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Eniko Forro et al.
FULL PAPERS
608Caffordedtheunreacted(S)-26{yield:232 mg(46%);[a]2D5:
À110 (c 0.49; EtOH); mp 123–1278C, (recrystallized from i-
Pr2O); ee¼99%} and b-amino acid (R)-19 {yield: 263 mg
(48%); recrystallized from H2O and Me2CO; [a]2D5: þ16.3 (c
0.33; H2O); mp 241–2448C with sublimation, lit.[10] mp 223–
2258C; ee¼99%} in 15 h.
(S)-40: {yield: 109 mg (84%); [a]2D5: þ5.3 (c 0.46; H2O); mp
185–1888C}.
(S)-41: {yield: 57 mg (91%); [a]2D5: þ3.8 (c 0.45; H2O); mp
191–1938C with sublimation}.
(S)-42: {yield: 108 mg (81%); [a]2D5: þ1.5 (c 0.47; H2O); mp
164–1688C}.
When 19 (100 mg) was treated with 18% HCl (3 mL), (R)-33
{yield: 106 mg, 90%; [a]2D5: À5.2 (c 0.46, H2O), lit.[10] [a]D25:
À3.33 (1.6 N HCl); mp 184–1888C (recrystallized from
EtOH and Et2O), ee¼99%} was formed.
Supporting Information
The spectroscopic and analytical data for racemates 1–7 and
enantiomers 15–42 are presented in the Supporting Informa-
tion.
Gram-Scale Resolution of (Æ)-6
Via the procedure described above, the reaction of racemic 6
(0.5 g, 2.21 mmol) and H2O (40 mL, 2.21 mmol) in i-Pr2O
(70 mL) in the presence of Lipolase (2.1 g, 30 mg mLÀ1) at
608C afforded the unreacted (S)-27 {220 mg (41%); [a]2D5:
À73 (c 0.16; EtOH); mp 151–1548C, (recrystallized from i-
Pr2O); ee¼96%} and b-amino acid (R)-20 {yield: 234 mg
(47%); recrystallized from H2O and Me2CO; [a]2D5: þ4 (c
0.45; H2O); mp 258–2608C, ee¼98%} in 14 h.
Acknowledgements
The authors acknowledge receipt of OTKA grants T 046440 and
T 049407, GVOP-3.1.1.-2004-05-0255/3.0 and a Bolyai Fellow-
ship for EF.
When 20 (50 mg) was treated with 18% HCl (3 mL), (R)-34
{yield: 52 mg (90%); [a]D25: À4.1 (c 0.45, H2O); mp 191–1938C
with sublimation (recrystallized from EtOH and Et2O), ee¼
99%} was formed.
References and Notes
[1] a) H. H. Wasserman, G. D. Berger, Tetrahedron 1983, 39,
2459–2464; b) H. H. Wasserman, H. Matsuyama, R. P.
Robinson, Tetrahedron 2002, 58, 7177–7190.
[2] a) O. Renault, J. Guillon, P. Dallemagne, S. Rault, Tetra-
hedron Lett. 2000, 41, 681–683; b) N. Leflemme, P. Dal-
lemagne, S. Rault, Tetrahedron Lett. 2004, 45, 1503–
1505.
[3] Enantioselective synthesis of b-amino acids, 2nd edn.,
(Eds.: E. Juaristi, V. A. Soloshonok), Wiley-Interscience,
Hoboken, NJ, 2005.
[4] R. L. Wolin, A. Santillan, T. Barclay, L. Tang, H. Venka-
tesan, S. Wilson, D. H. Lee, T. W. Lovenberg, Bioorg.
Med. Chem. 2004, 12, 4493–4509.
[5] a) M. Liu, M. P. Sibi, Tetrahedron 2002, 58, 7991–8035;
b) C. Y. K. Tan, D. F. Weaver, Tetrahedron 2002, 58,
7449–7461; c) H. Bergmann, H. Otto, Arch. Pharm.
1986, 319, 216–226; d) S. Laschat, H. Kunz, J. Org.
Chem. 1991, 56, 5883–5889; e) M. K. Mokhallalati,
L. N. Pridgen, Synth. Commun. 1993, 23, 2055–2064;
f) D. DiPietro, R. M. Borzilleri, S. M. Weinreb, J. Org.
Chem. 1994, 59, 5856–5857; g) M. C. Chung, H. J. Lee,
C. H. Lee, H. K. Chun, Y. H. Kho, J. Microbiol. Biotech-
nol. 1997, 7, 329–332; h) J. A. Carr, T. F. Al-Azemi, T. E.
Long, J. Shim, C. M. Coates, E. Turos, K. S. Bisht, Tetra-
hedron 2003, 59, 9147–9160; i) S. J. Faulconbridge, K. E.
Holt, L. G. Sevillano, C. J. Lock, P. D. Tiffin, N. Trem-
ayne, S. Winter, Tetrahedron Lett. 2000, 41, 2679–2681;
j) H. Groeger, H. Werner, Eur. Pat. Appl. JP
2003325197, 2003; k) H. Groeger, H. Werner, Eur. Pat.
Appl. EP 1361279, 2003; l) C. Salagnad, C. Gobert,
M. O. Dury, Fr. Demande FR 2829152, 2003; m) C. Salag-
nad, C. Gobert, M. O. Dury, PCT Int. Appl. WO
2003020943, 2003.
Gram-Scale Resolution of (Æ)-7
Via the procedure described above, the reaction of racemic 7
(0.5 g, 3.03 mmol) and H2O (55 mL, 3.03 mmol) in i-Pr2O
(70 mL) in the presence of Lipolase (2.1 g, 30 mg mLÀ1) at
608C afforded the unreacted (S)-28 {yield: 219 mg (44%);
[a]2D5:¼ À117 (c 0.45; EtOH); mp 97–1018C (recrystallized
from i-Pr2O); ee¼99%} and b-amino acid (R)-21 {yield:
268 mg (48%); recrystallized from H2O and Me2CO; [a]2D5:
þ4.9 (c 0.45; H2O), lit.[10] [a]D25: þ3.9 (c 0.4; H2O); mp 245–
2478C, ee¼99%} in 13 h.
When 21 (100 mg) was treated with 18% HCl (3 mL), (R)-35
{110 mg (91%); [a]D25: À1.2 (c 0.37, H2O), lit.[10] [a]2D5: À1.9 (1.9
N HCl); mp 166–1698C (recrystallized from EtOH and Et2O),
ee¼99%} was formed.
Ring Opening of (S)-22–(S)-28 with 18% HCl
The b-lactam enantiomer (S)-22 (50 mg, 0.34 mmol) or (S)-23
(50 mg, 0.31 mmol) or (S)-24 (100 mg, 0.55 mmol) or (S)-25
(100 mg, 0.55 mmol) or (S)-26 (100 mg, 0.55 mmol) or (S)-27
(50 mg, 0.22 mmol) or (S)-28 (100 mg, 0.60 mmol) was dis-
solved in 18% HCl (12 mL) and the solution was refluxed for
2 h. The solvent was then evaporated off, and the product
was recrystallized from EtOH and Et2O, which afforded white
crystals of the b-amino acid hydrochlorides.
(S)-36: {yield: 49 mg (72%); [a]2D5: þ3.0 (c 0.28; H2O); mp
197–2018C}.
(S)-37: {yield: 52 mg (78%); [a]2D5: þ4.0 (c 0.28; H2O); mp
196–2018C}.
(S)-38: {yield: 104 mg (80%); [a]2D5: À8.6 (c 0.46; H2O); mp
176–1798C}.
´ ´
[6] a) S. Gedey, A. Liljeblad, L. Lazar, F. Fülçp, L. T. Kaner-
(S)-39: {yield: 111 mg (86%); [a]2D5: þ3.3 (c 0.35; H2O); mp
201–2048C}.
va, Tetrahedron: Asymmetry 2001, 12, 105–110; b) M.
´
Solymar, F. Fülçp, L. T. Kanerva, Tetrahedron: Asymme-
922
asc.wiley-vch.de
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 917 – 923