Palladium-catalyzed highly regio- and stereoselective carbon-carbon bond formation reaction of γ-substituted vinylaziridines with a silylated masked acyl cyanide reagent

Article abstract of DOI:10.1016/j.tet.2013.04.129

Highly regio- and stereoselective carbon-carbon bond formation reaction of vinylaziridines using a masked acyl cyanide reagent possessing a tert-butyldimethylsilyl group occurred in the presence of a catalytic amount of palladium complex in excellent yield. It is considered that these excellent selectivities are the result of three simultaneous conditions, strained leaving group, small nucleophile, and ligand with small cone-angle.

Full text of DOI:10.1016/j.tet.2013.04.129

Accepted Manuscript
Palladium-catalyzed highly regio- and stereoselective carbon–carbon bond formation
reaction of γ-substituted vinylaziridines with a silylated masked acyl cyanide reagent
Tomoyuki Kawamura, Nanae Matsuo, Daisuke Yamauchi, Yoo Tanabe, Hisao
Nemoto
PII:
S0040-4020(13)00703-5
10.1016/j.tet.2013.04.129
TET 24329
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 1 March 2013
Revised Date: 24 April 2013
Accepted Date: 26 April 2013
Please cite this article as: Kawamura T, Matsuo N, Yamauchi D, Tanabe Y, Nemoto H, Palladium-
catalyzed highly regio- and stereoselective carbon–carbon bond formation reaction of γ-substituted
vinylaziridines with a silylated masked acyl cyanide reagent, Tetrahedron (2013), doi: 10.1016/
j.tet.2013.04.129.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Palladium-catalyzed highly regio- and stereoselective
carbon–carbon bond formation reaction of γ-substituted
vinylazrlidines with a silylated masked acyl cyanide reagent
Leave this area blank for abstract info.
Tomoyuki Kawamura,a Nanae Matsuo,b Daisuke Yamauchi,a Yoo Tanabe,b Hisao Nemoto a
a Department of Pharmaceutical Chemistry, Division of Heath Biosciences, Graduate School of The University of Tokushima, 1-78-1,
Sho-machi, Tokushima 770-8505, Japan
b Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sanda 669-1337, Japan

ACCEPTED MANUSCRIPT
1
Tetrahedron
journal homepage: www.elsevier.com
Palladium-catalyzed highly regio- and stereoselective carbon–carbon bond formation
reaction of γ-substituted vinylaziridines with a silylated masked acyl cyanide reagent
Tomoyuki Kawamuraa , Nanae Matsuob, Daisuke Yamauchia, Yoo Tanabeb, and Hisao Nemotoa*
a Department of Pharmaceutical Chemistry, Division of Heath Biosciences, Graduate School of The University of Tokushima, 1-78-1, Sho-machi, Tokushima
770-8505, Japan
b Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sanda 669-1337, Japan
Corresponding author: Tel & FAX: +81 88-633-7284; e-mail address: nem@ph.tokushima-u.ac.jp
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Highly regio- and stereoselective carbon–carbon bond formation reaction of vinylaziridines
using a masked acyl cyanide reagent possessing a tert-butyldimethylsilyl group occurred in the
presence of a catalytic amount of palladium complex in excellent yield. It is considered that
these excellent selectivities are the result of three simultaneous conditions, strained leaving
group, small nucleophile, and ligand with small cone-angle.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Keyword_1
Keyword_2
Keyword_3
Keyword_4
Keyword_5
palladium, aziridine, π-allyl complex, masked acyl
cyanide
1. Introduction
may be the presence of a bond reforming process between
the resulting η3-allylpalladium system and a leaving group
A number of reactions via ηꢀ -allylpalladium complexes
have been reported,1 and the reaction mechanism for the
stereochemistry (double inversion mechanism involving
intermolecular attack of nucleophile) is now broadly
accepted. In contrast, a consensus on the α- versus γ-
regioselectivity based on the position of the leaving group
(X of 1 in Figure 1) has not yet been established.2
to generate a mixture of original allylic compounds and the
corresponding regio isomer in situ. As far as we have
surveyed, Tsuji3 and Takahashi4 reported the sole
suggestible examples for the consensus, which was the
palladium-catalyzed intermolecular carbon–carbon bond
formation reaction between active methylene compounds
and acyclic vinyloxiranes bearing alkyl groups at both α-
and γ-positions such as 2 to afford the product with >90% γ-
regioselectivity. We also examined the reaction of sorbic
amide 4,5-monoxide with a masked acyl cyanide reagent
(MAC) possessing a tert-butyldimethylsilyl (TBS) group
(3)5 to afford the adduct in 100% γ-regioselectivity.6 Highly
selective formation of one diastereomer was also observed.6
In these cases,3,4,6 use of conformationally fixed tricyclic
ligands7 such as phosphite 4 was very effective for the
improvement of both chemical yield and selectivity.
Based on the above-mentioned examples, we
hypothesized that γ-regioselectivity was due to the nature of
the palladium-catalyzed carbon–carbon bond formation of
η3-allyl system by the nucleophilic attack far from the out
of ligand field. High γ-selectivity was the result of the two
following factors. The first is the exhaustive reduction of
steric factors of both ligands8 and nucleophiles to observe as
pure orbital control as possible. The second is the use of
Figure 1. Structures of an allylic compound 1, a β’,γ-
disubstituted vinyloxirane 2,
a silylated masked acyl
cyanide 3 (TBS = tert-butyldimethylsilyl), conformationally
fixed ligand 4, and a β’,γ-disubstituted vinylaziridine 5.
One reason for this may be due to the use of molecules
with different steric factor in the α- and γ-regions, which
gives unequal opportunity to the regioselectivity. Another

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2
Tetrahedron
highly strained leaving group such as an oxirane, which
prohibits the bond formation between a η3-allyl system and
a leaving group. To verify this hypothesis, additional
examples with high γ-regioselectivity must be
demonstrated. As an alternative strained leaving group, an
aziridine is a suitable candidate. Although a palladium-
catalyzed hydrogen–carbon bond formation reaction of
alkenylated aziridines by Shimizu et al9 and Ibuka et al,10
and a carbon–carbon bond formation reaction of aziridine
possessing terminal alkene by Sweeney et al11 have been
reported, these examples are unsuitable to explain the
regioselective nature of palladium-catalyzed carbon–carbon
bond formation reaction.12
The reaction of 6a was examined using 3 (1.2 equiv.) in
THF for 5–60 min at room temperature in the presence of a
catalytic amount of ligand (0.6 mol% in the case of
monodentate ligand, 0.3 mol% in the case of bidentate
ligand)
and
tris(dibenzylideneacetone)dipalladium–
chloroform complex [(dba)3Pd2•CHCl3] (0.1 mol%, 0.2
mol% based on Pd atom). In entries 1–3 [use of
triphenylphosphine
(PPh3),
1,2-
bis(diphenylphosphino)ethane (dppe) and 4, respectively],
adduct 7a was smoothly afforded in over 90% yield without
addition of base.14 In contrast, when tributylphosphine
(PnBu3) was used, the desired product was undetected
although complete consumption of 6a was observed (entry
4). This negative result was probably due to the large cone
angle of the ligand,2 which prohibited the approach of the
nucleophile to the allylpalladium species.
2. Results and discussion
In this paper, we report a highly γ-regioselective and
stereoselective palladium-catalyzed carbon–carbon bond
formation reaction of a vinylaziridine possessing alkyl
groups at both β’- and γ-positions 5 with a MAC reagent
such as 3. Because of the two electron withdrawing groups
possessing sp-hybridized orbital (–CN), MAC reagents
Based on the reaction time and the E/Z selectivity, the
conditions for entry 3 were applied to the aliphatic
derivatives 6b and 6c to afford the desired adducts 7b and
7c in 97% and 89% yields, respectively (entries 5 and 6).
Finally, the same conditions were applied to 6d (the α,β’-
cis-isomer of 6a) to afford 7a in 89% yield with E-geometry
(>99:1).
including
palladium-affinitive
3
are very small carbon nucleophiles of
active methyne
compound.13
Accordingly, the combination of 5 and 3 is a suitable
example for the demonstration of expected high γ-
regioselectivity.
Incidentally, we have examined the reaction of 6a with
three equivalents of diethyl malonate instead of 3 under the
conditions for entry 3 to afford the corresponding adducts (a
mixture of mono- and diallylated malonates) in ca. 60%
yield. This yield was consistent with that reported by
Sweeney.11 Attempt of diethyl 2-methylmalonate instead of
3 gave no carbon–carbon bond adducts. Accordingly, it
showed that 3 was more suitable than malonates to explore
the palladium-catalyzed reaction with vinylaziridine.13,15
As substrates for the palladium-catalyzed reactions, we
chose N-arylsulfonylated derivatives of 5 (R3 = ArSO2–)
because
the
corresponding
N-diphenylphosphinyl
derivatives of 511 [R3 = P(O)Ph2P(O)–] possessing aliphatic
group R1 cannot be easily prepared, and the corresponding
N-tert-butyloxycarbonylated derivative of 5 (R3 = tBuOCO–
)
was too unstable to purify by silica gel column
chromatography based on our preliminary attempts. Since
Sweeney’s reaction conditions using an aziridine possessing
a terminal alkene were not specified11,14 and may be in
discord with the optimized conditions for vinyloxiranes
reported by Tsuji,3 Takahashi4 and us,6 we first optimized
the reaction conditions by using aziridines possessing
terminal alkene 6 (Table 1).
We next examined the regioselectivity using eight γ-
substituted vinylaziridines 8, reasonable substrates for the
fare assessment of regioselectivity, which were prepared as
shown in Scheme 1. Because of the higher overall yield
from α-amino esters
diastereomeric separation of 13 and 14 by silica gel flash
column chromatography, the 2,4,6-
9 to 8, and more efficient
Table 1 Palladium-catalyzed reaction of 3 and 6 (Tol =
4-MeC6H4–)
trimethylbenzenesulfonyl group (MesSO2–) rather than
TolSO2 group was chosen as the N-protecting group.
Scheme 1
Thus, commercially available amino acid methyl ester
hydrochloride salt (±)-9e was sulfonylated at 0 ˚C with
MesSO2Cl in pyridine in the presence of a catalytic amount
of 4-(dimethylamino)pyridine (DMAP) to afford (±)-10e in
99% yield. Horner-Emmons agent (±)-11e was prepared
from (±)-10e and the carbanion generated from dimethyl
methylphosphonate [CH3P(O)(OMe)2] and butyllithium
(BuLi) at –78 ˚C in THF in 99% yield. Condensation of (±)-
11e and acetaldehyde in ethanol with anhydrous potassium
carbonate (K2CO3) at room temperature gave (±)-12g in
85% yield. Reduction of the ketone (±)-12g by sodium
borohydride (NaBH4) and cerium chloride heptahydrate
(CeCl3•7H2O) in methanol at 0 ˚C afforded 13g and 14g as
a diastereomeric mixture in 96% chemical yield. Mixtures
of 13h/14h, 13i/14i, and 13j/14j were also obtained in
similar manner as illustrated in Scheme 1. All four
diastereomers of (±)-13 were separable from (±)-14 by flash
column chromatography. Finally, each amino alcohol 13 or
––––––––––––––––––––––––––––––––––––––––––––––––
entry
6
ligand
time
Yield
E/Z
(min)
of 7 (%)
––––––––––––––––––––––––––––––––––––––––––––––––
1
2
3
4
5
6
7
6a
6a
6a
6a
6b
6c
PPh3
dppe
5
30
5
60
15
15
5
93
91
99
0
97
89
89
95:5
>99:1
>99:1
-
>99:1
>99:1
>99:1
4
PnBu3
4
4
4
6da
––––––––––––––––––––––––––––––––––––––––––––––––
a: diastereomer of 6a (α,β’-cis-isomer)

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3
14 was transformed to the corresponding (±)-8 in excellent
yield with diethyl diazene 1,2-dicarboxylate (DEAD) and
PPh3 in THF at 0 ˚C.10
Coupling constant between the α and β’ hydrogens of 8t
was clearly smaller than those of the corresponding 8c
(Table 2). Thus, 8t was assigned as trans-aziridine and 8c
was assigned as cis-aziridine.16 Relative stereochemistries
of 13 and 14 were assigned based on the mechanism of
Mitsunobu reaction,16 as illustrated in Scheme 1.
Results of the reaction of 3 and 8t are illustrated in
Scheme 2. Under the optimized conditions (entry 3 in Table
1), 8tg–8tj exclusively gave γ-adducts 15g–15j,
respectively, in >98% chemical yield. Incidentally, the
double inversion mechanism17 was also confirmed because
not even a trace amount of the corresponding diastereomer
16, illustrated in Scheme 3, was observed in the crude
mixture. It is further noted that PPh3 instead of 4 did not
work for the carbon–carbon bond formation. When the
reaction was prolonged or carried out at higher temperature
with PPh3, a small amount of unidentified compounds
(probably something like a complicated mixture of dienes
via β-elimination process) was detected.
minimization using MM2, the Cα–Cβ=Cγplane was still
approximately orthogonal to the σ-Cα–N bond in the cases
of 8cg, 8ch and 8ci (conformation A). In contrast, in the case
of 8cj, the relationship between the Cα–Cβ=Cγplane and σ-
Cα–N bond was not orthogonal any more, probably due to
the distortion caused by the steric repulsion between the Cβ
hydrogen and Cβ’ iPr (conformations B or C). In fact, as
listed in Table 2, the coupling constant between the α and
β’ hydrogens of 8cj was significantly greater than those of
8cg–8ci. Accordingly,
a distorted palladium complex
intermediate such as η1-allylpalladium may be generated as
a non-trivial conformational possibility to direct nucleophile
3 to the α-position to some extent.
Figure 2
The relative stereochemistry of each compound was
confirmed or determined as follows. The MAC moiety of
15g, 15h, 16g and 16h was smoothly transformed to the
corresponding methyl ester to afford 18g, 18h, 19g and 19h,
respectively, in excellent yields without a detection of the
corresponding
tris(dimethylamino)sulfonium
diastereomer6,18
difluorotrimethylsilicate
by
using
(TASF) as a mild deprotecting agent for TBS group19 in
methanol (Scheme 4). The relative stereochemistries of
18g, 18h, 19g and 19h were unambiguously determined by
the comparison of known compounds.10,16 Accordingly, the
stereochemistry of 15g, 15h, 16g and 16h was also
determined.
Table 2. Coupling constants between
hydrogens of 8
α and β’
Compounds
Coupling Constant
8tg / 8cg
8th / 8ch
8ti / 8ci
8tj / 8cj
4.5 / 5.5
4.0 / 5.5
- / 5.5
4.5 / 7.6
Scheme 2
In Scheme 3, results of the reaction of 8c are illustrated.
When either R1 or R2 was not an isopropyl group (iPr) (8cg
and 8ch), the desired reaction proceeded smoothly to afford
γ-adduct 16 in excellent yield. The corresponding
diastereomer 15 was not detected at all. In the case of 8ci,
however, a small amount of α-isomer 17i was detected. In
the case of 8cj, α-isomer 17j was produced with 42%
selectivity.
Scheme 4. Condition: TASF (1.2 eq), MeOH, 0 ˚C, 35
min.
The relative stereochemistry of 15i, 15j, 16i and 16j was
determined by the value of the coupling constants of the
two hydrogens as shown in Table 3. It was clearly observed
that J
of 15 was smaller than that of 16.20
β’–α
Scheme 3
Table 3. Coupling constant of H
H
β’– α
Except 8cj, all the substrates illustrated in Schemes 2 and
3 were successfully converted to the products with excellent
γ-regioslelectivity by the use of palladium-affinitive small
nucleophile, small ligand, and strained leaving group.
Thus, it cannot be simply concluded that iPr as R2 is too
bulky to undergo a palladium-catalyzed reaction. This is
because carbon–carbon bond formation at the γ-position
was successful in excellent yield even when R2 was a bulky
iPr (in the cases of 8ti and 8tj). Furthermore, low γ-
selectivity was observed by the influence of iPr at the β’-
position (R1) rather than the γ-position (R2) (8cj versus 8ci).
Compounds
J
(Hz)
comparison
–
β α
15g/16g
15h/16h
15i/16i
6.3/7.6
5.8/6.8
5.2/7.2
4.8/7.9
J15 < J16
J15 < J16
J15 < J16
J15 < J16
15j/16j
Thus, it is considered that palladium-catalyzed reactions
described in Schemes 2 and 3 proceeded via double
inversion mechanism by comparison of the stereochemistry
of 8t and 15 as well as that of 8c and 16.17
By our preliminary conformational analysis (ground state
using MM2 calculations) of four compounds 8cg–8cj, a
proposal for the regioselectivity is as follows (Figure 2). For
the initial xyz-coordinates of all 8c, the Cα–Cβ=Cγplane
was orthogonally drawn to the σ-Cα–N bond for the smooth
generation of the η3-allylpalladium complex. After energy
3. Conclusion
Highly regio- and stereoselective palladium-catalyzed
carbon–carbon bond formation reaction of γ-substituted
vinylaziridines was successfully demonstrated under the

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4
Tetrahedron
three simultaneous conditions: strained leaving group, small
nucleophile, and ligand with small cone-angle. Under the
conditions that we reported, very high γ-selectivity was
observed in many cases, even when a bulky iPr was
substituted at the γ-position. Finally, we would like to argue
that MAC reagents can be powerful and efficient
was recrystallized from hexane to give a colorless needle (mp 75˚C).
FT-IR (neat): 3278, 2960, 2933, 2861, 2242, 1471, 1328, 1261, 1160,
1047, 973, 842, 786, 734 cm–1; 1H NMR (CDCl3, 400 MHz) δ 7.73 (d,
J = 8.3 Hz, 2H, aromatic), 7.29 (d, J = 8.3 Hz, 2H, aromatic), 5.55 (dd,
J = 15.4, 7.1 Hz, 1H, –CH=C), 5.37 (dt, J = 15.4, 7.8 Hz, 1H, –
C=CHCH2), 4.66 (brd, J = 8.1 Hz, 1H, –NH), 3.67–3.59 (m, 1H, –
NCH), 2.67 (dd, J = 13.9, 6.6 Hz, 1H, –CHaHb), 2.60 (dd, J = 13.9, 8.1
Hz, 1H, –CHaHb), 2.43 (s, 3H, ArCH3), 1.80–1.71 (m, 1H, –CH(CH3)2),
0.91 (s, 9H, –SiC(CH3)3), 0.86 (d, J = 6.6 Hz, 3H, –CCH3), 0.85 (d, J =
6.6Hz, 3H, –CCH3), 0.34 (s, 6H, –SiCH3 ×2); 13C NMR (CDCl3, 100
MHz) δ 143.3 (C), 137.8 (C), 137.3 (CH), 129.5 (CH ×2), 127.1 (CH
×2), 121.2 (CH), 114.7 (C ×2), 63.6 (C), 60.9 (CH), 45.3 (CH2), 32.8
(CH), 25.2 (CH3 ×3), 21.6 (CH3), 18.2 (CH3), 18.0 (C), –4.5 (CH3 ×2);
HRMS (ESI-TOF) m/z calcd for C23H35N3O3NaSSi [M+Na]+ 484.2066,
found 484.2080.
nucleophiles to probe the regioselective nature of
a
palladium-catalyzed reaction and also are highly applicable
to the synthesis of various dipeptide isoster
derivatives.10,16,21
4. Experimental section
Melting points were determined on YAMAMOTO-MODEL 20 melting
point apparatus, and were uncorrected. NMR spectra were recorded on
a JEOL FT-NMR AL-400 spectrometer, operating at 400 MHz for 1H
NMR and 100 MHz for 13C NMR and JEOL DELTA 300 spectrometer,
operating at 300 MHz for 1H NMR and 75 MHz for 13C NMR.
Chemical shifts (δ ppm) in CDCl3 were downfield from
tetramethylsilane (0.00 ppm) for 1H NMR, and were reported in the
scale relative to CDCl3 (77.0 ppm) for 13C NMR. IR spectra were
recorded on a JASCO FT-IR 420 spectrometer. Mass spectra were
(5E)-N-(8-(tert-Butyldimethylsilyloxy)-8,8-dicyano-2-methyloct-5-
en-4-yl)-4-methylbenzenesulfonamide [(±)-7c]
Synthesis of (±)-7c was carried out starting from (±)-6c (42.5 mg,
0.152 mmol, 1.0 eq.) as described for (±)-15g. Purified by silica gel
column chromatography with hexane and ethyl acetate (3:1) to as an
eluent give (±)-7c (64 mg, 0.14 mmol, 89% yield) as a solid, which was
recrystallized from hexane to give a colorless needle (mp 82˚C). FT-IR
(neat): 3272, 2956, 2933, 2861, 2242, 1471, 1328, 1261, 1159, 1047,
971, 842, 786 cm–1; 1H–NMR (CDCl3, 400 MHz) δ 7.73 (d, J = 8.3 Hz,
2H, aromatic), 7.30 (d, J = 8.3 Hz, 2H, aromatic), 5.52 (dd, J = 15.4,
6.6 Hz, 1H, –CH=C), 5.43 (dt, J = 15.4, 6.6 Hz, 1H, –C=CHCH2), 4.60
(brd, J = 7.3 Hz, 1H, –NH), 3.82 (ddd, J = 7.6, 7.3, 7.1 Hz, 1H, –NCH),
2.67 (dd, J = 13.7, 6.1 Hz, 1H, –C=CCHaHb), 2.58 (dd, J = 13.7, 7.6
Hz, 1H, –C=CCHaHb), 2.43 (s, 3H, ArCH3), 1.64–1.55 (m, 1H, –
CH(CH3)2), 1.38–1.25 (m, 2H, –CHCH2CH), 0.91 (s, 9H, –SiC(CH3)3
×3), 0.82 (d, J = 6.6Hz, 3H, –CCH3), 0.78 (d, J = 6.6Hz, 3H, –CCH3),
0.33 (s, 6H, –SiCH3 ×2); 13C–NMR (CDCl3, 100 MHz) δ 143.3 (C),
139.4 (CH), 137.8 (C), 129.5 (CH ×2), 127.1 (CH ×2), 120.2 (CH),
114.6 (C ×2), 63.5 (C), 53.8 (CH), 45.1 (CH2), 44.8 (CH2), 25.2 (CH3
×3), 24.3 (CH), 22.2 (CH3 ×2), 21.6 (CH3), 18.1 (C), –4.5 (CH3 ×2);
HRMS (ESI–TOF) m/z calcd for C24H37N3O3NaSSi [M+Na]+ 498.2223,
found 498.2198.
recorded on
a JEOL JMS-DX 303 or Waters/Micromass LCT
PREMIRE Mass spectrometer. Column chromatography was
performed with silica-gel KANTO KAGAKU 60N (spherical, neutral,
63–210 µm). Flash column chromatography was performed with silica-
gel KANTO KAGAKU 60N (spherical, neutral, 40–50 µm). TLC
analysis was performed on precoated plates (0.25 mm, Silica gel Merk
Kieselgel 60 F254). All reactions were carried out in oven-dried
glassware under an agron atmosphere, unless otherwise noted. Reaction
mixtures were stirred magnetically. Ethanol was distilled over sodium.
Methanol was distilled over magnesium. Pyridine was distilled from
calusium hydride. Anhydrous tetrahydrofuran (THF) was purchased
from Kanto Chemical Co., Inc.
(2E)-N-(5-(tert-Butyldimethylsilyloxy)-5,5-dicyano-1-(4-
methoxyphenyl)pent-2-enyl)-4-methylbenzenesulfonamide [(±)-7a]
Synthesis of (±)-7a was carried out starting from (±)-6a (50.0 mg,
0.152 mmol, 1.0 eq.) as described for (±)-15g. Purified by silica gel
column chromatography with hexane and ethyl acetate (3:1) as an
eluent to give (±)-7a (79 mg, 0.15 mmol, 99% yield) as a pale yellow
oil. FT-IR (neat): 3276, 2956, 2933, 2859, 2256, 1513, 1328, 1253,
1159, 1033, 973, 842, 786, 732 cm–1; 1H NMR (CDCl3, 400 MHz) δ
7.64 (d, J = 8.3 Hz, 2H, aromatic), 7.24 (d, J = 8.3 Hz, 2H, aromatic),
6.99 (d, J = 8.5 Hz, 2H, aromatic), 6.75 (d, J = 8.5 Hz, 2H, aromatic),
5.89 (dd, J = 15.4, 5.6 Hz, 1H, –CH=C), 5.56 (dt, J = 15.4, 7.3 Hz, 1H,
–C=CHCH2), 4.91 (t, J = 6.4 Hz, 1H, –NCH), 4.73 (brd, J = 6.4 Hz,
1H, –NH), 3.76 (s, 3H, ArOCH3), 2.77 (d, J = 7.3 Hz, 2H, –CH2), 2.42
Methyl-2-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-3-phenyl-
propionate [(±)-10e]
To a suspension of DL-phenylalanine methyl ester hydrochloride [(±)-
9e] (3.00 g, 13.9 mmol, 1.00 eq.) and DMAP (0.170 g, 1.39 mmol,
0.100 eq.) in pyridine (11.4 mL, 139 mmol, 10.0 eq.) was added
MesSO2Cl (2.66 g, 16.7 mmol, 1.20 eq.) at 0˚C and the mixture was
stirred at room temperature for 20 h. The resulting mixture was
acidified with 1N HClaq (300 mL) and extracted with ethyl acetate
(200 mL × 3). The combined organic layers were washed with water
(100 mL), a saturated aqueous solution of sodium hydrogen carbonate
(NaHCO3aq) (100 mL) and brine (100 mL), dried over anhydrous
sodium sulfate (Na2SO4) and concentrated in vacuo. The residue was
purified by silica gel column chromatography (hexane : ethyl acetate =
1:1) to give (±)-10e (5.0 g, 14 mmol, 99% yield). Colorless crystal: mp
135–136 ˚C (recrystallized from ethyl acetate); FT-IR (KBr) 3294,
2937, 2364, 1745, 1604, 1160, 1105, 1037, 950, 902, 846, 661 cm–1; 1H
NMR (400 MHz, CDCl3) δ 2.28 (s, 3H), 2.55 (s, 6H), 2.99 (dd, J = 6.0,
13.6 Hz, 1H), 3.03 (dd, J = 5.6, 13.6 Hz, 1H), 3.52 (s, 3H), 4.10 (ddd, J
= 5.6, 6.0, 8.8 Hz, 1H), 5.13 (brd, J = 8.8 Hz, 1H, −NH), 6.89 (s, 2H),
6.99–7.06 (m, 2H), 7.19–7.24 (m, 3H); 13C NMR (100 MHz, CDCl3) δ
20.9 (CH3), 22.9 (CH3 × 2), 39.2 (CH2), 52.4 (CH3), 56.4 (CH), 127.0
(CH), 128.4 (CH × 2), 129.1 (CH × 2), 131.8 (CH × 2), 133.1 (C),
(s, 3H, ArCH3), 0.87 (s, 9H, –SiC(CH3)3), 0.32 (s, 6H, –SiCH3 ×2); 13
C
NMR (CDCl3, 100 MHz) δ 159.2 (C), 143.3 (C), 138.6 (CH), 137.4
(C), 130.7 (C), 129.5 (CH ×2), 128.2 (CH ×2), 127.1 (CH ×2), 121.3
(CH), 114.7 (C), 114.6 (C), 114.1 (CH ×2), 63.4 (C), 58.4 (CH), 55.3
(CH3), 45.1 (CH2), 25.2 (CH3 ×3), 21.6 (CH3), 18.0 (C), –4.5 (CH3 ×2);
HRMS (ESI-TOF) m/z calcd for C27H35N3O4NaSSi [M+Na]+ 548.2015,
found 548.2040.
(4E)-N-(7-(tert-Butyldimethylsilyloxy)-7,7-dicyano-2-methylhept-
4-en-3-yl)-4-methylbenzenesulfonamide [(±)-7b]
Synthesis of (±)-7b was carried out starting from (±)-6b (40.3 mg,
0.152 mmol, 1.0 eq.) as described for (±)-15g. Purified by silica gel
column chromatography with hexane and ethyl acetate (3:1) as an
eluent to give (±)-7b (68 mg, 0.15 mmol, 97% yield) as a solid, which

ACCEPTED MANUSCRIPT
5
135.0 (C), 139.2 (C × 2), 142.2 (C), 171.4 (C=O); HRMS (ESI-HRMS)
m/z calcd for C19H23NO4NaS [M+Na]+ 384.1245, found 384.1249.
23.4 Hz, 1H), 3.70 (d, JH–P = 11.4 Hz, 3H), 3.75 (d, JH–P = 11.4 Hz,
3H), 3.96 (dd, J = 3.8, 9.3 Hz, 1H), 6.02 (brd, J = 9.3 Hz, 1H, –NH),
6.94 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 16.3 (CH3), 19.7 (CH3),
20.9 (CH3), 22.9 (CH3 × 2), 29.6 (CH), 38.6 (d, JC–P = 128.6 Hz, –
CH2P), 53.0 (d, JC–P = 6.5 Hz, –POCH3), 53.3 (d, JC–P = 6.5 Hz, –
POCH3), 67.3 (CH), 131.9 (CH × 2), 134.2 (C), 138.9 (C × 2), 142.2
(C), 200.6 (d, JC–P = 5.8 Hz, C=O); HRMS (ESI-HRMS) m/z calcd for
C17H28NO6NaSP [M+Na]+ 428.1273, found 428.1281.
Methyl-2-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-3-methyl-
butanoate [(±)-10f]
Preparation of (±)-10f was carried out starting from DL-valine methyl
ester hydrochloride [(±)-9f] (1.68 g, 10.0 mmol) as described for (±)-
10e from (±)-9e. Purified by silica gel column chromatography (hexane
: ethyl acetate = 1:1) to give (±)-10f (3.1 g, 10 mmol, 99% yield from
(±)-9f). Colorless crystal: mp 120–121 ˚C (recrystallized from ethyl
acetate); FT-IR (KBr) 3309, 3247, 2971, 2358, 1757, 1740, 1470,
1397, 1375, 1346, 1260, 1206, 1185, 1140, 1059, 941, 884, 851, 657
cm–1; 1H NMR (300 MHz, CDCl3) δ 0.87 (d, J = 6.9 Hz, 3H), 0.89 (d, J
= 6.9 Hz, 3H), 1.91–2.02 (m, 1H), 2.29 (s, 3H), 2.64 (s, 6H), 3.46 (s,
3H), 3.61 (dd, J = 5.5, 10.0 Hz, 1H), 5.14 (brd, J = 10.0 Hz, 1H, –NH),
6.94 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 17.7 (CH3), 18.8 (CH3),
20.9 (CH3), 23.0 (CH3 × 2), 31.6 (CH), 52.1 (CH3), 60.1 (CH), 131.8
(CH × 2), 133.4 (C), 139.3 (C × 2), 142.3 (C), 171.9 (C=O); HRMS
(ESI-HRMS) m/z calcd for C15H23NO4NaS [M+Na]+ 336.1245, found
336.1260.
(4E)-2-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-1-phenyl-4-
hexen-3-one [(±)-12g]
To
a solution of (±)-11e (1.00 g, 2.21 mmol, 1.00 eq.) and
acetoaldehyde (0.15 mL, 2.65 mmol, 1.20 eq.) in ethanol (10 mL) was
added oven-dried potassium carbonate (0.305 g, 2.21 mmol, 1.00 eq.)
portionwise over 15 min at room temperature, and the mixture was
stirred for 5 h at room temperature. The resulting suspension was
filtered and the residue was washed with ethyl acetate (20 mL). The
combined filtrates were neutralized with glacial acetic acid and
concentrated in vacuo. The residue was diluted with ethyl acetate (30
mL), and washed with water (30 mL). The aqueous phase was
extracted with ethyl acetate (30 mL × 2). The combined organic layers
were washed with water (30 mL), NaHCO3aq (30 mL), brine (30 mL),
dried over Na2SO4 and concentrated in vacuo. The residue was purified
by silica gel column chromatography (hexane : ethyl acetate = 9:1) to
give (±)-12g (0.70 g, 1.9 mmol, 85% yield). Colorless crystal: mp 125–
126 ˚C (recrystallized from hexane); FT-IR (KBr) 3250, 3026, 2972,
2920, 1699, 1631, 1605, 1497, 1454, 1425, 1325, 1295, 1158, 1114,
1072, 1059, 968, 950, 918, 846, 757, 741, 702, 657, 588 cm–1; 1H NMR
(300 MHz, CDCl3) δ 1.82 (dd, J = 1.7, 6.9 Hz, 3H), 2.26 (s, 3H), 2.53
(s, 6H), 2.90 (dd, J = 6.2, 14.1 Hz, 1H), 3.00 (dd, J = 6.5, 14.1 Hz, 1H),
4.28 (ddd, J = 6.2, 6.5, 7.6 Hz, 1H), 5.45 (brd, J = 7.6 Hz, 1H, –NH),
6.07 (dq, J = 1.7, 15.5 Hz, 1H), 6.80 (dq, J = 6.9, 15.5 Hz, 1H), 6.86 (s,
2H), 6.96–7.02 (m, 2H), 7.16–7.20 (m, 3H); 13C NMR (75 MHz,
CDCl3) δ 18.5 (CH3), 20.9 (CH3), 22.8 (CH3 × 2), 39.1 (CH2), 60.2
(CH), 127.0 (CH), 127.9 (CH), 128.4 (CH × 2), 129.4 (CH × 2), 131.9
(CH × 2), 133.6 (C), 135.3 (C), 139.0 (C × 2), 142.2 (C), 145.6 (CH),
196.0 (C=O); HRMS (ESI-HRMS) m/z calcd for C21H26NO3S [M+H]+
372.1633, found 372.1624.
Dimethyl-{3-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-2-oxo-4-
phenyl-butyl}-phosphonate [(±)-11e]
To a solution of dimethyl methylphosphate (3.6 mL, 33.2 mmol, 4.00
eq.) in anhydrous THF (50 mL) was added a solution of BuLi in
hexane (2.77 M, 12 mL, 33.2 mmol, 4.0 eq) dropwise over 15 min at –
78 ˚C. After 30 min, to the mixture was added a solution of (±)-10e
(3.00 g, 8.30 mmol, 1.00 eq.) in THF (30 mL) dropwise over 15 min at
–78 ˚C. The resulting mixture was stirred for 1 h at –78 ˚C, for 4 h at 0
˚C, quenched with acetic acid (10% aqueous solution) at 0 ˚C, and
extracted with ethyl acetate (100 mL × 3). The combined organic layers
were washed with water (100 mL), NaHCO3aq (100 mL), brine (100
mL), dried over Na2SO4 and concentrated in vacuo. The residue was
purified by silica gel column chromatography (hexane : ethyl acetate =
1:9) to give [(±)-11e] (3.7 g, 8.2 mmol, 99% yield). Colorless crystal:
mp 130–131˚C (recrystallized from ethyl acetate); FT-IR (KBr) 3183,
2950, 2360, 1733, 1604, 1457, 1299, 1224, 1162, 1029, 952, 919, 842,
703, 665 cm–1; 1H NMR (400 MHz, CDCl3) δ 2.28 (s, 3H), 2.41 (s,
6H), 2.85 (dd, J = 8.8, 14.1 Hz, 1H), 3.06 (dd, J = 14.0, JH–P = 29.0 Hz,
1H), 3.09 (dd, J = 6.0, 14.1 Hz, 1H), 3.72 (d, JH–P = 11.4 Hz, 3H), 3.73
(dd, J = 14.0, JH–P = 29.0 Hz, 1H), 3.78 (d, JH–P = 11.4 Hz, 3H), 4.13
(ddd, J = 6.0, 8.0, 8.8 Hz, 1H), 5.96 (brd, J = 8.0 Hz, 1H, –NH), 6.81
(s, 2H), 6.90–6.94 (m, 2H), 7.06–7.15 (m, 3H); 13C NMR (100 MHz,
CDCl3) δ 20.9 (CH3), 22.8 (CH3 × 2), 37.6 (CH2), 38.3 (d, JC–P = 127.8
Hz, –CH2P), 53.2 (d, JC–P = 6.6 Hz, –POCH3), 53.3 (d, JC–P = 6.6 Hz, –
POCH3), 63.5 (CH), 126.8 (CH), 128.4 (CH × 2), 128.8 (CH × 2),
131.8 (CH × 2), 133.2 (C), 135.5 (C), 138.8 (C × 2), 142.1 (C), 201.0
(4E)-2-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-7-methyl-1-
phenyl-4-octen-3-one [(±)-12h]
Preparation of (±)-12h was carried out starting from (±)-11e (1.00 g,
2.21 mmol) and isovaleraldehyde as described for (±)-12g from (±)-11e
and acetoaldehyde. Purified by silica gel column chromatography
(hexane : ethyl acetate = 9:1) to give (±)-12h (0.79 g, 1.9 mmol, 87%
yield from (±)-11e). Colorless oil; FT-IR (neat) 3299, 3029, 2956,
1693, 1625, 1565, 1495, 1454, 1334, 1159, 1078, 1031, 983, 904, 852,
750, 770, 655 cm–1; 1H NMR (400 MHz, CDCl3) δ 0.86 (d, J = 6.8 Hz,
3H), 0.86 (d, J = 6.8 Hz, 3H), 1.63–1.73 (m, 1H), 1.98–2.02 (m, 2H),
2.26 (s, 3H), 2.55 (s, 6H), 2.93 (dd, J = 6.4, 14.0 Hz, 1H), 3.00 (dd, J =
6.4, 14.0 Hz, 1H), 4.31 (ddd, J = 6.4, 6.4, 7.2 Hz, 1H), 5.50 (brd, J =
7.2 Hz, 1H, –NH), 5.97 (dt, J = 1.2, 15.6 Hz, 1H), 6.73 (dt, J = 7.6,
(d, JC–P
= 5.7Hz, C=O); HRMS (ESI-HRMS) m/z calcd for
C21H29NO6NaPS [M+H]+ 454.1453, found 454.1409.
Dimethyl-{3-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-4-methyl-
2-oxo-pentyl}-phosphonate [(±)-11f]
Preparation of (±)-11f was carried out starting from (±)-10f (6.20 g,
19.8 mmol) as described for (±)-11e from (±)-10e. Purified by silica gel
column chromatography (hexane : ethyl acetate = 1:4) to give (±)-11f
(7.8 g, 19 mmol, 97% yield from (±)-10f). Colorless crystal: mp 129–
131 ˚C (recrystallized from ethyl acetate); FT-IR (KBr) 3253, 2971,
2938, 1727, 1467, 1450, 1287, 1187, 1095, 931, 880, 850, 662, 584,
537, 497, 463 cm–1; 1H NMR (300 MHz, CDCl3) δ 0.71 (d, J = 6.9 Hz,
3H), 0.79 (d, J = 6.9 Hz, 3H), 2.19–2.31 (m, 1H), 2.28 (s, 3H), 2.67 (s,
15.6 Hz, 1H), 6.87 (s, 2H), 6.97–7.04 (m, 2H), 7.15–7.21 (m, 3H); 13
C
NMR (100 MHz, CDCl3) δ 21.0 (CH3), 22.39 (CH3), 22.42 (CH3), 22.9
(CH3 × 2), 27.8 (CH), 39.5 (CH2), 41.9 (CH2), 60.0 (CH), 127.0 (CH),
127.4 (CH), 128.4 (CH × 2), 129.3 (CH × 2), 131.8 (CH × 2), 133.6
(C), 135.2 (C), 138.9 (C × 2), 142.1 (C), 149.3 (CH), 196.0 (C=O);
HRMS (ESI-HRMS) m/z calcd for C24H31NO3NaS [M+Na]+ 436.1922,
found 436.1952.
(4E)-2-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-6-methyl-1-
6H), 2.98 (dd, J = 14.1, JH–P = 21.7 Hz, 1H), 3.38 (dd, J = 14.1, JH–P
=
phenyl-4-hepten-3-one [(±)-12i]

ACCEPTED MANUSCRIPT
6
Tetrahedron
Preparation of (±)-12i was carried out starting from (±)-11e (1.00 g,
2.21 mmol) and isobutyraldehyde as described for (±)-12g from (±)-
11e and acetoaldehyde. Purified by silica gel column chromatography
(hexane : ethyl acetate = 9:1) to give (±)-12i (0.65 g, 1.6 mmol, 73%
yield). Colorless oil; FT-IR (neat) 3297, 3029, 2965, 2871, 1694, 1624,
1566, 1497, 1455, 1336, 1157, 1059, 984, 851, 700, 656 cm–1; 1H NMR
(300 MHz, CDCl3) δ 0.94 (d, J = 6.5 Hz, 3H), 0.95 (d, J = 6.5 Hz, 3H),
2.26 (s, 3H), 2.26–2.38 (m, 1H), 2.56 (s, 6H), 2.96 (d, J = 6.5 Hz, 2H),
4.34 (dt, J = 6.5, 7.6 Hz, 2H), 5.53 (brd, J = 7.6 Hz, 1H, –NH), 5.85
(dd, J = 1.4, 15.8 Hz, 1H), 6.65 (dd, J = 6.5, 15.8 Hz, 1H), 6.87 (s, 2H),
7.00–7.03 (m, 2H), 7.17–7.20 (m, 3H); 13C NMR (75 MHz, CDCl3) δ
22.8 (CH3), 20.9 (CH3 × 2), 22.8 (CH3 × 2), 31.2 (CH), 39.6 (CH2),
59.9 (CH), 123.8 (CH), 127.0 (CH), 128.4 (CH × 2), 129.4 (CH × 2),
131.9 (CH × 2), 133.7 (C), 135.4 (C), 139.0 (C × 2), 142.2 (C), 156.3
(CH), 196.9 (C=O); HRMS (ESI-HRMS) m/z calcd for C23H29NO3NaS
[M+Na]+ 422.1766, found 422.1750.
(CH3), 20.8 (CH3), 22.9 (CH3 × 2), 36.0 (CH2), 59.5 (CH), 73.2 (CH),
126.3 (CH), 128.4 (CH × 2), 128.8 (CH × 2), 129.0 (CH), 129.4 (CH),
131.9 (CH × 2), 133.2 (C), 137.0 (C), 138.9 (C × 2), 142.0 (C); HRMS
(ESI-HRMS) m/z calcd for C21H27NO3NaS [M+Na]+ 396.1609, found
396.1583.
(±)-14g: Colorless crystal: mp 72–74 ˚C (recrystallized from hexane);
FT-IR (KBr) 3510, 3335, 3027, 2936, 1604, 1563, 1454, 1420, 1336,
1236, 1187, 1160, 1149, 1123, 1058, 968, 850, 749, 702, 662, 574, 540,
469 cm–1; 1H NMR (300 MHz, CDCl3) δ 1.54 (ddd, J = 0.7, 1.7, 6.5
Hz, 3H), 1.72–1.76 (brm, 1H, –OH), 2.28 (s, 3H), 2.58 (s, 6H), 2.72
(dd, J = 6.2, 13.4 Hz, 1H), 2.93 (dd, J = 8.3, 13.4 Hz, 1H), 3.34–3.43
(m, 1H), 3.98–4.04 (m, 1H), 4.93 (brd, J = 8.6 Hz, 1H, –NH), 5.24
(ddq, J = 1.7, 6.9, 15.5 Hz, 1H), 5.58 (ddq, J = 1.0, 6.5, 15.5 Hz, 1H),
6.88 (s, 2H), 7.04–7.07 (m, 2H), 7.10–7.21 (m, 3H); 13C NMR (75
MHz, CDCl3) δ 17.6 (CH3), 20.8 (CH3), 23.1 (CH3 × 2), 38.4 (CH2),
59.2 (CH), 71.8 (CH), 126.4 (CH), 128.4 (CH × 2), 129.0 (CH), 129.1
(CH × 2), 130.3 (CH), 131.9 (CH × 2), 134.5 (C), 137.6 (C), 138.6 (C
× 2), 141.8 (C); HRMS (ESI-HRMS) m/z calcd for C21H27NO3NaS
[M+Na]+ 396.1609, found 396.1613.
(5E)-3-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-2,7-dimethyl-5-
octen-4-one [(±)-12j]
Preparation of (±)-12j was carried out starting from (±)-11f (2.00 g,
4.93 mmol) and isobutyraldehyde as described for (±)-12g and
acetoaldehyde. Purified by silica gel column chromatography (hexane :
ethyl acetate = 9:1) to give (±)-12j (1.6 g, 4.5 mmol, 91% yield).
Colorless oil; FT-IR (neat) 3298, 2968, 2874, 1694, 1624, 1605, 1566,
(4E)(2R*,3S*)-2-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-3-
hydroxy-7-methyl-1-phenyl-4-octene [(±)-13h] and (4E)(2R*,3R*)-
2-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-3-hydroxy-7-methyl-
1-phenyl-4-octene [(±)-14h]
1
1455, 1328, 1159, 1059, 980, 891, 852, 725, 656 cm-1; H NMR (300
Preparation of (±)-13h and (±)-14h was carried out starting from enone
(±)-12h (500 mg, 1.21 mmol) as described for (±)-13g and (±)-14g
from (±)-12g. Purified by silica gel column chromatography (hexane :
ethyl acetate = 4:1) to give the mixture of diastereomers (461 mg, 1.11
mmol, 92% yield, (±)-13h : (±)-14h = 65 : 35). These diastereomers
were separated by flash column chromatography (hexane : diethyl ether
= 3 : 2).
MHz, CDCl3) δ 0.77 (d, J = 6.9 Hz, 3H), 0.94 (d, J = 6.9 Hz, 3H), 1.00
(d, J = 6.9 Hz, 6H), 1.90–2.01 (m, 1H), 2.25 (s, 3H), 2.32–2.43 (m,
1H), 2.64 (s, 6H), 3.97 (dd, J = 4.2, 8.9 Hz, 1H), 5.56 (brd, J = 8.9 Hz,
1H, –NH), 5.86 (dd, J = 1.2, 15.8 Hz, 1H), 6.66 (dd, J = 6.5, 15.8 Hz,
1H), 6.89 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 16.7 (CH3), 19.8
(CH3), 20.8 (CH3), 20.9 (CH3), 21.0 (CH3), 22.9 (CH3 × 2), 31.0 (CH),
31.2 (CH), 63.5 (CH), 124.3 (CH), 131.9 (CH × 2), 133.8 (C), 138.9 (C
× 2), 142.1 (C), 155.7 (CH), 197.5 (C=O); HRMS (ESI-HRMS) m/z
calcd for C19H29NO3NaS [M+Na]+ 374.1766, found 374.1771.
(±)-13h: Colorless oil; FT-IR (neat) 3500, 3305, 2952, 2360, 1604,
1454, 1317, 1151, 1056, 970, 914, 848, 742, 698, 649 cm–1; 1H NMR
(400 MHz, CDCl3) δ 0.91 (d, J = 6.8 Hz, 6H), 1.59–1.71 (m, 1H),
1.48–1.82 (brm, 1H, –OH), 1.93 –1.99 (m, 2H), 2.28 (s, 3H), 2.44 (s,
6H), 2.64 (dd, J = 8.8, 14.3 Hz, 1H), 2.78 (dd, J = 5.8, 14.3 Hz, 1H),
3.40–3.50 (m, 1H), 4.23–4.29 (m, 1H), 4.65 (brd, J = 7.6 Hz, 1H, –
NH), 5.46 (ddt, J = 0.8, 6.2, 15.5 Hz, 1H), 5.74 (ddt, J = 0.8, 7.0, 15.5
Hz, 1H), 6.82 (s, 2H), 6.87–6.93 (m, 2H), 7.07–7.16 (m, 3H); 13C NMR
(100 MHz, CDCl3) δ 21.0 (CH3), 22.38 (CH3), 22.41 (CH3), 23.1 (CH3
× 2), 28.6 (CH), 36.2 (CH2), 41.8 (CH2), 59.7 (CH), 73.2 (CH), 126.4
(CH), 128.4 (CH × 2), 128.6 (CH), 128.8 (CH × 2), 131.9 (CH × 2),
133.2 (C), 133.5 (CH), 136.9 (C), 138.9 (C × 2), 142.0 (C); HRMS
(ESI-HRMS) m/z calcd for C24H33NO3NaS [M+Na]+ 438.2079, found
438.2076.
(4E)(2R*,3S*)-2-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-3-
hydroxy-1-phenyl-4-hexene [(±)-13g] and (4E)(2R*,3R*)-2-[N-
(2,4,6-trimethylbenzenesulfonyl)amino]-3-hydroxy-1-phenyl-4-
hexene [(±)-14g]
To a solution of (±)-12g (500 mg, 1.35 mmol, 1.00 eq.) and cerium(III)
chloride heptahydrate (503 mg, 1.35 mmol, 1.00 eq.) in methanol (6.8
mL) was added sodium borohydride (51.1 mg, 1.35 mmol, 1.00 eq.) in
small portions over 15 min at 0 ˚C, and stirred for 30 min at 0 ˚C. The
resulting mixture was neutralized with glacial acetic acid and
concentrated in vacuo. The residue was diluted with ethyl acetate (10
mL), and washed with H2O (10 mL). The aqueous phase was extracted
with ethyl acetate (10 mL × 2). The combined organic layers were
washed with water (10 mL), NaHCO3aq (10 mL), brine (10 mL), dried
over Na2SO4 and concentrated in vacuo. The residue was purified by
silica gel column chromatography (hexane : ethyl acetate = 4:1) to give
a mixture of diastereomers (483 mg, 1.29 mmol, 96% yield, (±)-13g :
(±)-14g = 61 : 39). These diastereomers were separated by flash
column chromatography (hexane : diethyl ether = 1 : 1).
(±)-14h: Colorless crystal mp 84–85 ˚C (recrystallized from hexane);
FT–IR (KBr) 3448, 3164, 2952, 2360, 1602, 1434, 1313, 1147, 1058,
931, 850, 744, 700 cm–1; 1H NMR (400 MHz, CDCl3) δ 0.81 (d, J = 6.8
Hz, 3H), 0.83 (d, J = 6.8 Hz, 3H), 1.46–1.60 (m, 1H), 1.50–1.67 (brm,
1H, –OH), 1.67–1.82 (m, 2H), 2.28 (s, 3H), 2.57 (s, 6H), 2.71 (dd, J =
5.8, 13.7 Hz, 1H), 2.94 (dd, J = 8.4, 13.7 Hz, 1H), 3.34–3.45 (m, 1H),
3.98–4.07 (m, 1H), 4.89 (brd, J = 8.4 Hz, 1H, –NH), 5.28 (ddt, J = 1.2,
7.2, 15.4 Hz, 1H), 5.56 (dt, J = 7.2, 15.4 Hz, 1H), 6.88 (s, 2H), 7.02–
7.08 (m, 2H), 7.12–7.22 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 20.9
(CH3), 22.32 (CH3), 22.37 (CH3), 23.2 (CH3 × 2), 28.1 (CH), 38.4
(CH2), 41.6 (CH2), 59.2 (CH), 72.1 (CH), 126.4 (CH), 128.4 (CH × 2),
129.1 (CH × 2), 130.1 (CH), 131.8 (CH × 2), 133.4 (CH), 134.5 (C),
137.4 (C), 138.5 (C × 2), 141.7 (C); HRMS (ESI-HRMS) m/z calcd for
C24H33NO3NaS [M+Na]+ 438.2079, found 438.2019.
(±)-13g: Colorless oil; FT-IR (neat) 3733, 3308, 3027, 2938, 1604,
1567, 1497, 1455, 1319, 1188, 1152, 1057, 967, 850, 743, 698, 652
cm–1; 1H NMR (300 MHz, CDCl3) δ 1.73 (brd, J = 6.5 Hz, 3H), 2.28 (s,
3H), 2.35 (brd, J = 5.5 Hz, 1H, –OH), 2.45 (s, 6H), 2.65 (dd, J = 8.3,
14.1 Hz, 1H), 2.78 (dd, J = 5.6, 14.1 Hz, 1H), 3.40–3.48 (m, 1H), 4.17–
4.24 (m, 1H), 4.65 (brd, J = 7.9 Hz, 1H, –NH), 5.46 (ddq, J = 1.5, 6.3,
15.5 Hz, 1H), 5.77 (ddq, J = 1.2, 6.6, 15.5 Hz, 1H), 6.83 (s, 2H), 6.88–
6.94 (m, 2H), 7.08–7.16 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 17.9

ACCEPTED MANUSCRIPT
7
(4E)(2R*,3S*)-2-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-3-
hydroxy-6-methyl-1-phenyl-4-heptene [(±)-13i] and (4E)(2R*,3R*)-
2-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-3-hydroxy-6-methyl-
1-phenyl-4-heptene [(±)-14i]
CDCl3) δ 18.6 (CH3), 20.4 (CH3), 20.9 (CH3), 22.2 (CH3 × 2), 23.2
(CH3 × 2), 29.5 (CH), 30.8 (CH), 63.7 (CH), 72.9 (CH), 124.9 (CH),
132.0 (CH × 2), 134.8 (C), 138.6 (C × 2), 141.2 (CH), 142.1 (C);
HRMS (ESI-HRMS) m/z calcd for C19H31NO3NaS [M+Na]+ 376.1922,
found 376.1910.
(±)-14j: Colorless crystal: mp 108–109 ˚C (recrystallized from
hexane); FT-IR (KBr) 3496, 3343, 3281, 2938, 1604, 1457, 1399,
1382, 1345, 1305, 1267, 1161, 1148, 1071, 1054, 972, 945, 852, 689,
648, 569, 540, 514 cm–1; 1H NMR (300 MHz, CDCl3) δ 0.78 (d, J = 6.9
Hz, 3H), 0.84 (d, J = 6.9 Hz, 3H), 0.87 (d, J = 6.9 Hz, 6H), 0.89 (d, J =
6.9 Hz, 6H), 1.78–1.91 (m, 2H), 2.02–2.13 (m, 1H), 2.28 (s, 3H), 2.65
(s, 6H), 2.99–3.06 (m, 1H), 4.03–4.08 (m, 1H), 4.93 (brd, J = 8.9 Hz,
1H, –NH), 5.11 (ddd, J = 1.4, 7.6, 15.5 Hz, 1H), 5.58 (dd, J = 6.5, 15.5
Hz, 1H), 6.94 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 17.9 (CH3), 19.7
(CH3), 20.8 (CH3), 20.87 (CH3), 21.95 (CH3), 23.2 (CH3 × 2), 30.5
(CH), 30.6 (CH), 63.5 (CH), 72.9 (CH), 127.1 (CH), 131.9 (CH × 2),
135.6 (C), 138.3 (C × 2), 141.0 (CH), 141.7 (C); HRMS (ESI-HRMS)
m/z calcd for C19H31NO3NaS [M+Na]+ 376.1922, found 376.1927.
Preparation of (±)-13i and (±)-14i was carried out starting from (±)-12i
(500 mg, 1.25 mmol) as described for (±)-13g and (±)-14g from (±)-
12g. Purified by silica gel column chromatography (hexane : ethyl
acetate = 5:1) to give the mixture of diastereomers (497 mg, 1.23
mmol, 99% yield, (±)-13i and (±)-14i = 59 : 41). These diastereomers
were separated by flash column chromatography (hexane : diethyl ether
= 2 : 1).
(±)-13i: Colorless oil; FT-IR (neat) 3307, 3028, 2956, 1738, 1666,
1605, 1566, 1497, 1455, 1150, 1058, 971, 851, 743 cm–1; 1H NMR
(300 MHz, CDCl3) δ 0.99 (d, J = 6.9 Hz, 3H), 1.02 (d, J = 6.9 Hz, 3H),
2.25 (brd, J = 5.5 Hz, 1H, –OH), 2.28 (s, 3H), 2.29–2.35 (m, 1H), 2.46
(s, 6H), 2.64 (dd, J = 8.6, 14.1 Hz, 1H), 2.78 (dd, J = 5.9, 14.1 Hz, 1H),
3.42–3.50 (m, 1H), 4.20–4.25 (m, 1H), 4.65 (brd, J = 7.6 Hz, 1H, –
NH), 5.40 (ddd, J = 1.3, 6.2, 15.5 Hz, 1H), 5.72 (ddd, J = 1.4, 6.5, 15.5
Hz, 1H), 6.83 (s, 2H), 6.90–6.93 (m, 2H), 7.09–7.13 (m, 3H); 13C NMR
(75 MHz, CDCl3) δ 20.9 (CH3), 22.2 (CH3 × 2), 23.0 (CH3 × 2), 30.9
(CH), 35.8 (CH2), 59.8 (CH), 73.4 (CH), 124.8 (CH), 126.3 (CH),
128.4 (CH × 2), 128.9 (CH × 2), 131.9 (CH × 2), 133.3 (C), 137.2 (C),
138.9 (C × 2), 141.5 (CH), 142.0 (C); HRMS (ESI-HRMS) m/z calcd
for C23H31NO3SK [M+K]+ 440.1662, found 440.1657.
(2R*,3R*)-2-phenylmethyl-3-[(1E)-1-propenyl]-1-[N-(2,4,6-
trimethylbenzenesulfonyl)]aziridine [(±)-8tg]
To a solution of amino alcohol (±)-13g (93.4 mg, 0.250 mmol, 1.00
eq.) and PPh3 (163 mg, 0.625 mmol, 2.50 eq.) in THF (2.5 mL) was
added a solution of diethyl azodicarboxylate in toluene (40%, 0.29 mL,
0.625 mmol, 2.50 eq.) dropwise over 5 min at 0 ˚C, and the mixture
was stirred for 5 h at 0 ˚C. The resulting mixture was concentrated in
vacuo. The residue was purified by silica gel column chromatography
(hexane : diethyl ether : triethylamine = 95 : 5 : 1) to give (±)-8tg (80.9
mg, 0.228 mmol, 91% yield). Colorless oil: FT-IR (neat) 3029, 2853,
1737, 1666, 1604, 1567, 1496, 1380, 1232, 1187, 1152, 1033, 920, 851,
(±)-14i: Colorless crystal mp 85–87 ˚C (recrystallized from hexane);
FT-IR (KBr) 3490, 3307, 3029, 2961, 2870, 1604, 1567, 1454, 1381,
1337, 1225, 1155, 1059, 971, 932, 852, 747, 702, 662, 575, 543, 475
cm–1; 1H NMR (300 MHz, CDCl3) δ 0.86 (d, J = 6.9 Hz, 3H), 0.88 (d, J
= 6.9 Hz, 3H), 1.70 (brd, J = 3.1 Hz, 1H, –OH), 2.06–2.18 (m, 1H),
2.27 (s, 3H), 2.59 (s, 6H), 2.74 (dd, J = 5.4, 13.4 Hz, 1H), 2.94 (dd, J =
8.3, 13.4 Hz, 1H), 3.34–3.43 (m, 1H), 3.98–4.01 (m, 1H), 4.90 (brd, J =
8.6 Hz, 1H, –NH), 5.23 (ddd, J = 1.4, 7.2, 15.5 Hz, 1H), 5.54 (ddd, J =
1.0, 6.5, 15.5 Hz, 1H), 6.88 (s, 2H), 7.04–7.07 (m, 2H), 7.13–7.22 (m,
3H); 13C NMR (75 MHz, CDCl3) δ 20.8 (CH3), 21.8 (CH3), 21.9 (CH3),
23.1 (CH3 × 2), 30.6 (CH), 59.3 (CH2), 72.0 (CH), 126.2 (CH), 126.4
(CH), 128.4 (CH × 2), 129.2 (CH × 2), 131.9 (CH × 2), 134.5 (C),
137.6 (C), 138.6 (C × 2), 141.4 (CH), 141.8 (C); HRMS (ESI-HRMS)
m/z calcd for C23H31NO3SK [M+K]+ 440.1662, found 440.1678.
1
807, 772, 746, 721 cm–1; H NMR (300 MHz, CDCl3) δ 1.75 (dd, J =
1.4, 6.5 Hz, 3H), 2.30 (s, 3H), 2.54 (s, 6H), 2.63 (dd, J = 7.2, 14.5 Hz,
1H), 2.96 (dd, J = 4.8, 14.5 Hz, 1H), 3.12 (ddd, J = 4.5, 4.8, 7.2 Hz,
1H), 3.17 (dd, J = 4.5, 8.9 Hz, 1H), 5.72 (ddq, J = 1.4, 8.9, 15.1 Hz,
1H), 5.95 (dq, J = 6.5, 15.1 Hz, 1H), 6.84 (s, 2H), 6.89–6.93 (m, 2H),
7.03–7.14 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 18.0 (CH3), 20.9
(CH3), 22.7 (CH3 × 2), 37.3 (CH2), 48.8 (CH), 50.8 (CH), 124.9 (CH),
126.2 (CH), 128.2 (CH × 2), 128.5 (CH × 2), 131.5 (CH × 2), 133.2
(CH), 134.4 (C), 137.2 (C), 139.6 (C × 2), 142.2 (C); HRMS (ESI-
HRMS) m/z calcd for C21H26NO2S [M+H]+ 356.1684, found 356.1703.
(2R*,3R*)-2-phenylmethyl-3-[(1E)-4-methyl-1-pentenyl]-1-[N-
(2,4,6-trimethylbenzenesulfonyl)]aziridine [(±)-8th]
(5E)(2R*,3S*)-2-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-4-
hydroxy-2,7-dimethyl-5-octene [(±)-13j] and (5E)(2R*,3R*)-2-[N-
(2,4,6-trimethylbenzenesulfonyl)amino]-4-hydroxy-2,7-dimethyl-5-
octene [(±)-14j]
Preparation of (±)-8th was carried out starting from amino alcohol (±)-
13h (100 mg, 0.241 mmol) as described for (±)-8tg from (±)-13g.
Purified by silica gel column chromatography (hexane : diethyl ether :
triethylamine = 95 : 5 : 1) to give (±)-8th (80.5 mg, 0.202 mmol, 84%
yield). Colorless oil; FT-IR (neat) 3029, 2954, 1662, 1604, 1565, 1494,
1454, 1382, 1322, 1320, 1186, 1155, 1054, 1031, 925, 850, 769, 746,
721, 684 cm–1; 1H NMR (400 MHz, CDCl3) δ 0.87 (d, J = 6.4 Hz, 3H),
0.89 (d, J = 6.4 Hz, 3H), 1.58–1.69 (m, 1H), 1.90–2.04 (m, 2H), 2.29
(s, 3H), 2.54 (s, 6H), 2.66 (dd, J = 6.8, 14.4 Hz, 1H), 2.99 (dd, J = 5.2,
14.4 Hz, 1H), 3.19–3.16 (m, 1H), 3.18 (dd, J = 4.0, 9.2 Hz, 1H), 5.68
(dd, J = 9.2, 15.2 Hz, 1H), 5.90 (dt, J = 7.2, 15.2 Hz, 1H), 6.84 (s, 2H),
6.89–6.95 (m, 2H), 7.02–7.14 (m, 3H); 13C NMR (100 MHz, CDCl3) δ
21.0 (CH3) 22.29 (CH3), 22.33 (CH3), 23.0 (CH3 × 2), 28.2 (CH), 37.3
(CH2), 41.7 (CH2), 48.9 (CH), 51.0 (CH), 124.7 (CH), 126.2 (CH),
128.2 (CH × 2), 128.5 (CH × 2), 131.5 (CH × 2), 134.4 (C), 137.2 (C),
137.3 (CH), 139.6 (C × 2), 142.2 (C); HRMS (ESI-HRMS) m/z calcd
for C24H31NO2NaS [M+Na]+ 420.1973, found 420.1948.
Preparation of (±)-13j and (±)-14j was carried out starting from (±)-12j
(600 mg, 1.71 mmol) as described for (±)-13g and (±)-14g from (±)-
12g. Purified by silica gel column chromatography (hexane : ethyl
acetate = 5:1) to give the mixture of diastereomers (588 mg, 1.66
mmol, 97% yield, (±)-13j : (±)-14j = 35 : 65). These diastereomers
were separated by flash column chromatography (hexane : diethyl ether
= 20 : 1).
(±)-13j: Colorless oil; FT-IR (neat) 3051, 3297, 2961, 2872, 1716,
1605, 1566, 1465, 1324, 1187, 1155, 1059, 972, 928, 851, 756, 719,
657 cm–1; 1H NMR (300 MHz, CDCl3) δ 0.79 (d, J = 6.9 Hz, 3H), 0.80
(d, J = 6.9 Hz, 3H), 0.99 (d, J = 6.9 Hz, 6H), 1.64–1.76 (m, 1H), 2.17
(brd, J = 6.5 Hz, 1H, –OH), 2.24–2.35 (m, 1H), 2.30 (s, 3H), 2.66 (s,
6H), 3.12 (ddd, J = 3.8, 6.2, 10.0 Hz, 1H), 4.11–4.19 (m, 1H), 4.63
(brd, J = 10.0, 1H, –NH), 5.36 (ddd, J = 1.4, 6.2, 15.5 Hz, 1H), 5.68
(ddd, J = 1.4, 6.6, 15.5 Hz, 1H), 6.95 (s, 2H); 13C NMR (75 MHz,

ACCEPTED MANUSCRIPT
8
Tetrahedron
Preparation of (±)-8ch was carried out starting from amino alcohol (±)-
14h (100 mg, 0.241 mmol) as described for (±)-8tg from (±)-13g.
Purified by silica gel column chromatography (hexane : diethyl ether :
triethylamine = 95 : 5 : 1) to give (±)-8ch (89.1 mg, 0.224 mmol, 93%
yield). Colorless oil; FT-IR (neat): 3027, 2954, 2869, 1604, 1565,
1496, 1454, 1405, 1382, 1322, 1232, 1186, 1155, 1056, 1033, 966, 933,
850, 786, 730, 700, 671 cm–1; 1H NMR (400 MHz, CDCl3) δ 0.86 (d, J
= 6.4 Hz, 6H), 1.58–1.69 (m, 1H), 1.19–2.03 (m, 2H), 2.29 (s, 3H),
2.58 (s, 6H), 2.68 (dd, J = 7.6, 14.4 Hz, 1H), 2.76 (dd, J = 5.6, 14.4 Hz,
1H), 3.03–3.10 (m, 1H), 3.44 (dd, J = 7.2, 7.2 Hz, 1H), 5.37 (ddt, J =
1.2, 7.2, 15.4 Hz, 1H), 5.89 (dt, J = 7.2, 15.4 Hz, 1H), 6.85 (s, 2H),
6.96–7.01 (m, 2H), 7.05 –7.14 (m, 3H); 13C NMR (100 MHz, CDCl3) δ
21.0 (CH3), 22.6 (CH3 × 2), 23.0 (CH3 × 2), 28.2 (CH), 33.5 (CH2),
41.8 (CH2), 43.8 (CH), 46.3 (CH), 122.7 (CH), 126.2 (CH), 128.3 (CH
× 2), 128.4 (CH × 2), 131.6 (CH × 2), 132.7 (C), 137.0 (CH), 137.6
(C), 139.8 (C × 2), 142.5 (C); HRMS (ESI-HRMS) m/z calcd for
C24H32NO2S [M+H]+ 398.2154, found 398.2128.
(2R*,3R*)-2-phenylmethyl-3-[(1E)-3-methyl-1-butenyl]-1-[N-(2,4,6-
trimethylbenzenesulfonyl)]aziridine [(±)-8ti]
Preparation of (±)-8ti was carried out starting from amino alcohol (±)-
13i (100 mg, 0.250 mmol) as described for (±)-8tg from (±)-13g.
Purified by silica gel column chromatography (hexane : diethyl ether :
triethylamine = 95 : 5 : 1) to give (±)-8ti (87.3 mg, 0.228 mmol, 91%
yield). Colorless oil; FT-IR (neat) 3029, 2959, 2869, 1604, 1467, 1496,
1455, 1382, 1323, 1229, 1187, 1154, 1056, 1033, 925, 851, 773, 748,
721, 688, 602 cm–1; 1H NMR (300 MHz, CDCl3) δ 0.98 (d, J = 6.9 Hz,
3H), 0.99 (d, J = 6.9 Hz, 3H), 2.26–2.40 (m, 1H), 2.29 (s, 3H), 2.54 (s,
6H), 2.64 (dd, J = 6.9, 14.1 Hz, 1H), 2.98 (dd, J = 4.1, 14.1 Hz, 1H),
3.10–3.16 (m, 2H), 5.64 (ddd, J = 1.4, 8.9, 15.5 Hz, 1H), 5.87 (dd, J =
6.5, 15.5 Hz, 1H), 6.83 (s, 2H), 6.90–6.94 (m, 2H), 7.03–7.13 (m, 3H);
13C NMR (75 MHz, CDCl3) δ 20.9 (CH3), 21.8 (CH3), 21.9 (CH3), 22.8
(CH3 × 2), 30.9 (CH), 37.3 (CH2), 48.7 (CH), 51.1 (CH), 120.9 (CH),
126.2 (CH), 128.2 (CH × 2), 128.5 (CH × 2), 131.5 (CH × 2), 134.5
(C), 137.2 (C), 139.5 (C × 2), 142.2 (C), 145.2 (CH); HRMS (ESI-
HRMS) m/z calcd for C23H30NO2S [M+H]+ 384.1997, found 384.2011.
(2R*,3S*)-2-phenylmethyl-3-[(1E)-3-methyl-1-butenyl]-1-[N-
(2,4,6-trimethylbenzenesulfonyl)]aziridine [(±)-8ci]
Preparation of (±)-8ci was carried out starting from amino alcohol (±)-
14i (100 mg, 0.250 mmol) as described for (±)-8tg from (±)-13g.
Purified by silica gel column chromatography (hexane : diethyl ether :
triethylamine = 95 : 5 : 1) to give (±)-8ci (95.1 mg, 0.248 mmol, 99%
yield). Colorless oil; FT-IR (neat) 3027, 2974, 1696, 1604, 1566, 1497,
1455, 1382, 1323, 1217, 1187, 1154, 1057, 969, 852, 752, 700, 658
cm–1; 1H NMR (300 MHz, CDCl3) δ 1.00 (d, J = 6.5 Hz, 6H), 2.29 (s,
3H), 2.28, (m, 1H), 2.57 (s, 6H), 2.64 (dd, J = 7.6, 14.5 Hz, 1H), 2.74
(dd, J = 5.5, 14.5 Hz, 1H), 3.04 (dt, J = 7.2, 5.5 Hz, 1H), 3.45 (t, J =
7.2 Hz, 1H), 5.31 (ddd, J = 1.4, 7.2, 15.5 Hz, 1H), 5.89 (ddd, J = 0.6,
6.5, 15.5 Hz, 1H), 6.84 (s, 2H), 6.94–6.98 (m, 2H), 7.04–7.11 (m, 3H);
13C NMR (75 MHz, CDCl3) δ 20.1 (CH3), 22.0 (CH3 × 2), 22.9 (CH3 ×
2), 31.1 (CH), 33.4 (CH2), 43.7 (CH), 46.4 (CH), 118.9 (CH), 126.2
(CH), 128.3 (CH × 2), 128.4 (CH × 2), 131.6 (CH × 2), 132.8 (C),
137.7 (C), 139.8 (C × 2), 142.6 (C), 145.1 (CH); HRMS (ESI-HRMS)
m/z calcd for C23H30NO2S [M+H]+ 384.1997, found 384.1996.
(2R*,3R*)-2-methylethyl-3-[(1E)-3-methyl-1-butenyl]-1-[N-(2,4,6-
trimethylbenzenesulfonyl)]aziridine [(±)-8tj]
Preparation of (±)-8tj was carried out starting from amino alcohol (±)-
13j (106 mg, 0.300 mmol) as described for (±)-8tg from (±)-13g.
Purified by silica gel column chromatography (hexane : diethyl ether :
triethylamine = 95 : 5 : 1) to give (±)-8tj (87.9 mg, 0.262 mmol, 87%
yield). Colorless oil; FT-IR (neat) 2962, 2868, 1605, 1470, 1382, 1312,
1232, 1188, 1156, 1054, 1032, 978, 945, 907, 849, 797, 719, 696, 659,
620 cm–1; 1H NMR (300 MHz, CDCl3) δ 0.71 (d, J = 6.9 Hz, 3H), 0.86
(d, J = 6.9 Hz, 3H), 0.99 (d, J = 6.9 Hz, 6H), 1.43–1.59 (m, 1H), 2.28–
2.40 (m, 1H), 2.29 (s, 3H), 2.70 (s, 6H), 2.77 (dd, J = 4.5, 7.2 Hz, 1H),
3.06 (dd, J = 4.5, 8.9 Hz, 1H), 5.71 (ddd, J = 1.0, 8.9, 15.5 Hz, 1H),
5.84 (dd, J = 6.2, 15.5 Hz, 1H), 6.92 (s, 2H); 13C NMR (75 MHz,
CDCl3) δ 19.1 (CH3), 19.3 (CH3), 21.0 (CH3), 21.8 (CH3), 21.9 (CH3),
23.0 (CH3 × 2), 30.1 (CH), 31.0 (CH), 51.1 (CH), 53.1 (CH), 121.2
(CH), 131.6 (CH × 2), 134.5 (C), 139.7 (C × 2), 142.3 (C), 145.1 (CH);
HRMS (ESI-HRMS) m/z calcd for C19H29NO2NaS [M+Na]+ 358.1817,
found 358.1789.
(2R*,3S*)-2-methylethyl-3-[(1E)-3-methyl-1-butenyl]-1-[N-(2,4,6-
trimethylbenzenesulfonyl)]aziridine [(±)-8cj]
Preparation of (±)-8cj was carried out starting from amino alcohol (±)-
14j (106 mg, 0.300 mmol) as described for (±)-8tg from (±)-13g.
Purified by silica gel column chromatography (hexane : diethyl ether :
triethylamine = 95 : 5 : 1) to give (±)-8cj (96.0 mg, 0.286 mmol, 95%
yield). Colorless oil; FT-IR (neat) 2960, 2871, 1604, 1567, 1468, 1384,
1323, 1237, 1187, 1156, 1057, 1007, 968, 944, 884, 842, 807, 747, 671,
583 cm–1; 1H NMR (300 MHz, CDCl3) δ 0.74 (d, J = 6.9 Hz, 3H), 0.86
(d, J = 6.9 Hz, 3H), 0.95 (d, J = 6.9 Hz, 6H), 1.34–1.51 (m, 1H), 2.22–
2.34 (m, 1H), 2.30 (s, 3H), 2.49 (dd, J = 7.6, 10.0 Hz, 1H), 2.70 (s,
6H), 3.38 (dd, J = 7.6, 7.6 Hz, 1H), 5.18 (ddd, J = 1.4, 7.6, 15.5 Hz,
1H), 5.81 (dd, J = 6.5, 15.5 Hz, 1H), 6.94 (s, 2H); 13C NMR (75 MHz,
CDCl3) δ 18.8 (CH3), 20.5 (CH3), 21.0 (CH3), 22.0 (CH3 × 2), 23.1
(CH3 × 2), 26.9 (CH), 31.0 (CH), 44.8 (CH), 51.3 (CH), 119.2 (CH),
131.6 (CH × 2), 133.0 (C), 139.9 (C × 2), 142.7 (C), 144.7 (CH);
HRMS (ESI-HRMS) m/z calcd for C19H29NO2NaS [M+Na]+ 358.1817,
found 358.1790.
(2R*,3S*)-2-phenylmethyl-3-[(1E)-1-propenyl]-1-[N-(2,4,6-
trimethylbenzenesulfonyl)]aziridine [(±)-8cg]
Preparation of (±)-8cg was carried out starting from amino alcohol (±)-
14g (93.4 mg, 0.250 mmol) as described for (±)-8tg from (±)-13g.
Purified by silica gel column chromatography (hexane : diethyl ether :
triethylamine = 95 : 5 : 1) to give (±)-8cg (87.1 mg, 0.245 mmol, 98%
yield). Colorless oil; FT-IR (neat) 3029, 2938, 1604, 1567, 1497, 1454,
1406, 1380, 1321, 1233, 1187, 1155, 1056, 1033, 963, 922, 875, 788,
729, 699, 669 cm–1; 1H NMR (300 MHz, CDCl3) δ 1.76 (dd, J = 1.7,
6.5 Hz, 3H), 2.29 (s, 3H), 2.57 (s, 6H), 2.63 (dd, J = 7.5, 14.5 Hz, 1H),
2.76 (dd, J = 5.5, 14.5 Hz, 1H), 3.03 (dt, J = 5.5, 7.5 Hz, 1H), 3.47 (t, J
= 7.5 Hz, 1H), 5.41 (ddq, J = 1.7, 7.5, 15.5 Hz, 1H), 5.96 (dq, J = 6.5,
15.5 Hz, 1H), 6.84 (s, 2H), 6.94–6.98 (m, 2H), 7.03–7.13 (m, 3H); 13
C
NMR (75 MHz, CDCl3) δ 18.0 (CH3), 20.9 (CH3), 22.8 (CH3 × 2), 33.4
(CH2), 43.4 (CH), 46.3 (CH), 123.0 (CH), 126.1 (CH), 128.26 (CH ×
2), 128.34 (CH × 2), 131.6 (CH × 2), 132.6 (C), 132.9 (CH), 137.6 (C),
(3E)(2R*,5R*)-5-[18-dicyano-1-(tert-butyldimethylsilyloxy)methyl]-
2-[N-(2,4,6-trimethylbenzenesulfonyl)amino]-1-phenyl-3-hexene
[(±)-15g]
139.8 (C
× 2), 142.5 (C); HRMS (ESI-HRMS) m/z calcd for
C21H26NO2S [M+H]+ 356.1684, found 356.1710.
(2R*,3S*)-2-phenylmethyl-3-[(1E)-4-methyl-1-pentenyl]-1-[N-
(2,4,6-trimethylbenzenesulfonyl)]aziridine [(±)-8ch]
To a solution of (dba)3Pd2•CHCl3 (15.5 mg, 0.0150 mmol, 0.100 eq.)
and 4 (14.6 mg, 0.0900 mmol, 0.600 eq.) in THF (1.0 mL) was added

ACCEPTED MANUSCRIPT
9
to a mixture of (±)-8tg (53.3 mg, 0.150 mmol, 1.00 eq.) and 3 (35.3 mg,
0.180 mmol, 1.20 eq.) in THF (1.0 mL), and the mixture was stirred for
1 h at room temperature. The resulting mixture was filtered through a
celite™ pad, and the residue was washed with ethyl acetate (5.0 mL).
The combined eluents were concentrated in vacuo. The residue was
purified by silica gel column chromatography (hexane : ethyl acetate =
19 : 1) to give (±)-15g (82.5 mg, 0.150 mmol, 99% yield). Colorless
oil; FT-IR (neat) 3308, 2933, 2860, 2242, 1739, 1605, 1455, 1327,
1259, 1156, 1057, 974, 844, 787, 750, 700, 658 cm–1; 1H NMR (300
MHz, CDCl3) δ 0.34 (s, 6H), 0.91 (s, 9H), 1.05 (d, J = 6.9 Hz, 3H),
2.29 (s, 3H), 2.49 (s, 6H), 2.61–2.70 (m, 1H), 2.78 (dd, J = 6.9, 13.5
Hz, 1H), 2.85 (dd, J = 6.6, 13.5 Hz, 1H), 3.97–4.06 (m, 1H), 4.46 (brd,
J = 6.9 Hz, 1H, –NH), 5.45 (ddd, J = 0.7, 7.2, 15.5 Hz, 1H), 5.62 (dd, J
= 6.3, 15.5 Hz, 1H), 6.89 (s, 2H), 7.05–7.08 (m, 2H), 7.20–7.25 (m,
3H); 13C NMR (75 MHz, CDCl3) δ –4.72 (CH3), –4.69 (CH3), 13.3
(CH3), 18.1 (C), 20.8 (CH3), 22.9 (CH3 × 2), 25.2 (CH3 × 3), 42.0
(CH2), 47.0 (CH), 56.1 (CH), 67.6 (C), 114.2 (CN), 114.5 (CN), 126.7
(CH), 127.0 (CH), 128.7 (CH × 2), 129.3 (CH × 2), 131.9 (CH × 2),
134.1 (CH), 135.78 (C), 135.82 (C), 138.9 (C × 2), 142.1 (C); HRMS
(ESI-HRMS) m/z calcd for C30H41N3O3NaSSi [M+Na]+ 574.2536,
found 574.2536.
13C NMR (75 MHz, CDCl3) δ –4.7 (CH3), –4.6 (CH3), 17.3 (CH3), 18.1
(C), 20.9 (CH3), 22.2 (CH3), 23.1 (CH3 × 2), 25.2 (CH3 × 3), 27.7 (CH),
42.3 (CH2), 55.7 (CH), 58.2 (CH), 66.8 (C), 114.8 (CN), 115.3 (CN),
122.7 (CH), 126.9 (CH), 128.7 (CH × 2), 129.3 (CH × 2), 132.1 (CH ×
2), 133.9 (C), 136.1 (C), 138.6 (CH), 138.9 (C × 2), 142.1 (C); HRMS
(ESI-HRMS) m/z calcd for C32H45N3O3NaSSi [M+Na]+ 602.2849,
found 602.2869.
(4E)(3R*,6R*)-6-[1,1-dicyano-1-(tert-
butyldimethylsilyloxy)methyl]-2,7-dimethyl-3-[N-(2,4,6-
trimethylbenzenesulfonyl)amino]-4-octene [(±)-15j]
Synthesis of (±)-15j was carried out starting from aziridine (±)-8tj
(67.0 mg, 0.200 mmol) as described for (±)-15g. Purified by silica gel
column chromatography (hexane : ethyl acetate = 30 : 1) to give (±)-
15j (104 mg, 0.197 mmol, 98% yield). Colorless oil; FT-IR (neat)
3307, 2961, 2240, 1605, 1567, 1471, 1330, 1260, 1152, 976, 891, 844,
787, 659 cm–1; 1H NMR (300 MHz, CDCl3) δ 0.35 (s, 3H), 0.37 (s,
3H), 0.80 (d, J = 6.9 Hz, 3H), 0.82 (d, J = 6.9 Hz, 3H), 0.87 (d, J = 6.9
Hz, 6H), 0.93 (s, 9H), 1.83–1.94 (m, 1H), 2.15–2.26 (m, 1H), 2.28 (s,
3H), 2.44 (dd, J = 3.4, 10.0 Hz, 1H), 2.65 (s, 6H), 3.81–3.87 (m, 1H),
4.48 (brd, J = 8.6 Hz, 1H, –NH), 5.43 (ddd, J = 1.7, 10.0, 15.1 Hz, 1H),
5.70 (dd, J = 4.8, 15.1 Hz, 1H), 6.94 (s, 2H); 13C NMR (75 MHz,
CDCl3) δ –4.7 (CH3), –4.6 (CH3), 17.2 (CH3), 17.9 (CH3), 18.0 (CH3),
18.1 (C), 20.8 (CH3), 22.2 (CH3), 23.2 (CH3 × 2), 25.2 (CH3 × 3), 27.6
(CH), 32.8 (CH), 58.4 (CH), 59.6 (CH), 66.9 (C), 114.8 (CN), 115.3
(CN), 122.4 (CH), 132.1 (CH × 2), 134.9 (C), 137.9 (CH), 138.5 (C ×
2), 141.9 (C); HRMS (ESI-HRMS) m/z calcd for C28H45N3O3NaSSi
[M+Na]+ 554.2849, found 554.2845.
(3E)(2R*,5R*)-5-[1,1-dicyano-1-(tert-
butyldimethylsilyloxy)methyl]-7-methyl-2-[N-(2,4,6-
trimethylbenzenesulfonyl)amino]-1-phenyl-3-octene [(±)-15h]
Synthesis of (±)-15h was carried out starting from aziridine (±)-8th
(50.0 mg, 0.126 mmol) as described for (±)-15g. Purified by silica gel
column chromatography (hexane : ethyl acetate = 19 : 1) to give (±)-
15h (71.6 mg, 0.123 mmol, 98% yield). Colorless oil; FT-IR (neat)
3305, 3027, 2956, 2933, 2861, 2240, 1604, 1565, 1496, 1469, 1365,
1328, 1261, 1186, 1155, 1056, 971, 937, 904, 844, 786, 748, 700, 657
cm–1; 1H NMR (400 MHz, CDCl3) δ 0.33 (s, 3H), 0.34 (s, 3H), 0.73 (d,
J = 6.4 Hz, H), 0.83 (d, J = 6.8 Hz), 0.91 (s, 9H), 1.10–1.44 (m, 3H),
2.29 (s, 3H), 2.53 (s, 6H), 2.46–2.58 (m, 1H), 2.81 (dd, J = 7.8, 13.7
Hz, 1H), 2.90 (dd, J = 6.4, 13.7 Hz, 1H), 3.96–4.05 (m, 1H), 4.52 (brd,
J = 6.8 Hz, 1H, –NH), 5.24 (ddd, J = 0.8, 9.2, 15.3 Hz, 1H), 5.71 (dd, J
= 5.8, 15.3 Hz, 1H), 6.09 (s, 2H), 7.01–7.07 (m, 2H), 7.17–7.28 (m,
3H); 13C NMR (100 MHz, CDCl3) δ –4.45 (CH3), –4.52 (CH3), 18.2
(C), 20.8 (CH3), 21.0 (CH3), 23.1 (CH3 × 2), 23.9 (CH3), 24.7 (CH),
25.3 (CH3 × 3), 36.9 (CH2), 42.3 (CH2), 51.4 (CH), 55.9 (CH), 67.5
(C), 114.2 (CN), 114.8 (CN), 126.1 (CH), 126.8 (CH), 128.6 (CH × 2),
129.2 (CH × 2), 132.0 (CH × 2), 133.8 (C), 136.0 (C), 137.3 (CH),
(3E)(2R*,5S*)-5-[1,1-dicyano-1-(tert-
butyldimethylsilyloxy)methyl]-2-[N-(2,4,6-
trimethylbenzenesulfonyl)amino]-1-phenyl-3-hexene [(±)-16g]
Synthesis of (±)-16g was carried out starting from (±)-8cg (53.3 mg,
0.150 mmol) as described for (±)-15g. Purified by silica gel column
chromatography (hexane : ethyl acetate = 19 : 1) to give (±)-16g (82.3
mg, 0.149 mmol, 99% yield). Colorless crystal mp 108–110 ˚C
(recrystallized from hexane); FT-IR (KBr) 3302, 3034, 2932, 2860,
2241, 1604, 1497, 1455, 1407, 1318, 1148, 1045, 981, 848, 788, 739,
1
694, 661, 600, 536, 518 cm–1; H NMR (300 MHz, CDCl3) δ 0.33 (s,
3H), 0.34 (s, 3H), 0.91 (s, 9H), 1.15 (d, J = 6.9 Hz, 3H), 2.29 (s, 3H),
2.44 (s, 6H), 2.56–2.67 (m, 1H), 2.76 (dd, J = 7.6, 13.8 Hz, 1H), 2.89
(dd, J = 5.9, 13.8 Hz, 1H), 3.88–3.98 (m, 1H), 4.33 (brd, J = 6.0 Hz,
1H, –NH), 5.34 (ddd, J = 1.0, 8.6, 15.3 Hz, 1H), 5.65 (dd, J = 7.6, 15.3
Hz, 1H), 6.88 (s, 2H), 7.07–7.10 (m, 2H), 7.25–7.27 (m, 3H); 13C NMR
(75 MHz, CDCl3) δ –4.8 (CH3), –4.7 (CH3), 14.1 (CH3), 18.0 (C), 20.9
(CH3), 22.8 (CH3 × 2), 25.1 (CH3 × 3), 42.0 (CH2), 47.9 (CH), 56.0
(CH), 67.6 (C), 114.2 (CN), 114.6 (CN), 126.9 (CH), 127.1 (CH),
128.8 (CH × 2), 129.3 (CH × 2), 131.9 (CH × 2), 133.8 (C), 135.5 (C),
136.7 (CH), 138.9 (C × 2), 142.1 (C); HRMS (ESI-HRMS) m/z calcd
for C30H41N3O3NaSSi [M+Na]+ 574.2536, found 574.2538.
138.8 (C
× 2), 142.1 (C); HRMS (ESI-HRMS) m/z calcd for
C33H47N3NaO3SSi [M+Na]+ 616.3005, found 616.3024.
(3E)(2R*,5R*)-5-[1,1-dicyano-1-(tert-
butyldimethylsilyloxy)methyl]-6-methyl-2-[N-(2,4,6-
trimethylbenzenesulfonyl)amino]-1-phenyl-3-heptene [(±)-15i]
Synthesis of (±)-15i was carried out starting from aziridine (±)-8ti (57.5
mg, 0.150 mmol) as described for (±)-15g. Purified by silica gel
column chromatography (hexane : ethyl acetate = 19 : 1) to give (±)-
15i (86.8 mg, 0.150 mmol, 99% yield). Colorless crystal mp 122–124
˚C (recrystallized from hexane); FT-IR (KBr) 3291, 3027, 2958, 2859,
2240, 1305, 1471, 1454, 1414, 1320, 1263, 1188, 1162, 1121, 1057,
(3E)(2R*,5S*)-5-[1,1-dicyano-1-(tert-
butyldimethylsilyloxy)methyl]-7-methyl-2-[N-(2,4,6-
trimethylbenzenesulfonyl)amino]-1-phenyl-3-octene [(±)-16h]
Synthesis of (±)-16h was carried out starting from (±)-8ch (50.0 mg,
0.126 mmol) as described for (±)-15g. Purified by silica gel column
chromatography (hexane : ethyl acetate = 14 : 1) to give (±)-16h (72.3
mg, 0.125 mmol, 99% yield). Colorless oil; FT-IR (neat) 3291, 3029,
2956, 2861, 2240, 1604, 1565, 1496, 1469, 1328, 1261, 1155, 1058,
970, 939, 904, 844, 786, 748, 700, 657 cm–1; 1H NMR (400 MHz,
CDCl3) δ 0.33 (s, 3H), 0.34 (s, 3H), 0.81 (d, J = 5.6 Hz, 3H), 0.88–0.98
1
975, 845, 793, 784, 696, 655, 593, 539, 501, 475 cm–1; H NMR (300
MHz, CDCl3) δ 0.357 (s, 3H), 0.362 (s, 3H), 0.78 (d, J = 6.9 Hz, 3H),
0.81 (d, J = 6.9 Hz, 3H), 0.92 (s, 9H), 2.15–2.25 (m, 1H), 2.28 (s, 3H),
2.40 (dd, J = 3.4, 10.0 Hz, 1H), 2.54 (s, 6H), 2.81 (dd, J = 7.5, 13.7 Hz,
1H), 2.89 (dd, J = 6.8, 13.7 Hz, 1H), 4.01–4.11 (m, 1H), 4.47 (brd, J =
7.2 Hz, 1H, –NH), 5.49 (ddd, J = 1.4, 10.0, 15.3 Hz, 1H), 5.73 (dd, J =
5.2, 15.3 Hz, 1H), 6.89 (s, 2H), 7.03–7.06 (m, 2H), 7.18–7.24 (m, 3H);

ACCEPTED MANUSCRIPT
10
Tetrahedron
(m, 12H), 1.21–1.52 (m, 3H), 2.29 (s, 3H), 2.44 (s, 6H), 2.52–2.61 (m,
1H), 2.79 (dd, J = 7.0, 13.8 Hz, 1H), 2.92 (dd, J = 5.8, 13.8 Hz, 1H),
3.90–3.99 (m, 1H), 4.46 (brd, J = 6.4 Hz, 1H, –NH), 5.25 (dd, J = 9.6,
15.6 Hz, 1H), 5.78 (dd, J = 6.8, 15.6 Hz, 1H), 6.88 (s, 2H), 7.02–7.09
(m, 2H), 7.19–7.27 (m, 3H); 13C NMR (100 MHz, CDCl3) δ –4.6
(CH3), –4.5 (CH3), 18.2 (C), 20.9 (CH3), 21.0 (CH3), 22.9 (CH3 × 2),
23.9 (CH3), 24.8 (CH), 25.3 (CH3 × 3), 37.4 (CH2), 42.1 (CH2), 51.7
(CH), 55.7 (CH), 67.5 (C), 114.3 (CN), 114.7 (CN), 125.8 (CH), 127.1
(CH), 128.7 (CH × 2), 129.3 (CH × 2), 131.9 (CH × 2), 133.4 (C),
135.5 (C), 138.6 (CH), 138.9 (C × 2), 142.1 (C); HRMS (ESI-HRMS)
m/z calcd for C33H47N3NaO3SSi [M+Na]+ 616.3005, found 616.3027.
142.0 (C); HRMS (ESI-HRMS) m/z calcd for C28H45N3O3NaSSi
[M+Na]+ 554.2849, found 554.2840.
(±)-17j: Colorless oil; FT-IR (neat) 3272, 2959, 2218, 1698, 1605,
1471, 1361, 1256, 1158, 1088, 1013, 836, 772, 666 cm–1; 1H NMR
(300 MHz, CDCl3) δ 0.39 (s, 3H), 0.41 (s, 3H), 0.66 (d, J = 6.9 Hz,
3H), 0.79 (d, J = 6.9 Hz, 3H), 0.95 (s, 9H), 1.03 (d, J = 6.5 Hz, 6H),
1.76–1.87 (m, 1H), 2.29 (s, 3H), 2.38 (dq, J = 1.4, 6.9 Hz, 1H), 2.64 (s,
6H), 2.70 (dd, J = 3.8, 10.0 Hz, 1H), 3.82 (dt, J = 3.8, 10.0 Hz, 1H),
4.46 (brd, J = 10.0 Hz, 1H, –NH), 5.38 (ddd, J = 1.4, 10.0, 15.1 Hz,
1H), 5.81 (dd, J = 6.9, 15.1 Hz, 1H), 6.93 (s, 2H); 13C NMR (75 MHz,
CDCl3) δ –4.5 (CH3 × 2), 17.5 (CH3), 18.1 (C), 19.0 (CH3), 20.9 (CH3),
21.8 (CH3), 21.9 (CH3), 23.2 (CH3 × 2), 25.3 (CH3 × 3), 31.6 (CH),
32.9 (CH), 54.8 (CH), 56.8 (CH), 66.9 (C), 114.0 (CN), 115.0 (CN),
118.3 (CH), 132.0 (CH × 2), 136.0 (C), 138.1 (C), 141.9 (C), 149.3
(CH); HRMS (ESI-HRMS) m/z calcd for C28H45N3O3NaSSi [M+Na]+
554.2849, found 554.2858.
(3E)(2R*,5R*)-5-[1,1-dicyano-1-(tert-
butyldimethylsilyloxy)methyl]-6-methyl-2-[N-(2,4,6-
trimethylbenzenesulfonyl)amino]-1-phenyl-3-heptene [(±)-16i]
Synthesis of (±)-16i was carried out starting from (±)-8ci (57.5 mg,
0.150 mmol) as described for (±)-15g. Purified by silica gel column
chromatography (hexane : ethyl acetate = 14 : 1) to give (±)-16i (85.2
mg, 0.147 mmol, 98% yield). Colorless crystal mp 131–133 ˚C
(recrystallized from hexane); FT-IR (KBr) 3276, 3030, 2959, 2860,
2241, 1604, 1496, 1455, 1417, 1131, 1263, 1187, 1115, 1054, 983, 949,
886, 744, 698, 649, 588, 509 cm–1; 1H NMR (300 MHz, CDCl3) δ 0.34
(s, 3H), 0.36 (s, 3H), 0.89 (d, J = 7.2 Hz, 3H), 0.92 (s, 9H), 0.92 (d, J =
7.2 Hz, 3H), 2.20–2.31 (m, 1H), 2.29 (s, 3H), 2.40–2.44 (m, 1H), 2.44
(s, 6H), 2.78 (dd, J = 7.6, 13.8 Hz, 1H), 2.93 (dd, J = 5.5, 13.8 Hz, 1H),
3.92–4.01 (m, 1H), 4.44 (brd, J = 6.5 Hz, 1H, –NH), 5.47 (ddd, J = 0.7,
10.0, 15.5 Hz, 1H), 5.75 (dd, J = 7.2, 15.5 Hz, 1H), 6.87 (s, 2H), 7.02–
7.08 (m, 2H), 7.20–7.25 (m, 3H); 13C NMR (75 MHz, CDCl3) δ –4.7
(CH3), –4.6 (CH3), 17.4 (CH3), 18.1 (C), 20.9 (CH3), 22.4 (CH3), 22.9
(CH3 × 2), 25.2 (CH3 × 3), 27.8 (CH), 42.1 (CH2), 55.9 (CH), 58.3
(CH), 66.9 (C), 114.8 (CN), 115.2 (CN), 122.7 (CH), 127.1 (CH),
128.8 (CH × 2), 129.4 (CH × 2), 132.0 (CH × 2), 133.5 (C), 135.5 (C),
139.0 (C × 2), 139.9 (CH), 142.1 (C); HRMS (ESI-HRMS) m/z calcd
for C32H45N3O3NaSSi [M+Na]+ 602.2849, found 602.2867.
Methyl
(3E)(2R*,5R*)-2-methyl-5-[N-(2,4,6-
trimethylbenzenesulfonyl)amino]-6-phenyl-3- hexenoate [(±)-18g]
To a solution of (±)-15g (20 mg, 0.036 mmol, 1.0 eq.) in methanol
(0.50 mL) was added a solution of TASF (12 mg, 0.044 mmol, 1.2 eq.)
in methanol (0.50 mL) dropwise over 5 min at 0˚C, and the mixture
was stirred at 0˚C for 30 min. The resulting mixture was quenched with
phosphate buffer (pH 7.0, 5.0 mL) at 0˚C, and the aqueous phase was
extracted with diethyl ether (10 mL × 3). The combined organic layers
were washed with brine (10 mL), dried over sodium sulfate,
concentrated in vacuo. The residue was purified by silica gel column
chromatography (hexane : ethyl acetate = 5 : 1) to give (±)-18g (15 mg,
0.36 mmol, 99% yield). Colorless oil; FT-IR (neat) 3300, 2939, 1732,
1605, 1497, 1455, 1324, 1155, 1057, 967, 852, 749, 701, 659 cm–1; 1H
NMR (300 MHz, CDCl3) δ 1.03 (d, J = 7.2 Hz, 3H), 2.29 (s, 3H), 2.49
(s, 6H), 2.78 (d, J = 6.9 Hz, 2H), 2.86–2.96 (m, 1H), 3.64 (s, 3H),
3.88–3.98 (m, 1H), 4.44 (brd, J = 6.5 Hz, 1H, –NH), 5.27 (dd, J = 7.2,
15.5 Hz, 1H), 5.46 (dd, J = 7.2, 15.5 Hz, 1H), 6.87 (s, 2H), 7.04 (dd, J
= 2.1, 7.6 Hz, 2H), 7.20–7.24 (m, 3H); 13C NMR (75 MHz, CDCl3) δ
16.6 (CH3), 20.9 (CH3), 22.8 (CH3 × 2), 41.9 (CH), 42.1 (CH2), 51.8
(CH), 56.3 (CH), 126.8 (CH), 128.5 (CH × 2), 129.4 (CH × 2), 130.4
(CH), 130.9 (CH), 131.8 (CH × 2), 134.3 (C), 136.2 (C), 138.9 (C × 2),
142.0 (C), 174.4 (C=O); HRMS (ESI-HRMS) m/z calcd for
C23H29NO4NaS [M+Na]+ 438.1715, found 438.1702.
(4E)(3R*,6S*)-
6-[1,1-dicyano-1-(tert-
butyldimethylsilyloxy)methyl]-2,7-dimethyl-3-[N-(2,4,6-
trimethylbenzenesulfonyl)amino]-4-octene [(±)-16j] and (5E)-4-
[1,1-dicyano-1-(tert-butyldimethylsilyloxy)methyl]-2,7-dimethyl-3-
[N-(2,4,6-trimethylbenzenesulfonyl)amino]-5-octene [(±)-17j]
Synthesis of (±)-16j was carried out starting from aziridine (±)-8cj (503
mg, 1.50 mmol) as described for (±)-15g. The corresponding regio-
isomer (±)-17j was also obtained. Purified by silica gel column
chromatography (hexane : ethyl acetate = 30 : 1) to give the mixture of
regio-isomers (726 mg, 1.37 mmol, 91% yield, (±)-16j : (±)-17j = 58 :
42). These isomers were separated flash column chromatography
(hexane : ethyl acetate = 30 : 1).
Methyl
(3E)(2R*,5R*)-2-(2-methylpropyl)-5-[N-(2,4,6-
trimethylbenzenesulfonyl)amino]-6-phenyl-3- hexenoate [(±)-18h]
Synthesis of (±)-18h was carried out starting from (±)-15h (20 mg,
0.034 mmol) as described for (±)-18g. Purified by silica gel column
chromatography (hexane : ethyl acetate = 5 : 1) to give (±)-18h (14 mg,
0.030 mmol, 90% yield). Colorless crystal: mp 76–77˚C (recrystallized
from hexane); FT-IR (neat) 3288, 3025, 2952, 1936, 1735, 1604, 1567,
1494, 1455, 1367, 1317, 1259, 1230, 1147, 1108, 1060, 979, 935, 848,
813, 744 cm–1; 1H NMR (400 MHz, CDCl3) δ 0.77 (d, J = 6.8 Hz, 3H),
0.80 (d, J = 6.8 Hz, 3H), 1.07–1.17 (m, 1H), 1.19–1.30 (m, 1H), 1.35–
1.45 (m, 1H), 2.29 (s, 3H), 2.49 (s, 6H), 2.76 (dd, J = 7.2, 13.6 Hz,
1H), 2.82 (dd, J = 6.4, 13.6 Hz, 1H), 2.84–2.92 (m, 1H), 3.88–3.97 (m,
1H), 4.49 (brd, J = 6.4 Hz, 1H, –NH), 5.26–5.36 (m, 2H,), 6.87 (s, 2H),
7.00–7.06 (m, 2H), 7.17–7.28 (m, 3H); 13C NMR (100 MHz, CDCl3) δ
21.0 (CH3), 22.0 (CH3), 22.6 (CH3), 22.9 (CH3 × 2), 25.4 (CH), 41.0
(CH2), 42.3 (CH2), 46.6 (CH), 51.7 (CH), 56.3 (CH), 126.8 (CH), 128.5
(CH × 2), 129.3 (CH × 2), 130.1 (CH), 131.3 (CH), 131.8 (CH × 2),
134.1 (C), 136.1 (C), 138.8 (C × 2), 141.9 (C), 174.1 (C); HRMS (ESI-
HRMS) m/z calcd for C26H35NNaO4S [M+Na]+ 480.2185, found
480.2164.
(±)-16j: Colorless crystal mp 118–119 ˚C (recrystallized from hexane);
FT-IR (KBr) 3275, 2958, 2935, 2860, 2239, 1604, 1565, 1471, 1326,
1268, 1220, 1165, 1053, 991, 954, 909, 846, 789, 722, 660, 581, 538
cm–1; 1H NMR (300 MHz, CDCl3) δ 0.34 (s, 3H), 0.36 (s, 3H), 0.80 (d,
J = 6.9 Hz, 3H), 0.88 (d, J = 6.9 Hz, 6H), 0.89 (d, J = 6.9 Hz, 3H), 0.91
(s, 9H), 1.75–1.86 (m, 1H), 2.18–2.29 (m, 1H), 2.28 (s, 3H), 2.37 (dd, J
= 3.4, 9.6 Hz, 1H), 2.64 (s, 6H), 3.60 (ddd, J = 5.2, 7.9, 7.9 Hz, 1H),
4.48 (brd, J = 7.9 Hz, 1H, –NH), 5.38 (dd, J = 9.6, 15.1 Hz, 1H), 5.59
(dd, J = 7.9, 15.1 Hz, 1H), 6.93 (s, 2H); 13C NMR (75 MHz, CDCl3) δ
–4.7 (CH3), –4.6 (CH3), 17.3 (CH3), 18.0 (CH3), 18.1 (C), 18.4 (CH3),
20.9 (CH3), 22.3 (CH3), 23.1 (CH3 × 2), 25.2 (CH3 × 3), 27.8 (CH),
33.3 (CH), 58.4 (CH), 61.0 (CH), 67.0 (C), 114.9 (CN), 115.2 (CN),
123.7 (CH), 132.1 (CH × 2), 134.6 (C), 137.9 (CH), 138.7 (C × 2),

ACCEPTED MANUSCRIPT
11
3.
4.
Tsuji, J.; Kataoka, H.; Kobayashi, Y. Tetrahedron Lett. 1981,
22, 2575–2578.
Methyl
(3E)(2S*,5R*)-2-methyl-5-[N-(2,4,6-
trimethylbenzenesulfonyl)amino]-6-phenyl-3- hexenoate [(±)-19g]
(a) Takahashi, T.; Ootake, A.; Tsuji, J.; Tachibana, K.
Tetrahedron 1985, 41, 5747–5754. (b) Takahashi, T.;
Miyazawa, M.; Ueno, H.; Tsuji, J. Tetrahedron Lett. 1986, 27,
3881–3884.
Preparation of 3. (a) Nemoto, H.; Kubota, Y.; Yamamoto, Y. J.
Org. Chem. 1990, 45, 4515–4516. (b) Nemoto, H.; Li, X.; Ma,
R.; Suzuki, I.; Shibuya, M. Tetrahedron Lett. 2003, 44, 73–75.
(c) Nemoto, H. Protected Dicyanomethanol (H-MAC-R).
Electronic Encyclopedia of Reagents for Organic Synthesis (e-
EROS) 2007.
(http://onlinelibrary.wiley.com/o/eros/articles/rn00761/frame.ht
ml)
H–MAC–Ac has been commercially available from Sigma-
Aldrich since 2013.
Nemoto, H.; Ibaragi, T.; Bando, M.; Kido, M.; Shibuya, M.
Tetrahedron Lett. 1999, 40, 1319–1322.
Synthesis of (±)-19g was carried out starting from (±)-16g (20 mg,
0.036 mmol, 1.0 eq.) as described for (±)-18g. Purified by silica gel
column chromatography (hexane : ethyl acetate = 5 : 1) to give (±)-19g
(15 mg, 0.36 mmol, 99% yield). Colorless crystal: mp 70–72 ˚C
(recrystallized from hexane); FT-IR (neat) 3289, 2977, 2949, 1731,
1496, 1456, 1377, 1319, 1273, 1244, 1190, 1148, 1049, 977, 939, 852,
751, 696, 663, 597, 538, 518, 474 cm–1; 1H NMR (300 MHz, CDCl3) δ
1.05 (d, J = 7.2 Hz, 3H), 2.28 (s, 3H), 2.48 (s, 6H), 2.65–2.93 (m, 2H),
2.92 (dq, J = 7.2, 7.2 Hz, 1H), 3.62 (s, 3H), 3.87–3.96 (m, 1H), 4.45
(brd, J = 6.3 Hz, 1H, –NH), 5.29 (ddd, J = 0.7, 7.2, 15.5 Hz, 1H), 5.41
(dd, J = 7.2, 15.5 Hz, 1H), 6.86 (s, 2H), 7.02–7.06 (m, 2H), 7.17–7.26
(m, 3H); 13C NMR (75 MHz, CDCl3) δ 16.6 (CH3), 20.9 (CH3), 22.9
(CH3 × 2), 42.16 (CH), 42.22 (CH2), 51.8 (CH3), 56.3 (CH), 126.9
(CH), 128.6 (CH × 2), 129.5 (CH × 2), 130.8 (CH), 131.0 (CH), 131.9
(CH × 2), 134.2 (C), 136.1 (C), 138.9 (C × 2), 142.0 (C), 174.4 (C=O);
HRMS (ESI-HRMS) m/z calcd for C23H29NO4NaS [M+Na]+ 438.1715,
found 438.1706.
5.
6.
7.
When a non-strained (not highly reactive) leaving group such
as an alkoxycarbonyl was used, 4 was not effective because the
nucleophilicity of a Pd-phosphite complex is generally weaker
than that of a phosphine complex. However, 4-methyl-3,5,8-
trioxa-1-phosphabicyclo[2.2.2]octane (A), a tricyclic phosphine
ligand, was effective. Takahashi, T.; Jinbo, Y.; Kitamura, K.;
Tsuji, J. Tetrahedron Lett. 1984, 25, 5921–5924.
Methyl
(3E)(2S*,5R*)-2-(2-methylpropyl)-5-[N-(2,4,6-
trimethylbenzenesulfonyl)amino]-6-phenyl-3- hexenoate [(±)-19h]
Synthesis of (±)-19h was carried out starting from (±)-16h (20 mg,
0.034 mmol) as described for (±)-18g. Purified by silica gel column
chromatography (hexane : ethyl acetate = 5 : 1) to give (±)-19h (15 mg,
0.032 mmol, 96% yield). Colorless crystal: mp 105–106 ˚C
(recrystallized from hexane); FT-IR (neat) 3297, 2956, 1951, 1733,
1668, 1602, 1558, 1540, 1494, 1455, 1322, 1243, 1151, 1058, 981, 927,
848, 754 cm–1; 1H NMR (400 MHz, CDCl3) δ 0.81 (d, J = 7.0 Hz, 3H),
0.83 (d, J = 7.0 Hz, 3H), 1.09–1.18 (m, 1H), 1.30–1.42 (m, 1H), 1.43–
1.52 (m, 1H), 2.28 (s, 3H), 2.49 (s, 6H), 2.80 (d, J = 6.4 Hz, 1H), 2.89
(dd, J = 7.6, 15.6 Hz, 1H), 3.85–3.95 (m, 1H), 4.47 (brd, J = 6.4 Hz,
1H, –NH), 5.28 (dd, J = 8.0, 15.6 Hz, 1H), 5.34 (dd, J = 6.8, 15.6 Hz,
1H) 6.88 (s, 2H), 6.99–7.07 (m, 2H), 7.17–7.26 (m, 3H); 13C NMR
(100 MHz, CDCl3) δ 21.0 (CH3), 22.3 (CH3), 22.4 (CH3), 23.0 (CH3 ×
2), 25.5 (CH), 41.1 (CH2), 42.3 (CH2), 46.8 (CH), 51.7 (CH), 56.2
(CH), 126.8 (CH), 128.5 (CH × 2), 129.4 (CH × 2), 130.2 (CH), 131.5
(CH), 131.8 (CH × 2), 134.1 (C), 136.0 (C), 138.8 (C × 2), 141.9 (C),
174.1 (C=O); HRMS (ESI-HRMS) m/z calcd for C26H35NNaO4S
[M+Na]+ 480.2185, found 480.2163.
A
8.
Cone angle for ligands: Bunten, K. A.; Chen, L.; Fernandez, A.
L.; Poë A. J. Coord. Chem. Rev. 2002, 233–234, 41–51.
Satake, A.; Shimizu, I.; Yamamoto, A. Synlett 1995, 64–68.
Ohno, H.; Mimura, N.; Otaka, A.; Tamamura, H.; Fujii, N.;
Ibuka, T. Tetrahedron 1997, 53, 12933–12946.
Sweeney et al mainly reported the reaction of vinylaziridines
with copper reagents. Thus, the detail of the palladium-
catalyzed reaction such as mol% of
tetrakis(triphenylphosphine)palladium, temperature, or
equivalents of diethyl malonate were not specified. Cantrill, A.
A.; Jarvis, N. A.; Osborn, I. M.; Ouadi, A.; Sweeney, B. J.
Synlett 1996, 847.
Synthetic application of a MAC reagent with palladium catalyst
in high γ-selectivity according to reference 5 was reported.
They mentioned that the unmasking step from the MAC moiety
to carbonyl functionality proceeded in greater yield under
milder conditions than the step for the acidic hydrolysis of the
cyanide group. (a) Yamatsugu, K.; Yin, L.; Kamijo, S.;
Kimura, Y.; Kanai, M.; Shibasaki, M. Angew. Chem. 2008, 48,
1070–1076. (b) Yamatsugu, M.; Kanai, M.; Shibasaki, M.
Tetrahedron 2009, 65, 6017–6024.
Active methylene and methyne compounds bearing a cyano
group as an electron withdrawing group are known to be very
palladium-affinitive nucleophiles. (a) Naota, T.; Taki, H.;
Mizuno, M.; Murahashi, S.-I. J. Am. Chem. Soc. 1989, 111,
5954–5955. (b) Nemoto, H.; Kubota, Y.; Yamamoto, Y. J.
Chem. Soc., Chem. Commun. 1994, 1665–1666. (c) Kadota, I.;
Shibuya, A.; Gyoung, Y. S.; Yamamoto, Y. J. Am. Chem. Soc.
1998, 120, 10262–10263. (d) Patil, N. T.; Kadota, I.; Shibuya,
A.; Gyoung Y. S.; Yamamoto, Y. Adv. Synth. Catal. 2004, 346,
800–804.
9.
10.
11.
12.
Acknowledgement
This work was partly supported by a Grant-in-Aid for
Scientific Research of the Ministry of Education of Japan
(Grant No. 18550094 in 2006-2007).
13.
References and notes
1.
(a) Tsuji, J. “Palladium Reagents and Catalysts”, John Wiley
& Sons, New York, 1995. (b) Tsuji, J. “Perspectives in
Organopalladium Chemistry for the 21st Century”, Elsevier,
New York, 1999. (c) Tsuji, J. “Palladium Reagents and
Catalysts: New Perspectives for 21st Century”, John Wiley &
Sons, New York, 2004. (d) Davies, J. A. in ”Comprehensive
Organometallic Chemistry II; Vol.9” (Eds: E. W. Abel, F. G. A.
Stone, G. Wilkinson and R. J. Puddephatt) Elsevier, New York,
1995, Chapt. 6. (e) Godleski, S. A. in “Comprehensive Organic
Synthesis; Vol.4” (Eds: B. M. Trost and I. Flemming)
14.
15.
16.
Based on reviews,1 bases such as sodium hydride might not be
essential in the case of Sweeney’s reported reaction11 because
the resulting H–NP(O)Ph2 moiety is not highly acidic.
Furthermore, they only examined triphenylphosphine but not 4.
The second smallest active methyne compound must be
ROCH(CN)2 (MAC reagents), which are smaller than 2-
methylmalononitrile. Incidentally, the smallest active methyne
must be hydrogen cyanide.
Pergamon Press, New York, 1991, Chapt. 3.3.
ꢀ
(f) Tsuji, J.
Tetrahedron 1986, 42, 4361–4401. (g) Trost, B. M. Acc. Chem.
Res. 1980, 13, 385–393.
Theoretical studies on the η3-allylpalladium complex: (a)
Szabó, K. J. J. Am. Chem. Soc. 1996, 118, 7818–7826. (b)
Szabó, K. J. Chem. Eur. J. 1997, 3, 592–600.
Tamamura, H.; Yamashita, M.; Nakajima, Y.; Sakano, K.;
Otaka, A.; Ohno, H.; Ibuka, T.; Fujii, N. J. Chem. Soc., Perkin
Trans I 1999, 2983–2996.
2.

ACCEPTED MANUSCRIPT
12
Tetrahedron
17.
Although very high stereoselectivity was observed, the double
19.
Scheidt, K. A.; Chen, H.; Follows, B. C.; Chemler, S. R.;
inversion mechanism has been generally accepted. Therefore,
the proposed mechanism for stereochemistry is illustrated in
Supplementary Data in order to focus the discussion on the
regiochemistry.
(a) Nemoto, H.; Ma, R.; Moriguchi, H.; Suzuki, I.; Shibuya, M.
J. Organomet. Chem. 2000, 611, 445–448. (b) Nemoto, H.; Ma,
R.; Ibaragi, T.; Suzuki, I.; Shibuya, M. Tetrahedron 2000, 56,
1463–1468.
Coffey, D. S.; Roush, W. R. J. Org. Chem. 1998, 63, 6436–
6437.
20.
21.
Tables for typical 1H data for 15g–15j and 16g–16j, are
available in Supplementary Data.
18.
Ibuka, T.; Taga, T.; Habashita, H.; Nakai, K.; Tamamura, H.;
Fujii, N.; Chounan, Y.; Nemoto, H.; Yamamoto, Y. J. Org.
Chem. 1993, 58, 1207–1214.

ACCEPTED MANUSCRIPT
13
Scheme 1. Preparation of γ-substituted vinylaziridines. Conditions and reagents: i) MesSO2Cl (1.2 eq),
DMAP (0.10 eq) in pyridine (10 eq), 0 ˚C; ii) BuLi (4.0 eq), CH3P(O)(OMe)2 (4.0 eq) in THF, –78 ˚C; iii)
R2CHO (1.2 eq), K2CO3 (1.0 eq) in ethanol, rt; iv) NaBH4 (1.0 eq), CeCl3•7H2O (1.0 eq) in methanol, 0 ˚C;
v) flash column separation; vi) DEAD (2.5 eq), PPh3 (2.5 eq) in THF, 0 ˚C.
Scheme 2. Reaction of γ-substituted trans-azidirine 8t and a masked acyl cyanide reagent 3
Scheme 3. Reaction of γ-substituted cis-azidirine 8c and a masked acyl cyanide reagent 3

ACCEPTED MANUSCRIPT
14
Tetrahedron
Figure 2. Energy minimized conformations A (8cg, 8ch and 8ci) and B/C (8cj)

ACCEPTED MANUSCRIPT
entry
6
ligand
time
(min)
5
Yield
of 7 (%)
93
E/Z
PPh3
1
2
3
4
5
6
7
6a
6a
6a
6a
6b
6c
95:5
>99:1
>99:1
-
dppe
30
5
91
4
99
PnBu3
60
15
15
5
0
4
4
4
97
>99:1
>99:1
>99:1
89
6da
89
a: diastereomer of 6a (α,β’-cis -isomer)

ACCEPTED MANUSCRIPT
Compounds
8tg / 8cg
8th / 8ch
8ti / 8ci
Coupling Constant
4.5 / 5.5
4.0 / 5.5
- / 5.5
8tj / 8cj
4.5 / 7.6

ACCEPTED MANUSCRIPT
Compounds
comparison
J
(Hz)
–
β α
J15 < J16
J15 < J16
J15 < J16
J15 < J16
15g/16g
15h/16h
15i/16i
6.3/7.6
5.8/6.8
5.2/7.2
4.8/7.9
15j/16j

ACCEPTED MANUSCRIPT
Palladium-catalyzed highly regio- and stereoselective carbon–carbon
bond formation reaction of γ-substituted vinylaziridines with a silylated
masked acyl cyanide reagent
Tomoyuki Kawamura, Nanae Matsuo, Daisuke Yamauchi, Yoo Tanabe, Hisao Nemoto*
E-mail: nem@ph.tokushima-u.ac.jp
Comparison of 1H NMR for 15 and 16
R2
R2
SO2Mes
SO2Mes
β
g: R1 = –CH2Ph, R2 = –CH3
β
γ
HN
R1
HN
R1
γ
h: R1 = –CH2Ph, R2 = –CH2CH(CH3)2
i: R1 = –CH2Ph, R2 = –CH(CH3)2
j: R1 = –CH(CH3)2, R2 = –CH(CH3)2
OTBS
α
OTBS
β'
α
β'
NC
CN
NC
CN
16
15
Compound
15g/16g
J
J
J
relative stereochemistry
’
–
–
α β
–
β γ
β α
6.3/7.6 15.5/15.3
5.8/6.8 15.3/15.5
7.2/8.6
determined by authentic sample
determined by authentic sample
15h/16h
9.2/9.6
15i/16i
5.2/7.2 15.3/15.5
4.8/7.9 15.1/15.1
10.0/10.0
10.0/9.6
assumed by mechanism and the value of J
assumed by mechanism and the value of J
’
–
β α
15j/16j
’
–
β α
analysis
J15 < J16 trans-olefin NR
NR = no relationship
Typical 1H NMR data of 15 and 16
γ
β'
β
α
5.45 (ddd, J = 0.7, 7.2,
15.5 Hz, 1H)
5.62 (dd, J = 6.3, 15.5
Hz, 1H)
15g
15h
15i
2.61–2.70 (m, 1H)
3.97–4.06 (m, 1H)
3.96–4.05 (m, 1H)
4.01–4.11 (m, 1H)
3.81–3.87 (m, 1H)
3.88–3.98 (m, 1H)
3.90–3.99 (m, 1H)
3.92–4.01 (m, 1H)
5.24 (ddd, J = 0.8, 9.2,
15.3 Hz, 1H)
5.49 (ddd, J = 1.4, 10.0,
15.3 Hz, 1H)
5.43 (ddd, J = 1.7, 10.0,
15.1 Hz, 1H)
5.34 (ddd, J = 1.0, 8.6,
15.3 Hz, 1H)
5.71 (dd, J = 5.8, 15.3
Hz, 1H)
5.73 (dd, J = 5.2, 15.3
Hz, 1H)
5.70 (dd, J = 4.8, 15.1
Hz, 1H)
5.65 (dd, J = 7.6, 15.3
Hz, 1H)
2.46–2.58 (m, 1H)
2.40 (dd, J = 3.4,
10.0 Hz, 1H)
2.44 (dd, J = 3.4,
10.0 Hz, 1H)
15j
16g
16h
16i
2.56–2.67 (m, 1H)
2.52–2.61 (m, 1H)
2.40–2.44 (m, 1H)
5.25 (dd, J = 9.6, 15.6 Hz, 5.78 (dd, J = 6.8, 15.6
1H)
Hz, 1H)
5.75 (dd, J = 7.2, 15.5
Hz, 1H)
5.47 (ddd, J = 0.7, 10.0,
15.5 Hz, 1H)
2.37 (dd, J = 3.4, 9.6
Hz, 1H)
3.60 (ddd, J = 5.2,
7.9, 7.9 Hz, 1H)
5.38 (dd, J = 9.6, 15.1 Hz, 5.59 (dd, J = 7.9, 15.1
1H) Hz, 1H)
16j

ACCEPTED MANUSCRIPT
Proposed Double Inversion Mechanism
8c
8t
SO2Mes
N
SO2Mes
N
R2
R2
R1
H
H
R1
H
H
H
H
Pd
Pd
OTBS
OTBS
C(CN)2
H
C(CN)2
H
MesO2S
MesO2S
N
N
R2
R2
R1
H
H
H
H
H
R1
H
Pd
Pd
OTBS
OTBS
MesO2S
MesO2S
CH(CN)2
CH(CN)2
NH
NH
R2
R1
H
R2
H
H
H
R1
H
H
16
15