Stereoselective total synthesis of penaresidin A starting from d-galactal

Article abstract of DOI:10.1016/j.tetlet.2013.10.095

A stereoselective total synthesis of penaresidin A has been accomplished involving Sharpless asymmetric epoxidation, regioselective ring-opening of epoxide, azetidine formation via S_N2 reaction, Jung's protocol, and Julia-Kocienski olefination.

Full text of DOI:10.1016/j.tetlet.2013.10.095

Tetrahedron Letters 55 (2014) 49–51
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Stereoselective total synthesis of penaresidin A starting
from D-galactal
⇑
B. V. Subba Reddy , Ch. Kishore, A. Srinivas Reddy
Natural Product Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A stereoselective total synthesis of penaresidin A has been accomplished involving Sharpless asymmetric
epoxidation, regioselective ring-opening of epoxide, azetidine formation via SN2 reaction, Jung’s protocol,
and Julia–Kocienski olefination. This approach has successfully demonstrated the synthetic utility of
Received 6 September 2013
Revised 17 October 2013
Accepted 20 October 2013
Available online 26 October 2013
D-galactal in the construction of azetidine core of the natural product.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
D-Galactal
Asymmetric epoxidation
Azetidine formation
Jung’s protocol
Julia–Kocienski olefination
Marine sponge is a rich source of various sphingosine deriva-
tives. In particular, penaresidin A (1) and B (2) were isolated from
Okinawan marine sponge Penares sp.1 in 1991 as a mixture of the
corresponding tetraacetyl derivatives (Fig. 1). They are known to
behave as potent actomyosin ATPase activators. Penaresidin A con-
stitutes an azetidine core which is separated from a hydroxy isobu-
tyl subunit by a long alkyl chain. The absolute configuration of the
five stereogenic centers was established as 2S,3R,4S,15S and 16S by
spectroscopic methods1,2 and subsequent synthetic studies.3
Following our interest on the total synthesis of natural prod-
ucts,4 we herein report a concise approach for the total synthesis
of allyl alcohol 7 under Sharpless conditions7 followed by ring
opening of the epoxide with Red-Al gave triol 9 in 57% yield. Pro-
tection of triol 9 with 2,2-DMP in the presence of cat. p-TSA gave
1,3-acetonide 10. The secondary hydroxyl group of 10 was pro-
tected as its mesylate and then converted into azide 11 using
NaN3 in DMF under reflux conditions. Reduction of azide with
LAH followed by tosylation with tosyl chloride and triethylamine
provided the tosyl derivative 12 in 90% yield. Removal of acetonide
12 using p-TSA in methanol followed by selective protection of the
primary hydroxyl group with tert-butyldiphenylsilyl chloride
afforded the TBDPS ether 6 in good yields. Conversion of free hy-
droxyl group of 6 as its mesylate using methanesulfonyl chloride
in pyridine followed by cyclization with NaH gave azetidine 13
in 51% yield over two steps. Desilylation of 13 using TBAF followed
by oxidation of the hydroxyl group with IBX in DMSO gave the key
of penaresidin A (1) starting from 3,4,6-tri-O-benzyl-D-galactal.
Our retrosynthetic analysis is shown in Scheme 1.
According to our approach, we envisaged that the target mole-
cule could be accomplished from the intermediate 3 through a Ju-
lia–Kocienski olefination of aldehyde 4 with sulfoxide 5. The
azetidine core 4 was assumed to be accessed from amino alcohol
6 which could in turn be prepared from allyl alcohol 7, derived
OH
OH
from 3,4,6-tri-O-benzyl-
be prepared from epoxy alcohol 8, derived from nonanediol.
The synthesis of the key fragment 4 began with -galactal.
-galactal with HgSO4
D-galactal. The sulfoxide moiety 5 could
HO
N
H
Penaresidin A (1)
D
OH
OH
Accordingly, treatment of 3,4,6-tri-O-benzyl-
D
in the presence of aq H2SO4 in dioxane5 at room temperature affor-
ded the hydroxy-trans-enal exclusively which was then subjected
to chemoselective reduction with CeCl3ꢀ7H2O/NaBH4 under Luche
conditions6 to furnish the allyl alcohol 7. Asymmetric epoxidation
HO
N
H
Penaresidin B (2)
OH
HO
N
H
Penazetidine
⇑
Corresponding author. Fax: +91 40 27160512.
E-mail address: basireddy@iict.res.in (B.V. Subba Reddy).
Figure 1. Representative examples of azetidine natural products.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.10.095

50
B. V. Subba Reddy et al. / Tetrahedron Letters 55 (2014) 49–51
OBn
OTBS
( )7
O
a
b
d
( )7
BnO
BnO
OEt
Penaresidin A (1)
HO
( )7 OH
N
Ts
14
3
OTBS
( )7
O
c
BnO
( )7
OH
BnO
OTBS
( )7
OBn
N
N
N
O
S
O
+
15
BnO
8
N
Ph
N
O
Ts
4
5
OTBS
( )7
OTBS
( )7
17
N
N
e
HO
N
O
S
N
OBn
( )7
BnO
O
OH
Ph
OTBDPS
16
BnO
8
6
NHTsOH
OTBS
N
N
N
N
N
O
S
f
N
A =
( )7
Nonanediol
N
SH
N
O
Ph
Ph
OBn
BnO
BnO
7
OH
BnO
OH
Scheme 3. Reagents and conditions: (a) (i) NaH, BnBr, DMF, 0 °C–rt, 5 h, (ii) (COCl)2,
DMSO, Et3N, ꢁ78 °C, (iii) Ph3P@C(CH3)CO2Et, benzene, reflux, 6 h, 73%; (b) (i)
DIBAL-H, CH2Cl2, 0 °C, (ii) (+)-DIPT, Ti(OiPr)4, TBHP, CH2Cl2, 4 Å MS, ꢁ20 °C, 4 h; (c)
TBSOTf, DIPEA, MS 4 Å, ꢁ78 °C, 3 h, (ii) n-BuLi, Ph3PCH3Br, THF, ꢁ78 °C, 56%; (d)
Pd(OH)2, MeOH, H2, 5 h, 90%; (e) A, Ph3P, DIAD, THF, 0–rt, 3 h, 80%; (f) ammonium
molybdate, H2O2, EtOH, 6 h, 85%.
7
OBn
Scheme 1. Retrosynthetic analysis of penaresidin A.
OBn
O
a
b
BnO
BnO
OH
BnO
OBn
OTBS
( )7
N
N
N
a
O
S
O
OH
7
O
+
BnO
BnO
OBn
OBn
N
N
Ph
Ts
4
5
OBn
d
c
OH
OBn
OH
( )7
BnO
BnO
BnO
OBn
OTBS
( )7
b
OH OH
9
OH
O
O
BnO
N
N
10
Ts
Ts
3
18
OBn
OBn
e
f
BnO
OH
OH
( )7
N3
11
O
O
NHTsO
O
c
HO
N
H
12
.AcOH
19
OBn
OBn
g
OTBDPS
OTBDPS
OBn
Scheme 4. Reagents and conditions: (a) KHMDS, THF, ꢁ78 °C, 70%; (b) P-TSA,
MeOH, rt; (c) (i) Pd/C, H2, EtOH, 4 h, 85%, (ii) Na, naphthalene, DME, 0 °C.
BnO
BnO
N
Ts
NHTsOH
6
13
then subjected to Sharpless asymmetric epoxidation9 to afford
the epoxy alcohol 8. Protection of 8 with TBSOTf and DIPEA in
DCM at ꢁ20 °C under Jung’s conditions10 afforded the aldehyde,
which was further treated with a C1 ylide to give the terminal ole-
fin 15. Reduction of 15 with Pd(OH)2/C afforded the alcohol 16 in
90% yield, which was then converted into thioester 17 using 1-phe-
nyl-1H-tetrazole-5-thiol in the presence of TPP/DIAD. Oxidation of
thioester with molybdenum salt and hydrogen peroxide gave sul-
fone 5 in 85% yield (Scheme 3).
Having both aldehyde and sulfone fragments in hand, we next
attempted the Julia–Kocienski olefination using KHMDS as a base
at ꢁ78 °C to give the olefin 3 in 70% yield. Desilylation of 3 with
p-TSA in methanol gave alcohol 18 in 80% yield (Scheme 4). Treat-
ment of 18 with 10% Pd/C under hydrogen atmosphere followed by
treatment with Na/naphthalene and a subsequent salt formation
with acetic acid gave the acetic acid salt of the target molecule
19 in 60% yield (Scheme 4). The spectral data of penaresidin A
(1) were in good agreement with the data reported in the
literature.3e,11
h
O
BnO
N
Ts
4
Scheme 2. Reagents and conditions: (a) (i) HgSO4/aq H2SO4, dioxane, rt, 12 h, (ii)
CeCl3ꢀ7H2O, NaBH4, CH3OH, 0 °C, 1 h, 65% two steps; (b) (i) (+)-DIPT, Ti(OiPr)4, TBHP,
CH2Cl2, 4 Å MS, ꢁ20 °C, 6 h, (ii) Red-Al, THF, 0 °C, 8 h, 57% two steps; (c) 2,2-DMP,
p-TSA, CH2Cl2, 4 h, 85%; (d) (i) MsCl, Et3N, CH2Cl2, 0 °C, 4 h, (ii) NaN3, DMF, 90 °C,
6 h, 75%; (e) (i) LiAlH4, THF, 0 °C, (ii) TsCl, Et3N, CH2Cl2, 0 °C, 3 h, 90%; (f) (i) p-TSA,
CH3OH, 0 °C, 1 h, (ii) TBDPSCl, imidazole, CH2Cl2, rt, 72%; (g) (i) MsCl, pyridine, 0 °C,
(ii) NaH, THF, 0 °C, 51%; (h) (i) TBAF, THF, rt, 3 h, (ii) IBX, DMSO, CH2Cl2, 0 °C, 2 h,
56% two steps.
aldehyde 4, which was used directly in Julia–Kocienski olefination
(Scheme 2).
Another key fragment 5 was prepared from 1,9-nonanediol.
Mono-protection of nonanediol as its benzyl ether followed by oxi-
dation and a subsequent Wittig reaction with a stable ylide gave
the 2,3-unsaturated ester 14 in 73% yield with E-stereoselectivity.
The stereochemistry of olefin was confirmed by comparing the
chemical shift value of methyl protons attached to olefinic carbon
with previous reports.8 Further treatment of ester 14 with DIBAL-H
in CH2Cl2 gave the methyl substituted allylic alcohol, which was
In conclusion, we have developed an efficient synthetic
approach for the synthesis of penaresidin A starting from 3,4,6-
D-galactal and 1,9-nonanediol. The key steps
involved in this synthesis are Sharpless asymmetric epoxidation,
tri-O-benzyl-

B. V. Subba Reddy et al. / Tetrahedron Letters 55 (2014) 49–51
51
(E)-Ethyl 11-(benzyloxy)-2-methylundec-2-enoate (14): IR (neat):
1710, 1648, 1448, 1366, 1266, 1096, 1028, 742, 670 cmꢁ1
m
2930, 2860,
regioselective ring-opening of epoxide, SN2 reaction for azetidine
formation, Jung’s protocol, and Julia–Kocienski olefination. The
azedine core was constructed from the allyl alcohol 7, which was
in turn derived from D-galactal in two steps with 65% yield. The
reactions involved in the azetidine formation, are highly stereose-
lective with no possibility of formation of other stereoisomers. The
;
1H NMR (500 MHz,
CDCl3): d 7.31 (m, 5H), 6.76 (m,1H), 4.50 (s, 2H, 4.19) (q, J = 7.2 Hz, 2H), 3.46 (t,
J = 6.6 Hz, 2H), 2.19–2.12 (m, 2H), 1.82 (s, 3H), 1.60 (m, 2H), 1.43–1.28 (m,
13H); 13C NMR (75 MHz, CDCl3): d 169.0, 138.6, 133.2, 129.5, 128.2, 127.5,
127.4, 72.7, 70.3, 60.1, 34.3, 29.6, 29.2, 29.1, 28.9, 17.2, 14.2; ESI-MS [M+Na]
341.
((2S,3S)-3-(8-(Benzyloxy)octyl)-2-methyloxiran-2-yl)methanol (8): ½a D25
ꢁ50 (c
ꢂ
0.3, CHCl3); IR (neat):
m 3428, 2929, 2858, 1602, 1455, 1384, 1276, 1114, 1070,
present synthetic approach involves 19 steps from
2.1% overall yield.
D-galactal with
713 cmꢁ1 1H NMR (300 MHz, CDCl3): d 7.33 (m, 5H), 4.51 (s, 2H), 3.63 (m, 2H),
;
3.47 (t, J = 6.8 Hz, 2H), 3.03 (t, J = 6.8 Hz, 1H), 1.60 (m, 4H), 1.34 (m, 10H, 1.28
(s, 3H); 13C NMR (75 MHz, CDCl3): d 132.7, 129.9, 128.2, 73.9, 67.3, 65.0, 62.6,
29.3, 29.1, 28.5, 26.7, 25.8. ESI-MS [M+Na] 329; HRMS [M+Na] calcd for
Acknowledgements
C19H30O3Na 329.2087, found: 329.2084.
(((3S,4S)-12-(Benzyloxy)-3-methyldodec-1-en-4-yl)oxy)(tert-butyl)dimethylsilane
Ch.K. thanks UGC New Delhi, for the award of a fellowship.
B.V.S. thanks CSIR, New Delhi for financial support as a part of
XII five year plan under title DENOVA (CSC-0205).
(15): ½a 2D5
ꢂ
ꢁ7 (c 1.7, CHCl3). IR (neat):
m 3067, 2930, 2855, 1638, 1431, 1253,
1102, 836, 773 cmꢁ1
;
1H NMR (300 MHz, CDCl3): d 7.30 (m, 5H), 5.85 (m, 1H),
4.98 (m, 2H), 4.50 (s, 2H), 3.52 (m, 1H), 3.46 (t, J = 6.0 Hz, 2H), 1.61 (m, 2H),
1.32 (m, 12H), 0.96 (d, J = 6.8 Hz, 3H), 0.89 (s, 9H), 0.03 (s, 6H); 13C NMR
(75 MHz, CDCl3): d 141.7, ‘138.7, 128.3, 127.4, 113.6, 75.9, 72.8, 70.5, 42.7, 33.8,
29.7, 29.5, 29.4, 26.2, 25.9, 25.2, 18.2, 14.8, ꢁ4.3, ꢁ4.4; ESI-MS [M+Na] 441.
References and notes
(9S,10S)-9-((tert-Butyldimethylsilyl)oxy)-10-methyldodecan-1-ol (16): ½a D25
ꢁ2 (c
ꢂ
3.0, CHCl3); IR (neat):
m 3339, 2930, 2857, 1464, 1381, 1252, 1056, 835, 773,
1. Kobayashi, J.; Cheng, J.-F.; Ishibashi, M.; Wälchli, M. R.; Yamamura, S.; Ohizumi,
Y. J. Chem. Soc., Perkin Trans. 1 1991, 1135.
2. Kobayashi, J.; Tsuda, M.; Cheng, J.-F.; Ishibashi, M.; Takikawa, H.; Mori, K.
Tetrahedron Lett. 1996, 37, 6775–6776.
3. (a) Knapp, S.; Dong, Y. Tetrahedron Lett. 1997, 38, 3813; (b) Takikawa, H.;
Maeda, T.; Seki, M.; Koshino, H.; Mori, K. J. Chem. Soc., Perkin Trans. 1 1997, 111;
(c) Takikawa, H.; Maeda, T.; Mori, K. Tetrahedron Lett. 1995, 36, 7689; (d) Liu,
D.-G.; Lin, G.-Q. Tetrahedron Lett. 1999, 40, 337; (e) Raghavan, S.; Krishnaiah, V.
J. Org. Chem. 2010, 75, 748.
4. (a) Reddy, B. V. S.; Reddy, B. P.; Pandurangam, T.; Yadav, J. S. Tetrahedron Lett.
2011, 52, 2306; (b) Reddy, P. J.; Reddy, A. S.; Yadav, J. S.; Reddy, B. V. S.
Tetrahedron Lett. 2012, 53, 4051; (c) Kishore, Ch.; Reddy, A. S.; Yadav, J. S.;
Reddy, B. V. S. Tetrahedron Lett. 2012, 53, 4551.
5. (a) Gonzalez, F.; Lesage, S.; Perlin, A. S. Carbohydr. Res. 1975, 42, 267; (b) Sagar,
R.; Pathak, R.; Shaw, A. K. Carbohydr. Res. 2004, 339, 2031; (c) Hirata, N.;
Yamagiwa, Y.; Kamikawa, T. J. Chem. Soc., Perkin Trans 1 1991, 2279.
6. Germal, A. L.; Luche, J. L. J. Am. Chem. Soc. 1981, 103, 5454.
7. Sagar, R.; Reddy, L. V. R.; Shaw, A. K. Tetrahedron: Asymmetry 2006, 17, 1189.
8. (a) Gaich, T.; Karig, G.; Martin, H. J.; Mulzer, J. Eur. J. Org. Chem. 2006, 3372; (b)
Yadav, J. S.; Raju, A.; Ravinder, K.; Reddy, B. V. S. Tetrahedron Lett. 2013, 54,
3227.
9. (a) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974; (b) Gao, Y.;
Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J. Am.
Chem. Soc. 1987, 109, 5765.
10. (a) Jung, M. E.; D’Amico, D. C. J. Am. Chem. Soc. 1993, 115, 12208; (b) Jung, M. E.;
D’Amico, D. C. J. Am. Chem. Soc. 1997, 119, 12150; (c) Jung, M. E.; Lee, W. S.; Sun,
D. Org. Lett. 1999, 1, 307.
667 cmꢁ1 1H NMR (300 MHz, CDCl3): d 3.64 (J = 6.6 Hz), 3.51 (m, 1H), 1.57 (m,
;
2H), 1.28 (m, 14H), 0.88 (s, 9H), 0.83 (m, 16H), 0.03 (s, 3H), 0.02 (s, 3H); 13C
NMR (75 MHz, CDCl3): d 75.6, 63.1, 39.6, 36.6, 33.5, 32.8, 29.8, 29.6, 29.4, 27.1,
25.9, 25.2, 19.2, 18.2, 14.1, 13.8, 12.2, ꢁ4.2, ꢁ4.4. ESI-MS [M+H] 331.
5-(((9S,10S)-9-((tert-Butyldimethylsilyl)oxy)-10-methyldodecyl)thio)-2-phenyl-
2H-tetrazole (17): ½a D25
ꢂ
ꢁ3.5 (c 3.0, CHCl3); IR (neat):
m 3090, 2929, 2855, 1597,
1500, 1463, 1385, 1250, 1053, 835, 765 cmꢁ1
;
1H NMR (300 MHz, CDCl3): d
7.56 (m, 5H), 3.51 (m, 1H), 3.40 (t, J = 7.5 Hz, 2H), 1.82 (q, J = 5.5 Hz, 2H), 1.44
(m, 2H), 1.27 (m, 10H), 0.88 (s, J = 5.0 Hz, 9H), 0.83 (m, 6H), 0.03 (s, 3H), 0.02 (s,
3H); 13C NMR (75 MHz, CDCl3): d 154.4, 133.7, 129.9, 129.7, 123.8, 75.6, 39.6,
33.3, 33.5, 29.7, 29.4, 29.0, 28.6, 25.9, 25.8, 25.1, 18.1, 13.8, 12.2, ꢁ4.2, ꢁ4.5;
ESI-MS [M+H] 491; HRMS [M+H] calcd for C26H47ON4SSi 491.3234, found:
491.3222.
(2S,3R,4S)-3-(Benzyloxy)-2-((benzyloxy)methyl)-4-((11S,12S)-11-((tert-Butyldimethyl-
silyl)oxy)-12-methyltetradec-2-en-1-yl)-1-tosylazetidine (3): ½a D25
ꢁ15.0 (c 0.1,
ꢂ
CHCl3). IR (neat):
m ;
3448, 2925, 2854, 1461, 1259, 1159, 1093, 800, 772 cmꢁ1
1H NMR (300 MHz, CDCl3): d 7.68 (m, 2H), 7.24 (m, 12H), 6.16–5.64 (m, 1H),
5.52–4.86 (m, 1H), 4.49–4.35 (m, 4H), 4.19 (m, 1H), 3.67 (m, 1H), 3.45 (m, 2H),
2.55 (t, J = 6.6 Hz, 1H), 2.38 (s, 3H), 2.13–1.90 (m, 1H), 1.29 (s, 16H), 0.88 (s,
9H), 0.82 (m, 6H), 0.03 (s, 6H); 13C NMR (75 MHz, CDCl3): d 143.0, 136.5, 135.4,
133.8, 129.4, 129.0, 128.3, 127.7, 127.5, 127.4, 127.3, 127.2, 126.8, 125.1, 78.0,
75.6, 73.1, 72.2, 71.5, 70.5, 56.6, 39.6, 33.5, 32.7, 30.6, 29.8, 29.6, 29.5, 29.3,
29.1, 25.9, 25.2, 22.7, 21.5, 13.9, 12.3, ꢁ4.2, ꢁ4.4. ESI-MS [M+Na] 798.
(3S,4S)-14-((2S,3R,4S)-3-(Benzyloxy)-4-((benzyloxy)methyl)-1-tosylazetidin-2-yl)
-3-methyltetradec-12-en-4-ol (18): ½a D25
ꢂ
ꢁ13.3 (c 0.3, CHCl3). IR (neat):
m
3486,
.
3030, 2927, 2866, 1598, 1495, 1453, 1337, 1155, 1093, 1047, 700, 676 cmꢁ1
1H
NMR (300 MHz, CDCl3): d 7.67 (m, 2H), 7.24 (m, 12H), 6.12 (m, 1H), 5.96–5.66
(m, 1H), 5.49–5.19 (m, 1H), 4.41 (m, 4H), 4.18 (m, 1H), 3.93 (m, 1H), 3.71–3.36
(m, 3H), 2.39 (s, 2H), 2.11–1.93 (m, 2H), 1.33 (m, 16H), 0.88 (m, 6H); 13C NMR
(75 MHz, CDCl3): d 143.1, 138.0, 137.7, 137.9, 136.4, 135.4, 133.7, 129.4, 129.1,
128.3, 128.2, 127.7, 127.6, 127.5, 127.4, 127.3, 127.2, 126.8, 121.6, 78.9, 74.9,
73.1, 72.2, 71.5, 70.5, 69.8, 68.6, 68.4, 68.2, 56.6, 39.9, 34.5, 32.6, 31.9, 29.6,
29.5, 29.3, 26.2, 22.6, 21.5, 14.1, 13.1, 11.8. ESI-MS [M+Na] 684; HRMS [M+Na]
calcd for C40H55NO5SNa 684.3699, found: 684.3696.
11. (R)-4-((1S,2S)-2-Azido-1,3-bis(benzyloxy)propyl)-2,2-dimethyl-1,3-dioxane (11):
½
a 2D5
ꢂ
ꢁ1.0 (c 5.5, CHCl3). IR (neat):
m 3063, 2989, 2868, 2097, 1455, 1375,
1270, 1104, 741, 699 cmꢁ1 1H NMR (300 MHz, CDCl3): d 7.29 (m, 10H), 4.64 (s,
;
2H), 4.53 (d, J = 4.5 Hz, 2H), 3.98–3.43 (m, 7H), 1.67 (m, 1H), 1.46 (m, 1H), 1.36
(s, 3H), 1.32 (s, 3H); 13C NMR (75 MHz, CDCl3): d 137.8, 128.4, 128.1, 127.9,
127.8, 127.7, 127.6, 98.3, 81.0, 74.2, 73.3, 69.5, 68.9, 61.5, 59.7, 29.7, 27.1, 18.8;
ESI-MS [M+Na] 434; HRMS [M+Na] calcd for C23H29O4N3Na 434.2050, found:
434.2043.
Penaresidine A acetic acid salt (19): ½a D25
ꢂ
ꢁ15.0 (c 0.25, CHCl3); IR (neat):
m 3427,
(2S,3R,4S)-3-(Benzyloxy)-2-((benzyloxy)methyl)-4-(2-((tert-butyldiphenylsilyl)oxy)
2924, 2854, 1565, 1410, 1123, 654 cmꢁ1
;
1H NMR (500 MHz, CD3OD): d 4.53–
ethyl)-1-tosylazetidine (13): ½a D25
ꢂ
+16.9 (c 7.3, CHCl3). IR (neat):
m
3282, 3066,
;
3031, 2927, 2857, 2097, 1596, 1455, 1331, 1160, 1107,740, 703 cmꢁ1
1H NMR
4.49 (m, 1H), 4.21–4.15 (m, 1H), 4.07–4.02 (m, 1H), 3.85–3.80 (m, 2H), 3.45–
3.41 (m, 1H), 1.96–1.79 (m, 2H), 1.90 (s, 3H), 1.53–1.44 (m, 1H), 1.43–1.22 (m,
19H), 1.20–1.14 (m, 1H), 0.91 (t, J = 7.3 Hz, 3H), 0.86 (t, J = 6.3 Hz, 3H); 13C NMR
(75 MHz, CD3OD): d 178.3, 75.5, 69.8, 66.6, 65.1, 60.0, 41.5, 35.4, 30.9, 30.8,
30.75, 30.7, 30.6, 30.5, 27.9, 27.5, 27.1, 26.2, 13.9, 12.3. ESI-MS: 330 [M+H].
HRMS (ESI): m/z [M+H] calcd for C19H40NO3 330.3008, found: 330.2994.
(300 MHz, CDCl3): d 7.67 (m, 5H), 7.42 (m, 5H), 5.12 (d, J = 7.7 Hz, 1H), 4.63 (m,
2H), 4.30 (d, J = 2.4 Hz, 2H), 3.81 (m, 2H), 3.69 (t, J = 5.2 Hz, 1H), 3.57 (m, 1H),
3.31 (m, 1H), 2.34 (s, 3H), 1.76 (m, 2H), 1.05 (s, 9H); 13C NMR (75 MHz, CDCl3):
d 138.8, 129.5, 128.3, 127.8, 127.5, 113.8, 75.9, 74.9, 70.9, 70.7, 60.1, 55.2, 39.5,
36.0, 33.8, 32.0, 24.5, 22.6, 14.0. ESI-MS [M+H] 720; HRMS [M+H] calcd for
C
43H50O5NSSi 720.3173, found: 720.3172.