Samarium Iodide-Promoted Asymmetric Reformatsky Reaction of 3-(2-Haloacyl)-2-oxazolidinones with Enals

Article abstract of DOI:10.1021/acs.joc.9b01219

3-(2-Haloacyl)-2-oxazolidinones were shown to react with enals in an asymmetric SmI₂-promoted Reformatsky reaction to give stereochemically well-defined 3-hydroxy-4-alkenyl- and 3-hydroxy-2-methyl-4-alkenyl imides. Chirality transfer of the Evans (S)-oxazolidinone unit via a Zimmerman-Traxler-like transition state resulted in Reformatsky products with a relative syn-configuration. The absolute configuration of compounds obtained is opposite to the corresponding products obtained via aldol addition of boron enolates to enals using the same Evans oxazolidinones.

Full text of DOI:10.1021/acs.joc.9b01219

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Article
Samarium Iodide-Promoted Asymmetric Reformatsky
Reaction of 3-(2-Haloacyl)-2-oxazolidinones with Enals
Moritz Sinast, Marco Zuccolo, Jonathan Wischnat, Tobias Sube,
Fabian Hasnik, Angelika Baro, Sabrina Dallavalle, and Sabine Laschat
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01219 • Publication Date (Web): 25 Jul 2019
Downloaded from pubs.acs.org on July 25, 2019
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Samarium Iodide-Promoted Asymmetric
Reformatsky Reaction of 3-(2-Haloacyl)-2-
oxazolidinones with Enals
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Moritz Sinast,†,§ Marco Zuccolo,†,‡,§ Jonathan Wischnat, Tobias Sube, Fabian Hasnik,
†
†
†
†
‡
*,†,iD
Angelika Baro, Sabrina Dallavalle, and Sabine Laschat
†Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart,
Germany
e-mail: sabine.laschat@oc.uni-stuttgart.de
‡Department of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano,
Via Celoria 2, 20133 Milano, Italy
Supporting Information
ABSTRACT: 3-(2-Haloacyl)-2-oxazolidinones were shown to react with enals in an asymmetric
SmI -promoted Reformatsky reaction to give stereochemically well-defined 3-hydroxy-4-
2
alkenyl- and 3-hydroxy-2-methyl-4-alkenyl imides. Chirality transfer of the Evans (S)-
oxazolidinone unit via a Zimmerman-Traxler-like transition state resulted in Reformatsky
products with a relative syn-configuration. The absolute configuration of compounds obtained is
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opposite to the corresponding products obtained via aldol addition of boron enolates to enals
using the same Evans oxazolidinones.
KEYWORDS: asymmetric synthesis, C-C coupling, Reformatsky reaction, Evans auxiliary,
samarium
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Graphical abstract
OH R4
O
O
samarium iodide-promoted
Reformatsky reaction
O
O
O
X
O
N
O
N
N
R3 this work
R2
R2
R1
R4
R1
O
H
R3
OH R4
O
O
O
O
N
O
R3
previous work
R2
aldol addition
via boron enolates
R2
R1
R1
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
INTRODUCTION
In 1977 Kagan discovered samarium(II) iodide as a powerful single electron reducing agent,
1
that mediates both radical and ionic reactions. This finding led to its broad applications in
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organic synthesis. Prominent examples of SmI -mediated reactions are pinacol-type couplings,
2
radical alkene-alkyne couplings, aldol-type reactions, Barbier, Grignard and Reformatsky
2
reactions. While Reformatsky reactions of -bromo esters and -bromo ketones in the presence
3
of SmI to the corresponding -hydroxy esters have been already reported by Kagan, the first
2
4
intramolecular asymmetric variant has been studied by Molander. Much later, the first
intermolecular asymmetric samarium Reformatsky reactions were developed by Fukuzawa
utilizing -bromoacetyl-2-oxazolidinones as source of chirality.5–7 Skrydstrup employed N-
8
acyloxazolidinones as acyl radical equivalents in SmI -promoted couplings to N-acrylamides. In
2
Reformatsky reactions with -haloacetyl-2-oxazolidinones the substrate scope was further
extended by Burke towards -aminoaldehydes paving the way for pharmacologically relevant
9
isostatine and dolaisoleucine. Despite these impressive results, progress in asymmetric
intermolecular samarium Reformatsky reactions is still slow,10 in particular enals were only
rarely employed as electrophilic substrates.11–13 Such stereoselective cross couplings would be
interesting, because the resulting -hydroxy--alkenyl-ketones (amides, esters or acids) are
1
4
15
16
subunits of natural products such as eremofortin F, stellatolide H, stellettapeptins A and B,
mohangic acids,17 ieodomycin C,18 or largazole19 (Figure 1). Furthermore, they are valuable
synthetic scaffolds for the synthesis of complex target molecules, as was exemplified in the total
synthesis of pleuraspiroketals A, B,20 (–)-clavosolide A, B,21 bistramide K,22 solomonamide,23
azaspirene,24 dolatrienoic acid, and ferrulactone. The -hydroxy--alkenyl-ketone unit has
7
25
been previously accessed via stereoselective aldol reactions using Evans oxazolidinones.26–29
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O
O
OH
OH
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HO
eremofortin F
OH
OH
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OH
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ieodomycin C
OH
OH
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O
OH
HN
subunit of stellatolide H
O
OH
HN
subunit of stellettapeptins A, B
O
O
O
S
N
H
subunit of largazole
Figure 1. Natural compounds or subunits of natural compounds containing the -hydroxy--
alkenyl-ketone (amide, ester or acid) residue
Regarding chirality transfer, these studies revealed that the aldol addition of boron enolates
strongly favoured the syn-aldol products and the stereogenic centre at C-4 of the oxazolidinone
directed the hydroxy group to the opposite face,21,26,28 while the E- or Z-configuration of the enal
had almost no influence on the stereochemical outcome of the C–C coupling (Scheme 1, routes
2
8
5
9
a
-
c
)
.
I
n
c
o
n
t
r
a
s
t
,
t
h
e
s
a
m
a
r
i
u
m
R
e
f
o
r
m
a
t
s
k
y
r
e
a
c
t
i
o
n
s
r
e
p
o
r
t
e
d
b
y
F
u
k
u
z
a
w
a
a
n
d
B
u
r
k
e
provided the -hydroxyimides lacking an -substituent with the hydroxy group and the
stereodirecting isopropyl moiety of the Evans auxiliary positioned on the same side (Scheme 1,
routes d,e). Thus, it was our intention to probe the suitability of enals as substrates in such
samarium Reformatsky reactions. We were particularly interested in terpene-derived enals,
which might enable the C–C coupling with complementary stereocontrol as compared to the
boron aldol reaction.28
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Scheme 1. Selected C–C coupling reactions from the literature and the current work
OH R4
O
O
O
O
1) via boron enolate
a)
R3 [21,26]
O
N
O
N
R4
R2
R
R2
O
R
2)
R
R1
R
R1
H
R3
1
2
3
1
1
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0
O
O
O
O
O
OH
1
) via boron enolate
b)
O
O
N
O
O
N
[28]
O
)
2
4a
6a
dr > 95:5
H
neral (Z)-5
O
O
O
OH
1) via boron enolate
c)
N
N
O
)
2
[28]
H
4b
geranial (E)-5
6b
dr > 99:1
O
O
O
O
O
O
OH
SmI2
Br
Cl
d) O
N
N
O
O
N
R
[5]
[9]
O
H
R
7a
8
9
O
O
OH
SmI2
R
e)
O
N
O
N
R
Boc
H
10
7b
N
11
Boc
O
O
O
O
OH R4
X
SmI2
R4
R3
O
N
O
N
R2
O
R2
this work
R1
R1
R3
H
2 X = Br, R2 = Me
7a,b
2
13 R2 = H
1
14 R2 = Me
In addition, we were curious about the chirality transfer to the -substituent in the N-acyl chain
C-2'). In the current manuscript we demonstrate the successful implementation of aliphatic and
(
aryl-substituted enals in the SmI -promoted Reformatsky reaction and elucidate the stereocontrol
2
at the -position. Moreover, by using the Evans oxazolidinone auxiliary with the same
configuration as in reaction a) in Scheme 1, syn--hydroxy--alkenyl-imides are obtained, which
are stereocomplementary to the boron-enolate-derived aldol products (Scheme 1). The results are
discussed below.
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
RESULTS AND DISCUSSION
Reformatsky Reactions of Terpene Enals (E)- and (Z)-5. Initially, Reformatsky reactions
were carried out with 3-(2-haloacetyl)oxazolidinones 7a,b30,31 and geranial (E)-5 and neral (Z)-
0
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.31,32 The results are summarized in Table 1. In a preliminary experiment geranial (E)-5 and 3-
(2-bromoacetyl)oxazolidinone 7a were added simultaneously to a cooled solution of 2.2 equiv
SmI (SmI source see Experimental Section) in THF at –78 °C, and the reaction mixture was
2
2
stirred for 1 h (method A). After aqueous workup and chromatographic purification, compound
(3'R,4'E)-13a was obtained as a single diastereomer albeit in a low yield of 32% (entry 1). In a
similar fashion neral (Z)-5 yielded one diastereomeric product (3'R,4'Z)-13a in 23% (entry 2).
Monitoring of these reactions by TLC revealed several spots. The ability of SmI to reduce
2
carbonyl compounds and to promote reductive pinacol-type carbonyl couplings or
2
polymerizations is well known. Presumably, reduction of terpene enals and coupling of radical
intermediates compete with the SmI -mediated Reformatsky reaction leading to the consumption
2
of SmI and formation of byproducts. Hence, the reaction was modified, and a solution of SmI
2
2
in THF was cooled to –78 °C prior to addition of a solution of 3-(2-bromoacetyl)oxazolidinone
a in THF. The resulting mixture was stirred for 5 min in the dark to permit formation of the
7
Sm(III) enolate, followed by slow addition of the enal 5 (method B). After 0.5 h, TLC indicated
almost complete conversion. The reaction mixture was stirred for a further 0.5 h followed by
workup. Under these conditions the Reformatsky reactions proceeded much cleaner with less
byproducts. Geranial (E)-5 gave the diastereomers (3'R,4'E)-13a and (3'S,4'E)-13a in 73% and
6
% yield (dr 92 : 8, entry 3), while neral (Z)-5 yielded (3'R,4'Z)-13a and (3'S,4'Z)-13a in 71%
and 7% yield (dr 91 : 9, entry 4). Both yields and diastereoselectivities were not affected by the
configuration of the enal C=C double bond.
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Table 1. SmI -Mediated Reformatsky Reaction of 3-(Haloacetyl)oxazolidinones 7a,b with
2
Terpene Enals (E)-5 and (Z)-5a,b
O
O
X
H
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
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4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
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8
9
0
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8
9
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8
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0
O
N
+
O
7
7
a X = Br
b X = Cl
(E)-5 or (Z)-5
SmI , THF, 1 h
2
O
O
OH
O
O
OH
3
'
O
N
O
+ O
N
O
2
'
4'
(
3'R,4'E)-13a
(3'S,4'E)-13a
O
OH
O
OH
O
N
+
O
N
(
3'R,4'Z)-13a
(3'S,4'Z)-13a
entry 7
enal
T (°C) method isolated yield (%) ratioc
1
2
3
7a (E)-5 –78
7a (Z)-5 –78
7a (E)-5 –78
A
A
B
(3'R,4'E)-13a 32
(3'R,4'Z)-13a 23
(3'R,4'E)-13a 73
100 : 0
100 : 0
92 : 8
(3'S,4'E)-13a
(3'R,4'Z)-13a 71
3'S,4'Z)-13a
6
4
7a (Z)-5 –78
B
91 : 9
(
7
5
6
7
8
9
7a (E)-5 –100
7a (Z)-5 –100
7b (E)-5 –78
7b (Z)-5 –78
7b (E)-5 –100
B
B
B
B
B
B
(3'R,4'E)-13a 59
(3'R,4'Z)-13a 54
(3'R,4'E)-13a 48
(3'R,4'Z)-13a 43
(3'R,4'E)-13a 56
(3'R,4'Z)-13a 50
90 : 10
90 : 10
89 : 11
90 : 10
90 : 10
91 : 9
1
0
7b (Z)-5 –100
a
b
SmI (0.1 M, THF). Method A: simultaneous addition of enal and
2
oxazolidinone to a cooled solution of SmI in THF; method B: 1) ad-
2
dition of oxazolidinone to a cooled solution of SmI in THF; 2) equi-
2
c
libration for 5 min; 3) addition of enal. Diastereomeric ratios were de-
termined by isolation.
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Lowering the temperature to –100 °C led to decreased yields, but comparable diastereomeric
ratios, i.e. (3'R,4'E)-13a (59%, dr 90 : 10) and (3'R,4'Z)-13a (54%, dr 90 : 10) (entries 5, 6). The
decreased reaction rate is probably due to the poor solubility of the Sm(III) enolate at –100 °C. It
should be noted that additives such as HMPA enhance the reduction potential of SmI2.2b,d,33
0
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However, we avoided using toxic additives in the reaction. Alternatively, SmI might lead to
2
reductive cleavage of the oxazolidinone auxiliary as recently reported by Frontier.34
When the corresponding 3-(2-chloroacetyl)oxazolidinone 7b was employed under these con-
ditions, yields were generally lower than those with 3-(2-bromoacetyl)oxazolidinone 7a, but in-
creased with decreasing temperature. The diastereoselectivity, however, remained unchanged
(dr ~ 90 : 10) (Table 1, entries 7, 9 and 8, 10).
To investigate the reactivity of secondary halides and the effect of chirality at the halide on the
outcome of the Reformatsky reaction, 3-(2-bromopropanoyl)oxazolidinone 1231,35 was employed
in a series of experiments (Table 2). First, diastereomeric mixtures of 12 (dr 67 : 33) were
reacted with geranial (E)-5 and neral (Z)-5, respectively, under the conditions of method B
described above, providing diastereomeric mixtures of (E)-14a (dr 63 : 21 : 16) and (Z)-14a
(
dr 71 : 20 : 9), respectively, from which the major diastereomers (2'R,3'S,4'E)-14a and
2'R,3'S,4'Z)-14a could be isolated in 55% and 59%, respectively (entries 1 and 2).
(
3
5
Because of the rapid epimerization of 3-(2-bromopropanoyl)oxazolidinone, the diastereomers
(2'R)-12 and (2'S)-12 were separated by chromatography and immediately used for the reactions.
However, diastereomeric ratios and yields did not change markedly (entries 3–6), suggesting that
neither rate nor selectivity forming step is affected by the stereogenic centre at the 2-bromo-
propanoyl unit.
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7
8
9
Table 2. SmI -Mediated Reformatsky Reaction of 3-(2-Bromopropanoyl)oxazolidinone 12
2
with Terpene Enals (E)-5 and (Z)-5a,b
O
O
O
O
Br
or
Br
E/Z
H
O
N
O
N
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
O
(E)-5 or (Z)-5
(
2'R)-12
(2'S)-12
SmI , THF, 78 °C, 1 h
2
O
O
O
OH
O
O
OH
2'
4'
O
O
N
3'
+
+
O
N
N
(2'R,3'S,4'E)-14a
2'R,3'S,4'Z)-14a
(2'S,3'R,4'E)-14a
(2'S,3'R,4'Z)-14a
(
syn,syn
anti,syn
O
OH
O
O
OH
N
O
(
(
2'R,3'R,4'E)-14a
2'R,3'R,4'Z)-14a
(2'S,3'S,4'E)-14a
(2'S,3'S,4'Z)-14a
syn,anti
anti,anti
entry 12
enal
yieldc (%)
ratio (R,S):(S,R):(R,R)d
(E)-14a 63 : 21 : 16
1
2
3
4
5
6
a
12 (67:33) (E)-5 (2'R,3'S,4'E)-14a 55
12 (67:33) (Z)-5 (2'R,3'S,4'Z)-14a 59
(Z)-14a 71 : 20 : 9
(E)-14a 63 : 22 : 15
(Z)-14a 70 : 19 : 11
(E)-14a 62 : 22 : 16
(Z)-14a 71 : 19 : 10
(2'R)-12
(2'R)-12
(2'S)-12
(2'S)-12
(E)-5 (2'R,3'S,4'E)-14a 52
(Z)-5 (2'R,3'S,4'Z)-14a 59
(E)-5 (2'R,3'S,4'E)-14a 53
(Z)-5 (2'R,3'S,4'Z)-14a 57
b
SmI (0.1 M, THF). Method B: 1) addition of oxazolidinone to a cooled
2
c
solution of SmI in THF; 2) equilibration for 5 min; 3) addition of enal. Isolated
yields; diastereomeric ratios were determined by isolation. (2'S,3'S)-diastereo-
2
d
mers were not observed.
Assignment of Relative and Absolute Configuration of Reformatsky Products 13, 14 and
Proposed Mechanism. The absolute configuration at the C-3' atom in the Reformatsky products
3
6
(
4'E)-13a and (4'Z)-13a was determined by applying Mosher’s method. Adopting a procedure
reported by Laschat28 geranial-derived Reformatsky product (4'E)-13a was esterified with
Mosher acyl chloride (R)- and (S)-MTPACl to afford the corresponding (S)- and (R)-MTPA
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1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
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4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
esters (S)-15a and (R)-15a in 85 and 84% yield, respectively (Scheme 2). In an analogous
fashion (S)- and (R)-MTPA esters (S)-15b and (R)-15b were prepared from neral-derived
Reformatsky products (4'Z)-13a in 70% and 80%, respectively.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Scheme 2. Conversion of Reformatsky Products 13a and 14a into the Corresponding
Mosher Esters (R)- and (S)-15a,b and (R)- and (S)-16a,b, respectively
4' H
H
O
9'
7'
5'
O
O
8
'
6'
(R) 3'
(S)
R)
(
R) CF3
(R)
CF3
O
O
O
2'
(
or
(S)-MTPACl
1'
MeO Ph
MeO Ph
O
N
O
O
N
O
(
(
R,E)-15a 84%
(R,E)-16a 87%
(R,Z)-16b 88%
(
E)-13a
(Z)-13a
15b
R,Z)-
80%
py, DMAP,
or
0 °Crt, 12 h
(
E)-14a
(Z)-14a
H
H
O
O
(
R)
(S)
(
S) CF3
(S) CF3
O
O
O
O
O
(R)
or
Ph OMe
Ph OMe
N
O
O
N
O
(R)-MTPACl
(S,E)-15a 85%
S,Z)-15b 70%
(S,E)-16a 88%
(S,Z)-16b 85%
(
3
6
1
Analysis of the differences in the chemical shifts between (R)- and (S)-Mosher ester in the H
NMR indicated the absolute configuration at C-3' as (3'R) for both (E)-geranial- and (Z)-neral-
derived Mosher esters (S)-15a, (R)-15a and (S)-15b, (R)-15b [Table S1, see Supporting Informa-
tion (SI)]. Following the same procedure, the Mosher esters 16 of diastereomerically pure (E)-
1
4a and (Z)-14a were prepared (Scheme 2). From the chemical shift differences between (R) and
(S) Mosher ester the (3'S) configuration at C-3' was assigned for (E)-geranial- and (Z)-neral-
derived Mosher esters (S)-16a, (R)-16a and (S)-16b, (R)-16b, respectively (Table S2, SI).
In order to assign the configuration at C-2', Reformatsky products (E)-14a, (Z)-14a were
converted into the conformationally locked cyclic acetals (E)- and (Z)-18 following a known
28
procedure (Scheme 3).
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Scheme 3. Synthesis of Acetals (E)- and (Z)-18 from Reformatsky Products (E)- and (Z)-14a
E/Z
4'
9'
7'
5'
8'
6'
3'
LiBH4
THF, MeOH
LiBH4
THF, MeOH
O
OH
2'
1'
0
°C, 3 h
O
N
O
0 °C, 3 h
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(E)-14a, (Z)-14a
OH
OH
OH
E)-17 (64%)
OH
(Z)-17 (60%)
(
(MeO)CMe2, PPTS, acetone, rt, 3 h
9'
7'
6'
8'
5'
4'
E
Z
3'
2
'
O
O
1'
O
O
(E)-18 (90%)
(Z)-18 (88%)
H
3'
H
4'
O
O
O
O
H
H
1'
2'
CH3
CH3
The chiral auxiliary was removed from (E)- and (Z)-14a in a (100 : 1) mixture of THF / MeOH
with LiBH in THF to yield the respective diols (E)- and (Z)-17 in 64% and 60% after workup
4
and chromatographic purification. Diols 17 were then reacted with 2,2-dimethoxypropane and
PPTS in acetone followed by workup and chromatography to provide acetals (E)- and (Z)-18 in
9
0% and 88%, respectively (Scheme 3).
NOESY correlations were used to assign the relative configuration at C-2'/C-3'.28 A strong
NOE between 2'-H and 3'-H was observed for acetal (E)-18, confirming a syn-configuration of
the stereogenic centers C-2'/C-3'. Analogous results revealed a syn-configuration of the
stereogenic centers C-2'/C-3' in acetal (Z)-18. Thus, irrespective of the geometry of the C=C
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
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3
4
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4
4
4
4
4
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4
5
5
5
5
5
5
5
5
5
5
6
double bond for both acetals (E)- and (Z)-18 a (2'S,3'S)-configuration was found. Consequently,
the major diastereomers (E)- and (Z)-14a are (2'R,3'S) configurated.
However, this procedure could not be used for minor diastereomers of 14a because of their
very low amounts. Hence, the absolute and relative configuration at C-2'/C-3' for these products
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
5
a
was proposed considering the transition state geometries published by Fukuzawa. In agreement
with the evidence reported by Evans and coworkers, enolization of N-acyl oxazolidinones leads
3
7
to the selective formation of (Z)-metal enolates. It is therefore reasonable to assume that this
5
a
geometry is involved also in case of samarium enolates. According to Fukuzawa, asymmetric
samarium(II) iodide-promoted Reformatsky reactions proceed via formation of a chelated
transition state. Adapting this model to our reaction we propose that samarium coordinates both
the enolate oxygen and the carbonyl group of the oxazolidinone auxiliary as well as the oxygen
of the incoming aldehyde (Scheme 4).
Scheme 4. Proposed Mechanism of Diastereomer Formation
SmIII
O
O
O
O
Br
SmI2
RCHO
O
N
O
O
N (Z)
1
2
(Z)-19
O
O
O
O
OH
O
O
OH
O
O
N
N
N
R
O
N
R
SmIII
SmIII
H
H
O
O
O
O
R
R
Me
Me
(2'R,3'S,4'E or Z)-14a (2'S,3'R,4'E or Z)-14a
main syn diastereomer minor syn diastereomer
A
Re attack
B
Si attack
O
O
O
O
O
OH
O
O
OH
O
N
N
O
N
R
O
N
R
SmIII
SmIII
H
H
O
O
Me Me
O
O
R
R
(
2'R,3'R,4'E or Z)-14a (2'S,3'S,4'E or Z)-14a
C
Re attack
D
Si attack
main anti diastereomer not observed
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Depending on the geometry of the enolate double bond and the relative topicity of enolate and
aldehyde four different transition state geometries A–D are possible. Re face attack at the enal
seems to be favoured (transition states A, C), because steric interactions between the
oxazolidinone isopropyl group and the enolate methyl group are minimized as compared to
transition states B, D. The observed stereochemistry of the main diastereomers 14 is fully
consistent with this hypothesis. The disfavored Si face attack at the enals (transition state B)
could yield the minor syn diastereomers. Magnesium(II) chloride-catalyzed aldol reactions of N-
acyl oxazolidinones with non-enolizable aldehydes were reported to afford selectively the anti
adducts. The authors suggest the involvement of a magnesium-chelating boat transition
structure.38 Assuming a similar structure in the case of samarium enolates could lead to the
formation of the minor anti diastereomer. However, from preliminary DFT calculations a boat
transition state seems to be unlikely because in such highly strained geometry the chelating
coordination of the samarium enolate by the oxazolidinone carbonyl group is not possible.
The mechanistic proposal is supported by the observation that (2E,6E)-8-[(4-methoxy-
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
1
benzyl)oxy]-3-(methoxymethyl)-7-methylocta-2,6-dienal 36 carrying an allylic methoxy group
did not react with 3-(2-bromoacetyl)oxazolidinone 7a (Scheme S5, SI). Presumably, the allylic
methoxy group in close proximity to the reactive site of the enol interfered with the chelate
complex between Sm(III) enolate and the oxazolidinone carbonyl, thus suppressing the C–C
bond forming step.
Reformatsky Reaction with Aryl- and Alkyl-substituted Enals. In order to further broaden
the scope of the samarium Reformatsky reaction, a series of aryl-substituted enals 2a–e31,39,40
was investigated using method B described above (Table 3).
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9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Table 3. SmI -Mediated Reformatsky Reaction of N-(2-Bromoacetyl)- and N-(2-Bromopro-
2
pionyl)oxazolidinone 7a, 12 with Enals 2a–ea,b
+
7a
O
O
OH
O
O
OH
SmI2 (0.1 M)
O
3
'
O
N
Ar + O
N
N
Ar
Ar
R1
THF, 78 °C, 1 h
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2ae
Ar
12 SmI2 (0.1 M), THF, 78 °C, 1 h
(
3'R)-13bf
(3'S)-13bf
+
O
O
OH
O
O
OH
O
O
OH
O
O
OH
2'
3'
Ar + O
O
N
Ar + O
N
Ar + O
N
(
2'R,3'S)-14bf
(2'S,3'R)-14bf
anti,syn
(2'R,3'R)-14bf
syn,anti
(2'S,3'S)-14bf
syn,syn
anti,anti
entry 7a, 12 2
Ar
yield c (%) ratio 13 ratio 14
(R):(S) (R,S):(S,R):(R,R):(S,S)
96 : 4
98 : 2
R1
H
1
2
3
4
5
6
7
8
9
1
7a
7a
7a
7a
7a
12
12
12
12
12
2a
(3'R)-13b
51
30
22
33
24
–
2b OMe (3'R)-13c
–
2c Me
2d Cl
(3'R)-13d
(3'R)-13e
99 : 1
–
94 : 6
–
2e NO2 (3'R)-13f
2a
2b OMe (2'R,3'S)-14c 63
–
–
–
–
–
–
–
H
(2'R,3'S)-14b 92
92 : 5 : 2 : 1
85 : 15 : 0 : 0
93 : 6 : 1 : 0
86 : 9 : 3 : 2
94 : 4 : 2 : 0
2c Me
2d Cl
(2'R,3'S)-14d 30
(2'R,3'S)-14e 34
0
2e NO2 (2'R,3'S)-14f 52
a
b
SmI (0.1 M, THF). Method B: 1) addition of oxazolidinone to a cooled solution of
2
c
SmI in THF; 2) equilibration for 5 min; 3) addition of enal. Isolated yields; dia-
2
stereomeric ratios were determined by HPLC.
Reaction of 3-(2-bromoacetyl)oxazolidinone 7a with cinnamic aldehyde 2a under the conditions
described above yielded a (96 : 4) diastereomeric mixture of the Reformatsky products 13b in
5
1% yield, from which the major diastereomer was (3'R)-13b (entry 1). Under similar conditions
p-substituted cinnamic aldehydes 2b–e gave poorer yields of 22–33%, but the diastereomeric
ratios were only little affected by the electronic influence of the p-substituent (dr 94 : 6 up to
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9 : 1) (entries 2–4). The Reformatsky reaction of 2e proceeded to 13f, but attempts to separate
the diastereomers by HPLC failed (entry 5).
Next, a series of experiments with 3-(2-bromopropionyl)oxazolidinone 12 was carried out. As
can be seen from Table 3, cinnamic aldehyde 2a yielded products 14b in 92% in a
diastereomeric ratio of (92 : 5 : 2 : 1) and the major isomer was assumed to be (2'R,3'S)-14b
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
entry 6). The other enals 2b–e gave Reformatsky products 14c–f in yields of 30–63% (entries 7–
0), which were generally higher as compared to 13c–f. Good diastereoselectivities ranging from
dr 85 : 15 : 0 : 0) up to (94 : 4 : 2 : 0) were obtained for 14c–f. All diastereomeric ratios for
1
(
compounds 13b–f and 14b–f were determined by analytical HPLC. In the case of derivatives
13d,e and 14c,d, the separation succeeded by HPLC on chiral stationary phases.
The minor anti (2'S,3'S)-diastereomer of 14b and 14e could be detected (entries 6 and 9) in
contrast to the other products 14c,d,f and the terpene enal derived (E)- and (Z)-14a (Table 2).
In an analogous manner to Reformatsky products 14a (Scheme 2), pure major diastereomer
1
4b was reacted with (R)- and (S)-MTPACl to yield the corresponding (S)- and (R)-Mosher
esters 16c31 (Table S3, SI). The NMR analysis confirmed for both (R)- and (S)-16c the (S)-
1
configuration at C-3'. NOESY H NMR experiments were performed for the assumed major
diastereomer (2'S,3'R)-14b revealing a syn-configuration (Figure S1, SI), which is in good
accordance with the transition state described above and thus, the (R)-configuration at C-2' was
concluded. The two other diastereomers (2'S,3'S)-14b and (2'R,3'R)-14b could not be isolated
and assigned due to their small amount. For the major diastereomers 14c–f the (2'R,3'S)-
configuration was assumed as well.
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1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
When crotonic aldehyde 2f was reacted with oxazolidinone 7a, product 13g was isolated in
4% (dr 90 : 10). Analogously, cyclopentene-1-carbaldehyde 2g yielded Reformatsky product
5
13h in 56% (dr 59 : 41) (Scheme 5).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Scheme 5. SmI -Mediated Reformatsky Reaction of Aldehydes 2a,f,g with Oxazolidinones
2
7a, 12 and 20a
O
O
OH
O
2f
2'
3'
O
N
R
O
O
SmI2 (0.1 M)
THF
Br
1
3g R = H (54%, dr 90:10)
O
N
14g R = Me (90%, dr 85:12:3)
R
78 °C, 1 h
O
O
OH
2'
7a or 12
3'
O
N
R
O
2g
13h R = H (56%, dr 59:41)
14h R = Me (78%, dr 52:35:7:6)
+
2a
O
O
SmI2 (0.1 M)
THF
O
O
OH
2'
3'
O
N
OH
O
N
90 °C, 2 h
Cl
OH
syn,syn-21 (27%)
20
a
The diastereomers of 13 and 14 could not be clearly assigned.
Under the same conditions the Reformatsky reaction of both 2f and 2g with oxazolidinone 12
resulted in diastereomeric mixtures 14g (85 : 12 : 3) and 14h (52:35:7:6) in isolated yields of
90% and 78%, respectively, which, however, could not be completely separated and assigned by
HPLC. To further probe the substrate scope of the Reformatsky reaction 3-(2-chloroacyl)ox-
3
1
azolidinone 20 carrying a quaternary carbon and a free alcohol moiety adjacent to the -carbon
was treated with SmI and cinnamic aldehyde 2a (Scheme 5). Gratifyingly, the desired product
2
syn,syn-21 was isolated as a single diastereomer, albeit in 27% yield. Thus, even under these
sterically demanding conditions the syn,syn-diastereomer was strongly favored.
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
CONCLUSION
Enals have been employed in asymmetric samarium Reformatsky reactions with 3-(2-haloacyl)-
-oxazolidinones 7a,b, 12 providing access to stereochemically well-defined 3-hydroxy-4-
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
alkenyl- and 3-hydroxy-2-methyl-4-alkenyl imides (13, 14). Chirality transfer of the Evans (S)-
oxazolidinone unit via a Zimmerman-Traxler-like transition state resulted in the (R)-
configuration of the hydroxy group in products 13a–f in case of 3-(2-haloacetyl)oxazolidinones
7
a,b. When 3-(2-bromopropionyl)oxazolidinone 12 was employed, the (S)-oxazolidinone moiety
led to the preferred formation of the (2'R,3'S)-configuration of the aldol unit, thus giving a
relative syn-configuration in Reformatsky products 14a–f. Moreover, their absolute
configuration is opposite to the corresponding products obtained via aldol addition of boron
enolates to enals using (S)-configurated oxazolidinones. Thus, the SmI -promoted Reformatsky
2
reaction of enals not only demonstrates the power of the Evans auxiliary to effectively control
the stereochemistry of C–C cross coupling reactions, but also provides a complementary entry
towards syn-3-hydroxy-2-methyl-4-alkenyl imides, yielding the mirror images of boron-enolate-
4
1
derived aldol products or titanium-enolate derived products. The synthetic utility of this novel
methodology can now be further explored in the synthesis of complex target molecules.

EXPERIMENTAL SECTION
All reactions were performed under nitrogen atmosphere using common Schlenk technique. All
reagents were used as purchased unless otherwise stated. Solvents were purified and dried by
standard procedures prior to use. SmI was purchased as solution (0.1 M, THF) in a sealed bottle
2
42
which could be used for several weeks without decomposition if stored at 4°C. NMR spectra
were recorded on 300, 400, 500 and 700 MHz spectrometers at room temperature with TMS as
1
13
an internal standard. Signals in H and C NMR spectra were assigned using COSY, HSQC,
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6
HMBC, and NOESY techniques. IR spectra were recorded on an FT-IR spectrometer at room
temperature. Mass spectra (MS) were recorded using the ESI-TOF technique. Optical rotation
was recorded at room temperature (Na-D-line, 589 nm). Diastereomeric ratios were determined
by analytical HPLC using a variable wave detector (180–800 nm), performed on a MS-
Analytical Kromasil column (250  4.6 mm, 100 Si 5 μm), a Chiralcel OJ-H column
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
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7
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9
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8
9
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1
2
3
4
5
6
7
8
9
0
(150  4.6 mm, 5 µm) or a Chiralcel OD-H column (250  4.6 mm, 5 µm). For preparative
HPLC a MZ-Analytical Orbit column (250  20 mm, 100 Sil 5 µm) was used. Thin layer chro-
matography was performed on silica gel 60 F254 precoated aluminium plates. Column chroma-
tography was carried out using silica gel (40–60 µm) with solvents distilled prior to use.
General Procedure for the Samarium-Mediated Reformatsky Reaction of N-Haloacyl-2-
oxazolidinones with Enals (GP1). To a solution of SmI (0.1 M in THF, 2.20 equiv) at –78 °C
2
was added dropwise a solution of the respective 7a,b, 12 or 20 (1.0 equiv) in abs. THF (3 mL),
and the reaction mixture was stirred for 5 min followed by dropwise addition of a solution of the
appropriate enal 5 or 2 (1.2 equiv) in abs. THF (3 mL). The reaction mixture was stirred at
–78 °C for 1 h. Then a satd solution of NH Cl–H O (20 mL) was added at –78 °C, and the
4
2
reaction mixture was allowed to warm to room temperature. The layers were separated and the
aqueous layer was extracted with EtOAc (3 × 15 mL). The combined organic layers were washed
with a satd solution of Na S O , dried (MgSO ) and concentrated under vacuum. The residue
2
2
3
4
was purified by chromatography on SiO2.
4S)-3-[(3R,4E)- and (3S,4E)-3-Hydroxy-5,9-dimethyldeca-4,8-dienoyl)-4-isopropyl-1,3-oxa-
(
zolidin-2-one [(3'R,4'E)- and (3'S,4'E)-13a]. Chromatography (PE/EtOAc 2:1) afforded
1
(3'R,4'E)-13a (236 mg, 0.73 mmol, 73%, purity 95% H NMR, R = 0.32) and (3'S,4'E)-13a
f
2
0
1
(
20 mg, 60 μmol, 6%, purity 95% H NMR, R = 0.38) as colorless oils. (3'R,4'E)-13a: [α]
=
D
f
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+
33.5 (c = 1.2 in CH Cl ); H NMR (400 MHz, CDCl ) δ (ppm) = 0.88 (d, J = 6.9 Hz, 3H, 5’-H
2 2 3
or 6’-H), 0.92 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 1.59 (s, 3H, 10-H or 11-H), 1.67 (s, 3H, 10-H or
11-H), 1.71 (s, 3H, 12H), 1.95-2.14 (m, 4H, 6-H, 7-H), 2.32-2.43 (m, 1H, 4’-H), 3.06-3.16 (m,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
5
H, 2-H), 4.20-4.30 (m, 2H, 2’-H, 3’-H ), 4.39-4.48 (m, 1H, 3’-H ), 4.85-4.91 (m, 1H, 3-H),
a b
.04-5.11 (m, 1H, 8-H), 5.25 (dd, J = 8.5 Hz, 1.1 Hz, 1H, 4-H); 13C{ H} NMR (100 MHz,
1
CDCl ) δ (ppm) = 14.9 (C-6’), 16.8 (C-5’), 17.8 (C-12), 18.1 (C-10, C-11), 25.8 (C-10), 26.5 (C-
3
7
), 28.6 (C-4’), 39.6 (C-2), 43.0 (C-6), 58.6 (C-3), 63.8 (C-3’), 65.2 (C-2’), 124.0 (C-8), 125.5
(
C-4), 131.9 (C-9), 139.5 (C-5), 154.1 (C-1’), 172.3 (C-1); FT-IR (ATR): 휈 = 3485 (w), 2964
(
m), 2920 (m), 1777 (vs), 1696 (s), 1486 (w), 1441 (w), 1372 (s), 1301 (m), 1202 (s), 1141 (m),
1120 (m), 1104 (m), 1058 (s), 1020 (s), 928 (w), 814 (w), 774 (m), 753 (m), 713 (m), 640 (m),
–1
+
5
3
90 (w), 526 (w) cm ; HRMS (ESI) m/z: [M+Na] Calcd for C H NO Na 346.1989; Found
18 29 4
1
46.1996. (3'S,4'E)-13a: H NMR (400 MHz, CDCl ) δ (ppm) = 0.88 (d, J = 6.9 Hz, 3H, 5’-H or
3
6’-H), 0.93 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 1.59 (s, 3H, 10-H or 11-H), 1.67 (s, 3H, 10-H or
1
2
1-H), 1.71 (s, 3H, 12-H), 1.95-2.14 (m, 4H, 6-H, 7-H), 2.32-2.43 (m, 1H, 4’-H), 3.06-3.16 (m,
H, 2-H), 4.20-4.30 (m, 2H, 2’-H, 3’-H ), 4.48-4.41 (m, 1H, 3’-H ), 4.83-4.92 (m, 1H, 3-H),
a
b
5.07-5.15 (m, 1H, 8-H), 5.28 (d, J = 8.9 Hz, 1H, 4-H); 13C{ H} NMR (100 MHz, CDCl ) δ
1
3
(
ppm) = 14.9 (C-6’), 16.8 (C-5’), 17.8 (C-12), 18.1 (C-10, C-11), 25.8 (C-10), 26.5 (C-7), 28.6
C-4’), 39.6 (C-2), 43.0 (C-6), 58.6 (C-3), 63.8 (C-3’), 65.2 (C-2’), 124.0(C-8), 125.5 (C-4),
(
1
31.9 (C-9), 139.5 (C-5), 154.1 (C-1’), 172.3 (C-1); FT-IR (ATR): 휈 = 3495 (w), 2964 (w), 2925
(w), 2976 (w), 1778 (s), 1699 (m), 1447 (w), 1386 (s), 1373 (s), 1302 (m), 1204 (s), 1179 (m),
1
143 (w), 1120 (w), 1102 (w), 1058 (m), 1020 (m), 972 (w), 845 (w), 775 (w), 754 (w), 713 (w),
–
1
+
6
40 (w), 587 (w), 527 (w), 454 (w) cm ; HRMS (ESI) m/z: [M+Na] Calcd for C H NO Na
18 29 4
346.1989; Found 346.1973.
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2
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2
2
2
2
2
2
3
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(
4S)-3-[(3R,4Z)- and (3S,4Z)-3-Hydroxy-5,9-dimethyldeca-4,8-dienoyl)-4-isopropyl-1,3-oxa-
zolidin-2-one [(3'R,4'Z)- and (3'S,4'Z)-13a]. Chromatography (PE/EtOAc 2 : 1) afforded
1
(3'R,4'Z)-13a (230 mg, 0.71 mmol, 71%, purity 95% H NMR, R = 0.32) and (3'S,4'Z)-13a
f
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
20
1
(
21 mg, 0.07 mmol, 7%, purity 90% H NMR, R = 0.35) as coloress oils. (3'R,4'Z)-13a: [α]D
=
f
1
+38.7 (c = 1.0 in CH Cl ); H NMR (400 MHz, CDCl ) δ (ppm) = 0.88 (d, J = 6.9 Hz, 3H, 5’-H
2
2
3
or 6’-H), 0.92 (d, J = 7.0 Hz, 3H, 5’-H or 6’-H), 1.60 (s, 3H, 10-H or 11-H), 1.68 (s, 3H, 10-H or
1
2
5
1-H), 1.73 (s, 3H, 12-H), 2.03-2.20 (m, 4H, 6-H, 7-H), 2.33-2.44 (m, 1H, 4’-H), 3.09-3.14 (m,
H, 2-H), 4.19-4.32 (m, 2H, 2’-H, 3’-H ), 4.41-4.49 (m, 1H, 3’-H ), 4.85-4.90 (m, 1H, 3-H),
a
b
.08-5.15 (m, 1H, 8-H), 5.28 (d, J = 8.9 Hz, 1H, 4-H); 13C{ H} NMR (100 MHz, CDCl ) δ
1
3
(
ppm) = 14.9 (C-6’), 16.8 (C-5’), 17.8 (C-12), 18.1 (C-10, C-11), 25.8 (C-10), 26.5 (C-7), 28.6
C-4’), 39.6 (C-2), 43.0 (C-6), 58.6 (C-3), 63.8 (C-3’), 65.2 (C-2’), 124.0 (C-8), 125.5 (C-4),
(
131.9 (C-9), 139.5 (C-5), 154.1 (C-1’), 172.3 (C-1); FT-IR (ATR): 휈 = 3495 (w), 2964 (w), 2925
w), 2976 (w), 1778 (s), 1699 (m), 1447 (w), 1386 (s), 1373 (s), 1302 (m), 1204 (s), 1179 (m),
143 (w), 1120 (w), 1102 (w), 1058 (m), 1020 (m), 972 (w), 845 (w), 775 (w), 754 (w), 713 (w),
(
1
–
1
+
640 (w), 587 (w), 527 (w), 454 (w) cm ; HRMS (ESI) m/z: [M+Na] Calcd for C H NO Na
1
8
29
4
1
3
46.1989; Found 346.1988. (3'S,4'Z)-13a: H NMR (400 MHz, CDCl ) δ (ppm) = 0.88 (d, J =
3
6
.9 Hz, 3H, 5’-H or 6’-H), 0.93 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 1.59 (s, 3H, 10-H or 11-H),
1.67 (s, 3H, 10-H or 11-H), 1.71 (s, 3H, 12-H), 1.95-2.14 (m, 4H, 6-H, 7-H), 2.32-2.43 (m, 1H,
4
4
’-H), 3.06-3.16 (m, 2H, 2-H), 4.20-4.30 (m, 2H, 2’-H, 3’-H ), 4.48-4.41 (m, 1H, 3’-H ), 4.83-
a b
1
3
1
.92 (m, 1H, 3-H), 5.07-5.15 (m, 1H, 8-H), 5.28 (d, J = 8.9 Hz, 1H, 4-H); C{ H} NMR (100
MHz, CDCl ) δ (ppm) = 14.9 (C-6’), 16.8 (C-5’), 17.8 (C-12), 18.1 (C-10, C-11), 25.8 (C-10),
3
26.5 (C-7), 28.6 (C-4’), 39.6 (C-2), 43.0 (C-6), 58.6 (C-3), 63.8 (C-3’), 65.2 (C-2’), 124.0(C-8),
1
25.5 (C-4), 131.9 (C-9), 139.5 (C-5), 154.1 (C-1’), 172.3 (C-1); FT-IR (ATR): 휈 = 3495 (w),
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2
964 (w), 2925 (w), 2976 (w), 1778 (s), 1699 (m), 1447 (w), 1386 (s), 1373 (s), 1302 (m), 1204
(s), 1179 (m), 1143 (w), 1120 (w), 1102 (w), 1058 (m), 1020 (m), 972 (w), 845 (w), 775 (w), 754
–
1
+
(w), 713 (w), 640 (w), 587 (w), 527 (w), 454 (w) cm ; HRMS (ESI) m/z: [M+Na] Calcd for
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
C H NO Na 346.1989; Found 346.2006.
1
8
29
4
(4S)-3-[(4E)-3-Hydroxy-2,5,9-trimethyldeca-4,8-dienoyl)-4-isopropyl-1,3-oxazolidin-2-one
[(E)-14a]. Chromatography (PE/EtOAc 2 : 1) afforded (3'R,4'E)-14a (46.1 mg, 0.14 mmol, 14%,
1
1
purity 95% H NMR, R = 0.37), (2'R,3'S,4'E)-14a (184 mg, 0.55 mmol, 55%, purity 95% H
f
1
NMR, R = 0.28) and (4'E)-14a (60.6 mg, 0.18 mmol, 18%, purity 90% H NMR, R = 0.20) as
f
f
2
D
0
1
colorless oils. (2'R,3'S,4'E)-14a: [α] = +43.6 (c = 1.0 in CH Cl ); H NMR (400 MHz, CDCl )
2
2
3
δ (ppm) = 0.86 (d, J = 7.0 Hz, 3H, 5’-H or 6’-H), 0.91 (d, J = 7.0 Hz, 3H, 5’-H or 6’-H), 1.19 (d,
J = 6.9 Hz, 3H, 13-H), 1.60 (s, 3H, 10-H or 11-H), 1.68 (s, 3H, 10-H or 11-H), 1.70 (s, 3H, 12-
H), 1.96-2.14 (m, 4H, 6-H, 7-H), 2.26-2.42 (m, 1H, 4’-H), 3.94-4.04 (m, 1H, 2-H), 4.17-4.31 (m,
2
H, 2’-H, 3’-H ), 4.16-4.32 (m, 1H, 3’-H ), 4.42-4.49 (m, 1H, 3-H), 5.01-5.11 (m, 1H, 8-H), 5.22
a b
1
3
1
(dd, J = 8.7 Hz, 1.1 Hz, 1H, 4-H); C{ H} NMR (100 MHz, CDCl ) δ (ppm) = 11.9 (C-13), 14.8
3
(C-6’), 17.0 (C-5’), 17.8 (C-12), 18.1 (C-10, C-11), 25.8 (C-10), 26.5 (C-7), 28.7 (C-4’), 39.9 (C-
), 43.1 (C-2), 58.8 (C-3), 63.4 (C-3’), 69.8 (C-2’), 124.0 (C-8), 125.7 (C-4), 131.9 (C-9), 140.4
C-5), 154.3 (C-1’), 175.9 (C-1); FT-IR (ATR): 휈 = 3496 (w), 2965 (m), 2926 (m), 2878 (w),
1775 (vs), 1697 (s), 1487 (w), 1453 (w), 1375 (s), 1300 (m), 1203 (vs), 1143 (w), 1120 (m),
6
(
1
5
101 (m), 1054 (w), 1015 (w), 989 (m), 954 (m), 904 (w), 818 (w), 776 (w), 709 (w), 640 (w),
–
1
+
37 (w), 441 (w) cm ; HRMS (ESI) m/z: [M+Na] Calcd for C H NO Na 360.2145; Found
1
9
31
4
2
D
0
1
360.2155. (3'R,4'E)-14a: [α] = +42.7 (c = 1.0 in CH Cl ); H NMR (400 MHz, CDCl ) δ (ppm)
2
2
3
=
0.89 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 0.96 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 1.08 (d, J = 6.9
Hz, 3H, 13-H), 1.60 (s, 3H, 10-H or 11-H), 1.67 (s, 3H, 10-H or 11-H), 1.70 (s, 3H, 12-H), 1.95-
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2
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4
.16 (m, 4H, 6-H, 7-H), 2.34-2.50 (m, 1H, 4’-H), 3.91 (dq, J = 13.8 Hz, 6.9 Hz, 1H, 2-H), 4.19-
.32 (m, 2H, 2’-H, 3’-H ), 4.16-4.32 (m, 1H, 3’-H ), 4.40-4.51 (m, 1H, 3-H), 5.01-5.12 (m, 1H,
a
b
1
3
1
8-H), 5.19 (d, J = 8.3 Hz, 4-H); C{ H} NMR (100 MHz, CDCl ) δ (ppm) = 14.2 (C-13), 14.7
3
0
1
2
3
4
5
6
7
8
9
0
1
2
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7
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9
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1
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9
0
1
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8
9
0
(
C-6’), 17.0 (C-5’), 17.8 (C-12), 18.1 (C-10, C-11), 25.8 (C-10), 26.5 (C-7), 28.6 (C-4’), 39.8 (C-
), 44.2 (C-2), 59.1 (C-3), 63.4 (C-3’), 71.9 (C-2’), 124.0 (C-8), 125.7 (C-4), 132.0 (C-9), 140.9
C-5), 154.5 (C-1’), 176.7 (C-1); FT-IR (ATR): 휈 = 3501 (w), 2966 (m), 2924 (m), 2878 (w),
6
(
1
1
7
775 (vs), 1698 (s), 1487 (w), 1454 (m), 1383 (vs), 1301 (m), 1251 (m), 1202 (vs), 1142 (m),
121 (m), 1107 (m), 1081 (m), 1054 (m), 990 (s), 954 (m), 901 (w), 817 (w), 775 (w), 760 (w),
–
1
+
09 (w), 636 (w), 530 (w), 462 (w) cm ; HRMS (ESI) m/z: [M+Na] Calcd for C H NO Na
19 31
4
2
0
1
3
60.2145; Found 360.2162. (4'E)-14a: [α] = +38.3 (c = 1.2 in CH Cl ); H NMR (400 MHz,
D
2 2
CDCl ) δ (ppm) = 0.87 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 0.91 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H),
3
1.10 (d, J = 7.0 Hz, 3H, 13-H), 1.58 (s, 3H, 10-H or 11-H), 1.65 (s, 3H, 10-H or 11-H), 1.68 (s,
3
1
H, 12-H), 1.97-2.15 (m, 4H, 6-H, 7-H), 2.29-2.38 (m, 1H, 4’-H), 3.82 (dq, J = 14.1 Hz, 7.0 Hz,
H, 2-H), 4.13-4.30 (m, 2H, 2’-H, 3’-H ), 4.44-4.58 (m, 2H, 3-H, 3’-H ), 4.99-5.09 (m, 1H, 8-
a
b
1
3
1
H), 5.16 (d, J = 9.1 Hz, 1H, 4-H); C{ H} NMR (100 MHz, CDCl ) δ (ppm) = 14.7 (C-13), 14.9
3
(
C-6’), 16.9 (C5’), 17.8 (C-12), 18.0 (C-10, C-11), 25.5 (C-10), 26.4 (C-7), 28.7 (C-4’), 39.7 (C-
), 44.5 (C-2), 58.6 (C-3), 63.6 (C-3’), 76.1.8 (C-2’), 123.9 (C-8), 125.2 (C-4), 131.9 (C-9),
140.9 (C-5), 154.0 (C-1’), 176.6 (C-1); FT-IR (ATR): 휈 = 3445 (w), 2645 (m), 2928 (m), 2878
w), 1778 (vs), 1696 (s), 1485 (w), 1455 (m), 1382 (vs), 1300 (m), 1256 (s), 1225 (s), 1202 (vs),
6
(
1
7
142 (m), 1120 (m), 1104 (m), 1076 (m), 1055 (m), 988 (s), 954 (m), 901 (w), 846 (w), 818 (w),
–
1
75 (w), 760 (w), 733,6 (w), 707 (m), 638 (w), 527 (w), 461 (w) cm ; HRMS (ESI) m/z:
+
[M+Na] Calcd for C H NO Na 360.2145; Found 360.2153.
1
9
31
4
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(
4S)-3-[(4Z)-3-Hydroxy-2,5,9-trimethyldeca-4,8-dienoyl)-4-isopropyl-1,3-oxazolidin-2-one
[
(Z)-14a]. Chromatography (PE/EtOAc 2 : 1) afforded (4'Z)-14a (25.2 mg, 0.07 mmol, 7%,
1
1
purity 80% H NMR, R = 0.35), (2'R,3'S,4'Z)-14a (201 mg, 0.59 mmol, 59%, purity 95% H
f
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
NMR, R = 0.31) and (3'R,4'Z)-14a (56 mg, 0.17 mmol, 17%, purity 95% H NMR, R = 0.20) as
f
f
2
D
0
1
colorless oils. (2'R,3'S,4'Z)-14a: [α] = +26.7 (c = 1.2 in CH Cl ); H NMR (400 MHz, CDCl ) δ
2
2
3
(
ppm) = 0.87 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 0.91 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 1.12 (d, J
7.0 Hz, 3H, 13-H), 1.60 (s, 3H, 10-H or 11-H), 1.67 (s, 3H, 10-H or 11-H), 1.74 (s, 3H, 12-H),
.98-2.22 (m, 4H, 6-H, 7-H), 2.26-2.42 (m, 1H, 4’-H), 3.77-3.88 (m, 1H, 2-H), 4.15-4.31 (m, 2H,
2’-H, 3’-H ), 4.44-4.56 (m, 2H, 3-H, 3’-H ), 5.05-5.15 (m, 1H, 8-H), 5.18 (d, J = 9.3 Hz, 1H, 4-
=
1
a
b
13
1
H); C{ H} NMR (100 MHz, CDCl ) δ (ppm) = 15.0 (C-13, C-6’), 17.8 (C-5’), 18.0 (C-12),
3
2
3.5 (C-10, C-11), 25.7 (C-10), 26.7 (C-7), 28.7 (C-4’), 32.5 (C-6), 44.3 (C-2), 58.6 (C-3), 63.6
(C-3’), 70.3 (C-2’), 123.9 (C-8), 126.1 (C-4), 132.4 (C-9), 141.4 (C-5), 154.0 (C-1’), 176.6 (C-
1
1
); FT-IR (ATR): 휈 = 3497 (w), 2965 (m), 2926 (m), 2877 (m), 1774 (vs), 1696 (s), 1487 (w),
454 (m), 1374 (vs), 1300 (m), 1201 (vs), 1142 (m), 1119 (m), 1100 (m), 1054 (m), 1014 (m),
989 (s), 965 (m), 954 (m), 904 (w), 845 (w), 819 (w), 775 (w), 761 (w), 709 (m), 640 (w), 555
–1
+
(
w), 533 (w), 451 (w) cm ; HRMS (ESI) m/z: [M+Na] Calcd for C H NO Na 360.2145;
19 31 4
2
D
0
1
Found 360.2159. (3'S,4'Z)-14a: [α] = +24.6 (c = 1.1 in CH Cl ); H NMR (400 MHz, CDCl ) δ
2
2
3
(ppm) = 0.87 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 0.91 (d, J = 7.0 Hz, 3H, 5’-H or 6’-H), 1.12 (d, J
7.0 Hz, 3H, 13-H), 1.60 (s, 3H, 10-H or 11-H), 1.67 (s, 3H, 10-H or 11-H), 1.74 (s, 3H, 12-H),
.98-2.22 (m, 4H, 6-H, 7-H), 2.26-2.42 (m, 1H, 4’-H), 3.77-3.88 (m, 1H, 2’-H), 4.15-4.31 (m,
2H, 2’-H, 3’-H ), 4.44-4.56 (m, 2H, 3-H, 3’-H ), 5.05-5.15 (m, 1H, 8-H), 5.18 (d, J = 9.3 Hz, 1H,
=
1
a
b
13
1
4
2
-H); C{ H} NMR (100 MHz, CDCl ) δ (ppm) = 15.0 (C-13, C-6’), 17.8 (C-5’), 18.0 (C-12),
3
3.5 (C-10, C-11), 25.7 (C-10), 26.7 (C-7), 28.7 (C-4’), 32.5 (C-6), 44.3 (C-2), 58.6 (C-3), 63.6
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(
C-3’), 70.3 (C-2’), 123.9 (C-8), 126.1 (C-4), 132.4 (C-9), 141.4 (C-5), 154.0 (C-1’), 176.6 (C-
1
); FT-IR (ATR): 휈 = 3469 (w), 2964 (m), 2931 (m), 2977 (w), 1777 (s), 1696 (s), 1455 (m),
1382 (s), 1300 (m), 1255 (m), 1225 (s), 1202 (s), 1143 (w), 1120 (m), 1101 (m), 1055 (m), 988
s), 954 (m), 901 (w), 848 (w), 819 (w), 775 (w), 707 (m), 638 (w), 595 (w), 528 (w), 449 (w)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
–
1
+
cm ; HRMS (ESI) m/z: [M+Na] Calcd for C H NO Na 360.2145; Found 360.2161. (4'Z)-
1
9
31
4
2
D
0
1
14a: [α] = +30.2 (c = 1.2 in CH Cl ); H NMR (400 MHz, CDCl ) δ (ppm) =0.88 (d, J = 7.0
2
2
3
Hz, 3H, 5’-H or 6’-H), 0.90 (d, J = 7.1 Hz, 3H, 5’-H or 6’-H), 1.06 (d, J = 6.9 Hz, 3H, 13-H),
.58 (s, 3H, 10-H or 11-H), 1.66 (s, 3H, 10-H or 11-H), 1.73 (s, 3H, 12-H), 2.03-2.19 (m, 4H, 6-
H, 7-H), 2.30-2.46 (m, 1H, 4’-H), 3.82-3.95 (m, 1H, 2-H), 4.15-4.34 (m, 3H, 2’-H, 3’-H ), 4.36-
1
a
13
1
4
.51 (m, 2H, 3-H, 3’-H ), 5.00-5.14 (m, 1H, 8-H), 5.18 (d, J = 9.2 Hz, 1H, 4-H); C{ H} NMR
b
(100 MHz, CDCl ) δ (ppm) = 14.4 (C-13), 14.6 (C-6’), 17.9 (C-5’), 18.2 (C-12), 23.4 (C-10, C-
3
11), 25.7 (C-10), 26.6 (C-7), 28.0 (C-4’), 38.6 (C-6), 44.9 (C-2), 59.9 (C-3), 63.3 (C-3’), 71.3 (C-
’), 123.9 (C-8), 126.6 (C-4), 132.3 (C-9), 141.2 (C-5), 154.3 (C-1’), 176.7 (C-1); FT-IR (ATR):
2
휈 = 3517 (w), 2965 (m), 2931 (m), 2877 (w), 1776 (vs), 1700 (s), 1487 (w), 1450 (w), 1386 (s),
1373 (s), 1301 (w), 1248 (m), 1205 (s), 1143 (w), 1121 (m), 1056 (m), 1015 (m), 990 (m), 953
–1
(w), 900 (w), 816 (w), 773 (w), 757 (w), 698 (w), 634 (w), 533 (w) cm ; HRMS (ESI) m/z:
+
[M+Na] Calcd for C H NO Na 360.2145; Found 360.2148.
1
9
31
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(4S)-3-[(4E)-3-Hydroxy-5-phenylpent-4-enoyl]-4-isopropyl-1,3-oxazolidin-2-one (13b). Chro-
matography (PE/EtOAc 3 : 1) afforded 13b (93 mg, 307 μmol, 51%) as a colorless solid.
–
1
R = 0.30. Analytical HPLC (Kromasil, flow 0.8 mL min , hexane/isopropanol 90 : 10): t
=
R1
f
2
0
1
2.741 min (minor, 4%), t = 15.086 min (major, syn,syn 13b, 96%). [α] = + 79.1 (c = 1.1 in
R2
D
1
CHCl ); H NMR (400 MHz, CDCl ) δ (ppm) = 0.89 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 0.93 (d,
3
3
J = 6.9 Hz, 3H, 5’-H or 6’-H), 2.34–2.43 (m, 1H, 4’-H), 3.01 (s, 1H, OH), 3.22 (dd, J = 17.1 Hz,
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.6 Hz, 1H, 2-H ), 3.35 (dd, J = 17.1 Hz, 3.4 Hz, 1H, 2-H ), 4.23 (dd, J = 9.2 Hz, 3.1 Hz, 1H,
a
b
-H ), 4.28 (dd, J = 9.2 Hz, 8.1 Hz, 1H, 3’-H ), 4.46 (dt, J = 8.1 Hz, 3.4 Hz, 1H, 2’-H), 4.79–
a
b
4.87 (m, 1H, 3-H), 6.28 (dd, J = 16.0 Hz, 6.0 Hz, 1H, 4-H), 6.68 (dd, J = 16.0, 1.4 Hz, 1H, 5-H),
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
.20–7.28 (m, 1H, p-H), 7.27–7.35 (m, 2H, m-H), 7.35–7.41 (m, 2H, o-H); 13C{ H} NMR
1
7
(101 MHz, CDCl ) δ (ppm) = 14.7 (C-6’), 18.0 (C-5’), 28.5 (C-4’), 42.6 (C-2), 58.5 (C-2’), 63.6
3
(C-3’), 68.8 (C-3), 126.6 (C-m), 127.8 (C-o), 128.6 (C-p), 130.0 (C-4), 130.8 (C-5), 136.5 (C-i),
1
1
54.1 (C-1’), 171.9 (C-1); FT-IR (ATR): 휈 = 3465 (w), 3026 (vw), 2963 (w), 2876 (w), 1774 (s),
696 (s), 1487 (w), 1465 (w), 1449 (w), 1386 (s), 1373 (s), 1301 (m), 1204 (s), 1143 (w), 1119
(m), 1058 (m), 1020 (m), 970 (m), 914 (w), 750 (m), 715 (w), 695 (m), 640 (w), 587 (vw),
–
1
+
543.38 (w), 472 (w) cm ; HRMS (ESI) m/z: [M+Na] Calcd for C H NO Na 326.1363;
1
7
21
4
Found: 326.1344.
4S)-3-[(4E)-3-Hydroxy-5-(4-methoxyphenyl)pent-4-enoyl]-4-isopropyl-1,2-oxazolidin-2-one
(
(13c). Chromatography (PE/EtOAc 2 : 1) afforded 13c (64 mg, 192 μmol, 30%) as a pale yellow
–1
oil. R = 0.21. Analytical HPLC (Kromasil, flow 0.8 mL min , hexane/isopropanol 95 : 5):
f
2
D
0
t = 35.312 min (minor, 2%), t = 39.530 min (major, syn,syn 13c, 98%). [α] = + 50.5 (c = 1.0
R1
R2
1
in CHCl ); H NMR (500 MHz, CDCl ) δ (ppm) = 0.89 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 0.93
3
3
(
d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 2.35–2.44 (m, 1H, 4’-H), 2.93 (d, J = 4.5 Hz, 1H, OH), 3.22
dd, J = 17.1 Hz, 8.7 Hz, 1H, 2-H ), 3.34 (dd, J = 17.1 Hz, 3.3 Hz, 1H, 2-H ), 3.81 (s, 3H, OMe),
(
a
b
4.23 (dd, J = 9.1 Hz, 3.0 Hz, 1H, 3’-H ), 4.29 (dd, J = 9.1 Hz, 8.2 Hz, 1H, 3’-H ), 4.44–4.49 (m,
a
b
1
5
H, 2’-H), 4.76–4.84 (m, 1H, 3-H), 6.14 (dd, J = 15.9 Hz, 6.2 Hz, 1H, 4-H), 6.59–6.64 (m, 1H,
-H), 6.83–6.87 (m, 2H, m-H), 7.29–7.34 (m, 2H, o-H); 13C{ H} NMR (126 MHz, CDCl )
1
3
δ (ppm) = 14.7 (C-6’), 18.0 (C-5’), 28.5 (C-4’), 42.7 (C-2), 55.3 (OMe), 58.5 (C-2’), 63.6 (C-3’),
6
9.0 (C-3), 114.0 (C-m), 127.7 (C-4), 127.8 (C-o), 129.2 (C-i), 130.4 (C-5), 154.1 (C-1’), 159.4
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(
C-p), 172.0 (C-1); FT-IR (ATR): 휈 = 3490 (w), 2961 (m), 2930 (m), 2837 (w), 1778 (vs), 1698
(s), 1607 (s), 1578 (w), 1511 (vs), 1464 (w), 1387 (s), 1301 (m), 1249 (vs), 1207 (s), 1176 (s),
–
1
1143 (w), 1108 (m), 1032 (s), 971 (m), 816 (w), 775 (w), 714 (w), 641 (w), 538 (w) cm ;
0
1
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5
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9
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1
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2
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4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
HRMS (ESI) m/z: [M+Na] Calcd for C H NO Na 356.1468; Found 356.1470.
1
8
23
5
(4S)-3-[(4E)-3-Hydroxy-5-(4-methylphenyl)pent-4-enoyl]-4-isopropyl-1,2-oxazolidin-2-one
(13d). Chromatography (PE/EtOAc 2.5 : 1) afforded 13d (36 mg, 113 μmol, 22%) as a pale
–1
yellow oil. R = 0.18. Analytical HPLC (OJ-H, flow 2.0 mL min , hexane/isopropanol 85 : 15):
f
2
D
0
t = 12.593 min (minor, 1%), t = 16.199 min (major, syn,syn 13d, 99%). [α] = + 57.1
R1
R2
1
(c = 1.0 in CHCl ); H NMR (500 MHz, CDCl ) δ (ppm) = 0.89 (d, J = 7.0 Hz, 3H, 5’-H or 6’-
3
3
H), 0.93 (d, J = 7.0 Hz, 3H, 5’-H or 6’-H), 2.30–2.43 (m, 4H, 4-H, CH ), 2.96 (s, 1H, OH), 3.22
3
(dd, J = 17.2 Hz, 8.7 Hz, 1H, 2-H ), 3.34 (dd, J = 17.2 Hz, 3.3 Hz, 1H, 2-H ), 4.23 (dd,
a
b
J = 9.0 Hz, 3.1 Hz, 1H, 3’-H ), 4.29 (t, J = 9.0 Hz, 1H, 3’-H ), 4.44–4.49 (m, 1H, 2’-H), 4.79–
a
b
4
7
.86 (m, 1H, 3-H), 6.22 (dd, J = 15.9 Hz, 6.1 Hz, 1H, 4-H), 6.64 (d, J = 15.9 Hz, 1H, 5-H), 7.09–
1
3
1
.15 (m, 2H, m-H), 7.27–7.31 (m, 2H, o-H); C{ H} NMR (126 MHz, CDCl ) δ (ppm) = 14.7
3
(C-6’), 18.0 (C-5’), 21.2 (CH ), 28.5 (C-4’), 42.6 (C-2), 58.5 (C-2’), 63.6 (C-3’), 68.9 (C-3),
3
1
26.5 (C-o), 128.8 (C-4), 129.3 (C-m), 130.7 (C-5), 133.6 (C-i), 137.7 (C-p), 154.0 (C-1’), 175.0
C-1); FT-IR (ATR): 휈 = 3445 (w), 2961 (m), 2923 (m), 1779 (vs), 1698 (s), 1514 (m), 1485 (w),
464 (w), 1386 (vs), 1302 (m), 1206 (s), 1143 (w), 1106 (m), 1059 (m), 1020 (m), 971 (m), 802
(
1
–
1
+
(m), 775 (w), 715 (w), 641 (w), 529 (w), 464 (w) cm ; HRMS (ESI) m/z: [M+Na] Calcd for
C H NO Na 340.1519; Found 340.1529.
1
8
23
4
(4S)-3-[(4E)-5-(4-Chlorophenyl)-3-hydroxypent-4-enoyl)-4-isopropyl-1,3-oxazolidin-2-one
(13e). Chromatography (PE/EtOAc 3 : 1) afforded 13e (70 mg, 207 μmol, 33%) as a pale yellow
–1
oil. R = 0.20. Analytical HPLC (OJ-H, flow 1.0 mL min , hexane/isopropanol 85 : 15):
f
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20
t = 24.473 min (minor, 6%), t = 28.815 min (major, syn,syn 13e, 94%). [α]D = + 53.3 (c = 1.0
R1
R2
1
in CHCl ); H NMR (500 MHz, CDCl ) δ (ppm) = 0.89 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 0.94
3
3
(
d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 2.34–2.43 (m, 1H, 4’-H), 3.05 (s, 1H, OH), 3.19 (dd,
1
1
1
1
1
1
1
1
1
1
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2
2
2
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3
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3
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4
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4
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4
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5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
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7
8
9
0
1
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7
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9
0
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0
J = 17.2 Hz, 8.8 Hz, 1H, 2-H ), 3.36 (dd, J = 17.2 Hz, 3.2 Hz, 1H, 2-H ), 4.24 (dd, J = 9.2 Hz,
a
b
3
6
4
4
.2 Hz, 1H, 3’-H ), 4.27–4.32 (m, 1H, 3’-H ), 4.44–4.49 (m, 1H, 2’-H), 4.79–4.85 (m, 1H, 3-H),
a b
.25 (dd, J = 15.9 Hz, 5.9 Hz, 1H, 4-H), 6.64 (dd, J = 15.9 Hz, 1.5 Hz, 1H, 5-H), 7.27–7.33 (m,
1
3
1
H, o-H, m-H); C{ H} NMR (126 MHz, CDCl ) δ (ppm) = 14.7 (C-6’), 18.0 (C-5’), 28.5 (C-
3
’), 42.5 (C-2), 58.5 (C-2’), 63.7 (C-3’), 68.6 (C-3), 127.8 (C-m), 128.8 (C-o), 129.5 (C-5), 130.5
(C-4), 133.4 (C-p), 135.0 (C-i), 154.0 (C-1’), 172.1 (C-1); FT-IR (ATR): 휈 = 3468 (w), 2964
(
m), 2162 (w), 2026 (w), 1780 (vs), 1699 (s), 1492 (m), 1387 (s), 1302 (m), 1207 (s), 1092 (m),
–
1
+
1
059 (w), 1014 (m), 971 (m), 808 (w), 776 (w) cm ; HRMS (ESI) m/z: [M+Na] Calcd for
C H ClNO Na 360.0973; Found 360.0975.
1
7
20
4
(
4S)-3-[(4E)-3-Hydroxy-5-(4-nitrophenyl)pent-4-enoyl]-4-isopropyl-1,3-oxazolidin-2-one
(
13f). Chromatography (PE/EtOAc 2.5 : 1) afforded 13f (51 mg, 146 μmol, 24%) as an orange
2
D
0
1
oil. R = 0.30; [α] = + 41.3 (c = 1.0 in CHCl ); H NMR (500 MHz, CDCl ) δ (ppm) = 0.90 (d,
f
3
3
J = 7.0 Hz, 3H, 5’-H or 6’-H), 0.95 (d, J = 7.0 Hz, 3H, 5’-H or 6’-H), 2.31–2.44 (m, 1H, 4’-H),
.18 (dd, J = 17.4 Hz, 8.9 Hz, 1H, 2-H ), 3.41 (dd, J = 17.4 Hz, 3.2 Hz, 1H, 2-H ), 4.26 (dd,
3
a
b
J = 9.2 Hz, 3.0 Hz, 1H, 3’-H ), 4.31 (dd, J = 9.2 Hz, 8.2 Hz, 1H, 3’-H ), 4.45–4.50 (m, 1H, 2’-
a
b
H), 4.82–4.93 (m, 1H, 3-H), 6.45 (dd, J = 16.0 Hz, 5.3 Hz, 1H, 4-H), 6.78 (dd, J = 16.0 Hz,
1
3
1
1
.6 Hz, 1H, 5-H), 7.49–7.53 (m, 2H, o-H), 8.17–8.21 (m, 2H, m-H); C{ H} NMR (126 MHz,
CDCl ) δ (ppm) = 14.7 (C-6’), 18.0 (C-5’), 28.5 (C-4’), 42.4 (C-2), 58.5 (C-2’), 63.7 (C-3’), 68.2
3
(
C-3), 124.0 (C-m), 127.1 (C-o), 128.4 (C-5), 134.7 (C-4), 143.0 (C-i), 147.1 (C-p), 154.1 (C-1’),
1
71.8 (C-1); FT-IR (ATR): 휈 = 3428 (w), 2963 (m), 2928 (w), 2875 (w), 1777 (vs), 1698 (s),
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597 (m), 1516 (s), 1487 (w), 1466 (w), 1387 (s), 1342 (vs), 1302 (w), 1207 (m), 1143 (w), 1109
(m), 1058 (m), 1019 (m), 973 (m), 863 (w), 824 (w), 800 (w), 773 (m), 717 (w), 692 (w), 640
–
1
+
(w) cm ; HRMS (ESI) m/z: [M+Na] Calcd for C H N O Na 371.1214; Found 371.1189.
1
7
20
2
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
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0
1
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(S)-3-((2'R,3'S,E)- or (S)-3-((2'S,3'R,E)-3-Hydroxy-2-methyl-5-phenylpent-4-enoyl)-4-isopro-
pyloxazolidin-2-one (14b). Chromatography (PE/EtOAc 3 : 1) afforded 14b (185 mg, 582 μmol,
–
1
9
2%) as a colorless solid. R = 0.27. Analytical HPLC (Kromasil, flow 0.8 mL min , hexane/
f
isopropanol 90 : 10): t = 7.950 min (minor, 1%), t = 8.565 min (minor, 2%), t = 9.612 min
R1
R2
R3
(minor, syn,anti 5%), t = 11.212 min (major, syn,syn 14b, 93%). The diastereomers could be
R4
separated via preparative HPLC: syn,syn 14b (170 mg, 536 µmol, 85%) and anti,syn 14b
2
D
0
1
(9.0 mg, 28.4 µmol, 5%). syn,syn 14b: [α] = + 46.6 (c = 0.9 in CHCl ); H NMR (500 MHz,
3
CDCl ) δ (ppm) = 0.83 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 0.90 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H),
3
1.22 (d, J = 6.9 Hz, 3H, 6-H), 2.28–2.38 (m, 1H, 4’-H), 2.80 (d, J = 3.1 Hz, 1H, OH), 4.11 (qd,
J = 6.9 Hz, 4.1 Hz, 1H, 2-H), 4.22 (dd, J = 9.2 Hz, 3.1 Hz, 1H, 3’-H ), 4.29 (dd, J = 9.2 Hz,
a
8
4
1
2
.2 Hz, 1H, 3’-H ), 4.47 (ddd, J = 8.2 Hz, 3.9 Hz, 3.1 Hz, 1H, 2’-H), 4.67 (dddd, J = 5.9 Hz,
b
.1 Hz, 3.1 Hz, 1.4 Hz, 1H, 3-H), 6.22 (dd, J = 15.9 Hz, 5.9 Hz, 1H, 4-H), 6.67 (dd, J = 15.9 Hz,
.4 Hz, 1H, 5-H), 7.21–7.27 (m, 1H, p-H), 7.31 (dd, J = 8.4 Hz, 6.8 Hz, 2H, m-H), 7.36–7.40 (m,
1
3
1
H, o-H); C{ H} NMR (126 MHz, CDCl ) δ (ppm) = 11.3 (C-6), 14.6 (C-6’), 17.9 (C-5’), 28.6
3
(
C-4’), 42.8 (C-2), 58.7 (C-2’), 63.4 (C-3’), 73.5 (C-3), 126.6 (C-m), 127.7 (C-o), 128.5 (C-4),
128.6 (C-o), 131.7 (C-5), 136.6 (C-i), 154.1 (C-1’), 175.8 (C-1); FT-IR (ATR): 휈 = 3476 (w),
965 (w), 2933 (w), 2877 (w), 1773 (vs), 1696 (s), 1488 (w), 1451 (w), 1385 (s), 1300 (m), 1203
s), 1143 (w), 1121 (m), 1055 (w), 1016 (w), 988 (w), 967 (m), 754 (m), 696 (m), 639 (w), 490
2
(
–
1
+
(w) cm ; HRMS (ESI) m/z: [M+Na] Calcd for C H NO Na 340.1519; Found 340.1519.
1
8
23
4
1
anti,syn 14b: H NMR (500 MHz, CDCl ) δ (ppm) = 0.79 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 0.89
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The Journal of Organic Chemistry
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(
d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 1.24 (d, J = 6.9 Hz, 3H, 6-H), 2.35 (qd, J = 7.0 Hz, 3.9 Hz, 1H,
4
’-H), 2.84 (d, J = 7.7 Hz, 1H, OH), 4.13 (qd, J = 7.1 Hz, J = 6.8 Hz, 1H, 2-H), 4.21 (dd,
J = 9.1 Hz, 3.0 Hz, 1H, 3’-H ), 4.28 (dd, J = 9.1 Hz, 8.3 Hz, 1H, 3’-H ), 4.39 (dd, J = 6.8 Hz,
a
b
1
1
1
1
1
1
1
1
1
1
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2
2
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5
5
5
5
5
6
0
1
2
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4
5
6
7
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9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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7
8
9
0
1
2
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6
7
8
9
0
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6
7
8
9
0
6
1
2
.5 Hz, 1H, 3-H), 4.46 (ddd, J = 8.2 Hz, 3.9 Hz, 3.0 Hz, 1H, 2’-H), 6.25 (dd, J = 15.9 Hz, 6.5 Hz,
H, 4-H), 6.65 (dd, J = 15.9 Hz, 1.3 Hz, 1H, 5-H), 7.25 (d, J = 9.3 Hz, 1H, p-H), 7.29–7.34 (m,
1
3
1
H, m-H), 7.35–7.40 (m, 2H, o-H); C{ H} NMR (126 MHz, CDCl ) δ (ppm) = 14.5 (C-6), 14.6
3
(
C-6’), 17.9 (C-5’), 28.4 (C-4’), 43.0 (C-2), 58.8 (C-2’), 63.3 (C-3’), 75.8 (C-3), 126.6 (C-m),
27.9 (C-o), 128.6 (C-o), 129.7 (C-4), 132.0 (C-5), 136.4 (C-i), 154.2 (C-1’), 176.3 (C-1); FT-IR
ATR): 휈 = 3487 (w), 2964 (w), 2925 (w), 2876 (w), 1775 (vs), 1698 (s), 1599 (vw), 1492 (w),
1
(
1453 (w), 1383 (s), 1301 (m), 1202 (s), 1143 (w), 1118 (m), 1052 (w), 1016 (m), 988 (m), 966
–1
(m), 906 (w), 846 (w), 802 (w), 749 (m), 694 (m), 635 (w), 555 (w), 459 (w) cm ; HRMS (ESI)
+
m/z: [M+Na] Calcd for C H NO Na 340.1519; Found 340.1525.
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8
23
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(4S)-3-[(4E)-3-Hydroxy-5-(4-methoxyphenyl)-2-methylpent-4-enoyl]-4-isopropyl-1,3-oxazoli-
din-2-one (14c). Chromatography (PE/EtOAc 3 : 1 → 2 : 1) afforded 14c (125 mg, 360 μmol,
–
1
6
3%) as a pale yellow oil. R = 0.44 (2 : 1). Analytical HPLC (OJ-H, flow 1.5 mL min , hexane/
f
isopropanol 80 : 20): t = 19.310 min (major, syn,syn 14c, 85%), t = 22.686 min (minor,
R1
R2
2
0
1
1
6
5%). [α] = + 23.6 (c = 1.0 in CHCl ); H NMR (500 MHz, CDCl ) δ (ppm) = 0.82 (d, J =
D
3 3
.9 Hz, 3H, 5’-H or 6’-H), 0.90 (d, J = 6.9 Hz, 3H, 5’-H or 6’-H), 1.22 (d, J = 6.9 Hz, 3H, 6-H),
2.27–2.41 (m, 1H, 4’-H), 2.71 (d, J = 3.0 Hz, 1H, OH), 3.81 (s, 3H, OMe), 4.05–4.16 (m, 2H, 2-
H), 4.22 (dd, J = 9.1 Hz, 3.0 Hz, 1H, 3’-H ), 4.26–4.31 (m, 1H, 3’-H ), 4.42–4.50 (m, 1H, 2’-H),
a
b
4
.60–4.68 (m, 1H, 3-H), 6.08 (dd, J = 15.9 Hz, 6.2 Hz, 1H, 4-H), 6.58–6.63 (m, 1H, 5-H), 6.82–
1
3
1
6.87 (m, 2H, m-H), 7.29–7.34 (m, 2H, o-H); C{ H} NMR (126 MHz, CDCl ) δ (ppm) = 11.4
3
(C-6), 14.6 (C-6’), 18.0 (C-5’), 28.5 (C-4’), 42.9 (C-2), 55.3 (OMe), 58.7 (C-2’), 63.4 (C-3’),
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