Stereocomplementary Synthesis of cis- and trans-2-(p-Bromophenyl)-5-methylthiazolidin-4-ones: Useful Umpolung-type Suzuki–Miyaura Cross-coupling Partner and Donor

Article abstract of DOI:10.1002/jhet.3141

Novel cis- and trans-2-(p-bromophenyl)-5-methylthiazolidin-4-ones, S,N-containing heterocyclic compounds, were provided in a cis-stereocomplementary and trans-stereocomplementary synthetic manner. cis-Selective cyclo-condensation proceeded between 2-sulfanylpropanoic acid (thiolactic acid) and an imine derived from 4-bromobenzaldehyde and methylamine, whereas Ti(OiPr)₄ and Ti(OiBu)₄-promoted trans-selective cyclo-condensation proceeded between benzyl 2-sulfanylpropanoate and the imine. The obtained cis- and trans-2-(p-bromophenyl)-5-methylthiazolidin-4-ones were successfully converted to 2-(3-furyl)phenyl derivatives and bis(pinacolato)diborane derivatives utilizing Suzuki–Miyaura and Miyaura–Ishiyama cross-coupling reactions, respectively, in an umpolung manner.

Full text of DOI:10.1002/jhet.3141

Month 2018
Stereocomplementary Synthesis of cis- and trans-2-(p-Bromophenyl)-5-
methylthiazolidin-4-ones: Useful Umpolung-type Suzuki–Miyaura Cross-
coupling Partner and Donor
*
Ryosuke Sasaki, Hidefumi Nakatsuji, and Yoo Tanabe
Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo 669-1337, Japan
*
E-mail: tanabe@kwansei.ac.jp
Received November 5, 2017
DOI 10.1002/jhet.3141
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
Novel cis- and trans-2-(p-bromophenyl)-5-methylthiazolidin-4-ones, S,N-containing heterocyclic com-
pounds, were provided in a cis-stereocomplementary and trans-stereocomplementary synthetic manner.
cis-Selective cyclo-condensation proceeded between 2-sulfanylpropanoic acid (thiolactic acid) and an
imine derived from 4-bromobenzaldehyde and methylamine, whereas Ti(OiPr)4 and Ti(OiBu)4-promoted
trans-selective cyclo-condensation proceeded between benzyl 2-sulfanylpropanoate and the imine. The
obtained cis- and trans-2-(p-bromophenyl)-5-methylthiazolidin-4-ones were successfully converted to
2-(3-furyl)phenyl derivatives and bis(pinacolato)diborane derivatives utilizing Suzuki–Miyaura and
Miyaura–Ishiyama cross-coupling reactions, respectively, in an umpolung manner.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
5-(carbonyl methylene) derivatives as bacterial and fungal
growth inhibitors [6], and (v) 2-aryl-5-carboxymethyl
derivatives as nematicidal agents against Bacillus subtilis,
Staphlococcus aureus, and Escherichia coli [7].
Thiazolidin-4-ones are representative S,N-containing
heterocycles as isosters of oxazoles and thiazoles. These
compounds comprise
pharmaceuticals, such as antimicrobial, antiviral, anti-
inflammatory, and antitubercular agents. recent
comprehensive review to index original studies published
between 2000 and 2011 revealed the significance of a
number of biologically active thiazolidin-4-ones [1].
Synthetic studies of thiazolidin-4-ones, therefore, have
been well-investigated to date from the standpoint of both
medicinal and process chemistries [2].
Compared with simple 5-unsubstituted thiazolidin-4-
ones, the construction of more complex 2,5-disubstituted
thiazolidin-4-ones 1 is, however, quite limited due to the
cis/trans stereoselection issue (Fig. 1). Recent
representative studies of 1 include the following: (i) 2-
phenyl-5-methyl derivative as mycelial growth inhibitor
[3], (ii) 2-aryl-5-(amide methylene) derivatives as C–C
chemokine receptor type 4 (CCR4) antagonists [4], (iii)
2-aryl-5-(amide methylene) derivatives as follicle-
stimulating hormone receptor antagonists [5], (iv) 2-aryl-
a
variety of clinically used
Beside the bioorganic and medicinal chemistries,
Sausa’s group reported unique photolytic and thermal
ring-contractions using sulfone derivatives of 2-phenyl-5-
methyl-thiazolidin-4-ones to β-lactams [8]. Feringa’s and
Kellogg’s groups utilized 2-(2-pyridyl)-5-methylthiazolidin-
A
4-ones
asymmetric1,4-addition to enones [9]. Bazureau and Fraga-
Dubreuil reported task-specific ionic liquid and
as
chiral
ligands
for
Cu(I)-catalyzed
a
microwave-assisted method for preparing 2,5-disubstituted
thiazolidin-4-ones [10].
This background led us to investigate a cis/trans
stereocomplementary preparative method and its
extension to Suzuki–Miyaura (SM) cross-coupling
reactions.
stereocomplementary
Here,
we
synthesis
describe
of
a
cis/trans
novel
2-(4-
bromopheneyl)-3,5-dimethyl-2-thiazolidin-4-ones (cis-2)
and (trans-2) (Fig. 2). Moreover, cis-2 and trans-2 served
as useful precursors of umpolung-type SM cross-
couplings. 2-(3-Furyl)phenyl derivatives cis-3 and trans-3
© 2018 Wiley Periodicals, Inc.

R. Sasaki, H. Nakatsuji, and Y. Tanabe
Vol 000
analogues, we performed a cis/trans stereocomplementary
synthesis of these compounds [14] and revealed the
stereostructure–activity relationship between all the four
chiral stereoisomers [15]. Utilizing this method, our initial
attempt toward the cis-selective cyclo-condensation
between 2-sulfanylpropanoic acid (thiolactic acid) (5) and
N-(4-bromobenzylidene)methylamine (6) afforded novel
2,5-disubstituted thiazolidin-4-ones cis-2 (82%) with small
amounts of trans-2 (14%) (Scheme 1).
For metal alkoxide-mediated trans-selective cyclo-
condensations, benzyl 2-sulfanylpropanoate (7) was
selected instead of the original methyl ester due to its
unpleasant odor. The reaction between ester 7 and imine
6 proceeded smoothly to afford thiazolidin-4-ones trans-2
as a major stereoisomer. The successful results are listed in
Table 1. Among boronium, aluminum, and titanium
alkoxides, Ti(OiPr)4 and Ti(OiBu)4 produced the best
results in terms of both yield and trans-selectivity (entries
3 and 4). To the best of our knowledge, this is the first
and most reliable method for preparing less accessible
trans-2,5-disubstituted thiazolidin-4-ones.
Figure 1. Structure of 2,5-disubstituted thiazolidin-4-ones.
To further investigate the cis-selectivity and trans-
selectivity issue, cyclo-condensations using the t-Butyl
dimethylsilyl (TBS) ester 8 as an isoster of acid 5 and
benzyl ester 7 were examined (Scheme 2). TBS ester 8
was readily prepared from acid 5 using TBSCl/Et3N in
84% yield (Experimental section). The cyclo-
condensation reaction of 8 with imine 6 proceeded
smoothly to give cis-2, mainly with trans-2 (total
94%). In contrast, Al(OsBu)3 and Ti(OiPr)4 catalysts
promoted trans-selective cyclo-condensation to yield
trans-2. Their effects on these cis-selectivities and
trans-selectivities, however, were in a similar those of
intact acid 5 and benzyl ester 7.
Figure 2. cis/trans Stereocomplementary synthesis of novel 2-(4-
bromopheneyl)-3,5-dimethyl-2-thiazolidin-4-ones and the derivatives.
were produced from cis-2 and trans-2 as the SM acceptor,
and (pinB)2 [bis(pinacolato)diborane] derivatives cis-4 and
trans-4 were also provided from cis-2 and trans-2 as SM
donors.
These successful outcomes and along with our recent
interest in practical cross-coupling reactions [16] led us to
investigate a couple of SM cross-couplings (Scheme 3).
The reaction of thiazolidin-4-ones trans-2 with
phenylboronic acid under several SM cross-coupling
conditions was initially investigated (Table 2). Salient
features are as follows. (i) Among various ligands for
RESULTS AND DISCUSSION
The most traditional procedure for the preparation of 2,5-
disubstituted thiazolidin-4-ones cis-1 and trans-1 involves a
three- (or two-) component cyclo-condensation reaction
using 2-sulfanyl(or mercapto)carboxylic acids, aldehydes,
and amines (or their imines derived from aldehydes, and
amines) [2]. This reaction predominantly yields cis-rich
products, consistent with the related preparative method
for chiral cis-2,5-disubstituted 1,3-dioxolan-4-ones
(Seebach and Fráter’s chiral template) [11,12] and 2,5-
oxathiol-4-ones [13]. During our synthetic studies of the
antiplatelet factor drug possessing-specific 2-(3-pyridyl)-
3,5-dimethylthiazolidin-4-one and 5-(p-chloro)phenyl
Scheme 1. cis-Selective cyclo-condensation between thiolactic acid (5)
and imine 7.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Stereocomplementary Synthesis of cis- and trans-2,5-disubstituted Thiazolidin-4-
ones: Useful Umpolung-type Suzuki–Miyaura Cross-coupling Partner and Donor
Table 1
M(OR)n-mediated trans-selective cyclo-condensation of benzyl ester 7.
Entry
Lewis acid
Yield/%a
cis/transa
1
2
3
4
B(OiPr)3
Al(OsBu)3
Ti(OiPr)4
Ti(OiBu)4
20
52
86:14
26:74
18:82
18:82
85 (cis: 14; trans:71)b
93
aDetermined by 1H nuclear magnetic resonance of the crude products.
bIsolated.
In conclusion, we performed cis-stereocomplementary
and trans-stereocomplementary synthesis of novel
Scheme 2. cis-Selective and trans-selective cyclo-condensation between
thiolactic acid TBS ester (5) and imine 7.
2-(p-bromophenyl)-5-methylthiazolidin-4-ones.
The
cyclo-condensation of 2-sulfanylpropanoic acid with N-(4-
bromobenzylidene)methylamine afforded the desired cis-
product, whereas use of the Ti(OiPr)4 or Ti(OiBu)4 catalyst
afforded the complementary trans-product with high
diastereoselectivity. As a notable application of the obtained
thiazolidin-4-ones, a set of umpolung-type cross-couplings
(SM and Miyura–Ishiyama) was performed to afford the
corresponding coupling products. This strategy to obtain
thiazolidin-4-one core building blocks will contribute to the
research for medicinal and process chemistry.
EXPERIMENTAL
Benzyl 2-sulfanylpropanoate (7) [14].
A
Pd(OAc)2, SPhos gave the best result in yield (entry 7). (ii)
K3PO4 base was somewhat more effective than K2CO3
(entries 10–13). (iii) THF solvent gave the best yield
(entry 13).
With this successful result in hands, SM cross-coupling
reaction using 3-furylboronic acid in the presence of
Pd(OAc)2 (5 mol%)/SPhos ligand (10 mol%)/K3PO4
furnished the desired coupling product cis-3 in 66%
yield, wherein the thiazolidin-4-one skeleton tolerated
during the reaction conditions. The trans-3 isomer was
similarly obtained from trans-2 in 99% excellent yield
under the identical conditions.
mixture of 2-sulfanylpropanoic acid (thiolactic acid)
(1.77 mL, 20.0 mmol), benzyl alcohol (4.33 g,
40.0 mmol), and p-toluenesulfonic acid (190 mg,
1.00 mmol) in toluene was refluxed for 5 h using Dean–
Stark apparatus with continual removal of water. After
cooling to room temperature, water was added to the
mixture, which was extracted twice with AcOEt. The
combined organic phase was washed with water, brine,
dried (Na2SO4), and concentrated. The obtained crude
product
was
purified
by
silica-gel
column
chromatography (hexane/AcOEt = 8:1) to give the
Finally, we focused our interest on the related
Miyaura–Ishiyama cross-couplings [17] of cis-2 and
trans-2 with (pinB)2 [bis(pinacolato)diborane] to obtain
the corresponding (pinB)-products cis-4 and trans-4 as
the umpolung-type cross-coupling partners. The desired
reaction catalyzed by Pd(dppf)Cl2 (5 mol%)/KOAc
proceeded successfully to produce the pinB-substituted
derivatives cis-4 and trans-4 products in 76% and in 74%
yields, respectively.
desired product 1 (3.61 g, 92%).
Colorless oil; H nuclear magnetic resonance (NMR)
1
(500 MHz, CDCl3): δ = 1.54 (d, J = 6.87 Hz, 3H), 2.17 (d,
J = 8.02 Hz, 1H), 3.55 (dq, J = 6.87 Hz, 8.02 Hz, 1H), 5.16
(d, J = 12.03 Hz, 1H), 5.19 (d, J = 12.03 Hz, 1H),
7.31–7.41 (m, 5H); 13C NMR (125 MHz, CDCl3):
δ = 21.0, 35.6, 67.0, 128.1 (2C), 128.3, 128.5 (2C), 135.5,
173.4; IR (neat): νmax = 1732, 1454, 1379, 1325, 1163,
1103 cmÀ1
.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Sasaki, H. Nakatsuji, and Y. Tanabe
Vol 000
Scheme 3. Umpolung-type Suzuki–Miyaura cross-coupling using cis-2 and trans-2.
Table 2
Suzuki–Miyaura cross-coupling using trans-2.
Entry
Pd catalyst
Pd(OAc)2
Ligand
Base
Solvent
Toluene
Temp./°C
Yield/%a
1
2
PPh3
PBu3
K2CO3
60–65
37
50
3
PCy3
54
4
5
6
7
8
9
10
11
12
13
tBuXPhos
JhonPhos
DavePhos
SPhos
–
28
65
73
81
36
45
93
39
Pd(PPh3)2
Pd(dppe)Cl2
Pd(OAc)2
–
SPhos
K3PO4
MeCN
iPrOH
THF
40–45
90
,
99 (94)b
c
aDetermined by 1H nuclear magnetic resonance of the crude products.
bIsolated.
cReaction time is 4 h.
tert-Butyldimethylsilyl 2-sulfanylpropanoate (8).
(1.17 g, 11.0 mmol) in CH2Cl2 (10 mL) at 0–5°C under
an Ar atmosphere, and the mixture was stirred at the
same temperature for 1 h. Water was added to the
mixture, which was extracted twice with AcOEt. The
combined organic phase was washed with 1 M aqueous
Et3N (1.52 mL, 11.0 mmol) and a solution of
TBSCl (1.51 g, 10.0 mmol) in CH2Cl2 (5.0 mL) were
successively added to a stirred solution of thiolactic acid
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Stereocomplementary Synthesis of cis- and trans-2,5-disubstituted Thiazolidin-4-
ones: Useful Umpolung-type Suzuki–Miyaura Cross-coupling Partner and Donor
HCl, brine, dried (Na2SO4), and concentrated. The
obtained product (1.85 g, 84%) was sufficient pure.
Colorless oil; 1H NMR (500 MHz, CDCl3): δ = 0.290 (s,
3H), 0.294 cmÀ1 (s, 3H), 0.96 (s, 9H), 1.50 (d, J = 7.45 Hz,
3H), 2.10 (d, J = 7.45 Hz, 1H), 3.50 (quin, J = 7.45 Hz,
1H); 13C NMR (125 MHz, CDCl3): δ = À5.1, À5.0,
17.7, 21.0, 25.4 (3C), 37.3, 173.5.
atomosphere, and the mixture was stirred at the same
temperature for 2 h. Water was added to the mixture, and
organic phase was separated by Celite filtration using
CHCl3. The separated organic phase was dried (Na2SO4)
and concentrated. The obtained crude product was
purified by silica-gel column chromatography (hexane/
AcOEt = 5:1–2:1) to give the desired product trans-3
(1.01 g, 71%) and cis-3 (199 mg, 14%).
N-(4-bromobenzylidene)methylamine
(6)
[18].
Colorless crystals; mp 153–155°C; 1H NMR
(500 MHz, CDCl3): δ = 1.59 (d, J = 7.45 Hz, 3H), 2.75
(s, 3H), 4.05 (dq, J = 1.72, 7.45 Hz, 1H), 5.42 (d,
J = 1.72 Hz, 1H), 7.14–7.17 (m, 2H), 7.50–7.54 (m,
2H); 13C NMR (125 MHz, CDCl3): δ = 19.9, 30.3,
41.5, 62.7, 122.8, 128.2 (2C), 132.2 (2C), 138.6, 173.8;
IR (neat): νmax = 1672, 1487, 1448, 1390, 1259, 1215,
PhCHO (9.25 g, 50.0 mmol) in EtOH
(70 mL) was added to a stirred 40% aqueous MeNH2
solution (100 mL) at 0–5°C, and the mixture was stirred
at the same temperature for 2 h. The mixture was
extracted twice with AcOEt, and the combined organic
phase was washed with water, brine, dried (Na2SO4), and
concentrated. The obtained crude product was distilled
under reduced pressure to give the desired product 2
(8.41 g, 85%).
1070, 1008 cmÀ1
.
(2S*,5R*)-cis-2-([1,1’-biphenyl]-4-yl)-3,5-dimethylthiazolidin-
Pale yellow oil; BP 119–123°C/23 mmHg; 1H NMR
(500 MHz, CDCl3): δ = 3.51 (d, J = 1.72 Hz, 3H), 7.52–
7.60 (m, 4H), 8.23 (d, J = 1.72 Hz); 13C NMR
(125 MHz, CDCl3): δ = 48.1, 124.8, 129.2 (2C), 131.8
(2C), 135.0, 161.1; IR (neat): νmax = 2847, 1651, 1589,
4-one (cis-3a).
A mixture of cis-2
(286 mg, 1.0 mmol), phenylboronic acid (183 mg,
1.5 mmol), K3PO4 (637 mg, 3.0 mmol), Pd(OAc)2 (11 mg,
0.05 mmol), and SPhos (41 mg, 0.1 mmol) in THF (2 mL)
was stirred at 40–45°C for 4 h. After cooling down, water
was added to the mixture, which was extracted twice with
AcOEt. The combined organic phase was washed with
water, brine, dried (Na2SO4), and concentrated. The
obtained crude product was purified by silica-gel column
chromatography (hexane/AcOEt = 4:1) to give the desired
1487, 1400, 1067, 1009 cmÀ1
.
2S*,5R*)-cis-2-(4-bromophenyl)-3,5-dimethylthiazolidin-4-
one (cis-2).
Thiolactic acid (318 mg,
3.00 mmol) was added to a stirred solution of imine 2
(713 mg, 3.60 mmol) in THF (6 mL) at room
temperature under an Ar atmosphere, and the mixture
was stirred at the same temperature for 6 h. The mixture
was concentrated. The obtained crude product was
purified by silica-gel column chromatography (hexane/
AcOEt = 5:1–3:1) to give the desired product cis-3
(701 mg, 82%) and trans-3 (123 mg, 14%).
product cis-3a (246 mg, 87%).
Pale yellow crystals; mp 87–89°C; 1H NMR (500 MHz,
CDCl3): δ = 1.68 (d, J = 7.45 Hz, 3H), 2.76 (s, 3H), 3.98
(q, J = 7.45 Hz, 1H), 5.52 (s, 1H), 7.35–7.41 (m, 3H),
7.43–7.48 (m, 2H), 7.57–7.63 (m, 4H); 13C NMR
(125 MHz, CDCl3): δ = 20.4, 30.4, 42.4, 63.4, 127.0
(2C), 127.59, 127.65 (2C), 127.7 (2C), 128.8 (2C),
137.8, 140.1, 142.1, 173.9; IR (neat): νmax = 1674, 1485,
1449, 1389, 1341, 1263, 1209, 1120 cmÀ1; Anal. Calcd
for C17H17NOS (283.39): C, 72.05; H, 6.05; N, 4.94; O,
5.65; S, 11.31. Found C, 71.91; H, 5.91; N, 4.91. HRMS
(ESI): m/z calcd for C17H17NOS [M + Na]+ 306.0929;
found: 306.0918.
Colorless crystals; mp 113–115°C; 1H NMR
(500 MHz, CDCl3): δ = 1.64 (d, J = 6.87 Hz), 2.70 (s,
3H), 3.95 (q, J = 6.87, 1H), 5.42 (s, 1H), 7.18–7.22
(m, 2H), 7.51–7.55 (m, 2H); 13C NMR (125 MHz,
CDCl3): δ = 20.2, 30.4, 42.3, 63.0, 123.0, 128.9 (2C),
132.1 (2C), 138.0, 173.8; IR (neat): νmax = 1674, 1487,
1448, 1388, 1334, 1263, 1211 cmÀ1; Anal. Calcd for
C11H12BrNOS (286.19): C, 46.17; H, 4.23; N, 4.89.
Found C, 46.01; H, 4.19; N, 4.80. HRMS (ESI): m/z
calcd for C11H12BrNOS [M + Na]+ 307.9721; found:
307.9742.
(2R*,5R*)-trans-2-([1,1’-biphenyl]-4-yl)-3,5-dimethylthiazolidin-
4-one (trans-3a).
Following a similar
procedure for the preparation of cis-2, the reaction of
trans-2 (286 mg, 1.0 mmol), phenylboronic acid
(183 mg, 1.5 mmol), K3PO4 (637 mg, 3.0 mmol),
Pd(OAc)2 (11 mg, 0.05 mmol), and SPhos (41 mg,
0.1 mmol) in THF (2 mL) at 40–45°C for 4 h yielded
the crude oil, which was purified by silica-gel column
chromatography (hexane/AcOEt = 5:1) to give the
desired product trans-3a (267 mg, 94%).
(2R*,5R*)-trans-2-(4-bromophenyl)-3,5-dimethylthiazolidin-
4-one (trans-2).
Ti(OiPr)4 (1.58 mL,
6.0 mmol) was added to a stirred solution of ester 7
(981 mg, 5.0 mmol) and imine 6 (1.19 g, 6.0 mmol) in
CH2Cl2 (10 mL) at room temperature under an Ar
Journal of Heterocyclic Chemistry
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R. Sasaki, H. Nakatsuji, and Y. Tanabe
Vol 000
1
Pale yellow oil; H NMR (500 MHz, CDCl3): δ = 1.61
(2C), 127.1 (2C), 133.4, 138.3, 138.8, 143.8, 174.0; IR
(d, J = 6.87 Hz, 3H), 2.79 (s, 3H), 4.09 (dq, J = 1.72,
7.45 Hz, 1H), 5.50 (d, J = 1.72 Hz, 1H), 7.31–7.38 (m,
3H), 7.41–7.47 (m, 2H), 7.54–7.62 (m, 4H); 13C NMR
(125 MHz, CDCl3): δ = 20.5, 31.1, 42.3, 63.7, 127.61
(2C), 127.63 (2C), 128.2, 128.4 (2C), 129.4 (2C), 139.0,
140.8, 142.5, 174.6; IR (neat): νmax = 1672, 1485, 1449,
(neat): νmax = 1759, 1668, 1392, 1259, 1161, 1055,
1014 cmÀ1
.
(2S*,5R*)-cis-3,5-dimethyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-
dioxaborolan-2-yl)phenyl)thiazolidin-4-one (cis-4).
1391, 1339, 1258, 1213, 1122 cmÀ1
.
A
mixture of cis-3 (143 mg,
(2S*,5R*)-cis-2-(4-(furan-3-yl)phenyl)-3,5-dimethylthiazolidin-
0.50
mmol),
bis(pinacolato)diborane
(190
mg,
0.75 mmol), KOAc (147 mg, 1.50 mmol), and Pd(dppf)
Cl2 (18 mg, 0.025 mmol) in dioxane (2.5 mL) was stirred
at 95–100°C for 16 h. After cooling down, water was
added to the mixture, which was filtered. Filtrate was
extracted twice with AcOEt. The combined organic phase
was washed with water, brine, dried (Na2SO4), and
concentrated. The obtained crude product was purified by
silica-gel column chromatography (hexane/AcOEt = 3:1)
to give the desired product (126 mg, 76%).
4-one (cis-3).
A mixture of cis-2
(143 mg, 0.50 mmol), 3-furylboronic acid (84 mg,
0.75 mmol), K3PO4 (318 mg, 1.50 mmol), Pd(OAc)2
(5.6 mg, 0.025 mmol), and SPhos (21 mg, 0.05 mmol)
in THF (1 mL) was stirred at 40–45°C for 2 h. After
cooling down, water was added to the mixture, which
was extracted twice with AcOEt. The combined organic
phase was washed with water, brine, dried (Na2SO4),
and concentrated. The obtained crude product was
purified by silica-gel column chromatography (hexane/
AcOEt = 3:1) to give the desired product (91 mg, 66%).
Pale yellow crystals; mp 72–76°C; 1H NMR
(500 MHz, CDCl3): δ = 1.67 (d, J = 6.87 Hz, 3H), 2.73
(s, 3H), 3.97 (q, J = 6.87 Hz, 1H), 5.48 (s, 1H), 6.68–
6.72 (m, 1H), 7.30–7.34 (m, 2H), 7.48–7.52 (m, 3H),
7.74–7.76 (m, 1H); 13C NMR (125 MHz, CDCl3):
δ = 20.3, 30.4, 42.4, 63.4, 108.6, 125.7, 126.4 (2C),
127.7 (2C), 133.4, 137.4, 138.8, 143.8, 173.9; IR (neat):
Colorless crystals; mp 163–164°C, 1H NMR
(500 MHz, CDCl3): δ = 1.35 (s, 12H), 1.65 (d,
J = 6.87 Hz, 3H), 2.71 (s, 3H), 3.95 (q, J = 6.87 Hz,
1H), 5.47 (s, 1H), 7.29–7.32 (m, 2H), 7.81–7.85 (m,
2H); 13C NMR (125 MHz, CDCl3): δ = 20.5, 24.9
(2C), 25.0 (2C), 30.6, 42.5, 63.7, 84.1 (2C), 126.5 (2C),
135.6 (2C), 142.0, 174.2; IR (neat): νmax = 2976, 1678,
1611, 1357, 1265, 1142, 1088 cmÀ1; Anal. Calcd for
C17H24BNO3S (333.25): C, 61.27; H, 7.26; N, 4.20.
Found C, 61.15; H, 7.21; N, 4.18. HRMS (ESI): m/z
calcd for C17H24BNO3S [M + Na]+ 356.1471; found:
356.1470.
νmax = 1668, 1520, 1362, 1263, 1161, 1053, 1015 cmÀ1
;
Anal. Calcd for C15H15NO2S (273.35): C, 65.91; H,
5.53; N, 5.12; Found C, 65.87; H, 5.49; N, 5.05. HRMS
(ESI): m/z calcd for C15H15NO2S [M + Na]+ 296.0721;
found: 296.0733.
(RS*,5R*)-trans-3,5-dimethyl-2-(4-(4,4,5,5-tetramethyl-1,3,
2-dioxaborolan-2-yl)phenyl)thiazolidin-4-one (trans-4).
(2R*,5R*)-trans-2-(4-(furan-3-yl)phenyl)-3,5-dimethylthiazolidin-
Following a similar procedure for
4-one (trans-3).
Following the similar
the preparation of cis-5, the reaction of trans-3 (143 mg,
0.50 mmol), bis(pinacolato)diborane (140 mg, 0.55 mmol),
KOAc (147 mg, 1.50 mmol), and Pd(dppf)Cl2 (18 mg,
0.025 mmol) in dioxane (2.5 mL) at 95–100°C for 4 h gave
the crude product, which was purified by silica-gel column
chromatography (hexane/AcOEt = 3:1) that gave the
desired product (122 mg, 74%).
procedure for the preparation of cis-3, the reaction of
trans-2 (143 mg, 0.50 mmol), 3-furylboronic acid
(84 mg, 0.75 mmol), K3PO4 (318 mg, 1.50 mmol),
Pd(OAc)2 (5.6 mg, 0.025 mmol), and SPhos (21 mg,
0.05 mmol) in THF (1 mL) at 40–45°C for 2 h gave the
crude product, which was purified by silica-gel column
chromatography (hexane/AcOEt = 4:1) that gave the
desired product (135 mg, 99%).
Colorless crystals; mp 115–116°C, 1H NMR
(500 MHz, CDCl3): δ = 1.35 (s, 12H), 1.60 (d,
J = 6.87 Hz, 3H), 2.76 (s, 3H), 4.70 (dq, J = 1.72,
6.87 Hz, 1H), 5.46 (d, J = 1.72 Hz, 1H), 7.24–7.28
(m, 2H), 7.81–7.85 (m, 2H); 13C NMR (125 MHz,
CDCl3): δ = 19.8, 24.8 (2C), 24.8 (2C), 30.4, 41.5,
63.2, 83.9 (2C), 125.7 (2C), 135.5 (2C), 142.5, 174.0;
IR (neat): νmax = 2976, 1678, 1611, 1358, 1265, 1144,
Pale yellow oil; 1H NMR (500 MHz, CDCl3):
δ = 1.61 (d, J = 6.87 Hz, 3H), 2.77 (s, 3H), 4.08 (dq,
J = 1.72, 6.87 Hz, 1H), 5.47 (d, J = 1.72 Hz, 1H),
6.68–6.71 (m, 1H), 7.25–7.30 (m, 2H), 7.48–7.52 (m,
3H), 7.73–7.77 (m, 1 H); 13C NMR (125 MHz, CDCl3,
59°C): δ = 19.9, 30.4, 41.6, 63.3, 108.7, 125.9, 126.5
1088 cmÀ1
.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Stereocomplementary Synthesis of cis- and trans-2,5-disubstituted Thiazolidin-4-
ones: Useful Umpolung-type Suzuki–Miyaura Cross-coupling Partner and Donor
[9] de Vries, A. H. M.; Hof, R. F.; Staal, D.; Kellogg, R. M.;
Feringa, B. L. Tetrahedron Asymmetry 1997, 8, 1539.
Acknowledgments. This research was partially supported by
Grant-in-Aids for Scientific Research on Basic Areas (B)
“18350056,” Priority Areas (A) “17035087” and “18037068,”
(C) 15K05508, and Exploratory Research “17655045” from the
Ministry of Education, Culture, Sports, Science and
Technology (MEXT). One of the authors (Y. T.) offers his
warmest congratulations to Professor Ben L. Feringa
(University of Groningen, The Netherlands) on being awarded
the 2016 Nobel Prize in Chemistry. Dedication to Professor
Teruaki Mukaiyama on the celebration of his 90th birthday
(Sotuju).
[10] Dubreuil, J. F.; Bazureau, J. P. Tetrahedron 2003, 59, 6121.
[11] Original syntheses: (a) Seebach, D.; Naef, R. Helv Chim Acta
Theriol 1981, 64, 2704; (b) Fráter, G.; Müller, U.; Günther, W. Tetrahedron
Lett 1981, 22, 4221; (c) Seebach, D.; Sting, A. R.; Hoffmann, M. Angew
Chem Int Ed Engl 1996, 35, 2708; (d) Clayden, J.; Greeves, N.; Warren,
S.; Wothers, P. Organic Chemistry; Oxford: New York, 2001, p. 855.
[12] For practical syntheses: (a) Mase, T.; Houpis, I. N.; Akao, A.;
Dorziotis, I.; Emerson, K.; Hoang, T.; Iida, T.; Itoh, T.; Kamei, K.; Kato,
S.; Kato, Y.; Kawasaki, M.; Lang, F.; Lee, J.; Lynch, J.; Maligres, P.;
Molina, A.; Nemoto, T.; Okada, S.; Reamer, R.; Song, J. Z.; Tschaen,
D.; Wada, T.; Zewge, D.; Volante, R. P.; Reider, P. J.; Tomimoto, K. J
Org Chem 2001, 66, 6775; (b) Misaki, T.; Ureshino, S.; Nagase, R.;
Oguni, Y.; Tanabe, Y. Org Process Res Dev 2006, 10, 500; (c) Nagase,
R.; Oguni, Y.; Misaki, T.; Tanabe, Y. Synthesis (PSP) 2006, 3915.
[13] Strijtveen, B.; Kellogg, R. M. Tetrahedron 1987, 43, 5039.
[14] (a) Tanabe, Y.; Kubota, Y.; Sanemitsu, Y.; Itaya, N.;
Suzukamo, G. Tetrahedron Lett 1991, 32, 383; (b) Tanabe, Y.; Yama-
moto, H.; Murakami, M.; Yanagi, K.; Kubota, Y.; Okumura, H.;
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[15] Tanabe, Y.; Suzukamo, G.; Komuro, Y.; Imanishi, N.;
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[16] Representative examples: (a) Nakatsuji, H.; Ueno, K.; Misaki,
T.; Tanabe, Y. Org Lett 2008, 10, 2131; (b) Nakatsuji, H.; Nishikado, H.;
Ueno, K.; Tanabe, Y. Org Lett 2009, 11, 4258; (c) Ashida, Y.; Sato, Y.;
Suzuki, T.; Ueno, K.; Kai, K.; Nakatsuji, H.; Tanabe, Y. Chem Eur J
2015, 21, 5934; (d) Nakatsuji, H.; Ashida, Y.; Hori, H.; Sato, Y.; Honda,
A.; Taira, M.; Tanabe, Y. Org Biomol Chem 2015, 13, 8205; (e) Ashida,
Y.; Honda, A.; Sato, Y.; Nakatsuji, H.; Tanabe, Y. ChemistryOpen 2017, 6,
73; (f) Ashida, Y.; Sato, Y.; Honda, A.; Nakatsuji, H.; Tanabe, Y. Synform
2017 A38; (g) Nakatsuji, H.; Kamada, R.; Kitaguchi, H.; Tanabe, Y. Adv
Synth Catal, ASAP; (h) Ashida, Y.; Nakatsuji, H.; Tanabe, Y. Org Synth
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet