Convenient syntheses of chiral 3-substituted 2-ethynylaziridines

Article abstract of DOI:10.1039/a905027b

Two convenient methods for the synthesis of chiral 2-ethynylaziridines from natural α-amino acids are described. Sodium hydride-promoted aziridination of mesylates of 4-arylsulfonylamino-2-bromoalk-2-en-1-ols yields trans-2-(1-bromovinyl)aziridines in a highly stereoselective manner, and subsequent dehydrobromination of the aziridines by potassium tert-butoxide gives separable stereoisomeric mixtures of trans- and cis-2-ethynylaziridines in enantiomerically pure forms (>98% ee). Simple synthesis of 2-ethynylaziridines with high optical purities (91-98% ee) from chiral amino alcohols bearing an ethynyl group under Mitsunobu conditions is also presented. The Royal Society of Chemistry 1999.

Full text of DOI:10.1039/a905027b

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Convenient syntheses of chiral 3-substituted 2-ethynylaziridines
Hiroaki Ohno, Ayako Toda, Yoshiji Takemoto, Nobutaka Fujii and Toshiro Ibuka*
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501,
Japan
Received (in Cambridge, UK) 23rd June 1999, Accepted 26th August 1999
Two convenient methods for the synthesis of chiral 2-ethynylaziridines from natural α-amino acids are described.
Sodium hydride-promoted aziridination of mesylates of 4-arylsulfonylamino-2-bromoalk-2-en-1-ols yields
trans-2-(1-bromovinyl)aziridines in a highly stereoselective manner, and subsequent dehydrobromination of the
aziridines by potassium tert-butoxide gives separable stereoisomeric mixtures of trans- and cis-2-ethynylaziridines
in enantiomerically pure forms (>98% ee). Simple synthesis of 2-ethynylaziridines with high optical purities
(91–98% ee) from chiral amino alcohols bearing an ethynyl group under Mitsunobu conditions is also presented.
Activated aziridines constitute an interesting class of com-
pounds because of their high electrophilicity enabling them
to undergo ring-opening reactions with a wide variety of
nucleophiles in a stereoselective manner.1,2 Particularly, acti-
vated or unactivated aziridines bearing an alkenyl group on
one of the aziridine-ring carbon atoms have proven to be
extremely valuable intermediates. Alkenylaziridines function
as useful substrates for such carbon–carbon bond-forming
reactions as the organocopper-mediated SN2Ј reaction,3 aza-
2,3-Wittig rearrangement,4 palladium(0)-catalyzed carbonyl-
ation,5 and thermal pyrrolysis.6 These reactions provide efficient
synthetic routes to (E)-alkene dipeptide isosteres,3a–d
allylamines,3e,f indolizidine alkaloids,4b,c β-lactams,5 and
pyrrolizidine alkaloids.6 However, relatively little investigation
has been undertaken on the synthesis and reactivity of
Scheme 1
2-ethynylaziridines, although these compounds could
serve as potentially useful building blocks for the stereoselective
synthesis of allenes or alkynes bearing an amino group.
Recently, Dai and co-workers have reported the synthesis of
racemic 2-ethynylaziridines by the reaction of N-tosylimines
with sulfonium ylide.7a They also reported an asymmetric ver-
sion of this reaction in moderate to good enantioselectivities
(14–85% ee) by use of -(ϩ)-camphor-derived sulfonium
ylide.7b,c
As part of an ongoing program aimed at the stereoselective
synthesis and reaction of chiral amino allenes,8,9 we required
a reliable and efficient method for synthesizing 2-ethynyl-
aziridines with high optical purity.10
Results and discussion
1. Synthesis of the mesylates of brominated allylic alcohols
For the synthesis of alkynylaziridines, an efficient preparative
method for allylic mesylates bearing a bromo group on the
double bond is required as synthetic intermediates. As shown in
Scheme 2, the requisite chiral mesylates (11, 17, 25, and 26) of
the corresponding N-arylsulfonylamino alcohols (10, 16, 23,
and 24) were prepared in acceptable yields starting from the N-
protected amino alcohols (7, 12, and 18) which were readily
available from natural (S)-α-amino acids.12
Based on our recent successful results on the efficient and
stereoselective synthesis of trans-2-alkenylaziridines of the type
2 from mesylates of N-protected (E)-4-amino-2-alkylalk-2-en-
1-ols like 1 by treatment with sodium hydride in DMF,11 it was
our expectation to be able to synthesize 2-alkynylaziridines 6
via intermediates 4 and 5 in a stereoselective manner starting
from readily available N-protected amino alcohols 3 as shown
in Scheme 1. In principle, reaction of the bromo mesylate 4 with
bases such as sodium hydride and potassium hydride could
afford trans-2-(1-bromoethenyl)aziridine 5 predominantly or
exclusively. Subsequent dehydrobromination of 5 with such
bases as potassium tert-butoxide would produce the target
alkynylaziridine 6. In this paper we detail a synthetic method
for the preparation of enantiopure 2-alkynylaziridines based
on the above-described chemistry.10 In addition, a simple and
convenient synthesis of 2-ethynylaziridines from N-protected
4-aminoalk-1-yn-3-ols following the Mitsunobu procedure is
also presented.
Typically, (S)-N-arylsulfonyl valinol 7 was treated succes-
sively with oxalyl chloride–DMSO–N,N-diisopropylethylamine
and the bromo-ylide [Ph P᎐C(Br)CO Me]13 to afford a 74:13
᎐
3
2
mixture of the (Z)- and (E)-enoates 8 and 9 in 87% combined
yield which were separated by flash chromatography. Reduction
of the (Z)-enoate 8 with DIBAL-H yielded the allylic alcohol
10, which can be readily converted into the mesylate 11 follow-
ing the standard procedure. In a similar manner, the allylic
mesylates 17 and (25 and 26) were readily prepared from the
corresponding N-protected amino alcohols 12 and 18.
Configurational assignments of the double bond geometry in
α,β-unsaturated esters of type 8 and 9 were rather difficult.
However, it turned out that the determination of configurations
can be readily done by the use of allylic alcohols or their
mesylates. For example, irradiation of the signals of the vinylic
proton at δ 5.91 (Hb in structure 10) led to a 1.6% NOE
enhancement of the signals of one of the methylene protons at
δ 4.21 (Ha in structure 10). In contrast, no NOE enhancement
J. Chem. Soc., Perkin Trans. 1, 1999, 2949–2962
This journal is © The Royal Society of Chemistry 1999
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Scheme 3
Scheme 2 Reagents: i, (COCl)2–DMSO–(i-Pr)2NEt; ii, Ph3P᎐C(Br)-
᎐
CO2Me; iii, DIBAL; iv, MeSO2Cl–Et3N; v, TFA, then TsCl–Et3N; vi,
TFA, then MtsCl–Et3N; vii, TFA, then MtrCl–Et3N. Abbreviations:
Mts = 2,4,6-trimethylbenzenesulfonyl;
methylbenzenesulfonyl; Ts = p-tolylsulfonyl.
Mtr = 4-methoxy-2,3,6-tri-
between the vinylic proton and one of the methylene protons
was observed in the (E)-isomeric alcohol of 10. By using similar
1H NMR analyses, configurational assignments for other allylic
alcohols 16, 23, and 24 as well as the mesylates 17, 25, and 26
were unambiguously made.
Fig. 1
in DMSO at 30 ЊC gave a mixture of the bromo aziridine 27
and its cis-isomer. Analysis by HPLC or H NMR indicated a
97:3 ratio of diastereomers in favor of trans-isomer 27 as
It should be noted that the reaction of some aldehydes
bearing an N-arylsulfonylamino group with the bromo-ylide
1
[Ph P᎐C(Br)CO Me] gave poorer results. For example, reaction
᎐
expected.11b
3
2
of (S)-N-(2,4,6-trimethylphenylsulfonyl)phenylalaninal with
the bromo-ylide gave a 97:3 inseparable mixture of (Z)- and
(E)-enoate in only 28% combined yield. On the other hand,
treatment of (S)-N-Boc-leucinal and (S)-N-Boc-phenylalaninal
with the same bromo-ylide gave the corresponding bromo
esters (13 and 14) and (19 and 20) in high combined yields.
The stereostructure of the major aziridines (27–30) was
proved to be trans by H NMR analysis. We have previously
1
reported that trans-2-(alk-1-enyl)aziridines show smaller JHab
values (J = ca. 4.0 Hz) than those of the cis-isomers (J = ca. 7.0
Hz).11,12 The aziridines (27–30) show JHab values of 3.8–4.3 Hz,
which indicate the configuration of these compounds is trans.
It should be clearly noted that, in all cases examined, separ-
ation of trans-2-ethynylaziridines (27–30) from the correspond-
ing cis-isomers was quite difficult. Only two trans-aziridines 28
and 29 could be isolated in a pure state by repeated flash chrom-
atographic separation.
The predominant formation of trans-bromo aziridines (27–
30) could be rationalized considering the 1,3-allylic strain of
two aza-anionic intermediates A and B (Fig. 1). Although the
ground state and the reactive conformer are not necessarily the
same, the ground state conformations of various olefinic mole-
cules containing the alkene moiety play an important role in the
stereochemical outcome of π-facial selectivity.14 If the reaction
conformers are as depicted in A and B, the higher diastereo-
selectivity is readily understood. Examination of the non-
bonded interactions in the conformers A and B reveals that in
conformer B, which could lead to the cis-isomer 33 via the SN2Ј
pathway, a substantial non-bonded interaction does exist to
2. Aziridination reaction of the N-protected amino allylic
mesylates with sodium hydride
Based on the previous synthetic studies of alkenylaziridines
from the corresponding allylic mesylates,11 we anticipated that
3-alkyl-2-(1-bromovinyl)aziridines of the type 27 could easily
be prepared from the corresponding allylic mesylates of the
type 11 (Scheme 3). However, this was not to be the case. The
reaction could not be completed even after prolonged reaction
time (20 h). After considerable experimentation, we found that
improved yields in the aziridine ring-forming reaction could be
obtained by the use of sodium hydride in DMSO or mixed
solvents containing DMSO. As illustrated in Scheme 3, except
for the bromo aziridine 28, other aziridines (27, 29, and 30)
were obtained from the corresponding allylic mesylates (11, 25,
and 26) in both acceptable yields and high diastereoselectivities.
Typically, the treatment of 11 with sodium hydride (1.2 equiv.)
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destabilize this conformer. Thus, an aziridine ring-forming
reaction would proceed preferentially from the more abundant
conformer A to yield trans-aziridines 32 predominantly.
3. Dehydrobromination reaction of trans-2-(1-bromovinyl)-
aziridines with potassium tert-butoxide
Having synthesized the four bromo aziridines (27–30), we next
investigated the dehydrobromination reaction for the synthesis
of 2-ethynylaziridines.
Exposure of pure bromo aziridine 29 to t-BuOK in THF
unexpectedly gave a separable 65:35 mixture of trans- and cis-
ethynylaziridines 38 and 39 in 80% combined yield. Con-
sequently, without separating the mixtures of bromo aziridines,
all the trans- and cis-mixtures (trans:cis = 95–97:5–3) were
dehydrobrominated to yield the corresponding ethynyl-
aziridines (trans:cis = 65–77:35–23) in good to excellent yields.
The results are listed in Scheme 4. It should be clearly noted
Fig. 2
will generate either only trans-34 or cis-35 or a mixture of both
via an allenic intermediate A. Considering the fact that the
trans-isomer 34 was isolated as the major product, we propose
that the reaction of the bromo aziridine 27 proceeds via two
competitive paths B and C to yield trans- and cis-ethynyl-
aziridines 34 and 35.
Enantiopurities of all the ethynylaziridines (34–41) have
been determined by HPLC with a chiral stationary phase
(CHIRALCEL OD and/or OJ column; hexane:propan-2-
ol = 98.5–93:1.5–7). It was shown that all compounds were
found to be essentially enantiopure (ee >98%).15
4. Synthesis of 2-ethynylaziridines under Mitsunobu conditions
We next investigated the simple synthesis of 2-ethynylaziridines
from amino alcohols bearing an ethynyl group under Mitsu-
nobu conditions.
The requisite amino alcohols (43, 44, 46, 48, 49, and 50) were
synthesized by a sequence of reactions as shown in Scheme 5.
Typically, (S)-N-Boc-valinal derived from (S)-N-Boc-valinol
Scheme 4
that, among various reaction conditions, only t-BuOK in THF
gave satisfactory results. In addition, separation of the four
stereoisomeric pairs of the 2-ethynylaziridines (34 and 35), (36
and 37), (38 and 39), and (40 and 41) was accomplished quite
easily by flash chromatography.
As will be discussed later in more detail, cis- and trans-
configurations of 2-ethynylaziridines were readily determined
1
by H NMR analysis (cis: JHab = 6.2–7.0 Hz; trans: JHab = 3.2–
4.2 Hz).
The formation of cis-2-alkynylaziridines as minor products
from the corresponding trans-2-(1-bromovinyl)aziridines could
be rationalized in the following way. Firstly, treatment of the
ethynylaziridine 34 with t-BuOK under otherwise identical
reaction conditions to those of dehydrobromination (Ϫ78→
0 ЊC, 30 min) resulted in complete recovery of unchanged start-
ing material. Secondly, treatment of 27 with t-BuOK in THF
containing 5 equiv. of t-BuOD gave a mixture of trans- and cis-
2-ethynylaziridines as expected. Although no evidence was
obtained of the incorporation of deuterium in the C-2 position
of trans-2-ethynylaziridine 34, it is found that ca. 10% of
deuterium was incorporated at the C-2 position of cis-2-
ethynylaziridine 35.
Although the details of the dehydrobromination reactions
have still not been elucidated, we are working under the
assumption that both paths B and C are involved as depicted in
Fig. 2. If deprotonation of bromo aziridine 27 by t-BuOK
occurs at the vinylic position (path C), it will produce only the
trans-ethynylaziridine 34 and if it proceeds only by path B, it
Scheme
5
Reagents: i, (COCl)2–DMSO–(i-Pr)2NEt; ii, n-BuLi–
trimethylsilylacetylene; iii, TFA, then MtsCl–Et3N; iv, TBAF.
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423f was treated with trimethylsilylacetylide to give a separable
stereoisomeric mixture of amino alcohols 43 and 44 in low
yields. For reasons unknown, however, the yields of products
were not improved. The N-Boc protecting group in 43 and
44 can be readily replaced by the N-(2,4,6-trimethylphenyl-
sulfonyl) (Mts) group by treatment with trifluoroacetic acid
(TFA) followed by MtsCl and Et3N to yield the corresponding
products 45 and 47 in good yields. Exposure of 43, 44, 45, and
47 to tetrabutylammonium fluoride (Bu4NF) in THF afforded
the desilylation products 49, 50, 46, and 48, respectively, in
good to high yields (see the Experimental section).
As shown in Scheme 6, the N-Mts amino alcohols (54, 56, 57,
Scheme 7 Reagents: i, NaH; ii, NaH–MtsCl.
Scheme 6 Reagents: i, DIBAL; ii, n-BuLi–trimethylsilylacetylene; iii,
TFA, then MtsCl–Et3N; iv, TBDMSCl–imidazole; v, NaOMe(cat)–
MeOH. Abbreviations: TBDMS = tert-butyldimethylsilyl.
and 59) were prepared from (S)-N-Boc-serine derivative 5116 by
a sequence of reactions. Thus, reduction of 51 with DIBAL-H
followed by treatment with lithium trimethylsilylacetylide
yielded a separable mixture of syn- and anti-alcohols 52 and 53.
Not unexpectedly, deprotection of the N-Boc group in 52 with
TFA followed by treatment with MtsCl–Et3N gave a 62:17 mix-
ture of two products 54 and 55. The latter compound 55 could
be readily converted into the former 54 by following the stand-
ard silylation procedure. Finally, the alcohol 56 can be obtained
in high yield from 54 by selective removal of the trimethylsilyl
group by exposure to a catalytic amount of sodium methoxide
in MeOH. In a similar manner, the requisite ethynyl amino
alcohols 57 and 59 were prepared from the anti-amino alcohol
53.
Stereostructural assignments for the synthesized diastereo-
meric amino alcohols (43 and 44) and (52 and 53) were readily
made by transformation into three sets of two stereoisomeric
oxazolidinone derivatives (60 and 62), (61 and 63), (64 and 65).
As can be seen from Scheme 7, the trans-oxazolidinones (60,
61, and 64) show JHab values (J = 1.9–5.9 Hz) smaller than the
JHab values (J = 7.3–8.1 Hz) of the corresponding cis-isomers
(62, 63, and 65). The data are in good agreement with 1H NMR
data for related oxazolidinones.12,16
Scheme 8
and 6 in Table 1) proceeded more slowly at 0 ЊC than that of the
N-Mts derivatives (46, 48, 54, 56, 57, and 59; 0 ЊC; entries 3, 4,
and 7–10 in Table 1). Notably, the cyclization reaction of the
anti-amino alcohols 44 and 50 required 2 h at 25 ЊC to give the
expected trans-aziridines 70 and 71 in rather low yields (73 and
64% respectively; entries 2 and 6).
Although the compounds 34, 35, 46, and 48 synthesized from
(S)-valinol derivative 42 were essentially enantiomerically pure
(>98% ee), the compounds such as 56, 57, 59, 72, and 73 pre-
pared from methyl (S)-serinate derivative 51 were not optically
pure (91–97% ee).
Table 2 lists spin–spin coupling constants for JHab of the cis-
and trans-3-alkyl-2-ethynylaziridines. As can be seen from Table
2, the cis-aziridines show JHab values (J = 6.2–7.0 Hz: entries 1–
10, Table 2) larger than the JHab values (J = 3.2–4.3 Hz: entries
11–18, Table 2) of the trans-isomers. The data for 2-ethynyl-
aziridines are in good agreement with 1H NMR data for
2-ethenylaziridines.12
Next, we investigated aziridination reactions of ethynyl
amino alcohols under Mitsunobu conditions. The results are
summarized in Scheme 8 and Table 1. Typically, treatment of 43
with triphenylphosphine and diethyl azodicarboxylate in THF
at 25 ЊC for 0.5 h yielded the cis-2-ethynylaziridine 66 in 96%
yield (entry 1, Table 1). In all cases, the ethynyl amino alcohols
were effectively cyclized into the corresponding ethynylazirid-
ines in good to excellent yields. However, aziridination reaction
of N-Boc amino alcohols (43, 44, 49, and 50: entries 1, 2, 5,
5. Cross-coupling reaction at the terminal position of the ethynyl
group of 2-ethynylaziridines with some electrophiles
Finally, substitution reaction of the ethynylaziridines 34 and 35
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Table 1 Synthesis of 2-ethynylaziridines from amino alcohols under Mitsunobu conditionsa
Entry
Substrate
R1
R2
R3
T/ЊC
t/h
Product
cis/trans
Yieldb(%)
1
2
3
4
5
6
7
8
9
43
44
46
48
49
50
54
56
57
59
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
TBDMSOCH2
TBDMSOCH2
TBDMSOCH2
TBDMSOCH2
Boc
Boc
Mts
Mts
Boc
Boc
Mts
Mts
Mts
Mts
TMS
TMS
H
H
H
H
TMS
H
TMS
H
25
25
0
0.5
2.0
0.5
0.5
0.5
2.0
0.5
0.5
0.5
0.5
66
67
35
34
68
69
70
71
72
73
cis
trans
cis
trans
cis
trans
cis
cis
trans
trans
96
73
97
98
87
64
94
96
99
95
0
25
25
0
0
0
10
0
a All reactions were carried out in THF using diethyl azodicarboxylate (1.2–2.0 equiv.) and triphenylphosphine (1.2–2.0 equiv.). b Isolated yields.
a
Table 2 Spin–spin coupling constants for JHab of the cis- and trans-2-ethynylaziridines in CDCl3
Entry
Compound
R1
R2
R3
cis/trans
JHab
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
35
37
39
41
66
68
70
71
76
77
34
36
38
40
67
69
72
73
74
75
i-Pr
i-Bu
Bn
Bn
i-Pr
i-Pr
Mts
Ts
Mts
Mtr
Boc
Boc
H
H
H
H
TMS
H
TMS
H
CO2Me
TMS
H
H
H
H
TMS
H
TMS
H
CO2Me
TMS
cis
cis
cis
cis
cis
cis
cis
cis
6.8
7.0
6.8
6.8
6.2
6.5
6.8
7.0
7.0
6.8
4.2
3.8
3.8
4.1
3.2
3.2
4.3
TBDMSOCH2 Mts
TBDMSOCH2 Mts
i-Pr
i-Pr
i-Pr
i-Bu
Bn
Bn
i-Pr
i-Pr
TBDMSOCH2 Mts
TBDMSOCH2 Mts
i-Pr
i-Pr
Mts
Mts
Mts
Ts
Mts
Mtr
Boc
Boc
cis
cis
trans
trans
trans
trans
trans
trans
trans
trans
trans
trans
4.3
b
Mts
Mts
b
a All 1H NMR spectra were recorded in CDCl3 at 300 K. For designations of Ha and Hb, see structures A and B. b J values were unreadable because
of an overlap of the two signals, Ha and Hb.
or 75 in good yields. Similarly, cis-2-ethynylaziridine 35 was
converted into the terminally-substituted ethynylaziridines 76
and 77. From the above experimentation, it is apparent that
lithium aziridinylacetylides are stable at Ϫ78 ЊC for at least a
short period of time and they are reactive to undergo nucle-
ophilic attack to methyl chloroformate or chlorotrimethylsilane
at Ϫ78 ЊC.
In summary, we have developed two procedures for the
preparation of cis- and trans-2-ethynylaziridines from natural
α-amino acids. Exposure of brominated allylic mesylates to
NaH in DMSO gives trans-2-(1-bromovinyl)aziridines stereo-
selectively in good yield, which could be easily transformed into
separable mixtures of cis- and trans-2-ethynylaziridines (>98%
ee) by treatment with t-BuOK in THF. Alternatively, cyclization
of amino alcohols bearing an ethynyl group under Mitsunobu
conditions also gives 2-ethynylaziridines efficiently (91–98% ee).
The synthesized compounds could serve as useful synthetic
Scheme 9
at the acetylene terminus was briefly investigated (Scheme 9).
Treatment of 34 with LDA at Ϫ78 ЊC for 1 h followed by addi-
tion of methyl chloroformate or chlorotrimethylsilane gave 74
intermediates to chiral allenes and acetylenes bearing an amino
group, and we are now undertaking synthetic studies involving
this class of compounds.
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cm3) at Ϫ78 ЊC under argon. After stirring for 3 h with warming
Experimental
General methods
to Ϫ20 ЊC, a saturated NH4Cl solution (30 cm3) was added with
vigorous stirring. The mixture was made acidic with saturated
citric acid and extracted with EtOAc. The extract was washed
successively with water and NaHCO3, and dried over MgSO4.
The usual workup followed by recrystallization from n-hexane–
EtOAc (1:1) gave the title compound 10 (21.9 g, 94% yield) as
colourless crystals, mp 104 ЊC (Found: C, 49.1; H, 6.3; N, 3.5.
C16H24BrNO3S requires C, 49.2; H, 6.2; N, 3.6%); [α]D19 ϩ44.6
(c 0.866 in CHCl3); δH (300 MHz, CDCl3; 258 K) 0.76 (3 H, d,
J 6.8, CMe), 0.81 (3 H, d, J 6.8, CMe), 1.65–1.76 (1 H, m, 5-H),
2.33 (3 H, s, CMe), 2.68 (6 H, s, 2 × CMe), 3.31–3.38 (1 H, m,
OH), 3.95 (1 H, ddd, J 9.0, 8.3 and 5.8, 4-H), 4.08 (1 H, dd,
J 14.4 and 6.9, 1-CHH), 4.21 (1 H, dd, J 14.4 and 6.5, 1-CHH),
5.78 (1 H, d, J 8.3, NH), 5.91 (1 H, J 9.0, 3-H), 6.99 (2 H, s, Ph).
The instrumentation has been described previously.16 All reac-
tions were carried out under a positive pressure of argon. All
glassware and syringes were dried in an electric oven at 100 ЊC
prior to use. All melting points are uncorrected. 1H NMR
spectra were recorded using a JEOL EX-270 (270 MHz) or
Bruker AC-300 (300 MHz) spectrometer in CDCl3. Chemical
shifts are reported in parts per million downfield from internal
Me4Si. J Values are given in Hz. For flash chromatography,
silica gel 60 H (silica gel for thin-layer chromatography, Merck)
or silica gel 60 (finer than 230 mesh, Merck) was employed. For
the determination of optical purity, Chiralcel OD and OJ
(DAICEL, 4.6 × 260 mm) was used. For reversed-phase HPLC,
µ-Bondasphere–C-18 (3.9 × 150 mm, Waters) was employed
(28 ЊC).
General procedure for the preparation of allylic methanesulfon-
ates (11, 17, 25, and 26). (4S,2Z)-2-Bromo-O-methylsulfonyl-5-
methyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]hex-2-en-1-ol
11
General procedure for the preparation of E/Z pairs of methyl 4-
amino-2-bromo-2-enoates (8 and 9), (13 and 14), and (19, and 20)
from amino alcohols (7, 12, and 18). Methyl (4S,2Z)-2-bromo-5-
methyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]hex-2-enoate
8 and its (4S,2E) isomer 9
To a stirred mixture of the alcohol 10 (3.12 g, 8 mmol) and
Et3N (5.53 cm3, 40 mmol) in THF (15 cm3) was added dropwise
methanesulfonyl chloride (2.17 cm3, 28 mmol) at Ϫ78 ЊC. The
mixture was stirred for 1 h with warming to 0 ЊC. Saturated
aqueous NaHCO3 (5 cm3) was added with vigorous stirring.
The whole was extracted with EtOAc and the extract was
washed successively with 5% citric acid, water, 5% NaHCO3,
and water, and dried over MgSO4. Usual workup followed by
flash chromatography over silica gel with n-hexane–EtOAc
(1:1) gave the title compound 11 (3.71 g, 99% yield) as colour-
less crystals, mp 86 ЊC (from Et2O) (Found: C, 43.4; H, 5.5; N,
3.0. C17H26BrNO5S2 requires C, 43.6; H, 5.6; N, 3.0%); [α]D18
ϩ30.2 (c 1.32 in CHCl3); δH (270 MHz, CDCl3) 0.88 (3 H, d,
J 6.8, CMe), 0.92 (3 H, d, J 7.0, CMe), 1.78–1.90 (1 H, m, 5-H),
2.31 (3 H, s, CMe), 2.64 (6 H, s, 2 × CMe), 3.04 (3 H, s,
SO2Me), 3.94 (1 H, ddd, J 8.9, 8.6 and 6.2, 4-H), 4.52–4.62
(2 H, m, 1-CH2), 4.76 (1 H, d, J 6.2, NH), 5.86 (1 H, d, J 8.9,
3-H), 6.95 (2 H, s, Ph).
To a stirred solution of oxalyl chloride (2.6 cm3, 27.2 mmol) in a
mixed solvent of CHCl3 (25 cm3) and n-hexane (20 cm3) at
Ϫ78 ЊC under argon was added dropwise a solution of DMSO
(10.6 cm3, 150 mmol) in CHCl3 (15 cm3). After 30 min, a solu-
tion of the alcohol 7 (8.56 g, 30 mmol) in CHCl3 (15 cm3) was
added to the above reagent at Ϫ78 ЊC, and the mixture was
stirred for 1 h. Diisopropylethylamine (36.6 cm3, 210 mmol)
was added to the above solution at Ϫ78 ЊC and the mixture was
stirred for 30 min with warming to 0 ЊC. Saturated aqueous citric
acid (40 cm3) was added to the mixture and the whole was
extracted with Et2O. The extract was washed successively with
water, 5% NaHCO3, and water, and dried over MgSO4. Usual
workup gave a crude aldehyde, which was dissolved in CHCl3
(40 cm3). Bromo ylide [Ph P᎐C(Br)CO Me; 12.4 g, 30 mmol]
᎐
3
2
was added to the above solution at 0 ЊC, and the mixture
was stirred for 15 h at this temperature. Concentration under
reduced pressure gave an oily residue, which was flash chrom-
atographed over silica gel. Elution with n-hexane–EtOAc (4:1)
gave 9 (1.59 g, 12.7%) and further elution yielded 8 (9.3 g, 74%
yield). Compound 8: 98% ee (S) by HPLC [Daicel Chiralcel
OD, n-hexane:propan-2-ol = 95:5 (0.5 cm3 minϪ1), (R)-isomer
28.9 min, (S)-isomer 36.7 min]; colourless crystals, mp 112 ЊC
(from Et2O) (Found: C, 48.8; H, 5.8; N, 3.4. C17H24BrNO4S
requires C, 48.8; H, 5.8; N, 3.35%); [α]D20 ϩ20.9 (c 1.15 in CHCl3);
δH (270 MHz, CDCl3) 0.91 (3 H, d, J 6.8, CMe), 0.95 (3 H, d,
J 7.0, CMe), 1.84–1.97 (1 H, m, 5-H), 2.27 (3 H, s, CMe), 2.63
(6 H, s, 2 × CMe), 3.75 (3 H, s, OMe), 4.02 (1 H, ddd, J 9.2, 8.6
and 5.9, 4-H), 4.81 (1 H, d, J 8.6, NH), 6.83 (1 H, d, J 9.2, 3-H),
6.91 (2 H, s, Ph). Compound 9: 98% ee (S) by HPLC [Daicel
Chiralcel OD, n-hexane:propan-2-ol = 97:3 (0.5 cm3 minϪ1),
(R)-isomer 39.4 min, (S)-isomer 41.8 min]; colourless crystals,
mp 135 ЊC (from Et2O) (Found: C, 48.75; H, 5.75; N, 3.4.
C17H24BrNO4S requires C, 48.8; H, 5.8; N, 3.35%); [α]D20 Ϫ60.1
(c 1.53 in CHCl3); δH (270 MHz, CDCl3) 0.90 (3 H, d, J 7.0,
CMe), 0.94 (3 H, d, J 7.0, CMe), 1.75–1.88 (1 H, m, 5-H), 2.30
(3 H, s, CMe), 2.59 (6 H, s, 2 × CMe), 3.74 (3 H, s, OMe), 4.50
(1 H, ddd, J 10.0, 8.9 and 5.9, 4-H), 4.73 (1 H, d, J 8.9, NH),
6.22 (1 H, d, J 10.0, 3-H), 6.93 (2 H, s, Ph).
Methyl (4S,2Z)-2-bromo-4-[N-(tert-butoxycarbonyl)amino]-6-
methylhept-2-enoate 13 and its (4S,2E) isomer 14
By a procedure identical with that described for the preparation
of the enoates 8 and 9 from 7, the alcohol 12 (13.7 g, 63 mmol)
was converted into the title compound 13 (12.2 g, 55% yield)
and 14 (8.49 g, 39% yield). Compound 13: colourless crystals,
mp 71 ЊC (from n-hexane) (Found: C, 47.9; H, 7.1; N, 3.9.
C14H24BrNO4 requires C, 48.0; H, 6.9; N, 4.0%); [α]D28 ϩ43.3
(c 1.08 in CHCl3); δH (270 MHz, CDCl3) 0.96 (3 H, d, J 6.8,
CMe), 0.98 (3 H, d, J 6.5, CMe), 1.30–1.45 (2 H, m, 5-CH2),
1.44 (9 H, s, CMe3), 1.61–1.74 (1 H, m, 6-H), 3.83 (3 H,
s, OMe), 4.50–4.65 (2 H, m, 4-H and NH), 7.13 (1 H, d,
J 6.6, 3-H). Compound 14: colourless crystals, mp 91 ЊC (from
n-hexane) (Found: C, 47.9; H, 6.7; N, 3.9. C14H24BrNO4
requires C, 48.0; H, 6.9; N, 4.0%); [α]D28 Ϫ3.0 (c 1.37 in CHCl3);
δH (270 MHz, CDCl3) 0.93 (3 H, d, J 6.8, CMe), 0.97 (3 H, d,
J 6.8, CMe), 1.35–1.50 (2 H, m, 5-CH2), 1.43 (9 H, s, CMe3),
1.60–1.75 (1 H, m, 6-H), 3.84 (3 H, s, OMe), 4.56 (1 H, br s,
NH), 4.88–5.02 (1 H, m, 4-H), 6.50 (1 H, d, J 8.9, 3-H).
General procedure for the preparation of N-arenesulfonamide
(15, 21, 22, 45, 47, 54, 57) from the corresponding N-Boc
derivatives. Methyl (4S,2Z)-2-bromo-6-methyl-4-[N-(4-
methylphenylsulfonyl)amino]hept-2-enoate 15
Trifluoroacetic acid (20 cm3) was added to a stirred solution of
the enoate 13 (6.75 g, 19 mmol) in CHCl3 (20 cm3) at 0 ЊC, and
the mixture was stirred for 1 h at this temperature. The mixture
was concentrated to an oil under reduced pressure, which was
made alkaline with 28% NH4OH at 0 ЊC and extracted with
General procedure for the preparation of allylic alcohols (10, 16,
23, and 24). (4S,2Z)-2-Bromo-5-methyl-4-[N-(2,4,6-trimethyl-
phenylsulfonyl)amino]hex-2-en-1-ol 10
DIBAL-H (1.0 M solution in toluene; 209 cm3, 209 mmol) was
added dropwise to a stirred solution of the enoate 8 (25 g, 59.8
mmol) in a mixed solvent of toluene (150 cm3) and CHCl3 (60
2954
J. Chem. Soc., Perkin Trans. 1, 1999, 2949–2962

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CHCl3. The extract was washed with water, and dried over
MgSO4. Usual workup gave an oily residue. To a stirred mixture
of the oil and Et3N (5 cm3, 36 mmol) in CHCl3 (100 cm3) was
added toluene-p-sulfonyl chloride (4.3 g, 24.7 mmol) at 0 ЊC,
and the mixture was stirred for 1 h at this temperature, followed
by quenching with aqueous 5% NaHCO3 (20 cm3). The mixture
was made acidic with saturated aqueous citric acid, and the
whole was extracted with Et2O. The extract was washed succes-
sively with water, aqueous 5% NaHCO3, and water, and dried
over MgSO4. Usual workup followed by recrystallization from
n-hexane–Et2O (4:1) gave the title compound 15 (6.49 g,
83% yield). 98% ee (S) by HPLC [Daicel Chiralcel OD,
n-hexane:propan-2-ol = 95:5 (0.5 cm3 minϪ1), (S)-isomer 37.9
min]; colourless needles, mp 115 ЊC [from n-hexane–Et2O (4:1)]
(Found: C, 47.6; H, 5.5; N, 3.4. C16H22BrNO4S requires C, 47.5;
H, 5.5; N, 3.5%); [α]D30 Ϫ42.7 (c 1.19 in CHCl3); δH (270 MHz,
CDCl3) 0.80 (3 H, d, J 6.2, CMe), 0.89 (3 H, d, J 6.5, CMe),
1.27 (1 H, ddd, J 13.8, 8.6 and 5.1, 5-CHH), 1.45 (1 H, ddd,
J 13.8, 9.5 and 5.4, 5-CHH), 1.55–1.72 (1 H, m, 6-H), 2.41 (3 H,
s, CMe), 3.75 (3 H, s, OMe), 4.19–4.31 (1 H, m, 4-H), 4.91 (1 H,
d, J 7.6, NH), 6.86 (1 H, d, J 8.6, 3-H), 7.26–7.29 (2 H, m, Ph),
7.74–7.77 (2 H, m, Ph).
CMe3), 2.65 (1 H, br s, OH), 2.82–2.85 (2 H, m, 3-CH2), 3.54
(1 H, dd, J 10.8 and 5.4, 1-CHH), 3.65 (1 H, dd, J 10.8 and 3.8,
1-CHH), 3.80–3.93 (1 H, m, 2-H), 4.82 (1 H, br s, NH), 7.19–
7.33 (5 H, m, Ph).
Methyl (4S,2Z)-2-bromo-4-[N-(tert-butoxycarbonyl)amino]-5-
phenylpent-2-enoate 19 and its (4S,2E) isomer 20
By a procedure identical with that described for the preparation
of the enoates 8 and 9 from 7, the alcohol 18 (28.4 g, 113 mmol)
was converted into the title compound 19 (23.6 g, 54% yield)
and 20 (14.2 g, 33% yield). Compound 19: colourless needles,
mp 133–135 ЊC [from n-hexane–EtOAc (5:1)] (Found: C, 53.0;
H, 5.7; N, 3.6. C17H22BrNO4 requires C, 53.1; H, 5.8; N, 3.6%);
[α]D28 ϩ56.3 (c 0.742 in CHCl3); δH (270 MHz, CDCl3) 1.39 (9 H,
s, CMe3), 2.80–2.95 (1 H, m, 5-CHH), 2.96 (1 H, dd, J 13.8 and
4.9, 5-CHH), 3.83 (3 H, s, OMe), 4.60–4.79 (2 H, m, 4-H and
NH), 7.18–7.36 (6 H, m, Ph and 3-H). Compound 20: colour-
less needles, mp 124 ЊC [from n-hexane–EtOAc (5:1)] (Found:
C, 53.0; H, 5.6; N, 3.65. C17H22BrNO4 requires C, 53.1; H, 5.8;
N, 3.6); [α]D28 ϩ34.2 (c 1.30 in CHCl3); δH (270 MHz, CDCl3) 1.38
(9 H, s, CMe3), 2.81–2.96 (1 H, m, 5-CHH), 2.97 (1 H, dd,
J 13.2 and 5.1, 5-CHH), 3.82 (3 H, s, OMe), 4.62 (1 H, br s,
NH), 5.07–5.18 (1 H, m, 4-H), 6.62 (1 H, d, J 8.9, 3-H), 7.20–
7.36 (5 H, m, Ph).
(4S,2Z)-2-Bromo-6-methyl-4-[N-(4-methylphenylsulfonyl)-
amino]hept-2-en-1-ol 16
Methyl (4S,2Z)-2-bromo-5-phenyl-4-[N-(2,4,6-trimethyl-
phenylsulfonyl)amino]pent-2-enoate 21
By a procedure identical with that described for the preparation
of the alcohol 10 from 8, the enoate 15 (6.48 g, 16 mmol) was
converted into the title compound 16 (5.67 g, 94% yield) as
colourless crystals, mp 119 ЊC (from Et2O) (Found: C, 48.2;
H, 5.8; N, 3.6. C15H22BrNO3S requires C, 47.9; H, 5.9; N, 3.7%);
[α]D30 ϩ11.6 (c 1.46 in CHCl3); δH (300 MHz, CDCl3) 0.78 (3 H, d,
J 6.5, CMe), 0.86 (3 H, d, J 6.6, CMe), 1.26 (1 H, ddd, J 13.9,
8.0 and 6.2, 5-CHH), 1.41 (1 H, ddd, J 13.9, 8.5 and 6.0,
5-CHH), 1.52–1.65 (1 H, m, 6-H), 2.08 (1 H, br s, OH), 2.43
(3 H, s, CMe), 3.99 (1 H, dd, J 14.4 and 1.1, 1-CHH), 4.03 (1 H,
dd, J 14.4 and 1.1, 1-CHH), 4.13–4.24 (1 H, m, 4-H), 4.89 (1 H,
d, J 7.4, NH), 5.74 (1 H, ddd, J 8.6, 1.1 and 1.1, 3-H), 7.28–7.32
(2 H, m, Ph), 7.75–7.80 (2 H, m, Ph).
By a procedure similar to that described for the preparation of
15 from 13, the enoate 19 (10.0 g, 26 mmol) was converted into
the title compound 21 (10.0 g, 82% yield). 98% ee (S) by HPLC
[Daicel Chiralcel OD, n-hexane:propan-2-ol = 95:5 (0.5 cm3
minϪ1), (S)-isomer 59.4 min]; colourless needles, mp 109 ЊC
[from n-hexane–Et2O–CHCl3 (3:1:1)] (Found: C, 53.95; H, 5.3;
N, 2.9. C21H24BrNO4S requires C, 54.1; H, 5.2; N, 3.0%); [α]D28
Ϫ2.13 (c 0.937 in CHCl3); δH (270 MHz, CDCl3) 2.28 (3 H, s,
CMe), 2.34 (6 H, s, 2 × CMe), 2.68 (1 H, dd, J 13.8 and 9.2,
5-CHH), 2.96 (1 H, dd, J 13.8 and 4.6, 5-CHH), 3.80 (3 H, s,
OMe), 4.17–4.27 (1 H, m, 4-H), 4.68–4.74 (1 H, m, NH), 6.84
(2 H, s, Ph), 7.02–7.06 (2 H, m, Ph), 7.17 (1 H, d, J 7.8, 3-H),
7.20–7.29 (3 H, m, Ph).
(4S,2Z)-2-Bromo-O-methylsulfonyl-6-methyl-4-[N-(4-methyl-
phenylsulfonyl)amino]hept-2-en-1-ol 17
Methyl (4S,2Z)-2-bromo-4-[N-(4-methoxy-2,3,6-trimethyl-
phenylsulfonyl)amino]-5-phenylpent-2-enoate 22
By a procedure identical with that described for the preparation
of the mesylate 11 from 10, the alcohol 16 (5.67 g, 15.1 mmol)
was converted into the title compound 17 (6.37 g, 93% yield)
as colourless needles, mp 139 ЊC [from CHCl3–Et2O (1:9)]
(Found: C, 42.3; H, 5.3; N, 3.0. C16H24BrNO5S2 requires C,
42.3; H, 5.3; N, 3.1%); [α]D30 ϩ13.4 (c 0.984 in CHCl3); δH (270
MHz, CDCl3) 0.76 (3 H, d, J 6.2, CMe), 0.86 (3 H, d, J 6.5,
CMe), 1.24 (1 H, ddd, J 14.0, 8.4 and 5.7, 5-CHH), 1.41 (1 H,
ddd, J 14.0, 8.9 and 5.4, 5-CHH), 1.51–1.66 (1 H, m, 6-H), 2.44
(3 H, s, CMe), 3.05 (3 H, s, SO2Me), 4.10–4.22 (1 H, m, 4-H),
4.610 (1 H, d, J 13.2, 1-CHH), 4.614 (1 H, d, J 13.2, 1-CHH),
4.97 (1 H, d, J 7.3, NH), 5.92 (1 H, d, J 8.6, 3-H), 7.29–7.33
(2 H, m, Ph), 7.74–7.78 (2 H, m, Ph).
By a procedure similar to that described for the preparation of
15 from 13, the enoate 19 (14 g, 36.4 mmol) was converted into
the title compound 22 (17.5 g, 97% yield) as colourless crystals,
mp 142 ЊC [from n-hexane–EtOAc (5:2)] (Found: C, 53.05; H,
5.2; N, 2.5. C22H26BrNO5S requires C, 53.2; H, 5.3; N, 2.8%);
[α]D28 ϩ4.43 (c 1.31 in CHCl3); δH (270 MHz, CDCl3) 2.02 (3 H, s,
CMe), 2.09 (3 H, s, CMe), 2.53 (3 H, s, CMe), 2.67 (1 H, dd,
J 13.8 and 9.2, 5-CHH), 2.95 (1 H, dd, J 13.8 and 4.3, 5-CHH),
3.79 (3 H, s, OMe), 3.85 (3 H, s, OMe), 4.19 (1 H, dddd, J 9.2,
8.4, 4.9 and 4.3, 4-H), 4.67 (1 H, d, J 4.9, NH), 6.52 (1 H, s, Ph),
7.03–7.08 (2 H, m, Ph), 7.11 (1 H, d, J 8.4, 3-H), 7.20–7.27 (3 H,
m, Ph).
2-[N-(tert-Butoxycarbonyl)amino]-3-phenylpropan-1-ol 18
(4S,2Z)-2-Bromo-5-phenyl-4-[N-(2,4,6-trimethylphenyl-
sulfonyl)amino]pent-2-en-1-ol 23
To a stirred solution of (S)-phenylalaninol17 (14 g, 92.6 mmol)
and Et3N (25.6 cm3, 185 mmol) in DMF (60 cm3) was added
Boc2O (20.2 g, 92.6 mmol) at 0 ЊC, and the mixture was
stirred for 1 h at this temperature. Water (40 cm3) was added to
the mixture and the whole was extracted with Et2O, and the
extract was washed successively with 5% citric acid, water, 5%
NaHCO3, and water, and dried over MgSO4. Usual workup
followed by recrystallization from n-hexane–EtOAc (4:1) gave
the title compound 18 (20.2 g, 87% yield) as colourless needles,
mp 92 ЊC [from n-hexane–EtOAc (4:1)] (Found: C, 66.95; H,
8.65; N, 5.9. C14H21NO3 requires C, 66.9; H, 8.4; N, 5.6%); [α]D31
Ϫ24.2 (c 0.756 in CHCl3); δH (270 MHz, CDCl3) 1.41 (9 H, s,
By a procedure identical with that described for the preparation
of the alcohol 10 from 8, the enoate 21 (9.95 g, 21.3 mmol) was
converted into the title compound 23 (8.85 g, 95% yield)
as colourless crystals, mp 142 ЊC [from CHCl3–Et2O (1:2)]
(Found: C, 54.8; H, 5.6; N, 3.1. C20H24BrNO3S requires C, 54.8;
H, 5.5; N, 3.2%); [α]D28 ϩ24.6 (c 0.926 in CHCl3); δH (300 MHz,
CDCl3) 2.04 (1 H, dd, J 7.0 and 6.9, OH), 2.29 (3 H, s, CMe),
2.39 (6 H, s, 2 × CMe), 2.67 (1 H, dd, J 13.9 and 8.8, 5-CHH),
2.92 (1 H, dd, J 13.9 and 5.0, 5-CHH), 4.03–4.16 (2 H, m,
1-CH2), 4.24 (1 H, dddd, J 8.8, 8.1, 5.3 and 5.0, 4-H), 4.69 (1 H,
J. Chem. Soc., Perkin Trans. 1, 1999, 2949–2962
2955

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d, J 5.3, NH), 5.91 (1 H, ddd, J 8.1, 1.3 and 1.3, 3-H), 6.85–6.87
(2 H, m, Ph), 7.04–7.07 (2 H, m, Ph), 7.21–7.25 (3 H, m, Ph).
J 1.9, C᎐CHH), 5.57 (1 H, dd, J 1.9 and 1.1, C᎐CHH), 6.94
᎐ ᎐
(2 H, s, Ph); m/z (FAB) 374 (MHϩ, 81Br), 372 (MHϩ, 79Br), 318,
316, 190, 188, 183, 167, 119 (base peak), 91 and 55.
(4S,2Z)-2-Bromo-4-[N-(4-methoxy-2,3,6-trimethylphenyl-
sulfonyl)amino]-5-phenylpent-2-en-1-ol 24
(2S,3S)-2-(1-Bromovinyl)-3-(2-methylpropyl)-N-(4-methylphen-
ylsulfonyl)aziridine 28
By a procedure identical with that described for the preparation
of the alcohol 10 from 8, the enoate 22 (17.4 g, 35 mmol) was
converted into the title compound 24 (15.5 g, 95% yield) as
colourless crystals, mp 126 ЊC (from Et2O) (Found: C, 53.8; H,
5.6; N, 2.7. C21H26BrNO4S requires C, 53.85; H, 5.6; N, 3.0%);
[α]D29 ϩ31.5 (c 1.06 in CHCl3); δH (270 MHz, CDCl3) 2.04 (3 H, s,
CMe), 2.09 (3 H, s, CMe), 2.31–2.42 (1 H, m, OH), 2.55 (3 H, s,
CMe), 2.64 (1 H, dd, J 13.8 and 9.2, 5-CHH), 2.90 (1 H, dd,
J 13.8 and 4.6, 5-CHH), 3.86 (3 H, s, OMe), 4.05–4.20 (3 H, m,
1-CH2 and 4-H), 4.71 (1 H, d, J 4.9, NH), 6.01 (1 H, d, J 8.4,
3-H), 6.53 (1 H, s, Ph), 7.01–7.06 (2 H, m, Ph), 7.17–7.25 (3 H,
m, Ph).
By a procedure identical with that described for the preparation
of the aziridine 27 from 11, the mesylate 17 (2.9 g, 6.39 mmol)
was converted into a 95:5 mixture (1.08 g, 47% combined yield)
of the title compound 28 and its (2R,3S) isomer, by treatment
with NaH in DMF–DMSO (3:1) at room temperature for 3 h.
The major isomer 28 was isolated by repeated flash chrom-
atography over silica gel with n-hexane–EtOAc (10:1). Com-
pound 28: colourless oil [Found (FAB): (M ϩ H)ϩ, 358.0469.
C15H21BrNO2S requires M ϩ H; 358.0477]; [α]D30 ϩ30.6 (c 1.40
in CHCl3); δH (270 MHz, CDCl3) 1.02 (3 H, d, J 6.2, CMe),
1.03 (3 H, d, J 6.2, CMe), 1.73–1.93 (2 H, m, Me2CH and
Me2CHCHH), 2.21–2.29 (1 H, m, Me2CHCHH), 2.44 (3 H, s,
CMe), 2.82 (1 H, ddd, J 9.7, 4.3 and 3.8, 3-H), 3.42 (1 H, d,
(4S,2Z)-2-Bromo-O-methylsulfonyl-5-phenyl-4-[N-(2,4,6-
trimethylphenylsulfonyl)amino]pent-2-en-1-ol 25
J 4.3, 2-H), 5.47 (1 H, d, J 1.9, C᎐CHH), 5.67 (1 H, dd, J 1.9
᎐
and 0.8, C᎐CHH), 7.30–7.34 (2 H, m, Ph), 7.83–7.86 (2 H, m,
᎐
By a procedure identical with that described for the preparation
of the mesylate 11 from 10, the alcohol 23 (701 mg, 1.6 mmol)
was converted into the title compound 25 (776 mg, 94% yield)
as colourless crystals, mp 106 ЊC [from CHCl3–Et2O (1:2)]
(Found: C, 48.8; H, 5.05; N, 2.7. C21H26BrNO5S2 requires C,
48.8; H, 5.1; N, 2.7%); [α]D30 ϩ8.26 (c 1.03 in CHCl3); δH (270
MHz, CDCl3) 2.30 (3 H, s, CMe), 2.35 (6 H, s, 2 × CMe), 2.68
(1 H, dd, J 13.8 and 8.9, 5-CHH), 2.92 (1 H, dd, J 13.8 and 4.9,
5-CHH), 3.04 (3 H, s, SO2Me), 4.17 (1 H, dddd, J 8.9, 7.8, 5.1
and 4.9, 4-H), 4.64 (1 H, d, J 5.1, NH), 4.68–4.76 (2 H, m,
1-CH2), 6.14 (1 H, d, J 7.8, 3-H), 6.86 (2 H, s, Ph), 7.02–7.06
(2 H, m, Ph), 7.20–7.28 (3 H, m, Ph).
Ph); m/z (FAB) 360 (MHϩ, 81Br), 358 (MHϩ, 79Br), 204, 202, 155
(base peak), 139, 107 and 91.
(2S,3S)-3-Benzyl-2-(1-bromovinyl)-N-(2,4,6-trimethylphenyl-
sulfonyl)aziridine 29
By a procedure identical with that described for the preparation
of the aziridine 27 from 11, the mesylate 25 (670 mg, 1.3 mmol)
was converted into a 97:3 mixture (393 mg, 72% combined
yield) of the title compound 29 and (2R,3S) isomer, by treat-
ment with NaH in DMSO at 30 ЊC for 2.5 h. The major isomer
29 was isolated by repeated flash chromatography over silica
gel with n-hexane–EtOAc (20:1). Compound 29: colourless oil
[Found (FAB): (M ϩ H)ϩ, 420.0615. C20H23BrNO2S requires
M ϩ H, 420.0633]; [α]D31 ϩ43.7 (c 0.856 in CHCl3); δH (270 MHz,
CDCl3) 2.31 (3 H, s, CMe), 2.72 (6 H, s, 2 × CMe), 2.99 (1 H,
ddd, J 9.7, 4.1 and 3.8, 3-H), 3.29 (1 H, dd, J 14.6 and 9.7,
PhCHH), 3.54 (1 H, dd, J 14.6 and 4.1, PhCHH), 3.64 (1 H, d,
(4S,2Z)-2-Bromo-O-methylsulfonyl-4-[N-(4-methoxy-2,3,6-
trimethylphenylsulfonyl)amino]-5-phenylpent-2-en-1-ol 26
By a procedure identical with that described for the preparation
of the mesylate 11 from 10, the alcohol 24 (15.4 g, 32.9 mmol)
was converted into the title compound 26 (17.0 g, 95% yield)
as colourless crystals, mp 101–103 ЊC (from Et2O) (Found: C,
48.05; H, 5.2; N, 2.4. C22H28BrNO6S2 requires C, 48.35; H, 5.2;
N, 2.6%); [α]D28 ϩ13.2 (c 1.59 in CHCl3); δH (270 MHz, CDCl3)
2.03 (3 H, s, CMe), 2.07 (3 H, s, CMe), 2.53 (3 H, s, CMe), 2.66
(1 H, dd, J 13.8 and 9.2, 5-CHH), 2.91 (1 H, dd, J 13.8 and 4.9,
5-CHH), 3.05 (3 H, s, SO2Me), 3.86 (3 H, s, OMe), 4.12 (1 H,
dddd, J 9.2, 8.1, 4.9 and 4.6, 4-H), 4.64 (1 H, d, J 4.6, NH),
4.72–4.75 (2 H, m, 1-CH2), 6.18 (1 H, d, J 8.1, 3-H), 6.54 (1 H, s,
Ph), 7.01–7.06 (2 H, m, Ph), 7.19–7.29 (3 H, m, Ph).
J 3.8, 2-H), 5.43 (1 H, d, J 2.2, C᎐CHH), 5.62 (1 H, dd, J 2.2
᎐
and 1.1, C᎐CHH), 6.96 (2 H, s, Ph), 7.22–7.36 (5 H, m, Ph); m/z
᎐
(FAB) 422 (MHϩ, 81Br), 420 (MHϩ, 79Br), 238, 236, 183, 156,
119 (base peak) and 91.
(2S,3S)-3-Benzyl-2-(1-bromovinyl)-N-(4-methoxy-2,3,6-
trimethylphenylsulfonyl)aziridine 30
By a procedure identical with that described for the prepar-
ation of the aziridine 27 from 11, the mesylate 26 (16.4 g, 30
mmol) was converted into a 97:3 mixture (8.84 g, 65% com-
bined yield) of the title compound 30 and its (2R,3S) isomer, by
treatment with NaH in DMSO at 30 ЊC for 2.5 h. Compound 30
[as a mixture containing 3% of (2R,3S) isomer]: colourless oil
[Found (FAB): (M ϩ H)ϩ, 450.0714. C21H25BrNO3S requires
M ϩ H, 450.0739]; [α]D31 ϩ33.7 (c 0.985 in CHCl3); δH (270 MHz,
CDCl3) 2.16 (3 H, s, CMe), 2.706 (3 H, s, CMe), 2.711 (3 H, s,
CMe), 2.98 (1 H, ddd, J 10.0, 4.1 and 3.8, 3-H), 3.30 (1 H, dd,
J 14.6 and 10.0, PhCHH), 3.52 (1 H, dd, J 14.6 and 4.1,
PhCHH), 3.64 (1 H, d, J 3.8, 2-H), 3.86 (3 H, s, OMe), 5.44
General procedure for aziridination of allylic mesylates (11, 17,
25 and 26) by exposure to sodium hydride in DMSO. (2S,3S)-2-
(1-Bromovinyl)-3-isopropyl-N-(2,4,6-trimethylphenylsulfonyl)-
aziridine 27 from the mesylate 11
To a stirred suspension of NaH (328 mg, 8.2 mmol) in DMSO
(14 cm3) under argon was added a solution of the allylic
mesylate 11 (3.2 g, 6.83 mmol) in DMSO (6 cm3) at room tem-
perature. After 1 h, the mixture was poured into ice–water sat-
urated with NH4Cl (20 cm3). The whole was extracted with
Et2O and the extract was washed with water, and dried over
MgSO4. Usual workup followed by flash chromatography over
silica gel with n-hexane–EtOAc (12:1) gave a 97:3 mixture
(2.23 g, 88% combined yield) of the title compound 27 and
(2R,3S) isomer. Compound 27 [as a mixture containing 3%
of (2R,3S) isomer]: colourless oil [Found (FAB): (M ϩ H)ϩ,
372.0630. C16H23BrNO2S requires M ϩ H, 372.0633]; [α]D27
Ϫ5.50 (c 0.945 in CHCl3); δH (270 MHz, CDCl3) 1.10 (3 H, d,
J 6.8, CMe), 1.21 (3 H, d, J 6.8, CMe), 2.19–2.30 (1 H, m,
Me2CH), 2.30 (3 H, s, CMe), 2.57 (1 H, dd, J 9.5 and 4.3, 3-H),
2.71 (6 H, s, 2 × CMe), 3.39 (1 H, d, J 4.3, 2-H), 5.42 (1 H, d,
(1 H, d, J 1.9, C᎐CHH), 5.66 (1 H, dd, J 1.9 and 1.1, C᎐CHH),
᎐
᎐
6.57 (1 H, s, Ph), 7.22–7.35 (5 H, m, Ph); m/z (FAB) 452 (MHϩ,
81Br), 450 (MHϩ, 79Br), 238, 236, 213, 197, 150, 149 (base peak),
119 and 91.
General procedure for the dehydrobromination of 2-(1-bromo-
vinyl)aziridines (27, 28, 29, and 30) by exposure to t-BuOK in
THF. (2S,3S)-2-Ethynyl-3-isopropyl-N-(2,4,6-trimethylphenyl-
sulfonyl)aziridine 34 and its (2R,3S) isomer 35 from 27
To a stirred solution of t-BuOK (1.5 g, 13.4 mmol) in THF (15
cm3) under argon was added a solution of the aziridine 27 (2.5
2956
J. Chem. Soc., Perkin Trans. 1, 1999, 2949–2962

View Article Online
g, 6.71 mmol) in THF (10 cm3) at Ϫ78 ЊC. The mixture was
stirred for 30 min with warming to 0 ЊC and the mixture was
made acidic with saturated citric acid. Concentration under
reduced pressure gave a residual oil, which was extracted with
Et2O. The extract was washed with water, and dried over
MgSO4. Usual workup followed by flash chromatography over
silica gel with n-hexane–EtOAc (10:1) gave, in order of elution,
ethynylaziridine 35 (0.496 g, 25% yield) and 34 (1.44 g, 74%
yield). Compound 34: 98% ee (2S,3S) by HPLC [Daicel Chiral-
cel OD, n-hexane:propan-2-ol = 98.5:1.5 (0.5 cm3 minϪ1),
(2S,3S)-isomer 25.9 min, (2R,3R)-isomer 28.7 min]; colourless
crystals, mp 73 ЊC [from n-hexane–Et2O (10:1)] (Found: C,
65.7; H, 7.2; N, 4.6. C16H21NO2S requires C, 65.95; H, 7.3; N,
4.8%); [α]D18 Ϫ20.5 (c 0.440 in CHCl3); δH (300 MHz, CDCl3) 0.71
CHCl3); δH (270 MHz, CDCl3) 2.31 (3 H, s, CMe), 2.49 (1 H, d,
᎐
J 2.2, C᎐CH), 2.55 (6 H, s, 2 × CMe), 2.59 (1 H, dd, J 14.0 and
᎐
7.3, PhCHH), 3.01 (1 H, dd, J 14.0 and 4.3, PhCHH), 3.07
(1 H, dd, J 3.8 and 2.2, 2-H), 3.33 (1 H, ddd, J 7.3, 4.3 and 3.8,
3-H), 6.86 (2 H, s, Ph), 6.87–6.92 (2 H, m, Ph), 7.02–7.16 (3 H,
m, Ph). Compound 39: 98% ee (2R,3S) by HPLC [Daicel
Chiralcel OJ, n-hexane:propan-2-ol = 97:3 (0.5 cm3 minϪ1),
(2R,3S)-isomer 61.8 min]; colourless prisms, mp 100 ЊC [from
n-hexane–Et2O (1:1)] (Found: C, 70.5; H, 6.4; N, 3.9. C20H21-
NO2S requires C, 70.8; H, 6.2; N, 4.1%); [α]D28 Ϫ61.9 (c 1.65 in
᎐
CHCl3); δH (270 MHz, CDCl ) 2.297 (1 H, d, J 2.2, C᎐CH),
᎐
3
2.304 (3 H, s, CMe), 2.58 (6 H, s, 2 × CMe), 2.81 (1 H, dd,
J 14.6 and 7.0, PhCHH), 2.96 (1 H, dd, J 14.6 and 5.7,
PhCHH), 3.07 (1 H, ddd, J 7.0, 6.8 and 5.7, 3-H), 3.44 (1 H, dd,
J 6.8 and 2.2, 2-H), 6.88 (2 H, s, Ph), 7.04–7.16 (5 H, m, Ph).
(3 H, d, J 6.7, CMe), 0.90 (3 H, d, J 6.8, CMe), 1.42–1.54 (1 H,
᎐
m, Me CH), 2.30 (3 H, s, CMe), 2.48 (1 H, d, J 2.0, C᎐CH),
᎐
2
2.72 (6 H, s, 2 × CMe), 2.96 (1 H, dd, J 7.0 and 4.2, 3-H), 2.99
(1 H, dd, J 4.2 and 2.0, 2-H), 6.94–6.96 (2 H, m, Ph). Com-
pound 35: 98% ee (2R,3S) by HPLC [Daicel Chiralcel OJ,
n-hexane:propan-2-ol = 98.5:1.5 (0.5 cm3 minϪ1), (2R,3S)-
isomer 15.8 min, (2S,3R)-isomer 17.7 min]; colourless crystals,
mp 70 ЊC [from n-hexane–Et2O (5:1)] (Found: C, 65.85; H, 7.3;
N, 4.7. C16H21NO2S requires C, 65.95; H, 7.3; N, 4.8%); [α]D24
Ϫ61.6 (c 0.941 in CHCl3); δH (300 MHz, CDCl3) 0.84 (3 H, d,
(2S,3S)-3-Benzyl-2-ethynyl-N-(4-methoxy-2,3,6-trimethyl-
phenylsulfonyl)aziridine 40 and its (2R,3S) isomer 41
By a procedure identical with that described for the preparation
of the 2-ethynylaziridines 34 and 35 from 27, the 2-(1-bromo-
vinyl)aziridine 30 (7.5 g, 16.7 mmol) was converted into the
2-ethynylaziridine 40 (2.88 g, 47% yield) and 41 (1.55 g, 25%
yield), by treatment with t-BuOK in THF at Ϫ78→Ϫ20 ЊC for
1 h. Compound 40: 98% ee (2S,3S) by HPLC [Daicel Chiralcel
OD, n-hexane:propan-2-ol = 97:3 (0.5 cm3 minϪ1), (2S,3S)-
isomer 46.9 min]; colourless oil [Found (FAB): (M ϩ H)ϩ,
370.1482. C21H24NO3S requires M ϩ H, 370.1477]; [α]D28 ϩ3.59 (c
J 6.7, CMe), 1.00 (3 H, d, J 6.4, CMe), 1.55–1.68 (1 H, m,
᎐
Me CH), 2.16 (1 H, d, J 1.9, C᎐CH), 2.31 (3 H, s, CMe), 2.55
᎐
2
(1 H, dd, J 9.7 and 6.8, 3-H), 2.70 (6 H, s, 2 × CMe), 3.36 (1 H,
dd, J 6.8 and 1.9, 2-H), 6.95–6.98 (2 H, m, Ph).
0.781 in CHCl3); δH (270 MHz, CDCl3) 2.12 (3 H, s, CMe), 2.48
᎐
(1 H, d, J 2.2, C᎐CH), 2.53 (3 H, s, CMe), 2.54 (3 H, s, CMe),
᎐
(2S,3S)-2-Ethynyl-N-(4-methylphenylsulfonyl)-3-(2-methyl-
propyl)aziridine 36 and its (2R,3S) isomer 37
2.58 (1 H, dd, J 14.6 and 7.6, PhCHH), 3.01 (1 H, dd, J 14.6
and 5.1, PhCHH), 3.06 (1 H, dd, J 4.1 and 2.2, 2-H), 3.32 (1 H,
ddd, J 7.6, 5.1 and 4.1, 3-H), 3.86 (3 H, s, OMe), 6.46 (1 H, s,
Ph), 6.88–6.92 (2 H, m, Ph), 7.01–7.13 (3 H, m, Ph); m/z (FAB)
370 (MHϩ), 213, 197, 156 (base peak), 150, 149, 119 and 91.
Compound 41: 98% ee (2R,3S) by HPLC [Daicel Chiralcel OJ,
n-hexane:propan-2-ol = 93:7 (0.5 cm3 minϪ1), (2R,3S)-isomer
44.3 min]; colourless needles mp 90 ЊC [from n-hexane–Et2O
(2:1)] (Found: C, 68.2; H, 6.3; N, 3.7. C21H23NO3S requires C,
68.3; H, 6.3; N, 3.8%); [α]D28 Ϫ56.3 (c 1.13 in CHCl3); δH (270
By a procedure identical with that described for the preparation
of the 2-ethynylaziridines 34 and 35 from 27, the 2-(1-bromo-
vinyl)aziridine 28 (900 mg, 2.51 mmol) was converted into the
ethynylaziridines 36 (465 mg, 67% yield) and 37 (135 mg, 19%
yield), by treatment with t-BuOK in THF at Ϫ78→Ϫ20 ЊC for
1 h. Compound 36: 98% ee (2S,3S) by HPLC [Daicel Chiralcel
OD, n-hexane:propan-2-ol = 98.5:1.5 (0.5 cm3 minϪ1), (2S,3S)-
isomer 38.2 min]; colourless oil [Found (FAB): (M ϩ H)ϩ,
278.1211. C15H20NO2S requires M ϩ H, 278.1215]; [α]D30 ϩ38.9
(c 0.812 in CHCl3); δH (270 MHz, CDCl3) 0.90 (3 H, d, J 6.8,
CMe), 0.94 (3 H, d, J 6.2, CMe), 1.34–1.45 (1 H, m, Me2-
᎐
MHz, CDCl ) 2.11 (3 H, s, CMe), 2.29 (1 H, d, J 1.9, C᎐CH),
᎐
3
2.55 (3 H, s, CMe), 2.57 (3 H, s, CMe), 2.79 (1 H, dd, J 14.3 and
7.6, PhCHH), 2.96 (1 H, dd, J 14.3 and 5.4, PhCHH), 3.04
(1 H, ddd, J 7.6, 6.8 and 5.4, 3-H), 3.44 (1 H, dd, J 6.8 and 1.9,
2-H), 3.86 (3 H, s, OMe), 6.47 (1 H, s, Ph), 7.02–7.12 (5 H, m,
Ph).
CHCHH), 1.52–1.71 (2 H, m, Me2CHCHH and Me2CH), 2.45
᎐
(4 H, m, CMe and C᎐CH), 2.97 (1 H, dd, J 3.8 and 1.9, 2-H),
᎐
3.09 (1 H, ddd, J 6.8, 6.8 and 3.8, 3-H), 7.32–7.35 (2 H, m, Ph),
7.86–7.89 (2 H, m, Ph); m/z (FAB) 278 (MHϩ, base peak).
Compound 37: 98% ee (2R,3S) by HPLC [Daicel Chiralcel OJ,
n-hexane:propan-2-ol = 93:7 (0.5 cm3 minϪ1), (2R,3S)-isomer
20.9 min]; colourless oil [Found (FAB): (M ϩ H)ϩ, 278.1223.
C15H20NO2S M ϩ H, 278.1215]; [α]D30 Ϫ88.2 (c 0.839 in CHCl3);
δH (270 MHz, CDCl3) 0.920 (3 H, d, J 6.8, CMe), 0.923 (3 H, d,
(3S,4S)-4-[N-(tert-Butoxycarbonyl)amino]-5-methyl-1-
trimethylsilylhex-1-yn-3-ol 43 and its (3R,4S)-isomer 44
To a stirred solution of oxalyl chloride (15.4 cm3, 148 mmol) in
a mixed solvent of CHCl3 (70 cm3) and n-hexane (50 cm3) at
Ϫ78 ЊC under argon was added dropwise a solution of DMSO
(40 cm3, 493 mmol) in CHCl3 (15 cm3). After 45 min, a solution
of the alcohol 42 (20 g, 98.5 mmol) in CHCl3 (50 cm3) was
added to the above reagent at Ϫ78 ЊC, and the mixture was
stirred for 1 h at this temperature. Diisopropylethylamine (120
cm3, 690 mmol) was added to the above solution at Ϫ78 ЊC and
the mixture was stirred for 30 min with warming to 0 ЊC. The
mixture was made acidic with saturated aqueous citric acid, and
the whole was extracted with Et2O. The extract was washed
successively with water, 5% NaHCO3, and water, and dried over
MgSO4. Usual workup gave a crude aldehyde. To a stirred solu-
tion of trimethylsilylacetylene (34.8 cm3, 246 mmol) in dry
THF (50 cm3) under argon was added n-BuLi (1.52 M in
n-hexane; 162 cm3, 246 mmol) at 0 ЊC, and the mixture was
stirred for 20 min at this temperature. The crude aldehyde in dry
THF (50 cm3) was added to the above reagent at Ϫ78 ЊC,
and the mixture was stirred for 2 h at this temperature, followed
by quenching with saturated aqueous NH4Cl (20 cm3). The
whole was extracted with Et2O, and the extract was washed
J 6.5, CMe), 1.48–1.54 (2 H, m, Me2CHCH2), 1.61–1.76 (1 H,
᎐
m, Me CH), 2.20 (1 H, d, J 1.9, C᎐CH), 2.45 (3 H, s, CMe),
᎐
2
2.95 (1 H, ddd, J 7.0, 6.5 and 6.5, 3-H), 3.32 (1 H, dd, J 7.0
and 1.9, 2-H), 7.33–7.37 (2 H, m, Ph), 7.82–7.86 (2 H, m, Ph);
m/z (FAB) 278 (MHϩ, base peak).
(2S,3S)-3-Benzyl-2-ethynyl-N-(2,4,6-trimethylphenylsulfonyl)-
aziridine 38 and its (2R,3S) isomer 39
By a procedure identical with that described for the preparation
of the 2-ethynylaziridines 34 and 35 from 27, the 2-(1-bromo-
vinyl)aziridine 29 (1.33 g, 3.16 mmol) was converted into the
2-ethynylaziridines 38 (558 mg, 52% yield) and 39 (302 mg,
28% yield), by treatment with t-BuOK in THF at Ϫ78→Ϫ20 ЊC
for 1 h. Compound 38: 98% ee (2S,3S) by HPLC [Daicel
Chiralcel OD, n-hexane:propan-2-ol = 96:4 (0.5 cm3 minϪ1),
(2S,3S)-isomer 35.3 min]; colourless needles, mp 104 ЊC [from
n-hexane–Et2O (1:1)] (Found: C, 70.85; H, 6.3; N, 3.8. C20H21-
NO2S requires C, 70.8; H, 6.2; N, 4.1%); [α]D29 ϩ9.76 (c 1.23 in
J. Chem. Soc., Perkin Trans. 1, 1999, 2949–2962
2957

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successively with 5% aqueous citric acid, water, 5% aqueous
NaHCO3, and water, and dried over MgSO4. Usual workup
followed by flash chromatography over silica gel with n-hexane–
EtOAc (8:1) gave, in order of elution, the title compound 43
(9.15 g, 31% yield) and 44 (7.23 g, 25% yield). Compound 43:
colourless crystals, mp 72–73 ЊC (from n-hexane) (Found: C,
59.9; H, 10.0; N, 4.8. C15H29NO3Si requires C, 60.2; H, 9.8; N,
4.7%); [α]D24 ϩ1.90 (c 1.16 in CHCl3); δH (270 MHz, CDCl3) 0.16
(9 H, s, SiMe3), 0.93 (3 H, d, J 7.0, CMe), 0.98 (3 H, d, J 6.5,
CMe), 1.46 (9 H, s, CMe3), 2.00–2.12 (1 H, m, 5-H), 2.84 (1 H,
d, J 5.7, OH), 3.44 (1 H, ddd, J 9.5, 7.0 and 5.7, 4-H), 4.43 (1 H,
dd, J 5.7 and 5.7, 3-H), 4.81 (1 H, d, J 9.5, NH). Compound 44:
colourless oil [Found (FAB): (M ϩ H)ϩ, 300.1999. C15H30NO3-
Si requires M ϩ H, 300.1995]; [α]D24 Ϫ99.7 (c 0.662 in CHCl3);
δH (270 MHz, CDCl3) 0.18 (9 H, s, SiMe3), 0.98 (6 H, d, J 7.0,
CMe2), 1.47 (9 H, s, CMe3), 1.72–1.85 (1 H, m, 5-H), 3.20 (1 H,
d, J 7.3, OH), 3.53–3.61 (1 H, m, 4-H), 4.52 (1 H, dd, J 7.3 and
3.2, 3-H), 4.66 (1 H, d, J 9.7, NH); m/z (FAB) 300 (MHϩ), 244
(base peak), 226, 116, 73, 72, and 57.
(1 H, d, J 9.5, OH), 2.68 (6 H, s, 2 × CMe), 3.17 (1 H, ddd,
J 10.0, 7.0 and 2.4, 4-H), 4.40 (1 H, dd, J 9.5 and 2.4, 3-H), 4.92
(1 H, d, J 10.0, NH), 6.97 (2 H, s, Ph); m/z (FAB) 382 (MHϩ),
364, 254, 183, 167, 119 (base peak), 73 and 72.
(3R,4S)-5-Methyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]-
hex-1-yn-3-ol 48
By a procedure identical with that described for the preparation
of 46 from 45, 47 (1.8 g, 4.72 mmol) was converted into the title
compound 48 (1.21 g, 83% yield) as colourless crystals, 98% ee
(3R,4S) by HPLC [Daicel Chiralcel OD, n-hexane:propan-2-
ol = 98:4 (0.5 cm3 minϪ1), (3R,4S)-isomer 34.2 min]; mp 122 ЊC
[from n-hexane–Et2O (2:1)] (Found: C, 62.0; H, 7.55; N, 4.5.
C16H23NO3S requires C, 62.1; H, 7.5; N, 4.5%); [α]D23 Ϫ55.6
(c 0.774 in CHCl3); δH (270 MHz, CDCl3) 0.846 (3 H, d, J 7.0,
CMe), 0.853 (3 H, d, J 6.8, CMe), 1.72–1.85 (1 H, m, 5-H), 2.30
(3 H, s, CMe), 2.55 (1 H, d, J 1.9, 1-H), 2.67 (6 H, s, 2 × CMe),
2.88 (1 H, d, J 9.7, OH), 3.15 (1 H, ddd, J 10.3, 7.6 and 3.0,
4-H), 4.45 (1 H, ddd, J 9.7, 3.0 and 1.9, 3-H), 4.95 (1 H, d,
J 10.3, NH), 6.97 (2 H, s, Ph).
(3S,4S)-5-Methyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]-
1-trimethylsilylhex-1-yn-3-ol 45
(3S,4S)-4-[N-(tert-Butoxycarbonyl)amino]-5-methylhex-1-yn-3-
ol 49
By a procedure similar to that described for the preparation of
21 from 19, 43 (2.1 g, 7.0 mmol) was converted into the title
compound 45 (1.76 g, 66% yield) as colourless needles, mp
107 ЊC [from n-hexane–Et2O (2:1)] (Found: C, 60.0; H, 8.0; N,
3.7. C19H31NO3SSi requires C, 59.8; H, 8.2; N, 3.7%); [α]D20 Ϫ62.8
(c 1.38 in CHCl3); δH (270 MHz, CDCl3) 0.15 (9 H, s, SiMe3),
0.69 (3 H, d, J 6.8, CMe), 0.85 (3 H, d, J 7.0, CMe), 2.05–2.17
(1 H, m, 5-H), 2.30 (3 H, s, CMe), 2.61 (1 H, d, J 5.4, OH), 2.67
(6 H, s, 2 × CMe), 3.20 (1 H, ddd, J 10.0, 6.8 and 3.8, 4-H), 4.29
(1 H, dd, J 6.8 and 5.4, 3-H), 4.86 (1 H, d, J 10.0, NH), 6.95
(2 H, s, Ph).
By a procedure identical with that described for the preparation
of 46 from 45, 43 (3.0 g, 7.96 mmol) was converted into the title
compound 49 (1.66 g, 72% yield) as colourless needles, mp 42–
43 ЊC [from n-hexane–Et2O (3:1)] (Found: C, 63.3; H, 9.25; N,
6.2. C12H21NO3 requires C, 63.4; H, 9.3; N, 6.2%); [α]D21 Ϫ8.75
(c 0.869 in CHCl3); δH (270 MHz, CDCl3) 0.94 (3 H, d, J 6.5,
CMe), 0.99 (3 H, d, J 7.0, CMe), 1.46 (9 H, s, CMe3), 2.05–2.18
(1 H, m, 5-H), 2.47 (1 H, d, J 1.4, 1-H), 3.06 (1 H, d, J 5.4, OH),
3.42–3.51 (1 H, m, 4-H), 4.42–4.48 (1 H, m, 3-H), 4.83 (1 H, d,
J 9.2, NH).
(3S,4S)-5-Methyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]-
hex-1-yn-3-ol 46
(3R,4S)-4-[N-(tert-Butoxycarbonyl)amino]-5-methylhex-1-yn-3-
ol 50
To a stirred solution of 45 (1.55 g, 4.06 mmol) in THF (15 cm3)
was added dropwise tetrabutylammonium fluoride (1.0 M in
THF; 4.06 cm3, 4.06 mmol) at 0 ЊC, and the mixture was stirred
for 15 min at this temperature. The mixture was made acidic
with saturated aqueous citric acid, followed by concentration
under reduced pressure to give a residual oil, which was
extracted with Et2O. The extract was washed with water, and
dried over MgSO4. Concentration under reduced pressure gave
a crystalline mass, which was recrystallized from n-hexane–
Et2O (2:1) to give the title compound 46 (1.21 g, 96% yield) as
colourless needles, 98% ee (3S,4S) by HPLC [Daicel Chiralcel
OD, n-hexane:propan-2-ol = 96:4 (0.5 cm3 minϪ1), (3S,4S)-
isomer 42.3 min]; mp 138 ЊC [from n-hexane–Et2O (2:1)]
(Found: C, 62.0; H, 7.4; N, 4.5. C16H23NO3S requires C, 62.1; H,
7.5; N, 4.5%); [α]D25 Ϫ32.4 (c 0.978 in CHCl3); δH (270 MHz,
CDCl3) 0.72 (3 H, d, J 7.0, CMe), 0.88 (3 H, d, J 6.8, CMe),
2.01–2.14 (1 H, m, 5-H), 2.27 (1 H, d, J 1.9, 1-H), 2.29 (3 H, s,
CMe), 2.62–2.66 (1 H, m, OH), 2.66 (6 H, s, 2 × CMe), 3.23
(1 H, ddd, J 9.5, 5.4 and 5.4, 4-H), 4.37 (1 H, ddd, J 5.4, 5.4 and
1.9, 3-H), 4.95 (1 H, d, J 9.5, NH), 6.94 (2 H, s, Ph).
By a procedure identical with that described for the preparation
of 46 from 45, 44 (1.5 g, 5.0 mmol) was converted into the title
compound 50 (1.03 g, 91% yield) as colourless needles, mp
81 ЊC [from n-hexane–Et2O (3:1)] (Found: C, 63.2; H, 9.3; N,
5.9. C12H21NO3 requires C, 63.4; H, 9.3; N, 6.2%); [α]D29 Ϫ84.3
(c 1.01 in CHCl3); δH (270 MHz, CDCl3) 0.97–1.01 (6 H, m,
2 × CMe), 1.46 (9 H, s, CMe3), 1.72–1.86 (1 H, m, 5-H), 2.46
(1 H, d, J 2.2, 1-H), 3.30 (1 H, d, J 7.6, OH), 3.59 (1 H, ddd,
J 9.2, 8.9 and 3.5, 4-H), 4.53–4.58 (1 H, m, 3-H), 4.70 (1 H, d,
J 8.9, NH).
(3S,4S)-4-[N-(tert-Butoxycarbonyl)amino]-5-(tert-butyl-
dimethylsiloxy)-1-trimethylsilylpent-1-yn-3-ol 52 and its
(3R,4S)-isomer 53
To a stirred solution of the ester 51 (32 g, 96 mmol) in toluene
(200 cm3) was added dropwise DIBAL-H (1.0 M in toluene;
192 cm3, 192 mmol) over 30 min at Ϫ78 ЊC under argon, and
the mixture was stirred for 1 h at this temperature. Saturated
aqueous citric acid (100 cm3) was added to the mixture, and the
whole was extracted with Et2O. The extract was washed with
water and brine, and dried over MgSO4. Concentration under
reduced pressure gave a crude aldehyde. To a stirred solution of
trimethylsilylacetylene (34.0 cm3, 240 mmol) in dry THF (100
cm3) under argon was added n-BuLi (1.53 M in n-hexane; 157
cm3, 240 mmol) at 0 ЊC, and the mixture was stirred for 30 min
at this temperature. The crude aldehyde in dry THF (50 cm3)
was added to the above reagent at Ϫ78 ЊC, and the mixture was
stirred for 1 h at this temperature, followed by quenching with
saturated aqueous NH4Cl (20 cm3). The whole was extracted
with Et2O, and the extract was washed successively with satur-
ated aqueous citric acid, water, saturated aqueous NaHCO3,
and water, and dried over MgSO4. Usual workup followed by
(3R,4S)-5-Methyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]-
1-trimethylsilylhex-1-yn-3-ol 47
By a procedure identical with that described for the preparation
of 21 from 19, 44 (2.10 g, 7.0 mmol) was converted into the title
compound 47 (2.00 g, 75% yield). 98% ee (3R,4S) by HPLC
[Daicel Chiralcel OD, n-hexane:propan-2-ol = 98:2 (0.5
cm3 minϪ1), (3R,4S)-isomer 22.4 min]; colourless oil [Found
(FAB): (M ϩ H)ϩ, 382.1877. C19H32NO3SSi requires M ϩ H,
382.1872]; [α]D23 Ϫ81.2 (c 1.30 in CHCl3); δH (270 MHz, CDCl3)
0.19 (9 H, s, SiMe3), 0.86 (3 H, d, J 6.5, CMe), 0.91 (3 H, d,
J 7.0, CMe), 1.69–1.82 (1 H, m, 5-H), 2.30 (3 H, s, CMe), 2.45
2958
J. Chem. Soc., Perkin Trans. 1, 1999, 2949–2962

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flash chromatography over silica gel with n-hexane–Et2O (10:3)
gave, in order of elution, the title compound 52 (6.86 g, 18%
yield), and 53 (5.03 g, 13% yield). Compound 52: colourless oil
[Found (FAB): (M ϩ H)ϩ, 402.2505. C19H40NO4Si2 requires
M ϩ H, 402.2496]; [α]D22 ϩ2.23 (c 1.35 in CHCl3); δH (270 MHz,
CDCl3) 0.09 (6 H, s, SiMe2), 0.17 (9 H, s, SiMe3), 0.90 (9 H, s,
CMe3), 1.46 (9 H, s, CMe3), 3.44 (1 H, d, J 5.4, OH), 3.74–3.90
(3 H, m, 5-CH2 and 4-H), 4.54 (1 H, dd, J 5.4 and 5.1, 3-H),
4.97–5.06 (1 H, m, NH); m/z (FAB) 402 (MHϩ), 346, 303, 302
(base peak), 288, 218, 174, 89, 75, 73 and 57. Compound 53:
colourless oil [Found (FAB): (M ϩ H)ϩ, 402.2490. C19H40NO4-
Si2 requires M ϩ H, 402.2496]; [α]D22 ϩ3.11 (c 0.996 in CHCl3);
δH (270 MHz, CDCl3) 0.09 (3 H, s, SiMe), 0.11 (3 H, s, SiMe),
0.18 (9 H, s, SiMe3), 0.91 (9 H, s, CMe3), 1.46 (9 H, s, CMe3),
3.65 (1 H, d, J 9.5, OH), 3.74–3.81 (2 H, m, 4-H and 5-CHH),
4.19–4.27 (1 H, m, 5-CHH), 4.50 (1 H, dd, J 9.5 and 4.1, 3-H),
5.24 (1 H, d, J 7.6, NH); m/z (FAB) 402 (MHϩ), 346, 303, 302
(base peak), 288, 218, 174, 89, 75, 73 and 57.
n-hexane–Et2O (1:1) gave the title compound 56 (2.03 g, 90%
yield) as colourless crystals, 97% ee (3S,4S) by HPLC [Daicel
Chiralcel OD, n-hexane:propan-2-ol = 95:5 (0.5 cm3 minϪ1),
(3R,4R)-isomer 18.3 min, (3S,4S)-isomer 19.9 min]; mp 117 ЊC
[n-hexane–Et2O (1:1)] (Found: C, 58.1; H, 8.2; N, 3.4.
C20H33NO4SSi requires C, 58.4; H, 8.1; N, 3.4%); [α]D24 ϩ21.7
(c 0.813 in CHCl3); δH (270 MHz, CDCl3) 0.04 (6 H, s, SiMe2),
0.87 (9 H, s, CMe3), 2.30 (3 H, s, CMe), 2.33 (1 H, d, J 1.9,
᎐
C᎐CH), 2.66 (6 H, s, 2 × CMe), 3.23 (1 H, d, J 5.1, OH), 3.29–
᎐
3.38 (1 H, m, 4-H), 3.59 (1 H, dd, J 10.3 and 5.9, 5-CHH), 3.83
(1 H, dd, J 10.3 and 3.0, 5-CHH), 4.43 (1 H, ddd, J 5.1, 5.1 and
1.9, 3-H), 5.21 (1 H, d, J 9.5, NH), 6.96 (2 H, s, Ph).
(3R,4S)-5-(tert-Butyldimethylsiloxy)-4-[N-(2,4,6-trimethyl-
phenylsulfonyl)amino]-1-trimethylsilylpent-1-yn-3-ol 57 and
(2S,3R)-2-[N-(2,4,6-trimethylphenylsulfonyl)amino]-5-
trimethylsilylpent-4-yne-1,3-diol 58
By a procedure identical with that described for the preparation
of 21 from 19, 53 (2.41 g, 6 mmol) was converted into the title
compound 57 (1.49 g, 51% yield) and 58 (315 mg, 14% yield).
Compound 57: 92% ee (3R,4S) by HPLC [Daicel Chiralcel OD,
n-hexane:propan-2-ol = 98:2 (0.5 cm3 minϪ1), (3S,4R)-isomer
15.6 min, (3R,4S)-isomer 17.1 min]; colourless oil [Found
(FAB): (M ϩ H)ϩ, 484.2376. C23H42NO4SSi2 requires M ϩ H,
484.2373]; [α]D26 ϩ4.40 (c 0.955 in CHCl3); δH (270 MHz, CDCl3)
0.02 (3 H, s, SiMe), 0.04 (3 H, s, SiMe), 0.16 (9 H, s, SiMe3),
0.87 (9 H, s, CMe3), 2.30 (3 H, s, CMe), 2.66 (6 H, s, 2 × CMe),
3.15 (1 H, d, J 9.5, OH), 3.32–3.39 (1 H, m, 4-H), 3.60 (1 H, dd,
J 10.3 and 4.3, 5-CHH), 4.08 (1 H, dd, J 10.3 and 3.2, 5-CHH),
4.36 (1 H, dd, J 9.5 and 3.2, 3-H), 5.35 (1 H, d, J 9.2, NH), 6.96
(2 H, s, Ph); m/z (FAB) 484 (MHϩ), 468, 426, 356, 283, 183, 173,
119, 89 and 73 (base peak). Compound 58: colourless crystals,
mp 95 ЊC [from n-hexane–Et2O (2:1)] (Found: C, 55.0; H, 7.2;
N, 3.9. C17H27NO4SSi requires C, 55.25; H, 7.4; N, 3.8%); [α]D26
Ϫ16.0 (c 0.562 in CHCl3); δH (270 MHz, CDCl3) 0.17 (9 H, s,
SiMe3), 2.25 (1 H, dd, J 8.4 and 4.3, 1-OH), 2.31 (3 H, s, CMe),
2.67 (6 H, s, 2 × CMe), 2.77 (1 H, d, J 7.3, 3-OH), 3.29–3.36
(1 H, m, 2-H), 3.58 (1 H, ddd, J 11.3, 8.4 and 4.6, 1-CHH), 4.02
(1 H, ddd, J 11.3, 4.3 and 4.1, 1-CHH), 4.47 (1 H, dd, J 7.3 and
3.2, 3-H), 5.53 (1 H, d, J 8.6, NH), 6.97 (2 H, s, Ph).
(3S,4S)-5-(tert-Butyldimethylsiloxy)-4-[N-(2,4,6-trimethyl-
phenylsulfonyl)amino]-1-trimethylsilylpent-1-yn-3-ol 54 and
(2S,3S)-2-[N-(2,4,6-trimethylphenylsulfonyl)amino]-5-trimethyl-
silylpent-4-yne-1,3-diol 55
By a procedure similar to that described for the preparation of
21 from 19, 52 (3.01 g, 7.5 mmol) was converted into the title
compound 54 (2.26 g, 62% yield) and 55 (471 mg, 17% yield).
Compound 54: colourless crystals, mp 84 ЊC (from n-hexane)
[Found (FAB): (M ϩ H)ϩ, 484.2366. C23H42NO4SSi2 requires
M ϩ H, 484.2373]; [α]D23 Ϫ11.2 (c 0.845 in CHCl3); δH (270 MHz,
CDCl3) 0.04 (6 H, s, SiMe2), 0.15 (9 H, s, SiMe3), 0.87 (9 H, s,
CMe3), 2.30 (3 H, s, CMe), 2.66 (6 H, s, 2 × CMe), 3.26 (1 H, d,
J 5.1, OH), 3.26–3.35 (1 H, m, 4-H), 3.53 (1 H, dd, J 10.3 and
5.7, 5-CHH), 3.85 (1 H, dd, J 10.3 and 3.0, 5-CHH), 4.36 (1 H,
dd, J 6.2 and 5.1, 3-H), 5.17 (1 H, d, J 9.2, NH), 6.96 (2 H, s,
Ph); m/z (FAB) 484 (MHϩ), 468, 426, 356, 173, 119, 89, 75 and
73 (base peak). Compound 55: colourless crystals, mp 95 ЊC
[from n-hexane–Et2O (2:1)] (Found: C, 55.2; H, 7.5; N, 3.7.
C17H27NO4SSi requires C, 55.25; H, 7.4; N, 3.8%); [α]D23 Ϫ16.1
(c 0.843 in CHCl3); δH (270 MHz, CDCl3) 0.15 (9 H, s, SiMe3),
2.27 (1 H, dd, J 5.4 and 5.4, 1-OH), 2.30 (3 H, s, CMe), 2.67
(6 H, s, 2 × CMe), 2.72 (1 H, d, J 4.1, 3-OH), 3.24–3.33 (1 H, m,
2-H), 3.72 (1 H, ddd, J 11.9, 6.5 and 5.4, 1-CHH), 3.86 (1 H,
ddd, J 11.9, 5.4 and 3.5, 1-CHH), 4.48 (1 H, dd, J 4.9 and 4.1,
3-H), 5.30 (1 H, d, J 7.6, NH), 6.97 (2 H, s, Ph).
(3R,4S)-5-(tert-Butyldimethylsiloxy)-4-[N-(2,4,6-trimethyl-
phenylsulfonyl)amino]pent-1-yn-3-ol 59
By a procedure identical with that described for the preparation
of 56 from 54, 57 (1.64 g, 3.39 mmol) was converted into the
title compound 59 (1.32 g, 95% yield). 92% ee (3R,4S) by
HPLC [Daicel Chiralcel OD, n-hexane:propan-2-ol = 95:5
(0.5 cm3 minϪ1), (3S,4R)-isomer 18.6 min, (3R,4S)-isomer
20.5 min]; colourless oil [Found (FAB): (M ϩ H)ϩ, 412.1975.
C20H34NO4SSi requires M ϩ H, 412.1978]; [α]D26 ϩ13.3 (c 0.813
in CHCl3); δH (270 MHz, CDCl3) 0.02 (3 H, s, SiMe), 0.03 (3 H,
s, SiMe), 0.86 (9 H, s, CMe3), 2.30 (3 H, s, CMe), 2.50 (1 H, d,
J 1.9, 1-H), 2.66 (6 H, s, 2 × CMe), 3.25 (1 H, d, J 9.5, OH),
3.31–3.39 (1 H, m, 4-H), 3.61 (1 H, dd, J 10.3 and 4.6, 5-CHH),
4.04 (1 H, dd, J 10.3 and 3.2, 5-CHH), 4.37 (1 H, ddd, J 9.5, 3.2
and 1.9, 3-H), 5.35 (1 H, d, J 9.2, NH), 6.96 (2 H, s, Ph); m/z
(FAB) 412 (MHϩ, base peak), 354, 280, 173, 167, 119, 89 and
73.
(3S,4S)-5-(tert-Butyldimethylsiloxy)-4-[N-(2,4,6-trimethyl-
phenylsulfonyl)amino]-1-trimethylsilylpent-1-yn-3-ol 54 from 55
To a stirred solution of 55 (450 mg, 1.21 mmol) in a mixed
solvent of CHCl3 (3 cm3) and DMF (3 cm3) were added imid-
azole (98.6 mg, 1.45 mmol) and tert-butyldimethylsilyl chloride
(219 mg, 1.45 mmol) at 0 ЊC, and the mixture was stirred for 2 h
at this temperature. Saturated aqueous NaHCO3 (2 cm3) was
added to the mixture, and the whole was extracted with Et2O.
The extract was washed successively with saturated aqueous
citric acid, water, saturated aqueous NaHCO3, and water,
and dried over MgSO4. Usual workup followed by flash chrom-
atography over silica gel with n-hexane–EtOAc (6:1) gave the
title compound 54 (490 mg, 83% yield) as colourless crystals
from n-hexane.
General procedure for the preparation of 1,3-oxazolidin-2-ones
(60, 62, 64, and 65)
(3S,4S)-5-(tert-Butyldimethylsiloxy)-4-[N-(2,4,6-trimethyl-
phenylsulfonyl)amino]pent-1-yn-3-ol 56
(4S,5S)-5-Ethynyl-4-isopropyl-1,3-oxazolidin-2-one 60. To a
stirred suspension of NaH (9.6 mg, 0.4 mmol) in DMF (2 cm3)
under argon was added 43 (60 mg, 0.2 mmol) in a mixed solvent
of dry THF (1 cm3) and DMF (1 cm3) at 0 ЊC, and the mixture
was stirred for 1 h. Saturated aqueous NH4Cl (3 cm3) was added
to the mixture at Ϫ78 ЊC, and the whole was extracted with
Et2O. The extract was washed with water, and dried over
To a stirred solution of 54 (2.64 g, 5.45 mmol) in MeOH (15
cm3) was added dropwise NaOMe (1.0 M solution in MeOH;
0.545 cm3, 0.545 mmol) at 0 ЊC, and the mixture was stirred for
4.5 h at room temperature. Concentration under reduced pres-
sure gave a crystalline mass, which was filtered though a short
pad of SiO2 with n-hexane–CHCl3 (1:1). Recrystallization from
J. Chem. Soc., Perkin Trans. 1, 1999, 2949–2962
2959

View Article Online
MgSO4. Usual workup followed by flash chromatography over
silica gel with n-hexane–EtOAc (3:1) gave the title compound
60 (22 mg, 72% yield) as a colourless oil [Found (FAB):
(M ϩ H)ϩ, 154.0872. C8H12NO2 requires M ϩ H, 154.0868];
[α]D24 Ϫ48.2 (c 1.29 in CHCl3); δH (270 MHz, CDCl3) 0.97 (3 H, d,
described for the preparation of the 1,3-oxazolidin-2-one 60
from 43, the alcohol 53 (201 mg, 0.5 mmol) was converted into
the title compound 65 (68 mg, 53% yield) as a colourless oil
[Found (FAB): (M ϩ H)ϩ, 256.1374. C12H22NO3Si requires
M ϩ H, 256.1369]; [α]D23 Ϫ34.4 (c 0.194 in CHCl3); δH (270 MHz,
J 6.8, CMe), 0.98 (3 H, d, J 6.5, CMe), 1.70–1.87 (1 H, m,
CDCl3) 0.08 (3 H, s, SiMe), 0.09 (3 H, s, SiMe), 0.90 (9 H, s,
᎐
᎐
Me CH), 2.69 (1 H, d, J 2.4, C᎐CH), 3.60–3.66 (1 H, m, 4-H),
CMe ), 2.69 (1 H, d, J 2.2, C᎐CH), 3.79 (1 H, dd, J 10.3 and 7.8,
᎐
᎐
2
3
4.83 (1 H, dd, J 5.9 and 2.4, 5-H), 7.17 (1 H, br s, NH); m/z
OCHH), 3.83 (1 H, dd, J 10.3 and 4.9, OCHH), 3.96 (1 H, ddd,
J 7.8, 7.8 and 4.9, 4-H), 5.30 (1 H, dd, J 7.8 and 2.2, 5-H), 5.76–
5.87 (1 H, m, NH); m/z (FAB) 256 (MHϩ, base peak), 240, 198,
168, 154, 137, 115, 105, 89, 75, 73 and 59.
(FAB) 154 (MHϩ, base peak), 137, 95, 81, 69, 57, 55 and 43.
(4S,5S)-5-Ethynyl-4-isopropyl-N-(2,4,6-trimethylphenyl-
sulfonyl)-1,3-oxazolidin-2-one 61. To a stirred suspension of
NaH (1.9 mg, 0.078 mmol) in DMF (0.2 cm3) were added 1,3-
oxazolidin-2-one 60 (10 mg, 0.065 mmol) in THF (0.1 cm3) and
2,4,6-trimethylphenylsulfonyl chloride (16 mg, 0.072 mmol) in
THF (0.1 cm3) at 0 ЊC under argon. The mixture was stirred for
1 h at this temperature. Saturated aqueous NH4Cl (1 cm3) was
added to the mixture, and the whole was extracted with Et2O.
The extract was washed with water, and dried over MgSO4.
Usual workup followed by flash chromatography over silica gel
with n-hexane–EtOAc (10:1) gave the title compound 61 (10
mg, 46% yield) as colourless crystals, mp 156–158 ЊC [from
n-hexane–Et2O (3:1)] [Found (FAB): (M ϩ H)ϩ, 336.1273.
C17H22NO4S requires M ϩ H, 336.1269]; [α]D25 ϩ208 (c 0.488 in
CHCl3); δH (270 MHz, CDCl3) 1.06 (6 H, d, J 7.0, 2 × CMe),
General procedure for the aziridination of ethynyl amino alcohols
(43, 44, 46, 48, 49, 50, 54, 56, 57, and 59) under Mitsunobu
conditions (Table 1)
(2R,3S)-N-(tert-Butoxycarbonyl)-3-isopropyl-2-(2-trimethyl-
silylethynyl)aziridine 66 from 43 (Table 1, entry 1). To a stirred
solution of the amino alcohol 43 (300 mg, 1 mmol) and tri-
phenylphosphine (393 mg, 1.5 mmol) in dry THF was added
dropwise a solution of diethyl azodicarboxylate (40% in tolu-
ene; 0.601 cm3, 1.5 mmol) at 0 ЊC and the mixture was stirred
for 30 min at room temperature. Concentration under reduced
pressure followed by flash chromatography over silica gel with
n-hexane–EtOAc (20:1) gave the title compound 66 (269
mg, 96% yield) as a colourless oil [Found (FAB): (M ϩ H)ϩ,
282.1887. C15H28NO2Si requires M ϩ H, 282.1889]; [α]D28 Ϫ128
(c 1.03 in CHCl3); δH (270 MHz, CDCl3) 0.16 (9 H, s, SiMe3),
1.01 (3 H, d, J 7.0, CMe), 1.16 (3 H, d, J 6.5, CMe), 1.44 (9 H, s,
CMe3), 1.50–1.68 (1 H, m, Me2CH), 2.14 (1 H, dd, J 9.2 and
6.2, 3-H), 2.98 (1 H, d, J 6.2, 2-H); m/z (FAB), 282 (MHϩ), 281,
226 (base peak), 181, 73 and 57.
2.32 (3 H, s, CMe), 2.55–2.67 (1 H, m, Me2CH), 2.69 (1 H, d,
᎐
J 2.4, C᎐CH), 2.72 (6 H, s, 2 × CMe), 4.47 (1 H, dd, J 3.0 and
᎐
1.9, 4-H), 4.90 (1 H, dd, J 2.4 and 1.9, 5-H), 6.99 (2 H, s, Ph);
m/z (FAB) 336 (MHϩ, base peak), 183, 137 and 119.
(4S,5R)-5-Ethynyl-4-isopropyl-1,3-oxazolidin-2-one 62. By a
procedure identical with that described for the preparation of
the 1,3-oxazolidin-2-one 60 from 43, the alcohol 44 (60 mg, 0.2
mmol) was converted into the title compound 62 (15 mg, 49%
yield) as a colourless oil [Found (FAB): (M ϩ H)ϩ, 154.0862.
C8H12NO2 requires M ϩ H, 154.0868]; [α]D24 ϩ41.2 (c 1.19 in
CHCl3); δH (270 MHz, CDCl3) 0.97 (3 H, d, J 6.8, CMe), 1.05
(3 H, d, J 6.5, CMe), 2.07–2.20 (1 H, m, Me2CH), 2.70 (1 H, d,
(2S,3S)-N-(tert-Butoxycarbonyl)-3-isopropyl-2-(2-trimethyl-
silylethynyl)aziridine 67 (Table 1, entry 2). A colourless oil
[Found (FAB): (M ϩ H)ϩ, 282.1894. C15H28NO2Si requires
M ϩ H, 282.1889]; [α]D27 ϩ25.4 (c 0.906 in CHCl3); δH (270 MHz,
CDCl3) 0.16 (9 H, s, SiMe3), 1.01 (3 H, d, J 7.0, CMe), 1.02
(3 H, d, J 6.5, CMe), 1.37–1.49 (1 H, m, Me2CH), 1.50 (9 H,
s, CMe3), 2.43 (1 H, dd, J 7.3 and 3.2, 3-H), 2.73 (1 H, d, J 3.2,
2-H); m/z (FAB) 282 (MHϩ), 281, 226 (base peak), 181, 73 and
57.
᎐
J 2.2, C᎐CH), 3.62 (1 H, dd, J 8.1 and 7.8, 4-H), 5.25 (1 H, dd,
᎐
J 8.1 and 2.2, 5-H), 6.82–6.95 (1 H, m, NH); m/z (FAB) 154
(MHϩ, base peak), 137, 136, 110, 107, 77 and 43.
(4S,5R)-5-Ethynyl-4-isopropyl-N-(2,4,6-trimethylphenyl-
sulfonyl)-1,3-oxazolidin-2-one 63. By a procedure identical with
that described for the preparation of 61 from 60, 62 (10 mg,
0.065 mmol) was converted into the title compound 63 (19 mg,
87% yield) as colourless crystals, mp 189–191 ЊC [from Et2O–
CHCl3 (5:1)] [Found (FAB): (M ϩ H)ϩ, 336.1263. C17H22NO4S
requires M ϩ H, 336.1269]; [α]D23 ϩ170 (c 0.637 in CHCl3);
δH (270 MHz, CDCl3) 1.22 (3 H, d, J 6.5, CMe), 1.30 (3 H, d,
(2R,3S)-N-(tert-Butoxycarbonyl)-2-ethynyl-3-isopropyl-
aziridine 68 (Table 1, entry 5). A colourless oil [Found (CI):
(M ϩ H)ϩ, 210.1499. C12H20NO2 requires M ϩ H, 210.1494];
[α]D28 Ϫ106 (c 1.18 in CHCl3); δH (270 MHz, CDCl3) 1.02 (3 H, d,
J 6.5, CMe), 1.16 (3 H, d, J 6.5, CMe), 1.45 (9 H, s, CMe3),
1.51–1.68 (1 H, m, Me2CH), 2.15 (1 H, dd, J 9.5 and 6.5, 3-H),
᎐
2.16 (1 H, d, J 1.9, C᎐CH), 2.98 (1 H, dd, J 6.5 and 1.9, 2-H);
᎐
J 7.3, CMe), 2.30 (3 H, s, CMe), 2.48–2.62 (1 H, m, Me2CH),
m/z (CI) 210 (MHϩ), 194, 182, 155, 154 (base peak), 110, 98.
᎐
2.65 (6 H, s, 2 × CMe), 2.85 (1 H, d, J 2.2, C᎐CH), 4.49 (1 H,
᎐
dd, J 7.3 and 2.4, 4-H), 5.24 (1 H, dd, J 7.3 and 2.2, 5-H), 6.98
(2 H, s, Ph); m/z (FAB) 336 (MHϩ, base peak), 183, 137 and
119.
(2S,3S)-N-(tert-Butoxycarbonyl)-2-ethynyl-3-isopropyl-
aziridine 69 (Table 1, entry 6). A colourless oil [Found (CI):
210.1493. C12H20NO2 requires M ϩ H, 210.1494]; [α]D28 Ϫ106 (c
1.18 in CHCl3); δH (270 MHz, CDCl3) 1.00 (3 H, d, J 7.0, CMe),
(4S,5S)-4-[(tert-Butyldimethylsiloxy)methyl]-5-ethynyl-1,3-
oxazolidin-2-one 64. By a procedure identical with that
described for the preparation of the 1,3-oxazolidin-2-one 60
from 43, the alcohol 52 (127 mg, 0.316 mmol) was converted
into the title compound 64 (31 mg, 38% yield) as a colourless
oil [Found (FAB): (M ϩ H)ϩ, 256.1364. C12H22NO3Si requires
M ϩ H, 256.1369]; [α]D23 Ϫ65.7 (c 0.280 in CHCl3); δH (270 MHz,
1.04 (3 H, d, J 6.8, CMe), 1.36–1.53 (1 H, m, Me2CH), 1.49
᎐
(9 H, s, CMe ), 2.24 (1 H, d, J 1.9, C᎐CH), 2.44 (1 H, dd, J 7.6
᎐
3
and 3.2, 3-H), 2.71 (1 H, dd, J 3.2 and 1.9, 2-H); m/z (CI)
210 (MHϩ), 194, 182, 155, 154 (base peak), 110.
(2R,3R)-3-[(tert-Butyldimethylsiloxy)methyl]-N-(2,4,6-
trimethylphenylsulfonyl)-2-(2-trimethylsilylethynyl)aziridine 70
(Table 1, entry 7). A colourless oil [Found (FAB): (M ϩ H)ϩ,
466.2259. C23H40NO3SSi2 requires M ϩ H, 466.2267]; [α]D27
Ϫ38.6 (c 0.273 in CHCl3); δH (270 MHz, CDCl3) Ϫ0.05 (3 H, s,
SiMe), Ϫ0.02 (3 H, s, SiMe), 0.15 (9 H, s, SiMe3), 0.81 (9 H, s,
CMe3), 2.30 (3 H, s, CMe), 2.69 (6 H, s, 2 × CMe), 3.04 (1 H,
ddd, J 6.8, 5.9 and 5.4, 2-H), 3.43 (1 H, d, J 6.8, 3-H), 3.66 (1 H,
dd, J 11.3 and 5.9, OCHH), 3.75 (1 H, dd, J 11.3 and 5.4,
CDCl3) 0.07 (6 H, s, SiMe2), 0.90 (9 H, s, CMe3), 2.67 (1 H, d,
᎐
J 1.9, C᎐CH), 3.60–3.72 (2 H, m, OCH ), 3.93 (1 H, ddd, J 5.1,
᎐
2
5.1 and 4.9, 4-H), 5.00 (1 H, dd, J 4.9 and 1.9, 5-H), 6.53 (1 H,
br s, NH); m/z (FAB) 256 (MHϩ, base peak), 240, 198, 168, 147,
137, 115, 89, 75, 73 and 59.
(4S,5R)-4-[(tert-Butyldimethylsiloxy)methyl]-5-ethynyl-1,3-
oxazolidin-2-one 65. By a procedure identical with that
2960
J. Chem. Soc., Perkin Trans. 1, 1999, 2949–2962

View Article Online
OCHH), 6.96 (2 H, s, Ph); m/z (FAB) 466 (MHϩ), 408, 378, 229,
119, 89 and 73 (base peak).
oil [Found (FAB): (M ϩ H)ϩ, 364.1761. C19H30NO2SSi requires
M ϩ H, 364.1766]; [α]D19 ϩ47.4 (c 1.01 in CHCl3); δH (270 MHz,
CDCl3) 0.18 (9 H, s, SiMe3), 0.76 (3 H, d, J 6.8, CMe), 0.93
(3 H, d, J 7.0, CMe), 1.44–1.58 (1 H, m, Me2CH), 2.30 (3 H, s,
CMe), 2.72 (6 H, s, 2 × CMe), 2.95–3.00 (2 H, m, 2-H and 3-H),
6.94 (2 H, s, Ph); m/z (FAB) 364 (MHϩ, base peak), 348, 229,
181, 180, 167, 119 and 73.
(2R,3R)-3-[(tert-Butyldimethylsiloxy)methyl]-2-ethynyl-N-
(2,4,6-trimethylphenylsulfonyl)aziridine 71 (Table 1, entry 8). A
colourless oil [Found (FAB): (M ϩ H)ϩ, 394.1870. C20H32NO3-
SSi requires M ϩ H, 394.1872]; [α]D27 Ϫ39.7 (c 1.21 in CHCl3);
δH (270 MHz, CDCl3) Ϫ0.06 (3 H, s, SiMe), Ϫ0.02 (3 H, s,
᎐
SiMe), 0.80 (9 H, s, CMe ), 2.19 (1 H, d, J 1.9, C᎐CH), 2.30
᎐
3
(2R,3S)-3-Isopropyl-2-[2-(methoxycarbonyl)ethynyl]-N-(2,4,6-
(3 H, s, CMe), 2.69 (6 H, s, 2 × CMe), 3.07 (1 H, ddd, J 7.0, 5.9
and 5.4, 2-H), 3.40 (1 H, dd, J 7.0 and 1.9, 3-H), 3.68 (1 H, dd,
J 11.3 and 5.9, OCHH), 3.77 (1 H, dd, J 11.3 and 5.4, OCHH),
6.96 (2 H, s, Ph); m/z (FAB) 394 (MHϩ), 337, 336, 306, 183, 167,
119 (base peak), 89 and 73.
trimethylphenylsulfonyl)aziridine 76
By a procedure identical with that described for the preparation
of 74 from 34, the aziridine 35 (204 mg, 0.7 mmol) was con-
verted into the title compound 76 (158 mg, 65% yield) as a
colourless oil [Found (FAB): (M ϩ H)ϩ, 350.1433. C18H24NO4S
requires M ϩ H, 350.1426]; [α]D22 Ϫ82.6 (c 0.860 in CHCl3);
δH (270 MHz, CDCl3) 0.85 (3 H, d, J 6.5, CMe), 1.01 (3 H, d,
J 7.0, CMe), 1.50–1.68 (1 H, m, Me2CH), 2.32 (3 H, s, CMe),
2.64 (1 H, dd, J 9.7 and 7.0, 3-H), 2.69 (6 H, s, 2 × CMe), 3.43
(1 H, d, J 7.0, 2-H), 3.76 (3 H, s, OMe), 6.98 (2 H, s, Ph); m/z
(FAB) 350 (MHϩ, base peak), 294, 183, 166, 137, 119, 91, 77
and 55.
(2R,3S)-3-[(tert-Butyldimethylsiloxy)methyl]-N-(2,4,6-
trimethylphenylsulfonyl)-2-(2-trimethylsilylethynyl)aziridine 72
(Table 1, entry 9). 91% ee (2R,3S) by HPLC [Daicel Chiralcel
OD, n-hexane:propan-2-ol = 99:1 (0.5 cm3 minϪ1), (2R,3S)-
isomer 9.3 min, (2S,3R)-isomer 10.2 min]; colourless oil [Found
(FAB): (M ϩ H)ϩ, 466.2277. C23H40NO3SSi2 requires M ϩ H,
466.2267]; [α]D29 ϩ35.1 (c 0.462 in CHCl3); δH (270 MHz, CDCl3)
Ϫ0.09 (3 H, s, SiMe), Ϫ0.08 (3 H, s, SiMe), 0.17 (9 H, s, SiMe3),
0.80 (9 H, s, CMe3), 2.30 (3 H, s, CMe), 2.71 (6 H, s, 2 × CMe),
3.18 (1 H, d, J 4.3, 3-H), 3.32 (1 H, ddd, J 4.3, 4.3 and 3.8, 2-H),
3.69 (1 H, dd, J 11.6 and 4.3, OCHH), 3.76 (1 H, dd, J 11.6 and
3.8, OCHH), 6.93 (2 H, s, Ph); m/z (FAB) 466 (MHϩ), 408, 378,
229, 119, 89 and 73 (base peak).
(2R,3S)-3-Isopropyl-N-(2,4,6-trimethylphenylsulfonyl)-2-(2-
trimethylsilylethynyl)aziridine 77
By a procedure similar to that described for the preparation of
74 from 34, the aziridine 35 (117 mg, 0.40 mmol) was converted
into the title compound 77 (128 mg, 88% yield) as a colourless
oil [Found (FAB): (M ϩ H)ϩ, 364.1772. C19H30NO2SSi requires
M ϩ H, 364.1766]; [α]D26 Ϫ62.4 (c 0.857 in CHCl3); δH (270 MHz,
CDCl3) 0.14 (9 H, s, SiMe3), 0.81 (3 H, d, J 6.5, CMe), 0.98
(3 H, d, J 6.8, CMe), 1.50–1.67 (1 H, m, Me2CH), 2.31 (3 H, s,
CMe), 2.52 (1 H, dd, J 9.7 and 7.0, 3-H), 2.70 (6 H, s, 2 × CMe),
3.38 (1 H, d, J 7.0, 2-H), 6.96 (2 H, s, Ph); m/z (FAB) 364 (MHϩ,
base peak), 362, 348, 271, 229, 181, 180, 167, 119 and 73.
(2R,3S)-3-[(tert-Butyldimethylsiloxy)methyl]-2-ethynyl-N-
(2,4,6-trimethylphenylsulfonyl)aziridine 73 (Table 1, entry 10).
94% ee (2R,3S) by HPLC [Daicel Chiralcel OD, n-hexane:
propan-2-ol = 98:2 (0.5 cm3 minϪ1), (2R,3S)-isomer 15.7 min,
(2S,3R)-isomer 17.9 min]; colourless crystals, mp 90 ЊC (from
n-hexane) [Found (FAB): (M ϩ H)ϩ, 394.1880. C20H32NO3SSi
requires M ϩ H, 394.1872]; [α]D27 ϩ5.94 (c 0.886 in CHCl3);
δH (270 MHz, CDCl3) Ϫ0.12 (3 H, s, SiMe), Ϫ0.10 (3 H, s,
SiMe), 0.78 (9 H, s, CMe3), 2.30 (3 H, s, CMe), 2.47 (1 H, d,
Acknowledgements
᎐
J 2.4, C᎐CH), 2.71 (6 H, s, 2 × CMe), 3.17 (1 H, dd, J 4.3 and
᎐
This work was supported in part by The Japan Health Sciences
Foundation and Grant-in-Aid for Scientific Research from the
Ministry of Education, Science, Sports, and Culture of Japan.
H. O. is grateful to the Japan Society for the Promotion of
Science for Young Scientists.
2.4, 3-H), 3.33 (1 H, ddd, J 4.9, 4.3 and 3.5, 2-H), 3.64 (1 H, dd,
J 11.6 and 4.9, OCHH), 3.73 (1 H, dd, J 11.6 and 3.5, OCHH),
6.95 (2 H, s, Ph); m/z (FAB) 394 (MHϩ), 336, 306, 210, 167, 157,
119, 89 and 73 (base peak).
(2S,3S)-3-Isopropyl-2-[2-(methoxycarbonyl)ethynyl]-N-(2,4,6-
trimethylphenylsulfonyl)aziridine 74
References
To a stirred solution of the aziridine 34 (291 mg, 1 mmol) in dry
THF (2 cm3) was added dropwise LDA (0.5 M in n-hexane–
THF (1:2) 2.4 cm3, 1.2 mmol) at Ϫ78 ЊC under argon. After
stirring for 1 h at this temperature, methyl chloroformate
(0.0852 cm3, 1.2 mmol) was added at Ϫ78 ЊC. The mixture was
stirred for 30 min at this temperature, followed by quenching
with saturated aqueous NH4Cl (2 cm3). The whole was
extracted with Et2O and the extract was washed with water and
dried over MgSO4. Usual workup followed by flash chrom-
atography over silica gel with n-hexane–EtOAc (5:1) gave the
title compound 74 (249 mg, 71% yield) as colourless crystals,
mp 75 ЊC [from n-hexane–Et2O (5:1)] (Found: C, 61.6; H, 6.5;
N, 3.9. C18H23NO4S requires C, 61.9; H, 6.6; N, 4.0%]; [α]D24
ϩ51.1 (c 0.951 in CHCl3); δH (270 MHz, CDCl3) 0.77 (3 H, d,
J 6.5, CMe), 0.92 (3 H, d, J 7.0, CMe), 1.48–1.61 (1 H, m,
Me2CH), 2.31 (3 H, s, CMe), 2.72 (6 H, s, 2 × CMe), 3.02–3.07
(2 H, m, 2-H and 3-H), 3.78 (3 H, s, OMe), 6.96 (2 H, s, Ph).
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(2S,3S)-3-Isopropyl-N-(2,4,6-trimethylphenylsulfonyl)-2-(2-
trimethylsilylethynyl)aziridine 75
By a procedure similar to that described for the preparation of
74 from 34, the aziridine 34 (437 mg, 1.5 mmol) was converted
into the title compound 75 (347 mg, 64% yield) as a colourless
J. Chem. Soc., Perkin Trans. 1, 1999, 2949–2962
2961

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15 Enantiomeric purities of ethynylaziridines 34 and 35 have been
determined by HPLC with a chiral stationary phase (Chiralcel OD
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enantiomerically pure (ee > 98%).
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Paper 9/05027B
11 (a) H. Ohno, K. Ishii, A. Honda, H. Tamamura, N. Fujii,
2962
J. Chem. Soc., Perkin Trans. 1, 1999, 2949–2962