Preparation of optically active 4-aminopyrrolidines by radical addition/cyclization to chiral n-(2-(methoxyimino)ethyl)-β-amino-α- methylene esters

Article abstract of DOI:10.1080/10426507.2012.736893

Optically active 4-aminopyrolidines were prepared by radical cyclization induced by addition of tin radical to N-(2-(methoxyimino)ethyl)-β-amino- α-methylene esters, which were readily prepared by Michael/aldol domino reaction to chiral sulfinimines.

Full text of DOI:10.1080/10426507.2012.736893

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Phosphorus, Sulfur, and Silicon and the
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Preparation of Optically Active
4-Aminopyrrolidines by Radical
Addition/Cyclization to Chiral N-(2-
(Methoxyimino)Ethyl)-β-Amino-α-
Methylene Esters
Akio Kamimura a , Yu Yamane a & Hidemitsu Uno b
a Department of Applied Molecular Bioscience , Graduate School of
Medicine, Yamaguchi University , Ube , 755-8611 , Japan
b Department of Chemistry, Graduate School of Science and
Engineering , Ehime University , Matsuyama , 790-8577 , Japan
Accepted author version posted online: 24 Oct 2012.Published
online: 29 May 2013.
To cite this article: Akio Kamimura , Yu Yamane & Hidemitsu Uno (2013) Preparation of Optically
Active 4-Aminopyrrolidines by Radical Addition/Cyclization to Chiral N-(2-(Methoxyimino)Ethyl)-β-
Amino-α-Methylene Esters, Phosphorus, Sulfur, and Silicon and the Related Elements, 188:4, 356-366,
DOI: 10.1080/10426507.2012.736893
To link to this article: http://dx.doi.org/10.1080/10426507.2012.736893
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Phosphorus, Sulfur, and Silicon, 188:356–366, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.736893
PREPARATION OF OPTICALLY ACTIVE
4-AMINOPYRROLIDINES BY RADICAL
ADDITION/CYCLIZATION TO CHIRAL
N-(2-(METHOXYIMINO)ETHYL)-β-AMINO-α-METHYLENE
ESTERS
Akio Kamimura,1 Yu Yamane,1 and Hidemitsu Uno2
1Department of Applied Molecular Bioscience, Graduate School of Medicine,
Yamaguchi University, Ube 755-8611, Japan
2Department of Chemistry, Graduate School of Science and Engineering, Ehime
University, Matsuyama 790-8577, Japan
GRAPHICAL ABSTRACT
SnBu3
MeOHN
NOMe
Ts
R
Ts
R
N
N
CO2t-Bu
CO2tBu
CO2tBu
R
N
Ts
Abstract Optically active 4-aminopyrolidines were prepared by radical cyclization induced
by addition of tin radical to N-(2-(methoxyimino)ethyl)-β-amino-α-methylene esters, which
were readily prepared by Michael/aldol domino reaction to chiral sulfinimines.
Keywords Radical cyclization; radical addition; 4-aminopyrroidine
INTRODUCTION
Radical cyclization is a good reaction for constructing carbo- or heterocyclic com-
pounds, and frequently used in organic synthesis.1 Among many known generation of
radicals, tin radical chemistry is recognized the most useful methodology and widely ap-
plied for synthetic reactions. Tin radical is usually generated by thermal treatment with tin
hydride in the presence of radical initiator such as AIBN. Bu3SnH is usually the first choice
of tin hydride reagent because it is readily available and the radical process with it is highly
efficient. The three butyl groups on tin atom are normally inert in the reaction. However,
we have recently found the reaction in which one of the butyl group was kicked out by SH2
Received 28 September 2012; accepted 30 September 2012.
The authors are grateful to financial support from Yamaguchi University based on The YU Strategic Program
for Fostering Research Activities (2010–2011).
Address correspondence to Akio Kamimura, Department of Applied Molecular Bioscience, Graduate School
of Medicine, Yamaguchi University, Ube 755-8611, Japan. E-mail: ak10@yamaguchi-u.ac.jp
356

PREPARATION OF OPTICALLY ACTIVE 4-AMINOPYRROLIDINES
357
process2 by vinyl radical and butyl radical and stannacyclopentane were generated in high
yields.3 This is a very new process and we were interested in the extension of the reaction
with other radical accepter such as oxime ethers,4 which were expected to give bicyclic
stannapyrrolidines containing tin-nitrogen bond. In this article, we report that optically
active N-(2-(methoxyimino)ethyl)-β-amino-α-methylene esters5 underwent simple radical
addition/cyclization to give chiral 4-aminopyrrolidines in good yield.
RESULTS AND DISCUSSION
The precursor of the radical cyclization was prepared by treatment of N-allyl-β-
amino-α-methylene ester 1 under oxidative conditions followed by oxime formation. The
results are summarized in Scheme 1.
Scheme 1 Reagents and conditions: i, OsO4, 2,6-lutidine,NalO4, dioxane/Water (3:1), r.t.; ii, NH2OMe.HCl,
NaOAc, MeOH, r.t.
For example, compound 1a underwent oxidation at the N-allylic unit that firstly
afforded corresponding diol, which then gave aldehyde 2a through carbon–carbon bond
cleavage by the presence of NaIO4. During the oxidation with OsO4 took place chemselec-
tively and the α, β-unsaturated alkene unit survived under these conditions. Exposure of
2a to hydroxylamine methyl ether resulted in desired formation of oxime ether smoothly
and cyclization precursor 3a was isolated in 70% yield in two steps.
With desired precursors 3 in hand, we examined radical addition/cyclization for these
compounds by treatment with Bu3SnH. The results are summarized in Scheme 2.
Scheme 2 Reagents and conditions: i, Bu3SnH, Et3B, toluene, r.t.

358
A. KAMIMURA ET AL.
Tin radical was generated by Et3B in the presence of air. The reaction took place
smoothly and the precursor 3 was consumed smoothly. For example, precursor 3a dis-
1
appeared within 2 h and two diastereomers of 4a was produced. H NMR spectrum for
compound 4a revealed that both isomers of 4a contained Bu3Sn unit. The terminal methyl
groups derived from Bu3Sn radical were observed as a single triplet. This observation
suggested that the butyl groups attaching to tin atom was chemically equivalent. Thus, the
formation of 5 did not happen during the reaction although we expected to obtain bicyclic
azastannolane 5 during the reaction. The SH2 substitution on tin atom by aminyl radical
did not takes place from the reaction of 3.
The structure of compound 4 was unambiguously determined by X-ray crystallo-
graphic analyses.6 For example, the two diastereomers of compound 4e was separated by
careful flash chromatography and these isomers were isolated as solid products. X-ray
crystallographic analyses for both compounds revealed trans structure for major 4e and cis
structure for minor 4e. It was interesting that the both isomer had the same configuration
at the quaternary center and the difference was the configuration at methoxyamino carbon.
Other derivatives for compounds 4 showed a similar pattern in NMR so all configurations
of the two isomers of 4 were determined.
Although the expected SH2 process to give compound 5 did not occur from the
precursor 3, we assumed the reaction mechanism as shown in Scheme 3.
Scheme 3
Compound 3 underwent radical addition by Bu3Sn radical to give intermediate A,
which contained the two conformational state, trans-A and cis-A. The difference of them is
conformation of the oxime ether unit, which occupies pseudoequatorial position in trans-A
and pseudoaxial position in cis-A. It should be noted that the favorable conformation at
radical center was always the same and the ester group occupies pseudoequatorial position,
becausebothisomers of 4havethesameconfigurationatthequaternarycarbonasmentioned

PREPARATION OF OPTICALLY ACTIVE 4-AMINOPYRROLIDINES
359
before. The radical in intermediate A attacks the oxime ether unit in a 5-exo-trig manner
to give intermediate trans-B and cis-B. If the resulting aminyl radical attack the tin atom,
desired SH2 reaction occurs and bicyclic azastannolane 5 should be formed. However, this
process never occurs. Instead, simple hydrogen abstraction from Bu3SnH dominates and
trans-4 and cis-4 were produced exclusively. One reason why no SH2 process happens is
hydrogen abstraction from intermediate B should be much faster than the SH2 process.
Also, geometry of aminyl radical in trans-B and cis-B should be important; the radical
center should be too far from the tin atom to progress efficient SH2 process. Unfortunately,
cis/trans selectivity for the formation of 4 was in a moderate level. This is probably due
to energy differences between intermediates cis-A and trans-A are close and probably the
stereoselectivity just reflected the conformational ratio for these two intermediates.
CONCLUSION
Radical treatment of N-(2-(methoxyimino)ethyl)-β-amino-α-methylene esters 3 lead
anefficientformationof4-aminopyrrolidinederivatives throughradical addition/cyclization
process. The aminyl radical intermediate did not undergo SH2 process but simple hydro-
gen abstraction from Bu3SnH dominates. Since the precursors of the reaction are readily
prepared in optically active form, the present method will provide a useful preparation of
multifunctionalized 4-aminopyrrrolidine derivatives.
EXPERIMENTAL
General: All 1H and 13C NMR spectra were recorded on JEOL JNM-ECA500 Delta2
(500 MHz for 1H and 126 MHz for 13C) spectrometer. High-resolution mass spectra (HRMS)
were measured at Tokiwa Instrumentation Center, Yamaguchi University. Compounds 1
were prepared by the reported methods.5
Preparation of (S)-tert-butyl 2-((N-(2-(methoxyimino)ethyl)-4-methylphenyl-
sulfonamido)(p-tolyl)methyl)acrylate (3a): A mixture of 1a (1.4170 g, 3,21 mmol),
2,6-lutidine (0.75 mL, 6.47 mmol), OsO4 (0.033 g, 0.130 mmol, 4 mol%) and NaIO4
(2.0689 g, 9.67 mmol) in dioxane-water (35 mL, 3:1 v/v) was stirred at room temperature
for 90 min. Saturated Na2S2O3aq (60 mL) and brine (20 mL) was added to the reaction
mixture and the resulting mixture was extracted with CH2Cl2 (60 mL × 5). Organic phase
was combined, washed with 1M HCl (5 mL × 2) and saturated Na2S2O3 (20 mL × 1),
and dried over Na2SO4. After filtration, the filtrate was concentrated in vacuo and the
residue was subjected to flash chromatography (silica gel/hexane-EtOAc 15:1 then 2:1
v/v) to give aldehyde 2a in 73% yield (1.0437g, 2.36 mmol), which was used for the next
1
step without further purification. Colorless oil; [α]D +45.6 (c 1.03, CHCl3); H NMR
(500 MHz, CDCl3) δ 8.85 (s, 1H), 7.72 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H),
7.06 (d, J = 7.9 Hz, 2H), 6.97 (d, J = 8.1 Hz, 2H), 6.25 (s, 1H), 6.19 (d, J = 1.6 Hz, 1H),
5.18 (d, J = 1.9 Hz, 1H), 3.84 (d, J = 19.6 Hz, 1H), 3.54 (dd, J = 18.7, 2.1 Hz, 1H), 2.44
(s, 3H), 2.28 (s, 3H), 1.24 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 199.2, 164.9, 144.2,
139.9, 138.6, 136.6, 129.9, 129.8, 128.4, 127.5, 125.6, 81.8, 61.7, 53.4, 27.8, 21.7, 21.2;
and HRMS (ESI M + MeOH + Na) m/z 498.1932. Calcd for C25H33NNaO6S 498.1926.
To a mixture of NaOAc (0.1879 g, 2.29 mmol) and p-methylhydroxylamine hy-
drochloride (0.1908 g, 2.28 mmol) in MeOH (40 mL) was added 2a (0.6730 g, 1.52 mmol)
in MeOH (10 mL) and the reaction mixture was stirred for 23 h at room temperature. Water
(20 mL) was added and the resulting mixture was extracted with CH2Cl2 (20 mL × 3).

360
A. KAMIMURA ET AL.
Organic phase was combined, washed with water (20 mL × 2) and dried over Na2SO4.
After filtration, the filtrate was concentrated in vacuo and the residue was subjected to
flash chromatography (silica gel/hexane-EtOAc 15:1 v/v) to give oxime ether 3a in 94%
◦
yield (0.6887 g, 1.40 mmol). White solid; mp 62–63 C; The enantiomeric purity was
determined by HPLC analysis (230 nm, 30 ◦C) tR 16.3 min (minor); tR 17.4 min (major)
[CHIRALPAK IC (0.46 cm × 25 cm) (from Daicel Chemical Ind., Ltd.) hexane/i-PrOH,
88/12, 1.00 mL/min] as 95%ee; [α]D +89.4 (c 1.03, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 7.70 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 8.1 Hz, 2H), 7.04 (d, J = 7.9 Hz, 2H), 6.90 (d, J
= 8.0 Hz, 2H), 6.54 (t, J = 5.6 Hz, 1H), 6.28 (d, J = 1.7 Hz, 1H), 6.13 (s, 1H), 5.43 (d, J
= 1.9 Hz, 1H), 3.99 (dd, J = 16.6, 6.1 Hz, 1H), 3.69 (dd, J = 16.6, 5.2 Hz, 1H), 2.42 (s,
3H), 2.29 (s, 3H), 1.25 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 165.0, 146.8, 143.7, 140.4,
138.1, 137.3, 134.2, 129.70, 129.5, 128.5, 127.7, 126.0, 81.6, 61.8, 61.5, 44.0, 27.8, 21.7,
21.2; and HRMS (ESI M + H) m/z 473.2064. Calcd for C25H33N2O5S 473.2110.
Other compounds 3 were prepared in a similar manner.
(S)-tert-butyl 2-((N-(2-(methoxyimino)ethyl)-4-methylphenylsulfonamido)(phe
◦
nyl)- methyl)acrylate (3b): White solid; mp 82–83 C; the enantiomeric purity was de-
◦
termined by HPLC analysis (230 nm, 30 C) tR 15.7 min (minor); tR 16.9 min (major)
[CHIRALPAK IC (0.46 cm × 25 cm) (from Daicel Chemical Ind., Ltd.) hexane/i-PrOH,
88/12, 1.00 mL/min] as 92%ee; [α]D +77.9 (CHCl3, c 1.02); 1H NMR (500 MHz, CDCl3)
δ 7.74–7.67 (m, 2H), 7.29–7.21 (m, 5H), 7.07–7.01 (m, 2H), 6.54 (t, J = 5.6 Hz, 1H), 6.30
(s, 1H), 6.18 (s, 1H), 4.01 (ddd, J = 16.5, 6.0, 2.5 Hz, 1H), 3.75–3.66 (m, 1H), 3.60 (s, 3H),
2.42 (s, 3H), 1.24 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 164.92, 146.63, 140.20, 137.33,
137.25, 129.81, 129.72, 128.83, 128.60, 128.23, 127.65, 126.35, 81.65, 61.99, 61.47, 44.08,
27.75, 21.67; and HRMS (ESI M + H) m/z 459.1960. Calcd for C24H31N2O5S 459.1954.
(S)-tert-butyl 2-((4-chlorophenyl)(N-(2-(methoxyimi◦no)ethyl)-4-methylphenyl-
sulfonamido)methyl)acrylate (3c): White solid; mp 82–83 C; the enantiomeric purity
was determined by HPLC analysis (230 nm, 30 ◦C) tR 16.3 min (minor); tR 17.4 min (major)
[CHIRALPAK IC (0.46 cm × 25 cm) (from Daicel Chemical Ind., Ltd.) hexane/i-PrOH,
88/12, 1.00 mL/min] as 92%ee; [α]D +58.9 (CHCl3, c 1.02); 1H NMR (500 MHz, CDCl3)
δ 7.67 (d, J = 8.2 Hz, 2H), 7.27 (d, J = 8.1 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.00 (d,
J = 8.4 Hz, 2H), 6.69 (t, J = 5.7 Hz, 1H), 6.29 (d, J = 1.6 Hz, 1H), 6.15 (s, 1H), 5.38
(d, J = 1.9 Hz, 1H), 3.99 (dd, J = 16.5, 5.3 Hz, 1H), 3.69 (dd, J = 16.6, 5.1 Hz, 1H),
3.61 (s, 3H), 2.42 (s, 3H), 1.27 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 164.7, 146.3,
144.0, 139.6, 137.1, 136.0, 134.2, 130.0, 129.8, 129.0, 127.6, 126.8, 81.9, 61.6, 61.2,
44.2, 27.8, 21.7; and HRMS (ESI M + H) m/z 493.1581. Calcd for C24H30ClN2O5S 493.
1564.
(S)-tert-butyl 2-((N-(2-(methoxyimino)ethyl)-4-methylphenylsulfonamido)(4-m
ethoxyphenyl)methyl)acrylate (3d): Colorless oil; the enantiomeric purity was deter-
◦
mined by HPLC analysis (230 nm, 40 C) tR 44.4 min (minor); tR 47.1 min (major)
[CHIRALPAK ID (0.46 cm × 25 cm) (from Daicel Chemical Ind., Ltd.) hexane/i-PrOH,
90/10, 0.50 mL/min] as 98%ee; [α]D +69.3 (CHCl3, c 1.01); 1H NMR (500 MHz, CDCl3)
δ 7.70 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 7.7 Hz, 2H), 6.95 (d, J = 8.7 Hz, 2H), 6.77 (d, J
= 8.8 Hz, 2H), 6.59 (t, J = 5.7 Hz, 1H), 6.27 (d, J = 1.8 Hz, 1H), 6.12 (s, 1H), 5.41 (d, J
= 1.9 Hz, 1H), 4.00 (dd, J = 16.7, 5.8 Hz, 1H), 3.76 (s, 3H), 3.68 (dd, J = 16.6, 5.4 Hz,
1H), 3.62 (s, 3H), 2.43 (s, 3H), 1.26 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 165.0, 159.5,
146.8, 143.7, 140.5, 137.3, 129.8, 129.7, 129.2, 127.6, 125.7, 114.1, 81.6, 61.5, 61.5, 55.3,
44.0, 27.8, 21.7; and HRMS (ESI M + H) m/z 489.2068. Calcd for C25H33N2O6S 489.
2059.

PREPARATION OF OPTICALLY ACTIVE 4-AMINOPYRROLIDINES
361
(S)-tert-butyl 2-((N-(2-(methoxyimino)ethyl)-4-methylphenylsulfonamido)(o-to
lyl)- methyl)acrylate (3e): Colorless oil; the enantiomeric purity was determined by HPLC
◦
analysis (230 nm, 30 C) tR 24.4 min (major); tR 34.8 min (minor) [CHIRALPAK AD
(0.46 cm × 25 cm) (from Daicel Chemical Ind., Ltd.) hexane/i-PrOH, 98/2, 0.80 mL/min]
as 97%ee; [α]D +135.0 (CHCl3, c 1.02); 1H NMR (500 MHz, CDCl3) δ 7.67 (d, J = 8.3 Hz,
2H), 7.25 (d, J = 7.8 Hz, 2H), 7.21–7.13 (m, 2H), 7.07 (td, J = 7.3, 2.0 Hz, 1H), 6.96 (dd,
J = 7.7, 1.2 Hz, 1H), 6.55 (t, J = 5.5 Hz, 1H), 6.39 (s, 1H), 6.24 (d, J = 1.6 Hz, 1H), 5.08
(d, J = 1.8 Hz, 1H), 3.98 (ddd, J = 16.7, 5.4, 0.8 Hz, 1H), 3.71 (dd, J = 16.8, 5.6 Hz, 1H),
3.56 (s, 3H), 2.41 (s, 3H), 2.39 (s, 3H), 1.21 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 164.8,
146.6, 143.8, 140.3, 137.6, 136.8, 135.3, 131.04, 129.6, 128.4, 128.1, 127.9, 126.2, 125.7,
81.6, 61.4, 59.2, 44.1, 27.7, 21.7, 19.5; and HRMS (ESI M + H) m/z 473.2146. Calcd for
C25H33N2O5S 473.2110.
(S)-tert-butyl 2-((N-(2-(methoxyimino)ethyl)-4-methylphenylsulfonamido)-(na
phthalen-2-yl)methyl)acrylate (3f): White solid; mp 137–138 ◦C; the enantiomeric
purity was determined by HPLC analysis (230 nm, 35 ◦C) tR 28.3 min (major); tR
35.5 min (minor) [CHIRALPAK AD (0.46 cm × 25 cm) (from Daicel Chemical Ind., Ltd.)
1
hexane/i-PrOH, 95/5, 1.00 mL/min] as 95%ee; [α]D +113.0 (c 1.03, CHCl3); H NMR
(500 MHz, CDCl3) δ 7.81–7.76 (m, 1H), 7.74 (d, J = 8.7 Hz, 2H), 7.72 (d, J = 8.3 Hz,
2H), 7.67–7.62 (m, 1H), 7.51–7.42 (m, 2H), 7.26 (d, J = 7.9 Hz, 2H), 7.18 (dd, J = 8.5,
1.9 Hz, 1H), 6.64 (t, J = 5.6 Hz, 1H), 6.36 (s, 2H), 5.43 (d, J = 1.5 Hz, 1H), 4.03 (dd, J =
16.5, 5.6 Hz, 1H), 3.79 (dd, J = 16.5, 5.8 Hz, 1H), 3.29 (s, 3H), 2.42 (s, 3H), 1.23 (s, 9H);
13C NMR (126 MHz, CDCl3) δ 165.0, 146.5, 143.8, 140.1, 137.2, 134.6, 133.2, 133.0,
129.8, 128.8, 128.1, 127.7, 127.6, 127.4, 126.7, 126.6, 126.5, 126.5, 81.8, 62.0, 61.2, 44.3,
27.8, 21.7; and HRMS (ESI M + H) m/z 509.2105. Calcd for C28H33N2O5S 509.2110.
(R)-tert-butyl 2-((N-(2-(methoxyimino)ethyl)-4-methylphenylsulfonamido)- (thi
ophen-2-yl)methyl)acrylate (3g): Colorless oil; the enantiomeric purity was determined by
HPLC analysis (230 nm, 40 ◦C) tR 38.9 min (minor); tR 41.7 min (major) [CHIRALPAK IC
(0.46 cm × 25 cm) (from Daicel Chemical Ind., Ltd.) hexane/i-PrOH, 95/5, 0.80 mL/min]
as 94%ee; [α]D +80.8 (CHCl3, c 1.03); 1H NMR (500 MHz, CDCl3) δ 7.68 (d, J = 8.4 Hz,
2H), 7.26 (d, J = 8.5 Hz, 2H), 7.18 (dd, J = 5.1, 1.2 Hz, 1H), 6.87 (dd, J = 5.1, 3.5 Hz,
1H), 6.76 (dd, J = 2.8, 1.8 Hz, 1H), 6.73 (dd, J = 6.1, 5.3 Hz, 1H), 6.37 (d, J = 1.8 Hz,
1H), 6.32 (d, J = 1.7 Hz, 1H), 5.60 (d, J = 1.9 Hz, 1H), 4.01 (dd, J = 16.5, 6.1 Hz,
1H), 3.78 (dd, J = 16.6, 5.2 Hz, 1H), 3.68 (s, 3H), 2.42 (s, 3H), 1.34 (s, 9H); 13C NMR
(126 MHz, CDCl3) δ 164.7, 146.5, 143.8, 140.6, 140.1, 136.8, 129.7, 127.7, 127.7, 126.9,
126.4, 126.3, 81.9, 61.6, 57.2, 44.0, 27.9, 21.7; and HRMS (ESI M + H) m/z 465.1528.
Calcd for C22H29N2O5S2 465.1518.
(S)-tert-butyl 3-(N-(2-(methoxyimino)ethyl)-4-methylphenylsulfonamido)-2- me
thylenehexanoate (3h): Pale yellow oil; the enantiomeric purity was determined by HPLC
◦
analysis (230 nm, 35 C) tR 16.4 min (major); tR 19.4 min (minor) [CHIRALPAK AD
(0.46 cm × 25 cm) (from Daicel Chemical Ind., Ltd.) hexane/i-PrOH, 95/5, 0.80 mL/min]
as 97%ee; [α]D –38.1 (c 1.00, CHCl3); 1H NMR (500 MHz, CDCl3) δ (a mixture of E/Z
isomers) 7.71 (dd, J = 8.4, 2.4 Hz, 2H for one isomer), 7.70 (dd, J = 8.4, 2.4 Hz, 2H for
other isomer), 7.33–7.16 (m, 3H), 6.55 (t, J = 4.1 Hz, 1H for one isomer), 6.19 (s, 1H for
one isomer), 6.16 (s, 1H for other isomer), 5.58 (s, 1H for one isoemr), 5.52 (s, 1H for other
isomer), 5.03 (t, J = 7.6 Hz, 1H for one isomer), 4.96 (t, J = 7.6 Hz, 1H for other isomer),
4.10 (dd, J = 19.3, 4.4 Hz, 1H), 3.86 (dd, J = 13.7, 7.9 Hz, 1H), 3.84 (d, J = 0.9 Hz, 3H for
one isomer), 3.78 (s, 3H for other isomer), 2.39 (s, 3H), 1.75–1.50 (m, 4H), 1.43 (s, 9H for
one isomer), 1.42 (s, 9H for other isomer), 0.89 (td, J = 7.4 Hz, 3H for one isomer), 0.88

362
A. KAMIMURA ET AL.
(td, J = 7.4 Hz, 3H for other isomer); 13C NMR (126 MHz, CDCl3) δ (a mixture of E/Z
isomers) 165.54, 165.42, 150.16, 147.90, 143.31, 143.31, 140.06, 140.05, 137.60, 137.53,
137.53, 129.48, 129.48, 127.84, 127.76, 126.41, 126.37, 81.54, 81.43, 62.11, 61.66, 57.20,
56.99, 43.20, 39.41, 33.76, 33.39, 28.03, 21.58, 21.57, 19.80, 19.78, 13.80, 13.74; and
HRMS (ESI M + H) m/z 425.2098. Calcd for C21H33N2O5S 425.2110.
Preparation of (2S,3S)-tert-butyl 4-(methoxyamino)-2-(p-tolyl)-1-tosyl-3-
((tributylstannyl)methyl)pyrrolidine-3-carboxylate (4a): Compound 3a (0.2363 g,
0.500 mmol) was dissolved in toluene (50 mL) and Bu3SnH (0.26 mL, 0.981 mmol) and
Et3B (1 M in hexane, 1.0 mL, 1 mmol) were added. The resulting solution was purged
by air for 5 min and stirred for 2 h at room temperature. Solvent was evaporated and the
residue was subjected to flash chromatography (silica gel/hexane-EtOAc 25:1 then 5:1
v/v) to give 4a in 76% yield (0.3049 g, 0.379 mmol). HPLC analysis revealed trans/cis
ratio was 64/36. HRMS (ESI M + H) m/z 765.3333. Calcd for C37H61N2O5SSn 765.
3323.
Careful chromatographic treatment separated trans-4a and cis-4a in pure form.
trans-4a: Colorless oil; the enantiomeric purity was determined by HPLC analysis
(230 nm, 30 ◦C) tR 10.6 min (minor); tR 17.5 min (major) [CHIRALPAK IC (0.46 cm ×
25 cm) (from Daicel Chemical Ind., Ltd.) hexane/i-PrOH, 90/10, 0.80 mL/min] as 95%ee;
[α]D -27.2 (c 1.03, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.36 (d, J = 8.1 Hz, 2H), 7.08
(d, J = 8.0 Hz, 2H), 6.98 (d, J = 7.7 Hz, 2H), 6.86 (d, J = 7.5 Hz, 2H), 5.90 (d, J = 9.5 Hz,
1H), 5.05 (s, 1H), 3.85 (dd, J = 9.3, 7.2 Hz, 1H), 3.77–3.63 (m, 1H), 3.54 (dt, J = 9.6,
7.6 Hz, 1H), 3.43 (s, 3H), 2.35 (s, 3H), 2.30 (s, 3H), 1.48 (s, 9H), 1.35–1.14 (m, 12H), 0.82
(t, J = 7.2 Hz, 9H), 0.66 (dd, J = 9.2, 7.2 Hz, 6H), 0.52 (d, J = 12.9 Hz, 1H), 0.47 (d, J
= 13.0 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 173.4, 142.8, 137.3, 136.6, 135.3, 129.1,
128.8, 128.4, 127.3, 82.5, 70.5, 67.3, 61.7, 59.4, 51.7, 29.1, 28.1, 27.5, 21.5, 21.2, 11.1.
cis-4a: 1H NMR (500 MHz, CDCl3) δ 7.58 (d, J = 8.2 Hz, 2H), 7.24 (d, J = 8.6 Hz,
2H), 7.11 (d, J = 7.6 Hz, 2H), 7.07 (d, J = 8.2 Hz, 2H), 5.33 (d, J = 9.0 Hz, 1H), 4.78
(s, 1H), 3.77–3.67 (m, 2H), 3.64–3.54 (m, 1H), 3.45 (s, 3H), 2.39 (s, 3H), 2.32 (s, 3H),
1.32 (s, 9H), 1.31–1.12 (m, 12H), 0.81 (t, J = 7.2 Hz, 9H), 0.71–0.62 (m, 6H), 0.51 (d, J
= 13.0 Hz, 1H), 0.26 (d, J = 12.9 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 173.6, 143.4,
137.3, 135.3, 134.1, 129.5, 128.7, 128.3, 128.0, 81.9, 71.2, 64.0, 62.0, 60.2, 51.5, 29.1,
27.8, 27.5, 21.6, 21.3, 13.8, 10.9.
Other compound 4 were prepared in a similar manner.
(2S,3S)-tert-butyl 4-(methoxyamino)-2-phenyl-1-tosyl-3-((tributylstannyl)met-
hyl)-pyrrolidine-3-carboxylate (4b): HRMS (ESI M + H) m/z 751.3202. Calcd for
C36H59N2O5SSn 751.3167.
trans-4b White solid; mp 55–56 ◦C; [α]D -24.2 (c 1.01, CHCl3); 1H NMR (500 MHz,
CDCl3) δ 7.36 (d, J = 8.2 Hz, 2H), 7.26–7.13 (m, 3H), 7.09 (d, J = 8.1 Hz, 2H), 6.97 (d, J
= 6.0 Hz, 2H), 5.92 (d, J = 9.7 Hz, 1H), 5.10 (s, 1H), 3.86 (dd, J = 9.3, 7.2 Hz, 1H), 3.70
(dd, J = 9.4, 7.9 Hz, 1H), 3.54 (dt, J = 9.7, 7.5 Hz, 1H), 3.43 (s, 3H), 2.35 (s, 3H), 1.49
(s, 9H), 1.40–1.13 (m, 12H), 0.81 (t, J = 7.2 Hz, 9H), 0.67 (dd, J = 9.2, 6.8 Hz, 6H), 0.52
(d, J = 12.9 Hz, 1H), 0.42 (d, J = 13.0 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 173.3,
142.9, 138.3, 136.5, 129.2, 128.3, 128.1, 127.7, 127.3, 82.6, 70.7, 67.2, 61.7, 59.4, 51.7,
29.1, 28.1, 27.4, 21.5, 13.8, 11.1.
cis-4b: 1H NMR (500 MHz, CDCl3) δ 7.57 (d, J = 8.2 Hz, 2H), 7.30–7.21 (m, 7H),
5.32 (d, J = 9.0 Hz, 1H), 4.83 (s, 1H), 3.80–3.70 (m, 2H), 3.65–3.58 (m, 1H), 3.46 (s, 3H),
2.39 (s, 3H), 1.34 (s, 9H), 1.33–1.13 (m, 12H), 0.81 (t, J = 7.3 Hz, 9H), 0.71–0.63 (m,
6H), 0.50 (d, J = 12.9 Hz, 1H), 0.23 (d, J = 13.0 Hz, 1H); 13C NMR (126 MHz, CDCl3)

PREPARATION OF OPTICALLY ACTIVE 4-AMINOPYRROLIDINES
363
δ 173.6, 143.5, 138.4, 134.2, 129.6, 128.4, 127.9 (2C), 127.7, 82.0, 71.3, 64.0, 62.0, 60.3,
51.5, 29.1, 27.8, 27.5, 21.6, 13.8, 10.9.
(2S,3S)-tert-butyl 2-(4-chlorophenyl)-4-(methoxyamino)-1-tosyl-3-((tributylst-
annyl)methyl)pyrrolidine-3-carboxylate (4c): HRMS (ESI M + H) m/z 785.2777. Calcd
for C36H58ClN2O5SSn 785.2759.
trans-4◦c: Colorless oil; the enantiomeric purity was determined by HPLC analysis
(230 nm, 30 C) tR 9.8 min (minor); tR 13.3 min (major) [CHIRALPAK IC (0.46 cm ×
25 cm) (from Daicel Chemical Ind., Ltd.) hexane/i-PrOH, 90/10, 0.70 mL/min] as 89%ee;
[α]D –15.5 (c 1.02, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.41 (d, J = 8.2 Hz, 2H), 7.17
(d, J = 8.1 Hz, 2H), 7.14 (d, J = 8.1 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 5.83 (d, J = 9.7 Hz,
1H), 5.05 (s, 1H), 3.85 (dd, J = 9.6, 6.9 Hz, 1H), 3.69 (dd, J = 9.6, 7.4 Hz, 1H), 3.50–3.44
(m, 1H), 3.42 (s, 3H), 2.38 (s, 3H), 1.47 (s, 9H), 1.37–1.15 (m, 12H), 0.82 (t, J = 7.2 Hz,
9H), 0.71–0.65 (m, 6H), 0.50 (d, J = 13.0 Hz, 1H), 0.41 (d, J = 13.0 Hz, 1H); 13C NMR
(126 MHz, CDCl3) δ 172.9, 143.3, 137.0, 136.1, 133.6, 129.7, 129.4, 128.2, 127.3, 82.8,
69.9, 67.2, 61.7, 59.4, 51.6, 29.1, 28.1, 27.5, 21.6, 13.8, 11.2.
cis-4c: 1H NMR (500 MHz, CDCl3) δ 7.56 (d, J = 8.2 Hz, 2H), 7.29–7.17 (m, 6H),
5.26 (d, J = 7.8 Hz, 1H), 4.78 (s, 1H), 3.79–3.66 (m, 2H), 3.58 (dd, J = 9.8, 5.2 Hz, 1H),
3.47 (s, 3H), 2.40 (s, 3H), 1.33 (s, 9H), 1.32–1.15 (m, 12H), 0.82 (t, J = 7.3 Hz, 9H),
0.72–0.65 (m, 6H), 0.45 (d, J = 12.9 Hz, 1H), 0.22 (d, J = 12.9 Hz, 1H); and 13C NMR
(126 MHz, CDCl3) δ 173.4, 143.7, 137.1, 134.0, 133.5, 129.9, 129.6, 128.1, 127.9, 82.2,
70.6, 64.0, 62.2, 60.2, 51.5, 29.1, 27.8, 27.5, 21.6, 13.8, 10.9.
(2S,3S,4S)-tert-butyl 4-(methoxyamino)-2-(4-methoxyphenyl)-1-tosyl-3- ((tribu-
tylstannyl)methyl)pyrrolidine-3-carboxylate (4d): HRMS (ESI M + H) m/z 781.3274.
Calcd for C37H61N2O6SSn 781.3272.
trans-4d: Colorless oil; the enantiomeric purity was determined by HPLC analysis
(230 nm, 40 ◦C) tR 13.6 min (minor); tR 22.0 min (major) [CHIRALPAK IC (0.46 cm ×
25 cm) (from Daicel Chemical Ind., Ltd.) hexane/i-PrOH, 95/5, 1.00 mL/min] as 99%ee;
[α]D –43.5 (c 0.54, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.37 (d, J = 8.3 Hz, 2H), 7.10
(d, J = 7.9 Hz, 2H), 6.90 (d, J = 8.0 Hz, 2H), 6.72 (d, J = 8.3 Hz, 2H), 5.92 (d, J =
9.7 Hz, 1H), 5.05 (s, 1H), 3.85 (dd, J = 9.4, 7.1 Hz, 1H), 3.79 (s, 3H), 3.68 (d, J = 8.2 Hz,
1H), 3.53 (dt, J = 10.0, 7.6 Hz, 1H), 3.44 (s, 3H), 2.36 (s, 3H), 1.49 (s, 9H), 1.37–1.16
(m, 12H), 0.83 (t, J = 7.2 Hz, 9H), 0.71–0.65 (m, 6H), 0.54 (d, J = 13.1 Hz, 1H), 0.47 (d,
J = 13.2 Hz, 1H); and 13C NMR (126 MHz, CDCl3) δ 173.4, 159.1, 142.8, 136.6, 130.4,
129.6, 129.2, 127.3, 113.4, 82.6, 70.3, 67.2, 61.7, 59.5, 55.3, 51.6, 31.7, 29.2, 28.2, 27.5,
21.5, 13.8, 11.1.
cis-4d: 1H NMR (500 MHz, CDCl3) δ 7.56 (d, J = 8.2 Hz, 2H), 7.24 (d, J = 10.7 Hz,
2H), 7.20–7.09 (m, 2H), 6.80 (d, J = 8.9 Hz, 2H), 5.32 (d, J = 8.3 Hz, 1H), 4.76 (s, 1H),
3.79 (s, 3H), 3.75–3.65 (m, 2H), 3.67–3.55 (m, 1H), 3.46 (s, 3H), 2.39 (s, 3H), 1.33 (s, 9H),
1.32–1.14 (m, 12H), 0.82 (t, J = 7.3 Hz, 9H), 0.70–0.64 (m, 6H), 0.50 (d, J = 13.0 Hz,
1H), 0.27 (d, J = 13.0 Hz, 1H); and 13C NMR (126 MHz, CDCl3) δ 173.7, 159.1, 143.4,
134.3, 130.4, 129.5, 129.2, 127.9, 113.3, 81.9, 70.9, 63.9, 62.0, 60.3, 55.3, 29.14, 27.8,
27.5, 13.8, 10.9.
(2S,3S)-tert-butyl4-(methoxyamino)-2-(o-tolyl)-1-tosyl-3-((tributylstannyl)met-
hyl)pyrrolidine-3-carboxylate (4e): HRMS (ESI M + H) m/z 765.3308. Calcd for
C37H61N2O5SSn 765.3323.
trans-4e: White solid; mp 124–125 ◦C; The enantiomeric purity was determined by
HPLC analysis (230 nm, 40 ◦C) tR 8.8 min (minor); tR 11.3 min (major) [CHIRALPAK IC
(0.46 cm × 25 cm) (from Daicel Chemical Ind., Ltd.) hexane/i-PrOH, 90/10, 1.00 mL/min]

364
A. KAMIMURA ET AL.
as 95%ee; [α]D +10.1 (c 1.00, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.39 (d, J = 8.2 Hz,
2H), 7.17–7.06 (m, 4H), 6.94 (td, J = 7.5, 1.7 Hz, 1H), 6.71 (dd, J = 7.9, 1.2 Hz, 1H), 6.35
(d, J = 12.2 Hz, 1H), 5.43 (s, 1H), 3.94 (dd, J = 8.7, 7.6 Hz, 1H), 3.67 (t, J = 8.9 Hz, 1H),
3.56 (ddd, J = 12.2, 9.1, 7.6 Hz, 1H), 3.47 (s, 3H), 2.41 (s, 3H), 2.34 (s, 3H), 1.47 (s, 9H),
1.38–1.13 (m, 12H), 0.87 (d, J = 13.1 Hz, 0H), 0.83 (d, J = 13.1 Hz, 1H), 0.81 (t, J =
7.3 Hz, 9H), 0.70 (t, J = 8.2 Hz, 6H), 0.05 (d, J = 12.9 Hz, 1H); and 13C NMR (126 MHz,
CDCl3) δ 174.2, 142.9, 136.9, 136.5, 130.4, 129.2, 127.3, 127.1, 126.0, 82.6, 67.1, 65.5,
61.3, 59.5, 29.2, 28.08, 27.4, 21.5, 20.2, 13.8, 13.0, 11.1.
cis-4e: White solid; mp 95–96 ◦C; [α]D +40.6 (c 0.51, CHCl3); 1H NMR (500 MHz,
CDCl3) δ 7.55 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 7.3 Hz, 1H), 7.21 (d, J = 9.4 Hz, 2H),
7.16–7.06 (m, 3H), 5.32 (d, J = 10.3 Hz, 1H), 5.17 (s, 1H), 3.93 (dd, J = 10.2, 1.6 Hz,
1H), 3.87–3.80 (m, 1H), 3.62 (dd, J = 10.1, 5.4 Hz, 1H), 3.50 (s, 3H), 2.38 (s, 3H), 2.34 (s,
3H), 1.55 (s, 9H), 1.36–1.15 (m, 12H), 0.81 (t, J = 7.3 Hz, 9H), 0.75–0.70 (m, 6H), 0.54
(d, J = 13.0 Hz, 1H), 0.05 (d, J = 13.0 Hz, 1H); and 13C NMR (126 MHz, CDCl3) δ 174.3,
143.4, 137.4, 136.1, 134.5, 130.4, 129.5, 128.2, 127.9, 127.3, 125.8, 82.2, 67.2, 64.2, 61.8,
60.8, 52.0, 29.1, 27.8, 27.4, 21.5, 20.3, 13.7, 10.7.
(2S,3S)-tert-butyl 4-(methoxyamino)-2-(naphthalen-2-yl)-1-tosyl-3- ((tributyl-
stannyl)methyl)pyrrolidine-3-carboxylate (4f): HRMS (ESI M + H) m/z 801.3330.
Calcd for C40H61N2O5SSn 801.3323.
trans-4f: Colorless oil; [α]D –22.5 (c 1.03, CHCl3); 1H NMR (500 MHz, CDCl3) δ
7.77 (dd, J = 6.2, 3.3 Hz, 1H), 7.68–7.58 (m, 2H), 7.50–7.42 (m, 2H), 7.29 (d, J = 8.0 Hz,
2H), 7.20–7.03 (m, 2H), 6.91 (d, J = 7.9 Hz, 2H), 5.98–5.89 (m, 1H), 5.28 (s, 1H), 3.95
(dd, J = 9.3, 7.2 Hz, 1H), 3.80 (dd, J = 9.3, 7.8 Hz, 1H), 3.66 (q, J = 8.1 Hz, 1H), 3.47
(s, 3H), 2.23 (s, 3H), 1.54 (d, J = 1.3 Hz, 9H), 1.31–1.05 (m, 12H), 0.75 (d, J = 7.6 Hz,
9H), 0.66–0.58 (m, 6H), 0.55 (s, 2H); and 13C NMR (126 MHz, CDCl3) δ 173.2, 142.9,
136.7, 135.6, 133.0, 132.9, 129.5, 129.5, 129.1, 128.1, 127.8, 127.6, 127.1, 126.2, 126.1,
82.7, 70.7, 61.9, 59.6, 51.9, 29.1, 28.2, 27.4, 21.4, 13.7, 11.1.
cis-4f: 1H NMR (500 MHz, CDCl3) δ 7.82–7.77 (m, 1H), 7.72 (d, J = 8.6 Hz, 2H),
7.57 (s, 1H), 7.54 (d, J = 8.1 Hz, 2H), 7.49–7.41 (m, 3H), 7.16 (d, J = 8.0 Hz, 2H), 5.38
(d, J = 8.1 Hz, 1H), 5.04 (s, 1H), 3.85–3.75 (m, 2H), 3.72 (dd, J = 9.6, 5.2 Hz, 1H), 3.48
(s, 3H), 2.33 (s, 3H), 1.39 (s, 9H), 1.32–1.06 (m, 12H), 0.75 (t, J = 7.2 Hz, 9H), 0.67–0.58
(m, 6H), 0.56 (d, J = 13.0 Hz, 1H), 0.30 (d, J = 12.9 Hz, 1H); and 13C NMR (126 MHz,
CDCl3) δ 173.7, 143.5, 135.9, 133.1, 133.0, 129.5, 129.1, 128.1, 127.8, 127.7, 127.5,
127.5, 126.7, 126.1, 126.0, 82.2, 71.4, 64.3, 62.1, 60.6, 51.7, 29.1, 27.9, 27.4, 21.5, 13.7,
10.9.
(2R,3S)-tert-butyl 4-(methoxyamino)-2-(thiophen-2-yl)-1-tosyl-3- ((tributyls-
tannyl)methyl)pyrrolidine-3-carboxylate (4g): HRMS (ESI M + H) m/z 757.2717.
Calcd for C34H57N2O5S2Sn 757.2731.
trans-4g: Pale yellow oil; the enantiomeric purity was determined by HPLC analysis
(230 nm, 30 ◦C) tR 11.5 min (minor); tR 13.7 min (major) [CHIRALPAK IC (0.46 cm ×
25 cm) (from Daicel Chemical Ind., Ltd.) hexane/i-PrOH, 90/10, 0.70 mL/min] as 94%ee;
[α]D –32.8 (c 1.00, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.32 (d, J = 8.3 Hz, 2H), 7.12
(dd, J = 5.0, 1.2 Hz, 1H), 7.07 (d, J = 7.9 Hz, 2H), 6.86 (dd, J = 5.1, 3.4 Hz, 1H), 6.82
(dd, J = 3.5, 1.2 Hz, 1H), 6.05 (d, J = 8.2 Hz, 1H), 5.44 (s, 1H), 3.80–3.57 (m, 3H), 3.46
(s, 3H), 2.34 (s, 3H), 1.56 (s, 9H), 1.42–1.16 (m, 12H), 0.83 (t, J = 7.3 Hz, 9H), 0.77 (d, J
= 13.1 Hz, 1H), 0.71 (ddd, J = 9.5, 7.0, 2.3 Hz, 6H), 0.64 (d, J = 12.9 Hz, 1H); and 13C
NMR (126 MHz, CDCl3) δ 172.9, 142.7, 141.8, 136.8, 129.4, 129.1, 128.0, 127.0, 126.2,
125.8, 82.9, 67.3, 66.4, 61.8, 59.4, 50.8, 29.1, 7.2, 27.5, 21.6, 13.8, 11.1.

PREPARATION OF OPTICALLY ACTIVE 4-AMINOPYRROLIDINES
365
cis-4g: 1H NMR (500 MHz, CDCl3) δ 7.53 (d, J = 8.1 Hz, 2H), 7.20 (d, J = 8.1 Hz,
2H), 7.18 (dd, J = 3.8, 2.8 Hz, 1H), 6.92–6.87 (m, 2H), 5.52 (d, J = 8.6 Hz, 1H), 5.29
(s, 1H), 3.82–3.75 (m, 1H), 3.67 (dd, J = 10.4, 2.9 Hz, 1H), 3.56 (dd, J = 10.4, 5.7 Hz,
1H), 3.47 (s, 3H), 2.38 (s, 3H), 1.38 (s, 9H), 1.37–1.17 (m, 12H), 0.83 (t, J = 7.3 Hz, 9H),
0.75–0.70 (m, 6H), 0.68 (d, J = 12.8 Hz, 1H), 0.52 (d, J = 12.7 Hz, 1H); and 13C NMR
(126 MHz, CDCl3) δ 173.5, 143.3, 142.6, 135.0, 129.4, 127.8, 127.7, 126.3, 125.8, 82.4,
66.7, 64.2, 62.1, 60.7, 51.1, 29.1, 27.9, 27.5, 21.6, 13.8, 10.9.
(2S,3S)-tert-butyl 4-(methoxyamino)-2-propyl-1-tosyl-3-((tributylstannyl)met-
hyl)pyrrolidine-3-carboxylate (4h): Colorless oil; [α]D +15.8 (c 0.53, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 7.71 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.0 Hz, 3H), 5.29 (d, J =
7.4 Hz, 1H), 3.80 (dd, J = 8.3, 4.6 Hz, 1H), 3.53 (d, J = 7.1 Hz, 2H), 3.44 (s, 3H),
3.38–3.30 (m, 1H), 2.41 (s, 3H), 1.92 (dtd, J = 11.4, 6.9, 6.5, 3.3 Hz, 1H), 1.76–1.62 (m,
1H), 1.50–1.24 (m, 16H), 1.24 (s, 9 H), 0.96–0.81 (m, 19H), 0.78 (d, J = 12.9 Hz, 1H);
and 13C NMR (126 MHz, CDCl3) δ 174.0, 143.4, 135.0, 129.6, 127.8, 81.7, 67.3, 64.1,
62.0, 58.7, 51.2, 34.3, 27.8, 27.5, 21.6, 20.3, 14.3, 13.8, 11.4, 8.5; HRMS (ESI M + H)
m/z 717.3328. Calcd for C33H61N2O5SSn 717.3323.
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6. CCDC 903025 for trans-4e (major 4e) and CCDC 903026 for cis-4e (minor 4e) contain the
supplementary crystallographic data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/retrieving.html