Stereodivergent synthesis of chiral 2-alkenylaziridines: Palladium(0)-catalyzed 2,3-cis-selective aziridination and base-mediated 2,3-trans-selective aziridination

Article abstract of DOI:10.1248/cpb.52.111

Whereas treatment of the allylic mesylates of N-protected 2-alkyl-4-amino-(E)-2-alken-1-ols with sodium hydride in DMF yields exclusively the corresponding thermodynamically less stable 2,3-trans-2-alkenyl-3- alkylaziridines, exposure of the methyl carbon

Full text of DOI:10.1248/cpb.52.111

January 2004
Chem. Pharm. Bull. 52(1) 111—119 (2004)
111
Stereodivergent Synthesis of Chiral 2-Alkenylaziridines: Palladium(0)-
Catalyzed 2,3-cis-Selective Aziridination and Base-Mediated
2,3-trans-Selective Aziridination
a
b
b
b,1)
Hiroaki OHNO, Yoshiji TAKEMOTO, Nobutaka FUJII, Tetsuaki TANAKA, ,a and Toshiro IBUKA
*
a Graduate School of Pharmaceutical Sciences, Osaka University; 1–6 Yamadaoka, Suita, Osaka 565–0871, Japan: and
b Graduate School of Pharmaceutical Sciences, Kyoto University; Sakyo-ku, Kyoto 606–8501, Japan.
Received September 18, 2003; accepted October 15, 2003; published online October 20, 2003
Whereas treatment of the allylic mesylates of N-protected 2-alkyl-4-amino-(E)-2-alken-1-ols with sodium
hydride in DMF yields exclusively the corresponding thermodynamically less stable 2,3-trans-2-alkenyl-3-alkyl-
aziridines, exposure of the methyl carbonates of N-protected 2-alkyl-4-amino-(E)-2-alken-1-ols to a catalytic
amount of Pd(PPh3)4 in THF or 1,4-dioxane affords predominantly the corresponding thermodynamically more
stable 2,3-cis-2-alkenyl-3-alkylaziridines. The kinetically favored trans-selective aziridination would be attributed
to the allylic 1,3-strain in aza-anionic intermediates. The conformational analysis of the sterically highly con-
gested 2-alkenylaziridines thus obtained is also presented.
Key words aziridine; palladium; cyclization; stereoselectivity; stereodivergent synthesis
Chiral N-activated aziridines are widely used as building a highly stereodivergent synthesis of 2,3-cis-2-alkenyl-
blocks for the asymmetric synthesis of biologically and syn- aziridines 7 (Eq. 5) and 2,3-trans-isomers 8 (Eq. 6), by the
thetically important compounds.2—8) Particularly, aziridines palladium-catalyzed decarboxylative ring closure of carbon-
bearing an alkenyl9—14) or ethynyl group15—18) on one of the ates 6a and the base-mediated aziridination of mesylates 6b,
aziridine-ring carbon atoms have proven to be extremely use- respectively, from single allylic alcohols having an alkyl
ful intermediates for asymmetric preparation of such com- group (R3) on the double bond.27)
pounds as alkaloids,9,10) b-lactams,11—13) vinylglycines,14)
amino allenes,15,16) amino alcohols,17,18) and (E)-alkene
dipeptide isosteres.19—22) Although some stereoselective syn-
theses of enantiomerically pure 2-alkenylaziridines have been
reported, most of the reported methods consist of two
processes, formation of the aziridine ring and construction of
the olefinic moiety, via several steps.
In connection with our program directed toward synthesis
of (E)-alkene dipeptide isosteres,19—21) we required an effi-
cient stereoselective synthetic method of chiral 2-alkenyl-
aziridines. Recently, we reported a palladium(0)-catalyzed
aziridination of allylic carbonates 1a preferentially affording
thermodynamically more stable 2,3-cis-2-vinylaziridines 2
over the corresponding trans isomers 3 in good selectivities
(2 : 3ϭ94 : 6—98 : 2, Eq. 1).23) In these reaction conditions,
the palladium catalyst not only converts the carbonates 1a
into the aziridines 2 and 3 but also equilibrates the isomeric
mixtures of 2 and 3 via p-allylpalladium(II) intermediates
A.20,21) In contrast, base-mediated intramolecular amination
of mesylates 1b with NaH in DMF produces mixtures of 2
and 3 in variable ratios (2,3-cis : transϭ8 : 92—51 : 49) de-
pending on the steric bulkiness of the alkyl substituent R1
(Eq. 2).23—25) Interestingly, while (Z)-allylic carbonates 4a
provide 2,3-cis-2-vinylaziridines 2 stereoselectively (2 : 3ϭ
94 : 6—97 : 3) under the palladium(0)-catalyzed cyclization
conditions (Eq. 3), sodium hydride-mediated cyclization of
(Z)-allylic mesylates 4b affords 3-pyrrolines 5 as the sole
isolable product (Eq. 4).26) Our present research is focused on
how the substituent on the double bond changes the stereose-
lectivities of the aziridine formation. We expected that the in-
troduction of the substituent on the double bond would im-
prove the trans-selectivity in the base-mediated aziridination
by increasing the unfavorable steric interaction in the anionic
intermediates leading to the cis-aziridines. Detailed here is
To whom correspondence should be addressed. e-mail: t-tanaka@phs.osaka-u.ac.jp
© 2004 Pharmaceutical Society of Japan

112
Vol. 52, No. 1
Yieldc)
Table 1. Pd(PPh3)4-Catalyzed 2,3-cis-Selective Aziridination of Allylic Methyl Carbonatesa)
Pd(PPh3)4
(mol%)
Temp.
(°C)
Time
(min)
Ratiob)
(14 : 15)
Entry
Substrate
Solvent
Products
1
2
12a (RϭMe)
12b (RϭEt)
THF
Dioxane
6
10
65
101
240
15
14a (RϭMe)
14b (RϭEt)
15a (RϭMe)
15b (RϭEt)
98 : 2
99 : 1
85%
87%
3
Dioxane
4
101
15
98 : 2
69%
12c
12d
12e
14c
15c
15d
15e
4
5
Dioxane
Dioxane
20
20
95
30
30
98 : 2
97 : 3
49%
68%
14d
101
14e
6
7
12f (RϭMts)
12g (RϭMs)
Dioxane
Dioxane
20
20
101
101
120
150
14f (RϭMts)
14g (RϭMs)
15f (RϭMts)
15g (RϭMs)
87 : 13
91 : 9
68%
64%
a) All reactions were carried out in dry THF or 1,4-dioxane (ca. 0.1 M solution) using a catalytic amount of Pd(PPh3)4. b) Product ratios were determined by HPLC. c)
Combined isolated yields.
Results and Discussion
Synthesis of the Methyl Carbonates and Mesylates of
Allylic Alcohols Bearing an N-(Arylsulfonyl)amino Group
As shown in Chart 1, the requisite chiral methyl allylic car-
bonates 12a—g and the mesylates 13a—g of N-(arylsul-
fonyl)amino alcohols were prepared in good to high yields
starting from the N-arylsulfonyl amino alcohols 9 which, in
turn, could be prepared from (S)-valinol, (S)-leucinol, (S)-
phenylalaninol, (S)-isoleucinol and (S)-tert-leucinol.28) Typi-
cally, Swern oxidation of N-protected (S)-valinol by succes-
sive treatment with oxalyl chloride, DMSO, and N,N-diiso-
propylethylamine, and olefination of the resulting aldehyde
with a phosphonium ylide [Ph3PϭC(Me)CO2Me] afforded
(E)-enoate 10a in 87% yield, which was treated with DIBAL-
H to give allylic alcohol 11a in 95% yield. Conversion of the
alcohol 11a into both carbonate 12a and mesylate 13a was
accomplished in high yields (94%, 98%, respectively) fol-
lowing standard procedures (see Experimental). The other
chiral methyl allylic carbonates 12b—g and mesylates 13b—
g listed in Chart 1 were prepared by a sequence of reactions
similar to that described for the synthesis of the carbonate
12a and the mesylate 13a (see Experimental). Exceptionally,
enoate 10g was synthesized from N-Boc derivative of 10g,
which was readily prepared from N-Boc tert-leucinol, by
Chart 1. Synthesis of Allyl Carbonates 12 and Mesylates 13 Bearing an
Alkyl (R3) Group

January 2004
113
Table 2. Spin–Spin Coupling Constant for JH2,3 of the Highly Congested Table 3. Sodium Hydride-Mediated 2,3-trans-Selective Aziridination of
2,3-cis- and 2,3-trans-2-Alkenylaziridines 14 and 15 in CDCl3
Allylic Mesylatesa)
Product
(Ratiob))
Entry
Substrate
Yieldc)
Entry
Aziridine
Stereochemistry
JH2,3
1
2
13a (RϭMe)
13b (RϭEt)
15a (RϭMe; Ͼ99 : 1)
15b (RϭEt; Ͼ99 : 1)
78%
95%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
14a
14b
14c
14d
14e
14f
14g
15a
15b
15c
15d
15e
15f
2,3-cis
2,3-cis
2,3-cis
2,3-cis
2,3-cis
2,3-cis
2,3-cis
2,3-trans
2,3-trans
2,3-trans
2,3-trans
2,3-trans
2,3-trans
2,3-trans
7.3 Hz
7.3 Hz
7.6 Hz
7.3 Hz
7.3 Hz
7.6 Hz
7.8 Hz
4.3 Hz
4.6 Hz
4.3 Hz
4.0 Hz
4.6 Hz
5.1 Hz
5.1 Hz
3
4
5
82%
86%
95%
13c
13d
13e
15c (Ͼ99 : 1)
15d (Ͼ99 : 1)
15e (Ͼ99 : 1)
15g
treatment with TFA followed by MtsCl/Et3N in 96% yield.
Yields of each reaction are summarized in Chart 1.
Palladium(0)-Catalyzed 2,3-cis-Selective Aziridination
Reaction of Allylic Carbonates Having synthesized the
substrates for the palladium(0)-catalyzed aziridination reac-
tion of allylic carbonates 12, the aziridination reaction was
then investigated (Table 1). As expected, when the carbonate
12a having a methyl group on the double bond was treated
with 6 mol% of Pd(PPh3)4 in THF at 65 °C for 4 h (entry 1), a
separable 98 : 2 mixture of 3-isopropyl-2-vinylaziridine was
obtained in 85% yield. The mixture was separated by recrys-
tallization followed by flash column chromatography, and we
confirmed that the major product was 2,3-cis-2-alkenylaziri-
dine 14a and the minor product was its 2,3-trans isomer 15a.
As shown in Table 1, methyl carbonates 12c—e also gave the
corresponding 2,3-cis-aziridines 14c—e in extremely high
diastereoselectivities by treatment with a catalytic amount of
Pd(PPh3)4 under equilibrated conditions (entries 3—5).20,21)
Interestingly, the methyl carbonates 12f and 12g having a
tert-butyl group also gave the corresponding sterically highly
congested 2,3-cis-aziridines 14f and 14g as the major prod-
ucts. Apparently, the relatively low 2,3-cis selectivities
(87 : 13—91 : 9) would be attributed to the unfavorable steric
interaction between the tert-butyl group and the alkenyl
group.
6
7
13f (RϭMts)
13g (RϭMs)
15f (RϭMts; Ͼ99 : 1)
15g (RϭMs; Ͼ99 : 1)
93%
92%
a) All reactions were carried out in DMF (ca. 0.1 M solution) using 1.5 eq of NaH.
b) Product ratios were determined by HPLC. c) Isolated yields.
nation Reaction of Allylic Mesylates Our previous results
have shown that mesylates 1b (Eq. 2) bearing a branched
alkyl group (R1) such as an isopropyl group afforded 2,3-
trans-2-vinylaziridines in moderate to good stereoselectivi-
ties (2,3-trans : cisϭ74 : 26—92 : 8), while mesylates 1b with
a smaller R1 group such as an isobutyl or a benzyloxymethyl
group gave almost 1 : 1 mixtures of 2,3-trans- and 2,3-cis-2-
vinylaziridines (2,3-trans : cisϭ49 : 51—57 : 43).23) We next
investigated the reaction of mesylates 13 and found that the
effect of the alkyl group on the double bond on the stereose-
lectivity was more significant than we expected. The results
are summarized in Table 3. Exposure of the mesylates 13a to
sodium hydride in DMF at 0 °C for 30 min gave exclusively
the corresponding 2,3-trans-aziridines 15a in 78% yields
(entry 1). Similarly, 2,3-trans-aziridines 15b—g were ob-
tained in high isolated yields (82—95%) as a single isomer
by the reaction of the mesylates 13b—g with sodium hydride
in DMF (entries 2—7). Irrespective of the structure of the
starting mesylates, the diastereoselection of the products 15
is over 99% judging from reverse-phase HPLC.
In some cases (entries 1, 2, 4, 5), pure 2,3-cis-2-alkenyl-
aziridines 14 can be obtained by purification of the reaction
mixture by a short column chromatography over silica gel
followed by recrystallization of the resulting isomeric mix-
tures. The 2,3-cis- and 2,3-trans-stereochemistries were read-
ily established from 1H-NMR analyses. As shown in Table 2,
the 2,3-cis-aziridines 14a—g show the JH2,3 value (Jϭ7.3—
7.8 Hz, entries 1—7) larger than that of the corresponding
2,3-trans-isomers 15a—g (Jϭ4.0—5.1 Hz, entries 8—14).
It should be noted that the N-activated29) 2,3-trans-2-vinyl-
aziridines are thermodynamically less stable than the corre-
sponding 2,3-cis isomers.20,21,23,30) The results of the palla-
dium(0)-catalyzed cyclization (Table 1) clearly show that this
1
The data are in good agreement with H-NMR data for re-
lated compounds.20,21)
Sodium Hydride-Mediated 2,3-trans-Selective Aziridi-

114
Vol. 52, No. 1
thermodynamic preference for cis-aziridines is also applica- tained by exposure of the mesylate 13a to sodium hydride,
ble to the sterically congested 2-alkenylaziridines 14 and 15. was stirred with 4 mol% of Pd(PPh3)4 for 12 h at 0 °C to yield
Actually, as shown in Chart 2, 2,3-trans-aziridine 15a, ob- a 98 : 2 equilibrated mixture of 2,3-cis-14a and 2,3-trans-15a
in 96% combined isolated yield. This equilibrated reaction
indicates that 14a is estimated to be ca. 2.0 kcal/mol more
stable than 15a.
These results show that sodium hydride-mediated aziridi-
nation of the allylic mesylates 13 exclusively yields thermo-
dynamically less stable 2,3-trans-2-alkenylaziridines 15. The
exclusive formation of 2,3-trans-aziridine 15 from the mesy-
Chart 2. Palladium(0)-Catalyzed Equilibration Reaction of 2,3-trans-2-
Alkenylaziridines 15a
late 13 may be rationalized by assuming two aza-anionic in-
termediates 16 and 17 (Chart 3). Conformer 16, which would
lead to 2,3-cis-aziridine 14 with 2,3-stereochemistry opposite
to what was observed experimentally, may be highly destabi-
lized in comparison with 17 owing to unfavorable interac-
tions (allylic 1,3-strain) between the R1 and R3 groups. In
conformer 17, the allylic 1,3-strain may be minimized.31) Ac-
cordingly, treatment of the mesylate 13 with sodium hydride
yields exclusively the 2,3-trans-aziridine 15 most probably
via the conformer 17.
Conformation of the Highly Congested 2-Alkenyl-
aziridines In vinylcyclopropane, it has been well docu-
mented that the stable conformation has the vinyl group syn-
periplanar to the cyclopropyl hydrogen on the adjacent car-
bon atom.32—36) Similarly, in simple non-congested 2,3-cis-
and 2,3-trans-N-mesyl-2-vinyl-3-methylaziridines 18 and 19
(Fig. 1), the C(2)–H bond of the aziridine ring was predicted
by ab initio calculations to be near-eclipsed with the vinyl
group (18-A and 19-A, respectively). In fact, solid conforma-
tion of 2,3-trans-N-mesyl-3-methyl-2-vinylaziridine has the
CϭCH2 group rotated only less than 5° away from perfect
eclipsing (synperiplanar arrangement).20)
Chart 3. Formation of the 2,3-trans-2-Alkenylaziridines 15 from the Me-
sylates 13
In sharp contrast to the vinylaziridine 18, the hydrogen
atom at the C-2 position of the sterically more congested
aziridine 14f and the CH2 group of the alkenyl are shown to
be anticlinal from both X-ray analysis and NOE investiga-
tions as shown in 14f-B in Fig. 2.37) The synplanar arrange-
ment 14f-A would be highly destabilized in comparison with
conformer 14f-B owing to unfavorable interactions between
the bulky tert-butyl group and the methyl group. Similarly,
the preferred conformation 15f-B of 2,3-trans-aziridine 15f
can be deduced from X-ray and NOE analyses (Fig. 2). From
these observations, both the congested 2,3-cis- and 2,3-trans-
2-alkenylaziridines decrease the steric hindrance by changing
Fig. 1. Stable Conformations of 2,3-cis- and 2,3-trans-3-Methyl-N-mesyl-
2-vinylaziridine 18 and 19
Fig. 2. Solid-State Conformation of the Highly Congested 2-Alkenylaziridines

January 2004
115
Methyl (4S,2E)-2,6-Dimethyl-4-[N-(4-methylphenylsulfonyl)amino]hept-
2-enoate (10c) (S)-N-(4-Methylphenylsulfonyl)leucinol 9c23) (4.07 g, 15
mmol) was converted into 10c (3.18 g, 63% yield): colorless needles from n-
hexane–Et2O (3 : 1); mp 72—74 °C; [a]D27 ϩ5.0° (cϭ1.06, CHCl3); 1H-NMR
(300 MHz, CDCl3) d: 0.84 (d, Jϭ6.5 Hz, 3H), 0.85 (d, Jϭ6.5 Hz, 3H), 1.22
their conformation from the generally-observed synperipla-
nar arrangement to the anticlinal one.
In summary, whereas treatment of the allylic mesylates of
N-protected 2-alkyl-4-amino-(E)-2-alken-1-ols with sodium
hydride in DMF yields exclusively the corresponding 2,3- (ddd, Jϭ13.9, 6.9, 6.9 Hz, 1H), 1.44 (ddd, Jϭ13.9, 7.8, 6.7 Hz, 1H), 1.52—
trans-2-alkenyl-3-alkylaziridines, exposure of the methyl car-
1.65 (m, 1H), 1.72 (d, Jϭ1.5 Hz, 3H), 2.39 (s, 3H), 3.64 (s, 3H), 4.08—4.20
(m, 1H), 4.66 (d, Jϭ7.7 Hz, 1H), 6.17 (dq, Jϭ9.7, 1.5 Hz, 1H), 7.22—7.26 (m,
2H), 7.67—7.71 (m, 2H). Anal. Calcd for C17H25NO4S: C, 60.15; H, 7.42; N,
4.13. Found: C, 60.02; H, 7.47; N, 4.15.
bonates of the same alcohols to a catalytic amount of
Pd(PPh3)4 in THF or 1,4-dioxane affords predominantly the
corresponding 2,3-cis-2-alkenyl-3-alkylaziridines. The exclu-
sive formation of 2,3-trans-aziridines from the mesylates
may be rationalized by assuming the 1,3-allylic strain in the
aza-anionic intermediates. It is interesting that the introduc-
tion of an alkyl group on the double bond of the vinyl-
aziridines improves the thermodynamic preference for the
2,3-cis-2-vinylaziridines over their 2,3-trans isomers to up to
99 : 1, although the alkyl group apparently makes the cis-iso-
mers more congested as well as the corresponding trans-iso-
mers. The present aziridination reactions provide a powerful
methodology for the synthesis of either of the two diastere-
omers of 2-alkenylaziridines from single intermediates.
Methyl (4S,2E)-2-Methyl-5-phenyl-4-[N-(2,4,6-trimethylphenylsul-
fonyl)amino]pent-2-enoate (10d) (S)-N-(2,4,6-Trimethylphenylsul-
fonyl)phenylalaninol 9d23) (4.0 g, 12.0 mmol) was converted into 10d
(3.56 g, 74% yield): colorless needles from n-hexane–Et2O (2 : 1); mp 118—
120 °C; [a]D30 Ϫ7.1° (cϭ0.505, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 1.48
(d, Jϭ1.4 Hz, 3H), 2.27 (s, 3H), 2.47 (s, 6H), 2.76 (dd, Jϭ13.5, 7.0 Hz, 1H),
2.83 (dd, Jϭ13.5, 6.8 Hz, 1H), 3.65 (s, 3H), 4.20 (dddd, Jϭ9.5, 7.0, 6.8,
5.9 Hz, 1H), 4.67 (d, Jϭ5.9 Hz, 1H), 6.34 (dq, Jϭ9.5, 1.4 Hz, 1H), 6.87 (s,
2H), 7.00—7.09 (m, 2H), 7.20—7.29 (m, 3H). Anal. Calcd for C22H27NO4S:
C, 65.81; H, 6.78; N, 3.49. Found: C, 65.66; H, 6.88; N, 3.34.
Methyl (4S,5S,2E)-2,5-Dimethyl-4-[N-(2,4,6-trimethylphenylsul-
fonyl)amino]hept-2-enoate (10e) To a stirred solution of (2S,3S)-isoleuci-
nol28) (10 g, 85.3 mmol) and Et3N (24.8 ml, 179 mmol) in a mixed solvent of
DMF (10 ml) and CHCl3 (20 ml) was added MtsCl (19.6 g, 89.6 mmol) in
CHCl3 (15 ml) at 0 °C, and the mixture was stirred at this tempetature for 4 h
followed by quenching with saturated NaHCO3 (2 ml). The whole was ex-
Experimental
General Methods Melting points are uncorrected. Chemical shifts are tracted with a mixed solvent of Et2O–EtOAc (3 : 1), and the extract was
reported in parts per million downfield from internal Me4Si (sϭsinglet, washed successively with saturated citric acid, water, saturated NaHCO3,
dϭdoublet, ddϭdouble doublet, dddϭdoublet of double doublet, tϭtriplet, and water, and dried over MgSO4. Usual workup followed by recrystalliza-
qϭquartet, mϭmultiplet). Optical rotations were measured in CHCl3. For tion from n-hexane–Et2O (3 : 1) gave (2S,3S)-N-(2,4,6-trimethylphenylsul-
flash chromatography, silica gel 60 H (silica gel for thin-layer chromatogra- fonyl)isoleucinol 9e (22.0 g, 86% yield): colorless crystals from n-
phy, Merck) or silica gel 60 (finer than 230 mesh, Merck) was employed. hexane–Et2O (3 : 1); mp 61 °C; [a]D28 Ϫ18.7° (cϭ1.39, CHCl3); 1H-NMR
The known compounds (S)-N-(2,4,6-trimethylphenylsulfonyl)valinol 9a,23) (270 MHz, CDCl3) d: 0.75 (t, Jϭ7.0 Hz, 3H), 0.76 (d, Jϭ7.0 Hz, 3H),
(S)-N-(4-methylphenylsulfonyl)leucinol 9c,23) (S)-N-(2,4,6-trimethylphenyl- 0.94—1.10 (m, 1H), 1.31—1.56 (m, 2H), 2.05—2.16 (m, 1H), 2.30 (s, 3H),
sulfonyl)phenylalaninol 9d,23) (2S,3S)-isoleucinol,28) and (S)-tert-leucinol28) 2.66 (s, 6H), 3.04—3.14 (m, 1H), 3.50—3.64 (m, 2H), 4.98—5.07 (m, 1H),
were synthesized according to the literature.
6.96 (s, 2H). Anal. Calcd for C15H25NO3S: C, 60.17; H, 8.42; N, 4.68.
General Procedure for the Synthesis of 2-Alkyl-2-enoates (10). Syn- Found: C, 60.23; H, 8.58; N, 4.54.
thesis of Methyl (4S,2E)-2,5-Dimethyl-4-[N-(2,4,6-trimethylphenylsul-
According to the general procedure for preparation of the enoate 10, the
fonyl)amino]hex-2-enoate (10a) To a stirred solution of oxalyl chloride alcohol 9e (4.0 g, 13.4 mmol) was converted into 10e (3.28 g, 67% yield):
1
(2.6 ml, 27.2 mmol) in CH2Cl2 (40 ml) at Ϫ78 °C under argon was added colorless oil; [a]D30 Ϫ16.1° (cϭ0.884, CHCl3); H-NMR (270 MHz, CDCl3)
dropwise a solution of DMSO (6.4 ml, 90.5 mmol) in CHCl3 (5 ml). After d: 0.84 (d, Jϭ7.0 Hz, 3H), 0.87 (t, Jϭ7.0 Hz, 3H), 1.00—1.18 (m, 1H),
30 min,
a
solution of (S)-N-(2,4,6-trimethylphenylsulfonyl)valinol 9a23) 1.39—1.64 (m, 2H), 1.58 (d, Jϭ1.6 Hz, 3H), 2.27 (s, 3H), 2.60 (s, 6H), 3.64
(5.16 g, 18.1 mmol) in CHCl3 (7 ml) was added to the above reagent at
(s, 3H), 3.93 (ddd, Jϭ9.5, 7.8, 5.1 Hz, 1H), 4.66 (d, Jϭ7.8 Hz, 1H), 6.23
Ϫ78 °C, and the mixture was stirred for 30 min. Diisopropylethylamine (dq, Jϭ9.5, 1.6 Hz, 1H), 6.89 (s, 2H); MS (FAB) m/z 368 (MHϩ), 366, 336,
(22 ml, 127 mmol) was added to the above solution at Ϫ78 °C and the mix- 310, 268, 198, 169, 137, 119 (base peak), 109; HR-MS (FAB) calcd for
ture was stirred for 30 min. Saturated citric acid (10 ml) was added to the C19H30NO4S (MHϩ) 368.1895; found: 368.1903.
mixture and the whole was extracted with Et2O. The extract was washed suc-
cessively with water, saturated NaHCO3, and water, and dried over MgSO4.
Methyl (4R,2E)-2,5,5-Trimethyl-4-[N-(2,4,6-trimethylphenylsul-
fonyl)amino]hex-2-enoate (10f) To a stirred solution of (S)-tert-leuci-
The filterate was concentrated under reduced pressure to give a residual oil, nol28) (3.4 g, 29 mmol) and Et3N (6.0 ml, 44 mmol) in a mixed solvent of
which was dessolved in CHCl3 (25 ml). A phosphonium ylide [Ph3Pϭ DMF (5 ml) and CHCl3 (10 ml) was added MtsCl (7.0 g, 32 mmol) in CHCl3
C(Me)CO2Me] (15.7 g, 45.3 mmol) was added to the above solution at 0 °C,
(5 ml) at 0 °C, and the mixture was stirred at this tempetature for 16 h fol-
and the mixture was stirred for 18 h at this temperature. Concentration under lowed by quenching with saturated NaHCO3 (2 ml). The whole was ex-
reduced pressure gave an oily residue, which was flash chromatographed tracted with a mixed solvent of Et2O–EtOAc (3 : 1) and the extract was
over silica gel with n-hexane–EtOAc (2 : 1) to give 10a (5.56 g, 87% yield) washed successively with saturated citric acid, water, saturated NaHCO3,
as colorless crystals from n-hexane–EtOAc (2 : 1): mp 109—111 °C; and water, and dried over MgSO4. Usual workup followed by recrystalliza-
[a]D25 Ϫ27.2° (cϭ0.619, CHCl3); 1H-NMR (300 MHz, CDCl3) d: 0.86 (d, tion from n-hexane–EtOAc (2 : 1) gave (S)-N-(2,4,6-trimethylphenylsul-
Jϭ6.8 Hz, 3H), 0.92 (d, Jϭ6.8 Hz, 3H), 1.59 (d, Jϭ1.5 Hz, 3H), 1.72—1.84 fonyl)-tert-leucinol 9f (8.18 g, 94% yield): colorless crystals; mp 140 °C;
(m, 1H), 2.26 (s, 3H), 2.60 (s, 6H), 3.64 (s, 3H), 3.83 (ddd, Jϭ10.1, 7.9, [a]D26 Ϫ49.0° (cϭ1.65, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.80 (s, 9H),
6.2 Hz, 1H), 4.68 (d, Jϭ7.9 Hz, 1H), 6.22 (dq, Jϭ10.1, 1.5 Hz, 1H), 6.89 (s, 2.17—2.27 (m, 1H), 2.30 (s, 3H), 2.67 (s, 6H), 2.96 (ddd, Jϭ9.7, 5.9,
2H). Anal. Calcd for C18H27NO4S: C, 61.16; H, 7.70; N, 3.96. Found: C,
61.13; H, 7.69; N, 3.92.
Methyl (4S,2E)-2-Ethyl-5-methyl-4-[N-(2,4,6-trimethylphenylsul-
fonyl)amino]hex-2-enoate (10b) According to the general procedure for
4.0 Hz, 1H), 3.61 (ddd, Jϭ11.1, 5.9, 4.0 Hz, 1H), 3.69 (ddd, Jϭ11.1, 7.0,
4.0 Hz, 1H), 4.91—5.03 (m, 1H), 6.95 (s, 2H). Anal. Calcd for C15H25NO3S:
C, 60.17; H, 8.42; N, 4.68. Found: C, 59.93; H, 8.62; N, 4.66.
According to the general procedure for preparation of the enoate 10, the
the preparation of the enoate 10 except that Ph3PϭC(Et)CO2Me was used alcohol 9f (4.0 g, 13.4 mmol) was converted into 10f (4.48 g, 91% yield):
as a phosphonium ylide, (S)-N-(2,4,6-trimethylphenylsulfonyl)valinol 9a23) colorless crystals from n-hexane–Et2O (3 : 1); mp 81 °C; [a]D29 Ϫ22.3°
(2.5 g, 8.76 mmol) was converted into 10b (3.12 g, 97% yield): colorless oil; (cϭ1.39, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.90 (s, 9H), 1.52 (d,
[a]D22 Ϫ6.0° (cϭ0.910, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.86 (dd, Jϭ1.4 Hz, 3H), 2.26 (s, 3H), 2.60 (s, 6H), 3.63 (s, 3H), 3.71 (dd, Jϭ10.5,
Jϭ7.5, 7.5 Hz, 3H), 0.88 (d, Jϭ6.8 Hz, 3H), 0.92 (d, Jϭ6.8 Hz, 3H), 1.71—
9.5 Hz, 1H), 4.66—4.75 (m, 1H), 6.24 (dq, Jϭ10.5, 1.4 Hz, 1H), 6.87 (s,
1.83 (m, 1H), 2.04 (dq, Jϭ17.3, 7.5 Hz, 1H), 2.08 (dq, Jϭ17.3, 7.5 Hz, 1H), 2H). Anal. Calcd for C19H29NO4S: C, 62.10; H, 7.95; N, 3.81. Found: C,
2.26 (s, 3H), 2.60 (s, 6H), 3.65 (s, 3H), 3.88 (ddd, Jϭ10.2, 7.9, 5.8 Hz, 1H), 61.92; H, 7.85; N, 3.82.
4.61 (d, Jϭ7.9 Hz, 1H), 6.19 (d, Jϭ10.2 Hz, 1H), 6.89 (s, 2H); MS (FAB)
Methyl
(4R,2E)-2,5,5-Trimethyl-4-[N-(methylsulfonyl)amino]hex-2-
m/z 368 (MHϩ), 366, 324, 322, 254, 198, 169, 167, 137, 119 (base peak), enoate (10g) To a stirred solution of (S)-tert-leucinol28) (3.3 g, 28.2 mmol)
109, 91; HR-MS (FAB) calcd for C19H30NO4S (MHϩ) 368.1895; found: and Et3N (8.19 ml, 59.2 mmol) in a mixed solvent of DMF (10 ml) and
368.1892.
CHCl3 (10 ml) was added Boc2O (6.46 g, 29.6 mmol) at 0 °C. After 10 h, sat-

116
Vol. 52, No. 1
urated NaHCO3 (5 ml) was added to the mixture and the whole was ex- 4.43.
tracted with a mixed solvent of Et2O–EtOAc (1 : 1). The extract was washed
(4S,2E)-2-Methyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]-5-
successively with saturated citric acid, water, saturated NaHCO3, and water, phenylpent-2-en-1-ol (11d) The enoate 10d (3.4 g, 8.47 mmol) was con-
and dried over MgSO4. Usual workup followed by recrystallization from n- verted into 11d (3.14 g, 99% yield): colorless oil; [a]D29 ϩ10.2° (cϭ0.492,
hexane–EtOAc (1 : 1) gave (S)-N-(tert-butoxycarbonyl)-tert-leucinol (4.87 g, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 1.12—1.17 (m, 1H), 1.29 (d,
80% yield): colorless prisms; mp 101 °C; [a]D19 Ϫ6.3° (cϭ0.896, CHCl3); Jϭ1.1 Hz, 3H), 2.29 (s, 3H), 2.50 (s, 6H), 2.72 (dd, Jϭ13.5, 7.0 Hz, 1H),
1H-NMR (270 MHz, CDCl3) d: 0.94 (s, 9H), 1.46 (s, 9H), 2.15—2.25 (m, 2.79 (dd, Jϭ13.5, 6.5 Hz, 1H), 3.64—3.78 (m, 2H), 4.20 (dddd, Jϭ9.2, 7.0,
1H), 3.44—3.54 (m, 2H), 3.79—3.90 (m, 1H), 4.57—4.68 (m, 1H). Anal.
6.5, 5.4 Hz, 1H), 4.63 (d, Jϭ5.4 Hz, 1H), 5.04 (dq, Jϭ9.2, 1.1 Hz, 1H), 6.90
Calcd for C11H23NO3: C, 60.80; H, 10.67; N, 6.45. Found: C, 60.71; H, (s, 2H), 7.04—7.10 (m, 2H), 7.17—7.28 (m, 3H); MS (FAB) m/z 374
10.90; N, 6.29.
(MHϩ), 356, 282, 200, 183, 157, 119 (base peak), 91; HR-MS (FAB) calcd
for C21H28NO3S (MHϩ) 374.1790; found: 374.1798.
(4S,5S,2E)-2,5-Dimethyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]-
hept-2-en-1-ol (11e) The enoate 10e (3.0 g, 8.16 mmol) was converted
According to the general procedure for the preparation of the enoate 10,
(S)-N-(tert-butoxycarbonyl)-tert-leucinol (4.78 g, 22 mmol) was converted
into methyl (4R,2E)-4-[N-(tert-butoxycarbonyl)amino]-2,5,5-trimethylhex-
2-enoate (6.00 g, 96% yield): colorless oil; [a]D14 Ϫ1.0° (cϭ0.834, CHCl3); into 11e (2.27 g, 82% yield): colorless crystals from n-hexane–Et2O (2 : 1);
1H-NMR (270 MHz, CDCl3) d: 0.92 (s, 9H), 1.43 (s, 9H), 1.94 (s, 3H), 3.75 mp 75 °C; [a]D28 ϩ28.3° (cϭ1.38, CHCl3); 1H-NMR (270 MHz, CDCl3) d:
(s, 3H), 4.26 (dd, Jϭ10.0, 8.1 Hz, 1H), 4.55 (d, Jϭ8.1 Hz, 1H), 6.56 (dd, 0.82 (d, Jϭ7.0 Hz, 3H), 0.86 (t, Jϭ7.0 Hz, 3H), 0.98—1.20 (m, 1H), 0.99
Jϭ10.0, 1.1 Hz, 1H); MS (FAB) m/z 286 (MHϩ), 230, 228, 186, 172, 154
(dd, Jϭ6.5, 6.5 Hz, 1H), 1.36—1.55 (m, 2H), 1.42 (d, Jϭ1.4 Hz, 3H), 2.30
(base peak), 128, 57; HR-MS (FAB) calcd for C15H28NO4 (MHϩ) 286.2018; (s, 3H), 2.62 (s, 6H), 3.66 (dd, Jϭ13.8, 6.5 Hz, 1H), 3.73 (dd, Jϭ13.8,
found: 286.2026. 6.5 Hz, 1H), 3.95 (ddd, Jϭ9.7, 7.0, 5.7 Hz, 1H), 4.62 (d, Jϭ7.0 Hz, 1H),
Trifluoroacetic acid (15 ml) was added to this enoate (2.85 g, 10 mmol) at 4.97 (dq, Jϭ9.7, 1.4 Hz, 1H), 6.93 (s, 2H). Anal. Calcd for C18H29NO3S: C,
0 °C, and the mixture was stirred for 30 min with warming to room tempera- 63.68; H, 8.61; N, 4.13. Found: C, 63.62; H, 8.76; N, 4.04.
ture. The mixture was concentrated under reduced pressure to an oily
(4R,2E)-2,5,5-Trimethyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]-
residue, which was made alkaline with 28% NH4OH and extracted with hex-2-en-1-ol (11f) The enoate 10f (4.36 g, 11.9 mmol) was converted into
CHCl3. The extract was washed with brine and dried over MgSO4. The fil- 11f (3.55 g, 88% yield): colorless crystals from n-hexane–CHCl3 (4 : 1); mp
trate was concentrated under reduced pressure to leave an oil. The oil was 138 °C; [a]D29 ϩ39.6° (cϭ1.12, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.86
dissovled in CHCl3 (15 ml) and Et3N (6.92 ml, 50 mmol), and MsCl (s, 9H), 1.08—1.26 (br s, 1H), 1.40 (d, Jϭ1.4 Hz, 3H), 2.29 (s, 3H), 2.62 (s,
(1.95 ml, 20 mmol) was added dropwise to the stirred mixture at Ϫ78 °C. 6H), 3.64 (dd, Jϭ13.2, 6.8 Hz, 1H), 3.68—3.72 (m, 1H), 3.72 (dd, Jϭ13.2,
The mixture was stirred for 30 min with warming to 0 °C followed by 6.5 Hz, 1H), 4.76—4.87 (m, 1H), 5.02 (dq, Jϭ10.0, 1.4 Hz, 1H), 6.92 (s,
quenching with saturated NaHCO3 (2 ml). The whole was extracted with 2H). Anal. Calcd for C18H29NO3S: C, 63.68; H, 8.61; N, 4.13. Found: C,
EtOAc and the extract was washed successively with saturated citric acid, 63.38; H, 8.56; N, 4.10.
water, saturated NaHCO3, and water, and dried over MgSO4. Usual workup
(4R,2E)-2,5,5-Trimethyl-4-[N-(methylsulfonyl)amino]hex-2-en-1-ol
followed by flash chromatography over silica gel with n-hexane–EtOAc (11g) The enoate 10g (2.45 g, 9.30 mmol) was converted into 11g (1.57 g,
(2 : 1) gave 10g (2.54 g, 96% yield): colorless oil; [a]D19 ϩ44.7° (cϭ1.03, 72% yield): colorless crystals from Et2O; mp 66 °C; [a]D16 ϩ60.2° (cϭ1.35,
CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.97 (s, 9H), 1.96 (d, Jϭ1.6 Hz, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.94 (s, 9H), 1.74 (d, Jϭ1.4 Hz,
1H), 2.86 (s, 3H), 3.78 (s, 3H), 3.99 (dd, Jϭ10.5, 9.2 Hz, 1H), 4.68 (d,
3H), 2.14 (br s, 1H), 2.88 (s, 3H), 3.89 (dd, Jϭ10.5, 10.3 Hz, 1H), 4.00—
4.10 (m, 2H), 4.67 (d, Jϭ10.3 Hz, 1H), 5.41 (dq, Jϭ10.5, 1.4 Hz, 1H). Anal.
Jϭ9.2 Hz, 1H), 6.61 (dq, Jϭ10.5, 1.6 Hz, 1H); MS (FAB) m/z 264 (MHϩ,
base peak), 232, 206, 184, 169, 154, 137, 128, 109, 98, 96, 57; HR-MS Calcd for C10H21NO3S: C, 51.04; H, 8.99; N, 5.95. Found: C, 50.75; H, 8.92;
(FAB) calcd for C11H22NO4S (MHϩ) 264.1269; found: 264.1273.
General Procedure for the Synthesis of Allylic Alcohols (11). Synthesis
of (4S,2E)-2,5-Dimethyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]hex-
N, 6.00.
General Procedure for the Synthesis of Methyl Carbonates (12). Syn-
thesis of (4S,2E)-O-Methoxycarbonyl-2,5-dimethyl-4-[N-(2,4,6-
trimethylphenylsulfonyl)amino]hex-2-en-1-ol (12a) from 11a To
2-en-1-ol (11a) from 10a DIBAL-H (1.0
M
solution in toluene; 49.5 ml,
a
49.5 mmol) was added dropwise to a stirred solution of the enoate 10a (5.0 g,
14.1 mmol) in a mixed solvent of toluene (15 ml) and CHCl3 (15 ml) at
Ϫ78 °C under argon. After 1 h, saturated NH4Cl (4 ml) was added with vigor-
stirred mixture of the alcohol 11a (2.2 g, 6.76 mmol) and pyridine (5.45 ml)
in a mixed solvent of CHCl3 (10 ml) and THF (10 ml) at Ϫ78 °C was added
dropwise methyl chloroformate (0.89 ml, 11.5 mmol), and the mixture was
ous stirring. The mixture was made acidic with saturated citric acid and ex- stirred with warming to 0 °C. After 1 h, saturated NaHCO3 (2 ml) was added
tracted with EtOAc. The extract was washed with water and dried over to the mixture with vigorous stirring. The whole was extracted with a mixed
MgSO4. The usual workup followed by recrystallization from n-
hexane–CHCl3 gave 11a (4.35 g, 95% yield) as colorless needles: mp 129—
131 °C; [a]D21 ϩ28.5° (cϭ0.555, CHCl3); 1H-NMR (270 MHz, CDCl3) d:
0.84 (d, Jϭ6.8 Hz, 3H), 0.86—0.89 (m, 1H), 0.90 (d, Jϭ6.8 Hz, 3H), 1.43 (d,
Jϭ1.4 Hz, 3H), 1.66—1.79 (m, 1H), 2.30 (s, 3H), 2.62 (s, 6H), 3.66 (dd,
Jϭ13.8, 5.7 Hz, 1H), 3.71 (dd, Jϭ13.8, 5.7 Hz, 1H), 3.84 (ddd, Jϭ9.7, 7.3,
5.9 Hz, 1H), 4.57 (d, Jϭ7.3 Hz, 1H), 4.94 (dq, Jϭ9.7, 1.4 Hz, 1H), 6.93 (s,
2H). Anal. Calcd for C17H27NO3S: C, 62.74; H, 8.36; N, 4.30. Found: C,
62.66; H, 8.37; N, 4.28.
solvent of Et2O–EtOAc (1 : 1), and the extract was washed successively with
saturated citric acid, water, saturated NaHCO3, and water, and dried over
MgSO4. Usual workup followed by flash chromatography over silica gel
with n-hexane–EtOAc (3 : 1) gave 12a (2.43 g, 94% yield) as colorless
prisms from n-hexane–EtOAc (5 : 1): mp 96—98 °C; [a]D24 ϩ13.9° (cϭ1.23,
CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.84 (d, Jϭ7.0 Hz, 3H), 0.90 (d,
Jϭ7.0 Hz, 3H), 1.38 (s, 3H), 1.67—1.79 (m, 1H), 2.29 (s, 3H), 2.60 (s, 6H),
3.72—3.81 (m, 1H), 3.78 (s, 3H), 4.188 (dd, Jϭ13.5 Hz, 1H), 4.192 (dd,
Jϭ13.5 Hz, 1H), 4.47 (d, Jϭ7.6 Hz, 1H), 5.03 (m, 1H), 6.91 (s, 2H). Anal.
Calcd for C19H29NO5S: C, 59.51; H, 7.62; N, 3.65. Found: C, 59.57; H, 7.70;
(4S,2E)-2-Ethyl-5-methyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]-
hex-2-en-1-ol (11b) The enoate 10b (3.0 g, 8.16 mmol) was converted into N, 3.74.
11b (2.70 g, 97% yield): colorless needles from n-hexane–Et2O (1 : 2); mp
(4S,2E)-2-Ethyl-O-methoxycarbonyl-5-methyl-4-[N-(2,4,6-tri-
methylphenylsulfonyl)amino]hex-2-en-1-ol (12b) The alcohol 11b (735
96 °C; [a]D22 ϩ50.1° (cϭ0.891, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.85
(d, Jϭ7.3 Hz, 3H), 0.87 (t, Jϭ7.6 Hz, 3H), 0.89 (d, Jϭ6.5 Hz, 3H), 1.67— mg, 2.0 mmol) was converted into 12b (794 mg, 99% yield): colorless
1.84 (m, 2H), 1.98—2.12 (m, 1H), 2.29 (s, 3H), 2.62 (s, 6H), 3.71—3.83 (m,
2H), 3.89 (ddd, Jϭ10.0, 7.0, 5.4 Hz, 1H), 4.64 (d, Jϭ7.0 Hz, 1H), 4.97 (d,
Jϭ10.0 Hz, 1H), 6.93 (s, 2H). Anal. Calcd for C18H29NO3S: C, 63.68; H, Jϭ7.0 Hz, 3H), 0.88 (d, Jϭ7.0 Hz, 3H), 1.65—1.79 (m, 2H), 1.88—2.05 (m,
prisms from n-hexane–Et2O (2 : 1); mp 50 °C; [a]D20 ϩ20.5° (cϭ0.945,
CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.84 (t, Jϭ7.6 Hz, 3H), 0.85 (d,
8.61; N, 4.13. Found: C, 63.52; H, 8.42; N, 4.09.
1H), 2.28 (s, 3H), 2.60 (s, 6H), 3.78 (s, 3H), 3.82 (ddd, Jϭ9.7, 7.6, 5.9 Hz,
1H), 4.27 (dd, Jϭ12.4, 1.1 Hz, 1H), 4.32 (dd, Jϭ12.4, 1.4 Hz, 1H), 4.49 (d,
Jϭ7.6 Hz, 1H), 5.07 (d, Jϭ9.7 Hz, 1H), 6.90 (s, 2H). Anal. Calcd for
C20H31NO5S: C, 60.43; H, 7.86; N, 3.52. Found: C, 60.31; H, 7.79; N, 3.45.
(4S,2E)-O-Methoxycarbonyl-2,6-dimethyl-4-[N-(4-methylphenylsul-
fonyl)amino]hept-2-en-1-ol (12c) The alcohol 11c (623 mg, 2.0 mmol)
(4S,2E)-2,6-Dimethyl-4-[N-(4-methylphenylsulfonyl)amino]hept-2-en-
1-ol (11c) The enoate 10c (3.0 g, 8.84 mmol) was converted into 11c
(2.20 g, 80% yield): colorless needles from n-hexane–Et2O (1 : 4); mp 91 °C;
[a]D24 ϩ28.8° (cϭ1.01, CHCl3); 1H-NMR (300 MHz, CDCl3) d: 0.830 (d,
Jϭ6.6 Hz, 3H), 0.833 (d, Jϭ6.6 Hz, 3H), 1.21 (ddd, Jϭ13.5, 7.2, 7.2 Hz,
1H), 1.22 (dd, Jϭ6.4, 6.4 Hz, 1H), 1.40 (ddd, Jϭ13.5 7.2, 7.2 Hz, 1H), 1.51 was converted into 12c (713 mg, 97% yield): colorless needles from n-
(d, Jϭ1.3 Hz, 3H), 1.52—1.63 (m, 1H), 2.42 (s, 3H), 3.67—3.80 (m, 2H), hexane–Et2O (3 : 1); mp 76 °C; [a]D28 +44.3° (cϭ0.716, CHCl3); 1H-NMR
4.08 (dddd, Jϭ9.5, 7.2, 7.2, 7.2 Hz, 1H), 4.62 (d, Jϭ7.2 Hz, 1H), 4.97 (dq, (270 MHz, CDCl3) d: 0.84 (d, Jϭ6.5 Hz, 3H), 0.84 (d, Jϭ6.5 Hz, 3H), 1.21
Jϭ9.5, 1.3 Hz, 1H), 7.25—7.29 (m, 2H), 7.69—7.74 (m, 2H). Anal. Calcd (ddd, Jϭ13.8, 6.8, 6.8 Hz, 1H), 1.40 (ddd, Jϭ13.8, 7.3, 7.3 Hz, 1H), 1.50—
for C16H25NO3S: C, 61.71; H, 8.09; N, 4.50. Found: C, 61.65; H, 8.26; N, 1.64 (m, 1H), 1.52 (s, 3H), 2.41 (s, 3H), 3.78 (s, 3H), 4.09 (dddd, Jϭ9.5,

January 2004
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7.5, 7.3, 6.8 Hz, 1H), 4.20—4.25 (m, 2H), 4.45 (d, Jϭ7.5 Hz, 1H), 5.00 (d, Jϭ6.5 Hz, 3H), 1.21 (ddd, Jϭ13.8, 6.8, 6.8 Hz, 1H), 1.38 (ddd, Jϭ13.8, 7.6,
Jϭ9.5 Hz, 1H), 7.23—7.26 (m, 2H), 7.67—7.70 (m, 2H). Anal. Calcd for 7.6 Hz, 1H), 1.49—1.59 (m, 1H), 1.62 (d, Jϭ1.4 Hz, 3H), 2.43 (s, 3H), 2.97
C18H27NO5S: C, 58.51; H, 7.37; N, 3.79. Found: C, 58.52; H, 7.42; N, 3.73.
(s, 3H), 4.08 (dddd, Jϭ9.7, 7.6, 7.3, 6.8 Hz, 1H), 4.30—4.38 (m, 2H),
(4S,2E)-O-Methoxycarbonyl-2-methyl-4-[N-(2,4,6-trimethylphenylsul- 4.45—4.58 (m, 1H), 5.17 (dq, Jϭ9.7, 1.4 Hz, 1H), 7.26—7.30 (m, 2H),
fonyl)amino]-5-phenylpent-2-en-1-ol (12d) The alcohol 11d (500 mg, 7.68—7.71 (m, 2H); MS (FAB) m/z 390 (MHϩ), 388, 332, 294 (base peak),
1.34 mmol) was converted into 12d (501 mg, 87% yield): colorless crystals 240, 184, 155, 123, 91, 82; HR-MS (FAB) calcd for C17H28NO5S2 (MHϩ)
1
from n-hexane–Et2O (1 : 1); mp 98 °C; [a]D28 ϩ10.2° (cϭ1.10, CHCl3); H- 390.1409; found: 390.1397.
NMR (270 MHz, CDCl3) d: 1.25 (d, Jϭ1.4 Hz, 3H), 2.28 (s, 3H), 2.50 (s,
(4S,2E)-2-Methyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]-O-
6H), 2.72 (dd, Jϭ13.2, 7.3 Hz, 1H), 2.81 (dd, Jϭ13.2, 6.2 Hz, 1H), 3.78 (s, methylsulfonyl-5-phenylpent-2-en-1-ol (13d) The alcohol 11d (500 mg,
3H), 4.14 (dddd, Jϭ9.2, 7.3, 6.2, 5.7 Hz, 1H), 4.22 (m, 2H), 4.52 (d, 1.34 mmol) was converted into 13d (502 mg, 83% yield): colorless needles
Jϭ5.7 Hz, 1H), 5.12 (dq, Jϭ9.2, 1.4 Hz, 1H), 6.88 (s, 2H), 7.03—7.10 (m, from Et2O; mp 86 °C; [a]D29 Ϫ6.7° (cϭ1.05, CHCl3); 1H-NMR (270 MHz,
2H), 7.17—7.28 (m, 3H). Anal. Calcd for C23H29NO5S: C, 64.01; H, 6.77;
N, 3.25. Found: C, 63.73; H, 6.80; N, 3.23.
(4S,5S,2E)-O-Methoxycarbonyl-2,5-dimethyl-4-[N-(2,4,6-trimethyl-
CDCl3) d: 1.37 (m, 3H), 2.29 (s, 3H), 2.48 (s, 6H), 2.72 (dd, Jϭ13.5, 7.3 Hz,
1H), 2.80 (dd, Jϭ13.5, 6.8 Hz, 1H), 2.91 (s, 3H), 4.08—4.20 (m, 1H), 4.34
(m, 2H), 4.56—4.63 (m, 1H), 5.29 (dq, Jϭ9.2, 1.4 Hz, 1H), 6.90 (s, 2H),
phenylsulfonyl)amino]hept-2-en-1-ol (12e) The alcohol 11e (679 mg, 7.02—7.10 (m, 2H), 7.18—7.28 (m, 3H). Anal. Calcd for C22H29NO5S2: C,
2.0 mmol) was converted into 12e (790 mg, 99% yield): colorless oil; 58.51; H, 6.47; N, 3.10. Found: C, 58.24; H, 6.44; N, 3.05.
[a]D29 ϩ15.9° (cϭ0.796, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.81 (d,
(4S,5S,2E)-2,5-Dimethyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]-
Jϭ7.0 Hz, 3H), 0.86 (t, Jϭ7.0 Hz, 3H), 0.97—1.15 (m, 1H), 1.35—1.56 (m, O-methylsulfonylhept-2-en-1-ol (13e) The alcohol 11e (680 mg, 2.0
2H), 1.37 (d, Jϭ1.4 Hz, 3H), 2.29 (s, 3H), 2.60 (s, 6H), 3.78 (s, 3H), 3.87 mmol) was converted into 13e (834 mg, 99% yield): colorless crystals from
(ddd, Jϭ9.7, 7.3, 5.7 Hz, 1H), 4.14—4.24 (m, 2H), 4.49 (d, Jϭ7.3 Hz, 1H), n-hexane–Et2O (1 : 1); mp 80 °C; [a]D27 Ϫ0.9° (cϭ0.920, CHCl3); H-NMR
5.05 (dq, Jϭ9.7, 1.4 Hz, 1H), 6.91 (s, 2H); MS (FAB) m/z 396 (MϪH), 338, (270 MHz, CDCl3) d: 0.82 (d, Jϭ6.5 Hz, 3H), 0.85 (t, Jϭ7.0 Hz, 3H),
278, 264, 183, 153, 151, 75 (base peak), 64; HR-MS (FAB) calcd for 0.99—1.15 (m, 1H), 1.34—1.58 (m, 2H), 1.48 (d, Jϭ1.4 Hz, 3H), 2.30 (s,
1
C20H30NO5S (MϪH) 396.1844; found: 396.1852.
(4R,2E)-O-Methoxycarbonyl-2,5,5-trimethyl-4-[N-(2,4,6-trimethyl-
3H), 2.61 (s, 6H), 2.97 (s, 3H), 3.88 (ddd, Jϭ9.7, 7.6, 5.4 Hz, 1H), 4.30 (m,
2H), 4.60 (d, Jϭ7.6 Hz, 1H), 5.19 (dq, Jϭ9.7, 1.4 Hz, 1H), 6.93 (s, 2H).
phenylsulfonyl)amino]hex-2-en-1-ol (12f) The alcohol 11f (976 mg, Anal. Calcd for C19H31NO5S2: C, 54.65; H, 7.48; N, 3.35. Found: C, 54.50;
2.87 mmol) was converted into 12f (1.02 g, 89% yield): colorless needles H, 7.43; N, 3.36.
from n-hexane–Et2O (3 : 1); mp 122—124 °C; [a]D27 ϩ22.3° (cϭ1.12,
(4R,2E)-2,5,5-trimethyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]-
CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.88 (s, 9H), 1.31 (d, Jϭ1.4 Hz, O-methylsulfonylhex-2-en-1-ol (13f) The alcohol 11f (651 mg, 1.92
3H), 2.28 (s, 3H), 2.59 (s, 6H), 3.63 (dd, Jϭ10.0, 8.9 Hz, 1H), 3.78 (s, 3H), mmol) was converted into 13f (580 mg, 72% yield): colorless needles from
4.13 (d, Jϭ13.0 Hz, 1H), 4.14 (d, Jϭ13.0 Hz, 1H), 4.49 (d, Jϭ8.9 Hz, 1H), n-hexane–EtOAc (3 : 1); mp 147—149 °C; [a]D26 Ϫ1.1° (cϭ1.46, CHCl3);
5.04 (dq, Jϭ10.0, 1.4 Hz, 1H), 6.89 (s, 2H). Anal. Calcd for C20H31NO5S: C, 1H-NMR (270 MHz, CDCl3) d: 0.87 (s, 9H), 1.45 (d, Jϭ1.4 Hz, 3H), 2.30
60.43; H, 7.86; N, 3.52. Found: C, 60.15; H, 7.75; N, 3.53.
(s, 3H), 2.60 (s, 6H), 2.97 (s, 3H), 3.66 (dd, Jϭ10.3, 8.6 Hz, 1H), 4.25 (d,
(4R,2E)-O-Methoxycarbonyl-2,5,5-trimethyl-4-[N-(methylsulfonyl)- Jϭ12.1 Hz, 1H), 4.26 (d, Jϭ12.1 Hz, 1H), 4.55 (d, Jϭ8.6 Hz, 1H), 5.18 (dq,
amino]hex-2-en-1-ol (12g) The alcohol 11g (706 mg, 3.0 mmol) was con- Jϭ10.3, 1.4 Hz, 1H), 6.92 (s, 2H). Anal. Calcd for C19H31NO5S2: C, 54.65;
verted into 12g (823 mg, 94% yield): colorless oil; [a]D19 ϩ46.5° (cϭ0.891, H, 7.48; N, 3.35. Found: C, 54.67; H, 7.70; N, 3.32.
CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.94 (s, 9H), 1.79 (d, Jϭ1.4 Hz,
3H), 2.86 (s, 3H), 3.79 (s, 3H), 3.91 (dd, Jϭ10.5, 9.5 Hz, 1H), 4.47 (d,
(4R,2E)-2,5,5-Trimethyl-O-methylsulfonyl-4-[N-(methylsulfonyl)-
amino]hex-2-en-1-ol (13g) The alcohol 11g (471 mg, 2.0 mmol) was con-
Jϭ9.5 Hz, 1H), 4.56 (d, Jϭ12.4 Hz, 1H), 4.57 (d, Jϭ12.4 Hz, 1H), 5.42 (dq, verted into 13g (430 mg, 69% yield): colorless needles from CHCl3–Et2O
Jϭ10.5, 1.4 Hz, 1H); MS (FAB) m/z 294 (MHϩ), 292, 236, 218 (base peak), (2 : 3); mp 116 °C; [a]D17 ϩ36.9° (cϭ0.943, CHCl3); 1H-NMR (270 MHz,
199, 162, 148, 123, 82, 57; HR-MS (FAB) calcd for C12H24NO5S (MHϩ) CDCl3) d: 0.95 (s, 9H), 1.84 (d, Jϭ1.4 Hz, 3H), 2.89 (s, 3H), 3.04 (s, 3H),
294.1375; found: 294.1365. 3.91 (ddd, Jϭ10.3, 9.5, 0.8 Hz, 1H), 4.54 (br s, 1H), 4.63 (d, Jϭ11.9 Hz,
General Procedure for the Synthesis of Methanesulfonates (13). Syn- 1H), 4.67 (d, Jϭ11.9 Hz, 1H), 5.54 (dq, Jϭ10.3, 1.4 Hz, 1H). Anal. Calcd
thesis of (4S,2E)-2,5-Dimethyl-4-[N-(2,4,6-trimethylphenylsulfo- for C11H23NO5S2: C, 42.15; H, 7.40; N, 4.47. Found: C, 42.37; H, 7.38; N,
nyl)amino]-O-methylsulfonylhex-2-en-1-ol (13a) from 11a To a stirred 4.58.
mixture of the alcohol 11a (500 mg, 1.54 mmol) and Et3N (2.13 ml,
General Procedure for the Aziridination Reaction of the Allylic
1.54 mmol) in THF (10 ml) was added dropwise MsCl (0.60 ml, 7.7 mmol) Cabonates (12) with Palladium(0). Synthesis of (2R,3S)-3-Isopropyl-N-
at 0 °C. The stirring was continued for 0.5 h at 0 °C followed by quenching (2,4,6-trimethylphenylsulfonyl)-2-(1-methylvinyl)aziridine (14a) and Its
with saturated NaHCO3 (1 ml) with vigorous stirring. The whole was ex- (2S,3S)-Isomer (15a) from 12a (Table 1, Entry 1) A stirred mixture of
tracted with Et2O and the extract was washed successively with saturated cit- the carbonate 12a (300 mg, 0.782 mmol) and Pd(PPh3)4 (54 mg, 0.047 mmol,
ric acid, water, saturated NaHCO3, and water, and dried over MgSO4. Usual 6 mol%) in dry THF (5 ml) was heated at 65 °C for 4 h. The mixture was
workup followed by flash chromatography over silica gel with n- concentrated under reduced pressure to leave an oil, which was flash chro-
hexane–EtOAc (3 : 2) gave 13a (605 mg, 98% yield) as a colorless oil: matographed over silica gel with n-hexane–EtOAc (10 : 1) to give a 98 : 2
[a]D30 Ϫ4.5° (cϭ0.927, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.84 (d,
mixture of 14a and 15a (204 mg, 85% combined yield). The mixture was
Jϭ6.8 Hz, 3H), 0.89 (d, Jϭ6.8 Hz, 3H), 1.50 (d, Jϭ1.4 Hz, 3H), 1.66—1.79 flash chromatographed over silica gel. Elution with n-hexane–EtOAc (20 : 1)
(m, 1H), 2.30 (s, 3H), 2.60 (s, 6H), 2.97 (s, 3H), 3.78 (ddd, Jϭ10.0, 7.3, gave 14a (200 mg) and further elution yielded 15a (4 mg).
6.2 Hz, 1H), 4.30 (m, 2H), 4.57 (d, Jϭ7.3 Hz, 1H), 5.18 (dq, Jϭ10.0, 1.4 Hz,
Compound 14a: Colorless needles from n-hexane; mp 83—85 °C;
1H), 6.93 (s, 2H); MS (FAB) m/z 404 (MHϩ), 402, 360, 308, 252, 220, 183, [a]D28 Ϫ88.2° (cϭ0.550, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.75 (d,
167, 124, 119 (base peak), 82; HR-MS (FAB) calcd for C18H30NO5S2 (MHϩ) Jϭ6.8 Hz, 3H), 0.88 (d, Jϭ6.8 Hz, 3H), 1.32—1.46 (m, 1H), 1.76 (s, 3H),
404.1565; found: 404.1554.
(4S,2E)-2-Ethyl-5-methyl-4-[N-(2,4,6-trimethylphenylsulfonyl)amino]-
2.30 (s, 3H), 2.57 (dd, Jϭ9.7, 7.3 Hz, 1H), 2.72 (s, 6H), 3.32 (d, Jϭ7.3 Hz,
1H), 4.93 (m, 2H), 6.95 (s, 2H). Anal. Calcd for C17H25NO2S: C, 66.41; H,
O-methylsulfonylhex-2-en-1-ol (13b) The alcohol 11b (735 mg, 2.0 8.20; N, 4.56. Found: C, 66.30; H, 8.11; N, 4.60.
1
mmol) was converted into 13b (746 mg, 89% yield): colorless prisms from
Compound 15a: Colorless oil; [a]D29 Ϫ18.9° (cϭ0.264, CHCl3); H-NMR
n-hexane–Et2O (1 : 2); mp 59—61 °C; [a]D23 Ϫ3.9° (cϭ0.712, CHCl3); 1H- (270 MHz, CDCl3) d: 1.03 (d, Jϭ6.8 Hz, 3H), 1.15 (d, Jϭ6.8 Hz, 3H), 1.57
NMR (270 MHz, CDCl3) d: 0.84 (d, Jϭ7.0 Hz, 3H), 0.88 (d, Jϭ7.0 Hz, 3H), (s, 3H), 2.11—2.24 (m, 1H), 2.29 (s, 3H), 2.55 (dd, Jϭ9.2, 4.5 Hz, 1H), 2.70
0.91 (dd, Jϭ7.6, 7.6 Hz, 3H), 1.66—1.78 (m, 1H), 1.87 (dq, Jϭ14.3, 7.6 Hz, (s, 6H), 3.20 (d, Jϭ4.5 Hz, 1H), 4.84—4.89 (m, 2H), 6.92 (s, 2H); MS
1H), 2.06 (dq, Jϭ14.3, 7.6 Hz, 1H), 2.29 (s, 3H), 2.61 (s, 6H), 2.98 (s, 3H),
(FAB) m/z 308 (MHϩ), 252, 183, 167, 124, 119 (base peak), 91, 77, 55, 41,
3.84 (ddd, Jϭ10.0, 7.0, 5.7 Hz, 1H), 4.40 (dd, Jϭ11.6, 1.1 Hz, 1H), 4.42 (dd, 39; HR-MS (FAB) calcd for C17H26NO2S (MHϩ) 308.1684; found:
Jϭ11.6, 1.1 Hz, 1H), 4.56 (d, Jϭ7.0 Hz, 1H), 5.22 (d, Jϭ10.0 Hz, 1H), 6.93
(s, 2H). Anal. Calcd for C19H31NO5S2: C, 54.65; H, 7.48; N, 3.35. Found: C,
54.45; H, 7.31; N, 3.34.
308.1686.
(2R,3S)-3-(1-Ethylvinyl)-2-isopropyl-N-(2,4,6-trimethylphenylsul-
fonyl)aziridine (14b) and Its (2S,3S)-Isomer (15b) (Table 1, Entry 2)
(4S,2E)-2,6-Dimethyl-4-[N-(4-methylphenylsulfonyl)amino]-O-methyl- The carbonate 12b (398 mg, 1.0 mmol) was converted into a 99 : 1 mixture
sulfonylhept-2-en-1-ol (13c) The alcohol 11c (623 mg, 2.0 mmol) was of 14b and 15b (280 mg, 87% combined yield) by treatment with Pd(PPh3)4
converted into 13c (669 mg, 86% yield): colorless oil; [a]D25 ϩ6.7° (cϭ1.26, (10 mol%) in dioxane under reflux for 15 min. The mixture was flash chro-
CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.81 (d, Jϭ6.8 Hz, 3H), 0.83 (d, matographed over silica gel. Elution with n-hexane–EtOAc (20 : 1) gave 14b

118
Vol. 52, No. 1
4.88 (m, 1H), 6.92 (s, 2H); MS (FAB) m/z 322 (MHϩ), 320, 266, 252, 183,
167, 138 (base peak), 119, 82, 57; HR-MS (FAB) calcd for C18H28NO2S
(MHϩ) 322.1841; found: 322.1835.
(277 mg) and further elution yielded 15b (3 mg).
Compound 14b: Colorless crystals from n-hexane; mp 47 °C; [a]D16
Ϫ88.4° (cϭ0.770, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.73 (d, Jϭ
6.5 Hz, 3H), 0.86 (d, Jϭ7.0 Hz, 3H), 1.05 (t, Jϭ7.3 Hz, 3H), 1.30—1.44 (m,
1H), 2.06 (q, Jϭ7.3 Hz, 2H), 2.30 (s, 3H), 2.56 (dd, Jϭ9.5, 7.0 Hz, 1H),
2.72 (s, 6H), 3.37 (d, Jϭ7.0 Hz, 1H), 4.91 (m, 1H), 4.95 (m, 1H), 6.95 (s,
2H). Anal. Calcd for C18H27NO2S: C, 67.25; H, 8.47; N, 4.36. Found: C,
67.20; H, 8.41; N, 4.30.
(2R,3S)-3-(tert-Butyl)-N-(2,4,6-trimethylphenylsulfonyl)-2-(1-methyl-
vinyl)aziridine (14f) and Its (2S,3S)-Isomer (15f) (Table 1, Entry 6)
The carbonate 12f (300 mg, 0.755 mmol) was converted into a 87 : 13 mix-
ture of 14f and 15f (166 mg, 68% combined yield) by treatment with
Pd(PPh3)4 (20 mol%) in dioxane under reflux for 2 h. The mixture was flash
chromatographed over silica gel. Elution with n-hexane–EtOAc (20 : 1) gave
14f (144 mg) and further elution yielded 15f (22 mg).
Compound 15b: Colorless prisms from n-hexane; mp 60 °C; [a]D23 Ϫ19.6°
1
(cϭ0.939, CHCl3); H-NMR (270 MHz, CDCl3) d: 1.04 (t, Jϭ7.6 Hz, 3H),
Compound 14f: Colorless needles from n-hexane; mp 83 °C; [a]D30 Ϫ29.7°
(cϭ1.01, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.83 (s, 9H), 1.76 (m,
3H), 2.31 (s, 3H), 2.59 (d, Jϭ7.6 Hz, 1H), 2.75 (s, 6H), 3.24 (m, 1H), 4.85—
4.88 (m, 1H), 4.96—4.98 (m, 1H), 6.96 (s, 2H). Anal. Calcd for
C18H27NO2S: C, 67.25; H, 8.47; N, 4.36. Found: C, 66.96; H, 8.44; N, 4.40.
1.14 (d, Jϭ6.8 Hz, 3H), 1.25 (d, Jϭ6.5 Hz, 3H), 2.01 (q, Jϭ7.6 Hz, 2H),
2.21—2.35 (m, 1H), 2.39 (s, 3H), 2.62 (dd, Jϭ9.7, 4.3 Hz, 1H), 2.80 (s, 6H),
3.31 (d, Jϭ4.3 Hz, 1H), 4.88—4.90 (m, 1H), 4.94—4.96 (m, 1H), 7.02 (s,
2H); MS (FAB) m/z 322 (MHϩ), 320, 266, 183, 138 (base peak), 119, 96;
HR-MS (FAB) calcd for C18H28NO2S (MHϩ) 322.1841; found: 322.1837.
(2R,3S)-3-Isobutyl-N-(4-methylphenylsulfonyl)-2-(1-methylvinyl)aziri-
dine (14c) and Its (2S,3S)-Isomer (15c) (Table 1, Entry 3) The carbon-
ate 12c (100 mg, 0.271 mmol) was converted into a 98 : 2 mixture of 14c and
15c (55 mg, 69% combined yield) by treatment with Pd(PPh3)4 (20 mol%) in
dioxane under reflux for 15 min. The mixture was flash chromatographed
over silica gel. Elution with n-hexane–EtOAc (20 : 1) gave 14c (54 mg) and
further elution yielded 15c (1 mg).
1
Compound 15f: Colorless oil; [a]D26 Ϫ58.1° (cϭ0.248, CHCl3); H-NMR
(270 MHz, CDCl3) d: 0.72 (s, 9H), 2.04 (m, 3H), 2.29 (s, 3H), 2.71 (s, 6H),
3.07 (d, Jϭ5.1 Hz, 1H), 3.14 (d, Jϭ5.1 Hz, 1H), 5.18—5.21 (m, 2H), 6.92
(s, 2H); MS (FAB) m/z 322 (MHϩ), 266, 252, 183, 167, 138 (base peak),
119, 82, 57; HR-MS (FAB) calcd for C18H28NO2S (MHϩ) 322.1841; found:
322.1837.
(2R,3S)-3-(tert-Butyl)-2-(1-methylvinyl)-N-(methylsulfonyl)aziridine
(14g) and Its (2S,3S)-Isomer (15g) (Table 1, Entry 7) The carbonate 12g
(147 mg, 0.5 mmol) was converted into a 91 : 9 mixture of 14g and 15g
(70 mg, 64% combined yield) by treatment with Pd(PPh3)4 (20 mol%) in
dioxane under reflux for 2.5 h. The mixture was flash chromatographed over
silica gel. Elution with n-hexane–EtOAc (7 : 1) gave 14g (64 mg) and further
elution yielded 15g (6 mg).
Compound 14c: Colorless oil; [a]D23 Ϫ48.6° (cϭ1.12, CHCl3); 1H-NMR
(270 MHz, CDCl3) d: 0.88 (d, Jϭ7.0 Hz, 3H), 0.89 (d, Jϭ6.5 Hz, 3H),
1.17—1.33 (m, 2H), 1.52—1.68 (m, 1H), 1.69 (m, 3H), 2.44 (s, 3H), 2.97
(ddd, Jϭ7.6, 7.3, 7.3 Hz, 1H), 3.22 (d, Jϭ7.6 Hz, 1H), 4.87 (m, 1H), 4.91
(m, 1H), 7.30—7.33 (m, 2H), 7.82—7.86 (m, 2H); MS (FAB) m/z 294
(MHϩ), 278, 238, 221, 155, 138 (base peak), 123, 91, 73; HR-MS (FAB)
calcd for C16H24NO2S (MHϩ) 294.1528; found: 294.1532.
Compound 14g: Colorless oil; [a]D16 Ϫ120° (cϭ0.284, CHCl3); H-NMR
1
Compound 15c: Colorless oil; [a]D31 Ϫ15.0° (cϭ0.846, CHCl3); H-NMR
1
(270 MHz, CDCl3) d: 1.00 (s, 9H), 1.85—1.87 (m, 3H), 2.67 (d, Jϭ7.8 Hz,
1H), 3.09 (s, 3H), 3.11—3.16 (m, 1H), 4.98—5.01 (m, 1H), 5.17—5.19 (m,
1H); MS (FAB) m/z 218 (MHϩ), 162, 138, 97, 95, 83, 81, 71, 69, 67, 57
(base peak), 55, 43, 41; HR-MS (FAB) calcd for C10H20NO2S (MHϩ)
218.1215; found: 218.1222.
(270 MHz, CDCl3) d: 0.98 (d, Jϭ6.2 Hz, 3H), 1.00 (d, Jϭ6.5 Hz, 3H), 1.53
(m, 3H), 1.69—1.89 (m, 2H), 2.18—2.31 (m, 1H), 2.42 (s, 3H), 2.75 (ddd,
Jϭ9.2, 4.3, 4.3 Hz, 1H), 3.26 (d, Jϭ4.3 Hz, 1H), 4.87—4.89 (m, 1H),
4.94—4.96 (m, 1H), 7.28—7.31 (m, 2H), 7.78—7.84 (m, 2H); MS (FAB)
m/z 294 (MHϩ), 292, 278, 238, 184, 155, 138 (base peak), 123, 91, 82, 55;
HR-MS (FAB) calcd for C16H24NO2S (MHϩ) 294.1528; found: 294.1533.
(2R,3S)-3-Benzyl-N-(2,4,6-trimethylphenylsulfonyl)-2-(1-methylvinyl)-
aziridine (14d) and Its (2S,3S)-Isomer (15d) (Table 1, Entry 4) The car-
bonate 12d (30 mg, 0.0695 mmol) was converted into a 98 : 2 mixture of 14d
and 15d (12 mg, 49% combined yield) by treatment with Pd(PPh3)4
(20 mol%) in dioxane at 95 °C for 30 min. The mixture was flash chro-
matographed over silica gel. Elution with n-hexane–EtOAc (20 : 1) gave 14d
(12 mg) and further elution yielded 15d (0.2 mg).
1
Compound 15g: Colorless oil; [a]D13 ϩ13.8° (cϭ0.781, CHCl3); H-NMR
(270 MHz, CDCl3) d: 0.98 (s, 9H), 1.99 (s, 3H), 3.06 (s, 3H), 3.08 (d,
Jϭ5.1 Hz, 1H), 3.16 (d, Jϭ5.1 Hz, 1H), 5.21—5.23 (m, 2H); MS (FAB) m/z
218 (MHϩ, base peak), 162, 148, 139, 138, 137, 123, 95, 83, 69, 57, 55, 43;
HR-MS (FAB) calcd for C10H20NO2S (MHϩ) 218.1215; found: 218.1206.
General Procedure for the Base-Promoted Aziridination of Allylic
Mesylates (13). Aziridination of the Mesylate (13a) by Exposure to
Sodium Hydride in DMF (Table 3, Entry 1) To a stirred suspension of
NaH (27 mg, 1.11 mmol) in DMF (2 ml) under argon was added a solution
of the mesylate 13a (300 mg, 0.743 mmol) in DMF (2 ml) at 0 °C. After
0.5 h, saturated NH4Cl (0.5 ml) was added to the mixture. The whole was ex-
tracted with Et2O and the extract was washed with water, and dried over
MgSO4. Usual workup followed by flash chromatography over silica gel
with n-hexane–EtOAc (10 : 1) gave 15a (179 mg, 78% yield). The corre-
sponding (2R,3S)-isomer 14a could not be detected by 1H-NMR and reverse
phase HPLC.
Compound 14d: Colorless crystals from n-hexane; mp 77 °C; [a]D31
Ϫ95.2° (cϭ0.540, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 1.78 (m, 3H),
2.29 (s, 3H), 2.57 (dd, Jϭ14.6, 7.8 Hz, 1H), 2.59 (s, 6H), 2.69 (dd, Jϭ14.6,
5.4 Hz, 1H), 3.10 (ddd, Jϭ7.8, 7.3, 5.4 Hz, 1H), 3.39 (d, Jϭ7.3 Hz, 1H),
5.05 (m, 1H), 5.11 (m, 1H), 6.84 (s, 2H), 6.93—6.99 (m, 2H), 7.02—7.12
(m, 3H). Anal. Calcd for C21H25NO2S: C, 70.95; H, 7.09; N, 3.94. Found: C,
71.07; H, 7.18; N, 3.87.
Compound 15d: Colorless needles from n-hexane; mp 72—74 °C;
[a]D28 ϩ38.1° (cϭ0.467, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 1.47 (m,
3H), 2.30 (s, 3H), 2.71 (s, 6H), 2.90 (ddd, Jϭ10.0, 4.0, 4.0 Hz, 1H), 3.26
(dd, Jϭ14.0, 10.0 Hz, 1H), 3.47 (d, Jϭ4.0 Hz, 1H), 3.51 (dd, Jϭ14.0, 4.0 Hz,
1H), 4.82 (m, 1H), 4.89 (m, 1H), 6.94 (s, 2H), 7.20—7.34 (m, 5H). Anal.
Calcd for C21H25NO2S: C, 70.95; H, 7.09; N, 3.94. Found: C, 70.67; H, 7.14;
N, 3.91.
Palladium(0)-Catalyzed Equilibrated Reaction of 2,3-trans-Aziridines
(15a) The 2,3-trans-aziridine 15a (54 mg, 0.176 mmol) and Pd(PPh3)4
(8.1 mg, 0.0070 mmol, 4 mol%) in dry THF (1 ml) was stirred at 0 °C for
12 h. The mixture was concentrated under reduced pressure to leave an oil,
which was flash chromatographed over silica gel with n-hexane–EtOAc
(10 : 1) to give 14a (51 mg) and 15a (1 mg) in 96% combined yield.
(3R,4S,5S)-3,4-Epimino-2,5-dimethyl-N-(2,4,6-trimethylphenylsul-
fonyl)hept-1-ene (14e) and Its (3S,4S,5S)-Isomer (15e) (Table 1, Entry 5)
The carbonate 12e (200 mg, 0.503 mmol) was converted into a 97 : 3 mixture
of 14e and 15e (110 mg, 68% combined yield) by treatment with Pd(PPh3)4
(20 mol%) in dioxane under reflux for 30 min. The mixture was flash chro-
matographed over silica gel. Elution with n-hexane–EtOAc (20 : 1) gave 14e
(107 mg) and further elution yielded 15e (3 mg).
Acknowledgements This article is dedicated to the memory of Profes-
sor Toshiro Ibuka, the conceptual originator of this treatise, deceased on Jan-
uary 20, 2000. This work was supported by Japan Health Sciences Founda-
tion and Grant-in-Aid for Scientific Research from the Ministry of Educa-
tion, Culture, Sports, Science and Technology of Japan. The authors are
grateful to Prof. Tooru Taga and Dr. Yoshihisa Miwa (Graduate School of
Pharmaceutical Sciences, Kyoto University) for X-ray analyses. The authors
are also indebted to Prof. Yumiko Yamaoka and Dr. Eriko Osawa (Faculty of
Pharmaceutical Sciences, Kobe Gakuin University) for the computational in-
vestigations. H.O. is grateful to Research Fellowships of the Japan Society
for the Promotion of Science for Young Scientists (JSPS).
Compound 14e: Colorless crystals from cold n-hexane; mp 49 °C;
[a]D25 Ϫ73.1° (cϭ0.446, CHCl3); 1H-NMR (270 MHz, CDCl3) d: 0.75 (t,
Jϭ7.0 Hz, 3H), 0.85 (d, Jϭ6.8 Hz, 3H), 0.98—1.39 (m, 3H), 1.75 (m, 3H),
2.30 (s, 3H), 2.67 (dd, Jϭ9.5, 7.3 Hz, 1H), 2.72 (s, 6H), 3.27 (d, Jϭ7.3 Hz,
1H), 4.91 (m, 2H), 6.95 (s, 2H). Anal. Calcd for C18H27NO2S: C, 67.25; H,
8.47; N, 4.36. Found: C, 67.16; H, 8.49; N, 4.35.
References and Notes
1) Deceased January 20, 2000.
1
Compound 15e: Colorless oil; [a]D29 Ϫ36.5° (cϭ0.895, CHCl3); H-NMR
(270 MHz, CDCl3) d: 0.92 (t, Jϭ7.3 Hz, 3H), 1.00 (d, Jϭ7.0 Hz, 3H),
1.20—1.37 (m, 1H), 1.58 (m, 3H), 1.75—2.05 (m, 2H), 2.29 (s, 3H), 2.62
(dd, Jϭ9.5, 4.6 Hz, 1H), 2.70 (s, 6H), 3.19 (d, Jϭ4.6 Hz, 1H), 4.84 (m, 1H),
2) Padwa A., Woolhouse A. D., “Comprehensive Heterocyclic Chem-
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