Chiral Auxiliary-Mediated Dynamic Kinetic Resolution
SHORT COMMUNICATION
fied on silica gel, eluent cyclohexane/ethyl acetate, 7:3. [α]2D5 = +5.4
temperatures, yields and diastereomeric ratios are indicated in
Table 3.
(c = 6.2, CHCl ). IR (KBr): ν = 1732, 1656 cm–1. 1H NMR
˜
3
(CDCl3): δ = 0.88 [d, J = 6.6 Hz, 6 H, (CH3)2CH], 1.31–1.41 [m, 6
H, NCH2(CH2)3], 1.41 (d, J = 6.6 Hz, 3 H, OCHCH3), 1.52 (d, J
= 6.9 Hz, 3 H, ArCHCH3), 1.80–1.89 [m, 1 H, (CH3)2CH], 2.43 (d,
J = 6.9 Hz, 2 H, CH2Ar), 3.07–3.11 and 3.45–3.50 (both m, 4 H,
CH2NCH2), 3.74 (q, J = 6.9 Hz, 1 H, ArCHCH3), 5.42 (q, J =
6.6 Hz, 1 H, OCHCH3), 7.08 and 7.22 (both d, J = 8.1 Hz, 4 H,
aromatic) ppm. 13C NMR (CDCl3): δ = 17.0 (ArCHCH3), 18.6
(OCHCH3), 22.5 [(CH3)2CH], 24.6 and 26.4 [NCH2(CH2)3], 30.3
[(CH3)2CH], 43.4 (CH2NCH2), 45.2 (CH2Ar), 46.3 (ArCHCH3),
67.6 (OCHCH3), 127.5 and 129.4 (CH aromatic), 137.5 and 140.8
(C aromatic), 168.0 (CON), 174.2 (COO) ppm. C21H31NO3
(345.476): calcd. C 73.01, H 9.04, N 4.05; found C 73.04, H 9.02,
N 4.04.
(1S)-1-Methyl-2-oxo-2-pyrrolidin-1-ylethyl (2R,S)-2-(4-Chlorophen-
oxy)butanoate [(R,S)-6d] and (S,S)-6d]: (diastereomeric mixture dr
98:2, Entry 7, Table 3) oil. IR (KBr): ν = 1746, 1652 cm–1. 1H
˜
NMR (CDCl3): δ = 1.08 (dt, J = 7.2 Hz, 3 H, CH3CH2), 1.45 (dd,
J = 7.2 Hz, 3 H, CH3CHCON), 1.78–2.10 [m, 6 H, CH3CH2 and
NCH2(CH2)2], 3.26–3.60 (m, 4 H, CH2NCH2), 4.44–4.62 (m, 1 H,
ArOCH), 5.23 (dq, J = 7.2 Hz, 1 H, CH3CHCON), 6.79 and 7.21
(both d, J = 9.0 Hz, 4 H, aromatic) ppm. 13C NMR (CDCl3): δ
= 9.8 (CH3CH2), 16.6 (CH3CHCON), 22.6 [NCH2(CH2)2], 26.2
(CH3CH2), 46.4 (CH2NCH2), 69.1 (CH3CHCON), 78.1 (ArOCH),
117.2 and 129.5 (CH aromatic), 156.2 (C aromatic), 168.6 (CON),
171.2 (C aromatic), 173.4 (COO) ppm. C17H22ClNO4 (339.814):
calcd. C 60.09, H 6.53, N 4.12; found C 60.18, H 6.51, N 4.13.
(1S)-1-Methyl-2-(morpholin-4-yl)-2-oxoethyl (2S)-2-(2-Fluoro-1,1Ј-
biphenyl-4-yl)propanoate [(S,S)-3c]: Isolated from a diastereomeric
mixture with dr = 97:3, see Entry 13 in Table 2), white solid, puri-
fied on silica gel, eluent cyclohexane/ethyl acetate, 7:3. [α]2D5 = +8.5
Acknowledgments
The authors gratefully acknowledge the Italian MIUR for financial
support.
(c = 1.0, CHCl ). IR (KBr): ν = 1735, 1653 cm–1. 1H NMR
˜
3
(CDCl3): δ = 1.45 (d, 3 H, J = 6.9 Hz, OCHCH3), 1.57 (d, J =
7.2 Hz, 3 H, ArCHCH3), 3.31–3.64 [m, 8 H, N(CH2)2O(CH2)2],
3.82 (q, J = 7.2 Hz, 1 H, ArCHCH3), 5.39 (q, J = 6.9 Hz, 1 H,
OCHCH3), 7.12–7.55 (m, 8 H, aromatic) ppm. 13C NMR (CDCl3):
δ = 16.9 (ArCHCH3), 18.5 (OCHCH3), 44.7 (CH2NCH2), 46.1
(ArCHCH3), 66.6 (CH2OCH2), 67.4 (OCHCH3), 115.7, 123.9,
127.9, 128.6, 129.1 and 131.0 (CH aromatic), 135.6, 141.7, 158.2
and 161.5 (C aromatic), 168.9 (CON), 173.8 (COO) ppm.
C22H24NO4 (385.429): calcd. C 68.56, H 6.28, N 3.63; found C
68.82, H 6.29, N 3.62.
[1] H. Pellissier, Tetrahedron 2003, 59, 8291–8327.
[2] For DKR with chiral auxiliaries, see: a) H. Kubota, A. Kubo,
M. Takahashi, R. Shimizu, D. T. Tadamasa, K. Okamura, K.-
I. Nunami, J. Org. Chem. 1995, 60, 6776–6784; b) S. Caddick,
K. Jenkins, Chem. Soc. Rev. 1996, 25, 447–456; c) J. A. O’Me-
ara, N. Gardee, M. Jung, R. N. Ben, T. Durst, J. Org. Chem.
1998, 63, 3117–3119; d) P. Camps, F. Perez, N. Soldevilla, Tet-
rahedron: Asymmetry 1998, 9, 2065–2079; e) A. Ammazzalorso,
R. Amoroso, G. Bettoni, B. De Filippis, Chirality 2001, 13,
102–108; f) S. Caddick, C. A. M. Afonso, S. X. Candeias, P. B.
Hitchcock, K. Jenkins, L. Murtagh, D. Pardoe, A. G. Santos,
N. R. Treweeke, R. Weaving, Tetrahedron 2001, 57, 6589–6605;
g) H. J. Kim, E.-k. Shin, J.-y. Chang, Y. Kim, Y. S. Park, Tetra-
hedron Lett. 2005, 46, 4115–4117.
[3] For asymmetric syntheses with lactamides, see: a) R. P. Hof,
R. M. Kellogg, J. Chem. Soc., Perkin Trans. 1 1995, 10, 1247–
1250; b) P. N. Devine, H. H. Dolling, R. M. Heid Jr, D. M.
Tschaen, Tetrahedron Lett. 1996, 37, 2683–2686; c) A. Kami-
mura, Y. Omata, A. Kakehi, M. Shirai, Tetrahedron 2002, 58,
8763–8770.
(1S)-1-Methyl-2-(morpholin-4-yl)-2-oxoethyl
(2S)-2-(4-Phenoxy-
phenyl)propanoate [(S,S)-4c]: Isolated from a diastereomeric mix-
ture with dr = 96:4, see Entry 15 in Table 2), colorless oil, purified
on silica gel, eluent cyclohexane/ethyl acetate, 7:3. [α]2D5 = +3.6 (c
= 1.8, CHCl ). IR (KBr): ν = 1730, 1653 cm–1. 1H NMR (CDCl ):
˜
3
3
δ = 1.41 (d, J = 6.9 Hz, 3 H, OCHCH3), 1.52 (d, J = 7.2 Hz, 3 H,
ArCHCH3), 3.21–3.67 [m, 8 H, N(CH2)2O(CH2)2], 3.73 (q, J =
7.2 Hz, 1 H, ArCHCH3), 5.38 (q, J = 6.9 Hz, 1 H, OCHCH3),
6.86–7.36 (m, 9 H, aromatic) ppm. 13C NMR (CDCl3): δ = 16.9
(ArCHCH3), 18.5 (OCHCH3), 45.4 (ArCHCH3), 46.0
(CH2NCH2), 66.6 (CH2OCH2), 67.5 (OCHCH3), 117.7, 118.4,
119.1, 122.6, 123.6, 130.0 and 130.1 (CH aromatic), 142.2, 157.2
and 157.7 (C aromatic), 168.9 (CON), 173.9 (COO) ppm.
C22H25NO5 (383.438): calcd. C 68.91, H 6.57, N 3.65; found C
69.01, H 6.56, N 3.66.
[4] A. Ammazzalorso, R. Amoroso, G. Bettoni, B. De Filippis, L.
Giampietro, M. Pierini, M. L. Tricca, Tetrahedron Lett. 2002,
43, 4325–4328.
[5] A. Ammazzalorso, R. Amoroso, G. Bettoni, B. De Filippis, L.
Giampietro, C. Maccallini, M. L. Tricca, Arkivoc 2004, 375–
381.
[6] M. L. Fein, E. M. Filachione, J. Am. Chem. Soc. 1953, 75,
2097–2099.
[7] For asymmetric syntheses of arylpropionic acids, see; a) R. D.
Larsen, E. G. Corley, P. Davis, P. J. Reider, E. J. J. Grabowsky,
J. Am. Chem. Soc. 1989, 111, 7650–7651; b) J. A. O’Meara, N.
Gardee, M. Jung, R. N. Ben, T. Durst, J. Org. Chem. 1998, 63,
3117–3119; c) L. Carde, D. H. Davies, S. M. Roberts, J. Chem.
Soc., Perkin Trans. 1 2000, 2455–2463; d) G. S. Coumbarides,
M. Dingjan, J. Eames, A. Flinn, J. Northen, Y. Yohannes, Tet-
rahedron Lett. 2005, 46, 2897–2902.
[8] M. Calmes, C. Glot, T. Michel, M. Rolland, J. Martinez, Tetra-
hedron: Asymmetry 2000, 11, 737–741.
[9] K. Koh, T. Durst, J. Org. Chem. 1994, 59, 4683–4686.
[10] R. Amoroso, G. Bettoni, B. De Filippis, M. L. Tricca, Chirality
1999, 11, 483–486.
General Procedure for Diastereoselective SN2 Reaction of 2-Bromo
Esters 5a–d with 4-Chlorophenoxide: Sodium 4-chlorophenoxide was
preformed by adding a solution of 4-chlorophenol (1.1 mmol) to a
stirred suspension of sodium (1.0 mmol) in dry THF (10 mL), at
room temperature under nitrogen. The resulting solution, occasion-
ally preheated, was then added dropwise to a solution of bromo
esters 5 (1.0 mmol in 6 mL of dry THF) and stirred until comple-
tion of reaction. After quenching with saturated NaCl (10 mL), the
mixture was extracted with CH2Cl2 (3×15 mL). The organic phase
was washed with H2O (3×15 mL), dried with Na2SO4 and concen-
trated at reduced pressure. The residue was purified by column
chromatography of silica gel (cyclohexane/ethyl acetate, 7:3) to give
the diastereomeric mixture of 4-chlorophenoxy esters 6. The times,
Received: June 6, 2006
Published Online: August 3, 2006
Eur. J. Org. Chem. 2006, 4088–4091
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4091