Rhodium-catalyzed asymmetric formal cycloadditions of racemic butadiene monoxide with imines

Article abstract of DOI:10.1021/ol301248d

A simple chiral sulfur-alkene hybrid ligand has proven to be highly effective for rhodium-catalyzed formal cycloaddition reactions of racemic butadiene monoxide and imines to furnish spirooxindole oxazolidines or 1,3-oxazolidines with high yields and stereoselectivities. A possible dynamic kinetic resolution as well as a kinetic resolution is considered to be involved in this catalytic process.

Full text of DOI:10.1021/ol301248d

ORGANIC
LETTERS
2012
Vol. 14, No. 12
3154–3157
Rhodium-Catalyzed Asymmetric Formal
Cycloadditions of Racemic Butadiene
Monoxide with Imines
Zhaoqun Liu, Xiangqing Feng, and Haifeng Du*
Beijing National Laboratory of Molecular Sciences, CAS Key Laboratory of Molecular
Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences,
Beijing 100190, China
haifengdu@iccas.ac.cn
Received May 7, 2012
ABSTRACT
A simple chiral sulfurꢀalkene hybrid ligand has proven to be highly effective for rhodium-catalyzed formal cycloaddition reactions of racemic
butadiene monoxide and imines to furnish spirooxindole oxazolidines or 1,3-oxazolidines with high yields and stereoselectivities. A possible
dynamic kinetic resolution as well as a kinetic resolution is considered to be involved in this catalytic process.
Rhodium catalysts can bring about a wide range of
synthetic transformations,1 and allylrhodium intermedi-
ates, involved in reactions, such as allylic substitution, are
generally thought to involve σ-allylrhodium complexes
rather than π-allylrhodium complexs.2 Because of the rela-
tively slow σꢀπꢀσ isomerization of σ-allylrhodium inter-
mediates, the regio- and stereochemistry of the starting
substrates can usually be well conserved in the products.3
This substrate-controlled feature of rhodium catalysts ap-
pears to be incompatible with the catalyst-controlled asym-
metric synthesis from racemic starting materials. Although
there are very few reports on the use of chiral rhodium
catalyst for such an asymmetric transformation, Pregosin,4a
Hayashi,4b and Vireze4c have shown that racemic allylic
acetates or carbonates can be converted to highly enan-
tioenriched products, which clearly indicates that the
σꢀπꢀσ isomerization can also occur in rhodium complexes
under suitable conditions.
Very recently, Jarvo and co-workers described a
Rh-catalyzed stereospecific reaction of (R)-butadiene monox-
ide (2) with arylimines 1 to provide synthetic and pharma-
ceutically important 1,3-oxazolidines 3 in high yields
(Scheme 1).5ꢀ7 Moreover, phosphine ligands were found
to inhibit this Rh-catalyzed reaction.5 Our own group has
(1) Evans, P. A. Modern Rhodium-Catalyzed Organic Reactions;
Wiley-VCH: Weinheim, 2005.
(2) Minami, I.; Shimizu, I.; Tsuji, J. J. Organomet. Chem. 1985, 296,
269.
(4) (a) Selvakumar, K.; Valentini, M.; Pregosin, P. S. Organometal-
lics 1999, 18, 4591. (b) Hayashi, T.; Okada, A.; Suzuka, T.; Kawatsura,
T. Org. Lett. 2003, 5, 1713. (c) Vrieze, D. C.; Hoge, G. S.; Hoerter, P. Z.;
Van Haitsma, J. T.; Samas, B. M. Org. Lett. 2009, 11, 3140.
(5) Shaghafi, M. B.; Grote, R. E.; Jarvo, E. R. Org. Lett. 2011, 13,
5188.
(6) For selected examples on oxazolidine synthesis by cycloadditions
of vinyl epoxides, see: (a) Larksarp, C.; Alper, H. J. Am. Chem. Soc.
1997, 119, 3709. (b) Larksarp, C.; Alper, H. J. Org. Chem. 1998, 63,
6229. (c) Shim, J.-G.; Yamamoto, Y. Tetrahedron Lett. 1999, 40, 1053.
(d) Shim, J.-G.; Yamamoto, Y. Heterocycles 2000, 52, 885.
(3) (a) Evans, P. A.; Nelson, J. D. J. Am. Chem. Soc. 1998, 120, 5581.
(b) Evans, P. A.; Robinson, J. E.; Nelson, J. D. J. Am. Chem. Soc. 1999, 121,
6761. (c) Fagnou, K.; Lautens, M. Org. Lett. 2000, 2, 2319. (d) Evans, P. A.;
Uraguchi, D. J. Am. Chem. Soc. 2003, 125, 7158. (e) Evans, P. A.; Leahy.,
D. K. J. Am. Chem. Soc. 2003, 125, 8974. (f) Evans, P. A.; Lawler, M. J.
J. Am. Chem. Soc. 2004, 126, 8642. (g) Ashfeld, B. L.; Miller, K. A.; Martin,
S. F. Org. Lett. 2004, 6, 1321. (h) Kazmaier, U.; Stolz, D. Angew. Chem.,
Int. Ed. 2006, 45, 3072. (i) Menard, F.; Chapman, T. M.; Dockendorff, C.;
Lautens, M. Org. Lett. 2006, 8, 4569. (j) Ashfeld, B. L.; Miller, K. A.; Smith,
A. J.; Tran, K.; Martin, S. F. J. Org. Chem. 2007, 72, 9018.
r
10.1021/ol301248d
Published on Web 06/06/2012
2012 American Chemical Society

Scheme 2. Initial Study on Rh-Catalyzed Formal Cycloaddi-
tions with Chiral Sulfur/Alkene Ligands
Scheme 1. Rh-Catalyzed Stereospecific Reaction of Butadiene
Monoxide with Imines5
been working on the development of novel chiral olefin
ligands,8ꢀ10 and in some cases, this type of ligand shows
higher activity and selectivity than many other types
of ligand. Because of this, we envisioned that the
Rh-catalyzed asymmetric reaction of racemic butadiene
monoxide (2) with imines could probably be achieved
using chiral olefin ligands. Herein, we report our efforts
in this area.
Initially, we selected the novel reaction of isatin imine 4a
with 1.2 equivalent of racemic butadiene monoxide (2)
which would produce spirooxindole oxazolidines.11,12 This
would serve as the model reaction to test our hypothesis on
(7) For recent reviews on oxazolidine, see: (a) Scott, J. D.; William,
R. M. Chem. Rev. 2002, 102, 1669. (b) Royer, J.; Bonin, M.; Micouin, L.
Chem. Rev. 2004, 104, 2311. (c) Wu, G.; Huang, M. Chem. Rev. 2006,
106, 2596.
Table 1. Optimization of Reaction Conditionsa
(8) For leading reviews on chiral alkene ligands, see: (a) Glorius, F.
Angew. Chem., Int. Ed. 2004, 43, 3364. (b) Johnson, J. B.; Rovis, T.
(()-2
€
Angew. Chem., Int. Ed. 2008, 47, 840. (c) Defieber, C.; Grutzmacher, H.;
entry (equiv) AgX solvent time (h) convb (%) drb eec (%)
Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47, 4482. (d) Shintani, R.;
Hayashi, T. Aldrichimica Acta 2009, 42, 31. (e) Tian, P.; Dong, H.-Q.;
Lin, G.-Q. ACS catal 2012, 2, 95.
1
1.2
1.2
1.2
1.2
1.2
1.2
2.0
2.0
AgOTf acetone
AgBF4 acetone
AgPF6 acetone
AgSbF6 acetone
AgOTf EtOAc
AgOTf EtOAc
AgOTf EtOAc
AgOTf EtOAc
1
84
90
80
99
74
83
99
99
99
99
86
50:1
20:1
50:1
20:1
10:1
10:1
10:1
10:1
12:1
20:1
20:1
68
56
60
42
84
65
84
88
94
95
95
2
1
(9) For leading references on chiral alkene ligands, see: (a) Hayashi,
T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003,
125, 11508. (b) Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E. M.
J. Am. Chem. Soc. 2004, 126, 1628. (c) Wang, Z.-Q.; Feng, C.-G.; Xu,
M.-H.; Lin, G.-Q. J. Am. Chem. Soc. 2007, 129, 5336. (d) Gendrineau,
T.; Chuzel, O.; Eijsberg, H.; Genet, J.-P.; Darses, S. Angew. Chem., Int.
Ed. 2008, 47, 7669. (e) Luo, Y.; Carnell, A. J. Angew. Chem., Int. Ed.
2010, 49, 2750. (f) Pattison, G.; Piraux, G.; Lam, H. W. J. Am. Chem.
Soc. 2010, 132, 14373. (g) Maire, P.; Deblon, S.; Breher, F.; Geier, J.;
3
1
4
1
5
2.5
6
12
7
1
8d
9d
10d
11e
2.5
2.5
2.5
3.0 AgOTf EtOAc
€
€
€
€
Bohler, C.; Ruegger, H.; Schonberg, H.; Grutzmacher, H. Chem.;Eur.
J. 2004, 10, 4198. (h) Shintani, R.; Duan, W.-L.; Nagano, T.; Okada, A.;
Hayashi, T. Angew. Chem., Int. Ed. 2005, 44, 4611. (i) Defieber, C.;
Ariger, M. A.; Moriel, P.; Carreira, E. M. Angew. Chem., Int. Ed. 2007,
4.0
3.0
AgOTf EtOAc
AgOTf EtOAc
12
a All of the reactions were carried out with 4a (0.20 mmol), (()-2 as
indicated, [Rh(C2H4)2Cl]2 (0.005 mmol), ligand 6f (0.012 mmol), and
AgX (0.012 mmol) in solvent (1.0 mL) at 20 °C unless other noted. b The
conversion and dr were determined by crude 1H NMR. c The ee was
determined by chiral HPLC (Chiralcel OD-H column). d 3 mol %
catalyst was used. e 1 mol % catalyst was used.
€
€
46, 3139. (j) Maire, P.; Breher, F.; Schonberg, H.; Grutzmacher, H.
€
Organometallics 2005, 24, 3207. (k) Hahn, B. T.; Tewes, F.; Frohlich, R.;
Glorius, F. Angew. Chem., Int. Ed. 2010, 49, 1143.
(10) For examples on alkene ligands developed by our group, see the
following. Acyclic diene: (a) Hu, X.; Zhuang, M.; Cao, Z.; Du, H. Org.
Lett. 2009, 11, 4744. P/alkene: (b) Liu, Z.; Du, H. Org. Lett. 2010, 12,
3054. S/alkene: (c) Feng, X.; Wang, Y.; Wei, B.; Yang, J.; Du, H. Org.
Lett. 2011, 13, 3300. (d) Feng, X.; Wei, B.; Yang, J.; Du, H. Org. Biomol.
Chem. 2011, 9, 5927. (e) Wang, Y.; Feng, X.; Du, H. Org. Lett. 2011, 13,
4954. (f) Feng, X.; Nie, Y.; Yang, J.; Du, H. Org. Lett. 2012, 14, 624.
(11) For recent reviews on spriooxindoles, see: (a) Marti, C.;
Carreira, E. M. Eur. J. Org. Chem. 2003, 2209. (b) Williams, R. M.;
Cox, R. J. Acc. Chem. Res. 2003, 36, 127. (c) Galliord, C. V.; Scheidt,
K. A. Angew. Chem., Int. Ed. 2007, 47, 8748. (d) Trost, B. M.; Brennan,
M. K. Synthesis 2009, 3003.
(12) For examples on spriooxindole oxazolidines, see: (a) Risitano,
F.; Grassi, G.; Foti, F.; Bruno, G.; Rotondo, A. Heterocycles 2003, 60,
857. (b) Badillo, J. J.; Arevalo, G. E.; Fettinger, J. C.; Franz, A. K. Org.
Lett. 2011, 13, 418.
(13) For examples on S/alkene hybrid ligands developed by other
groups, see: (a) Thaler, T.; Guo, L.-N.; Steib, A. K.; Raducan, M.;
Karaghiosoff, K.; Mayer, P.; Knochel, P. Org. Lett. 2011, 13, 3182. (b)
Jin, S.-S.; Wang, H.; Xu, M.-H. Chem. Commun. 2011, 47, 7230. (c) Qi,
W.-Y.; Zhu, T.-S.; Xu, M.-H. Org. Lett. 2011, 13, 3410. (d) Chen, G.;
Gui, J.; Li, L.; Liao, J. Angew. Chem., Int. Ed. 2011, 50, 7681. (e) Xue, F.;
Li, X.; Wan, B. J. Org. Chem. 2011, 76, 7256. (f) Zhu, T.-S.; Jin, S.-S.;
Xu, M.-H. Angew. Chem., Int. Ed. 2012, 51, 780.
the utility of chiral alkene ligands for allylrhodium trans-
formations. As shown in Scheme 2, a variety of easily
accessible chiral sulfur/alkene ligands10e,f,13 were found to
be effective for this reaction to afford optically active
spirooxindole oxazolidines 5a with up to 68% ee and high
diastereoselectivity, which indicated that the stereochem-
istry of this reaction is at least partially controlled by chiral
rhodium catalysts.
To further improve the enantioselectivity, various con-
ditions for the Rh-catalyzed reaction between 4a and (()-
2, with the use of ligand 6f, were thoroughly examined, and
some results are summarized in Table 1. Studies on the
influence of the counteranion on Rh center showed that
Org. Lett., Vol. 14, No. 12, 2012
3155

Table 3. Rh-Catalyzed Asymmetric Reaction of Imines Derived
from Aldehydes or Ketones with Racemic Butadiene Monoxide 2a
Scheme 3. Control Experiments with the Use of (R)-2
Table 2. Rh-Catalyzed Asymmetric Reaction of Isatin Imines 4
with Racemic Butadiene Monoxide 2a
a All of the reactions were carried out with imine (0.4 mmol), (()-2
(1.2 mmol), [Rh(C2H4)2Cl]2 (0.010 mmol), ligand 6f (0.024 mmol), and
AgOTf (0.024 mmol) in ethyl acetate (2.0 mL) at 20 °C for 4.0 h unless
other noted. b The reaction was performed with 3.0 mol % of catalyst for
1
2.5 h. c The diastereoisomer ratio was determined by crude H NMR.
d The relative stereochemistry was assigned according to ref 5. e The
absolute configuration of allyl carbon was determined by comparing
the optical rotation value of the hydrolysis product with that of ref 16.
f The relative stereochemistry was assigned by NOE experiment.
g Isolated yield. h The diastereoisomer ratio for isolated products. i The
ee for major isomer was determined by chiral HPLC unless other noted.
j The ee for both trans- and cis-isomers was determined.
a All the reactions were carried out with 4 (0.4 mmol), (()-2
(1.2 mmol), [Rh(C2H4)2Cl]2 (0.006 mmol), ligand 6f (0.0144 mmol),
and AgOTf (0.0144 mmol) in ethyl acetate (2.0 mL) at 20 °C for 2.5 h.
b The absolute configuration was tentatively assigned by analogy with 5i.
c Isolated yield. d The diastereoisomer ratio was determined by crude 1H
NMR. e The ee was determined by chiral HPLC.
isatinimine4atogive5awithupto95%ee(Table1, entries
7ꢀ10). Even with as low as a 1.0 mol % catalyst loading,
highenantioselectivity could still be maintained withonlya
slight drop of conversion (Table 1, entry 11).
With excellent enantio- and diastereoselectivity in hand,
a series of control experiments using enantiomerically pure
butadiene monoxide14 (2) as substrate were conducted in
order to have better insight into the course of this reaction.
OTf anion gave higher enantioselectivity (Table 1, entries
1ꢀ4). Ethyl acetate was a better solvent than acetone,
giving a higher ee (Table 1, entries 1 vs 5). Increasing the
amount of (()-2 and/or reducing the catalyst loading from
5.0 mol % to 3.0 mol % led to a complete conversion of the
(14) (a) Ready, J. M.; Jacobsen, E. N. J. Am. Chem. Soc. 2001, 123,
2687. (b) Hunter, L.; O’Hagan, D.; Slawin, A. M. Z. J. Am. Chem. Soc.
2006, 128, 16422.
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Org. Lett., Vol. 14, No. 12, 2012

The reaction of isatin imine 4a and (R)-2 (1.2 equiv) in
ethyl acetate, catalyzed by the combination of
[Rh(COD)Cl]2 and AgOTf, furnished the desired product
5a in only 10% conversion and with 16% ee (Scheme 3),
which suggested that a σꢀπꢀσ isomerization was occur-
ring under the current conditions. Ligand (R)-6f seems to
be mismatched with the substrate, giving the product 5a in
41% conversion with 54% ee, while matched ligand (S)-6f
led to a complete conversion of isatin imine 4a to 5a in 93%
ee (Scheme 3). On the basis of the aforementioned results,
some interesting features for this reaction were concluded:
(i) sulfur/alkene ligands can greatly accelerate this reac-
tion; (ii) the absolute configuration of products is depen-
dent on that of chiral ligand; (iii) a dynamic kinetic
resolution as well as a kinetic resolution is probably
involved in the reaction of imine 4a with excess (()-2.
Moreover, it is noteworthy that the configuration at the
stereogenic center of butadiene monoxide is reversed.
Although the reason remains unclear, we suppose that
the step of CꢀN bond formation is through a reductive
elimination instead of a nucleophilic substitution.3i,15
Subsequently, we examined the scope to isatin imines 4
in this formal [3 þ 2] cycloaddition. We were pleased to
find that a variety of isatin imines 4 possessing either
electron-donating or electron-withdrawing groups were
well tolerated in this reaction, furnishing the desired
spirooxindole oxazolidines 5aꢀi in 61ꢀ91% yield with
78ꢀ96% ee and 10:1ꢀ20:1 dr (Table 2, entries 1ꢀ9).
A single crystal of product 5i was obtained, and the
absolute configuration was determined accordingly.
racemic butadiene monoxide (2) efficiently to give the
corresponding 1,3-oxazolindines 5jꢀs with excellent en-
antioselectivities but relatively low diastereoselectivities
(Table 3, entries 1ꢀ10). It should be noted that trans-
oxazolidines were obtained as major products, instead of
more stable cis-oxazolidines, except for imines derived
from 4-methoxybenzaldehyde and cyclohexanecarbox-al-
dehyde (Table 3, entries 1ꢀ8 vs 9 and 10), which was
distinct from the reported results.5,6c,6d An epimerization is
supposed to exist under the reaction conditions on the
basis of similar ee values being obtained for trans- and cis-
isomers (Table 3, entries 1, 7, 10, and 12) and an observed
isomerizaion of trans-5k to cis-5k after being kept at room
temperature for several weeks. Moreover, imines derived
from ethyl benzoylformate and benzil were also suitable
substrates, affording the desired products with quaternary
stereocenters (Table 3, entries 11 and 12).
In summary, Rh-catalyzed formal [3 þ 2] cycloaddition
between racemic butadiene monoxide and imines has been
successfully achieved with the use of a simple and easily
accessible chiral sulfur/alkene ligand. A possible dynamic
kinetic resolution, besides a kinetic resolution, is presumed
to operate in this catalytic process. A wide range of imines
derived from isatins, simple aldehydes, and ketones were
tolerated in this reaction and highly enantioenriched spir-
ooxindole oxazolidines or 1,3-oxazolidines were formed in
high yields with good to excellent diastereoselectivities.
Acknowledgment. We are thankful for the financial
support from the National Natural Science Foundation
of China (21072194, 21172222) and 973 program (2010-
CB833300).
Since isatin imines proved suitable substrates, we next
examined the imines derived from simple aldehydes or
ketones, for thisreaction. Inthe presenceof3.0ꢀ5.0 mol %
of rhodium catalyst, a wide range of aldimines reacted with
Supporting Information Available. Procedure for
rhodium-catalyzed reactions, characterization of products,
data for the determination of enantiomeric excesses, X-ray
data for 5i, and NMR spectra. This material is available free
of charge via the Internet at http://pubs.acs.org.
(15) (a) Matsushita, H.; Negishi, E. J. Chem. Soc., Chem. Commun.
1982, 160. (b) Fiaud, J.-C.; Legros, J.-Y. J. Org. Chem. 1987, 52, 1907. (c)
Yorimitsu, H.; Oshima, K. Angew. Chem., Int. Ed. 2005, 44, 4435. (d)
Kar, A.; Argade, N. P. Synthesis 2005, 2995.
€
(16) Gnamm, C.; Franck, G.; Miller, N.; Stork, T.; Brodner, K.;
Helmchen, G. Synthesis 2008, 3331.
The authors declare no competing financial interest.
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