Highly endo- and enantioselective asymmetric nitrone cycloadditions catalyzed by the aqua complex of 4,6-dibenzofurandiyl-2,2'-bis(4-phenyl- oxazoline)-nickel(II) perchlorate. Transition structure based on dramatic effect of MS 4A on selectivities [3]

Full text of DOI:10.1021/ja982254e

J. Am. Chem. Soc. 1998, 120, 12355-12356
Scheme 1
12355
Highly Endo- and Enantioselective Asymmetric
Nitrone Cycloadditions Catalyzed by the Aqua
Complex of 4,6-Dibenzofurandiyl-2,2′-bis(4-phenyl-
oxazoline)-Nickel(II) Perchlorate. Transition
Structure Based on Dramatic Effect of MS 4A on
Selectivities
Shuji Kanemasa,* Yoji Oderaotoshi,† Junji Tanaka, and
Eiji Wada
Institute of AdVanced Material Study, Kyushu UniVersity,
Kasugakoen, Kasuga 816-8580, Japan
ReceiVed June 29, 1998
1,3-Dipolar cycloaddition to alkene dipolarophiles is now the
most useful method to make many stereochemically defined five-
membered heterocycles.1 Although a variety of diastereoselective
1,3-dipolar cycloadditions have been developed, enantioselective
versions are still limited.2 Nitrones3 are important 1,3-dipoles
that have been the target of catalyzed enantioselective reactions.
Three different approaches to catalyzed enantioselective reactions
have been taken: (1) activation of electron-deficient alkenes by
a chiral Lewis acid,4-8 (2) activation of nitrones in the reaction
with ketene acetals,9 and (3) coordination of both nitrones and
allylic alcohols on a chiral catalyst.10 Among these approaches,
the dipole/HOMO controlled reactions of electron-deficient al-
kenes such as N-alkenoyl-2-oxazolidinones or N-alkenoylsuccini-
mides4b are especially promising because a variety of combina-
tions between chiral Lewis acids and electron-deficient alkenes
have been investigated in the study of catalyzed enantioselective
Diels-Alder reactions. Enantioselectivities in catalyzed nitrone
cycloadditions sometimes exceed 90% ee, but the efficiency of
catalytic loading remains insufficient.
In the present communication, we report asymmetric 1,3-dipolar
cycloadditions of nitrones to 3-(2-alkenoyl)-2-oxazolidinones
catalyzed by the aqua complex derived from (R,R)-4,6-dibenzo-
furandiyl-2,2′-bis(4-phenyloxazoline) ligand (R,R-DBFOX/Ph)11
and Ni(ClO4)2‚6H2O.
In the presence of 10 mol % of the anhydrous nickel catalyst
1 (Ln ) none),12 which can be prepared in situ from (R,R)-
DBFOX/Ph ligand, NiBr2, and two equimolar amounts of Ag-
ClO4,13 the reaction of 3-crotonoyl-2-oxazolidinone (2a) with
N-benzylidenemethylamine N-oxide (3a) produces 3,4-trans-
isoxazolidine 4a in near perfect endo selectivity (endo:exo ) 99:
1) and enantioselectivity for the 3S,4R,5S enantiomer (>99% ee
for the endo isomer, Scheme 1 and Table 1, entry 1). The aqua
nickel complex 1 (Ln ) H2O), which can be simply prepared in
situ by stirring equimolar amounts of the (R,R)-DBFOX/Ph ligand
and Ni(ClO4)2‚6H2O in dichloromethane for a few hours, gives a
comparable result in a similar reaction in the presence of MS 4A
(entry 2). The simple preparation procedure of the aqua catalyst
should be attractive.
The presence of MS 4A is essential to attain high selectivities,
especially in the reactions catalyzed by the aqua complex. In
the absence of MS 4A, the endo selectivity and enantioselectivity
for 3,4-trans-isoxazolidines are both lowered.14 Jørgensen was
the first to observe a dramatic effect of MS 4A in Lewis acid-
catalyzed nitrone cycloadditions.5 In his reaction, the chemical
yield of the cycloadduct was not affected by the absence of MS
4A, but the endo selectivity was lowered (endo:exo, from 92:8
to 65:35) and the enantioselectivity almost disappeared (79 to
2% ee).15 Our results are comparable. Although the role of MS
4A cannot yet be fully explained,16 it certainly works as
dehydrating agent. In a reaction catalyzed by the aqua nickel
complex 1 (Ln ) H2O), anhydrous magnesium sulfate can replace
MS 4A, but the reaction becomes a little slower (entry 8).
Reactions of other nitrones 3b-f (entries 3-11) are also
diastereoselective (endo:exo g 95:5) and enantioselective for
endo-4b-f (higher than 95% ee for 4a,b,d,f and 89% ee for 4c,e).
High efficiency of the catalytic cycle can be demonstrated in the
† Department of Molecular Science and Technology, Interdisciplinary
Graduate School of Engineering Sciences, Kyushu University, Kasugakoen,
Kasuga 816-8580, Japan.
(1) 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; John Wiley &
Sons: New York, 1984.
(2) Gothelf, K. V.; Jørgensen, K. A. Chem. ReV. 1998, 98, 863-909.
(3) (a) Breuer, E.; Aurich, H. G.; Nielsen, A. Nitrones, Nitronates and
Nitroxides; Patai, S., Rappoport, Z., Eds.; John Wiley & Sons: Chichester,
UK, 1989; Chapters 2 and 3, pp 139-312. (b) Tufariello, J. J. 1,3-Dipolar
Cycloaddition Chemistry; Padwa, A., Ed.; John Wiley & Sons: New York,
1984; Vol. 9, pp 83-168.
(11) (a) Kanemasa, S.; Oderaotoshi, Y.; Yamamoto, H.; Tanaka, J.; Wada,
E.; Curran, D. P. J. Org. Chem. 1997, 62, 6454-6455. (b) Kanemasa, S.;
Oderaotoshi, Y.; Sakaguchi, S.; Yamamoto, H.; Tanaka, J.; Wada, E.; Curran,
D. P. J. Am. Chem. Soc. 1998, 120, 3074-3088.
(12) DBFOX/Ph complexes of iron(II), zinc(II), and magnesium perchlo-
rates show satisfactory selectivities in the reactions of 2 with nitrone 3c at
room temperature in the presence of MS 4A: DBFOX/Ph‚Fe(ClO4)2 (10 mol
%) 69%, endo:exo ) 95:5, >99% ee for endo isomer; DBFOX/Ph‚Zn(ClO4)2
(10 mol %) 100%, endo:exo ) 94:6, 86% ee for endo isomer; DBFOX/Ph‚
Mg(ClO4)2 (10 mol %) 100%, endo:exo ) 75:25, 86% ee for endo isomer.
(13) Although the resulting AgBr can be removed with the aid of a syringe
filter, this filtration procedure is not necessary. Equivalent selectivities result
without filtration procedure.
(14) The iron complex catalyzed reaction shown in ref 12 in the absence
of MS 4A gives lower selectivities (endo:exo ) 68:32, 21% ee for endo isomer
endo-4a).
(15) The reaction of N-benzylideneaniline N-oxide with 3-crotonoyl-2-
oxazolidinone in the presence of catalyst (10 mol %) prepared from
isopropylidene-2,2′-bis(4-phenyloxazoline) and MgI2/I2 at room temperature
for 24 h.
(4) (a) Jensen, K. B.; Gothelf, K. V.; Jørgensen, K. A. HelV. Chim. Acta
1997, 80, 2039-2046. (b) Jensen, K. B.; Gothelf, K. V.; Hazell, R. G.;
Jørgensen, K. A. J. Org. Chem. 1997, 62, 2471-2477. (c) Gothelf, K. V.;
Jørgensen, K. A. Acta Chem. Scand. 1996, 50, 652-660. (d) Gothelf, K. V.;
Thomsen, I.; Jørgensen, K. A. J. Am. Chem. Soc. 1996, 118, 59-64. (e)
Gothelf, K. V.; Jørgensen, K. A. J. Org. Chem. 1994, 59, 5687-5991.
(5) Gothelf, K. V.; Hazell, R. G.; Jørgensen, K. A. J. Org. Chem. 1996,
61, 346-355. They have recently reported a paper discussing the role of MS
4A: Gothelf, K. V.; Hazell, R. G.; Jørgensen, K. A. J. Org. Chem. 1998, 63,
5483-5488.
(6) Sanchez-Blanco, A. I.; Gothelf, K. V.; Jørgensen, K. A. Tetrahedron
Lett. 1997, 38, 7923-7926.
(7) Hori, K.; Kodama, H.; Ohta, T. Furukawa, I. Tetrahedron Lett. 1996,
37, 5947-5950.
(8) (a) Kobayashi, S.; Kawamura, M. J. Am. Chem. Soc. 1998, 120, 5840-
5841. (b) Kobayashi, S.; Akiyama, R.; Kawamura, M.; Ishitani, H. Chem.
Lett. 1997, 1039-1040.
(9) (a) Seerden, J.-P. G.; Boeren, M. M. M.; Scheeren, H. W. Tetrahedron
1997, 53, 11843-11852. (b) Seerden, J. P. G.; Scholte op Reimer, A. W. A.;
Scheeren, H. W. Tetrahedron Lett. 1994, 35, 4419-4422.
(10) Ukaji, Y.; Taniguchi, K.; Sada, K.; Inomata, K. Chem. Lett. 1997,
547-548.
(16) Many examples are known for the effect of MS 4A in Lewis acid-
catalyzed asymmetric reactions: (a) Posner, G. H.; Dai, H. Y.; Bull, D. S.;
Lee, J. K.; Eydoux, F.; Ishihara, Y.; Welsh, W.; Pryor, N. J. Org. Chem.
1996, 61, 671-676. (b) Mikami, K.; Motoyama, Y.; Terada, M. J. Am. Chem.
Soc. 1994, 116, 2812-2820 and references therein.
10.1021/ja982254e CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/11/1998

12356 J. Am. Chem. Soc., Vol. 120, No. 47, 1998
Communications to the Editor
Table 1. Nitrone Cycloadditions of 3-Crotonoyl-2-oxazolidinone (2a) in the Presence of the DBFOX/Ph‚Ni(ClO4)2 Complexes Leading to
Isoxazolidines 4a-i
entry
3
catalyst/mol %
MS 4Aa
temp/°C
time/h
product
yield/%
dsb
% eec
1
2
3
4
5
6
7
8
9
10
11
12
13
14
3a
3a
3b
3c
3d
3d
3d
3d
3e
3e
3f
Ni(ClO4)2/10
100
100
500
300
300
500
300
500d
100
300
500
500
500
500
rt
rt
rt
rt
rt
rt
reflux
rt
0
rt
rt
rt
rt
72
72
48
48
48
96
36
120
96
72
36
48
48
48
4a
4a
4b
4c
4d
4d
4d
4d
4e
4e
4f
63
72
76
96
73
75
37
100
87
100
100
25
99:1
98:2
>99:1
98:2
>99:1
>99:1
>99:1
97:3
95:5
>99:1
99:1
74:26
99:1
94:6
>99
>99
95
89
>99
99
93
99
89
87
Ni(ClO4)2‚6H2O/10
Ni(ClO4)2‚6H2O/10
Ni(ClO4)2‚6H2O/10
Ni(ClO4)2‚6H2O/10
Ni(ClO4)2‚6H2O/2
Ni(ClO4)2‚6H2O/1
Ni(ClO4)2‚6H2O/10
Ni(ClO4)2/10
Ni(ClO4)2‚6H2O/10
Ni(ClO4)2‚6H2O/10
Ni(ClO4)2‚6H2O/10
Ni(ClO4)2‚6H2O/10
Ni(ClO4)2‚6H2O/10
>99
3g
3h
3i
4g
4h
4i
9
100
92
45
97
rt
a Weight of MS 4A (mg) per 1-mmol scale. b Endo/exo ratio. c % ee for endo isomers (For conditions of chiral HPLC, see Supporting Information).
d In the presence of magnesium sulfate instead of MS 4A.
reactions of nitrone 3d: a 99% ee for endo-4d is recorded with
2 mol % of the catalyst at room temperature (entry 6) and a 93%
ee with 1 mol % even under reflux in dichloromethane (entry 7).
The nitrone having a bulky aromatic C-substituent such as N-(1-
naphthylmethylene)aniline N-oxide (3g) shows a decreased
reactivity, the chemical yield, diastereoselectivity, and enanti-
oselectivity being all poor (entry 12), while the isomer N-(2-
naphthylmethylene)aniline N-oxide (3h) is sufficiently reactive
(entry 13). It is pleasing that the nitrone 3i derived from an
aliphatic aldehyde also shows excellent diastereoselectivity as well
as enantioselectivity for the endo-4i (entry 14). Thus, the
DBFOX/Ph‚Ni(ClO4)2‚3H2O-catalyzed asymmetric nitrone cy-
cloaddition in the presence of MS 4A has the most promising
features with respect to the catalytic cycle, diastereoselectiVity,
and enantioselectiVity among the catalyzed reactions yet reported.
Absolute configurations of isoxazolidines endo-4b4d and endo-
4c5 were determined to be a 3S,4R,5S structure by comparison
of the optical rotations as well as retention times in a chiral HPLC
Figure 1. Proposed transition structure A for the endo approach of (Z)-
analysis with those of the authentic samples. Other 3,4-trans-
nitrones leading to (3S,4R,5S)-isoxazolidines 4a-h.
isoxazolidines 4a and 4d-i were assigned by similarity of the
proposed transition structures. Selection of the Si face at the Câ
position of alkene 2a in nitrone cycloadditions is the same as
that observed in the Diels-Alder reactions of cyclopentadiene
trigonal-bipyramid complex catalyst based on the trans effect by
the aqua ligand.
In conclusion, the aqua complex derived from the DBFOX/Ph
with 2a in the presence of the (R,R)-DBFOX/Ph‚Ni(ClO4)2‚3H2O
ligand and Ni(ClO4)2‚6H2O acts as excellent chiral Lewis acid
complex,11 and this indicates that the s-cis conformation of alkene
catalyst in the presence of MS 4A in asymmetric 1,3-dipolar
cycloadditions of nitrones to 3-(2-alkenoyl)-2-oxazolidinones.
Maximum enantioselectivities observed were as high as >99%
ee, and the minimum catalytic loading was 2 mol %. The
2a has participated in the reaction.
The simple structure of DBFOX complex catalysts facilitates
discussion of transition structures and provides insight into the
role of MS 4A. On the basis of ab initio molecular orbital
presence of MS 4A is essential to attain such high selectivities.
calculations of a model nitrone cycloaddition,17 a variable-
These excellent diastereoselectivities and enantioselectivities for
1
temperature H NMR study18 of the substrate complex derived
the 3,4-trans-isoxazolidines with 4S,5R absolute configurations
from DBFOX/Ph, Zn(ClO4)2, 3-acetyl-2-oxazolidinone, and the
arise from the transition structure involving a trigonal-bipyramid
observed high catalytic activity, the nitrone cycloaddition in the
substrate complex.
presence of MS 4A is most likely to proceed through the transition
structure TS-A with a trigonal-bipyramid structure (Figure 1). Face
shielding by one of the 4-phenyl substituents (the top 4-phenyl)
becomes very effective, and the other 4-phenyl substituent (the
bottom 4-phenyl) inhibits the exo approach of nitrone 3. As a
result, the reaction shows high endo and enantioselectivities in
the absence of water. In the reactions catalyzed by the aqua
DBFOX complex in the absence of MS 4A, a water molecule
coordinates on the nickel ion so that octahedral transition structure
TS-B becomes predominant.19 The reaction site of the coordi-
nated substrate in TS-B is more open for the approach of nitrone
3, and both the Si and Re faces (Câ) allow the attack of nitrone
3, showing low enantioselectivity.14 In addition, the exo approach
of nitrone 3 leading to 3,4-cis-isoxazolidines is not difficult, and
poor endo selectivity results. Even when a trace of water is
present, TS-A may participate predominatly in the reaction since
the octahedral complex catalyst should be less reactive than the
Supporting Information Available: Experimental procedures and
analytical data for important compounds are contained (7 pages, print/
PDF). See any current masthead page for ordering and Internet access
instructions.
JA982254E
(17) Transition structures were optimized by ab initio calculations for the
uncatalyzed and BH3-catalyzed reactions of CH2dN(O)H with CH2dCHCHO.
Bond formation of nitrone oxygen/acceptor â-carbon precedes that of nitrone
carbon/acceptor R-carbon. Remarkable pyramidalization can be seen at the
â-carbon of acceptor in the transition structure of the catalyzed reaction:
Kanemasa, S.; Tanaka, J.; Oderaotoshi, Y. Unpublished results.
(18) Kanemasa, S.; Oderaotoshi, Y.; Tanaka, J.; Wada, E. Tetrahedron Lett.
1998, 39, 7521-7524.
(19) In the variable-temperature 1H NMR study cited in ref 18, an octahedral
structure has been assigned to the substrate complex derived from DBFOX/
Ph, Zn(ClO4)2, and 3-acetyl-2-oxazolidinone. Isomerization between two
octahedral complexes should occur via the intermediacy of a trigonal-bipyramid
complex.