Enantioselective [2+2+2] cycloaddition of ketenes and carbon disulfide catalyzed by N-heterocyclic carbenes

Article abstract of DOI:10.1039/c1cc12316e

The chiral N-heterocyclic carbene-catalyzed [2+2+2] cycloaddition of ketenes and carbon disulfide was realized to give the cycloadduct of 1,3-oxathian-6-ones in good yields with excellent enantioselectivities.

Full text of DOI:10.1039/c1cc12316e

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
ChemComm
Cite this: Chem. Commun., 2011, 47, 8388–8390
www.rsc.org/chemcomm
COMMUNICATION
Enantioselective [2+2+2] cycloaddition of ketenes and carbon disulfide
catalyzed by N-heterocyclic carbenesw
Xiao-Na Wang, Li-Tao Shen and Song Ye*
Received 21st April 2011, Accepted 11th May 2011
DOI: 10.1039/c1cc12316e
The chiral N-heterocyclic carbene-catalyzed [2+2+2] cyclo-
addition of ketenes and carbon disulfide was realized to give the
cycloadduct of 1,3-oxathian-6-ones in good yields with excellent
enantioselectivities.
It is unexpected that NHCs 4g and 4h derived from mesityl
hydrazine offered only trace cycloadduct 3a (entries 7 and 8)
with ketene dimer as the major byproduct. Further improve-
ment of the reaction was realized by carrying out the reaction
at ꢀ40 1C, which gave the cycloadduct 3a in 99% yield with
96% ee (entry 9). Reaction catalyzed by the tetracyclic carbene 50,
derived from aminoindanol, gave cycloadduct with 96% ee
albeit in 24% yield (entry 10).
With the optimum reaction conditions in hand,15 a variety
of ketenes were then tested for the [2+2+2] cycloaddition
reaction (Table 2). Aryl(alkyl)ketenes 1b and 1c with electron-
withdrawing groups (Ar = 4-Cl, 4-BrC6H4) worked well to
give the cycloadduct in good yields with excellent enantio-
selectivities (entries 2 and 3). Ketene 1d with p-methylphenyl
group afforded cycloadduct in 72% with 92% ee (entry 4).
Carbon disulfide is an attractive C1 building block for the
synthesis of sulfur-containing organic compounds.1 Parti-
cularly, the cycloadditions with carbon disulfide afford rapid
construction of sulfur-heterocycles.2 Although the Lewis
bases-catalyzed3 and organometallic compounds-catalyzed4
cycloadditions with carbon disulfide have been widely reported,
to the best of our knowledge, the enantioselective catalytic cyclo-
addition reaction with carbon disulfide remains unexplored.
Over the past two decades, N-heterocyclic carbenes (NHCs)5
have been successfully used as reagents for heterocycles,6
ligands for organometallic catalysts,7 and Lewis base organo-
catalysts.8–10 In the line of our NHC-catalyzed reactions, we
found that NHCs are efficient catalysts for the cycloaddition
reactions of ketenes.11–13 In this communication, we wish to
report an NHC-catalyzed cycloaddition of ketenes with carbon
disulfide. Although the formation of the stable NHC-CS2
adduct is well established,14 our report shows that the NHC-
catalyzed reaction with carbon disulfide is also feasible.
Firstly, the reaction of phenyl(ethyl)ketene (1a) with carbon
disulfide was investigated (Table 1). In the presence of catalytic
NHC 4a0, generated freshly from its precursor 4a and Cs2CO3,
the reaction gave the corresponding [2+2+2] cycloadduct of
1,3-oxathian-6-one 3a, which involving two molecules of
ketene 1a and one molecule of carbon disulfide, in 69% yield
with 95% ee (entry 1). A series of NHCs derived from
L-pyroglutamic acid were then screened (entries 2–8). NHCs
4b and 4c with diphenylmethyl group showed similar results as
NHC 4a (entries 2 and 3). NHC 4d with two bulky aryl groups
resulted in a dramatic decrease of enantioselectivity (entry 4).
NHCs 4e and 4f with a free hydroxy group gave cycloadduct
3a in moderate yields with varied ee values (entries 5 and 6).
Table 1 Screening of NHCs
Entry
4 (Ar1, Ar2, R) or 5a
Yield (%)b
ee (%)c
1
2
3
4
5
6
7
4a (Ph, Ph, TBS)
4b (Ph, 2-iPrC6H4, TBS)
4c (Ph, Bn, TBS)
4d (2-naphtyl, 2-iPrC6H4, TBS)
4e (Ph, Ph, H)
4f (3,5-(CF3)2C6H3, Ph, H)
4g (Ph, Mes, TMS)
4h (3,5-(CF3)2C6H3, Mes, H)
4b
69
67
45
64
40
49
trace
trace
99
95
96
97
40
83
99
/
8
/
9d
10
96
ꢀ96e
Key Laboratory of Molecular Recognition and Function,
Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190,
China. E-mail: songye@iccas.ac.cn; Fax: (+86)106255 4449;
Tel: (+86)106264 1156
w Electronic supplementary information (ESI) available: Experimental
procedures and compound characterizations. CCDC 821640 & 821641.
For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c1cc12316e
5
24
a
NHC 40–50 was generated from the corresponding triazolium salt 4–5
in the presence of Cs2CO3 at room temperature for 1 h, and used
b
immediately. Isolated yield. Determined by chiral HPLC. The
c
d
e
reaction was carried out at ꢀ40 1C. The minus ee value indicates a
reversed enantioselectivity. Mes = mesityl.
c
8388 Chem. Commun., 2011, 47, 8388–8390
This journal is The Royal Society of Chemistry 2011

View Article Online
Table
reaction of ketenes with carbon disulfide
2
Enantioselective NHC-catalyzed [2+2+2]cycloaddition
The structure of cycloadduct rac-3h,18 and the relative and
absolute configuration of cyclic thioacetal (+)-cis-6 were
unambiguous established by the X-ray analysis of their
crystals.19
Considering both reactions of NHC with ketenes and with
carbon disulfide have been reported,11,12,14 we tried to clarify
whether this catalytic cycloaddition is initiated by addition of
NHC to ketenes or carbon disulfide (Scheme 2). Although no
reaction of NHC 4b0 and carbon disulfide was observed at
ꢀ40 1C, the NHC-CS2 adduct 10 was isolated in 33% at room
temperature.20 However no reaction of NHC-CS2 adduct with
ketene 1a was observed at ꢀ40 1C or room temperature
(reaction a). We have reported that NHCs could catalyze the
dimerization of ketene 1a to give lactone 11.8b However, the
further reaction of lactone 11 with CS2 was found nonfeasible
(reaction b). It is interesting that when the reaction of ketene
1a and CS2 was catalyzed by DMAP, 10% yield of [2+2]
cycloadduct 12 was isolated along with 52% of the corres-
ponding [2+2+2] cycloadduct 3a. Furthermore, the cyclo-
adduct 12 could react with one more molecule of ketene 1a in
the presence of catalytic NHC 4b0 to give the cycloadduct 3a in
good yield (reactions c).
Entry
1 (Ar, R)
3
yield (%)a
ee (%)b
1
2
3
4
5
6
7
8
1a Ph, Et
3a
3b
3c
3d
3e
3f
3g
3h
3i
99
87
79
72
96
97
96
92
(93)c
94
/
96
92
96
/
1b 4-ClC6H4, Et
1c 4-BrC6H4, Et
1d 4-MeC6H4, Et
1e 4-MeOC6H4, Et
1f 3-ClC6H4, Et
1g 2-ClC6H4, Et
1h Ph, Me
1i Ph, n-Pr
1j Ph, n-Bu
1k 4-ClC6H4, i-Pr
NR (32)c
71
NR
69
94
96
9
10
11
3j
3k
NR
a
b
c
Isolated yield. Determined by chiral HPLC. Reaction carried at
room temperature.
Based on those observations, we proposed that the catalytic
cycle is initiated by the addition of NHC to ketenes giving
intermediate A, which reacts with CS2 to afford intermediate B.
Cyclization of intermediate B furnishes [2+2] cycloadduct 12,
but 12 could also go back to intermediate B in the presence of
NHC. The reaction of one more molecule of ketene with
intermediate B gives intermediate C, which is ring-closed to
give final [2+2+2] cycloadduct 3 and regenerates the NHC
catalyst (Fig. 1).
However ketene 1e with strong electron-donating group
(Ar = 4-MeOC6H4) gave only trace product at ꢀ40 1C, and
32% yield with 93% ee was observed at room temperature
(entry 5). While ketene 1f with m-chlorophenyl group worked
well, ketene 1g with o-chlorophenyl group did not (entries 6
and 7). The reaction of phenyl(alkyl)ketenes 1h, 1i, 1j with
different linear alkyl groups (R = Me, n-Pr or n-Bu) went
smoothly (entries 8–10), but aryl(isopropyl)ketene 1k afforded
no cycloadduct (entry 11).16
In conclusion, a highly enantioselective N-heterocyclic
carbene-catalyzed [2+2+2] cycloaddition reaction of two
molecules of ketenes with one molecule of carbon disulfide
to give 1,3-oxathian-6-ones was developed. Control experi-
ments revealed that the catalytic reaction is initiated by the
addition of NHC to ketenes rather than carbon disulfide.
Several chemical transformations of 3a were summarized in
Scheme 1. It is interesting that the addition of methyl Grignard
reagent to cycloadduct 3a gave exclusive cyclic thioacetal 6 in
99% yield with 95% ee, without ring-opened corresponding
ketone or thioketone formed.17 Alcoholysis of 3a afforded
the corresponding ester-thioester 7 in 81% yield. Again,
selective methylation of 7 with Grignard reagent gave ester-
thioacetal 8. The b-hydroxy thioacetal 9 was obtained in 92%
yield with 96% ee by selective reduction of 8 with LiAlH4
in THF.
Scheme 1 Chemical transformations of 3a.
Scheme 2 Control experiments for mechanism investigation.
Chem. Commun., 2011, 47, 8388–8390 8389
c
This journal is The Royal Society of Chemistry 2011

View Article Online
2004, 43, 5130; (c) H.-R. Pan, Y.-J. Li, C.-X. Yan, J. Xing and
Y. Cheng, J. Org. Chem., 2010, 75, 6644; (d) Y. Cheng, M.-F. Liu,
D.-C. Fang and X.-M. Lei, Chem.–Eur. J., 2007, 4282;
(e) M.-F. Liu, B. Wang and Y. Cheng, Chem. Commun., 2006, 1215.
7 For reviews, see: (a) S. P. Nolan, Acc. Chem. Res., 2011, 44, 91;
(b) W. A. Herrmann, Angew. Chem., Int. Ed., 2002, 41, 1290.
8 For reviews, see: (a) D. Enders and T. Balensiefer, Acc. Chem.
Res., 2004, 37, 534; (b) D. Enders, O. Niemeier and A. Henseler,
Chem. Rev., 2007, 107, 5606; (c) A. J. Arduengo III and
L. I. Iconaru, Dalton Trans., 2009, 6903; (d) J. L. Moore and
T. Rovis, Top. Curr. Chem., 2010, 291, 77; (e) N. T. Patil, Angew.
Chem., Int. Ed., 2011, 50, 1759.
9 For early pioneering reports, see: (a) R. Breslow, J. Am. Chem.
Soc., 1958, 80, 3719; (b) H. Stetter, Angew. Chem., Int. Ed. Engl.,
1976, 15, 639; (c) D. Enders, K. Breuer and J. H. Teles, Helv. Chim.
Acta, 1996, 79, 1217; (d) R. Knight and F. J. Leeper, Tetrahedron
Lett., 1997, 38, 3611.
10 For recent examples, see: (a) D. T. Cohen, B. Cardinal-David and
K. A. Scheidt, Angew. Chem., Int. Ed., 2011, 50, 1678;
(b) T. Jousseaume, N. E. Wurz and F. Glorius, Angew. Chem.,
Int. Ed., 2011, 50, 1410; (c) S. J. Ryan, L. Candish and
D. W. Lupton, J. Am. Chem. Soc., 2011, 133, 4694;
(d) K.-J. Wu, G.-Q. Li, Y. Li, L.-X. Dai and S.-L. You, Chem.
Commun., 2011, 47, 493; (e) J. Ma, Y. Huang and R. Chen, Org.
Biomol. Chem., 2011, 9, 1791; (f) Y. Chen, J.-H. Peng, Y.-J. Li,
X.-Y. Xhi, M.-S. Tang and T.-Y. Tan, J. Org. Chem., 2011,
76, 1844; (g) P. Singh, S. Singh, V. K. Rai and L. D. S. Yadav,
Synlett, 2010, 2649; (h) A. T. Biju and F. Glorius, Angew. Chem.,
Int. Ed., 2010, 49, 9761; (i) S. De Sarkar and A. Studer, Angew.
Chem., Int. Ed., 2010, 49, 9266; (j) H. Jiang, B. Gschwend,
L. Albrecht and K. A. Jørgensen, Org. Lett., 2010, 12, 5052;
(k) C. A. Rose and K. Zeitler, Org. Lett., 2010, 12, 4552;
(l) C. Awasthi and L. D. S. Yadav, Synlett, 2010, 1783;
(m) D. Enders, A. Grossmann, J. Fronert and G. Raabe, Chem.
Commun., 2010, 46, 6282; (n) Z. Chen, X. Yu and J. Wu, Chem.
Commun., 2010, 46, 6356; (o) L. Lin, Y. Li, W. Du and
W.-P. Deng, Tetrahedron Lett., 2010, 51, 3571; (p) H. U. Vora
and T. Rovis, J. Am. Chem. Soc., 2010, 132, 2860.
Fig. 1 Possible catalytic cycle.
Financial support from National Science Foundation of
China (20932008), the Ministry of Science and Technology
of China (2011CB808600) and the Chinese Academy of
Sciences are greatly acknowledged.
Notes and references
1 (a) G. E. McCasland, A. B. Zanlungo and L. J. Durhan, J. Org.
Chem., 1974, 39, 1462; (b) P. Dallemagne, L. P. Khanh, A. Alsaıdi,
I. Varlet, V. Collot, M. Paillet, R. Bureau and S. Rault, Bioorg.
Med. Chem., 2003, 1161; (c) J. A. Souto, E. Vaz, I. Lepore,
A. Poppler, G. Franci, R. Alvarez, L. Altucci and A. R. de Lera,
J. Med. Chem., 2010, 53, 4654; (d) R. Munday, Y. Zhang,
J. D. Paonessa, C. M. Munday, A. L. Wilkins and J. Babu,
J. Med. Chem., 2010, 53, 4761; (e) G. Clave, C. Ronco,
H. Boutal, N. Kreich, H. Volland, X. Franck, R. Romieu and
P.-Y. Renard, Org. Biomol. Chem., 2010, 8, 676.
11 (a) Y.-R. Zhang, L. He, X. Wu, P.-L. Shao and S. Ye, Org. Lett.,
2008, 10, 277; (b) H. Lv, Y.-R. Zhang, X.-L. Huang and S. Ye,
Adv. Synth. Catal., 2008, 350, 2715; (c) X.-N. Wang, H. Lv,
X.-L. Huang and S. Ye, Org. Biomol. Chem., 2009, 7, 346;
(d) X.-L. Huang, L. He, P.-L. Shao and S. Ye, Angew. Chem.,
Int. Ed., 2009, 48, 192; (e) P. L. Shao, X.-Y. Chen and S. Ye,
Angew. Chem., Int. Ed., 2010, 49, 8412; (f) T.-Y. Jian, P.-L. Shao
and S. Ye, Chem. Commun., 2011, 47, 2381.
12 Smith et al. also independently report their NHC-catlyazed reactions
of ketenes: (a) N. Duguet, C. D. Campbell, A. M. Z. Slawin and
A. D. Smith, Org. Biomol. Chem., 2008, 6, 1108; (b) C. Concellon,
N. Duguet and A. D. Smith, Adv. Synth. Catal., 2009, 351, 3001;
(c) N. Duguet, A. M. Z. Slawin and A. D. Smith, Org. Lett., 2009,
11, 3858; (d) N. Duguet, A. Donaldson, S. M. Leckie, E. A.
Kallstrom, C. D. Campbell, P. Shapland, T. B. Brown, A. M. Z.
Slawin and A. D. Smith, Tetrahedron: Asymmetry, 2010, 21, 601.
13 For reviews on asymmetric reactions of ketenes, see: (a) R. K. Orr
and M. A. Calter, Tetrahedron, 2003, 59, 3545; (b) G. C. Fu, Acc.
Chem. Res., 2004, 37, 542; (c) T. T. Tidwell, Angew. Chem., Int. Ed.,
2005, 44, 5778; (d) D. H. Paull, A. Weatherwax and T. Lectka,
Tetrahedron, 2009, 65, 6771.
2 (a) J. Campora, E. Carmona, P. Palma and M. Poveda, J. Chem.
Soc., Perkin Trans. 1, 1990, 180; (b) R. A. Aitken, T. Massil and
S. V. Raut, J. Chem. Soc., Chem. Commun., 1994, 2603;
(c) D. Delaunay, L. Toupet and M. L. Corre, J. Org. Chem.,
1995, 60, 6604; (d) R. Temme, K. Polborn and R. Huisgen,
Tetrahedron, 1998, 54, 9849; (e) Y. Mitsumoto and M. Nitta,
J. Chem. Soc., Perkin Trans. 1, 2002, 2268; (f) J. Chen, W. Song
and Z. Xi, Tetrahedron Lett., 2002, 43, 3533; (g) T. Mizuhara,
S. Oishi, N. Fujii and H. Ohno, J. Org. Chem., 2010, 75, 265.
3 (a) N. Kihara, Y. Nakawaki and T. Endo, J. Org. Chem., 1995,
60, 473; (b) Y.-M. Shen, W.-L. Duan and M. Shi, Eur. J. Org.
Chem., 2004, 3080; (c) S. Gabillet, D. Lecercle, O. Loreau,
M. Carboni, S. Dezard, J.-M. Gomis and F. Taran, Org. Lett.,
2007, 9, 3925; (d) J.-Y. Wu, Z.-B. Luo, L.-X. Dai and X.-L. Hou,
J. Org. Chem., 2008, 73, 9137.
4 (a) Y. Yamamoto, H. Takagishi and K. Itoh, J. Am. Chem. Soc.,
2002, 124, 28; (b) Y. Yamamoto, K. Kinpara, T. Saigoku,
H. Takagishi, S. Okuda, H. Nishiyama and K. Itoh, J. Am. Chem.
Soc., 2005, 127, 605; (c) K. Tanaka, A. Wada and K. Noguchi,
Org. Lett., 2006, 8, 907; (d) W. Clegg, R. W. Harrington, M. North
and P. Villluendas, J. Org. Chem., 2010, 75, 6201.
5 (a) D. Bourissou, O. Guerret, F. P. Gabbaı and G. Bertrand,
Chem. Rev., 2000, 100, 39; (b) F. E. Hahn, Angew. Chem., Int. Ed.,
2006, 45, 1348; (c) T. Droge and F. Glorius, Angew. Chem.,
Int. Ed., 2010, 49, 6940.
14 L. Delaude, Eur. J. Inorg. Chem., 2009, 1681.
15 See ESIw for the optimization of reaction conditions.
16 Most of ketene 1g and 1k remain untouched without formation of
ketene dimer in the standard reaction conditions.
17 Thiophile addition of organomagnesium on dithioesters was
reported: A. I. Meyers, T. A. Tait and Daniel L. Comins, Tetrahedron
Lett., 1978, 19, 4657.
18 The preparation of the suitable crystal of (ꢀ)-3h for X-ray failed by
the same way as rac-3h.
19 All the cycloadducts 3 were assigned the same R-configuration
based on their optical rations and CD spectra compared with 3a.
20 The cycloaddition of ketenes and aldimines catalyzed by NHC-CS2
adduct was reported: O. Sereda, A. Blanrue and R. Wilhelm,
Chem. Commun., 2009, 1040.
6 (a) Y. Cheng and O. Meth-Cohn, Chem. Rev., 2004, 104, 2507;
(b) V. Nair, S. Bindu and V. Sreekumar, Angew. Chem., Int. Ed.,
c
8390 Chem. Commun., 2011, 47, 8388–8390
This journal is The Royal Society of Chemistry 2011