Asymmetric Diels-Alder reactions of N-allenoyloxazolidinones catalyzed by Cu(II)-bis(oxazoline) complexes

Article abstract of DOI:10.1016/j.tetlet.2014.10.051

Catalytic asymmetric Diels-Alder reactions of N-allenoyloxazolidinones were investigated. Various chiral metal-bis(oxazoline) and metal-pyridinebis(oxazoline) complexes were screened. Cu(SbF₆)₂(H₂O)₂(t-BuBox) wa

Full text of DOI:10.1016/j.tetlet.2014.10.051

Tetrahedron Letters xxx (2014) xxx–xxx
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Tetrahedron Letters
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Asymmetric Diels–Alder reactions of N-allenoyloxazolidinones
catalyzed by Cu(II)–bis(oxazoline) complexes
⇑
Torsak Luanphaisarnnont
Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahidol University, 272 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand
a r t i c l e i n f o
a b s t r a c t
Article history:
Catalytic asymmetric Diels–Alder reactions of N-allenoyloxazolidinones were investigated. Various chiral
metal–bis(oxazoline) and metal–pyridinebis(oxazoline) complexes were screened. Cu(SbF6)2(H2O)2
(t-BuBox) was found to be the most effective catalyst, giving the product in high yield, enantioselectivity,
and endo:exo selectivity. The relative reactivity between N-allenoyloxazolidinones and N-alkenoyloxazo-
lidinones was also investigated. A model for stereoinduction was proposed to account for the enantiose-
lectivity and endo:exo selectivity.
Received 13 August 2014
Revised 19 September 2014
Accepted 8 October 2014
Available online xxxx
Keywords:
Ó 2014 Elsevier Ltd. All rights reserved.
Diels–Alder cycloaddition
Enantioselective catalysis
Allenes
Bis(oxazoline)
Lewis acid catalysis
The Diels–Alder reaction is among the most powerful reactions
in organic chemistry because it allows for the formation of two car-
bonAcarbon bonds and the construction of up to four contiguous
stereogenic centers in a single step.1 The utility of Diels–Alder
reactions in total syntheses of natural products is well established.2
Catalytic asymmetric Diels–Alder reactions continue to be an
active area in asymmetric catalysis.3 One advance in this expand-
ing field has been the development of chiral C2 symmetric
bis(oxazoline) and pyridinebis(oxazoline) ligands for Lewis acid
catalysis.4,5 These types of chiral compounds are considered to be
privileged ligands because they can catalyze a wide range of reac-
tions, giving products with high enantioselectivity.6 Although
these classes of ligands have been applied to catalytic asymmetric
Diels–Alder reactions of various activated alkenes,7 their applica-
tion to allenic dienophiles has not been reported (Scheme 1).8,9 It
should be noted that the bicyclic products from the Diels–Alder
reaction of allenoic dienophiles have been shown to be useful in
syntheses of natural products such as (À)-b-santalene9a and
(À)-laurenditerpenol.9d This research is aimed at investigating
the use of bis(oxazoline) (Box) and pyridinebis(oxazoline) (PyBox)
classes of ligands in asymmetric Diels–Alder reactions of
N-allenoyloxazolidinones.
Cu(OTf)2(t-BuBox) was found to be an effective catalyst giving the
product with 100% conversion, 65% ee, and 1.4:1 endo:exo selectiv-
ity. Ni(OTf)2(t-BuBox) gave the product in low conversion, enanti-
oselectivity, and endo:exo selectivity. Cu(OTf)2(PhPyBox) and
Sc(OTf)3(PhPyBox) were found to be ineffective in this Diels–Alder
reaction.
The effect of the counter anion was subsequently investigated
(Table 2). Cu(SbF6)2(H2O)2(t-BuBox) was found to be a superior cat-
alyst, giving the product in 89% ee and 83:17 endo:exo selectivity.
Metal complexes with halide counter ions were ineffective.
Various solvents were screened (Table 3). The effect of the sol-
vent on the endo:exo selectivity was found to be minimal; however,
the enantioselectivity depended largely on the solvent. Chlorinated
solvents were found to be more suitable for the reaction, uniformly
giving the product in higher enantioselectivities and endo:exo
selectivities. Dichloromethane was chosen as the optimum
solvent (entry 1) because of the overall enantioselectivity and
regioselectivity.
Next, various bis(oxazoline) ligands were surveyed (Table 4).
Complexes with a t-BuBox ligand (6a) were found to be superior
in terms of both enantioselectivity and endo:exo selectivity. Other
bis(oxazoline) ligands gave the desired product in high conversion,
but the enantioselectivities were significantly decreased.
Lowering the temperature improved both the enantioselectivity
and the endo:exo selectivity of the reaction (Table 5). When the
reaction was performed at À78 °C for 20 h, the enantioselectivity
and the endo:exo selectivity increased to 95% ee and 90:10,
respectively.
During the initial optimization, metal–bis(oxazoline) and
metal–pyridinebis(oxazoline) complexes that have been reported
to be successful Lewis acid catalysts were screened (Table 1).10–12
⇑
Tel.: +66 2 201 5136; fax: +66 2 354 7151.
E-mail address: torsak.lua@mahidol.ac.th
http://dx.doi.org/10.1016/j.tetlet.2014.10.051
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Luanphaisarnnont, T. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.10.051

2
T. Luanphaisarnnont / Tetrahedron Letters xxx (2014) xxx–xxx
Scheme 1. Comparison between previous work7b and this work.
Table 1
Initial screening
O
O
catalyst (10 mol%)
CH2Cl2, 0 °C
•
H
O
O
N
N
O
5
4
2
O
Entry
Catalyst
Conversion (%)
ee (%)
endo:exo
1
2
3
4
Cu(OTf)2(t-BuBox)
Ni(OTf)2(t-BuBox)
Sc(OTf)3(PhPyBox)
Cu(OTf)2(PhPyBox)
100
20
NR
NR
65
10
NA
NA
58:42
55:45
NA
NA
NR = no reaction, NA = not available.
Me Me
O
O
O
O
N
N
N
N
N
t-Bu
t-Bu
Ph
Ph
(S,S)-PhPyBox
(S,S)-t-BuBox
Table 2
Counter anion screening
O
O
H
O
Cu catalyst (10 mol%)
•
O
N
N
CH2Cl2, 0 °C
O
5
4
2
O
Entry
Cu catalyst
Cu(OTf)2(t-BuBox)
Cu(OTf)2(H2O)2(t-BuBox)
Cu(SbF6)2(H2O)2(t-BuBox)
CuCl2 (t-BuBox)
Conversion (%)
ee (%)
endo:exo
1
2
3
4
5
100
46
100
NR
NR
65
4
89
NA
NA
58:42
80:20
83:17
NA
CuBr2(t-BuBox)
NA
NR = no reaction, NA = not available.
After the optimum conditions had been obtained, the scope of
this reaction was investigated. Although 3-buta-2,3-dienoyloxaz-
olidin-2-one (4) reacts with cyclopentadiene (2) to give bicyclic
product 5 in good yield, enantioselectivity, and endo:exo selectiv-
ity, less reactive dienes (cyclohexa-1,3-diene and hexa-2,4-diene)
were not viable substrates for the reaction. In the case of
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T. Luanphaisarnnont / Tetrahedron Letters xxx (2014) xxx–xxx
3
Table 3
Solvent screening
Cu(SbF6)2(H2O)2(t-BuBox)
O
O
H
O
•
(10 mol%)
O
N
N
solvent, 0 °C
O
5
O
4
2
Entry
Solvent
CH2Cl2
Toluene
Et2O
THF
ClCH2CH2Cl
CHCl3
Conversion (%)
ee (%)
endo:exo
1
2
3
4
5
6
100
8
50
11
100
62
89
55
61
32
88
73
83:17
89:11
88:12
83:17
82:18
83:17
Table 4
Ligand screening
Cu(SbF6)2(H2O)2(ligand)
O
O
H
O
•
(10 mol%)
O
N
N
CH2Cl2, 0 °C
O
5
O
4
2
Entry
Ligand
Conversion (%)
ee (%)
endo:exo
1
2
3
4
5
6
7
6a
6b
6c
6d
6e
ent-6f
6g
100
100
85
100
100
100
100
89
2
9
59
20
14
47
83:17
72:28
84:16
65:35
55:45
82:18
79:21
Me Me
O
O
Me Me
R2
R2
O
O
N
N
R2
R2
R1
R1
N
N
R1
R1
6e R1 = Ph, R2 = Ph
6a R1 = t-Bu, R2 = H
6f R1 = Me, R2 = Ph
1 = Bn, R2 = H
1 = i-Pr, R2 = H
Me Me
6b
6c
R
O
O
R
N
N
6d R1 = Ph, R2 = Ph
IndaBox (6g)
cyclohexa-1,3-diene, no desired product was observed even when
the reaction temperature was increased to room temperature.
Reaction with Danishefsky’s diene [(3-methoxy-1-methylene-2-
propen-1-yl)trimethylsilane] also did not give any of the desired
product.
and N-alkenoyloxazolidinones, a competition reaction was per-
formed. When 4 and 3-acryloyloxazolidin-2-one (1) were allowed
to react with cyclopentadiene under the optimum reaction condi-
tions, only the product from 1 was obtained at 30% conversion
(Scheme 2).
The limited scope of the Diels–Alder reaction of 3-buta-2,
3-dienoyloxazolidin-2-one (4) is most likely due to its low
reactivity. To compare the reactivity of N-allenoyloxazolidinones
A stereochemical model for the enantioselectivity (Fig. 1) based
on an A1,3-interaction is proposed to account for the observed
stereochemistry of the Diels–Alder product. The Cu atom in the
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T. Luanphaisarnnont / Tetrahedron Letters xxx (2014) xxx–xxx
Table 5
Temperature screening
Cu(SbF6)2(H2O)2(t-BuBox)
O
O
H
O
•
(10 mol%)
O
N
N
CH2Cl2, temp, time
O
O
4
2
5
Entry
Temp (°C), time (h)
Yield (%)
ee (%)
endo:exo
1
2
3
0, 6 h
–20, 10 h
–78, 20 h
90
88
87
89
91
95
83:17
85:15
90:10
Scheme 2. A competition reaction between 1 and 4.
Figure 1. A proposed model to account for the stereoinduction.
Cu(SbF6)2(H2O)2(t-BuBox) complex is expected to adopt
a
the allene. The A value of a vinyl group was reported to be
1.49 kcal molÀ1, while the A value of an alkyne (sp hybridized
distorted square planar geometry.13 N-Allenoyloxazolidinones
would be expected to orient such that the C2AH bond is aligned
with the CAN bond (s-cis conformation) to minimize A1,3-strain.
According to the model, it is expected that the steric environment
of the two prochiral faces will be significantly different. The t-Bu
group of the ligand is expected to block the Re face of C2. Dienes
should therefore approach from the less sterically hindered Si
face.14
carbon) was reported to be 0.41–0.52 kcal molÀ1 15
The energy
.
difference between the s-cis and s-trans conformations of
N-allenoyloxazolidinones is therefore anticipated to be smaller
than that of unsaturated N-alkenyloxazolidinones (Fig. 2).16,17
It is proposed that in the transition state of the s-trans conforma-
tion, the endo transition state may suffer from a steric interaction
between the diene and the oxazolidinone ring, while the exo transi-
tion state is not affected by this interaction (Fig. 3).18,19 Because of
this steric interaction, Diels–Alder reactions in the s-trans confor-
mation might be less endo selective for N-allenoyloxazolidinones.
This lower endo selectivity may therefore explain why
The endo:exo selectivity of the product 5 (90:10) is lower than
the selectivity of the previously reported product 3 (96:4)7b,9 under
the same reaction conditions. This relatively low endo:exo selectiv-
ity of the product from the allene may be due to the small size of
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T. Luanphaisarnnont / Tetrahedron Letters xxx (2014) xxx–xxx
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References and notes
1. For reviews of the Diels–Alder reaction, see: (a) Carruthers, W. Cycloaddition
Reactions in Organic Synthesis; Pergamon: Oxford, 1990; (b) Oppolzer, W. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Paquette, L. A., Eds.;
Pergamon Press: Oxford, 1991; Vol. 5, pp 315–399.
2. For
a review of the use of Diels–Alder reactions in total syntheses, see:
Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.; Vassilikogiannakis, G. Angew.
Chem., Int. Ed. 2002, 41, 1668–1698.
3. For comprehensive reviews of asymmetric catalysis, see: Noyori, R. Asymmetric
Catalysis in Organic Synthesis; Wiley & Sons: New York, 1994.
4. For reviews on catalytic asymmetric Diels-Alder reactions, see: (a) Jacobsen, E.
N.; Pfaltz, A.; Yamamoto, H. Comprehensive Asymmetric Catalysis; Springer:
Berlin, 1999. Vol. 3; (b) Kobayashi, S.; Jorgensen, K. A. Cycloaddition Reactions in
Organic Synthesis; Wiley-VCH Verlag: Weinheim, 2002.
5. For reviews of C2 symmetric chiral bis(oxazoline) and pyridinebis(oxazoline)
ligands in asymmetric catalysis, see: (a) Desimoni, G.; Faita, G.; Jorgensen, K. A.
Chem. Rev. 2006, 106, 3561–3651; (b) Desimoni, G.; Faita, G.; Quadrelli, P.
Chem. Rev. 2003, 103, 3119–3154; (c) McManus, H. A.; Guiry, P. J. Chem. Rev.
2004, 104, 4151–4202.
6. Yoon, T. P.; Jacobsen, E. N. Science 2003, 299, 1691–1693.
7. For early examples of the application of bis(oxazoline) ligands in Diels–Alder
reactions of activated alkenes, see: (a) Fe complexes: Corey, E. J.; Iami, N.;
Zhang, H.-Y. J. Am. Chem. Soc. 1991, 113, 728–729; Cu complexes: (b) Evans, D.
A.; Miller, S. J.; Lectka, T. J. Am. Chem. Soc. 1993, 115, 6460–6461.
8. (a) For reviews of allene chemistry, see: Modern Allene Chemistry; Krause, N.,
Hashmi, A. S. K., Eds.; Wiley-VCH Verlag: Weinheim, 2004; Vols. 1–2, (b) Ma, S.
Chem. Rev. 2005, 105, 2829–2871.
Figure 2. Energy differences between the s-cis and s-trans conformations of 1 and
4.
9. Asymmetric Diels–Alder reactions wherein allene acts as a dienophile have
been reported. For selected cases of auxiliary chemistry, see: (a) Oppolzer, W.;
Chapuis, C. Tetrahedron Lett. 1983, 24, 4665; (b) Henderson, J. R.; Chesterman, J.
P.; Parvez, M.; Keay, B. A. J. Org. Chem. 2010, 75, 988–991; For selected cases of
catalytic reactions, see: (c) Wei, L.-L.; Hsung, R. P.; Xiong, H.; Mulder, J. A.;
Nkansah, N. T. Org. Lett. 1999, 1, 2145–2148; (d) Mukherjee, S.; Scopton, A. P.;
Corey, E. J. Org. Lett. 2010, 12, 1836–1838.
10. For selected reviews on copper bis(oxazoline) catalysis, see: (a) Evans, D. A.;
Rovis, T.; Johnson, J. S. Pure Appl. Chem. 1999, 71, 1407–1415; (b) Johnson, J. S.;
Evans, D. A. Acc. Chem. Res. 2000, 33, 325–335.
11. For an example of the application of nickel bis(oxazoline) complexes in
catalytic asymmetric aldol reactions, see: Evans, D. A.; Downey, C. W.; Hubbs, J.
L. J. Am. Chem. Soc. 2003, 125, 8706–8707.
12. For a review of scandium(III) triflate pyridinebis(oxazoline) complexes, see:
Aye, Y. PhD. Thesis, Harvard University, Cambridge, MA, 2009.
13. The crystal structure of the Cu complex has been reported, see: Evans, D. A.;
Peterson, G. S.; Johnson, J. S.; Barnes, D. M.; Campos, K. R.; Woerpel, K. A. J. Org.
Chem. 1998, 63, 4541–4544.
14. This model agrees with the observed absolute stereochemistry of the product
5, which was determined by transforming the product 5 into its corresponding
benzyl ester and comparing the optical rotation of the ester with that of the
reported compound in Ref. 9d. See the Supporting information for more details.
15. Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds; Wiley & Sons:
New York, 1994. pp 696–697.
Figure 3. The steric interaction in the endo transition state of the s-trans
conformation of 4.
N-allenoyloxazolidinones gave products with lower endo:exo selec-
tivity than those with N-alkenyloxazolidinones.
In conclusion, Cu(SbF6)2(t-BuBox) was found to catalyze the
Diels–Alder reactions of 3-buta-2,3-dienoyloxazolidin-2-one in
high yield, endo:exo selectivity, and enantioselectivity. A competi-
tion experiment suggested that N-allenoyloxazolidinones are less
reactive than N-alkenoyloxazolidinones. A model for stereoinduc-
tion based on an A1,3 interaction was proposed to account for
the high enantioselectivity. A further detailed mechanistic and
computational investigation of this reaction will be reported in
due course.
16. The differences in energy between the s-cis and s-trans conformations of 3-
acryloyloxazolidin-2-one (1) and 3-buta-2,3-dienoyloxazolidin-2-one (4) were
calculated by Spartan’04 for Macintosh. The structures with fixed torsional
angles between C1@O and C2@C3 (0° for the s-cis conformation and 180° for
the s-trans conformation) were optimized using the DFT B3LYP/6-31G(d) level
of theory.
17. It should be noted that the larger difference between the energies of the s-cis
and s-trans conformations of
1 may also be the reason that the
enantioselectivity of the Diels–Alder reaction of 1 is higher than that of 4.
The endo-transition state of the s-trans conformation is expected to give the
opposite enantiomer to that produced from the endo-transition state of s-cis
conformation.
18. exo selective Diels–Alder reactions have been reported. For example,
oxazaborolidine-catalyzed Diels–Alder reactions of 2-methylacrolein and 2-
bromoacrolein gave exo products as the major products, see: (a) Hayashi, Y.;
Rohde, J. J.; Corey, E. J. J. Am. Chem. Soc. 1996, 118, 5502–5503; (b) Corey, E. J.;
Shibata, T.; Lee, T. W. J. Am. Chem. Soc. 2002, 124, 3808–3809.
19. Steric interactions have been utilized in exo selective Diels–Alder reactions.
Dienes with a bulky gem-dimethyl group and bulky dienophiles have been
shown to give exo selective Diels–Alder products under certain reaction
conditions, see: (a) Yoon, T.; Danishefsky, S. J.; de Gala, S. Angew. Chem., Int. Ed.
1994, 33, 853; (b) Maugel, N.; Mann, F. M.; Hillwig, M. L.; Peters, R. J.; Snider, B.
B. Org. Lett. 2010, 12, 2626–2629.
Acknowledgments
The author would like to thank Prof. David A. Evans for helpful
discussions. This research was supported in part by the Faculty of
Science, Mahidol University.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.10.
051.
Please cite this article in press as: Luanphaisarnnont, T. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.10.051