a) Oehlschlager, A. C.; Czyzewska, E. Tetrahedron Lett. 1983,
24, 5587. (b) Aurrecoechea, J. M.; Solay, M. Tetrahedron Lett.
1995, 36, 2501. (c) Bertozzi, F.; Crotti, P.; Macchia, F.;
Pineschi, M.; Arnold, A.; Feringa, B. L. Tetrahedron Lett. 1999,
40, 4893.
Chem. Soc. 1991, 113, 2652; Kimura, M.; Fugami, K.; Tanaka, S.;
Tamaru, Y. J. Org. Chem. 1992, 57, 6377; Davies, I. W.; Scopes,
D. I. C.; Gallagher, T. Synlett 1993, 85; Kimura, M.; Tanaka, S.;
Tamaru, Y. J. Org. Chem. 1995, 60, 3764.
16. Arseniyadis, S.; Sartoretti, J. Tetrahedron Lett. 1985, 26, 729.
Lathbury, D.; Gallagher, T. J. Chem. Soc., Chem. Commun. 1986,
114; Ha, J. D.; Lee, D.; Cha, J. K. J. Org. Chem. 1997, 62, 4550;
Meguro, M.; Yamamoto, Y. Tetrahedron Lett. 1998, 39, 5421;
Arredondo, V. M.; McDonald, F. E.; Marks, T. J. J. Am. Chem.
Soc. 1998, 120, 4871.
7. Marshall, J. A.; Wang, X. J. J. Org. Chem. 1991, 56, 4913.
8. Boivin, T. L. Tetrahedron 1987, 43, 3309.
9. Ganguli, M.; Burka, L. T.; Harris, T. M. J. Org. Chem. 1984, 49,
3762. Whang, K.; Cooke, R. J.; Okay, G.; Cha, J. K. J. Am. Chem.
Soc. 1990, 112, 8985; Hatakeyama, S.; Sakurai, K.; Numata, H.;
Ochi, N.; Takano, S. J. Am. Chem. Soc. 1988, 110, 5201.
10. (a) Smadja, W. Chem. Rev. 1983, 83, 263. (b) Marshall, J. A.;
Pinney, K. G. J. Org. Chem. 1993, 58, 7180. (c) Marshall, J. A.
Chem. Rev. 1996, 96, 31.
17. Ohno, H.; Toda, A.; Miwa, Y.; Taga, T.; Osawa, E.; Yamaoka,
Y.; Fujii, N.; Ibuka, T. J. Org. Chem. 1999, 64, 2992.
18. Anzai, M.; Toda, A.; Ohno, H.; Takemoto, Y.; Fujii, N.; Ibuka,
T. Tetrahedron Lett. 1999, 40, 7393.
19. Rutjes, F. P. J. T.; Tjen, K. C. M. F.; Wolf, L. B.; Karstens,
W. F. J.; Schoemaker, H. E.; Hiemstra, H. Org. Lett. 1999, 1, 717.
20. Ohno, H.; Toda, A.; Takemoto, Y.; Fujii, N.; Ibuka, T.
J. Chem. Soc., Perkin Trans. 1 1999, 2949.
11. (a) Alexakis, A.; Marek, I.; Mangeney, P.; Normant, J. F.
Tetrahedron Lett. 1989, 30, 2387. (b) Alexakis, A.; Marek, I.;
Mangeney, P.; Normant, J. F. Tetrahedron 1991, 47, 1677.
12. MuÈller, T. E.; Beller, M. Chem. Rev. 1998, 98, 675.
13. (a) Engelhardt, V. A. J. Am. Chem. Soc. 1956, 78, 107. (b)
Claesson, A.; Sahlberg, C. Tetrahedron Lett. 1978, 1319. (c)
Claesson, A.; Sahlberg, C.; Luthman, K. Acta Chem. Scand.
1979, B33, 309. (d) Sahlberg, C.; Claesson, A. Acta Chem.
Scand. 1982, B36, 179. (e) Breuil-Desvergnes, V.; Compain, P.;
21. A preliminary communication of this work has appeared:
Ohno, H.; Toda, A.; Miwa, Y.; Taga, T.; Fujii, N.; Ibuka, T.
Tetrahedron Lett. 1999, 40, 349.
22. Fujii, N.; Otaka, A.; Ikemura, O.; Akaji, K.; Funakoshi, S.;
Hayashi, Y.; Kuroda, Y.; Yajima, H. J. Chem. Soc., Chem.
Commun. 1987, 274.
23. Curate prepared from 2 equiv. of MeLi´LiBr, 1 equiv. of
CuCN, and 2 equiv. of LiCl may be better represented as
CuLi´LiCN´2LiBr´2LiCl rather than Me2Cu(CN)Li2´2LiBr´2LiCl.
See Krause, N. Angew. Chem., Int. Ed. Engl. 1999, 38, 79.
24. Claesson, A.; Olsson, L.-I. J. Chem. Soc., Chem. Commun.
1979, 524.
Á
Vatele, J.-M.; Gore, J. Tetrahedron Lett. 1999, 40, 5009. (f) Imada,
Y.; Vasapollo, G.; Alper, H. J. Org. Chem. 1996, 61, 7982. (g)
D'Aniello, F.; Schoenfelder, A.; Mann, A.; Taddei, M. J. Org.
Chem. 1996, 61, 9631. (h) Xu, Z.; Lu, X. J. Org. Chem. 1998,
63, 5031. (i) Jeong, I.-Y.; Nagao, Y. Tetrahedron Lett. 1998, 39,
8677. (j) Prasad, J. S.; Liebeskind, L. S. Tetrahedron Lett. 1988,
29, 4253. (k) Prasad, J. S.; Liebeskind, L. S. Tetrahedron Lett.
1988, 29, 4257.
25. X-Ray crystallographic data, and the table of atomic coordi-
nates have been deposited at the Cambridge Crystallographic
Centre. The CCDC reference number of the compound 28 is
CCDC 119274.
14. (a) Grimaldi, J.; Cormons, A. Tetrahedron Lett. 1986, 27,
5089. (b) Karstens, W. F. J.; Rutjes, F. P. J. T.; Hiemstra, H.
Tetrahedron Lett. 1997, 38, 6275. (c) Karstens, W. F. J.; Stol,
M.; Rutjes, F. P. J. T.; Hiemstra, H. Synlett 1998, 1126. (d)
Kang, S.-K.; Baik, T.-G.; Kulak, A. N. Synlett 1999, 324.
15. Arseniyadis, S.; Gore, J.; Tetrahedron Lett. 1983, 24, 3997;
Kinsman, R.; Lathbury, D.; Vernon, P.; Gallagher, T. J. Chem.
Soc., Chem. Commun. 1987, 243; Fox, D. N. A.; Lathbury, D.;
Mahon, M. F.; Molloy, K. C.; Gallagher, T. J. Chem. Soc.,
Chem. Commun. 1989, 1073; Fox, D. N. A.; Gallagher, T.
Tetrahedron 1990, 46, 4697; Kimura, M.; Fugami, K.; Tanaka,
S.; Tamaru, Y. Tetrahedron Lett. 1991, 32, 6359; Fox, D. N. A.;
Lathbury, D.; Mahon, M. F.; Molloy, K. C.; Gallagher, T. J. Am.
26. Madison, V.; Yound, P. E.; Blout, E. R. J. Am. Chem. Soc.
1976, 98, 5358; Young, P. E.; Madison, V.; Blout, E. R. J. Am.
Chem. Soc. 1976, 98, 5365; Fujiwara, H.; van der Veen, J. M.
J. Chem. Soc., Perkin Trans. II 1979, 659; Toniolo, C.; Valle,
G.; Formaggio, F.; Crisma, M.; Boesten, W. H. J.; Polinelli, S.;
Schoemaker, H. E.; Kamphuis, J. J. Chem. Soc., Perkin Trans. 1
1991, 3386; Jones, G. B.; Chapman, B. J.; Mathews, J. E. J. Org.
Chem. 1998, 63, 2928; Gottwald, K.; Seebach, D. Tetrahedron
1999, 55, 723.
27. Massey, V.; Hemmerich, P. The Enzymes 1975, 12, 466.
28. Halliday, R. P.; Davis, C. S.; Heotis, J. P.; Pals, D. T.; Watson,
E. J.; Bickerton, R. K. J. Pharm. Sci. 1968, 57, 430.