A 2,3-cis-selective synthesis of aziridines bearing a vinyl group from allyl methyl carbonates and allyl mesylates

Article abstract of DOI:10.1039/a806882h

A convenient method for the synthesis of synthetically useful chiral 2-vinylaziridines from natural α-amino acids is described. Satisfactory 2,3-cis-selectivities are obtained by exposure of methyl carbonates of various allylic alcohols bearing an N-protected amino group to a catalytic amount of tetrakis(triphenylphosphine)palladium(0), Pd(PPh₃)₄, in aprotic solvents such as THF. Base-promoted aziridination of mesylates of various N-protected amino allylic alcohols followed by Pd(PPh₃)₄ catalyzed isomerization for the 2,3-cis-selective synthesis of vinylaziridines is also presented.

Full text of DOI:10.1039/a806882h

View Article Online / Journal Homepage / Table of Contents for this issue
A 2,3-cis-selective synthesis of aziridines bearing a vinyl group
from allyl methyl carbonates and allyl mesylates
Hiroaki Ohno, Kiyonori Ishii, Asami Honda, Hirokazu Tamamura, Nobutaka Fujii,
Yoshiji Takemoto and Toshiro Ibuka*
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501,
Japan
Received (in Cambridge) 3rd September 1998, Accepted 28th September 1998
A convenient method for the synthesis of synthetically useful chiral 2-vinylaziridines from natural α-amino acids is
described. Satisfactory 2,3-cis-selectivities are obtained by exposure of methyl carbonates of various allylic alcohols
bearing an N-protected amino group to a catalytic amount of tetrakis(triphenylphosphine)palladium(0), Pd(PPh3)4,
in aprotic solvents such as THF. Base-promoted aziridination of mesylates of various N-protected amino allylic
alcohols followed by Pd(PPh3)4 catalyzed isomerization for the 2,3-cis-selective synthesis of vinylaziridines is also
presented.
The N-activated or N-unactivated aziridines bearing an
alkenyl group on one of the aziridine-ring carbon atoms have
proven to be extremely valuable intermediates in synthetic
chemistry today. Due to their very high reactivity and ability
to function as carbon electrophiles, vinylaziridines and their
analogues have been used as intermediates for the synthesis of
azinomycin,1 β-lactams,2 (R )-(Ϫ)-dysidazirine,3 azacyclessuchas
2,6-disubstituted tetrahydropyridines,4 indolizidine alkaloids,5
pyrrolizidine alkaloids,6 allyl imines,7 allyl amines,8 sphingo-
sines,9 3,7-disubstituted tetrahydroazepinone10 and alkene
dipeptide isosteres.11
solvent of the reaction.12 It has been reported that the stereo-
chemistry at the α-carbon in isosteres 6 and 7 is one of the
essential factors for biological activity.17 We also recently
reported that some peptides containing a dipeptide isostere
7 are more potent than peptides containing a dipeptide
isostere 6.18 In our continuing synthetic study of biologically
active polypeptides containing an (E)-alkene dipeptide
isostere, we were in need of a stereoselective synthetic route to
2,3-cis-aziridines 5, which can be used to generate (E)-alkene
dipeptide isosteres 7 with the desired stereochemistry at the
α-position.
One of the simplest methods for the synthesis of dipeptide
isosteres such as 6 and 7 via vinylaziridines of type 4 and 5
involves the use of anti- and syn-amino alcohols 2 and 3 which,
in turn, could be synthesized from chiral amino aldehydes 1
by treatment with vinylic organometallic reagents (Scheme 1).
Since the discovery of the palladium-catalyzed reactions of
allylic carbonates by Tsuji and co-workers,19,20 the method
has become an important tool for synthetic chemists today.
As shown in Scheme 2, we anticipated that, by employing
L
L
Pd+
R3
α
R1
OH
γ
H
3
2
R1
R1
R1
R1
CO2But
3
2
ii
H
H
β
H
N
NH-R2
NH-R2
2
H
H
H
H
R2
4
N
R2
OR3
a). PdL4
N
R2
R1
CHO
6
i
R1
OH
R3
A
NH-R2
4
R1
H
R1
R1
NH-R2
or
1
CO2But
ii
b). i. base
3 = CO2Me
L
L
Pd+
R1
H
H
8
9
R
H
NH-R2
3
NH-R2
N
R3 = Ms
ii. PdL4
R1
H
R2
5
7
H
H
N
H
N
R2
R2
Scheme 1 Reagents: i, vinyl-M (M = Li, Mg, etc.); ii, PPh3–(NCO2Et)2.
R1 = alkyl, aryl; R2 = Boc, Ts, etc.; R3 = alkyl.
B
5
Scheme 2 R1 = alkyl, aryl, etc.; R2 = Boc, Ts, etc.; L = PPh3.
However, when a chiral N-protected amino aldehyde 1 is
reacted with excess vinylmagnesium bromide, vinyllithium, or
vinylzinc halide a mixture of diastereomers 2 and 3 is always
obtained in only moderate yields, even after extended periods,
presumably due to enolization of the amino aldehydes to form
the corresponding magnesio enolates.12,13 In addition, the
diastereomeric mixture of amino alcohols 2 and 3 derived
from N-protected amino aldehydes such as (S)-alaninal and
(S)-leucinal can be separated only with difficulty by repeated
flash chromatography.12,14 Moreover, the ratio of 2 and 3 is
unpredictably highly dependent on the structure of the amino
aldehyde, the reagent, the nature of the N-protective group,12
the use of additives like boron trifluoride,15 zinc chloride,15
cerium trichloride16 and diethylaluminum chloride,15 and the
recent advances in palladium-catalyzed reactions of alkenyl-
aziridines,2,21,22 the palladium(0)-catalyzed reaction of
readily available methyl carbonates 8 of amino allyl alcohols
would aid in producing the desired, thermodynamically more
stable 2,3-cis-isomers 5 predominantly via π-allyl palladium
complexes A and B. Until now, a palladium(0)-catalyzed reac-
tion of methyl allylic carbonates 8 for constructing synthetically
important vinylaziridines has no precedent as far as we are
aware. Detailed here is a new straightforward method for the
synthesis of 2,3-disubstituted vinylaziridines 5 in a 2,3-cis-
stereoselective manner from methyl carbonates 8 and methane-
sulfonates (mesylates) 9 of N-protected amino allylic alcohols.
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716
3703

View Article Online
OR1
OR1
Results and discussion
CO2Me
OR1
Synthesis of the methyl carbonates and mesylates of N-aryl-
sulfonyl allylic alcohols
i
R2
R2
OH
NH-R3
35, 36, 37
NH-R3
ii
For the present study, it seemed that N-protection by the intro-
duction of a strong electron-withdrawing group on the nitrogen
atom was desirable. The choice of arylsulfonyl [e.g., 2,4,6-
trimethylphenylsulfonyl (Mts), 2,2,5,7,8-pentamethylchroman-
6-ylsulfonyl (Pmc),23 and 4-methoxy-2,3,6-trimethylphenyl-
sulfonyl (Mtr)24] as both activating and protecting groups was
based primarily on their ease of deprotection.
38, 39, 40
iv
R2
OR1
OCO2Me
NH-R3
iii
R2
OH
44, 45, 46
OR1
NH-R3
41, 42, 43
v
As shown in Scheme 3, the requisite chiral methyl allylic
R2
OMs
NH-R3
R1
R1
CO2Me
47, 48, 49
OH
i~ii
R1 = TBS; R2 = H; R3 = Mts
1 = Bn; R2 = H; R3 = Mts
1 = TBS; R2 = Me; R3 = Ts
35, 38, 41, 44, 47
36, 39, 42, 45, 48
37, 40, 43, 46, 49
NH-R2
NH-R2
R
R
14, 15, 16, 17
10, 11, 12, 13
R1
iv
Scheme 4 Reagents: i, (COCl) –DMSO–(i-Pr) NEt; ii, Ph P᎐CHCO2-
OCO2Me
2
᎐
Me; iii, DIBAL; iv, ClCO2Me–pyridine; v, MeS2O2Cl–Et3N.3
R1
iii
NH-R2
22, 23, 24, 25
OH
NH-R2
18, 19, 20, 21
R1
v
17, 31 and 38–40), the methyl carbonates (22–25, 33 and 44–46),
and the mesylates (26–29, 34 and 47–49) presented in Schemes 3
and 4 were ascertained from the coupling constant (ca. 15.5 Hz)
OMs
NH-R2
26, 27, 28, 29
1
10, 14, 18, 22, 26 R1 = Pri; R2 = Mts
11, 15, 19, 23, 27 R1 = Bui; R2 = Ts
12, 16, 20, 24, 28 R1 = Bui; R2 = Pmc
13, 17, 21, 25, 29 R1 = Bn; R2 = Mts
of the two olefinic protons by H NMR spectral analysis. In
addition, optical purities of all α,β-unsaturated esters (14–17,
31 and 38–40) as well as allylic alcohols (18–21, 32 and 41–43)
have been determined by HPLC with a chiral stationary phase
(CHIRALCEL OD column; hexane–propan-2-ol = 97–85:3–
15). Except for compounds 39 (ee 88%) and 42 (ee 88%) bearing
a benzyloxy group, all other compounds were found to be
essentially optically pure (ee >98%). Data for the optical
purities of these compounds are listed in Table 1.
Me
Me
CO2Me
i~ii
Et
OH
NH-Mtr
Et
NH-Mtr
31
30
Me
Me
Palladium(0)-catalyzed aziridination reactions of methyl
carbonates of N-arylsulfonyl amino alcohols
iii
iv
or v
Et
OH
Et
OR
NH-Mtr
NH-Mtr
Having synthesized substrates for the possible palladium(0)-
catalyzed aziridination reactions of methyl carbonates of
N-arylsulfonyl amino alcohols, the reaction of N-protected
methyl carbonates 52 and 53, which in turn were readily pre-
pared from the known corresponding allylic alcohols 50 and
51,21c with Pd(PPh3)4 was briefly investigated (Scheme 5). As
expected, when either the carbonate 52 or the isomeric carbon-
ate 53 was treated with 5 mol% of Pd(PPh3)4 in THF at 60 ЊC
for 20 min, a separable 94:6 ~ 95:5 mixture of 2,3-cis-3-
isopropyl-2-vinylaziridine 54 and its 2,3-trans-isomer 55 was
obtained in good yields via a decarboxylative ring closure.
Flash chromatographic separation of the mixture of 54 and
55 led to the isolation of the desired 2,3-cis-aziridine 54 in 85%
yield from the carbonate 52. The undesired 2,3-trans-aziridine
55 could be recycled for the palladium(0)-catalyzed isomeriz-
ation reaction with a catalytic amount of Pd(PPh3)4. The 2,3-
cis- and 2,3-trans-stereochemistries were readily established
32
33 R = CO2Me
34 R = Ms
Scheme
3
Abbreviations: Mts = 2,4,6-trimethylphenylsulfonyl; Ts =
p-tolylsulfonyl;
Pmc = 2,2,5,7,8-pentamethylchroman-6-ylsulfonyl;
Mtr = 4-methoxy-2,3,6-trimethylphenylsulfonyl. Reagents: i, (COCl)2–
DMSO–(i-Pr)2NEt; ii, Ph3P᎐CHCO2Me; iii, DIBAL; iv, ClCO2Me–
᎐
pyridine; v, MeSO2Cl–Et3N.
carbonates (22–25 and 33) and the mesylates (26–29 and 34) of
N-arylsulfonyl amino alcohols were prepared in acceptable
yields starting from the N-arylsulfonyl amino alcohols (10–13
and 30) which, in turn, could be prepared from (S)-valinol,25
(S)-leucinol,26 (S)-phenylalaninol25 and (S)-isoleucinol.25
Typically, the known N-protected (S)-valinol 1021c was treated
successively with oxalyl chloride–DMSO–N,N-diisopropylethyl-
amine
and
[(methoxycarbonyl)methylene]triphenylphos-
phorane to afford the (E)-enoate 14 which, on reduction with
DIBAL, yielded the allylic alcohol 18. Conversion of the alco-
hol 18 into both the carbonate 22 or the mesylate 26 was
accomplished following standard procedures (see the Experi-
mental section). The other chiral methyl allylic carbonates (23–
25 and 33) and mesylates (27–29 and 34) listed in Scheme 3 were
prepared from the corresponding N-protected amino alcohols
(11–13 and 30) by a sequence of reactions similar to that
described for the synthesis of the carbonate 22 and the mesylate
26 (see Experimental section).
In a similar manner, the N-protected amino alcohols 35–37,
readily available from methyl (S)-serinate hydrochloride,12
O-benzyl-N-tert-butoxycarbonyl-(S)-serine,27 and (S)-threo-
nine, were converted into the corresponding methyl allylic car-
bonates 44–46 and the allylic mesylates 47–49 via the sequence
of reactions shown in Scheme 4.
from 1H NMR analysis. The 2,3-cis-aziridine 54 has a JH
2,3
value (7.0 Hz) larger than the JH value (4.2 Hz) of the 2,3-
2,3
1
trans-isomer. The data are in good agreement with H NMR
data for related compounds.21b,c,28
In a similar manner, palladium(0)-catalyzed reactions of
carbonates (22–25 and 33) gave rise to the corresponding 2,3-
cis-vinylaziridines (54, 56, 58, 60 and 62) preferentially (Scheme
5 and Table 2). The stereoselection of the reaction of the carb-
onates was at least 94:6 favouring the thermodynamically more
stable 2,3-cis cyclization products in good agreement with the
ab initio calculations reported previously.21b,c
It should be clearly noted that the attempted palladium(0)-
catalyzed reactions of carbonates such as 52 at 0 ЊC resulted in
complete recovery of the unchanged starting substrates. The
failed aziridination reaction of the carbonate 52 at 0 ЊC must be
due to sluggishness in the formation of π-allyl intermediates.
Finally, (E)-geometrical assignments for the α,β-enoates (14–
3704
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716

View Article Online
Table 1 Synthesis of allylic methyl carbonates (22–25, 33 and 44–46) and allylic mesylates (26–29, 34 and 47–49)
α,β-Enoate
Allylic alcohol
Carbonate
Mesylate
Product Yield (%)d
Amino
alcohol
Entry
Product Yield (%)a
% eeb
Product Yield (%)c
% eeb
>98
>98
>98
>98
>98
>98
88
Product Yield (%)d
1
2
3
4
5
6
7
8
10
11
12
13
30
35
36
37
14
15
16
17
31
38
39
40
78
75
88
63
96
77
59
85
>98
>98
>98
>98
>98
>98
88
18
19
20
21
32
41
42
43
86
87
52
86
88
79
93
90
22
23
24
25
33
44
45
46
97
97
93
99
88
90
98
95
26
27
28
29
34
47
48
49
98
99
84
79
90
88
96
99
>98
>98
a Isolated yields based on amino alcohol. b Determined by chiral HPLC on a CHIRALCEL OD column (DAICEL; n-hexane–propan-2-ol =
97–83:3–15). c Isolated yields based on α,β-enoate. d Isolated yields based on allylic alcohol.
Table 2 Pd(PPh3)4 Catalyzed aziridination of allylic methyl carbonates 22–25 and 33a
Pd(PPh3)4
(mol%)
Entry
Substrate
T/ЊC
t/min
cis:transb
Yield (%)c
1
2
3
4
5
22
23
24
25
33
5
4
4
4
2
60
65
20
65
60
20
10
360
5
54:55 = 94:6
56:57 = 94:6
58:59 = 97:3
60:61 = 95:5
62:63 = 98:2
72
66
59
50
85
5
a All reactions were carried out in THF. b Ratios were determined by reverse-phase HPLC (MeOH:H2O = 85–70:15–30 except for entry 2,
MeCN:H2O = 1:1). c Combined isolated yields.
OR
R1
R1
3 2
R1
OMs
i. NaH
H
H
H
H
+
N
N
NH-Mts
50 R = H
52 R = CO2Me
NH-R2
Pd(PPh3)4
(cat.)
ii. Pd(PPh3)4
(4 mol%)
R2
R2
26, 27, 28, 29
54, 56, 58, 60
55, 57, 59, 61
(95%)
3 2
N
OR
26, 54, 55
27, 56, 57
28, 58, 59
29, 60, 61
R
R
R
R
1 = Pri; R2 = Mts
1 = Bui; R2 = Ts
1 = Bui; R2 = Pmc
1 = Bn; R2 = Mts
H
H
H
H
+
N
Mts
55
Mts
NH-Mts
Pd(PPh3)4
(cat.)
(94 : 6 ~ 95 : 5)
54
51 R = H
53 R = CO2Me
Me
Me
(81%)
Et
Et
Me
OMs
i. NaH
3 2
N
R1
R1
OCO2Me
3 2
H
H
+
H
H
Et
Pd(PPh3)4
(cat.)
N
R1
ii. Pd(PPh3)4
(4 mol%)
H
H
H
H
NH-Mtr
+
Mtr
Mtr
N
N
NH-R2
63
34
R2
R2
62
54, 56, 58, 60
55, 57, 59, 61
R1
22, 23, 24, 25
R1
R1
22, 54, 55 R1 = Pri; R2 = Mts
R2
OMs
R2
3 2
23, 56, 57
24, 58, 59
25, 60, 61
R
R
R
1 = Bui; R2 = Ts
i. NaH
R2
+
1 = Bui; R2 = Pmc
1 = Bn; R2 = Mts
H
H
H
H
ii. Pd(PPh3)4
(4 mol%)
N
NH-R3
N
R3
R3
47, 48, 49
Me
Me
65, 67, 69
64, 66, 68
Et
Et
Me MeO2CO
47, 64, 65 R1 = OTBS; R2 = H; R3 = Mts
48, 66, 67 R1 = OBn; R2 = H; R3 = Mts
49, 68, 69 R1 = β-OTBS; R2 = Me; R3 = Ts
Pd(PPh3)4
(cat.)
+
H
H
H
H
Et
N
N
NH-Mtr
Mtr
63
Mtr
Scheme 6
33
62
Scheme 5
to be the case since all attempts to cyclize the carbonates to
vinylaziridines in the presence of Pd(PPh3)4 gave an inseparable
mixture of products. The difficulty was overcome by treatment
of the mesylates with sodium hydride followed by Pd(PPh3)4 as
described below.
This was demonstrated by exposing an equimolar mixture of 52
and 55 to 5 mol% of Pd(PPh3)4 in THF at 0 ЊC for 1 h. Whereas
the carbonate 52 was completely recovered unchanged, a 95:5
equilibrium mixture of 2,3-cis- and trans-aziridines 54 and 55
was obtained. Thus, the N-activated vinylaziridine 55 forms π-
allyl intermediates more easily than the carbonate 52.
It was assumed that the carbonates 44–46 bearing a benzy-
loxy or a tert-butyldimethylsilyl group (Scheme 4) under similar
conditions would provide vinylaziridines. However, this was not
Aziridination reaction of the N-protected amino allylic mesylates
with sodium hydride followed by equilibrated reaction with a
catalytic amount of palladium(0)-catalyst
As shown in Scheme 6 and Table 3, following the Ohfune pro-
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716
3705

View Article Online
Table 3 Base-promoted aziridination of allylic mesylates 26–29, 34 and 47–49 followed by equilibrated reaction with a catalytic amount of
Pd(PPh3)4
Aziridination reactiona
Pd(0)-Catalyzed equilibrated reactionb
Entry
Substrate
t/h
cis:transc
Yield (%)d
t/h
cis:transc
Yield (%)e
1
2
3
4
5
6
7
8
26
27
28
29
34
47
48
49
0.5
1
0.5
0.5
0.5
4
54:55 = 26:74
56:57 = 45:55
58:59 = 48:52
60:61 = 43:57
62:63 = 22:78
64:65 = 51:49
66:67 = 51:49
68:69 = 8:92
66
61
88
70
86
62
67
58
24
18
18
3
18
2
54:55 = 96:4
56:57 = 96:4
58:59 = 97:3
60:61 = 95:5
62:63 = 98:2
64:65 = 92:8
66:67 = 94:6
68:69 = 92:8
99
97
95
82
95
90
77
92
3
2
0.4
18
a All the aziridination reactions were carried out in DMF by treatment with NaH (1.5 equiv) at 0 ЊC except for entry 8 (25 ЊC). b The equilibrated
reactions were carried out in THF at 0 ЊC using Pd(PPh3)4 (4 mol%). c Ratios were determined by reversed-phase HPLC (MeOH:H2O = 85–70:15–
30 except for entry 2, MeCN:H2O = 1:1). d Combined isolated yields based on the corresponding allylic mesylates. e Combined isolated yields based
on the base-promoted aziridination products.
cedure,2a the allylic mesylates (26–29 and 34) were treated with
Me
NaH in DMF at 0 ЊC to produce a mixture of the correspond-
ing 2,3-cis-vinylaziridines (54, 56, 58, 60 and 62) and their
2,3-trans-isomers (55, 57, 59, 61 and 63) in variable ratios in
moderate to high yields. Since the desired 2,3-cis-isomers
were obtained as the minor products in all cases examined by
base-promoted reactions, the mixtures of 2,3-cis- and 2,3-trans-
isomers were treated with 5 mol% of Pd(PPh3)4 to yield the
desired 2,3-cis-vinylaziridines as the major products.21b,c
Typically, a 26:74 mixture of 2,3-cis- and 2,3-trans-2-vinyl-
aziridines 54 and 55 obtained by exposure of the mesylate 26 to
sodium hydride was treated with 4 mol% of Pd(PPh3)4 in THF
to yield a separable equilibrated 96:4 mixture of 54 and 55 in
99% combined yield in favour of the 2,3-cis-isomer 54. Follow-
ing this two-step procedure, the desired 2,3-cis-aziridines (56,
58, 60 and 62) were obtained predominantly starting from the
corresponding mesylates (27–29 and 34) in satisfactory yields
(Scheme 6 and Table 3).
As stated before, although the carbonates 44–46 bearing a
tert-butyldimethylsiloxy or benzyloxy functionality could not
be transformed into the corresponding vinylaziridines by
treatment with a catalytic amount of Pd(PPh3)4, treatment of
the mesylates 47–49 with sodium hydride followed by exposure
to a catalytic amount of Pd(PPh3)4 gave the corresponding 2,3-
cis-vinylaziridines (64, 66 and 68) as the major products in syn-
thetically acceptable yields (Scheme 6 and entries 6–8 in Table
3). Optical purities of all 2-vinylaziridines synthesized have
been determined by HPLC with a chiral stationary phase (Chi-
ralcel OD column; hexane:propan-2-ol = 99.5–99.0:0.5–1.0).
Except for aziridines 66 (ee 88%) and 67 (ee 88%) bearing a
benzyloxy group, all other 2-vinylaziridines were found to be
essentially optically pure (ee >98%).
It should be clearly noted that treatment of the allylic
mesylates 26 and 34 bearing a branched alkyl group with
sodium hydride gave preferentially the corresponding 2,3-trans-
aziridines 55 and 63 (Scheme 7, entries 1 and 5 in Table 3).
Although the ground state and the reactive conformer are not
necessarily the same, the ground state conformations of various
olefinic molecules containing the alkene moiety play an import-
ant role in the stereochemical outcome of π-facial selectivity.29
The predominant formation of the 2,3-trans-isomers 55 and 63
from the corresponding mesylates 26 and 34 may be rational-
ized by assuming the preferred conformation B as shown in
Scheme 7. The 2,3-cis- and the 2,3-trans-ratios of the SN2Ј
products may reflect the transition state energy difference
related to the HA/HB staggered B and HA/HB eclipsed con-
formers A. In conformation B, the allylic 1,3-strain may be
minimized. On the other hand, conformer A, which could lead
to the 2,3-cis-isomer 54 via the SN2Ј pathway, should be dis-
favoured by steric crowding between the isopropyl or the sec-
butyl group and the HC hydrogen. Consequently, the reactions
OMs R1
HC
HB
3 2
N
HA
"branched"
H
H
Me
H
R1
R2
(Minor)
Me
R1
OMs
NaH
N
R2
54 R1 = Me;
2 = Mts
62 R1 = Et;
2 = Mtr
A (less stable)
R
NH-R2
26 R1 = Me; R2 = Mts
34 R1 = Et; R2 = Mtr
R
Me
OMs
HB
HC
HA
R1
Me
H
H
H
N
R1
N
R2
R2
(Major)
B (more stable)
55 R1 = Me;
2 = Mts
63 R1 = Et;
2 = Mtr
R
R
Scheme 7
of the mesylates 26 and 34 with a branched alkyl group with
sodium hydride yield the corresponding 2,3-trans-vinyl-
aziridines 55 and 63 as the major products most probably via
the conformer of type B (Scheme 7).
Finally, the synthesized 2,3-cis-vinylaziridines could be used
for the synthesis of (E)-alkene isosteres (Scheme 8). For
CO2But
Me
Me
Et
Et
4 3
N
5 4
i, ii
H
H
H
H
(85%)
N
Mtr
62
Mtr
70
Me
Me
Me
iii
(94%)
Et
CO2But
NH-Mtr
71
Scheme 8 Reagents: i, O3; ii, (EtO)2P(O)CH2CO2But–(i-Pr)2NEt–LiCl;
iii, i-PrCu(CN)MgCl.
example, ozonolysis of vinylaziridine 62 followed by exposure
to a mixture of tert-butyl diethylphosphonoacetate, lithium
chloride and diisopropylethylamine gave the enoate 70 in 85%
yield which, on reaction with PriCu(CN)MgCl, gave the (E)-
alkene isostere 71 in 94% yield as a single stereoisomer.
In summary, we have developed a reliable procedure for the
3706
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716

View Article Online
preparation of the synthetically useful 2,3-cis-vinylaziridines
from natural α-amino acids. Satisfactory 2,3-cis-selectivities are
obtained by exposure of methyl carbonates of various allylic
alcohols bearing an N-protected amino group to a catalytic
amount of Pd(PPh3)4 in aprotic solvents such as THF. Sodium
hydride-promoted aziridination of various mesylates of
N-protected amino allylic alcohols followed by Pd(PPh3)4-
catalyzed isomerization for the 2,3-cis-selective synthesis of
vinylaziridines is also presented. The described methodology
involving palladium(0)-catalyzed 2,3-cis-selective aziridination
has advantages over other methods in terms of mildness, select-
ivity and convenience.
2.09–2.12 (1 H, m, OH), 2.13 (3 H, s, CMe), 2.57 (3 H, s, CMe),
2.58 (3 H, s, CMe), 2.64 (1 H, t, J 7.0, 4Ј-CH2), 3.25–3.35 (1 H,
m, 2-H), 3.40–3.48 (1 H, m, 3-CHH), 3.57–3.65 (1 H, m,
3-CHH), 4.59 (1 H, d, J 8.1, NH).
(S)-N-(2,4,6-Trimethylphenylsulfonyl)phenylalaninol 13
To a stirred solution of (S)-phenylalaninol (6.05 g, 40 mmol)
and Et3N (8.3 cm3, 60 mmol) in a mixed solvent of DMF (10
cm3) and CHCl3 (20 cm3) was added mesitylenesulfonyl chlor-
ide (10.5 g, 48 mmol) in CHCl3 (10 cm3) at 0 ЊC and the mixture
was stirred at this temperature for 48 h followed by quenching
with 5% aqueous NaHCO3 (10 cm3). The whole was extracted
with Et2O and the extract was washed successively with 5%
aqueous citric acid, H2O, 5% aqueous NaHCO3, and H2O, and
dried over MgSO4. Usual work-up followed by flash chrom-
atography over silica gel with n-hexane–EtOAc (2:1) gave the
title compound 13 (12.3 g, 92%) as a colourless oil [Found
(FAB): (M ϩ H)ϩ, 334.1470. C18H24NO3S requires M ϩ H,
334.1477]; [α]D27 Ϫ29.4 (c 1.19 in CHCl3); δH(270 MHz, CDCl3)
1.90 (1 H, br s, OH), 2.29 (3 H, s, CMe), 2.51 (6 H, s, 2 ×
CMe), 2.72 (1 H, dd, J 13.8 and 7.0, 3-CHH), 2.79 (1 H, dd,
J 13.8 and 6.8, 3-CHH), 3.36–3.47 (1 H, m, 2-H), 3.52 (1 H, dd,
J 11.1 and 4.3, 1-CHH), 3.65 (1 H, dd, J 11.1 and 4.1, 1-CHH),
4.91 (1 H, d, J 7.0, NH), 6.88 (2 H, s, Ph), 6.94–7.00 (2 H, m,
Ph), 7.14–7.20 (3 H, m, Ph); m/z (FAB-LRMS) 334 (MHϩ, base
peak), 302, 242, 183, 152, 134, 119, 91, 60.
Experimental
General methods
The instrumentation has already been described.12b,c 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.Forthedeterminationofopticalpurity,CHIRALCEL
OD (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 preparation of ã-N-arylsulfonylamino-á,â-
unsaturated esters 14–17, 31 and 38–40: methyl (4S,2E)-5-
methyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]hex-2-enoate
14
To a stirred solution of oxalyl chloride (2.5 cm3, 26 mmol) in
a mixed solvent of CHCl3 (30 cm3) and n-hexane (30 cm3) at
Ϫ78 ЊC under argon was added dropwise a solution of DMSO
(5.67 cm3, 80 mmol) in CHCl3 (10 cm3). After 30 min, a solution
of (S)-N-(2,4,6-trimethylphenylsulfonyl)valinol 1021c (5.7 g, 20
mmol) in CHCl3 (10 cm3) was added to the above reagent at
Ϫ78 ЊC, and the mixture was stirred for 30 min. Diisopropyl-
ethylamine (20.9 cm3, 120 mmol) was added to the above solu-
tion at Ϫ78 ЊC and the mixture was stirred for 30 min with
warming to 0 ЊC. A saturated NH4Cl (10 cm3) solution was
added to the mixture and the whole was extracted with Et2O.
The extract was washed successively with 5% aqueous citric
acid and water, and dried over MgSO4. The extract was concen-
trated under reduced pressure to an oil, which was dissolved in
CHCl3 (50 cm3). (Methoxycarbonylmethylene)triphenylphos-
phorane (6.68 g, 20 mmol) was added to the above solution at
0 ЊC, and the mixture was stirred for 1 h with warming to room
temperature. Concentration under reduced pressure gave an
oily residue, which was flash chromatographed on silica gel with
n-hexane–EtOAc (3:1) to give the title compound 14 (5.3 g,
78%) as colourless needles, 98% ee (S) by HPLC [Daicel Chiral-
cel OD, n-hexane–propan-2-ol = 95:5 (0.5 cm3 minϪ1), (S)-
isomer 34.7 min, (R)-isomer 29.9 min], mp 97 ЊC (from Et2O)
(Found: C, 59.9; H, 7.4; N, 4.0. C17H25NO4S requires C, 60.15;
H, 7.4; N, 4.1%); [α]D20 Ϫ60.9 (c 0.70 in CHCl3); δH(270 MHz;
CDCl3) 0.82 (3 H, d, J 6.8, CMe), 0.90 (3H, d, J 6.5, CMe),
1.72–1.89 (1 H, m, 5-H), 2.28 (3 H, s, CMe), 2.62 (6 H, s,
2 × CMe), 3.64–3.68 (1 H, m, 4-H), 3.66 (3 H, s, OMe), 4.72
(1 H, d, J 8.6, NH), 5.61 (1 H, dd, J 15.4 and 1.1, 2-H), 6.54 (1
H, dd, J 15.4 and 7.3, 3-H), 6.92 (2 H, s, Ph).
(S)-N-(p-Tolylsulfonyl)leucinol 11
To a stirred mixture of (S)-leucinol (2.5 g, 21.3 mmol), Et3N
(5 cm3, 36 mmol), THF (5 cm3) and DMF (20 cm3) was added
toluene-p-sulfonyl chloride (4.87 g, 25.6 mmol) at 0 ЊC and the
mixture was stirred for 6 h with warming to room temperature
followed by quenching with 5 cm3 of 5% aqueous NaHCO3.
The whole was extracted with a mixed solvent of Et2O–EtOAc
(3:1). The extract was washed successively with 5% aqueous
citric acid, water, 5% aqueous NaHCO3, and water, and dried
over MgSO4. Usual work-up gave the title compound 11 (4.68
g, 81%) as colourless crystals, mp 102 ЊC [from n-hexane–
CHCl3 (4:1)] (Found: C, 57.3; H, 7.55; N, 4.9. C13H21NO3S
requires C, 57.5; H, 7.8; N, 5.2%); [α]D19 Ϫ25.2 (c 1.03 in CHCl3);
δH(270 MHz, CDCl3) 0.64 (3 H, d, J 6.2, CMe), 0.78 (3 H, d,
J 6.5, CMe), 1.16–1.33 (2 H, m, 3-CH2), 1.36–1.54 (1 H, m,
4-H), 2.12–2.19 (1 H, m, OH), 2.43 (3 H, s, CMe), 3.24–3.36
(1 H, m, 2-H), 3.46 (1 H, ddd, J 11.3, 4.9 and 4.9, 1-CHH), 3.57
(1 H, ddd, J 11.3, 7.0 and 3.8, 1-CHH), 4.76 (1 H, d, J 7.6, NH),
7.30–7.33 (2 H, m, Ph), 7.70–7.80 (2 H, m, Ph).
(S)-N-(2,2,5,7,8-Pentamethylchroman-6-ylsulfonyl)leucinol 12
To a stirred mixture of (S)-leucinol (2.34 g, 20 mmol), Et3N
(5.56 cm3, 40 mmol), THF (10 cm3) and EtOAc (50 cm3) was
added 2,2,5,7,8-pentamethylchroman-6-ylsulfonyl chloride (6.2
g, 20 mmol) at 0 ЊC and the mixture was stirred at this temper-
ature for 20 h followed by quenching with 5% aqueous
NaHCO3 (10 cm3). The whole was extracted with Et2O–EtOAc
(1:1) and the extract was washed successively with 5% aqueous
citric acid, brine, 5% aqueous NaHCO3, and brine, and dried
over MgSO4. Usual work-up followed by flash chromatography
over silica gel with n-hexane–EtOAc (2:3) gave the title com-
pound 12 (5.02 g, 66%) as colourless crystals, mp 118 ЊC [from
n-hexane–Et2O (1:1)] (Found: C, 62.6; H, 8.6; N, 3.6. C20H33-
NO4S requires C, 62.6; H, 8.7; N, 3.65%); [α]D19 Ϫ14.6 (c 0.997 in
CHCl3); δH(270 MHz, CDCl3) 0.68 (3 H, d, J 6.8, CMe), 0.76 (3
H, d, J 6.5, CMe), 1.19–1.29 (2 H, m, 3-CH2), 1.32 (6 H, s, 2 ×
CMe), 1.40–1.53 (1 H, m, 4-H), 1.83 (2 H, t, J 7.0, 3Ј-CH2),
Methyl (4S,2E)-6-methyl-4-[N-(p-tolylsulfonyl)amino]hept-2-
enoate 15. By a procedure identical with that described for the
preparation of the enoate 14 from 10, the alcohol 11 (4.68 g,
17.3 mmol) was converted into the title compound 15 (4.21 g,
75%), mp 76 ЊC [colourless crystals from n-hexane–Et2O (1:1)]
(Found: C, 58.9; H, 7.2; N, 4.1. C16H23NO4S requires C, 59.05;
H, 7.1; N, 4.3%); [α]D20 Ϫ51.3 (c 0.834 in CHCl3); δH(270 MHz,
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716
3707

View Article Online
CDCl3) 0.78 (3 H, d, J 6.5, CMe), 0.83 (3 H, d, J 6.5, CMe),
1.30–1.36 (2 H, m, 5-CH2), 1.53–1.62 (1 H, m, 6-H), 2.41 (3 H,
s, CMe), 3.68 (3 H, s, OMe), 3.90–4.01 (1 H, m, 4-H), 4.78 (1 H,
d, J 7.8, NH), 5.73 (1 H, dd, J 15.4 and 1.4, 2-H), 6.56 (1 H, dd,
J 15.4 and 6.8, 3-H), 7.26–7.30 (2 H, m, Ph), 7.69–7.74 (2 H, m,
Ph).
(4S,2E)-6-Methyl-4-[N-(p-tolylsulfonyl)amino]hept-2-en-1-ol
19. By a procedure identical with that described for the prepar-
ation of the alcohol 18 from 14, the enoate 15 (4.4 g, 13.5
mmol) was converted into the title compound 19 (3.5 g, 87%),
mp 104 ЊC [colourless crystals from CHCl3–Et2O (1:2)]
(Found: C, 60.4; H, 7.9; N, 4.8. C15H23NO3S requires C, 60.6; H,
7.8; N, 4.7%); [α]D20 Ϫ20.4 (c 2.45 in CHCl3); δH(270 MHz,
CDCl3) 0.76 (3 H, d, J 6.5, CMe), 0.80 (3 H, d, J 6.5, CMe),
1.25 (1 H, dd, J 13.5 and 7.3, 5-CHH), 1.33 (1 H, dd, J 13.5 and
7.6, 5-CHH), 1.48–1.67 (1 H, m, 6-H), 1.85 (1 H, t, J 5.9, OH),
2.42 (3 H, s, CMe), 3.77 (1 H, dddd, J 7.8, 7.6, 7.3 and 7.3, 4-H),
3.89–3.93 (2 H, m, 1-CH2), 5.12 (1 H, d, J 7.8, NH), 5.37 (1 H,
ddd, J 15.7, 7.3 and 1.4, 3-H), 5.55 (1 H, ddd, J 15.7, 5.1 and
5.1, 2-H), 7.27–7.30 (2 H, m, Ph), 7.73–7.76 (2 H, m, Ph).
Methyl
(4S,2E)-6-methyl-4-[N-(2,2,5,7,8-pentamethyl-
chroman-6-ylsulfonyl)amino]hept-2-enoate 16. By a procedure
identical with that described for the preparation of the enoate
14 from 10, the alcohol 12 (4.78 g, 12.5 mmol) was converted
into the title compound 16 (4.77 g, 88%) as a colourless oil
[Found (FAB): (M ϩ H)ϩ, 438.2290. C23H36NO5S requires
M ϩ H, 438.2314]; [α]D21 Ϫ28.2 (c 1.64 in CHCl3); δH(270 MHz,
CDCl3) 0.81 (3 H, d, J 5.9, CMe), 0.83 (3 H, d, J 6.8, CMe),
1.24–1.46 (2 H, m, 5-CH2), 1.31 (6 H, s, 2 × CMe), 1.52–1.67
(1 H, m, 6-H), 1.82 (2 H, t, J 7.0, 3Ј-CH2), 2.10 (3 H, s, CMe),
2.52 (3 H, s, CMe), 2.54 (3 H, s, CMe), 2.63 (2 H, t, J 7.0,
4Ј-CH2), 3.64 (3 H, s, OMe), 3.84–3.95 (1 H, m, 4-H), 4.44 (1 H,
d, J 7.8, NH), 5.59 (1 H, dd, J 15.7 and 1.1, 2-H), 6.43 (1 H, dd,
J 15.7 and 7.8, 3-H); m/z (FAB-LRMS) 438 (MHϩ), 437, 267
(base peak), 219, 203, 170, 147.
(4S,2E)-6-Methyl-4-[N-(2,2,5,7,8-pentamethylchroman-6-yl-
sulfonyl)amino]hept-2-en-1-ol 20. By a procedure similar to that
described for the preparation of the alcohol 18 from 14, the
enoate 16 (4.59 g, 10.5 mmol) was converted into the title com-
pound 20 (2.31 g, 52%), mp 113 ЊC [colourless crystals from
n-hexane–Et2O (1:1)] (Found: C, 64.3; H, 8.6; N, 3.3. C22H35-
NO4S requires C, 64.5; H, 8.6; N, 3.4%); [α]D19 Ϫ8.61 (c 1.05 in
CHCl3); δH(270 MHz, CDCl3) 0.80 (3 H, d, J 6.8, CMe), 0.81
(3 H, d, J 6.5, CMe), 1.05–1.15 (1 H, m, OH), 1.18–1.31 (1 H,
m, 5-CHH), 1.32 (6 H, s, 2 × CMe), 1.32–1.41 (1 H, m,
5-CHH), 1.49–1.63 (1 H, m, 6-H), 1.83 (2 H, t, J 6.8, 3Ј-CH2),
2.13 (3 H, s, CMe), 2.54 (3 H, s, CMe), 2.55 (3 H, s, CMe), 2.65
(2 H, t, J 6.8, 4Ј-CH2), 3.74–3.87 (3 H, m, 4-H and 1-CH2),
4.42–4.46 (1 H, m, NH), 5.26 (1 H, dddd, J 15.7, 7.6, 1.1 and
1.1, 3-H), 5.52 (1 H, dddd, J 15.7, 5.4, 5.4 and 0.5, 2-H).
Methyl
(4S,2E)-5-phenyl-4-[N-(2,4,6-trimethylphenyl-
sulfonyl)amino]pent-2-enoate 17 and its (4S,2Z)-isomer. By a
procedure identical with that described for the preparation of
the enoate 14 from 10, the alcohol 13 (4.0 g, 12.0 mmol) was
converted into the title compound 17 (2.92 g, 63%) and its (Z)-
isomer (190 mg, 4%). Compound 17: mp 132 ЊC [colourless
crystals from n-hexane–Et2O (1:3)] (Found: C, 65.0; H, 6.5; N,
3.4. C21H25NO4S requires C, 65.1; H, 6.5; N, 3.6%); [α]D27 Ϫ60.9 (c
1.14 in CHCl3); δH(270 MHz, CDCl3) 2.28 (3 H, s, CMe), 2.46
(6 H, s, 2 × CMe), 2.79 (1 H, dd, J 13.8 and 7.3, 5-CHH), 2.86
(1 H, dd, J 13.8 and 6.2, 5-CHH), 3.68 (3 H, s, OMe), 4.03–4.14
(1 H, m, 4-H), 4.60 (1 H, d, J 7.0, NH), 5.77 (1 H, dd, J 15.9 and
1.4, 2-H), 6.71 (1 H, dd, J 15.9 and 6.2, 3-H), 6.87 (2 H, s, Ph),
6.98–7.05 (2 H, m, Ph), 7.20–7.28 (3 H, m, Ph). (Z)-Isomer of
17: mp 154 ЊC [colourless crystals from n-hexane–CHCl3 (5:1)]
(Found: C, 64.85; H, 6.5; N, 3.6. C21H25NO4S requires C, 65.1;
H, 6.5; N, 3.6%); [α]D27 Ϫ42.7 (c 0.942 in CHCl3); δH(270 MHz,
CDCl3) 2.26 (6 H, s, 2 × CMe), 2.28 (3 H, s, CMe), 2.60 (1 H,
dd, J 14.0 and 9.7, 5-CHH), 2.98 (1 H, dd, J 14.0 and 4.3,
5-CHH), 3.70 (3 H, s, OMe), 4.74 (1 H, d, J 4.6, NH), 4.87–4.97
(1 H, m, 4-H), 5.79 (1 H, dd, J 11.3 and 1.4, 2-H), 6.29 (1 H, dd,
J 11.3 and 8.1, 3-H), 6.81 (2 H, s, Ph), 7.01–7.07 (2 H, m, Ph),
7.16–7.23 (3 H, m, Ph).
(4S,2E)-5-Phenyl-4-[N-(2,4,6-trimethylphenylsulfonyl)-
amino]pent-2-en-1-ol 21. By a procedure identical with that
described for the preparation of the alcohol 18 from 14, the
enoate 17 (2.7 g, 6.97 mmol) was converted into the title com-
pound 21 (2.16 g, 86%), mp 99–100 ЊC [colourless needles from
n-hexane–Et2O (2:1)] (Found: C, 66.6; H, 6.95; N, 3.6.
C20H25NO3S requires C, 66.8; H, 7.0; N, 3.9%); [α]D19 Ϫ27.5
(c 0.75 in CHCl3); δH(270 MHz, CDCl3) 1.27 (1 H, br s, OH),
2.29 (3 H, s, CMe), 2.48 (6 H, s, 2 × CMe), 2.75 (1 H, dd, J 13.5
and 7.6, 5-CHH), 2.81 (1 H, dd, J 13.5 and 6.8, 5-CHH), 3.88–
3.95 (2 H, m, 1-CH2), 3.92–4.02 (1 H, m, 4-H), 4.62–4.65 (1 H,
m, NH), 5.46 (1 H, dd, J 15.7 and 7.0, 3-H), 5.58 (1 H, ddd, J
15.7, 4.9 and 4.9, 2-H), 6.88 (2 H, s, Ph), 7.02–7.05 (2 H, m, Ph),
7.17–7.29 (3 H, m, Ph).
General procedure for preparation of allylic alcohols 18–21 and
32 and 41–43: (4S,2E)-5-methyl-4-[N-(2,4,6-trimethylphenyl-
sulfonyl)amino]hex-2-en-1-ol 18
General procedure for preparation of methyl carbonates 22–25,
33 and 44–46: (4S,2E)-O-methoxycarbonyl-5-methyl-4-[N-
(2,4,6-trimethylphenylsulfonyl)amino]hex-2-en-1-ol 22
DIBAL (1.0 mol dmϪ3 solution in toluene; 76.1 cm3, 76.1
mmol) was added dropwise to a stirred solution of the enoate
14 (5.2 g, 34.6 mmol) in a mixed solvent of toluene (80 cm3) and
CHCl3 (30 cm3) at Ϫ78 ЊC under argon. After 1 h, a saturated
NH4Cl solution (30 cm3) was added with vigorous stirring. The
mixture was made acidic with saturated aqueous citric acid and
extracted with EtOAc. The extract was washed with water and
dried over MgSO4. The usual work-up followed by recrystalliz-
ation from Et2O gave the title compound 18 (4.11 g, 86%) as
colourless crystals, 98% ee (S) by HPLC [Daicel Chiralcel OD,
n-hexane–propan-2-ol = 95:5 (0.5 cm3 minϪ1), (S)-isomer 46.4
min, (R)-isomer 42.0 min]; mp 122 ЊC (Found: C, 61.6; H, 8.15;
N, 4.3. C16H25NO3S requires C, 61.7; H, 8.1; N, 4.5); [α]D20 Ϫ22.8
(c 2.60 in CHCl3); δH(270 MHz; CDCl3) 0.80 (3 H, d, J 6.8,
CMe), 0.87 (3 H, d, J 6.5, CMe), 1.35 (1 H, dd, J 5.1 and 5.1,
OH), 1.62–1.80 (1 H, m, 5-H), 2.30 (3 H, s, CMe), 2.63 (6 H, s,
2 × CMe), 3.54 (1 H, ddd, J 7.8, 7.6 and 4.6, 4-H), 3.85 (1 H, d,
J 5.1, 1-CHH), 3.87 (1 H, d, J 5.1, 1-CHH), 4.84 (1 H, d, J 7.8,
NH), 5.32 (1 H, dddd, J 15.4, 7.8, 1.4 and 1.4, 3-H), 5.48 (1 H,
dddd, J 15.4, 4.6, 4.6 and 0.7, 2-H), 6.94 (2 H, s).
To a stirred mixture of the alcohol 18 (2.06 g, 6.62 mmol),
pyridine (5 cm3) and CHCl3 (3 cm3) at Ϫ78 ЊC was added drop-
wise methyl chloroformate (1.03 cm3, 13.2 mmol), and the mix-
ture was stirred with warming to 0 ЊC. After 1 h, 5% NaHCO3
(10 cm3) was added to the mixture with vigorous stirring. The
whole was extracted with a mixed solvent of Et2O–EtOAc
(3:1), and the extract was washed successively with 5% aqueous
citric acid, H2O, 5% aqueous NaHCO3, and H2O, and dried
over MgSO4. Usual work-up followed by flash chromatography
over silica gel with n-hexane–EtOAc (3:1) gave the title com-
pound 22 (2.37 g, 97%) as a colourless oil [Found (FAB):
(M ϩ H)ϩ, 370.1672. C18H28NO5S requires M ϩ H, 370.1688];
[α]D20 Ϫ10.4 (c 2.72 in CHCl3); δH(270 MHz, CDCl3) 0.81 (3 H, d,
J 7.0, CMe), 0.88 (3 H, d, J 6.5, CMe), 1.68–1.80 (1 H, m, 5-H),
2.29 (3 H, s, CMe), 2.61 (6 H, s, 2 × CMe), 3.49–3.57 (1 H, m,
4-H), 3.77 (3 H, s, OMe), 4.28–4.34 (2 H, m, 1-CH2), 4.63 (1 H,
d, J 7.8, NH), 5.35 (1 H, dd, J 15.7 and 4.9, CH᎐CH), 5.39 (1 H,
᎐
dd, J 15.7 and 6.2, CH᎐CH), 6.92 (2 H, s, Ph); m/z (FAB-
᎐
LRMS) 370 (MHϩ), 368, 326, 294, 183, 171, 119 (base peak),
95.
3708
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716

View Article Online
(4S,2E)-O-Methoxycarbonyl-6-methyl-4-[N-(p-tolylsulfonyl)-
amino]hept-2-en-1-ol 23. By a procedure identical with that
described for the preparation of the carbonate 22 from 18,
the alcohol 19 (1.55 g, 5.2 mmol) was converted into the title
compound 23 (1.80 g, 97%), mp 45 ЊC [colourless crystals
from n-hexane–Et2O (4:1)] (Found: C, 57.2; H, 7.0; N, 3.7.
C17H25NO5S requires C, 57.4; H, 7.1; N, 3.9%); [α]D20 Ϫ5.4 (c 2.07
in CHCl3); δH(270 MHz, CDCl3) 0.79 (3 H, d, J 7.0, CMe), 0.82
(3 H, d, J 7.3, CMe), 1.26 (1 H, ddd, J 13.5, 7.0 and 7.0,
5-CHH), 1.34 (1 H, ddd, J 13.5, 7.0 and 7.0, 5-CHH), 1.53–
1.68 (1 H, m, 6-H), 2.42 (3 H, s, CMe), 3.77 (3 H, s, OMe), 3.82
(1 H, dddd, J 7.8, 7.0, 7.0 and 6.2, 4-H), 4.34–4.41 (2 H, m,
1-CH2), 4.81 (1 H, dd, J 7.8 and 4.3, NH), 5.42 (1 H, dd, J 15.9
and 6.2, 3-H), 5.48 (1 H, ddd, J 15.9, 5.4 and 5.4, 2-H), 7.26–
7.29 (2 H, m, Ph), 7.71–7.74 (2 H, m, Ph).
5.49 (1 H, ddd, J 15.7, 5.7 and 5.7, 2-H), 5.55 (1 H, dd, J 15.7
and 6.5, 3-H), 6.94 (2 H, s).
(4S,2E)-O-Methylsulfonyloxy-6-methyl-4-[N-(p-tolylsulf-
onyl)amino]hept-2-en-1-ol 27. By a procedure similar to that
described for the preparation of the mesylate 26 from 18, the
alcohol 19 (100 mg, 0.336 mmol) was converted into the title
compound 27 (125 mg, 99%) as a colourless oil [Found (FAB):
(M ϩ H)ϩ, 376.1236. C16H26NO5S2 requires M ϩ H, 376.1252];
[α]D28 Ϫ24.7 (c 0.825 in CHCl3); δH(270 MHz, CDCl3) 0.76 (3 H,
d, J 6.5, CMe), 0.82 (3 H, d, J 6.5, CMe), 1.23–1.35 (2 H, m,
5-CH2), 1.55–1.65 (1 H, m, 6-H), 2.43 (3 H, s, CMe), 2.99 (3 H,
s, SO2Me), 3.80–3.90 (1 H, m, 4-H), 4.31 (1 H, d, J 7.8, NH),
4.52–4.54 (2 H, m, 1-CH2), 5.52–5.60 (1 H, m, 2-H), 5.62 (1 H,
dd, J 15.4 and 5.1, 3-H), 7.28–7.32 (2 H, m, Ph), 7.68–7.74 (2 H,
m, Ph); m/z (FAB-LRMS) 376 (MHϩ), 374, 280 (base peak),
240, 155, 139, 109, 91.
(4S,2E)-O-Methoxycarbonyl-6-methyl-4-[N-(2,2,5,7,8-penta-
methylchroman-6-ylsulfonyl)amino]hept-2-en-1-ol 24. By a pro-
cedure identical with that described for the preparation of the
carbonate 22 from 18, the alcohol 20 (2.11 g, 5 mmol) was
converted into the title compound 24 (2.23 mg, 93%), mp 54 ЊC
[colourless crystals from n-hexane–Et2O (2:1)] (Found: C, 61.5;
H, 8.0; N, 2.9. C24H37NO6S requires C, 61.6; H, 8.0; N, 3.0%);
[α]D18 Ϫ10.3 (c 1.00 in CHCl3); δH(270 MHz, CDCl3) 0.79 (3 H, d,
J 6.5, CMe), 0.81 (3 H, d, J 6.2, CMe), 1.26 (1 H, dd, J 13.5 and
7.3, 5-CHH), 1.32 (6 H, s, 2 × CMe), 1.36 (1 H, dd, J 13.5
and 7.3, 5-CHH), 1.49–1.62 (1 H, m, 6-H), 1.83 (2 H, t, J 6.8,
3Ј-CH2), 2.12 (3 H, s, CMe), 2.52 (3 H, s, CMe), 2.54 (3 H, s,
CMe), 2.65 (2 H, t, J 6.8, 4Ј-CH2), 3.73–3.84 (1 H, m, 4-H), 3.77
(3 H, s, OMe), 4.25–4.37 (3 H, m, NH and 1-CH2), 5.38 (1 H,
dd, J 15.9 and 6.2, 3-H), 5.45 (1 H, ddd, J 15.9, 5.4 and 5.4,
2-H).
(4S,2E)-O-Methylsulfonyl-6-methyl-4-[N-(2,2,5,7,8-penta-
methylchroman-6-ylsulfonyl)amino]hept-2-en-1-ol 28. By a pro-
cedure similar to that described for the preparation of the
mesylate 26 from 18, the alcohol 20 (90 mg, 0.22 mmol) was
converted into the title compound 28 (90 mg, 84%) as a colour-
less oil [Found (FAB): (M ϩ H)ϩ, 487.2070. C23H37NO6S2
requires M ϩ H, 487.2062]; [α]D24 Ϫ25.0 (c 1.17 in CHCl3); δH(270
MHz, CDCl3) 0.76 (3 H, d, J 6.2, CMe), 0.81 (3 H, d, J 6.8,
CMe), 1.18–1.43 (2 H, m, 5-CH2), 1.32 (6 H, s, 2 × CMe), 1.47–
1.61 (1 H, m, 6-H), 1.84 (2 H, t, J 7.0, 3Ј-CH2), 2.13 (3 H, s,
CMe), 2.53 (3 H, s, CMe), 2.54 (3 H, s, CMe), 2.65 (2 H, t, J 7.0,
4Ј-CH2), 2.98 (3 H, s, SO2Me), 3.75–3.87 (1 H, m, 4-H), 4.41
(1 H, d, J 7.6, NH), 4.43–4.53 (2 H, m, 1-CH2), 5.55 (1 H, dd,
J 15.6 and 2.1, 3-H), 5.57 (1 H, m, 2-H); m/z (FAB-LRMS) 487
(MHϩ), 392, 267, 251, 203 (base peak), 202, 147, 109.
(4S,2E)-O-Methoxycarbonyl-5-phenyl-4-[N-(2,4,6-trimethyl-
phenylsulfonyl)amino]pent-2-en-1-ol 25. By a procedure identi-
cal with that described for the preparation of the carbonate 22
from 18, the alcohol 21 (290 mg, 0.81 mmol) was converted into
the title compound 25 (335 mg, 99%) as a colourless oil [Found
(FAB): (M ϩ H)ϩ, 418.1683. C22H28NO5S requires M ϩ H,
418.1688]; [α]D22 Ϫ20.9 (c 0.766 in CHCl3); δH(270 MHz, CDCl3)
2.28 (3 H, s, CMe), 2.47 (6 H, s, 2 × CMe), 2.76 (1 H, dd, J 13.8
and 7.3, 5-CHH), 2.81 (1 H, dd, J 13.8 and 6.2, 5-CHH), 3.78
(3 H, s, OMe), 3.91–4.00 (1 H, m, 4-H), 4.38 (1 H, d, J 14.3,
1-CHH), 4.40 (1 H, d, J 14.3, 1-CHH), 4.50 (1 H, d, J 6.2, NH),
5.51 (1 H, ddd, J 15.4, 4.9 and 4.9, 2-H), 5.53 (1 H, dd, J 15.4
and 5.7, 3-H), 6.87 (2 H, s, Ph), 7.01–7.07 (2 H, m, Ph), 7.17–
7.28 (3 H, m, Ph); m/z (FAB-LRMS) 418 (MHϩ), 342, 326, 219,
183, 143, 119 (base peak), 91.
(4S,2E)-O-Methylsulfonyl-5-phenyl-4-[N-(2,4,6-trimethyl-
phenylsulfonyl)amino]pent-2-en-1-ol 29. By a procedure similar
to that described for the preparation of the mesylate 26 from
18, the alcohol 21 (100 mg, 0.278 mmol) was converted into the
title compound 29 (96 mg, 79%), mp 99–100 ЊC [colourless
crystals from CHCl3–Et2O (1:10)] (Found: C, 57.4; H, 6.2; N,
3.3. C21H27NO5S2 requires C, 57.6; H, 6.2; N, 3.2%); [α]D32 Ϫ34.2
(c 1.38 in CHCl3); δH(270 MHz, CDCl3) 2.29 (3 H, s, CMe), 2.46
(6 H, s, 2 × CMe), 2.74 (1 H, dd, J 13.8 and 7.6, 5-CHH), 2.81
(1 H, dd, J 13.8 and 6.2, 5-CHH), 2.93 (3 H, s, SO2Me), 3.92–
4.02 (1 H, m, 4-H), 4.51–4.54 (2 H, m, 1-CH2), 4.59 (1 H, d,
J 6.5, NH), 5.61 (1 H, ddd, J 15.4, 5.1 and 5.1, 2-H), 5.70 (1 H,
dd, J 15.4 and 6.2, 3-H), 6.88 (2 H, s, Ph), 6.97–7.03 (2 H, m,
Ph), 7.19–7.24 (3 H, m, Ph).
(2S,3S)-2-[N-(4-Methoxy-2,3,6-trimethylphenylsulfonyl)-
amino]-4-methylpentan-1-ol 30. To a stirred solution of (S)-
isoleucinol (10 g, 85.3 mmol) in a mixed solvent of CHCl3 (20
cm3) and DMF (10 cm3) were added Et3N (24.8 cm3, 179 mmol)
and 4-methoxy-2,3,6-trimethylphenylsulfonyl chloride (22.3 g,
89.6 mmol) at 0 ЊC, and the mixture was stirred for 6 h at this
temperature followed by quenching with 5 cm3 of 5% aqueous
NaHCO3. The whole was extracted with Et2O–EtOAc (1:1),
and the extract was washed successively with 5% aqueous citric
acid, water, 5% aqueous NaHCO3, and water, and dried over
MgSO4. Concentration under reduced pressure gave an oily
residue, which was filtered through a short pad of silica gel. The
filtrate was concentrated under reduced pressure to leave a
crystalline mass. Recrystallization from n-hexane–EtOAc (3:2)
gave the title compound 30 (22.5 g, 80%) as colourless crystals.
mp 63 ЊC (Found: C, 58.4; H, 8.2; N, 4.3. C16H27NO4S requires
C, 58.3; H, 8.3; N, 4.25%); [α]D25 Ϫ17.1 (c 1.51 in CHCl3); δH(270
MHz, CDCl3) 0.76 (3 H, t, J 7.8, CMe), 0.77 (3 H, d, J 7.3,
CMe), 0.95–1.11 (1 H, m, 4-CHH), 1.31–1.57 (2 H, m, 4-CHH
and 3-H), 2.15 (3 H, s, CMe), 2.17 (1 H, m, OH), 2.61 (3 H, s,
CMe), 2.68 (3 H, s, CMe), 3.10 (1 H, dddd, J 8.6, 5.4, 5.4 and
General procedure for preparation of allylic methanesulfonates
26–29, 34 and 47–49: (4S,2E)-1-methylsulfonyloxy-5-methyl-4-
[(2,4,6-trimethylphenylsulfonyl)amino]hex-2-ene 26
To a stirred mixture of the alcohol 18 (100 mg, 0.334 mmol),
Et3N (0.46 cm3, 3.34 mmol), and THF (5 cm3) was added drop-
wise methanesulfonyl chloride (0.13 cm3, 1.67 mmol) at 0 ЊC.
The stirring was continued for 0.5 h at 0 ЊC followed by quench-
ing with 1 cm3 of saturated aqueous NaHCO3 with vigorous
stirring. The whole was extracted with Et2O and the extract was
washed successively with 5% aqueous citric acid, water, 5%
aqueous NaHCO3, and water, and dried over MgSO4. Usual
work-up followed by flash chromatography over silica gel with
n-hexane–EtOAc (2:1) gave the title compound 26 (127 mg,
98%), mp 56 ЊC [colourless crystals from n-hexane–Et2O
(1:10)] (Found: C, 52.45; H, 7.15; N, 3.4. C17H27NO5S2 requires
C, 52.4; H, 7.0; N, 3.6%); [α]D31 Ϫ31.4 (c 0.63 in CHCl3); δH(270
MHz, CDCl3) 0.80 (3 H, d, J 6.8, CMe), 0.86 (3 H, d, J 7.0,
CMe), 1.68–1.80 (1 H, m, 5-H), 2.30 (3 H, s, CMe), 2.62 (6 H, s,
2 × CMe), 2.98 (3 H, s, SO2Me), 3.57 (1 H, ddd, J 7.8, 6.5 and
5.7, 4-H), 4.45–4.47 (2 H, m, 1-CH2), 4.59 (1 H, d, J 7.8, NH),
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716
3709

View Article Online
5.4, 2-H), 3.57 (1 H, d, J 5.4, 1-CHH), 3.59 (1 H, d, J 5.4,
1-CHH), 3.85 (3 H, s, OMe), 4.89–5.01 (1 H, m, NH), 6.58
(1 H, s, Ph).
(2R)-1-tert-Butyldimethylsiloxy-2-[N-(2,4,6-trimethylphenyl-
sulfonyl)amino]propan-3-ol 35. By a procedure identical with
that described for the preparation of the alcohol 18 from 14,
methyl (S)-O-tert-butyldimethylsilyl-N-(2,4,6-trimethylphenyl-
sulfonyl)serinate (8.3 g, 20.0 mmol) was converted into the title
compound 35 (4.87 g, 63%), mp 87 ЊC (colourless crystals from
n-hexane) (Found: C, 55.8; H, 8.6; N, 3.4. C18H33NO4SSi
requires C, 55.8; H, 8.6; N, 3.6%); [α]D26 ϩ16.3 (c 0.808 in CHCl3);
δH(270 MHz, CDCl3) 0.02 (6 H, s, 2 × SiMe), 0.86 (9 H, s,
CMe3), 2.27 (1 H, m, OH), 2.30 (3 H, s, CMe), 2.65 (6 H, s,
2 × CMe), 3.16–3.25 (1 H, m, 2-H), 3.48–3.57 (2 H, m, 1-CHH
and 3-CHH), 3.63–3.72 (2 H, m, 1-CHH and 3-CHH), 5.29
(1 H, d, J 7.8, NH), 6.96 (2 H, s, Ph).
Methyl (4S,5S,2E)-4-[N-(4-methoxy-2,3,6-trimethylphenyl-
sulfonyl)amino]-5-methylhept-2-enoate 31. By a procedure iden-
tical with that described for the preparation of the enoate 14
from 10, the alcohol 30 (4.5 g, 13.7 mmol) was converted into
the title compound 31 (5.04 g, 96%) as a colourless oil [Found
(FAB): (M ϩ H)ϩ, 384.1841. C19H30NO5S requires M ϩ H,
384.1845]; [α]D23 Ϫ31.9 (c 1.13 in CHCl3); δH(270 MHz, CDCl3)
0.80 (3 H, d, J 6.8, CMe), 0.85 (3 H, t, J 7.3, CMe), 1.02–1.26
(1 H, m, 6-CHH), 1.35–1.62 (2 H, m, 6-CHH and 5-H), 2.11
(3 H, s, CMe), 2.56 (3 H, s, CMe), 2.65 (3 H, s, CMe), 3.64 (3 H,
s, OMe), 3.72 (1 H, ddd, J 8.1, 7.8 and 5.4, 4-H), 3.84 (3 H, s,
OMe), 4.65 (1 H, d, J 8.1, NH), 5.53 (1 H, dd, J 15.7 and 1.1,
2-H), 6.47 (1 H, dd, J 15.7 and 7.8, 3-H), 6.55 (1 H, s, Ph); m/z
(FAB-LRMS) 384 (MHϩ), 382, 326, 213 (base peak), 197, 155,
149, 119, 91.
(2R)-1-Benzyloxy-2-[N-(2,4,6-trimethylphenylsulfonyl)-
amino]propan-3-ol 36. By a procedure identical with that
described for the preparation of the alcohol 18 from 14, methyl
(S)-O-benzyl-N-(2,4,6-trimethylphenylsulfonyl)serinate (5.7 g,
14.6 mmol) was converted into the title compound 36 (4.17 g,
79%) as a colourless oil [Found (FAB): (M ϩ H)ϩ, 364.1586.
C19H26NO4S requires M ϩ H, 364.1582]; [α]D27 ϩ22.6 (c 1.37 in
CHCl3); δH(270 MHz, CDCl3) 2.20–2.27 (1 H, m, OH), 2.30
(3 H, s, CMe), 2.62 (6 H, s, 2 × CMe), 3.34 (1 H, m, 2-H), 3.39
(1 H, dd, J 9.2 and 4.3, 1-CHH), 3.53 (1 H, dd, J 9.2 and 4.1,
1-CHH), 3.53–3.59 (1 H, m, 3-CHH), 3.69 (1 H, ddd, J 11.6,
4.3 and 4.3, 3-CHH), 4.38 (2 H, m, PhCH2), 5.31 (1 H, d, J 7.8,
NH), 6.93 (2 H, s, Ph), 7.19–7.38 (5 H, m, Ph); m/z (FAB-
LRMS) 364 (MHϩ), 362, 256, 242, 182, 167, 150, 119, 91 (base
peak), 74, 60.
(4S,5S,2E)-4-[N-(4-Methoxy-2,3,6-trimethylphenylsulfonyl)-
amino]-5-methylhept-2-en-1-ol 32. By a procedure identical with
that described for the preparation of the alcohol 18 from 14, the
enoate 31 (5.2 g, 13.6 mmol) was converted into the title com-
pound 32 (4.25 g, 88%) as a colourless oil [Found (FAB):
(M ϩ H)ϩ, 356.1900. C18H30NO4S requires M ϩ H, 356.1895];
[α]D25 Ϫ7.26 (c 1.02 in CHCl3); δH(270 MHz, CDCl3) 0.78 (3 H, d,
J 6.5, CMe), 0.83 (3 H, t, J 7.0, CMe), 0.99–1.15 (1 H, m,
6-CHH), 1.21–1.54 (2 H, m, 6-CHH and 5-H), 2.15 (3 H, s,
CMe), 2.58 (3 H, s, CMe), 2.66 (3 H, s, CMe), 3.65 (1 H, ddd,
J 7.8, 7.3 and 6.2, 4-H), 3.85 (3 H, s, OMe), 3.86 (1 H, d, J 5.4,
1-CHH), 3.88 (1 H, d, J 5.4, 1-CHH), 4.70 (1 H, d, J 7.3, NH),
5.31 (1 H, dd, J 15.4 and 7.8, 3-H), 5.49 (1 H, ddd, J 15.4, 5.4
and 5.4, 2-H), 6.56 (1 H, s, Ph); m/z (FAB-LRMS) 356 (MHϩ),
354, 338, 298, 230, 213 (base peak), 197, 165, 149, 119, 109, 91,
86.
(2R,3R)-3-tert-Butyldimethylsiloxy-2-[N-(p-tolylsulfonyl)-
amino]butan-1-ol 37. By a procedure identical with that
described for the preparation of the alcohol 18 from 14, methyl
(2S,3R)-O-tert-butyldimethylsilyl-N-(p-tolylsulfonyl)threo-
ninate (6.40 g, 15.9 mmol) was converted into the title
compound 37 (4.55 g, 76%) as a colourless oil [Found
(FAB): (M ϩ H)ϩ, 374.1823. C17H32NO4SSi requires M ϩ H,
374.1821]; [α]D25 Ϫ10.9 (c 1.32 in CHCl3); δH(270 MHz, CDCl3)
0.04 (6 H, s, SiMe2), 0.86 (9 H, s, CMe3), 0.92 (3 H, d, J 6.2,
CMe), 2.19 (1 H, dd, J 7.6 and 4.3, OH), 2.42 (3 H, s, CMe),
3.11 (1 H, dddd, J 7.8, 6.5, 5.7 and 2.2, 2-H), 3.50 (1 H, ddd,
J 10.8, 7.6 and 6.5, 1-CHH), 3.60 (1 H, ddd, J 10.8, 5.7 and 4.3,
1-CHH), 4.00 (1 H, qd, J 6.2 and 2.2, 3-H), 5.02 (1 H, d, J 7.8,
NH), 7.28–7.32 (2 H, m, Ph), 7.75–7.80 (2 H, m, Ph); m/z (FAB-
LRMS) 374 (MHϩ, base peak), 316, 242, 220, 198, 155, 139, 91,
73.
(4S,5S,2E)-O-Methoxycarbonyl-4-[N-(4-methoxy-2,3,6-
trimethylphenylsulfonyl)amino]-5-methylhept-2-en-1-ol 33. By a
procedure identical with that described for the preparation of
the carbonate 22 from 18, the alcohol 32 (2.0 g, 5.63 mmol) was
converted into the title compound 33 (2.05 g, 88%) as a colour-
less oil [Found (FAB): (M ϩ H)ϩ, 414.1945. C20H32NO6S
requires M ϩ H, 414.1950]; [α]D18
0
1 (c 1.12 in CHCl3); δH(270
MHz, CDCl3) 0.79 (3 H, d, J 6.5, CMe), 0.84 (3 H, t, J 7.3,
CMe), 0.99–1.16 (1 H, m, 6-CHH), 1.31–1.57 (2 H, m, 6-CHH
and 5-H), 2.14 (3 H, s, CMe), 2.56 (3 H, s, CMe), 2.64 (3 H, s,
CMe), 3.58–3.70 (1 H, m, 4-H), 3.77 (3 H, s, OMe), 3.85 (3 H, s,
OMe), 4.30 (1 H, dd, J 14.3 and 1.1, 1-CHH), 4.32 (1 H, dd,
J 14.3 and 1.6, 1-CHH), 4.49 (1 H, d, J 7.6, NH), 5.36 (1 H, dd,
J 15.1 and 1.6, 3-H), 5.37–5.44 (1 H, m, 2-H), 6.55 (1 H, s, Ph);
m/z (FAB-LRMS) 414 (MHϩ), 412, 356, 338, 213 (base peak),
197, 149, 109.
Methyl (4R,2E)-5-tert-butyldimethylsiloxy-4-[N-(2,4,6-tri-
methylphenylsulfonyl)amino]pent-2-enoate 38 and its (4R,2Z)
isomer. By a procedure identical with that described for the
preparation of the enoate 14 from 10, the alcohol 35 (4.6 g, 11.9
mmol) was converted into the title compound 38 (4.02 g, 77%)
and its (Z)-isomer (301 mg, 6%). Compound 38: a colourless oil
[Found (FAB): (M ϩ H)ϩ, 442.2079. C21H36NO5SSi requires
M ϩ H, 442.2083]; [α]D27 Ϫ47.4 (c 1.19 in CHCl3); δH(270 MHz,
CDCl3) 0.02 (6 H, s, 2 × SiMe), 0.86 (9 H, s, CMe3), 2.29 (3 H, s,
CMe), 2.61 (6 H, s, 2 × CMe), 3.50–3.61 (2 H, m, 5-CH2), 3.68
(3 H, s, OMe), 3.83–3.92 (1 H, m, 4-H), 5.19 (1 H, d, J 6.5, NH),
5.85 (1 H, d, J 15.4, 2-H), 6.65 (1 H, dd, J 15.4 and 6.5, 3-H),
6.94 (2 H, s, Ph); m/z (FAB-LRMS) 442 (MHϩ), 426, 384 (base
peak), 256, 243, 183, 167, 119, 89, 73. (Z)-Isomer of 38: mp
44 ЊC (colourless crystals from n-hexane) (Found: C, 56.8; H,
8.0; N, 2.9. C21H35NO5SSi requires C, 57.1; H, 8.0; N, 3.2%); [α]D24
Ϫ23.9 (c 0.977 in CHCl3); δH(270 MHz, CDCl3) 0.05 (6 H, s,
2 × SiMe), 0.86 (9 H, s, CMe3), 2.29 (3 H, s, CMe), 2.59 (6 H, s,
2 × CMe), 3.51 (1 H, dd, J 9.7 and 5.7, 5-CHH), 3.65 (3 H, s,
OMe), 3.66 (1 H, dd, J 9.7 and 4.1, 5-CHH), 4.79–4.89 (1 H, m,
4-H), 5.43 (1 H, d, J 5.4, NH), 5.72 (1 H, d, J 11.9, 2-H), 6.12
(1 H, dd, J 11.9 and 8.4, 3-H), 6.93 (2 H, s, Ph).
(4S,5S,2E)-O-Methylsulfonyl-4-[N-(4-methoxy-2,3,6-
trimethylphenylsulfonyl)amino]-5-methylhept-2-en-1-ol 34. By a
procedure similar to that described for the preparation of the
mesylate 26 from 18, the alcohol 32 (711 mg, 2.0 mmol) was
converted into the title compound 34 (780 mg, 90%) as a colour-
less oil [Found (FAB): (M ϩ H)ϩ, 434.1659. C19H32NO6S2
requires M ϩ H, 434.1671]; [α]D24 Ϫ17.5 (c 0.902 in CHCl3);
δH(270 MHz, CDCl3) 0.78 (3 H, d, J 6.5, CMe), 0.83 (3 H, t,
J 7.3, CMe), 0.99–1.15 (1 H, m, 6-CHH), 1.30–1.53 (2 H, m,
6-CHH and 5-H), 2.15 (3 H, s, CMe), 2.57 (3 H, s, CMe), 2.64
(3 H, s, CMe), 2.97 (3 H, s, SO2Me), 3.64–3.71 (1 H, m, 4-H),
3.86 (3 H, s, OMe), 4.43–4.51 (2 H, m, 1-CH2), 4.54 (1 H, d,
J 7.8, NH), 5.50 (1 H, dd, J 15.7 and 5.4, 3-H), 5.53 (1 H, m,
2-H), 6.57 (1 H, s, Ph); m/z (FAB-LRMS) 434 (MHϩ), 376, 338,
213 (base peak), 197, 149, 134, 109.
3710
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716

View Article Online
Methyl
(4R,2E)-5-benzyloxy-4-[N-(2,4,6-trimethylphenyl-
(2 H, s, Ph), 7.22–7.38 (5 H, m, Ph); m/z (FAB-LRMS) 390
sulfonyl)amino]pent-2-enoate 39 and its (4R,2Z) isomer. By a
procedure identical with that described for the preparation of
the enoate 14 from 10, the alcohol 36 (4.0 g, 11.0 mmol) was
converted into the title compound 39 (2.7 g, 59%) and its (Z)-
isomer (320 mg, 7%). Compound 39: a colourless oil [Found
(FAB): (M ϩ H)ϩ, 418.1684. C22H28NO5S requires M ϩ H,
418.1688]; [α]D25 Ϫ35.5 (c 1.41 in CHCl3); δH(270 MHz, CDCl3)
2.29 (3 H, s, CMe), 2.58 (6 H, s, 2 × CMe), 3.37–3.46 (2 H, m,
5-CH2), 3.69 (3 H, s, OMe), 3.95–4.05 (1 H, m, 4-H), 4.41 (1 H,
d, J 12.2, PhCHH), 4.42 (1 H, d, J 12.2, PhCHH), 5.20 (1 H, d,
J 6.8, NH), 5.88 (1 H, dd, J 15.7 and 1.4, 2-H), 6.68 (1 H, dd,
J 15.7 and 6.5, 3-H), 6.91 (2 H, s, Ph), 7.20–7.38 (5 H, m, Ph);
m/z (FAB-LRMS) 418 (MHϩ), 416, 386, 310, 296, 290, 234,
209, 183, 167, 128, 119, 91 (base peak), 77. (Z)-Isomer of 39: a
colourless oil [Found (FAB): (M ϩ H)ϩ, 418.1692. C22H28NO5S
requires M ϩ H, 418.1688]; [α]D25 Ϫ14.6 (c 0.632 in CHCl3);
δH(270 MHz, CDCl3) 2.29 (3 H, s, CMe), 2.55 (6 H, s,
2 × CMe), 3.44 (1 H, dd, J 9.7 and 6.5, 5-CHH), 3.52 (1 H, dd,
J 9.7 and 4.1, 5-CHH), 3.65 (3 H, s, OMe), 4.37 (1 H, d, J 12.2,
PhCHH), 4.38 (1 H, d, J 12.2, PhCHH), 4.99–5.09 (1 H, m,
4-H), 5.43 (1 H, d, J 5.1, NH), 5.73 (1 H, dd, J 11.3 and 1.6,
2-H), 6.16 (1 H, dd, J 11.3 and 8.4, 3-H), 6.90 (2 H, s, Ph), 7.20–
7.37 (5 H, m, Ph); m/z (FAB-LRMS) 418 (MHϩ), 296, 234, 212,
183, 167, 119, 91 (base peak).
(MHϩ), 372, 290, 268, 200, 183, 167, 119, 91 (base peak).
(4R,5R,2E)-5-tert-Butyldimethylsiloxy-4-[N-(p-tolylsulfonyl)-
amino]hex-2-en-1-ol 43. By a procedure identical with that
described for the preparation of the alcohol 18 from 14, the
enoate 40 (3.93 g, 9.19 mmol) was converted into the title com-
pound 43 (3.32 g, 90%), mp 79 ЊC [colourless crystals from
n-hexane–Et2O (4:1)] (Found: C, 56.8; H, 8.6; N, 3.2. C19H33-
NO4SSi requires C, 57.1; H, 8.3; N, 3.5%); [α]D31 Ϫ26.4 (c 1.39 in
CHCl3); δH(270 MHz, CDCl3) 0.01 (3 H, s, SiMe), 0.02 (3 H, s,
SiMe), 0.86 (9 H, s, CMe3), 1.07 (3 H, d, J 5.9, CMe), 1.26 (1 H,
dd, J 5.9 and 5.9, OH), 2.41 (3 H, s, CMe), 3.56–3.64 (1 H, m,
5-H), 3.73–3.81 (1 H, m, 4-H), 3.92 (1 H, d, J 5.1, 1-CHH), 3.94
(1 H, d, J 5.1, 1-CHH), 4.95 (1 H, d, J 7.3, NH), 5.43 (1 H, dd,
J 15.4 and 6.5, 3-H), 5.58 (1 H, ddd, J 15.4, 5.1 and 5.1, 2-H),
7.26–7.30 (2 H, m, Ph), 7.69–7.73 (2 H, m, Ph).
(4R,2E)-5-tert-Butyldimethylsiloxy-O-methoxycarbonyl-4-
[N-(2,4,6-trimethylphenylsulfonyl)amino]pent-2-en-1-ol 44. By a
procedure identical with that described for the preparation of
the carbonate 22 from 18, the alcohol 41 (1.5 g, 3.63 mmol) was
converted into the title compound 44 (1.54 g, 90%), mp 57 ЊC
[colourless shiny needles from n-hexane–Et2O (4:1)] [Found
(FAB): (M ϩ H)ϩ, 472.2186. C22H38NO6SSi requires M ϩ H,
472.2189]; [α]D27 Ϫ22.8 (c 0.996 in CHCl3); δH(300 MHz, CDCl3)
0.019 (3 H, s, SiMe), 0.020 (3 H, s, SiMe), 0.86 (9 H, s, CMe3),
2.29 (3 H, s, CMe), 2.61 (6 H, s, 2 × CMe), 3.48 (1 H, dd, J 9.9
and 5.4, 5-CHH), 3.54 (1 H, dd, J 9.9 and 4.1, 5-CHH), 3.70–
3.76 (1 H, m, 4-H), 3.77 (3 H, s, OMe), 4.38–4.41 (2 H, m,
1-CH2), 5.12 (1 H, d, J 5.9, NH), 5.51 (1 H, dd, J 15.6 and 6.8,
3-H), 5.61 (1 H, ddd, J 15.6, 5.9 and 5.9, 2-H), 6.93 (2 H, s, Ph);
m/z (FAB-LRMS) 472 (MHϩ), 414, 396, 366, 326, 298, 256,
213, 197, 167, 119, 73 (base peak).
Methyl (4R,5R,2E)-5-tert-butyldimethylsiloxy-4-[N-(p-tolyl-
sulfonyl)amino]hex-2-enoate 40. By a procedure identical with
that described for the preparation of the enoate 14 from 10, the
alcohol 37 (4.34 g, 11.6 mmol) was converted into the title com-
pound 40 (4.23 g, 85%). mp 63 ЊC (colourless needles from
n-hexane) [Found (FAB): (M ϩ H)ϩ, 428.1918. C20H34NO5SSi
requires M ϩ H, 428.1927]; [α]D30 Ϫ47.4 (c 1.00 in CHCl3); δH(270
MHz, CDCl3) Ϫ0.02 (3 H, s, SiMe), 0.02 (3 H, s, SiMe), 0.84
(9 H, s, CMe3), 1.08 (3 H, d, J 5.9, CMe), 2.41 (3 H, s, CMe),
3.68 (3 H, s, OMe), 3.78–3.89 (2 H, m, 4-H and 5-H), 4.99 (1 H,
d, J 7.8, NH), 5.76 (1 H, d, J 15.9, 2-H), 6.67 (1 H, dd, J 15.9
and 5.9, 3-H), 7.26–7.30 (2 H, m, Ph), 7.69–7.73 (2 H, m, Ph);
m/z (FAB-LRMS) 428 (MHϩ), 412, 370, 296, 257, 228, 214,
159, 155, 91, 73 (base peak).
(4R,2E)-5-Benzyloxy-O-methoxycarbonyl-4-[N-(2,4,6-tri-
methylphenylsulfonyl)amino]pent-2-en-1-ol 45. By a procedure
identical with that described for the preparation of the carbon-
ate 22 from 18, the alcohol 42 (1.0 g, 2.57 mmol) was converted
into the title compound 45 (1.13 g, 98%) as a colourless oil
[Found (FAB): (M ϩ H)ϩ, 448.1801. C23H30NO6S requires
M ϩ H, 448.1794]; [α]D25 Ϫ18.4 (c 0.706 in CHCl3); δH(270 MHz,
CDCl3) 2.29 (3 H, s, CMe), 2.58 (6 H, s, 2 × CMe), 3.33–3.43
(2 H, m, 5-CH2), 3.77 (3 H, s, OMe), 3.85–3.93 (1 H, m, 4-H),
4.37–4.47 (4 H, m, 1-CH2 and PhCH2), 5.13 (1 H, d, J 5.9, NH),
5.55 (1 H, dd, J 15.7 and 5.9, 3-H), 5.62 (1 H, ddd, J 15.7, 5.1
and 5.1, 2-H), 6.91 (2 H, s, Ph), 7.22–7.38 (5 H, m, Ph); m/z
(FAB-LRMS) 448 (MHϩ), 446, 372, 342, 326, 264, 183, 159,
119, 91 (base peak).
(4R,2E)-5-tert-Butyldimethylsiloxy-4-[N-(2,4,6-trimethyl-
phenylsulfonyl)amino]pent-2-en-1-ol 41. By a procedure identi-
cal with that described for the preparation of the alcohol 18
from 14, the enoate 38 (3.9 g, 8.83 mmol) was converted into the
title compound 41 (2.88 g, 79%) as a colourless oil [Found
(FAB): (M ϩ H)ϩ, 414.2138. C20H36NO4SSi requires M ϩ H,
414.2134]; [α]D24 Ϫ26.6 (c 1.53 in CHCl3); δH(270 MHz, CDCl3)
0.029 (3 H, s, SiMe), 0.032 (3 H, s, SiMe), 0.87 (9 H, s, CMe3),
1.11 (1 H, m, OH), 2.30 (3 H, s, CMe), 2.62 (6 H, s, 2 × CMe),
3.47 (1 H, dd, J 10.0 and 5.4, 5-CHH), 3.57 (1 H, dd, J 10.0 and
4.3, 5-CHH), 3.70–3.78 (1 H, m, 4-H), 3.89–3.92 (2 H, m,
1-CH2), 5.18 (1 H, d, J 5.4, NH), 5.39 (1 H, dddd, J 15.7, 7.8,
1.6 and 1.6, 3-H), 5.65 (1 H, dddd, J 15.7, 5.1, 5.1 and 0.8, 2-H),
6.94 (2 H, s, Ph); m/z (FAB-LRMS) 414 (MHϩ), 396, 356, 314,
298, 256, 215, 197, 167, 119, 89, 73 (base peak), 59.
(4R,5R,2E)-5-tert-Butyldimethylsiloxy-O-methoxycarbonyl-
4-[N-(p-tolylsulfonyl)amino]hex-2-en-1-ol 46. By a procedure
identical with that described for the preparation of the carbon-
ate 22 from 18, the alcohol 43 (1.72 g, 4.30 mmol) was con-
verted into the title compound 46 (1.87 g, 95%) as a colourless
oil [Found (FAB): (M ϩ H)ϩ, 458.2039. C21H36NO6SSi requires
M ϩ H, 458.2032]; [α]D32 Ϫ15.1 (c 1.39 in CHCl3); δH(270 MHz,
CDCl3) Ϫ0.01 (3 H, s, SiMe), 0.02 (3 H, s, SiMe), 0.85 (9 H, s,
CMe3), 1.08 (3 H, d, J 5.9, CMe), 2.41 (3 H, s, CMe), 3.63–3.70
(1 H, m, 5-H), 3.76–3.82 (1 H, m, 4-H), 3.77 (3 H, s, OMe), 4.40
(2 H, m, 1-CH2), 4.89 (1 H, d, J 7.8, NH), 5.51 (1 H, dd, J 15.7
and 3.8, 3-H), 5.52 (1 H, d, J 15.7, 2-H), 7.25–7.28 (2 H, m, Ph),
7.68–7.72 (2 H, m, Ph); m/z (FAB-LRMS) 458 (MHϩ), 400, 382,
338, 228, 159 (base), 155, 115, 73.
(4R,2E)-5-Benzyloxy-4-[N-(2,4,6-trimethylphenylsulfonyl)-
amino]pent-2-en-1-ol 42. By a procedure identical with that
described for the preparation of the alcohol 18 from 14, the
enoate 39 (2.6 g, 6.23 mmol) was converted into the title com-
pound 42 (2.26 g, 93%) as a colourless oil [Found (FAB):
(M ϩ H)ϩ, 390.1747. C21H28NO4S requires M ϩ H, 390.1739];
[α]D26 Ϫ23.2 (c 0.896 in CHCl3); δH(270 MHz, CDCl3) 1.25 (1 H,
dd, J 5.9 and 5.9, OH), 2.29 (3 H, s, CMe), 2.59 (6 H, s,
2 × CMe), 3.37 (1 H, dd, J 9.2 and 5.7, 5-CHH), 3.40 (1 H, dd,
J 9.2 and 4.9, 5-CHH), 3.85–3.93 (3 H, m, 4-H and 1-CH2),
4.42 (1 H, d, J 11.9, PhCHH), 4.43 (1 H, d, J 11.9, PhCHH),
5.19 (1 H, d, J 5.9, NH), 5.44 (1 H, dddd, J 15.9, 7.6, 1.4 and
1.4, 3-H), 5.67 (1 H, dddd, J 15.9, 5.4, 5.4 and 1.1, 2-H), 6.92
(4R,2E)-5-tert-Butyldimethylsiloxy-O-methylsulfonyl-4-[N-
(2,4,6-trimethylphenylsulfonyl)amino]pent-2-en-1-ol 47. By a
procedure similar to that described for the preparation of the
mesylate 26 from 18, the alcohol 41 (300 mg, 0.725 mmol) was
converted into the title compound 47 (314 mg, 88%) as colour-
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716
3711

View Article Online
less crystals, mp 57–59 ЊC [from n-hexane–Et2O (1:1)] [Found
(FAB): (M ϩ H)ϩ, 492.1917. C21H38NO6S2 requires M ϩ H,
492.1910]; [α]D26 Ϫ29.8 (c 1.33 in CHCl3); δH(270 MHz in CDCl3)
0.02 (6 H, s, SiMe2), 0.86 (9 H, s, CMe3), 2.30 (3 H, s, CMe),
2.61 (6 H, s, 2 × CMe), 2.98 (3 H, s, SO2Me), 3.48 (1 H, dd, J 9.7
and 5.1, 5-CHH), 3.52 (1 H, dd, J 9.7 and 4.3, 5-CHH), 3.72–
3.77 (1 H, m, 4-H), 4.52-4.54 (2 H, m, 1-CH2), 5.17 (1 H,
5.02 (1 H, dddd, J 5.9, 4.6, 1.1 and 1.1, 3-H), 5.23 (1 H, ddd,
J 10.6, 1.1 and 1.1, 1-CHH), 5.26 (1 H, ddd, J 17.3, 1.4 and 1.4,
1-CHH), 5.67 (1 H, ddd, J 17.3, 10.6 and 5.9, 2-H), 6.93 (2 H, s,
Ph).
General procedure for aziridination reaction of acyclic allylic
carbonates 22–25 and 33 with tetrakis(triphenylphosphine)-
palladium(0): synthesis of (2R,3S)-3-isopropyl-N-(2,4,6-
trimethylphenylsulfonyl)-2-vinylaziridine 54 and its (2S,3S)-
isomer 55 from the carbonate 22
d, J 5.9, NH), 5.61–5.67 (1 H, m, CH᎐CH), 5.69 (1 H, dd,
᎐
J 15.7 and 5.4, CH᎐CH), 6.95 (2 H, s, Ph); m/z (FAB-
᎐
LRMS) 492 (MHϩ), 490, 434, 396, 366, 256, 153, 119, 73 (base
peak).
A stirred mixture of the allylic carbonate 22 (369 mg, 1 mmol)
and Pd(PPh3)4 (57.7 mg, 0.05 mmol, 5 mol%) in dry THF (3
cm3) was heated at 60 ЊC for 20 min. The mixture was concen-
trated under reduced pressure to leave an oil, which was flash
chromatographed on a short silica gel column with n-hexane–
EtOAc (10:1) to give a 94:6 mixture of the title compounds 54
and 55 (210 mg, 72% combined yield). The mixture was flash
chromatographed over silica gel. Elution with n-hexane–EtOAc
(12:1) gave 54 (197 mg, 68%) and further elution yielded 55
(13 mg, 4%). Compound 54: 98% ee (2R,3S) by HPLC [Daicel
Chiralcel OD, n-hexane–propan-2-ol = 99.5:0.5 (0.5 cm3 minϪ1),
(2R,3S)-isomer 24.7 min, (2S,3R)-isomer 22.1 min]; colourless
prisms, mp 46 ЊC (from cold n-hexane) (Found: C, 65.4; H, 8.0;
N, 4.7. C16H23NO2S requires C, 65.5; H, 7.9; N, 4.8%); [α]D20
Ϫ11.0 (c 1.20 in CHCl3); δH(270 MHz, CDCl3) 0.78 (3 H, d,
J 6.8, CMe), 0.88 (3 H, d, J 7.0, CMe), 1.34–1.53 (1 H, m,
Me2CH), 2.30 (3 H, s, CMe), 2.56 (1 H, dd, J 10.3 and 7.6,
3-H), 2.70 (6 H, s, 2 × CMe), 3.41 (1 H, dd, J 7.6 and 6.8, 2-H),
(4R,2E)-5-Benzyloxy-O-methylsulfonyl-4-[N-(2,4,6-trimethyl-
phenylsulfonyl)amino]pent-2-en-1-ol 48. By a procedure similar
to that described for the preparation of the mesylate 26 from
18, the alcohol 42 (100 mg, 0.257 mmol) was converted into the
title compound 48 (115 mg, 96%) as a colourless oil [Found
(FAB): (M ϩ H)ϩ, 468.1518. C22H30NO6S2 requires M ϩ H,
468.1514]; [α]D26 Ϫ20.7 (c 1.09 in CHCl3); δH(270 MHz, CDCl3)
2.30 (3 H, s, CMe), 2.58 (6 H, s, 2 × CMe), 2.95 (3 H, s,
SO2Me), 3.33–3.42 (2 H, m, 5-CH2), 3.85–3.95 (1 H, m, 4-H),
4.40 (1 H, d, J 11.9, PhCHH), 4.42 (1 H, d, J 11.9, PhCHH),
4.47–4.60 (2 H, m, 1-CH2), 5.17 (1 H, d, J 6.5, NH), 5.64–5.72
(1 H, m, 2-H), 5.72 (1 H, dd, J 15.4 and 4.9, 3-H), 6.92 (2 H, s,
Ph), 7.20–7.37 (5 H, m, Ph); m/z (FAB-LRMS) 468 (MHϩ), 372,
342, 282, 183, 159, 119, 91 (base peak).
(4R,5R,2E)-5-tert-Butyldimethylsiloxy-O-methylsulfonyl-4-
[N-(p-tolylsulfonyl)amino]hex-2-en-1-ol 49. By a procedure
similar to that described for the preparation of the mesylate 26
from alcohol 18, the alcohol 43 (100 mg, 0.25 mmol) was con-
verted into the title compound 49 (119 mg, 99%) as a colour-
less oil [Found (FAB): (M ϩ H)ϩ, 478.1745. C20H36NO6S2Si
requires M ϩ H, 478.1753]; [α]D27 Ϫ24.5 (c 1.24 in CHCl3); δH(270
MHz, CDCl3) Ϫ0.01 (3 H, s, SiMe), 0.02 (3 H, s, SiMe), 0.85 (9
H, s, CMe3), 1.03 (3 H, d, J 6.2, CMe), 2.42 (3 H, s, CMe), 2.98
(3 H, s, SO2Me), 3.63–3.69 (1 H, m, 4-H), 3.79 (1 H, qd, J 6.2
and 3.0, 5-H), 4.54–4.58 (2 H, m, 1-CH2), 4.93 (1 H, d, J 7.6,
5.27 (1 H, dd, J 10.3 and 1.1, C᎐CHH), 5.41 (1 H, dd, J 17.1
᎐
and 1.1, C᎐CHH), 5.64 (1 H, ddd, J 17.1, 10.3 and 6.8,
᎐
CH᎐CH ), 6.95 (2 H, s, Ph). Compound 55: 98% ee (2S,3S) by
᎐
2
HPLC [Daicel Chiralcel OD, n-hexane–propan-2-ol = 99.5:0.5
(0.5 cm3 minϪ1), (2S,3S)-isomer 27.5 min, (2R,3R)-isomer 24.4
min]; colourless prisms, mp 67 ЊC (from n-hexane) (Found: C,
65.3; H, 8.0; N, 4.55. C16H23NO2S requires C, 65.5; H, 7.9; N,
4.8%); [α]D20 Ϫ88.9 (c 1.90 in CHCl3); δH(270 MHz, CDCl3) 0.70
(3 H, d, J 6.5, CMe), 0.87 (3 H, d, J 7.0, CMe), 1.42–1.57 (1 H,
m, Me2CH), 2.29 (3 H, s, CMe), 2.70 (6 H, 2 × CMe), 2.80 (1 H,
dd, J 7.3 and 4.3, 3-H), 3.11 (1 H, dd, J 9.5 and 4.3, 2-H), 5.35
NH), 5.58–5.66 (1 H, m, CH᎐CH), 5.67 (1 H, dd, J 15.7 and
᎐
5.4, CH᎐CH), 7.27–7.31 (2 H, m, Ph), 7.69–7.73 (2 H, m, Ph);
᎐
m/z (FAB-LRMS) 478 (MHϩ), 420, 382, 338, 228, 159, 115, 73
(1 H, dd, J 10.3 and 1.4, C᎐CHH), 5.50 (1 H, dd, J 17.3 and 1.4,
᎐
C᎐CHH), 6.17 (1 H, ddd, J 17.3, 10.3 and 9.5, CH᎐CH ), 6.93
᎐
᎐
2
(base peak), 59.
(2 H, s, Ph).
(3S,4S)-O-Methoxycarbonyl-5-methyl-4-[N-(2,4,6-tri-
methylphenylsulfonyl)amino]hex-1-en-3-ol 52. By a procedure
identical with that described for the preparation of the carbon-
ate 22 from 18, the known alcohol 5021c (218 mg, 0.7 mmol) was
converted into the title compound 52 (232 mg, 90%) as colour-
less prisms, mp 72 ЊC [from n-hexane–Et2O (2:1)] (Found: C,
58.2; H, 7.4; N, 3.9. C18H27NO5S requires C, 58.5; H, 7.4; N,
3.8%); [α]D20 Ϫ29.6 (c 1.03 in CHCl3); δH(270 MHz, CDCl3) 0.88
(3 H, d, J 6.8, CMe), 0.89 (3 H, d, J 6.2, CMe), 1.75–1.92 (1 H,
m, 5-H), 2.29 (3 H, s, CMe), 2.62 (6 H, s, 2 × CMe), 3.33 (1 H,
ddd, J 9.5, 6.2 and 3.8, 4-H), 3.71 (3 H, s, OMe), 4.75 (1 H, d,
J 9.5, NH), 5.01 (1 H, ddd, J 10.3, 0.8 and 0.8, 1-CHH), 5.15
(1 H, dd, J 7.0 and 3.8, 3-H), 5.20 (1 H, ddd, J 17.1, 1.4 and 1.4,
1-CHH), 5.48 (1 H, ddd, J 17.1, 10.3 and 7.0, 2-H), 6.92 (2 H, s,
Ph).
General procedure for base-promoted aziridination of allylic
mesylates 26–29, 34 and 47–49: aziridination of the mesylate 26
by exposure to sodium hydride in DMF. Synthesis of 3-isopropyl-
2-vinyl-N-(2,4,6-trimethylphenylsulfonyl)aziridines 54 and 55
To a stirred suspension of NaH (7.2 mg, 0.3 mmol) in DMF
(0.6 cm3) under argon was added a solution of the allylic
mesylate 26 (78 mg, 0.2 mmol) in DMF (0.4 cm3) at 0 ЊC. After
0.5 h, 0.5 cm3 of a saturated NH4Cl solution was added to the
mixture. The whole was extracted with Et2O and the extract was
washed with water, and dried over MgSO4. Usual work-up
followed by flash chromatography over a short silica gel
column with n-hexane–EtOAc (12:1) gave a 26:74 mixture of
the aziridines 54 and 55 (39 mg, 66% combined yield). The
mixture was flash chromatographed over silica gel. Elution with
n-hexane–EtOAc (12:1) gave 54 (10.1 mg, 17%) and further
elution yielded 55 (29 mg, 49%).
(3R,4S)-O-Methoxycarbonyl-5-methyl-4-[N-(2,4,6-trimethyl-
phenylsulfonyl)amino]hex-1-en-3-ol 53. By a procedure identical
with that described for the preparation of the carbonate 22
from 18, the known alcohol 5121c (80 mg, 0.257 mmol) was
converted into the title compound 53 (85 mg, 89%) as colourless
crystals, mp 91 ЊC [from n-hexane–Et2O (4:1)] (Found: C, 58.3;
H, 7.3; N, 3.7. C18H27NO5S requires C, 58.5; H, 7.4; N, 3.8%);
[α]D20 ϩ11.4 (c 0.70 in CHCl3); δH(270 MHz, CDCl3) 0.86 (3 H, d,
J 7.0, CMe), 0.91 (3 H, d, J 6.8, CMe), 1.75–1.92 (1 H, m, 5-H),
2.29 (3 H, s, CMe), 2.62 (6 H, s, 2 × CMe), 3.39 (1 H, ddd, J 9.7,
4.9 and 4.6, 4-H), 3.69 (3 H, s, OMe), 4.65 (1 H, d, J 9.7, NH),
Synthesis of (2R,3S)-N-(p-tolylsulfonyl)-3-(2-methylpropyl)-2-
vinylaziridine 56 and its (2S,3S)-isomer 57 from the carbonate 23
By a procedure similar to that described for the aziridination of
22, the allylic carbonate 23 (50 mg, 0.141 mmol) was converted
into a 94:6 mixture of the title compounds 56 and 57 (26 mg,
66% combined yield) by treatment with 4 mol% of Pd(PPh3)4 in
THF at 65 ЊC for 10 min followed by flash chromatography on a
short silica gel column with n-hexane–EtOAc (4:1). The mix-
3712
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716

View Article Online
ture was flash chromatographed over silica gel. Elution with
n-hexane–EtOAc (8:1) gave 56 (24.4 mg, 62%) and further elu-
tion yielded 57 (1.6 mg, 4%). Compound 56: 98% ee (2R,3S) by
HPLC [Daicel Chiralcel OD, n-hexane–propan-2-ol = 99.4:0.6
(0.5 cm3 minϪ1), (2R,3S)-isomer 30.6 min]; a colourless oil
[Found (FAB): (M ϩ H)ϩ, 280.1376. C15H22NO2S requires
M ϩ H, 280.1371]; [α]D25 Ϫ6.08 (c 0.987 in CHCl3); δH(270
MHz, CDCl3) 0.88 (3 H, d, J 6.5, CMe), 0.89 (3 H, d, J 6.8,
CMe), 1.30 (1 H, ddd, J 14.0, 7.8 and 6.2, CHH), 1.39 (1 H,
ddd, J 14.0, 7.0 and 5.7, CHH), 1.53–1.68 (1 H, m, Me2CH),
2.44 (3 H, s, CMe), 2.97 (1 H, ddd, J 7.8, 7.3 and 7.0, 3-H),
3.33 (1 H, dd, J 7.3 and 7.3, 2-H), 5.26 (1 H, ddd, J 10.3, 1.1
Synthesis of (2R,3S)-3-benzyl-N-(2,4,6-trimethylphenylsulfonyl)-
2-vinylaziridine 60 and its (2S,3S)-isomer 61 from the carbonate
25
By a procedure similar to that described for the aziridination of
22, the allylic carbonate 25 (160 mg, 0.383 mmol) was converted
into a 95:5 mixture of the title compounds 60 and 61 (65 mg,
50% combined yield) by treatment with 4 mol% of Pd(PPh3)4 in
THF at 65 ЊC for 5 min followed by flash chromatography over
a short silica gel column with n-hexane–EtOAc (5:1). The mix-
ture was flash chromatographed over silica gel. Elution with
n-hexane–EtOAc (10:1) gave 60 (62 mg, 48%) and further elu-
tion yielded 61 (3 mg, 2%). Compound 60: 98% ee (2R,3S)
by HPLC [Daicel Chiralcel OD, n-hexane–propan-2-ol =
99.2:0.8 (0.5 cm3 minϪ1), (2R,3S)-isomer 39.2 min]; colourless
needles, mp 71 ЊC [from n-hexane–Et2O (3:1)] (Found: C,
70.15; H, 6.8; N, 4.15. C20H23NO2S requires C, 70.35; H, 6.8; N,
4.1%); [α]D24 Ϫ24.8 (c 0.935 in CHCl3); δH(270 MHz, CDCl3) 2.30
(3 H, s, CMe), 2.58 (6 H, s, 2 × CMe), 2.66 (1 H, dd, J 14.6 and
7.6, PhCHH), 2.74 (1 H, dd, J 14.6 and 5.7, PhCHH), 3.10
(1 H, ddd, J 7.6, 6.8 and 5.7, 3-H), 3.48 (1 H, dd, J 6.8 and
and 1.1, C᎐CHH), 5.38 (1 H, ddd, J 17.3, 1.1 and 1.1,
᎐
C᎐CHH), 5.59 (1 H, ddd, J 17.3, 10.3 and 7.3, CH᎐CH ),
᎐
᎐
2
7.31–7.34 (2 H, m, Ph), 7.80–7.84 (2 H, m, Ph); m/z (FAB-
LRMS) 280 (MHϩ, base peak), 155, 139, 124, 91, 82, 68.
Compound 57: 98% ee (2S,3S) by HPLC [Daicel Chiralcel
OD, n-hexane–propan-2-ol = 99.4:0.6 (0.5 cm3 minϪ1),
(2S,3S)-isomer 41.1 min]; colourless crystals, mp 59 ЊC (from
n-hexane) [Found (FAB): (M ϩ H)ϩ, 280.1368. C15H22NO2S
requires M ϩ H, 280.1371]; [α]D25 Ϫ69.8 (c 0.106 in CHCl3);
δH(270 MHz, CDCl3) 0.88 (3 H, d, J 6.2, CMe), 0.90 (3 H, d,
J 6.2, CMe), 1.36–1.41 (1 H, m, CHH), 1.58–1.68 (2 H, m,
CHH and Me2CH), 2.43 (3 H, s, CMe), 2.92–2.98 (1 H, m,
3-H), 3.08 (1 H, dd, J 8.9 and 4.3, 2-H), 5.34 (1 H, d, J 10.3,
6.8, 2-H), 5.38 (1 H, d, J 10.5, C᎐CHH), 5.50 (1 H, d, J 17.3,
᎐
C᎐CHH), 5.78 (1 H, ddd, J 17.3, 10.5 and 6.8, CH᎐CH ),
᎐
᎐
2
6.85 (2 H, s, Ph), 6.95–7.00 (2 H, m, Ph), 7.05–7.11 (3 H, m,
Ph). Compound 61: colourless needles, mp 105–106 ЊC [from
n-hexane–Et2O (3:1)] [Found (FAB): (M ϩ H)ϩ, 342.1520.
C20H24NO2S requires M ϩ H, 342.1528]; [α]D25 Ϫ35.5 (c 0.077,
CHCl3); δH(270 MHz, CDCl3) 2.30 (3 H, s, CMe), 2.54 (6 H,
s, 2 × CMe), 2.66 (1 H, dd, J 14.0 and 6.8, PhCHH), 3.00
(1 H, dd, J 14.0 and 4.9, PhCHH), 3.16 (1 H, ddd, J 6.8, 4.9 and
3.8, 3-H), 3.21 (1 H, dd, J 8.9 and 3.8, 2-H), 5.36 (1 H, dd,
C᎐CHH), 5.47 (1 H, d, J 16.7, C᎐CHH), 6.02 (1 H, ddd,
᎐
᎐
J 16.7, 10.3 and 8.9, CH᎐CH ), 7.29–7.32 (2 H, m, Ph), 7.81–
᎐
2
7.84 (2 H, m, Ph); m/z (FAB-LRMS) 280 (MHϩ, base peak),
155, 139, 124, 91, 82, 55.
Synthesis of (2R,3S)-3-(2-methylpropyl)-N-(2,2,5,7,8-penta-
methylchroman-6-ylsulfonyl)-2-vinylaziridine 58 and its (2S,3S)-
isomer 59 from the carbonate 24
J 10.0 and 1.1, C᎐CHH), 5.52 (1 H, dd, J 17.3 and 1.1,
᎐
C᎐CHH), 6.08 (1 H, ddd, J 17.3, 10.0 and 8.9, CH᎐CH ), 6.85
᎐
᎐
2
(2 H, s, Ph), 6.89–6.93 (2 H, m, Ph), 7.02–7.15 (3 H, m, Ph); m/z
(FAB-LRMS) 342 (MHϩ), 183, 158, 143, 119 (base peak), 91.
By a procedure similar to that described for the aziridination of
22, the allylic carbonate 24 (480 mg, 1.03 mmol) was converted
into a 97:3 mixture of the title compounds 58 and 59 (238 mg,
59% combined yield) by treatment with 4 mol% of Pd(PPh3)4 in
THF at 20 ЊC for 6 h followed by flash chromatography over a
short silica gel column with n-hexane–EtOAc (8:1). The mix-
ture was flash chromatographed over silica gel. Elution with
n-hexane–EtOAc (12:1) gave 58 (231 mg, 57%) and further elu-
tion yielded 59 (7 mg, 2%). Compound 58: 98% ee (2R,3S) by
HPLC [Daicel Chiralcel OD, n-hexane–propan-2-ol = 99.5:0.5
(0.5 cm3 minϪ1), (2R,3S)-isomer 26.3 min]; a colourless oil
[Found (FAB): (M ϩ H)ϩ, 392.2252. C22H34NO3S requires
M ϩ H, 392.2259]; [α]D16 ϩ4.65 (c 1.00 in CHCl3); δH(270 MHz,
CDCl3) 0.83 (3 H, d, J 6.6, CMe), 0.87 (3 H, d, J 6.6, CMe),
1.18–1.44 (2 H, m, Me2CHCH2), 1.31 (6 H, s, 2 × CMe), 1.53–
1.59 (1 H, m, Me2CH), 1.83 (2 H, t, J 6.8, 3Ј-CH2), 2.12 (3 H, s,
CMe), 2.59 (3 H, s, CMe), 2.61 (3 H, s, CMe), 2.65 (2 H, t, J 6.8,
4Ј-CH2), 2.92–3.00 (1 H, m, 3-H), 3.38 (1 H, dd, J 6.8 and 6.8,
Synthesis of (3R,4S,5S)-5-methyl-3,4-epimino-N-(4-methoxy-
2,3,6-trimethylphenylsulfonyl)hept-1-ene 62 and its (3S,4S,5S)-
isomer 63 from the carbonate 33
By a procedure similar to that described for the aziridination of
22, the allylic carbonate 33 (980 mg, 2.37 mmol) was converted
into a 98:2 mixture of the title compounds 62 and 63 (680 mg,
85% combined yield) by treatment of 33 with 2 mol% Pd(PPh3)4
in THF at 60 ЊC for 5 min followed by chromatography over
a short silica gel column with n-hexane–EtOAc (15:1). The
mixture was flash chromatographed over silica gel. Elution with
n-hexane–EtOAc (30:1) gave 62 (666 mg, 83%) and further elu-
tion yielded 63 (14 mg, 2%). Compound 62: 98% ee (3R,4S,5S)
by HPLC [Daicel Chiralcel OD, n-hexane–propan-2-ol =
99.4:0.6 (0.5 cm3 minϪ1), (3R,4S,5S)-isomer 43.0 min]; a col-
ourless oil [Found (FAB): (M ϩ H)ϩ, 338.1798. C18H28NO3S
requires M ϩ H, 338.1789]; [α]D26 ϩ0.83 (c 0.803 in CHCl3);
δH(270 MHz, CDCl3) 0.79 (t, J 7.6, CMe), 0.85 (d, J 7.0, CMe),
1.04–1.45 (3 H, m, 5-H and 6-CH2), 2.15 (3 H, s, CMe), 2.63–
2.68 (1 H, m, 4-H), 2.68 (3 H, s, CMe), 2.69 (3 H, s, CMe), 3.35
(1 H, dd, J 7.0 and 7.0, 3-H), 3.85 (3 H, s, OMe), 5.26 (1 H, d,
J 10.0, 1-CHH), 5.38 (1 H, d, J 17.0, 1-CHH), 5.64 (1 H, ddd,
J 17.0, 10.0 and 7.0, 2-H), 6.56 (1 H, s, Ph); m/z (FAB-LRMS)
338, (MHϩ), 336, 213, 197, 165, 149, 124 (base peak), 119,
69, 41. Compound 63: 98% ee (3S,4S,5S) by HPLC [Daicel
Chiralcel OD, n-hexane–propan-2-ol = 99.4:0.6 (0.5 cm3
minϪ1), (3R,4S,5S)-isomer 47.6 min]; colourless prisms, mp
72 ЊC (from n-hexane) (Found: C, 64.1; H, 8.1; N, 4.0.
C18H27NO3S requires C, 64.1; H, 8.1; N, 4.15%); [α]D26 Ϫ50.7
(c 0.856 in CHCl3); δH(270 MHz, CDCl3) 0.75 (3 H, t, J 7.3,
CMe), 0.86 (3 H, d, J 6.8, CMe), 0.97–1.14 (1 H, m, 6-CHH),
1.19–1.38 (2 H, m, 5-H and 6-CHH), 2.15 (3 H, s, CMe), 2.68
(6 H, s, 2 × CMe), 2.87 (1 H, dd, J 7.3 and 4.3, 4-H), 3.07 (1 H,
dd, J 9.5 and 4.3, 3-H), 3.85 (3 H, s, OMe), 5.32 (1 H, d, J 10.3,
2-H), 5.26 (1 H, dd, J 10.3 and 0.7, C᎐CHH), 5.37 (1 H, dd,
᎐
J 17.1 and 0.7, C᎐CHH), 5.63 (1 H, ddd, J 17.1, 10.3 and 6.8,
᎐
CH᎐CH ); m/z (FAB-LRMS) 392 (MHϩ), 267 (base peak), 251,
᎐
2
219, 203, 187, 147, 124. Compound 59: 98% ee (2S,3S) by
HPLC [Daicel Chiralcel OD, n-hexane–propan-2-ol = 99.5:0.5
(0.5 cm3 minϪ1), (2S,3S)-isomer 30.8 min]; a colourless oil
[Found (FAB): (M ϩ H)ϩ, 329.2260. C22H34NO3S requires
M ϩ H, 392.2259]; [α]D25 Ϫ54.7 (c 0.42 in CHCl3); δH(270 MHz,
CDCl3) 0.87 (3 H, d, J 6.2, CMe), 0.88 (3 H, d, J 6.5, CMe),
1.31 (3 H, s, CMe), 1.32 (3 H, s, CMe), 1.34–1.44 (1 H, m,
Me2CHCHH), 1.52–1.75 (2 H, m, Me2CHCHH and Me2CH),
1.82 (2 H, t, J 7.0, 3Ј-CH2), 2.12 (3 H, s, CMe), 2.58 (3 H, s,
CMe), 2.60 (3 H, s, CMe), 2.64 (2 H, t, J 7.0, 4Ј-CH2), 2.93 (1 H,
ddd, J 7.6, 5.1 and 4.1, 3-H), 3.09 (1 H, dd, J 9.2 and 4.1, 2-H),
5.28 (1 H, dd, J 10.3 and 1.4, C᎐CHH), 5.44 (1 H, dd, J 17.0
᎐
and 1.1, C᎐CHH), 6.01 (1 H, ddd, J 17.0, 10.3 and 9.2,
᎐
CH᎐CH ); m/z (FAB-LRMS) 392 (MHϩ), 267, 251, 219, 203,
᎐
2
187, 147, 124 (base peak).
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716
3713

View Article Online
1-CHH), 5.47 (1 H, d, J 17.3, 1-CHH), 6.18 (1 H, ddd, J 17.3,
10.3 and 9.5, 2-H), 6.55 (1 H, s, Ph).
(FAB): (M ϩ H)ϩ, 372.1632. C21H26NO3S requires M ϩ H,
372.1633]; [α]D31 Ϫ0.86 (c 0.463 in CHCl3); δH(270 MHz, CDCl3)
2.28 (3 H, s, CMe), 2.70 (6 H, s, 2 × CMe), 3.18 (1 H, ddd, J 7.3,
6.5 and 5.9, 3-H), 3.45 (1 H, dd, J 7.3 and 6.5, 2-H), 3.47 (1 H,
dd, J 11.1 and 6.5, BnOCHH), 3.54 (1 H, dd, J 11.1 and 5.9,
BnOCHH), 4.38 (1 H, d, J 11.9, PhCHH), 4.39 (1 H, d, J 11.9,
Synthesis of (2R,3R)-2-tert-butyldimethylsiloxymethyl-N-(2,4,6-
trimethylphenylsulfonyl)-3-vinylaziridine 64 and its (2R,3S)-
isomer 65 from the mesylate 47
PhCHH), 5.27 (1 H, ddd, J 10.3, 1.6 and 0.5, C᎐CHH), 5.40
᎐
By a procedure identical with that described for the aziridin-
ation of 26, the allylic mesylate 47 (98.3 mg, 0.2 mmol) was
converted into a mixture of 2,3-cis- and 2,3-trans-aziridines 64
and 65 (64:65 = 51:49) by treatment with NaH in DMF. The
mixture was flash chromatographed over silica gel. Elution with
n-hexane–CHCl3–EtOAc (20:5:1) gave 65 (24 mg, 30%) and
further elution yielded 64 (25 mg, 32%). Compound 64: 98% ee
(2R,3R) by HPLC [Daicel Chiralcel OD, n-hexane–propan-2-
ol = 99.5:0.5 (0.5 cm3 minϪ1), (2R,3R)-isomer 19.4 min]; a
colourless oil [Found (FAB): (M ϩ H)ϩ, 396.2024. C20H34NO3-
SSi requires M ϩ H, 396.2028]; [α]D29 Ϫ0.74 (c 1.44 in CHCl3);
δH(270 MHz, CDCl3) Ϫ0.09 (3 H, s, SiMe), Ϫ0.06 (3 H, s,
SiMe), 0.79 (9 H, s, CMe3), 2.29 (3 H, s, CMe), 2.69 (6 H, s,
2 × CMe), 3.07 (1 H, ddd, J 7.3, 5.9 and 5.9, 3-H), 3.44 (1 H,
dd, J 7.3 and 6.8, 2-H), 3.58 (1 H, dd, J 11.6 and 5.9, OCHH),
3.61 (1 H, dd, J 11.6 and 5.9, OCHH), 5.28 (1 H, ddd, J 10.3,
(1 H, ddd, J 17.3, 1.6 and 0.8, C᎐CHH), 5.69 (1 H, ddd, J 17.3,
᎐
10.3 and 6.5, CH᎐CH ), 6.94 (2 H, s, Ph), 7.14-7.34 (5 H, m,
᎐
2
Ph); m/z (FAB-LRMS) 372 (MHϩ), 342, 188, 183, 159, 119, 91
(base peak). Compound 67: 98% ee (2R,3S) by HPLC [Daicel
Chiralcel OD, n-hexane–propan-2-ol = 99.0:1.0 (0.5 cm3
minϪ1), (2R,3S)-isomer 48.5 min]; colourless prisms. mp 64 ЊC
[from n-hexane–Et2O (4:1)] [Found (FAB): (M ϩ H)ϩ,
372.1637. C21H26NO3S requires M ϩ H, 372.1633]; [α]D31 Ϫ39.2 (c
1.31 in CHCl3); δH(300 MHz, CDCl3) 2.28 (3 H, s, CMe), 2.69
(6 H, s, 2 × CMe), 3.22 (1 H, dd, J 8.8 and 4.2, 2-H), 3.24 (1 H,
ddd, J 5.1, 4.3 and 4.2, 3-H), 3.51 (1 H, dd, J 11.1 and 5.1,
BnOCHH), 3.68 (1 H, dd, J 11.1 and 4.3, BnOCHH), 4.35
(1 H, d, J 12.1, PhCHH), 4.38 (1 H, d, J 12.1, PhCHH), 5.36
(1 H, dd, J 10.2 and 1.0, C᎐CHH), 5.49 (1 H, dd, J 17.1 and 1.1,
᎐
C᎐CHH), 6.07 (1 H, ddd, J 17.1, 10.2 and 8.8, CH᎐CH ), 6.93
᎐
᎐
2
(2 H, s, Ph), 7.10–7.13 (2 H, m, Ph), 7.24–7.30 (3 H, m, Ph); m/z
(FAB-LRMS) 372 (MHϩ), 280, 243, 188, 183, 159, 119, 105, 91
(base peak), 73.
1.1 and 0.5, C᎐CHH), 5.41 (1 H, ddd, J 17.0, 2.2 and 1.1,
᎐
C᎐CHH), 5.66 (1 H, ddd, J 17.0, 10.3 and 6.8, CH᎐CH ), 6.94
᎐
᎐
2
(2 H, s, Ph); m/z (FAB-LRMS) 396 (MHϩ), 366, 338, 308, 241,
212, 177, 154, 119, 73 (base peak). Compound 65: 98% ee
(2R,3S) by HPLC [Daicel Chiralcel OD, n-hexane–propan-2-
ol = 99.5:0.5 (0.5 cm3 minϪ1), (2R,3S)-isomer 26.3 min]; a
colourless oil [Found (FAB): (M ϩ H)ϩ, 396.2037. C20H34NO3-
SSi requires M ϩ H, 396.2028]; [α]D29 Ϫ38.7 (c 2.35, CHCl3);
δH(270 MHz, CDCl3) Ϫ0.13 (3 H, s, SiMe), Ϫ0.10 (3 H, s,
SiMe), 0.78 (9 H, s, CMe3), 2.28 (3 H, s, CMe), 2.69 (6 H, s,
2 × CMe), 3.18 (1 H, ddd, J 5.4, 4.3 and 4.1, 3-H), 3.22 (1 H,
dd, J 9.2 and 4.3, 2-H), 3.60 (1 H, dd, J 11.6 and 5.4, OCHH),
3.75 (1 H, dd, J 11.6 and 4.1, OCHH), 5.36 (1 H, dd, J 10.3 and
Synthesis of (3R,4R,5R)-5-tert-butyldimethylsiloxy)-3,4-
epimino-N-(p-tolylsulfonyl)hex-1-ene 68 and its (3S,4R,5R)-
isomer 69 from the mesylate 49
By a procedure similar to that described for the aziridination of
26, the allylic mesylate 49 (191 mg, 0.4 mmol) was converted
into a mixture of 2,3-cis- and 2,3-trans-aziridines 68 and 69
(68:69 = 8:92) by treatment with NaH in DMF. The mixture
was flash chromatographed over silica gel. Elution with n-
hexane–CHCl3–EtOAc (20:5:1) gave 69 (81 mg, 53%) and fur-
ther elution yielded 68 (7 mg, 5%). Compound 68: 98% ee
(3R,4R,5R) by HPLC [Daicel Chiralcel OD, n-hexane–propan-
2-ol = 99.4:0.6 (0.5 cm3 minϪ1), (3R,4R,5R)-isomer 26.3 min]; a
colourless oil [Found (FAB): (M ϩ H)ϩ, 382.1877. C19H32NO3-
SSi requires M ϩ H, 382.1872]; [α]D32 ϩ0.78 (c 2.04 in CHCl3);
δH(270 MHz, CDCl3) Ϫ0.16 (3 H, s, SiMe), Ϫ0.04 (3 H, s,
SiMe), 0.78 (9 H, s, CMe3), 1.13 (3 H, d, J 6.2, CMe), 2.43 (3 H,
s, CMe), 2.93 (1 H, dd, J 8.6 and 7.3, 4-H), 3.36 (1 H, dd, J 7.3
and 7.3, 3-H), 3.52 (1 H, dq, J 8.6 and 6.2, 5-H), 5.29 (1 H, ddd,
J 10.0, 1.9 and 0.8, 1-CHH), 5.44 (1 H, dd, J 17.1 and 1.6,
1-CHH), 5.57 (1 H, ddd, J 17.3, 10.0 and 7.3, 2-H), 7.30–7.33
(2 H, m, Ph), 7.80–7.85 (2 H, m, Ph); m/z (FAB-LRMS) 382
(MHϩ), 366, 338, 324, 280 (base peak), 226, 213, 159, 139,
115, 73. Compound 69: 98% ee (3S,4R,5R) by HPLC [Daicel
Chiralcel OD, n-hexane–propan-2-ol = 99.4:0.6 (0.5 cm3
minϪ1), (3S,4R,5R)-isomer 38.2 min]; a colourless oil [Found
(FAB): (M ϩ H)ϩ, 382.1866. C19H32NO3SSi requires M ϩ H,
382.1872]; [α]D31 Ϫ31.2 (c 0.746 in CHCl3); δH(270 MHz, CDCl3)
Ϫ0.15 (3 H, s, SiMe), Ϫ0.06 (3 H, s, SiMe), 0.80 (9 H, s, CMe3),
1.13 (3 H, d, J 6.5, CMe), 2.43 (3 H, s, CMe), 3.12 (1 H, dd,
J 5.1 and 4.3, 4-H), 3.19 (1 H, dd, J 9.5 and 4.3, 3-H), 3.72 (1 H,
qd, J 6.5 and 5.1, 5-H), 5.42 (1 H, dd, J 10.0 and 0.8, 1-CHH),
5.51 (1 H, dd, J 16.7 and 1.1, 1-CHH), 6.21 (1 H, ddd, J 16.7,
10.0 and 9.5, 2-H), 7.28–7.31 (2 H, m, Ph), 7.82–7.85 (2 H, m,
Ph); m/z (FAB-LRMS) 382 (MHϩ), 338, 324, 280 (base peak),
226, 213, 159, 139, 115, 73.
0.8, C᎐CHH), 5.51 (1 H, dd, J 16.7 and 0.8, C᎐CHH), 6.12
᎐
᎐
(1 H, ddd, J 16.7, 10.3 and 9.2, CH᎐CH ), 6.92 (2 H, s, Ph); m/z
᎐
2
(FAB-LRMS) 396 (MHϩ), 366, 338, 308, 241, 212, 177, 154,
119, 73 (base peak).
General procedure for palladium-catalyzed equilibrated reaction
of mixtures of 2,3-cis- and 2,3-trans-aziridines 54, 56, 58, 60, 62,
64, 66, 68 and 55, 57, 59, 61, 63, 65, 67, 69: equilibrated reaction
of a mixture of (2R,3R)-2-tert-butyldimethylsiloxymethyl-N-
(2,4,6-trimethylphenylsulfonyl)-3-vinylaziridine 64 and its
(2R,3S)-isomer 65
A 51:49 mixture of 2,3-cis- and 2,3-trans-aziridines 64 and 65
(68 mg, 0.172 mmol) and Pd(PPh3)4 (7.9 mg, 0.0069 mmol,
4 mol%) in dry THF (3 cm3) was stirred at 0 ЊC for 2 h. The
mixture was concentrated under reduced pressure to leave
an oil, which was flash chromatographed over silica gel with
n-hexane–EtOAc (12:1) to give the title compounds 64 (57 mg,
83%) and 65 (4.3 mg, 7%).
Synthesis of (2R,3R)-2-benzyloxymethyl-N-(2,4,6-trimethyl-
phenylsulfonyl)-3-vinylaziridine 66 and its (2R,3S)-isomer 67
from the mesylate 48
By a procedure identical with that described for the aziridin-
ation of 26, the allylic mesylate 48 (234 mg, 0.5 mmol) was
converted into a 51:49 mixture of the title compounds 66 and
67 (125 mg, 67% combined yield) by treatment with NaH fol-
lowed by flash chromatography over a short silica gel column
with n-hexane–EtOAc (8:1). The mixture was flash chromato-
graphed over silica gel. Elution with n-hexane–CHCl3–EtOAc
(20:5:1) gave 67 (61 mg, 33%) and further elution yielded 66
(64 mg, 34%). Compound 66: 98% ee (2R,3R) by HPLC [Daicel
Chiralcel OD, n-hexane–propan-2-ol = 99.0:1.0 (0.5 cm3
minϪ1), (2R,3R)-isomer 54.0 min]; a colourless oil [Found
tert-Butyl (4R,5S,6S,2E)-6-methyl-4,5-epimino-N-(4-methoxy-
2,3,6-trimethylphenylsulfonyl)oct-2-enoate 70
Ozone was bubbled through a solution of the vinylaziridine 62
(300 mg, 0.889 mmol) in a mixed solvent of CHCl3 (5 cm3) and
n-hexane (3 cm3) at Ϫ78 ЊC for 40 min. Zn powder (0.25 g) was
added to the mixture at Ϫ78 ЊC, and the mixture was stirred for
1 h with warming to 0 ЊC. The inorganic precipitates were
3714
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716

View Article Online
4 (a) J. Åhman, T. Jareva˚ng and P. Somfai, J. Org. Chem., 1996, 61,
removed by filtration through a short pad of SiO2 with Et2O.
The filtrate was concentrated under reduced pressure to give a
crude aldehyde as an oil. To a stirred suspension of LiCl (75
mg, 1.78 mmol) in MeCN (3 cm3) under argon at room tem-
perature were added tert-butyl diethylphosphonoacetate (0.45
g, 1.78 mmol) and N,N-diisopropylethylamine (0.31 cm3, 1.78
mmol), and the mixture was cooled to 0 ЊC. To the above
reagent, the crude aldehyde in MeCN (3 cm3) was added at 0 ЊC
and the mixture was stirred for 1 h with warming to room tem-
perature. The mixture was made acidic with saturated aqueous
citric acid followed by concentration under reduced pressure to
yield an oily residue. The residue was dissolved in Et2O and the
solution was washed successively with H2O, 5% aqueous
NaHCO3, and H2O, and dried over MgSO4. Usual work-up
followed by flash chromatography over silica gel with n-hexane–
EtOAc (6:1) gave the title compound 70 (330 mg, 85% yield) as
colourless crystals, mp 83–85 ЊC (from n-hexane) (Found: C,
63.0; H, 8.1; N, 3.0. C23H35NO5S requires C, 63.1; H, 8.1; N,
3.2%); [α]D26 Ϫ48.6 (c 0.951 in CHCl3); δH(270 MHz, CDCl3) 0.78
(3 H, t, J 7.3, CMe), 0.85 (3 H, d, J 6.5, CMe), 1.04–1.40 (3 H,
m, 6-H and 7-CH2), 1.48 (9 H, s, CMe3), 2.16 (3 H, s, CMe),
2.67 (3 H, s, CMe), 2.69 (3 H, s, CMe), 2.74 (1 H, dd, J 9.7 and
7.8, 5-H), 3.41 (1 H, dd, J 7.8 and 6.8, 4-H), 3.86 (3 H, s, OMe),
6.01 (1 H, d, J 15.6, 2-H), 6.57 (1 H, s, Ph), 6.59 (1 H, dd, J 15.6
and 6.8, 3-H).
8148; (b) J. Åhman and P. Somfai, J. Am. Chem. Soc., 1994, 116,
9781; (c) J. Åhman and P. Somfai, Tetrahedron Lett., 1996, 37, 2495.
5 J. Åhman and P. Somfai, Tetrahedron Lett., 1995, 36, 303; J. Åhman
and P. Somfai, Tetrahedron, 1995, 51, 9747.
6 T. Hudlicky, J. O. Frazier, G. Seoane, M. Tiedje, A. Seoane,
L. D. Kwart and C. Beal, J. Am. Chem. Soc., 1986, 108, 3755;
T. Hudlicky, G. Seoane and T. C. Lovelace, J. Org. Chem., 1988, 53,
2094; T. Hudlicky, H. Luna, J. D. Price and F. Rulin, J. Org. Chem.,
1990, 55, 4683; W. H. Pearson, S. C. Bergmeier, S. Degan, K.-C. Lin,
Y.-F. Poon, J. M. Schkeryantz and J. P. Williams, J. Org. Chem.,
1990, 55, 5719.
7 (a) J. Åhman, P. Somfai and D. Tanner, J. Chem. Soc., Chem.
Commun., 1994, 2785; (b) P. Somfai and J. Åhman, Tetrahedron
Lett., 1995, 36, 1953.
8 (a) A. A. Cantrill, A. N. Jarvis, H. M. I. Osborn, A. Ouadi and
J. B. Sweeney, Synlett, 1996, 847; (b) H. Aoyama, N. Mimura,
H. Ohno, K. Ishii, A. Toda, H. Tamamura, A. Otaka, N. Fujii and
T. Ibuka, Tetrahedron Lett., 1997, 38, 7383.
9 F. A. Davis and G. V. Reddy, Tetrahedron Lett., 1996, 37, 4349.
10 U. M. Lindström and P. Somfai, J. Am. Chem. Soc., 1997, 119, 8385.
11 (a) T. Ibuka, K. Nakai, H. Habashita, Y. Hotta, N. Fujii,
N. Mimura, Y. Miwa, T. Taga and Y. Yamamoto, Angew. Chem., Int.
Ed. Engl., 1994, 33, 652; (b) P. Wipf and P. C. Fritch, J. Org. Chem.,
1994, 59, 4875; (c) N. Fujii, K. Nakai, H. Tamamura, A. Otaka,
N. Mimura, Y. Miwa, T. Taga, Y. Yamamoto and T. Ibuka, J. Chem.
Soc., Perkin Trans. 1, 1995, 1359; (d) A. Satake, I. Shimizu and
Y. Yamamoto, Synlett, 1995, 64; (e) P. Wipf and T. C. Henninger,
J. Org. Chem., 1997, 62, 1586.
12 (a) T. Ibuka, H. Habashita, S. Funakoshi, N. Fujii, Y. Oguchi,
T. Uyehara and Y. Yamamoto, Angew. Chem., Int. Ed. Engl., 1990,
29, 801; (b) T. Ibuka, H. Habashita, A. Otaka, N. Fujii, Y. Oguchi,
T. Uyehara and Y. Yamamoto, J. Org. Chem., 1991, 56, 4370;
(c) T. Ibuka, T. Taga, H. Habashita, K. Nakai, H. Tamamura,
N. Fujii, Y. Chounan, H. Nemoto and Y. Yamamoto, J. Org. Chem.,
1993, 58, 1207; (d) D. Gryko, Z. Urbanczyk-Lipkowska and
J. Jurczak, Tetrahedron: Asymmetry, 1997, 8, 4059.
13 (a) G. J. Hanson and T. Lindberg, J. Org. Chem., 1985, 50, 5399;
(b) S. Thaisrivongs, D. T. Pals, L. T. Kroll, S. R. Turner and
F.-S. Han, J. Med. Chem., 1987, 30, 976; (c) P. G. M. Wuts, S. R. Putt
and A. R. Ritter, J. Org. Chem., 1988, 53, 4503; (d) W. J. Thompson,
T. J. Tucker, J. E. Schwering and J. L. Barnes, Tetrahedron Lett.,
1990, 31, 6819; (e) D. J. Kempf, X. C. Wang and S. G. Spanton, Int.
J. Pept. Protein Res., 1991, 38, 237; ( f ) B. E. Green, X. Chen,
D. W. Norbeck and D. J. Kempf, Synlett, 1995, 613.
14 Y.-K. Shue, G. M. Carrera, Jr., and A. M. Nadzan, Tetrahedron
Lett., 1987, 28, 3225; Y.-K. Shue, M. D. Tufano and A. M. Nadzan,
Tetrahedron Lett., 1988, 29, 4041; Y.-K. Shue, G. M. Carrera, Jr.,
M. D. Tufano and A. M. Nadzan, J. Org. Chem., 1991, 56, 2107.
15 R. S. Coleman and A. J. Carpenter, Tetrahedron Lett., 1992, 33,
1697.
16 A. Spaltenstein, J. J. Leban, J. J. Huang, K. R. Reinhardt,
O. H. Viveros, J. Sigafoos and R. Crouch, Tetrahedron Lett., 1996,
37, 1343.
17 M. Kawai, A. S. Boparai, M. S. Bernatowicz and D. H. Rich, J. Org.
Chem., 1983, 48, 1876; L. S. L. de Gaeta, M. Czarniecki and
A. Spaltenstein, J. Org. Chem., 1989, 54, 4004 and references cited.
18 (a) M. Wada, R. Doi, R. Hosotani, R. Higashide, T. Ibuka,
H. Habashita, K. Nakai, N. Fujii and M. Imamura, Pancreas, 1995,
10, 301; (b) K. Miyasaka, S. Kanai, M. Masuda, T. Ibuka, K. Nakai,
N. Fujii and S. Funakoshi, J. Auton. Nerv. Syst., 1997, 63, 179;
(c) K. Fujimoto, R. Doi, R. Hosotani, M. Wada, J.-U. Lee,
T. Koshiba, T. Ibuka, H. Habashita, K. Nakai, N. Fujii and
M. Imamura, Life Sci., 1997, 60, 29.
tert-Butyl (2R,5S,6S,3E)-2-isopropyl-6-methyl-5-[N-(4-meth-
oxy-2,3,6-trimethylphenylsulfonyl)amino]oct-3-enoate 71
To a stirred solution of CuCN (108 mg, 1.2 mmol) and LiCl
(102 mg, 2.4 mmol) in dry THF (2 cm3) under argon was added
by syringe isopropylmagnesium chloride (1.3 mol dmϪ3 solu-
tion in THF; 0.93 cm3, 1.2 mmol) at Ϫ78 ЊC, and the mixture
was allowed to warm to 0 ЊC and stirred at this temperature for
5 min. The enoate 70 (132 mg, 0.3 mmol) in dry THF (2 cm3)
was added dropwise to the above reagent at Ϫ78 ЊC, and the
mixture was stirred for 30 min followed by quenching with a
1:1 solution (8 cm3) of saturated NH4Cl–28% NH4OH. The
whole was extracted with Et2O and the extract was washed with
H2O, and dried over MgSO4. Usual work-up followed by flash
chromatography over silica gel with n-hexane–EtOAc (5:1)
gave the title compound 71 (136 mg, 94% yield) as a colourless
oil [Found (FAB): (M ϩ H)ϩ, 482.2932. C26H44NO5S requires
M ϩ H, 482.2940]; [α]D24 Ϫ50.4 (c 0.164 in CHCl3); δH(270 MHz,
CDCl3) 0.69 (3 H, d, J 6.5, CMe), 0.79 (3 H, d, J 6.8, CMe),
0.817 (3 H, d, J 6.2, CMe), 0.822 (3 H, t, J 7.3, CMe), 0.98–1.14
(1 H, m, CH), 1.25–1.44 (1 H, m, CH), 1.40 (9 H, s, CMe3),
1.46–1.63 (1 H, m, CH), 1.72–1.85 (1 H, m, CH), 2.13 (3 H, s,
CMe), 2.40 (1 H, dd, J 8.1 and 8.1, 2-H), 2.57 (3 H, s, CMe),
2.67 (3 H, s, CMe), 3.62 (1 H, ddd, J 7.6, 7.3 and 5.4, 5-H), 3.84
(3 H, s, OMe), 4.46 (1 H, d, J 7.6, NH), 5.26 (1 H, dd, J 15.1 and
7.3, 4-H), 5.31 (1 H, dd, J 15.1 and 8.1, 3-H), 6.55 (1 H, s, Ph);
m/z (FAB-LRMS) 482 (MHϩ), 480, 424, 380, 368, 298, 268,
230, 213 (base peak), 197, 149, 119, 95, 57, 41.
19 J. Tsuji, I. Shimizu, I. Minami and Y. Ohashi, Tetrahedron Lett.,
1982, 23, 4809; J. Tsuji, I. Shimizu, I. Minami, Y. Ohashi, T. Sugiura
and K. Takahashi, J. Org. Chem., 1985, 50, 1523.
20 J. Tsuji, Palladium Reagents and Catalysis, Wiley, New York, 1995;
J. Tsuji and I. Minami, Acc. Chem. Res., 1987, 20, 140; J. Tsuji,
Tetrahedron, 1986, 42, 4361.
21 (a) K. Fugami, Y. Morizawa, K. Oshima and H. Nozaki,
Tetrahedron Lett., 1985, 26, 857; (b) N. Mimura, T. Ibuka, M. Akaji,
Y. Miwa, T. Taga, K. Nakai, H. Tamamura, N. Fujii and
Y. Yamamoto, Y. Chem. Commun., 1996, 351 and 1399; (c)
T. Ibuka, N. Mimura, H. Aoyama, M. Akaji, H. Ohno, Y. Miwa,
T. Taga, K. Nakai, H. Tamamura, N. Fujii and Y. Yamamoto,
J. Org. Chem., 1997, 62, 999; (d) synthesis of activated 2-vinyl-
aziridines from 1,4-amino alcohols has appeared recently, see
H. F. Olivo, M. S. Hemenway, A. C. Hartwig and R. Chan, Synlett,
1998, 247.
Acknowledgements
This work was supported in part by a Grant-in-Aid for
Scientific Research (B) and (C) from the Ministry of Education,
Science, Sports and Culture, Japan, to which the author’s
thanks are due.
References
1 E. J. Moran, J. E. Tellew, Z. Zhao and R. W. Armstrong, J. Org.
Chem., 1993, 58, 7848.
2 (a) G. W. Spears, K. Nakanishi and Y. Ohfune, Synlett, 1991, 91; (b)
D. Tanner and P. Somfai, Bioorg. Med. Chem. Lett., 1993, 3, 2415;
(c) for a review of cyclization reactions of amino allylic alcohols, see
Y. Hirai and H. Yokoyama, J. Synth. Org. Chem. Jpn., 1998, 56, 50.
3 F. A. Davis, G. V. Reddy and H. Liu, J. Am. Chem. Soc., 1995, 117,
3651.
22 (a) T. Ibuka, M. Akaji, N. Mimura, H. Habashita, K. Nakai,
H. Tamamura, N. Fujii and Y. Yamamoto, Tetrahedron Lett., 1996,
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716
3715

View Article Online
37, 2849; (b) T. Ibuka, N. Mimura, H. Ohno, K. Nakai, M. Akaji,
H. Habashita, H. Tamamura, Y. Miwa, T. Taga, N. Fujii and
Y. Yamamoto, J. Org. Chem., 1997, 62, 2982; (c) H. Ohno,
N. Mimura, A. Otaka, H. Tamamura, N. Fujii, T. Ibuka, I. Shimizu,
A. Satake and Y. Yamamoto, Tetrahedron, 1997, 53, 12933.
23 R. Ramage and J. Green, Tetrahedron Lett., 1987, 28, 2287; J. Green,
O. M. Ogunjobi, R. Ramage and A. S. J. Stewart, Tetrahedron Lett.,
1988, 29, 4341.
24 M. Fujino, M. Wakimatsu and C. Kitada, Chem. Pharm. Bull.,
1981, 29, 2825.
25 M. J. McKennon, A. I. Meyers, K. Drauz and M. Schwarm, J. Org.
Chem., 1993, 58, 3568.
Jackson, W. U. Primrose, G. C. K. Roberts, D. H. Robinson and
P. K. Slaich, J. Med. Chem., 1992, 35, 2939.
27 V. J. Hruby and K. W. Ehler, J. Org. Chem., 1970, 35, 1690;
H. Sugano and M. Miyoshi, J. Org. Chem., 1976, 41, 2352.
28 P. Coutrot, A. Elgadi and C. Grison, Heterocycles, 1989, 28, 1179;
F. A. Davis and P. Zhou, Tetrahedron Lett., 1994, 35, 7525;
F. A. Davis, P. Zhou and G. V. Reddy, J. Org. Chem., 1994, 59, 3243;
F. E. Ziegler and M. Belema, J. Org. Chem., 1994, 59, 7962.
29 (a) B. M. Trost and T. P. Klun, J. Org. Chem., 1980, 45, 4256;
(b) R. W. Hoffmann, Chem. Rev., 1989, 89, 1841; (c) S. D. Kahn,
C. F. Pau, A. R. Chamberlin and W. J. Hehre, J. Am. Chem. Soc.,
1987, 109, 650.
26 M.-C. Fournié-Zaluski, P. Coric, S. Turcaud, L. Bruetschy, E. Luce,
F. Noble and B. P. Roques, J. Med. Chem., 1992, 35, 1259;
C. Bennion, S. Connolly, N. P. Gensmantel, C. Hallam, C. G.
Paper 8/06882H
3716
J. Chem. Soc., Perkin Trans. 1, 1998, 3703–3716