Synthesis of spirooxindoles bearing 2,3-(or 2,5-)dihydrothiophene-2-thione moiety via [3+2] annulation of carbon disulfide with Morita-Baylis-Hillman carbonates of isatins

Article abstract of DOI:10.1016/j.tetlet.2018.03.056

Various spirooxindoles bearing 2,3-(or 2,5-)dihydrothiophene-2-thione moiety have been synthesized via [3+2] annulation reaction of carbon disulfide and the nitrogen ylides derived from Morita-Baylis-Hillman carbonates of isatins. 2,3-Dihydro- and 2,5-dih

Full text of DOI:10.1016/j.tetlet.2018.03.056

Accepted Manuscript
Synthesis of spirooxindoles bearing 2,3-(or 2,5-)dihydrothiophene-2-thione
moiety via [3+2] annulation of carbon disulfide with Morita-Baylis-Hillman
carbonates of isatins
Beom Kyu Min, Gieun Kim, Hwa Jung Roh, Da Young Seo, Jae Nyoung Kim
PII:
S0040-4039(18)30370-8
https://doi.org/10.1016/j.tetlet.2018.03.056
TETL 49825
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Reference:
Tetrahedron Letters
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19 March 2018
Please cite this article as: Min, B.K., Kim, G., Roh, H.J., Seo, D.Y., Kim, J.N., Synthesis of spirooxindoles bearing
2,3-(or 2,5-)dihydrothiophene-2-thione moiety via [3+2] annulation of carbon disulfide with Morita-Baylis-Hillman
carbonates of isatins, Tetrahedron Letters (2018), doi: https://doi.org/10.1016/j.tetlet.2018.03.056
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Synthesis of spirooxindoles bearing 2,3-(or
2,5-)dihydrothiophene-2-thione moiety via
[3+2] annulation of carbon disulfide with
Morita-Baylis-Hillman carbonates of isatins
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Beom Kyu Min, Gieun Kim, Hwa Jung Roh, Da Young Seo, Jae Nyoung Kim*

1
Tetrahedron Letters
Synthesis of spirooxindoles bearing 2,3-(or 2,5-)dihydrothiophene-2-thione
moiety via [3+2] annulation of carbon disulfide with Morita-Baylis-Hillman
carbonates of isatins
Beom Kyu Min, Gieun Kim, Hwa Jung Roh, Da Young Seo, Jae Nyoung Kima,
Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Various spirooxindoles bearing 2,3-(or 2,5-)dihydrothiophene-2-thione moiety have been
synthesized via [3+2] annulation reaction of carbon disulfide and the nitrogen ylides derived
from Morita-Baylis-Hillman carbonates of isatins. 2,3-Dihydro- and 2,5-dihydrothiophene-2-
thione moieties were formed selectively depending on steric hindrance around the nitrogen
ylides.
Available online
2018 Elsevier Ltd. All rights reserved.
Keywords:
[3+2] Annulation
Carbon disulfide
Dihydrothiophene-2-thione
Morita-Baylis-Hillman carbonates
Spirooxindoles
Spirooxindoles exist in a huge number of natural substances
and pharmaceutically interesting compounds.1 Thus, tremendous
efforts have been devoted to efficient protocols to access these
important motifs over the past years.1,2 Various spirooxindoles
bearing lactone moiety have been reported (see, A and B, Fig.
1).3,4 Recently, we5a and other group5b reported independently the
synthesis of spirooxindoles bearing iminothiolactone moiety (C
and D) from aryl isothiocyanates and phosphorous5a or nitrogen5b
ylides derived from Morita-Baylis-Hillman (MBH) carbonates of
isatins. In addition, spirooxindoles bearing thiolactone (E and F)
were also synthesized indirectly by acidic hydrolysis of the
iminothiolactone derivatives.5 However, spirooxindoles bearing
dihydrothiophene-2-thione moiety (2a and 3a) have not been
reported,6 to the best of our knowledge.
for 30 h. To our pleased, the reaction of 1a and carbon disulfide
in CH3CN in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene
Carbon disulfide has been used for the synthesis of various
sulfur-containing heterocyclic compounds.7 Thus, we reasoned
out that the reaction of phosphorous or nitrogen ylides derived
from MBH carbonates of isatins and carbon disulfide, instead of
phenyl isothiocyanate, would afford spirooxindoles bearing
dihydrothiophene-2-thione moiety, as shown in Scheme 1. The
formation of 2,3-dihydrothiophene-2-thione derivative 2a (-
adduct) or 2,5-dihydrothiophene-2-thione derivative 3a (-
adduct) would be expected (vide infra, for - and -adducts).
At the outset of our study, we examined the reaction of 1a
and PPh3 (0.2 equiv) in CH3CN in the presence of carbon
disulfide (30 equiv) at 50 oC.8 However, no reaction was
observed even after a long time (30 h). When we used an
Figure 1. Representative 5-membered heterocyclic spirooxindoles.
equivalent amount of PPh3, 2a was isolated in low yield (11%)
———
 Corresponding author. Tel.: +82 62 530 3381; fax: +82 62 530 3389.
E-mail address: kimjn@chonnam.ac.kr (J. N. Kim).

2
Tetrahedron Letters
Table 2. Regioselective synthesis of -adduct 2.a
Scheme 1. Synthetic rationale of spirooxindoles 2a and 3a.
(DBU, 0.2 equiv) afforded 2a in good yield (69%) along with a
small amount of 3a (6%).9 The carbanion character of nitrogen
ylide is larger than that of phosphorous ylide, because nitrogen
ylide shows no double bond character at all.10 Thus, the reaction
with less electrophilic carbon disulfide might be effective with
more reactive nitrogen ylide. The chemical shift of the
spirocarbon atom of 2a in 13C NMR spectrum appeared at 81.8
ppm, while that of 3a appeared at more up-field 72.9 ppm.11,12
In order to optimize the yield of 2a and increase the
selectivity of 2a/3a, we examined the reaction of 1a in the
presence of carbon disulfide (30 equiv)13 under various amine-
catalyzed conditions, as shown in Table 1. As noted above, the
reaction in the presence of PPh3 afforded 2a in low yield (entry
1). The reaction in the presence of DBU in 1,2-dichloroethane
(DCE, entry 2) afforded 2a in good yield (66%) along with a
small amount of 3a (5%). As noted above, the reaction in
CH3CN (entry 3) gave the highest yield of 2a (69%) along with
3a (6%). The reactions at lower temperature (entries 4 and 5)
were not better. The selectivity of 2a/3a was destroyed in DMF
(entry 6), and the reaction with an equivalent amount of DBU
(entry 7) showed a similar result. It is interesting to note that the
reaction with 1,5-diazabicyclo[4.3.0]non-5-ene (DBN, entry 8)
produced 2a and 3a in lower yield without selectivity. The
reactions in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene
aConditions: Substrate 1 (0.5 mmol).
the starting material 1a was completely disappeared and the
formation of some intractable polar compounds was observed.
Encouraged by the successful results, various spirooxindoles
bearing 2,3-dihydrothiophene-2-thiones 2b-2i were synthesized,
as summarized in Table 2.12 The reactions of 1b-1i in the
presence of DBU afforded -adducts 2b-2i as major products in
good to moderate yields (39-82%) along with minor -adducts
3b-3i (0-8%). The yield of nitro derivative 2e (39%) was
somewhat low due to the formation of some intractable side
products. The reaction of acetyl derivative 1i also produced 2i in
good yield (82%), and the formation of 3i was not observed in
this case. Unfortunately, the nitrile derivative 1j (X = H, EWG =
CN) did not produce the desired product in an appreciable yield.
The formation of many intractable side products was observed in
the reaction.
(TBD,
entry
9),
Et3N
(entry
10),
and
1,4-
diazabicyclo[2.2.2]octane (DABCO, entry 11) were less
effective. When we used 4-(dimethylamino)pyridine (DMAP,
entry 12), compound 3a was formed as a major product in good
yield (72%) along with a small amount of 2a (6%). The yield of
3a was not improved at low temperature (entry 13) or in 1,2-
dichloroethane (entry 14). The reaction in the presence of
dimethyl sulfide was completely ineffective (entry 15). Under
the optimized reaction conditions (entries 3 and 12 in Table 1),
Table 1. Optimization of reaction conditions of 1a.a
Entry
Catalystb
Solvent
CH3CN
DCE
Temp (oC)
50
Time (h)
30
Yield (%)c
1
PPh3 (1.0)
DBU (0.2)
DBU (0.2)
DBU (0.2)
DBU (0.2)
DBU (0.2)
DBU (1.0)
DBN (0.2)
TBD (0.2)
Et3N (0.2)
DABCO (0.2)
DMAP (0.2)
DMAP (0.2)
DMAP (0.2)
Me2S (30)
2a (11)/3a (0)
2a (66)/3a (5)
2a (69)/3a (6)
2a (63)/3a (5)
2a (62)/3a (4)
2a (50)/3a (16)
2a (65)/3a (5)
2a (38)/3a (27)
2a (10)/3a (16)
2a (4)/3a (9)
2a (42)/3a (2)
2a (6)/3a (72)
2a (5)/3a (61)
2a (5)/3a (67)
2a (0)/3a (0)
2
50
0.5
0.5
0.5
12
3
CH3CN
CH3CN
CH3CN
DMF
50
4
40
5
25
6
50
0.5
0.5
0.5
0.5
30
7
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DCE
50
8
50
9
50
10
11
12
13
14
15
50
50
0.5
0.5
0.5
0.5
20
50
40
50
CH3CN
40
aAll reactions were carried out in 0.5 mmol scale in the presence of CS2 (30 equiv).
bEquivalent in parenthesis.
cIsolated yields.

3
Table 3. Regioselective synthesis of -adduct 3.a
Scheme 2. Proposed mechanism.
hindered for the N-ylide generated from DMAP to produce 3a as
a major product. Similar regiodivergent syntheses of spirooxindoles
via [3+2] annulation have been reported from the phosphorous5a,8 or
nitrogen ylides5b,9 derived from MBH carbonates of isatins. The 
selectivity was dependent on nucleophilic catalysts (amine or
phosphine) and/or electrophilic partners.5,8,9
aConditions: Substrate 1 (0.5 mmol).
The synthesis of 1,4,2-oxathiazole by [3+2] cycloaddition
reaction between nitrile oxide and C=S double bond is well-
known.14 Thus, we examined the reaction of 2a and 4-
chlorobenzonitrile oxide, as shown in Scheme 3. The reaction of
2a and 4-chlorobenzohydroxamoyl chloride (1.5 equiv) in the
presence of Et3N (1.5 equiv) gave dispiro compound 4 in
quantitative yield (99%). Two diastereomeric isomers could be
separated in a ratio of 85:14, although we did not confirm their
stereochemistry. Similarly, the reaction of 3a afforded dispiro
compound 5 in quantitative yield (98%) in a diastereomeric ratio
of 85:13. Thermal rearrangement of the major isomer of 4 in
refluxing 1,2-dichlorobenzene (ODCB) gave spirooxindole E in
good yield (77%) along with 4-chlorophenyl isothiocyanate
(72%).14a,15 Similarly, the reaction of the major isomer of 5
afforded F (92%) and 4-chlorophenyl isothiocyanate (78%).16
As a last entry the reaction of 1k was examined, as shown in
Scheme 4. MBH carbonate 1k was prepared according to the
The reactions of 1b-1i in the presence of DMAP were also
carried out, and the results are summarized in Table 3.12 The
reactions afforded spirooxindoles bearing 2,5-dihydrothiophene-
2-thiones 3b-3i as major products in good to moderate yields
(34-75%) along with minor -adducts 2b-2i (4-11%). The
reaction of acetyl derivative 1i produced 3i in low yield (34%)
along with an appreciable amount of 2i (11%). The reason for
low yield and  selectivity in this case is not clear at this stage.
The reaction mechanism could be proposed as shown in
Scheme 2. The reaction of 1a and tertiary amine catalyst
afforded resonance-stabilized N-ylide I. The ylide I has two
nucleophilc - and -carbon centers. The reaction of -carbanion
and carbon disulfide produced 3a via zwitterionic intermediate
II, and the reaction with -carbanion generated 2a via
intermediate III. When we used DBU the corresponding -
position would be sterically less hindered to produce 2a as a
major product, while the -position would be sterically less
Scheme 3. Synthesis of dispiro derivatives 4 and 5, and their thermal rearrangement.

4
Tetrahedron
reported method.17a The reaction of 1k in the presence of DBU
Tetrahedron Lett. 2017, 58, 4094; (c) Min, B. K.; Lee, S.; Roh, H. J.;
Ryu, J. Y.; Lee, J.; Kim, J. N. Tetrahedron Lett. 2017, 58, 3251; (d)
Seo, D. Y.; Min, B. K.; Roh, H. J.; Kim, J. N. Bull. Korean Chem. Soc.
2017, 38, 1231; (e) Kim, S. Y.; Roh, H. J.; Seo, D. Y.; Ryu, J. Y.; Lee,
J.; Kim, J. N. Tetrahedron Lett. 2017, 58, 914; (f) Roh, H. J.; Kim, S.
Y.; Min, B. K.; Kim, J. N. Tetrahedron Lett. 2017, 58, 21; (g) Roh, H.
J.; Lim, J. W.; Ryu, J. Y.; Lee, J.; Kim, J. N. Tetrahedron Lett. 2016,
57, 4280; (h) Lim, J. W.; Kim, K. H.; Moon, H. R.; Kim, J. N.
Tetrahedron Lett. 2016, 57, 784; (i) Lim, J. W.; Moon, H. R.; Kim, S.
Y.; Kim, J. N. Tetrahedron Lett. 2016, 57, 133; (j) Kim, K. H.; Moon,
H. R.; Lee, J.; Kim, J.; Kim, J. N. Adv. Synth. Catal. 2015, 357, 1532;
(k) Kim, K. H.; Moon, H. R.; Lee, J.; Kim, J. N. Adv. Synth. Catal.
2015, 357, 701.
(0.2 equiv) was somewhat sluggish. We thought that the sluggish
reactivity might be due to steric hindrance around the -position
of 2-cyclohexen-1-one moiety of 1k, and the attack of DBU
might be difficult. However, we could not obtain desired -
adduct 2k or -adduct 3k at all even in the presence of an
equivalent amount of DBU. Instead, two unexpected compounds
6 (23%) and 7 (49%)17b were produced in moderate yields. When
we carried out the reaction without carbon disulfide, the
formation of 6 and 7 was not observed. The result stated that
carbon disulfide and DBU must be required for the formation of
these compounds. Literature survey revealed that DBU and
3. (a) Buxton, C. S.; Blakemore, D. C.; Bower, J. F. Angew. Chem. Int.
Ed. 2017, 56, 13824; (b) Ming, S.; Zhao, B.-L.; Du, D.-M. Org.
Biomol. Chem. 2017, 15, 6205; (c) Zhou, R.; Liu, R.; Zhang, K.; Han,
L.; Zhang, H.; Gao, W.; Li, R. Chem. Commun. 2017, 53, 6860.
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Org. Chem. 2012, 77, 11034; (b) Cao, T.; Deitch, J.; Linton, E. C.;
Kozlowski, M. C. Angew. Chem. Int. Ed. 2012, 51, 2448.
carbon
disulfide
produced
7-thia-1,5-
diazatricyclo[7.4.1.05,14]tetradec-9(14)-ene-6,8-dithione
and
DBU hydrogen sulfide salt (see, the box in Scheme 4).18 DBU
hydrogen sulfide salt might cause the conversion of 1k into 6
and 7; however, the mechanism is not clear at this stage.19
5. (a) Min, B. K.; Kim, S. Y.; Ryu, J. Y.; Lee, J.; Kim, J. N. Bull. Korean
Chem. Soc. 2017, 38, 140; (b) Zhao, Y.-Y.; Zhao, S.; Xie, J.-K.; Hu,
X.-Q.; Xu, P.-F. J. Org. Chem. 2016, 81, 10532.
6. For synthesis of thiophene-2-thione derivatives, see: (a) Labruere, R.;
Desbene-Finck, S.; Helissey, P.; Giorgi-Renault, S. Synthesis 2006,
4163; (b) Gladow, D.; Reissig, H.-U. J. Org. Chem. 2014, 79, 4492; (c)
Giofre, S. V.; Romeo, R.; Mancuso, R.; Cicero, N.; Corriero, N.;
Chiacchio, U.; Romeo, G.; Gabriele, B. RSC Adv. 2016, 6, 20777; (d)
Maercker, A.; Van de Flierdt, J.; Girreser, U. Tetrahedron 2000, 56,
3373; (e) Jenny, C.; Heimgartner, H. Helv. Chim. Acta 1986, 69, 419;
(f) Commercon, A.; Ponsinet, G. Tetrahedron Lett. 1985, 26, 5131; (g)
Jenny, C.; Obrecht, D.; Heingartner, H. Helv. Chim. Acta 1982, 65,
2583; (h) Meijer, J.; Ruitenberg, K.; Westmijze, H.; Vermeer, P.
Synthesis 1981, 551..
7. For synthesis of sulfur-containing heterocycles using carbon disulfide,
see: (a) Basavaiah, D.; Pal, S.; Veeraraghavaiah, G.; Bharadwaj, K. C.
Tetrahedron 2015, 71, 4659; (b) Dighe, S. U.; Yadav, V. D.;
Srivastava, R.; Mishra, A.; Gautam, S.; Srivastava, A. K.;
Balaramnavar, V. M.; Saxena, A. K.; Batra, S. Tetrahedron 2014, 70,
6841; (c) Pal, S. C.; Bhunia, S. C. Eur. J. Org. Chem. 2013, 4816; (d)
Chen, Z.; Clive, D. L. J. J. Org. Chem. 2010, 75, 7014; (e) Yadav, L. D.
S.; Patel, R.; Srivastava, V. P. Tetrahedron Lett. 2009, 50, 1335; (f)
Fukamachi, S.; Konishi, H.; Kobayashi, K. Heterocycles 2009, 78, 169;
(g) Gade, T.; Streek, M.; Voss, J. Chem. Ber. 1992, 125, 127 (h)
Aitken, R. A.; Raut, S. V.; Ferguson, G. Tetrahedron 1992, 48, 8023;
(i) Alemagna, A.; Buttero, P. D.; Licandro, E.; Maiorana, S.; Trave, R.
Tetrahedron 1984, 40, 971; (j) Villemin, D.; Alloum, A. B. Synth.
Commun. 1992, 22, 1351.
8. For synthetic applications of phosphorous ylides derived from MBH
adducts of isatin, see: (a) Li, H.; Lu, Y. Asian J. Org. Chem. 2017, 6,
1130; (b) Selvakumar, K.; Vaithiyanathan, V.; Shanmugam, P. Chem.
Commun. 2010, 46, 2826; (c) Wang, K.-K.; Jin, T.; Huang, X.; Ouyang,
Q.; Du, W.; Chen, Y.-C. Org. Lett. 2016, 18, 872; (d) Zhan, G.; Shi,
M.-L.; He, Q.; Du, W.; Chen, Y.-C. Org. Lett. 2015, 17, 4750; (e) Liu,
J.-Y.; Lu, H.; Li, C.-G.; Liang, Y.-M.; Xu, P.-F. Synlett 2016, 27, 1287;
(f) Wang, Y.; Liu, L.; Zhang, T.; Zhong, N.-J.; Wang, D.; Chen, Y.-J. J.
Org. Chem. 2012, 77, 4143.
Scheme 4. Unusual reaction of 1k.
In summary, various spirooxindoles bearing 2,3-(or 2,5-
)dihydrothiophene-2-thione moiety have been synthesized via
[3+2] annulation reaction of carbon disulfide and the nitrogen
ylides derived from Morita-Baylis-Hillman carbonates of isatins.
The ratio of two regioisomeric spirooxindoles could be
controlled by the steric hindrance around the corresponding
nitrogen ylides.20
Acknowledgments
This work was supported by National Research Foundation of
Korea (NRF) grant funded by the Korea government (NRF-
2015R1A4A1041036). Spectroscopic data were obtained from
the Korea Basic Science Institute, Gwangju branch.
9. For synthetic applications of nitrogen ylides derived from MBH
adducts of isatin, see: (a) He, Q.; Du, W.; Chen, Y.-C. Adv. Synth.
Catal. 2017, 359, 3782; (b) Wang, K.-K.; Du, W.; Zhu, J.; Chen, Y.-C.
Chin. Chem. Lett. 2017, 28, 512; (c) Zhan, G.; Shi, M.-L.; He, Q.; Lin,
W.-J.; Ouyang, Q.; Du, W.; Chen, Y.-C. Angew. Chem. Int. Ed. 2016,
55, 2147; (d) Ran, G.-Y.; Wang, P.; Du, W.; Chen, Y.-C. Org. Chem.
Front. 2016, 3, 861; (e) Wang, K.-K.; Wang, P.; Ouyang, Q.; Du, W.;
Chen, Y.-C. Chem. Commun. 2016, 52, 11104; (f) Peng, J.; Ran, G.-Y.;
Du, W.; Chen, Y.-C. Synthesis 2015, 47, 2538; (g) Jiang, K.; Chen, Y.-
C. Tetrahedron Lett. 2014, 55, 2049; (h) Peng, J.; Huang, X.; Jiang, L.;
Cui, H.-L.; Chen, Y.-C. Org. Lett. 2011, 13, 4584; (i) Fan, X.; Yang,
H.; Shi, M. Adv. Synth. Catal. 2017, 359, 49; (j) Wei, F.; Huang, H.-Y.;
Zhong, N.-J.; Gu, C.-L.; Wang, D.; Liu, L. Org. Lett. 2015, 17, 1688;
(k) Zhong, N.-J.; Wei, F.; Xuan, Q.-Q.; Liu, L.; Wang, D.; Chen, Y.-J.
Chem. Commun. 2013, 49, 11071; (l) Liu, Y.-L.; Wang, X.; Zhao, Y.-
L.; Zhu, F.; Zeng, X.-P.; Chen, L.; Wang, C.-H.; Zhao, X.-L.; Zhou, J.
Angew. Chem. Int. Ed. 2013, 52, 13735; (m) Viswambharan, B.;
Selvakumar, K.; Madhavan, S.; Shanmugam, P. Org. Lett. 2010, 12,
2108.
Supplementary data
Supplementary data associated with this article can be found,
in the online version, at xxxxxxxxxxxx.
References and notes
1. For reviews on spirooxindoles, see: (a) Ye, N.; Chen, H.; Wold, E. A.;
Shi, P.-Y.; Zhou, J. ACS Infect. Dis. 2016, 2, 382; (b) Yu, B.; Yu, D.-
Q.; Liu, H.-M. Eur. J. Med. Chem. 2015, 97, 673; (c) Santos, M. M. M.
Tetrahedron 2014, 70, 9735; (d) Cheng, D.; Ishihara, Y.; Tan, B.;
Barbas, C. F., III ACS Catal. 2014, 4, 743; (e) Hong, L.; Wang, R. Adv.
Synth. Catal. 2013, 355, 1023; (f) Singh, G. S.; Desta, Z. Y. Chem. Rev.
2012, 112, 6104; (g) Ball-Jones, N. R.; Badillo, J. J.; Franz, A. K. Org.
Biomol. Chem. 2012, 10, 5165; (h) Trost, B. M.; Brennan, M. K.
Synthesis 2009, 3003; (i) Marti, C.; Carreira, E. M. Eur. J. Org. Chem.
2003, 2209; (j) Moradi, R.; Ziarani, G. M.; Lashgari, N. Arkivoc 2017,
i, 148; (k) Ziarani, G. M.; Moradi, R.; Lashgari, N. Arkivoc 2016, i, 1.
2. For our recent synthesis of spirooxindoles, see: (a) Min, B. K.; Seo, D.
Y.; Ryu, J. Y.; Lee, J.; Kim, J. N. Bull. Korean Chem. Soc. 2018, 39,
115; (b) Roh, H. J.; Seo, D. Y.; Ryu, J. Y.; Lee, J.; Kim, J. N.
10. Naito, T.; Nagase, S.; Yamataka, H. J. Am. Chem. Soc. 1994, 116,
10080.
11. The synthesis of 3a has been examined by thionation reaction of
spirooxindole F (Fig. 1)5a with Lawesson’s reagent (LR) in refluxing
toluene. Spirooxindole 3a was produced in low yield (9%); however,

5
the formation of many intractable side products was observed
presumably due to the possibility of thionation at the thiolactone, isatin,
and ester group.
12. Typical procedure for the synthesis of 2a: To a stirred solution of 1a
(174 mg, 0.5 mmol) and carbon disulfide (1.14 g, 30 equiv) in CH3CN
(2 mL) was added DBU (15 mg, 20 mol%) at room temperature, and
the reaction mixture was heated to 50 oC for 30 min under N2 balloon
atmosphere. After the usual aqueous extractive workup and column
chromatographic
purification
process
(CH2Cl2/Et2O,
50:1)
spirooxindoles 2a (106 mg, 69%, orange solid) and 3a (9 mg, 6%,
brown solid) were obtained. Other compounds were synthesized
similarly, and the selected spectroscopic data of 2a and 3a are as
follows.
Compound 2a: orange solid, mp 174-176 oC; IR (KBr) 1717, 1608,
1338 cm-1; 1H NMR (CDCl3, 500 MHz)  3.29 (s, 3H), 3.64 (s, 3H),
6.93 (d, J = 7.7 Hz, 1H), 6.97 (d, J = 7.5 Hz, 1H), 7.03 (t, J = 7.5 Hz,
1H), 7.36 (t, J = 7.7 Hz, 1H), 8.15 (s, 1H); 13C NMR (CDCl3, 125
MHz)  27.4, 52.4, 81.8, 109.3, 122.7, 123.5, 130.1, 131.3, 134.2,
143.1, 144.7, 159.9, 171.1, 231.6; ESIMS m/z 306 [M++H]. Anal. Calcd
for C14H11NO3S2: C, 55.06; H, 3.63; N, 4.59. Found: C, 55.31; H, 3.91;
N, 4.42.
Compound 3a: brown solid, mp 163-164 oC; IR (KBr) 1725, 1610,
1341 cm-1; 1H NMR (CDCl3, 500 MHz)  3.33 (s, 3H), 3.68 (s, 3H),
6.93 (d, J = 7.8 Hz, 1H), 7.09 (t, J = 7.6 Hz, 1H), 7.23 (d, J = 7.6 Hz,
1H), 7.25 (s, 1H), 7.39 (t, J = 7.8 Hz, 1H); 13C NMR (CDCl3, 125
MHz)  27.5, 53.1, 72.9, 109.4, 123.7, 124.0, 124.5, 130.8, 143.8,
148.4, 151.5, 162.3, 170.7, 225.7; ESIMS m/z 306 [M++H]. Anal. Calcd
for C14H11NO3S2: C, 55.06; H, 3.63; N, 4.59. Found: C, 55.10; H, 3.89;
N, 4.53.
13. The yields of 2a (57%) and 3a (3%) decreased a little when we used
lesser amount (10 equiv) of carbon disulfide, due to the formation of
conjugated trienes,2c which were generated by SN2’ reaction between
the ylide I and 1a, and subsequent E2 elimination of DBU.
14. For synthesis of 1,4,2-oxathiazoles, see: (a) Chung, W.-S.; Tsai, T.-L.;
Ho, C.-C.; Chiang, M. Y. N.; le Noble, W. J. J. Org. Chem. 1997, 62,
4672; (b) Kim, J. N.; Ryu, E. K. Tetrahedron Lett. 1993, 34, 8283; (c)
Kim, J. N.; Jung, K. S.; Lee, H. J.; Son, J. S. Tetrahedron Lett. 1997,
38, 1597; (d) Vedejs, E.; Wilde, R. G. J. Org. Chem. 1986, 51, 117; (e)
Foye, W. O.; Kauffman, J. M. J. Org. Chem. 1966, 31, 2417.
15. For thermal rearrangement of 1,4,2-oxathiazoles, see: (a) Hewitt, R. J.;
Ong, M. J. H.; Lim, Y. W.; Burkett, B. A. Eur. J. Org. Chem. 2015,
6687; (b) Burkett, B. A.; Fu, P.; Hewitt, R. J.; Ng, S. L.; Toh, J. D. W.
Eur. J. Org. Chem. 2014, 1053; (c) O’Reilly, R. J.; Radom, L. Org.
Lett. 2009, 11, 1325; (d) Jung, K. S.; Lee, H. J.; Song, H. N.; Kim, J. N.
Synth. Commun. 1998, 28, 1897.
16. Similarly, the minor isomers of 4 and 5 were also converted into E and
F, respectively.
17. For preparation and reaction of 1k, see: (a) Basavaiah, D.; Badsara, S.
S.; Veeraraghvaiah, G. Tetrahedron 2013, 69, 7995; (b) Basavaiah, D.;
Roy, S.; Das, U. Tetrahedron 2010, 66, 5612.
18. For reaction of DBU and carbon disulfide, see: (a) Ang, M. T. C.; Phan,
L.; Alshamrani, A. K.; Harjani, J. R.; Wang, R.; Schatte, G.; Mosey, N.
J.; Jessop, P. G. Eur. J. Org. Chem. 2015, 7333; (b) Vlasse, M.;
Giandinoto, S.; Attarwala, S. T.; Okamoto, Y. Acta Crystallogr., Sect.
C 1986, 42, 487.
19. The reaction of 1k and carbon disulfide even in the presence of an
equivalent amount of DMAP showed no reaction.
20. During the evaluation process, one of the reviewers suggested that the
reactions in Table 2 using DBU could be catalyzed by 7-thia-1,5-
diazatricyclo[7.4.1.05,14]tetradec-9(14)-ene-6,8-dithione
(DBU/CS2
adduct). We could not exclude the possibility completely at this stage.

6
Tetrahedron
Synthesis of spirooxindoles bearing 2,3-
(or 2,5-)dihydrothiophene-2-thione
moiety via [3+2] annulation of carbon
disulfide with Morita-Baylis-Hillman
carbonates of isatins
Beom Kyu Min, Gieun Kim, Hwa Jung Roh, Da
Young Seo, Jae Nyoung Kim*
Highlights
*Synthesis of spirooxindoles bearing
dihydrothiophene-2-thione
*Control of regiochemistry by tertiary amine
catalysts
*Regioselective [3+2] annulation of N-ylides of
MBH carbonates and carbon disulfide