Copper-catalyzed desymmetrization of N-sulfonylaziridines with methylmagnesium halides

Article abstract of DOI:10.1021/ol990650b

(equation presented) Cyclohexene N-p-toluenesulfonylimine (1) undergoes enantioselective ring opening to 2b upon treatment with methylmagnesium halides or MeLi in the presence of chiral Cu-catalysts. No activation of the aziridine by Lewis acid is require

Full text of DOI:10.1021/ol990650b

ORGANIC
LETTERS
1
999
Vol. 1, No. 3
39-441
Copper-Catalyzed Desymmetrization of
N-Sulfonylaziridines with
Methylmagnesium Halides
Paul M u1 ller* and Patrice Nury
4
Department of Organic Chemistry, UniVersity of GeneVa, 30, Quai Ernest Ansermet,
CH-1211 GeneVa 4, Switzerland
paul.Muller@chiorg.unige.ch
Received May 10, 1999
ABSTRACT
Cyclohexene N-p-toluenesulfonylimine (1) undergoes enantioselective ring opening to 2b upon treatment with methylmagnesium halides or
MeLi in the presence of chiral Cu-catalysts. No activation of the aziridine by Lewis acid is required. Enantioselectivities of up to 91% have
been observed under optimized conditions with the chiral imine ligand derived from phenylalanine. The same system reacts with cyclohexene
oxide to afford trans-2-methylcyclohexanol with 50% yield and 10% ee.
1
The desymmetrization of meso-epoxides may be effected
via enantioselective â-deprotonation to afford allylic alco-
Sparteine was found even more efficient in epoxide opening
with organolithium reagents and produced enantioselectivities
of up to 87% in selected cases. Opening of epoxides by
2
7
hols, R-deprotonation to furnish carbenes and their subse-
3
quent products of intramolecular insertion, and nucleophilic
organocopper reagents proceeds without activation by Lewis
acids. However, enantioselectivities reported for opening of
cyclohexene oxide with organocuprates in the presence of
4
5
ring opening under stoichiometric and catalytic conditions.
The reaction of cyclohexene oxide with organometallic
reagents has been reported by several groups. Epoxide
opening with organolithium reagents requires activation by
a Lewis acid. Enantioselectivities of up to 47% have been
3
observed with BF and chiral ethers as external ligands.
8
chiral ligands are disappointing. In contrast, only a few
procedures for ring opening of aziridines are known. The
reaction usually requires strong nucleophiles. Opening of
aziridines has been reported with catalytic amounts of
6
9
lanthanides, in particular Yb(III). Organocuprates reportedly
open N-activated aziridines with high yield and high regio-
and stereoselectivity.
(
1) Hodgson, D. M.; Gibbs, A. R.; Lee, G. P. Tetrahedron 1996, 46,
4361-14384.
2) (a) Whitesell, J. K.; Felman, S. W. J. Org. Chem. 1980, 45, 755-
56. (b) Bhuniya, D.; Singh, V. K. Synth. Commun. 1994, 24, 375-385.
1
0,11
1
7
(
(6) Mizuno, M.; Kanai, M.; Iida, A.; Tomioka, K. Tetrahedron 1997,
53, 10699-10708.
(
c) Bhuniya, D.; Singh, V. K. Synth. Commun. 1994, 24, 1475-1481.
(3) Hodgson, D. M.; Lee, P. P.; Marriott, R. E.; Thompson, A. J.;
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(8) Davies, S. G.; Wollowits, S. Tetrahedron Lett. 1980, 21, 4175-4178.
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31, 6379-6380. (b) Meguro, M.; Asao, N.; Yamamoto, Y. Tetrahedron
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Y.; Yeung, L.-L. Tetrahedron Lett. 1995, 36, 107-108.
Wisedale, R.; Witherington, J. J. Chem. Soc., Perkin Trans. 1 1998, 2151-
2
161.
(4) (a) Brown, H. C.; Joshi, N. N.; Srebnik, M. J. Am. Chem. Soc. 1988,
1
4
1
10, 6246-6248. (b) Yamamoto, H. Naruse, Y.; Eraki, T. Tetrahedron 1988,
4, 4747-4756. (c) Yamashita, H.; Mukajyama, T. Chem. Lett. 1985, 1643-
646.
(10) (a) Tanner, D.; Birgresson, C.; Dhaliwal, H. K. Tetrahedron Lett.
1990, 31, 1903-1906. (b) Tanner, D.; Groth, T. Tetrahedron 1997, 53,
16139-16146.
(11) (a) Cantrill, A. A.; Jarvis, A. N.; Osbom, H. M. I.; Ouadi, A.;
Sweeney, J. B. Synlett 1996, 847. (b) Aoyama, H.; Mimura, N.; Ohno, H.;
Ishii, K.; Toda, A.; Tamamura, H.; Otaka, A.; Fujii, N.; Ibuka, T.
Tetrahedron Lett. 1997, 38 7383-7386. (c) Atkinson, R. S.; Ayscough, A.
P.; Gattrell, W. T.; Raynham, T. M. Tetrahedron Lett. 1998, 39, 497-500.
(
5) (a) Yamashita, H. Chem. Lett. 1987, 525-528. (b) Hayashi, M.;
Kademura, K.; Oguni, N. Synlett. 1991, 774-776. (c) Adolffson, H.;
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L. E.; Leighton, J. L.; Carsten, D. H.; Jacobsen, E. N. J. Am. Chem. Soc.
1
995, 117, 5897-5898. (e) Hansen, K. B.; Leighton, J. L.; Jacobsen, E. N.
J. Am. Chem. Soc. 1996, 118, 10924-10925. (f) Snapper, M. L. Angew.
Chem., Int. Ed. Engl. 1996, 35, 1668-1671.
1
0.1021/ol990650b CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/25/1999

In the context of our research on asymmetric aziridinations
of olefins, we observed that some N-sulfonated aziridines
underwent ring opening in the presence of electrophiles under
mild conditions.12 We have now explored this observation
with the objective of developing a catalytic protocol for
desymmetrization of meso-aziridines.
reaction was carried out in the presence of 10% of [Cu-
(acac)
], ring opening occurred readily (0 °C, 1 h) and 2b15
was formed in 85% yield.
2
Next, a series of known Cu-catalysts was tested in this
process. Reactions were carried out by adding the organo-
metallic reagent (1.0 equiv) in THF at 0 °C to a THF solution
containing the aziridine 1 and the catalyst with a 10:1
substrate/catalyst ratio. The catalysts 5, 6, and 7 were
prepared in situ, by addition of 2 equiv of the ligand of
Exploratory experiments with cyclohexene N-p-toluene-
sulfonyl imine (1) revealed only limited reactivity toward
Lewis acid-catalyzed ring opening. Typically, reaction of 1
with NaN
2
3
went to completion in refluxing acetonitrile within
interest to [Cu(OTf) ], and 4 by analogy with CuI. In the
case of 3 and 8a-8e the Cu-complexes were synthesized
2
4 h and aforded 2a13 in 85% yield (Scheme 1).
and isolated according to literature procedures. In general,
yields for aziridine opening varied in the range of 60-89%,
and competing halide attack on 1 was the principal cause
for low yields of 2b.
Scheme 1
Poor enantioselectivity for opening of 1 was observed with
1
6
a Cu-semicorrin catalyst (0%), a salicylaldehyde-derived
1
7
Schiff base complex, and a Schiff base complex derived
5
d,e
18
from 1,2-diaminocyclohexane. The Cu-pybox catalyst
was equally ineffective (6% ee). The results with the more
successful catalysts are summarized in Table 1.
TMSN
3
in CH
3
CN at reflux, in turn, even in the presence
of Cu(II)- or Zn(II)-catalysts afforded 2a in 58-81% yield
after up to 12 h. No reaction occurred with TMSN in
Table 1. Ring Opening of Aziridine 1 to 2b with MeMgBra
3
conjunction with Jacobsen’s [Cr(salen)] catalyst, which is
known to exhibit exceptional reactivity and selectivity in
opening of epoxides.5d,e The aziridine 1 reacted when exposed
catalyst
time, h
yield, %
ee, %b
abs conf
[Cu(acac2]
1.0
3.0
2.5
2.0
2.5
2.0
2.0
2.0
2.0
85
70
30
84
60
80
89
71
80
3
4
5
6
7
8
8
8
30
51
29
56
32
55
39
32
1S, 2S
1S, 2S
1S, 2S
1S, 2S
1S, 2S
1S, 2S
1S, 2S
1S, 2S
to MeMgBr in THF (0 °C, 6 h), but the resulting product
was not the expected trans-methyl-N-p-toluenesulfonylcy-
clohexanamine (2b), but rather the trans-2-bromo derivative
14
2
c, which was isolated in 91% yield. However, when the
c
d
e
a
Conditions: MeMgBr in THF/toluene added dropwise to 1 and catalyst
in THF at 0°.22 Determined by HPLC (OD,H column with hexane/2-
b
propanol, 9:1).
Inspection of Table 1 reveals no clear-cut relationship
between catalyst structure and catalyst efficiency. The highest
enantioselectivity resulted with the BINOL-derived amidites
(12) M u¨ ller, P.; Baud, C.; Jacquier, Y.; Moran, M.; N a¨ geli, I. J. Phys.
Org. Chem. 1996, 9, 341-347. M u¨ ller, P.; Baud, C.; Jacquier, I. Tetrahedron
1
1
996, 52, 1543-1548. M u¨ ller, P.; Baud, C.; Jacquier, Y. Can. J. Chem.
998, 76, 738-750.
(
13) Leung, W.-H.; Yu, M.-T.; Wu, M.-C.; Yeung, L.-L. Tetrahedron
Lett. 1996, 37, 891-892.
14) Barton, D. H. R.; Britten-Kelly, M. R.; Ferreira, D. J. Chem. Soc.,
Perkin Trans. 1 1978, 1090-1100.
(
(
15) Data of 2b: 1H NMR (CDCl3) 0.81(3H, d), 0.98-1.25 (5H, m);
.57-1.58 (2H, m); 1.70-1.72 (2H, m); 2.41 (3H, s); 2.64-2.65 (1H, m);
1
4
1
3
.71-4.82 (1H, m); 7.27 (2H, d, J ) 8); 7.76 (2H, d, J ) 8); C NMR-
CDCl3) 19.05 (q), 21.5 (q); 25.3 (t); 25.4 (t); 34.4 (t); 34.5 (t); 38.3 (d);
(
5
9.1 (d); 126.9 (d); 129.5 (d); 138.7 (s); 142.9 (s); HR MS 267.12804
•
+
(
C14H21NO2S , calcd 267.12930).
16) Pfaltz, A. Acc. Chem. Res. 1993, 26, 339-345. Fritschi, H.;
Leutenegger, U.; Siegmann, K.; Pfaltz, A. HelV. Chim. Acta 1988, 71, 1541-
552.
(
1
(
17) Sacconi, C.; Ciampolini, M. J. Org. Chem. 1963, 29, 276-280.
Figure 1. Chiral Cu-catalysts.
40
(18) Deng, L.; Jacobsen, E. N. J. Org. Chem. 1992, 57, 4320-4323.
Larrow, J. F.; Jacobsen, E. N. J. Org. Chem. 1994, 59, 1939-1942.
Org. Lett., Vol. 1, No. 3, 1999
4

619
8
and 7, respectively, and with the Schiff base complexes
20
30%. At still higher catalyst concentration bromide attack
predominated. However, acceptable yields could be obtained
when MeMgBr was added slowly (in 10 min) to the reaction
mixture rather than dropwise in 5 min. Thus with 30% of
catalyst 2b was formed in 52% yield and with 91% ee, but
with 40% of 8c the yield of 2b dropped to an insignificant
amount. The decrease in yield upon increasing catalyst
concentration may be due to the presence of electrophilic
Cu(II) species, which might catalyze bromide attack. Addi-
tion of excess ligand to the reaction with 10% of catalyst in
THF had no beneficial effect. A high enantioselectivity of
c-8e,21 which are obtained upon condensation of salicyl-
aldehyde with amino acids. Within this latter series of
catalysts, structural variation of the amino acid component
had a remarkable effect on the enantioselectivity. The
alanine- and methionine-derived complexes 8a and 8b were
essentially unselective, while those containing phenylglycine
(
8c) and tert-leucine (8d) afforded ee’s of 55% and 40%.
Introduction of tert-butyl groups into the salicylaldehyde
moiety (i.e., 8e) had, however, no beneficial effect.
Optimization of the reaction conditions was carried out
with the D-phenylglycine-derived Schiff base catalyst 8c
83% was also observed in Bu
The sulfonamide 2b which resulted from reaction of 1 with
d was cleaved to the amine 9 (Scheme 2), which had [R]22
+20.2 (c ) 10, ether). The absolute configuration of (+)-9
2
O with 10% of catalyst.
(
Table 2). The selectivity of 8c was found dependent not
8
D
)
1
9
23
([R]
D
) +30.8) has been determined to be 1S,2S. The
Table 2. Variation of Reaction Conditions for Ring Opening
of 1 with 8ca
absolute configurations assigned to the major enantiomers
of the sulfonamides 2b in Table 1 were assigned on the
grounds of the HPLC retention times relative to those
obtained with 8c.
reagent
cat,%
solvent
time, h
2b, yield, %
ee, %
MeMgCl
MeMgBr
MeMgI
10
10
10
10
2
THF
THF
THF
THF
THF
THF
THF
THF
Et2O
Et2O
Et2O
Et2O
Bu2O
Bu2O
Bu2O
2.0
2.0
2.0
3.0
1.0
1.0
1.0
1.5b
2.0
2.0
2.0
2.5
1.5
2.0
2.0
75
89
60
60
97
84
58
52
91
70
20
60
60
30
0a
20
55
62
45
4
11
77
91
25
70
61
40
41
83
MeLi
Scheme 2
MeMgBr
MeMgBr
MeMgBr
MeMgBr
MeMgCl
MeMgBr
MeMgI
5
20
30
10
10
10
10
10
10
10
MeLi
Application of the procedure to other organometallic
reagents is in progress. With PhMgBr the highest ee achieved
so far was 30%.
The reaction conditions are in principle also applicable to
ring opening of epoxides. Thus cyclohexene oxide reacted
with MeMgBr in the presence of 10% of 8c at -20 °C to
trans-2-methylcyclohexanol in 50% yield and 10% ee.
MeMgCl
MeMgBr
MeMgI
a
b
Conditions: see Table 1. Addition of MeMgBr in 10 min.
only upon the solvent but also upon the metal ion of the
reagent and its counterion. The tendencies are contradictory,
and no systematic trend may be spotted. MeMgCl is the least
efficient Grignard reagent. MeMgBr is superior to MeMgI
Acknowledgment. This work was supported by the Swiss
National Science Foundation (Grant Nos. 20-52581.97 and
027-048156) and by the European Commission for Science,
Research and Development (COST Action D12).
2
2
in THF, but is less efficient in Et O. In THF the yield
decreased with increasing the amount of catalyst from 2 to
OL990650B
(
19) (a) Feringa, M. L.; Pineschi, M.; Arnold, L. A.; Imbos, R.; de Vries,
(22) General Procedure for Ring Opening of 1. To 8c (28 mg, 0.08
mmol) and 1 (200 mg, 0.80 mmol) in THF (2.0 mL) at 0 °C was added
MeMgBr in THF/toluene (0.6 mL, 0.8 mmol), dropwise. After stirring for
3 h at 0 °C the mixture was decomposed (NH4Cl) and extracted with Et2O.
Purification of the crude product (column chromatography, SiO2, hexane/
AcOEt, 4:1) gave 2b (180 mg, 89% as colorless needles, mp 98-100 °C).
(23) Nohira, H.; Ehara, K.; Miyashita, A. Bull. Chem. Soc. Jpn. 1970,
43, 2230-2233.
A. H. M. Angew. Chem., Int. Ed. Engl. 1997, 36, 2620-2623. (b) de Vries,
A. H. M.; Meetsma, A.; Feringa, B. L. Angew. Chem., Int. Ed. Engl. 1996,
3
1
9
5, 2374-2376.
20) Zhang, F.-X.; Chan, A. S. C. Tetrahedron: Asymmetry 1998, 9,
179-1182.
21) Weinstein, G. N.; O’Connor, M. J.; Holm, R. H. Inorg. Chem. 1970,
, 2104-2111.
(
(
Org. Lett., Vol. 1, No. 3, 1999
441